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1.
Nano Lett ; 24(32): 9990-9997, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39101516

ABSTRACT

Liquid crystal elastomers (LCEs), consisting of polymer networks and liquid crystal mesogens, show a reversible phase change under thermal stimuli. However, the kinetic performance is limited by the inherently low thermal conductivity of the polymers. Transforming amorphous bulk into a fiber enhances thermal conductivity through the alignment of polymer chains. Challenges are present due to their rigid networks, while cross-links are crucial for deformation. Here, we employ hydrodynamic alignment to orient the LCE domains assisted by controlled in situ cross-linking and to remarkably reduce the diameter to submicrons. We report that the intrinsic thermal conductivity of LCE fibers at room temperature reaches 1.44 ± 0.32 W/m-K with the sub-100 nm diameter close to the upper limit determined in the quasi-1D regime. Combining the outstanding thermal conductivity and thin diameters, we anticipate these fibers to exhibit a rapid response and high force output in thermomechanical systems. The fabrication method is expected to apply to other cross-linked polymers.

2.
China CDC Wkly ; 6(34): 857-861, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39211412

ABSTRACT

What is already known about this topic?: Fine particulate matter (PM2.5) and ozone (O3) are prevalent pollutants in the atmosphere, which threaten human health, especially the respiratory system. Typically, people are exposed to a mixture of various pollutants in the environment. Thus, the single and combined effects of both pollutants need to be investigated. What is added by this report?: PM2.5 and O3 increase the risk of death from lung cancer, chronic obstructive pulmonary disease (COPD), and respiratory diseases, with their lagged and cumulative effects analyzed, indicating an acute effect. In addition, combined exposure to both pollutants can significantly affect disease deaths. What are the implications for public health practice?: This study provides further evidence of the single and combined effects of PM2.5 and O3 on respiratory diseases, emphasizing the need for sustained efforts in air pollution control, with greater attention to the synergistic management of air pollutants.

3.
Gut ; 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39089860

ABSTRACT

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

4.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3758-3768, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-39099350

ABSTRACT

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.


Subject(s)
Gene Expression Regulation, Plant , Multigene Family , Panax , Phylogeny , Plant Proteins , Stress, Physiological , Transcription Factors , Panax/genetics , Panax/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant/drug effects , Transcription Factors/genetics , Transcription Factors/metabolism , Stress, Physiological/genetics , Promoter Regions, Genetic , Gene Expression Profiling
5.
BMC Ophthalmol ; 24(1): 352, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160465

ABSTRACT

BACKGROUND: This study aimed to identify the differentially expressed proteins in the vitreous humor (VH) of eyes with and without pathologic myopia (PM), providing insights into the molecular pathogenesis. METHODS: A cross-sectional, observational study was conducted. VH samples were collected from patients undergoing vitrectomy for idiopathic epiretinal membrane (ERM), macular hole (MH), or myopic retinoschisis (MRS). Label-free quantitative proteomic analysis identified differential protein expression, with validation using ELISA. RESULTS: The proteomic profiling revealed significantly higher expressions of tubulin alpha 1a (TUBA1A) and eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) in PM groups (MH-PM, MRS-PM) compared to controls (MH, ERM). Conversely, xylosyltransferase 1 (XYLT1), versican core protein (VCAN), and testican-2 (SPOCK2) expressions were lower in PM. ELISA validation confirmed these findings. CONCLUSIONS: Our study provides novel insights into the molecular mechanisms of PM. The differentially expressed proteins EEF1A1, TUBA1A, XYLT1, VCAN, and SPOCK2 may play crucial roles in chorioretinal cell apoptosis, scleral extracellular matrix (ECM) synthesis, and scleral remodeling in PM. These proteins represent potential new targets for therapeutic intervention in PM, highlighting the importance of further investigations to elucidate their functions and underlying mechanisms in disease pathogenesis.


Subject(s)
Myopia, Degenerative , Proteomics , Vitreous Body , Humans , Vitreous Body/metabolism , Proteomics/methods , Male , Female , Cross-Sectional Studies , Aged , Middle Aged , Myopia, Degenerative/metabolism , Enzyme-Linked Immunosorbent Assay , Eye Proteins/metabolism , Vitrectomy
6.
Oral Oncol ; 157: 106963, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39032343

ABSTRACT

OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.


Subject(s)
B7-H1 Antigen , Cancer-Associated Fibroblasts , Chemokine CXCL1 , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , B7-H1 Antigen/metabolism , Male , Female , Nasopharyngeal Carcinoma/metabolism , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Middle Aged , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Chemokine CXCL1/metabolism , Cancer-Associated Fibroblasts/metabolism , Adult , Retrospective Studies , Neoplasm Metastasis , Prognosis , Phenotype , Biomarkers, Tumor/metabolism , Aged , Serine Endopeptidases/metabolism , Endopeptidases/metabolism , Membrane Proteins/metabolism
7.
Nano Lett ; 24(28): 8770-8777, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38968171

ABSTRACT

Oxygen-mediated triplet-triplet annihilation upconversion (TTA-UC) quenching limits the application of such organic upconversion materials. Here, we report that the photooxidation of organic amines is an effective and versatile strategy to suppress oxygen-mediated upconversion quenching in both organic solvents and aqueous solutions. The strategy is based on the dual role of organic amines in photooxidation, i.e., as singlet oxygen scavengers and electron donors. Under photoexcitation, the photosensitizer sensitizes oxygen to produce singlet oxygen for the oxidation of alkylamine, reducing the oxygen concentration. However, photoinduced electron transfer among photosensitizers, organic amines, and oxygen leads to the production of superoxide anions that suppress TTA-UC. To observe oxygen-tolerating TTA-UC, we find that alkyl secondary amines can balance the production of singlet oxygen and superoxide anions. We then utilize polyethyleneimine (PEI) to synthesize amphiphilic polymers to encapsulate TTA-UC pairs for the formation of water-dispersible, ultrasmall, and multicolor-emitting TTA-UC nanoparticles.

8.
Clin Pharmacol Ther ; 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39072721

ABSTRACT

Targeted covalent inhibitors (TCIs) are an emerging class of anticancer therapeutics. TCIs are designed to selectively engage their targeted proteins via covalent warheads. From the drug development standpoint, the covalent inhibition mechanism is anticipated to elicit the following theoretical benefits: (i) an extended duration of therapeutic action that is determined by the target protein turnover rate and not necessarily by drug half-life, (ii) a lower therapeutic dose owing to greater pharmacological potency, (iii) lower risk of off-target binding and associated adverse events, and (iv) reduced drug-drug interaction (DDI) liability due to high selectivity and low dose. Elucidating the clinical relevance of these expected benefits requires an integrated assessment of pharmacokinetics (PK), efficacy, safety, and DDI data. In this review, we compared the clinical pharmacology attributes of FDA-approved oncology TCIs within the last 10 years against their reversible inhibitor (RI) counterparts. Our findings indicated that (i) PK half-lives of TCIs were typically shorter and (ii) at their respective recommended clinical doses per drug label, the molar unbound steady state areas under the concentration-time curve (AUCss) of TCIs were lower than those of RIs, but with longer clinically observed durations of response. However, (iii) there was no conclusive evidence supporting improved clinical safety profiles for TCIs, and (iv) DDI perpetrator profiles appeared to be similar between TCIs and RIs. The overall clinical pharmacology comparison of TCI vs. RI surveyed in this paper suggested that at least two of the four forecasted clinical benefits were achieved by TCIs.

9.
Pharmaceutics ; 16(7)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39065618

ABSTRACT

The gut microbiota is closely associated with human health, and alterations in gut microbiota can influence various physiological and pathological activities in the human body. Therefore, microbiota regulation has become an important strategy in current disease treatment, albeit facing numerous challenges. Nanomaterials, owing to their excellent protective properties, drug release capabilities, targeting abilities, and good biocompatibility, have been widely developed and utilized in pharmaceuticals and dietary fields. In recent years, significant progress has been made in research on utilizing nanomaterials to assist in regulating gut microbiota for disease intervention. This review explores the latest advancements in the application of nanomaterials for microbiota regulation and offers insights into the future development of nanomaterials in modulating gut microbiota.

11.
J Am Chem Soc ; 146(31): 21791-21805, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39069661

ABSTRACT

The diagnosis of disease biomarkers is crucial for the identification, monitoring, and prognostic assessment of malignant disease. However, biological samples with autofluorescence, complex components, and heterogeneity pose major challenges to reliable biosensing. Here, we report the self-assembly of natural proteins and the triplet-triplet annihilation upconversion (TTA-UC) pair to form upconverted protein clusters (∼8.2 ± 1.1 nm), which were further assembled into photon upconversion supramolecular assemblies (PUSA). This PUSA exhibited unique features, including a small size (∼44.1 ± 4.1 nm), oxygen tolerance, superior biocompatibility, and easy storage via lyophilization, all of which are long sought after for photon upconversion materials. Further, we have revealed that the steric hindrance of the annihilator suppresses the stacking of the annihilator in PUSA, which is vital for maintaining the water dispersibility and enhancing the upconversion performance of PUSA. In conjunction with sarcosine oxidase, this near infrared (NIR)-excitable PUSA nanoprobe could perform background-free biosensing of urinary sarcosine, which is a common biomarker for prostatic carcinoma (PCa). More importantly, this nanoprobe not only allows for qualitative identification of urinary samples from PCa patients by the unaided eye under NIR-light-emitting diode (LED) illumination but also quantifies the concentration of urinary sarcosine. These remarkable findings have propelled photon upconversion materials to a new evolutionary stage and expedited the progress of upconversion biosensing in clinical diagnostics.


Subject(s)
Biosensing Techniques , Photons , Humans , Sarcosine/urine , Sarcosine/chemistry , Sarcosine Oxidase/chemistry , Proteins/analysis , Proteins/chemistry
12.
Front Med (Lausanne) ; 11: 1366362, 2024.
Article in English | MEDLINE | ID: mdl-39055692

ABSTRACT

Aims: The health management of end-stage renal disease patients is a complicated process, and mobile health management technology provides a new choice for the health management of end-stage renal disease patients. The scope of clinical studies on mobile health management for patients with end-stage renal disease was reviewed, and found that about mobile health management problems existing in the literature were identified to provide ideas for subsequent mobile health management research. Methods: The databases Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang Data, BMJ, and VIP were systematically searched for studies on Mobile health management among end-stage renal disease in adult and adolescent patients or children undergoing kidney replacement therapy. The search covered the period from the inception of the databases to June 20, 2023. Two independent reviewers conducted the literature screening process. Following eligibility screening, a total of 38 papers were included for data extraction and descriptive analysis. Results: A total of 38 studies from 14 countries were finally included. The majority of which were interventional trials. The platforms used in these studies included remote monitoring systems, apps, websites, mobile phones or tablets, and social platforms. These platforms provided patients with a wide range of services, including disease management, behavioral intervention, social support, and follow-up care. Most studies focused on patient clinical indicators, patient experience, quality of life, and healthcare costs. Conclusion: Our findings that mobile health management has been widely used in disease management of end-stage renal disease patients, with rich management content and many evaluation indicators. Future studies should strengthen the evaluation of patients' mental health, quality of life, and healthcare costs. Additionally, developing a clinical decision support system would enable mobile health management to play a more effective role in end-stage renal disease patients.

13.
Food Res Int ; 190: 114600, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945570

ABSTRACT

Browning commonly appeared in apple processing, which varied in different apple varieties. Present work investigated the metabolomics of four varieties apple of Yataka, Gala, Sansa, and Fuji, which possessed different browning characteristics and related enzymes. Sansa as browning insensitive apple variety, exhibited the least chroma change with the lowest PPO activity and the highest SOD activity among the four apple varieties. Browning inhibition pretreatment increased the activity of SOD and PAL and decreased PPO and POD activity. In addition, metabolomic variances among the four apple varieties (FC), their browning pulp (BR) and browning inhibition pulp (CM) were compared. And the key metabolites were in-depth analyzed to match the relevant KEGG pathways and speculated metabolic networks. There were 487, 644, and 494 significant differential metabolites detected in FC, BR and CM, which were consisted of lipids, benzenoids, phenylpropanoids, organheterocyclic compounds, organic acids, nucleosides, accounting for 23 %, 11 %, 15 %, 16 %, 11 % of the total metabolites. The differential metabolites were matched with 39, 49, and 36 KEGG pathways in FC, BR, and CM, respectively, in which other secondary metabolites biosynthesis metabolism was the most significant in FC, lipid metabolism was the most significant in BR and CM, and energy metabolism was markedly annotated in CM. Notably, Sansa displayed the highest number of differential metabolites in both its BR (484) and CM (342). The BR of Sansa was characterized by flavonoid biosynthesis, while the other three apple varieties were associated with α-linolenic acid metabolism. Furthermore, in browning sensitive apple varieties, the flavonoid and phenylpropanoid biosynthesis pathway was significantly activated by browning inhibition pretreatment. Phenolic compounds, lipids, sugars, organic acids, nucleotides, and adenosine were regulated differently in the four apple varieties, potentially serving as key regulatory sites. Overall, this work provides novel insight for browning prevention in different apple varieties.


Subject(s)
Fruit , Malus , Metabolomics , Malus/metabolism , Malus/classification , Fruit/metabolism , Fruit/chemistry , Food Handling/methods , Maillard Reaction
14.
Front Psychol ; 15: 1373892, 2024.
Article in English | MEDLINE | ID: mdl-38863665

ABSTRACT

Organizational climate has been shown to be an important factor associated with teachers' job satisfaction. However, the internal mechanism between them is unclear. The purpose of this study was to investigate whether the relationship between kindergarten organizational climate and kindergarten teachers' job satisfaction was affected by occupational stress and emotional labor. This study employed a questionnaire survey method to gather data from 1,091 kindergarten teachers nationwide. It conducted an analysis of the current status of kindergarten organizational climate and the job satisfaction of kindergarten teachers, elucidating the relationship between the two and the underlying mechanisms. Additionally, a chain mediation model was constructed. The findings indicated that: (1) organizational climate, kindergarten teachers' occupational stress and emotional labor all significantly predict kindergarten teachers' job satisfaction directly (2) organizational climate could indirectly influence kindergarten teachers' job satisfaction through three pathways: the separate mediating effect of occupational stress and emotional labor, and the chain mediating effect on both. The research findings highlight the significance of kindergarten organizational climate, occupational stress, and emotional labor in augmenting the job satisfaction of kindergarten teachers, offering valuable insights for the improvement of kindergarten teacher job satisfaction.

15.
Front Pharmacol ; 15: 1377055, 2024.
Article in English | MEDLINE | ID: mdl-38828450

ABSTRACT

Primary Sjögren's Syndrome (pSS) is a complex autoimmune disorder characterized by exocrine gland dysfunction, leading to dry eyes and mouth. Despite growing interest in biologic therapies for pSS, FDA approval has proven challenging due to trial complications. This review addresses the absence of a molecular-target-based approach to biologic therapy development and highlights novel research on drug targets and clinical trials. A literature search identified potential pSS treatment targets and recent advances in molecular understanding. Overlooking extraglandular symptoms like fatigue and depression is a notable gap in trials. Emerging biologic agents targeting cytokines, signal pathways, and immune responses have proven efficacy. These novel therapies could complement existing methods for symptom alleviation. Improved grading systems accounting for extraglandular symptoms are needed. The future of pSS treatment may involve gene, stem-cell, and tissue-engineering therapies. This narrative review offers insights into advancing pSS management through innovative biologic interventions.

16.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2478-2488, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812147

ABSTRACT

In order to analyze the similarities and differences of chemical compositions between the roots and stems and leaves of Isodon japonicus(IJ), this study utilized UPLC-Q-TOF-MS technology to systematically characterize its chemical compositions, analyzed and identified the structure of its main compounds, and established a method for simultaneous determination of its content by refe-rence substance. A total of 34 major compounds in IJ, including 14 reference compounds, were identified or predicted online. Moreover, an UPLC-UV content determination method was developed for 11 compounds [danshensu, caffeic acid, vicenin-2,(1S,2S)-globoidnan B, rutin,(+)-rabdosiin,(-)-rabdosiin,(1S,2S)-rabdosiin, shimobashiric acid C, rosmarinic acid, and pedalitin]. The method exhibited excellent separation, stability, and repeatability, with a wide linear range(0.10-520.00 µg·mL~(-1)) and high linearity(R~2>0.999). The average recovery rates ranged from 94.72% to 104.2%. The principal component analysis(PCA) demonstrated a clear difference between the roots and stems and leaves of IJ, indicating good separation by cluster. Furthermore, the orthogonal partial least squares discriminant analysis(OPLS-DA) model was employed, and six main differentially identified compounds were identified: rosmarinic acid, shimobashiric acid C, epinodosin, pedalitin, rutin, and(1S,2S)-rabdosiin. In summary, this study established a strategy and method for distinguishing different parts of IJ, providing a valuable tool for quality control of IJ and a basis for the ratio-nal utilization and sustainable development of IJ.


Subject(s)
Chemometrics , Drugs, Chinese Herbal , Isodon , Mass Spectrometry , Plant Leaves , Chromatography, High Pressure Liquid/methods , Isodon/chemistry , Mass Spectrometry/methods , Chemometrics/methods , Plant Leaves/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Plant Roots/chemistry , Plant Stems/chemistry
18.
Ecotoxicol Environ Saf ; 279: 116446, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38772138

ABSTRACT

The discovery of MPTP, an industrial chemical and contaminant of illicit narcotics, which causes parkinsonism in humans, non-human primates and rodents, has led to environmental pollutants exposure being convicted as key candidate in Parkinson's disease (PD) pathogenesis. Though MPTP-induced mitochondrial dysfunction and neuroinflammation are mainly responsible for the causative issue of MPTP neurotoxicity, the underlying mechanism involved remains unclear. Here, we reveal a novel signaling mechanism of CDK5-USP30-MAVS regulating MPTP/MPP+ induced PD. MPP+ (the toxic metabolite of MPTP) treatment not only led to the increased protein levels of USP30 but also to mitophagy inhibition, mitochondrial dysfunction, and MAVS-mediated inflammation in BV2 microglial cells. Both mitophagy stimulation (Urolithin A administration) and USP30 knockdown relieved MAVS-mediated inflammation via restoring mitophagy and mitochondrial function in MPP+-induced cell model. Notably, MPTP/MPP+-induced CDK5 activation regulated USP30 phosphorylation at serine 216 to stabilize USP30. Moreover, CDK5-USP30 pathway promoted MAVS-mediated inflammation in MPTP/MPP+-induced PD model. Inhibition of CDK5 not only had a protective effect on MPP+-induced cell model of PD via suppressing the upregulation of USP30 and the activation of MAVS inflammation pathway in vitro, but also prevented neurodegeneration in vivo and alleviated movement impairment in MPTP mouse model of PD. Overall, our study reveal that CDK5 blocks mitophagy through phosphorylating USP30 and activates MAVS inflammation pathway in MPTP/MPP+-induced PD model, which suggests that CDK5-USP30-MAVS signaling pathway represents a valuable treatment strategy for PD induced by environmental neurotoxic pollutants in relation to MPTP.


Subject(s)
Cyclin-Dependent Kinase 5 , Inflammation , Mitophagy , Signal Transduction , Animals , Male , Mice , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Adaptor Proteins, Signal Transducing/metabolism , Cell Line , Cyclin-Dependent Kinase 5/metabolism , Disease Models, Animal , Inflammation/chemically induced , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/metabolism , Mitophagy/drug effects , Parkinson Disease
19.
Plant J ; 119(2): 1059-1072, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761127

ABSTRACT

Most of kiwifruit cultivars (e.g. Actinidia chinensis cv. Donghong, "DH") were sensitive to waterlogging, thus, waterlogging resistant rootstocks (e.g. Actinidia valvata Dunn, "Dunn") were widely used for kiwifruit industry. Those different species provided ideal materials to understand the waterlogging responses in kiwifruit. Compared to the weaken growth and root activities in "DH", "Dunn" maintained the relative high root activities under the prolonged waterlogging. Based on comparative analysis, transcript levels of pyruvate decarboxylase (PDCs) and alcohol dehydrogenase (ADHs) showed significantly difference between these two species. Both PDCs and ADHs had been significantly increased by waterlogging in "DH", while they were only limitedly triggered by 2 days stress and subsided during the prolonged waterlogging in "Dunn". Thus, 19 differentially expressed transcript factors (DETFs) had been isolated using weighted gene co-expression network analysis combined with transcriptomics and transcript levels of PDCs and ADHs in waterlogged "DH". Among these DETFs, dual luciferase and electrophoretic mobility shift assays indicated AcMYB68 could bind to and trigger the activity of AcPDC2 promoter. The stable over-expression of AcMYB68 significantly up-regulated the transcript levels of PDCs but inhibited the plant growth, especially the roots. Moreover, the enzyme activities of PDC in 35S::AcMYB68 were significantly enhanced during the waterlogging response than that in wild type plants. Most interestingly, comparative analysis indicated that the expression patterns of AcMYB68 and the previously characterized AcERF74/75 (the direct regulator on ADHs) either showed no responses (AcMYB68 and AcERF74) or very limited response (AcERF75) in "Dunn". Taken together, the restricted responses of AcMYB68 and AcERF74/75 in "Dunn" endow its waterlogging tolerance.


Subject(s)
Actinidia , Gene Expression Regulation, Plant , Plant Proteins , Pyruvate Decarboxylase , Actinidia/genetics , Actinidia/physiology , Actinidia/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Pyruvate Decarboxylase/genetics , Pyruvate Decarboxylase/metabolism , Alcohol Dehydrogenase/genetics , Alcohol Dehydrogenase/metabolism , Plant Roots/genetics , Plant Roots/physiology , Water/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Stress, Physiological , Promoter Regions, Genetic/genetics
20.
Front Oncol ; 14: 1384105, 2024.
Article in English | MEDLINE | ID: mdl-38803533

ABSTRACT

Objective: The pathological classification and imaging manifestation of parotid gland tumors are complex, while accurate preoperative identification plays a crucial role in clinical management and prognosis assessment. This study aims to construct and compare the performance of clinical models, traditional radiomics models, deep learning (DL) models, and deep learning radiomics (DLR) models based on ultrasound (US) images in differentiating between benign parotid gland tumors (BPGTs) and malignant parotid gland tumors (MPGTs). Methods: Retrospective analysis was conducted on 526 patients with confirmed PGTs after surgery, who were randomly divided into a training set and a testing set in the ratio of 7:3. Traditional radiomics and three DL models (DenseNet121, VGG19, ResNet50) were employed to extract handcrafted radiomics (HCR) features and DL features followed by feature fusion. Seven machine learning classifiers including logistic regression (LR), support vector machine (SVM), RandomForest, ExtraTrees, XGBoost, LightGBM and multi-layer perceptron (MLP) were combined to construct predictive models. The most optimal model was integrated with clinical and US features to develop a nomogram. Receiver operating characteristic (ROC) curve was employed for assessing performance of various models while the clinical utility was assessed by decision curve analysis (DCA). Results: The DLR model based on ExtraTrees demonstrated superior performance with AUC values of 0.943 (95% CI: 0.918-0.969) and 0.916 (95% CI: 0.861-0.971) for the training and testing set, respectively. The combined model DLR nomogram (DLRN) further enhanced the performance, resulting in AUC values of 0.960 (95% CI: 0.940- 0.979) and 0.934 (95% CI: 0.876-0.991) for the training and testing sets, respectively. DCA analysis indicated that DLRN provided greater clinical benefits compared to other models. Conclusion: DLRN based on US images shows exceptional performance in distinguishing BPGTs and MPGTs, providing more reliable information for personalized diagnosis and treatment plans in clinical practice.

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