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1.
J Environ Sci (China) ; 148: 210-220, 2025 Feb.
Article de Anglais | MEDLINE | ID: mdl-39095158

RÉSUMÉ

Heterogeneous oxidation by gas-phase oxidants is an important chemical transformation pathway of secondary organic aerosol (SOA) and plays an important role in controlling the abundance, properties, as well as climate and health impacts of aerosols. However, our knowledge on this heterogeneous chemistry remains inadequate. In this study, the heterogeneous oxidation of α-pinene ozonolysis SOA by hydroxyl (OH) radicals was investigated under both low and high relative humidity (RH) conditions, with an emphasis on the evolution of molecular composition of SOA and its RH dependence. It is found that the heterogeneous oxidation of SOA at an OH exposure level equivalent to 12 hr of atmospheric aging leads to particle mass loss of 60% at 25% RH and 95% at 90% RH. The heterogeneous oxidation strongly changes the molecular composition of SOA. The dimer-to-monomer signal ratios increase dramatically with rising OH exposure, in particular under high RH conditions, suggesting that aerosol water stimulates the reaction of monomers with OH radicals more than that of dimers. In addition, the typical SOA tracer compounds such as pinic acid, pinonic acid, hydroxy pinonic acid and dimer esters (e.g., C17H26O8 and C19H28O7) have lifetimes of several hours against heterogeneous OH oxidation under typical atmospheric conditions, which highlights the need for the consideration of their heterogeneous loss in the estimation of monoterpene SOA concentrations using tracer-based methods. Our study sheds lights on the heterogeneous oxidation chemistry of monoterpene SOA and would help to understand their evolution and impacts in the atmosphere.


Sujet(s)
Aérosols , Polluants atmosphériques , Monoterpènes bicycliques , Humidité , Radical hydroxyle , Oxydoréduction , Aérosols/composition chimique , Radical hydroxyle/composition chimique , Monoterpènes bicycliques/composition chimique , Polluants atmosphériques/composition chimique , Polluants atmosphériques/analyse , Ozone/composition chimique , Modèles chimiques , Atmosphère/composition chimique , Monoterpènes/composition chimique
2.
Article de Anglais | MEDLINE | ID: mdl-39098378

RÉSUMÉ

BACKGROUND AND AIM: Cardiometabolic diseases (CMDs) are leading causes of death and disability, but little is known about the additive mortality effects of multiple CMDs. This study aimed to examine the association between single and multiple CMDs and all-cause mortality among older Chinese population. METHODS AND RESULTS: Using the Chinese Longitudinal Healthy Longevity Survey (CLHLS) database, we analyzed data from 2008 to 2018 to assess the relationship between CMDs and mortality. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for single and multiple CMDs. At baseline, 11,351 participants (56.9% female) aged 60 years or older were included. 11.91% of participants had a single CMD, 1.51% had two CMDs, and 0.22% had three CMDs. Over a decade follow-up, 8992 deaths (79.2%) were recorded. A dose-response relationship was observed, with the mortality risk increasing by 17% for each additional disease. The fully-adjusted HRs for all-cause mortality were 1.16, 1.36, and 2.03 for one, two, and three CMDs, respectively. Larger effects of single and multiple CMDs were observed in the male group (P = 0.015) and the younger senior group (P < 0.001). CONCLUSIONS: This large-scale study found that CMDs multiply mortality risks, especially in younger seniors and males. The risk is highest when heart disease and stroke coexist, and diabetes further increases it. Public health efforts should prioritize evidence-based management and prevention of CMDs.

3.
Sci Total Environ ; : 175207, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39097012

RÉSUMÉ

Secondary organic aerosol (SOA) is a major component of atmospheric fine particulate matter. Both particle viscosity and particle-phase chemistry play a crucial role in the formation and evolution of SOA; however, our understanding on how these two factors together with gas-phase chemistry collectively determine the formation of SOA is still limited. Here we developed a kinetic aerosol multilayer model coupled with gas-phase and particle-phase chemistry to simulate SOA formation. We take the atmospherically important α-pinene + OH oxidation system as an example application of the model. The simulations show that although the particle viscosity has negligible to small influences on the total SOA mass concentration, it strongly changes the concentration and distribution of individual compounds within the particle. This complicated effect of particle viscosity on SOA formation is a combined result of inhibited condensation or evaporation of specific organics due to slowed particle-phase diffusion. Furthermore, the particle-phase reactions alter the volatility and abundance of specific compounds and exacerbate their non-uniform distribution in highly viscous particles. Our results highlight an important species-specific effect of particle viscosity and particle-phase chemistry on SOA formation and demonstrate the capability of our model for quantifying such complicated effects on SOA formation and evolution.

5.
Clin Respir J ; 18(8): e13810, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39107961

RÉSUMÉ

BACKGROUND: Pulmonary resection is an important part of comprehensive treatment of lung cancer. Despite the progress in recent thoracic surgery, reoperation is occasionally inevitable for managing severe perioperative complications. This study aimed to investigate the incidence and causes of perioperative reoperation in lung cancer patients. METHODS: We retrospectively collected patients who underwent reoperation following pulmonary resection from January 2010 to February 2021 in China-Japan Friendship Hospital. RESULTS: Among the 5032 lung cancer patients who received primary pulmonary resection in our institute, 37 patients underwent perioperative reoperation with the rate being 0.74%. Lobectomy was the most frequently executed procedure (56.8%). The mean duration of the primary surgery was 143.6 ± 65.1 min. About half of the cases received secondary surgery within 24 h of the primary surgery, whereas only one case underwent secondary surgery 30 days after the primary surgery (due to chylous leakage). The major causes of the reoperation were bleeding (73.0%), chylous leakage (13.5%), lobar torsion (5.4%), air leakage (2.7%), atelectasis (2.9%), and cardiac herniation (2.7%). CONCLUSION: The most prevalent reasons for unplanned reoperation following pulmonary resection in lung cancer patients include bleeding, chylous leakage, and lobar torsion. The strict control of the surgical indications and standardization of surgical procedures are fundamental to reduce unplanned secondary operations after pulmonary resections. Timely identification of the need to secondary surgery is also important to ensure patients' safety.


Sujet(s)
Tumeurs du poumon , Pneumonectomie , Complications postopératoires , Réintervention , Humains , Tumeurs du poumon/chirurgie , Réintervention/statistiques et données numériques , Mâle , Femelle , Études rétrospectives , Adulte d'âge moyen , Complications postopératoires/épidémiologie , Complications postopératoires/chirurgie , Complications postopératoires/étiologie , Sujet âgé , Pneumonectomie/effets indésirables , Pneumonectomie/méthodes , Chine/épidémiologie , Incidence , Japon/épidémiologie
6.
J Clin Anesth ; 98: 111573, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39094442

RÉSUMÉ

STUDY OBJECTIVE: Hyperlipidemia and postoperative delirium (POD) significantly affect patients' quality of life; however, the question of whether hyperlipidemia constitutes a risk factor for POD remain unclear. This study aimed to investigate whether patients with hyperlipidemia face elevated risks of developing POD and to identify potential causes for this increased risk. DESIGN: A prospective cohort study. SETTING: Operating room. PATIENTS: Patients were adults scheduled for colorectal cancer surgery in 2023. EXPOSURES: The exposure factor was hyperlipidemia, and the patients were divided into hyperlipidemia group and non-hyperlipidemia group. MEASUREMENTS: POD occurrence within three days post-surgery was assessed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Over one year, these patients were monitored through telephone to evaluate their survival and cognitive function. Logistic regression analysis was performed to evaluate the risk factors for POD development in patients with hyperlipidemia and to construct a clinical prediction model. MAIN RESULTS: This study included 555 patients. POD incidence was 21.6% in the hyperlipidemia group and 12.7% in the non-hyperlipidemia group. One year following surgery, patients with hyperlipidemia and POD exhibited significantly higher rates of mortality and cognitive decline than did those without POD (p < 0.001). A multifactorial logistic clinical prediction model was constructed from seven independent risk factors for POD development in patients with hyperlipidemia, including education, preoperative total cholesterol (TC), preoperative triglyceride (TG), diet, history of hypertension, Sedation-Agitation Scale, and postoperative trimethylamine N-oxide expression level, and it had the highest predictive value for POD development in patients with hyperlipidemia. CONCLUSIONS: Compared with those without hyperlipidemia, patients with hyperlipidemia had higher POD incidence. Elevated serum TC and TG levels are independent risk factors for POD in patients with hyperlipidemia. The study's findings could help develop strategies for improving POD and hyperlipidemia treatment.

7.
Ann Med ; 56(1): 2373199, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38956857

RÉSUMÉ

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS. METHODS: We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats. RESULTS: We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels. CONCLUSION: These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.


Obesity was negatively correlated with negative emotions in patients with PCOS.Obesity may affect the downregulation of LH and testosterone and participate in the regulation of emotions.Increased BMI may be beneficial for patients with PCOS in terms of the psychological aspects.


Sujet(s)
Anxiété , Indice de masse corporelle , Dépression , Alimentation riche en graisse , Obésité , Syndrome des ovaires polykystiques , Syndrome des ovaires polykystiques/psychologie , Syndrome des ovaires polykystiques/complications , Femelle , Animaux , Humains , Obésité/psychologie , Rats , Études transversales , Adulte , Anxiété/psychologie , Anxiété/étiologie , Dépression/psychologie , Dépression/étiologie , Alimentation riche en graisse/effets indésirables , Modèles animaux de maladie humaine , Rat Sprague-Dawley , Jeune adulte , Émotions , Stress psychologique/psychologie
8.
Int J Biol Macromol ; 275(Pt 1): 133645, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38964686

RÉSUMÉ

Fas-associated protein with death domain (FADD) was initially identified as a crucial adaptor protein in the apoptotic pathway mediated by death receptor (DR). Subsequently, many studies have confirmed that FADD plays a vital role in innate immunity and inflammatory responses in animals. However, the function of this pleiotropic molecule in mollusk species has not been well explored. In this study, we successfully verified the gene sequence of FADD in the Zhikong scallop (Chlamys farreri) and designated it as CfFADD. The CfFADD protein contains a conserved death effector and death domains. Phylogenetic analysis showed that CfFADD is a novel addition to the molluscan FADD family with a close evolutionary relationship with molluscan FADD subfamily proteins. CfFADD mRNA expression in various scallop tissues was significantly induced by challenge with pathogen-associated molecular patterns (lipopolysaccharide, peptidoglycan, and poly(I:C)), suggesting its role in innate immunity in scallops. Co-immunoprecipitation showed that CfFADD interacted with the scallop DR (tumor necrosis factor receptor) and a signaling molecule involved in the Toll-like receptor pathway (interleukin-1 receptor-associated kinase), confirming that CfFADD may be involved in DR-mediated apoptosis and innate immune signaling pathways. Further studies showed that CfFADD interacted with CfCaspase-8 and activated caspase-3. HEK293T cells exhibited distinct apoptotic features after transfection with a CfFADD-expression plasmid, suggesting a functional DR-FADD-caspase apoptotic pathway in scallops. Overexpression of CfFADD led to a significant dose-dependent activation of interferon ß and nuclear factor-κB reporter genes, demonstrating the key role of CfFADD in innate immunity. In summary, our research has confirmed the critical roles of CfFADD in innate immunity and apoptosis and provides valuable information for developing comparative immunology theories.

9.
Lipids Health Dis ; 23(1): 209, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38965618

RÉSUMÉ

BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.


Sujet(s)
Cholestérol HDL , Enquêtes nutritionnelles , Syndrome d'apnées obstructives du sommeil , Humains , Syndrome d'apnées obstructives du sommeil/sang , Syndrome d'apnées obstructives du sommeil/épidémiologie , Adulte d'âge moyen , Mâle , Femelle , Études transversales , Adulte , Cholestérol HDL/sang , Sujet âgé , Facteurs de risque , Marqueurs biologiques/sang , Maladies cardiovasculaires/sang , Maladies cardiovasculaires/épidémiologie
10.
World J Surg Oncol ; 22(1): 198, 2024 Jul 27.
Article de Anglais | MEDLINE | ID: mdl-39068445

RÉSUMÉ

BACKGROUND: Neoadjuvant therapy (NT) has increased survival rates for patients with locally advanced esophageal cancer (EC), but estimating the impact of NT treatment prior to surgery is still very difficult. METHODS: A retrospective study of the clinical information of 150 patients with locally advanced EC who got NT at Qilu Hospital of Shandong University between June 2018 and June 2023. Patients were randomized into training and internal validation groups at a 3:1 ratio. Furthermore, an external validation cohort comprised 38 patients who underwent neoadjuvant therapy at Qianfoshan Hospital in the Shandong Province between June 2021 and June 2023. Independent risk factors were identified using univariate and multivariate logistic regression (forward stepwise regression). Predictive models and dynamic web nomograms were developed by integrating these risk factors. RESULTS: A total of 188 patients with locally advanced EC were enrolled, of whom 118 achieved stage I of neoadjuvant pathologic TNM (ypTNM) after receiving NT and 129 achieved grades 0-1 in the tumor regression grade (TRG). Logistic regression analysis identified five independent predictors of TRG grades 0-1: pulmonary function tests (PFT), prognostic nutritional index (PNI), triglyceride (TG) levels, squamous cell carcinoma antigen (SCC-Ag) levels, and combination immunotherapy. The areas under the receiver operating characteristic (ROC) curves for the training, internal validation, and external validation groups were 0.87, 0.75, and 0.80, respectively. Meanwhile, two independent predictors of stage I of ypTNM were identified: prealbumin (PA) and SCC antigen. The areas under the ROC curves for the training, internal validation, and external validation groups were 0.78, 0.67, and 0.70, respectively. The Hosmer-Lemeshow test for both predictive models showed excellent calibration, with well-fitted calibration curves. Decision curve analysis (DCA) and clinical impact curves (CIC) have demonstrated that nomograms are of clinical utility. CONCLUSION: The nomograms performed well in predicting the likelihood of stage I of ypTNM and TRG grade 0-1 after NT in patients with locally advanced EC. It helps thoracic surgeons to predict the sensitivity of patients to NT before surgery, which enables precise treatment of patients with locally advanced EC.


Sujet(s)
Tumeurs de l'oesophage , Traitement néoadjuvant , Stadification tumorale , Nomogrammes , Humains , Tumeurs de l'oesophage/anatomopathologie , Tumeurs de l'oesophage/thérapie , Mâle , Femelle , Traitement néoadjuvant/méthodes , Adulte d'âge moyen , Études rétrospectives , Pronostic , Études de suivi , Sujet âgé , Grading des tumeurs , Oesophagectomie
11.
Microorganisms ; 12(7)2024 Jul 19.
Article de Anglais | MEDLINE | ID: mdl-39065241

RÉSUMÉ

Cotton is highly sensitive to potassium, and Xinjiang, China's leading cotton-producing region, faces a severe challenge due to reduced soil potassium availability. Biofertilizers, particularly potassium-solubilizing rhizobacteria (KSR), convert insoluble potassium into plant-usable forms, offering a sustainable solution for evergreen agriculture. This study isolated and characterized KSR from cotton, elucidated their potassium solubilization mechanisms, and evaluated the effects of inoculating KSR strains on cotton seedlings. Twenty-three KSR strains were isolated from cotton rhizosphere soil using modified Aleksandrov medium. Their solubilizing capacities were assessed in a liquid medium. Strain A10 exhibited the highest potassium solubilization capacity (21.8 ppm) by secreting organic acids such as lactic, citric, acetic, and succinic acid, lowering the pH and facilitating potassium release. A growth curve analysis and potassium solubilization tests of A10 under alkali stress showed its vigorous growth and maintained solubilization ability at pH 8-9, with significant inhibition at pH 10. Furthermore, 16S rRNA sequencing identified strain A10 as Pseudomonas aeruginosa. Greenhouse pot experiments showed that inoculating cotton plants with strain A10 significantly increased plant height and promoted root growth. This inoculation also enhanced dry biomass accumulation in both the aerial parts and root systems of the plants, while reducing the root-shoot ratio. These results suggest that Pseudomonas aeruginosa A10 has potential as a biofertilizer, offering a new strategy for sustainable agriculture.

12.
Neuroimage ; 297: 120744, 2024 Jul 20.
Article de Anglais | MEDLINE | ID: mdl-39033791

RÉSUMÉ

The fragmentation of the functional brain network has been identified through the functional connectivity (FC) analysis in studies investigating anesthesia-induced loss of consciousness (LOC). However, it remains unclear whether mild sedation of anesthesia can cause similar effects. This paper aims to explore the changes in local-global brain network topology during mild anesthesia, to better understand the macroscopic neural mechanism underlying anesthesia sedation. We analyzed high-density EEG from 20 participants undergoing mild and moderate sedation of propofol anesthesia. By employing a local-global brain parcellation in EEG source analysis, we established binary functional brain networks for each participant. Furthermore, we investigated the global-scale properties of brain networks by estimating global efficiency and modularity, and examined the changes in meso-scale properties of brain networks by quantifying the distribution of high-degree and high-betweenness hubs and their corresponding rich-club coefficients. It is evident from the results that the mild sedation of anesthesia does not cause a significant change in the global-scale properties of brain networks. However, network components centered on SomMot L show a significant decrease, while those centered on Default L, Vis L and Limbic L exhibit a significant increase during the transition from wakefulness to mild sedation (p<0.05). Compared to the baseline state, mild sedation almost doubled the number of high-degree hubs in Vis L, DorsAttn L, Limbic L, Cont L, and reduced by half the number of high-degree hubs in SomMot R, DorsAttn R, SalVentAttn R. Further, mild sedation almost doubled the number of high-betweenness hubs in Vis L, Vis R, Limbic R, Cont R, and reduced by half the number of high-betweenness hubs in SomMot L, SalVentAttn L, Default L, and SomMot R. Our results indicate that mild anesthesia cannot affect the global integration and segregation of brain networks, but influence meso-scale function for integrating different resting-state systems involved in various segregation processes. Our findings suggest that the meso-scale brain network reorganization, situated between global integration and local segregation, could reflect the autonomic compensation of the brain for drug effects. As a direct response and adjustment of the brain network system to drug administration, this spontaneous reorganization of the brain network aims at maintaining consciousness in the case of sedation.

13.
Article de Anglais | MEDLINE | ID: mdl-39038342

RÉSUMÉ

Objective: To appraise the application value of psychological counseling based on the concept of solution-focused brief therapy (SFBT) concept in patients with premature ovarian failure. Methods: A total of 176 patients with premature ovarian failure admitted to China-Japan Union Hospital hospital between January 2020 and February 2021 were enrolled for prospective analysis and were randomly assigned to the control group and the experimental group using the random number table method, with 88 cases in each group. The control group received the normal psychological counseling intervention, whereas the experimental group received the SFBT-based counseling intervention. The serum indexes follicle-stimulating hormone (FSH), luteinizing hormone (LH), Estradiol (E2), Fertility Quality of Life (FertiQoL) score, Symptom Checklist 90 (SCL-90) score, Memorial University of Newfoundland Scale of Happiness (MUNSH) score, self-rating depression scale (SDS) score, self-rating anxiety scale (SAS) score, and the satisfaction rate were recorded and compared between the two groups of patients. Results: After the intervention, patients in the experimental group achieved lower FSH and LH levels and higher E2 levels than the control group (P < .05). After the intervention, the scores of emotional response, mind-body relationship, and tolerability and overall scores increased in both groups, with the experimental group scoring significantly higher than the control group (P < .05). After the intervention, the differences in hostility and compulsion scores between the two groups were not statistically significant (P > .05). Compared with the control group, patients in the experimental group scored lower on somatization, interpersonal relationship, and psychosis and overall score, while positive factor scores were higher (P < .05). Before the intervention, SDS and SAS scores were comparable in both groups. In contrast, SDS and SAS scores decreased in both groups and in the experimental group compared to the control group after the intervention. (P < .05). Conclusion: Psychological counseling based on the SFBT concept in patients with premature ovarian failure could improve the patients' serum indexes, quality of life, and sense of well-being, which is worthy of clinical promotion. It is recommended that most researchers conduct studies with larger samples in our hospital to provide better evidence-based evidence.

14.
J Extracell Vesicles ; 13(7): e12484, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39041344

RÉSUMÉ

Pancreatic ductal adenocarcinoma (PDAC) is characterised by immune evasion that contribute to poor prognosis. Cancer-associated fibroblasts (CAFs) play a pivotal role in orchestrating the PDAC tumour microenvironment. We investigated the role of CAF-derived extracellular vesicle (EV)-packaged long non-coding RNAs (lncRNAs) in immune evasion and explored gene therapy using engineered EVs loading small interfering RNAs (siRNAs) as a potential therapeutic strategy. Our findings highlight the significance of EV-packaged lncRNA RP11-161H23.5 from CAF in promoting PDAC immune evasion by downregulating HLA-A expression, a key component of antigen presentation. Mechanistically, RP11-161H23.5 forms a complex with CNOT4, a subunit of the mRNA deadenylase CCR4-NOT complex, enhancing the degradation of HLA-A mRNA by shortening its poly(A) tail. This immune evasion mechanism compromises the anti-tumour immune response. To combat this, we propose an innovative approach utilising engineered EVs as natural and biocompatible nanocarriers for siRNA-based gene therapy and this strategy holds promise for enhancing the effectiveness of immunotherapy in PDAC. Overall, our study sheds light on the critical role of CAF-derived EV-packaged lncRNA RP11-161H23.5/CNOT4/HLA-A axis in PDAC immune evasion and presents a novel avenue for therapeutic intervention.


Sujet(s)
Fibroblastes associés au cancer , Carcinome du canal pancréatique , Vésicules extracellulaires , Antigènes HLA-A , Tumeurs du pancréas , ARN long non codant , Humains , ARN long non codant/génétique , ARN long non codant/métabolisme , Fibroblastes associés au cancer/métabolisme , Fibroblastes associés au cancer/immunologie , Vésicules extracellulaires/métabolisme , Vésicules extracellulaires/immunologie , Tumeurs du pancréas/immunologie , Tumeurs du pancréas/génétique , Tumeurs du pancréas/thérapie , Carcinome du canal pancréatique/immunologie , Carcinome du canal pancréatique/génétique , Carcinome du canal pancréatique/thérapie , Lignée cellulaire tumorale , Antigènes HLA-A/génétique , Antigènes HLA-A/immunologie , Antigènes HLA-A/métabolisme , Échappement immunitaire , Régulation de l'expression des gènes tumoraux , Régulation négative , Petit ARN interférent , Microenvironnement tumoral/immunologie , Animaux , Échappement de la tumeur à la surveillance immunitaire , Souris
15.
Int J Mol Sci ; 25(13)2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-39000589

RÉSUMÉ

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.


Sujet(s)
Alanine , MAP Kinase Kinase 1 , Simulation de dynamique moléculaire , MAP Kinase Kinase 1/métabolisme , MAP Kinase Kinase 1/composition chimique , Alanine/analogues et dérivés , Alanine/composition chimique , Alanine/pharmacologie , Alanine/métabolisme , Humains , Domaine catalytique , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/composition chimique , Activation enzymatique/effets des médicaments et des substances chimiques , Benzimidazoles/pharmacologie , Benzimidazoles/composition chimique
16.
Sensors (Basel) ; 24(13)2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-39000931

RÉSUMÉ

Internet of Things (IoT) applications and resources are highly vulnerable to flood attacks, including Distributed Denial of Service (DDoS) attacks. These attacks overwhelm the targeted device with numerous network packets, making its resources inaccessible to authorized users. Such attacks may comprise attack references, attack types, sub-categories, host information, malicious scripts, etc. These details assist security professionals in identifying weaknesses, tailoring defense measures, and responding rapidly to possible threats, thereby improving the overall security posture of IoT devices. Developing an intelligent Intrusion Detection System (IDS) is highly complex due to its numerous network features. This study presents an improved IDS for IoT security that employs multimodal big data representation and transfer learning. First, the Packet Capture (PCAP) files are crawled to retrieve the necessary attacks and bytes. Second, Spark-based big data optimization algorithms handle huge volumes of data. Second, a transfer learning approach such as word2vec retrieves semantically-based observed features. Third, an algorithm is developed to convert network bytes into images, and texture features are extracted by configuring an attention-based Residual Network (ResNet). Finally, the trained text and texture features are combined and used as multimodal features to classify various attacks. The proposed method is thoroughly evaluated on three widely used IoT-based datasets: CIC-IoT 2022, CIC-IoT 2023, and Edge-IIoT. The proposed method achieves excellent classification performance, with an accuracy of 98.2%. In addition, we present a game theory-based process to validate the proposed approach formally.

17.
Fish Shellfish Immunol ; 152: 109764, 2024 Jul 14.
Article de Anglais | MEDLINE | ID: mdl-39002558

RÉSUMÉ

NF-κB (Nuclear factor-kappa B) family proteins are versatile transcription factors that play crucial regulatory roles in cell development, growth, apoptosis, inflammation, and immune response. However, there is limited research on the function of these key genes in echinoderms. In this study, an NF-κB family gene (SiRel) was identified in sea urchin Strongylocentrotus intermedius. The gene has an open reading frame length of 1809 bp and encodes for 602 amino acids. Domain prediction results revealed that the N-terminal of SiRel protein encodes a conserved Rel homology domain (RHD), including the RHD-DNA binding domain and the RHD-dimerization domain. Multiple sequence comparison results showed that the protein sequences of these two domains were conserved. Phylogenetic analysis indicated that SiRel clustered with Strongylocentrotus purpuratus p65 protein and Rel protein of other echinoderms. Results from quantitative real-time PCR demonstrated detectable SiRel mRNA expression in all tested sea urchin tissues, with the highest expression level found in the gills. And SiRel mRNA expression levels were significantly induced after LPS (Lipopolysaccharide) and poly(I:C) (Polyinosinic:polycytidylic acid) stimulation. In addition, SiRel protein expression can be found in cytoplasm and nucleus of HEK293T cells. Co-immunoprecipitation results showed that SiRel could interact with sea urchin IκB (Inhibitor of NF-κB) protein. Western blotting and dual-luciferase reporter gene assay results indicated that overexpression of SiRel in HEK293T cells could impact the phosphorylation levels of JNK (c-Jun N-terminal kinase) and Erk1/2 (Extracellular signal-regulated kinases1/2) and activate interleukin-6 (IL-6), activating protein 1 (AP-1), interferon (IFN)α/ß/γ, and signal transducer and activator of transcription 3 (STAT3) reporter genes in HEK293T cells. In conclusion, this study reveals that SiRel plays an important role in the innate immune response of sea urchins and enriches our understanding of comparative immunology theory.

18.
Adv Mater ; : e2402681, 2024 Jul 30.
Article de Anglais | MEDLINE | ID: mdl-39077938

RÉSUMÉ

Due to the unique "Grotthus mechanism", aqueous proton batteries (APBs) are promising energy devices with intrinsic safety and sustainability. Although polymers with tunable molecular structures are ideal electrode materials, their unsatisfactory proton-storage redox behaviors hinder the practical application in APB devices. Herein, a novel planar phenazine (PPHZ) polymer with a robust and extended imine-rich skeleton is synthesized and used for APB application for the first time. The long-range planar configuration achieves ordered molecular stacking and reduced conformational disorder, while the high conjugation with strong π-electron delocalization optimizes energy bandgap and electronic properties, enabling the polymer with low proton diffusion barriers, high redox activity, and superior electron affinity. As such, the PPHZ polymer as an electrode material exhibits fast, stable, and unrivaled proton-storage redox behaviors with a large capacity of 273.3 mAh g-1 at 0.5 A g-1 (1 C) in 1 M H2SO4 electrolyte, which is the highest value among proton-inserted electrodes in aqueous acidic electrolytes. Dynamic in situ techniques confirm the high redox reversibility upon proton uptake/removal, and the corresponding protonation pathways are elucidated by theoretical calculations. Moreover, a pouch-type APB cell using PPHZ electrode exhibits an ultralong lifespan over 30 000 cycles, further verifying its promising application prospect.

19.
Chin Med J (Engl) ; 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38973297

RÉSUMÉ

BACKGROUND: The global rise in diabetes prevalence is a pressing concern. Despite initiatives like "The Healthy Beijing Action 2020-2030" advocating for increased awareness, treatment, and control, the specific situation in Beijing remains unexplored. This study aimed to analyze the trends in diabetes prevalence, awareness, treatment, and control among Beijing adults. METHODS: Through a stratified multistage probability cluster sampling method, a series of representative cross-sectional surveys were conducted in Beijing from 2005 to 2022, targeting adults aged 18-79 years. A face-to-face questionnaire, along with body measurements and laboratory tests, were administered to 111,943 participants. Data from all survey were age- and/or gender-standardized based on the 2020 Beijing census population. Annual percentage rate change (APC) or average annual percentage rate change (AAPC) was calculated to determine prevalence trends over time. Complex sampling logistic regression models were employed to explore the relationship between various characteristics and diabetes. RESULTS: From 2005 to 2022, the total prevalence of diabetes among Beijing adults aged 18-79 years increased from 9.6% (95% CI: 8.8-10.4%) to 13.9% (95% CI: 13.1-14.7%), with an APC/AAPC of 2.1% (95% CI: 1.1-3.2%, P <0.05). Significant increases were observed among adults aged 18-39 years and rural residents. Undiagnosed diabetes rose from 3.5% (95% CI: 3.2-4.0%) to 7.2% (95% CI: 6.6-7.9%) with an APC/AAPC of 4.1% (95% CI: 0.5-7.3%, P <0.05). However, diabetes awareness and treatment rates showed annual declines of 1.4% (95% CI: -3.0% to -0.2%, P <0.05) and 1.3% (95% CI: -2.6% to -0.2%, P <0.05), respectively. The diabetes control rate decreased from 21.5% to 19.1%, although not statistically significant (APC/AAPC = -1.5%, 95% CI: -5.6% to 1.9%). Overweight and obesity were identified as risk factors for diabetes, with ORs of 1.65 (95% CI: 1.38-1.98) and 2.48 (95% CI: 2.07-2.99), respectively. CONCLUSIONS: The prevalence of diabetes in Beijing has significantly increased between 2005 and 2022, particularly among young adults and rural residents. Meanwhile, there has been a concerning decrease in diabetes awareness and treatment rates, while control rates have remained stagnant. Regular blood glucose testing, especially among adults aged 18-59 years, should be warranted. Furthermore, being male, elderly, overweight, or obese was associated with higher diabetes risk, suggesting the needs for targeted management strategies.

20.
Chem Sci ; 15(27): 10491-10498, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38994426

RÉSUMÉ

The development of novel near-infrared (NIR) materials with extremely small energy gaps and high stability is highly desirable in bioimaging and phototherapy. Here we report an effective strategy for narrowing the energy gaps of porphyrins by synergistic regulation of meso/ß substituents. The novel NIR absorbing/emitting meso-alkynyl naphthoporphyrins (Zn-TNP and Pt-TNP) are synthesized via the retro-Diels-Alder reaction. X-ray crystallography analysis confirms the highly distorted structures of the complexes. Both compounds exhibit intense Q bands around 800 nm, while Zn-TNP shows deep NIR fluorescence at 847 nm. Pt-TNP displays NIR-II room temperature phosphorescence peaking at 1106 nm with an extremely large Stokes shift of 314 nm, which are the longest wavelengths observed among the reported platinum porphyrinoids. Furthermore, Pt-TNP shows remarkable photostability and a notable capacity for synchronous singlet oxygen and heat generation under NIR light irradiation, demonstrating potential in combined photodynamic/photothermal therapy. A theoretical analysis reveals the progressive lifting of the HOMO by the ß-fused benzene ring, the decrease of the LUMO upon meso-alkynyl substitution, and energy-releasing pathways varying with metal ions. This dual regulation approach demonstrates great promise in designing innovative multifunctional NIR porphyrin materials.

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