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1.
Chem Sci ; 15(32): 13041-13048, 2024 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-39148785

RÉSUMÉ

Herein, a catalytic photoredox-neutral strategy for alkyne deuterocarboxylation with tetrabutylammonium oxalate as the carbonyl source and D2O as the deuteration agent was described. For the first time, the oxalic salt acted as both the reductant and carbonyl source through single electron transfer and subsequential homolysis of the C-C bond. The strongly reductive CO2 radical anion species in situ generated from oxalate played significant roles in realizing the global deuterocarboxylation of terminal and internal alkynes to access various tetra- and tri-deuterated aryl propionic acids with high yields and deuteration ratios.

2.
Heliyon ; 10(14): e34891, 2024 Jul 30.
Article de Anglais | MEDLINE | ID: mdl-39149002

RÉSUMÉ

Wind-blow sand (WBS) is widely distributed in the "Desert Gobi" region. This study is aimed at exploring the mechanism of how different thicknesses of the WBS layer influence the slope movement of external dumps in open-pit mines. To achieve this aim, the slope of the external dump in the open-pit mining area of Panel 3 in Daliuta Coal Mine was taken as the research object. First, similar simulation experiments were performed for investigating the failure modes and deformation characteristics of the external dump slopes under three geo-morphological conditions: loess base, 10-m-thick WBS base, and 20-m-thick WBS base, respectively. The following results were obtained from the experiments. For the slope with a loess base, its failure is mainly caused by circular sliding from the dump to the interior of the loess layer. For the slope with a 10-m-thick WBS base, the sliding mode involves circular sliding from the dump area to the interior of the WBS layer, linear sliding along the WBS base, and shearing along the foot of the dump area. For the slope with a 20-m-thick WBS base, the sliding mode is circular sliding from the dump area to the interior of the WBS layer. Besides, the sliding area of the dump slope expands as the WBS layer thickens. Furthermore, the results of similar simulation experiments were verified by the finite difference software FLAC3D based on the strength reduction method, and an equation of relationship between the safety factor of the dump slope with a WBS base and the thickness of the WBS layer was derived.

3.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39150548

RÉSUMÉ

The pulsed optically pumped (POP) atomic clock has demonstrated unexpected performance in terms of frequency stability and drift. However, it remains a huge challenge to make this type of atomic clock more compact. Herein, we report the design of a miniaturized physics package, which is equipped with a magnetron microwave cavity holding a vapor cell of 1.3 cm internal diameter. The Zeeman transition spectrum reveals that the microwave cavity resonates in TE011-like mode. Based on a low-noise testbed, we also quantitatively analyze the relaxation time, linewidth, and noise sources of the resulting POP atomic clock. The population and coherence relaxation time are measured to be 3.16(0.16) and 2.97(0.03) ms under the temperature of 333 K, which are compatible well with the theoretical calculation. The Ramsey signal shows a contrast of 35% and a linewidth of 192 Hz. The total volume of the physics package is about 44 cm3, including a layer of magnetic shielding. The short-term frequency stability is measured to be 4.8 × 10-13τ-1/2 (where τ is the averaging time), which is mainly limited by the relative intensity noise of the laser system.

4.
World J Hepatol ; 16(6): 966-972, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38948434

RÉSUMÉ

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.

5.
Trials ; 25(1): 377, 2024 Jun 11.
Article de Anglais | MEDLINE | ID: mdl-38863026

RÉSUMÉ

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. METHODS: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. DISCUSSION: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage. ETHICS AND DISSEMINATION: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.


Sujet(s)
Hydrogène , Oxygénothérapie , Oxygène , Essais contrôlés randomisés comme sujet , Hémorragie meningée , Humains , Hémorragie meningée/traitement médicamenteux , Études prospectives , Hydrogène/administration et posologie , Oxygénothérapie/effets indésirables , Oxygène/administration et posologie , Résultat thérapeutique , Facteurs temps , Adulte , Vasospasme intracrânien/prévention et contrôle , Vasospasme intracrânien/étiologie , Vasospasme intracrânien/traitement médicamenteux , Adulte d'âge moyen , Femelle , Mâle , Sujet âgé , Administration par inhalation , Encéphalopathie ischémique/prévention et contrôle , Encéphalopathie ischémique/traitement médicamenteux , Jeune adulte
6.
Imeta ; 3(2): e181, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38882496

RÉSUMÉ

Lactobacillus rhamnosus GG (LGG), the well-characterized human-derived probiotic strain, possesses excellent properties in the maintenance of intestinal homeostasis, immunoregulation and defense against gastrointestinal pathogens in mammals. Here, we demonstrate that the SpaC pilin of LGG causes intestinal epithelium injury by inducing cell pyroptosis and gut microbial dysbiosis in zebrafish. Dietary SpaC activates Caspase-3-GSDMEa pathways in the intestinal epithelium, promotes intestinal pyroptosis and increases lipopolysaccharide (LPS)-producing gut microbes in zebrafish. The increased LPS subsequently activates Gaspy2-GSDMEb pyroptosis pathway. Further analysis reveals the Caspase-3-GSDMEa pyroptosis is initiated by the species-specific recognition of SpaC by TLR4ba, which accounts for the species-specificity of the SpaC-inducing intestinal pyroptosis in zebrafish. The observed pyroptosis-driven gut injury and microbial dysbiosis by LGG in zebrafish suggest that host-specific beneficial/harmful mechanisms are critical safety issues when applying probiotics derived from other host species and need more attention.

7.
Micromachines (Basel) ; 15(6)2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38930730

RÉSUMÉ

The branch prediction units (BPUs) generally have security vulnerabilities, which can be used by attackers to tamper with the branches, and the existing protection methods cannot defend against these attacks. Therefore, this article proposes a hardware security protection method for conditional branches of embedded systems. This method calculates the number of branch target buffer (BTB) updates every 80 clock cycles. If the number exceeds the set threshold, the BTB will be locked and prevent any process from tampering with the BTB entries, thereby resisting branch prediction analysis (BPA) attacks. Moreover, to prevent attackers from stealing the critical information of branches, the method designs the hybrid arbiter physical unclonable function (APUF) circuit to encrypt and decrypt the directions, addresses, and indexes of branches. This circuit combines the advantages of double APUF and Feed-Forward APUF, which can enhance the randomness of output response and resist machine learning attacks. If attackers still successfully tamper with the branches and disrupt the control flow integrity (CFI), this method detects tampering with the instruction codes, jump addresses, and jump directions in a timely manner through dynamic and static label comparison. The proposed method is implemented and tested on FPGA. The experimental results show that this method can achieve fine-grained security protection for conditional branches, with about 5.4% resource overhead and less than 5.5% performance overhead.

8.
J Headache Pain ; 25(1): 72, 2024 May 07.
Article de Anglais | MEDLINE | ID: mdl-38714978

RÉSUMÉ

BACKGROUND: Due to the high mortality and disability rate of intracranial hemorrhage, headache is not the main focus of research on cerebral arteriovenous malformation (AVM), so research on headaches in AVM is still scarce, and the clinical understanding is shallow. This study aims to delineate the risk factors associated with headaches in AVM and to compare the effectiveness of various intervention treatments versus conservative treatment in alleviating headache symptoms. METHODS: This study conducted a retrospective analysis of AVMs who were treated in our institution from August 2011 to December 2021. Multivariable logistic regression analysis was employed to assess the risk factors for headaches in AVMs with unruptured, non-epileptic. Additionally, the effectiveness of different intervention treatments compared to conservative management in alleviating headaches was evaluated through propensity score matching (PSM). RESULTS: A total of 946 patients were included in the analysis of risk factors for headaches. Multivariate logistic regression analysis identified that female (OR 1.532, 95% CI 1.173-2.001, p = 0.002), supply artery dilatation (OR 1.423, 95% CI 1.082-1.872, p = 0.012), and occipital lobe (OR 1.785, 95% CI 1.307-2.439, p < 0.001) as independent risk factors for the occurrence of headaches. There were 443 AVMs with headache symptoms. After propensity score matching, the microsurgery group (OR 7.27, 95% CI 2.82-18.7 p < 0.001), stereotactic radiosurgery group(OR 9.46, 95% CI 2.26-39.6, p = 0.002), and multimodality treatment group (OR 8.34 95% CI 2.87-24.3, p < 0.001) demonstrate significant headache relief compared to the conservative group. However, there was no significant difference between the embolization group (OR 2.24 95% CI 0.88-5.69, p = 0.091) and the conservative group. CONCLUSIONS: This study identified potential risk factors for headaches in AVMs and found that microsurgery, stereotactic radiosurgery, and multimodal therapy had significant benefits in headache relief compared to conservative treatment. These findings provide important guidance for clinicians when developing treatment options that can help improve overall treatment outcomes and quality of life for patients.


Sujet(s)
Céphalée , Malformations artérioveineuses intracrâniennes , Humains , Femelle , Malformations artérioveineuses intracrâniennes/complications , Malformations artérioveineuses intracrâniennes/thérapie , Mâle , Céphalée/étiologie , Céphalée/thérapie , Adulte , Études rétrospectives , Facteurs de risque , Adulte d'âge moyen , Jeune adulte , Traitement conservateur/méthodes , Résultat thérapeutique , Embolisation thérapeutique/méthodes , Adolescent
9.
Sci Data ; 11(1): 519, 2024 May 22.
Article de Anglais | MEDLINE | ID: mdl-38778070

RÉSUMÉ

Endosymbionts regulate the behavior of pest species, which could provide insights into their control. The citrus leafminer (Phyllocnistis citrella Stainton) is a widely distributed pest associated with diseases of citrus, especially of young trees. Here, we determined the endosymbiont composition of P. citrella in citrus orchards across China. The resulting dataset comprised average 50,430 high-quality reads for bacterial 16S rRNA V3-V4 regions of endosymbionts from 36 P. citrella larvae sampled from 12 citrus orchards across China. The sequencing depth and sampling size of this dataset were sufficient to reveal most of the endosymbionts of P. citrella. In total, 2,875 bacterial amplicon sequence variants were obtained; taxonomic analysis revealed a total of 372 bacterial genera, most of which were Proteobacteria phylum with Undibacterium being the most abundant genus. This dataset provides the first evidence of P. citrella endosymbionts that could support the development of pest management approaches in citrus orchards.


Sujet(s)
Bactéries , Citrus , Papillons de nuit , Symbiose , Animaux , Bactéries/classification , Bactéries/génétique , Chine , Larve/microbiologie , Papillons de nuit/microbiologie , ARN ribosomique 16S/génétique
10.
Front Pharmacol ; 15: 1389271, 2024.
Article de Anglais | MEDLINE | ID: mdl-38783953

RÉSUMÉ

Aims: The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients. Methods: Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets. A PPK model was developed using the training group data. ML models were then established based on individual pharmacokinetic data derived from the PPK basic model. The prediction performances of the PPK-based ML model and Bayesian forecasting approach were compared using data from the test group. Results: The final PPK model, incorporating hematocrit and CYP3A5 genotypes as covariates, was successfully established. Individual predictions of TAC using the PPK basic model, postoperative date, CYP3A5 genotype, and hematocrit showed improved rankings in ML model construction. XGBoost, based on the TAC PPK, exhibited the best prediction performance. Conclusion: The PPK-based machine learning approach emerges as a superior option for predicting TAC concentrations in Chinese renal transplant recipients.

11.
Fish Shellfish Immunol ; 149: 109595, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38692381

RÉSUMÉ

This study aimed to elucidate the effects of dietary fermented products of Bacillus velezensis T23 on the growth, immune response and gut microbiota in Pacific white shrimp (Litopenaeus vannamei). Shrimp were fed with diets containing fermentation products of B. velezensis T23 at levels of (0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 g/kg) for 4 weeks, to assess the influence on shrimp growth. The results showed that 0.3 and 0.4 g/kg T23 supplementation improved shrimp growth and feed utilization. Based on these results we selected these three diets (Control, 0.3T23 and 0.4T23) to assess the effect on immune response and gut microbiota of shrimp. Compared with the control, the 0.3T23 and 0.4T23 groups enhanced lipase and α-amylase activities in the gut significantly. Moreover, the 0.4T23 group decreased TAG and MDA levels in hepatopancreas, ALT and AST levels of serum significantly (P < 0.05). In hepatopancreas, CAT and SOD activities were improved observably and the MDA content was reduced markedly in both T23 groups. The expressions of antimicrobial related genes, Cru and peroxinectin in the 0.3T23 group, and proPO and peroxinectin in the 0.4T23 group were up-regulated remarkably (P < 0.05). Moreover, hepatopancreas of shrimp fed with a diet amended with T23 showed a significant down-regulated expression of nf-kb and tnf-α genes, while expressions of tgf-ß was considerably up-regulated. Furthermore, serum LPS and LBP contents were reduced markedly in T23 groups. Intestinal SOD and CAT were noteworthy higher in T23 groups (P < 0.05). In the intestine of shrimp fed on the diet enriched with T23 the expression of nf-κb and tnf-α exhibited markedly down-regulated, whereas hif1α was up-regulated (P < 0.05). Besides, in the intestine of shrimp grouped under T23, Cru and peroxinectin genes were markedly up-regulated (P < 0.05). Dietary 0.3 g/kg T23 also upregulated the ratio of Rhodobacteraceae to Vibrionaceae in the gut of the shrimp. Taken together, the inclusion of B. velezensis T23 in the diet of shrimp enhanced the growth and feed utilization, enhanced hepatopancreas and intestine health.


Sujet(s)
Aliment pour animaux , Bacillus , Régime alimentaire , Hépatopancréas , Intestins , Penaeidae , Probiotiques , Animaux , Penaeidae/immunologie , Penaeidae/croissance et développement , Penaeidae/microbiologie , Aliment pour animaux/analyse , Régime alimentaire/médecine vétérinaire , Hépatopancréas/immunologie , Hépatopancréas/métabolisme , Probiotiques/administration et posologie , Probiotiques/pharmacologie , Compléments alimentaires/analyse , Fermentation , Répartition aléatoire , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Immunité innée , Relation dose-effet des médicaments
12.
J Environ Manage ; 360: 121090, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38772228

RÉSUMÉ

Microplastics (MPs) and antibiotic resistance genes (ARGs) are important pollutants in waste activated sludge (WAS), but their interactions during anaerobic digestion (AD) still need to be further explored. This study investigated variations in ARGs, mobile genetic elements (MGEs), and host bacteria during AD under the pressure of polyamide (PA), polyethylene (PE), and polypropylene (PP). The results showed that the MPs increased methane production by 11.7-35.5%, and decreased ARG abundance by 5.6-24.6%. Correlation analysis showed that the decrease of MGEs (plasmid, prophage, etc.) promoted the decrease of the abundance of multidrug, aminoglycoside and tetracycline resistance genes. Metagenomic annotation revealed that the reduction of key host bacteria (Arenimonas, Lautropia, etc.) reduced the abundance of major ARGs (rsmA, rpoB2, etc.). Moreover, PP MPs contributed to a reduction in the abundance of functional genes related to the production of reactive oxygen species, ATP synthesis, and cell membrane permeability, which was conducive to reducing the potential for horizontal gene transfer of ARGs. These findings provide insights into the treatment of organic waste containing MPs.


Sujet(s)
Résistance microbienne aux médicaments , Transfert horizontal de gène , Microplastiques , Eaux d'égout , Résistance microbienne aux médicaments/génétique , Anaérobiose , Eaux d'égout/microbiologie , Antibactériens/pharmacologie
13.
J Agric Food Chem ; 72(13): 7010-7020, 2024 Apr 03.
Article de Anglais | MEDLINE | ID: mdl-38529524

RÉSUMÉ

Cyetpyrafen is a recently developed acaricide. The citrus red mite, Panonychus citri (McGregor), has developed significant resistance to cyetpyrafen. However, the molecular mechanism underlying the cyetpyrafen resistance in P. citri remains unclear. Glutathione S-transferases (GSTs) play a critical role in arthropod pesticide resistance. This study showed that GSTs were potentially related to the resistance of P. citri to cyetpyrafen through synergistic experiments and enzyme activity analysis. An omega-family GST gene, PcGSTO1, was significantly up-regulated in the egg, nymph, and adult stages of the cyetpyrafen-resistant strain. Additionally, silencing of PcGSTO1 significantly increased the mortality of P. citri to cyetpyrafen and recombinant PcGSTO1 demonstrated the ability to metabolize cyetpyrafen. Our results indicated that the overexpression of PcGSTO1 is associated with cyetpyrafen resistance in P. citri, and they also provided valuable information for managing resistance in P. citri.


Sujet(s)
Acaricides , Tetranychidae , Animaux , Glutathione transferase/génétique , Glutathione transferase/métabolisme , Tetranychidae/génétique , Tetranychidae/métabolisme , Acaricides/pharmacologie , Acaricides/métabolisme
14.
World J Diabetes ; 15(2): 251-259, 2024 Feb 15.
Article de Anglais | MEDLINE | ID: mdl-38464369

RÉSUMÉ

BACKGROUND: Early screening and accurate staging of diabetic retinopathy (DR) can reduce blindness risk in type 2 diabetes patients. DR's complex pathogenesis involves many factors, making ophthalmologist screening alone insufficient for prevention and treatment. Often, endocrinologists are the first to see diabetic patients and thus should screen for retinopathy for early intervention. AIM: To explore the efficacy of non-mydriatic fundus photography (NMFP)-enhanced telemedicine in assessing DR and its various stages. METHODS: This retrospective study incorporated findings from an analysis of 93 diabetic patients, examining both NMFP-assisted telemedicine and fundus fluorescein angiography (FFA). It focused on assessing the concordance in DR detection between these two methodologies. Additionally, receiver operating characteristic (ROC) curves were generated to determine the optimal sensitivity and specificity of NMFP-assisted telemedicine, using FFA outcomes as the standard benchmark. RESULTS: In the context of DR diagnosis and staging, the kappa coefficients for NMFP-assisted telemedicine and FFA were recorded at 0.775 and 0.689 respectively, indicating substantial intermethod agreement. Moreover, the NMFP-assisted telemedicine's predictive accuracy for positive FFA outcomes, as denoted by the area under the ROC curve, was remarkably high at 0.955, within a confidence interval of 0.914 to 0.995 and a statistically significant P-value of less than 0.001. This predictive model exhibited a specificity of 100%, a sensitivity of 90.9%, and a Youden index of 0.909. CONCLUSION: NMFP-assisted telemedicine represents a pragmatic, objective, and precise modality for fundus examination, particularly applicable in the context of endocrinology inpatient care and primary healthcare settings for diabetic patients. Its implementation in these scenarios is of paramount significance, enhancing the clinical accuracy in the diagnosis and therapeutic management of DR. This methodology not only streamlines patient evaluation but also contributes substantially to the optimization of clinical outcomes in DR management.

15.
Plant Biotechnol J ; 22(8): 2113-2128, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38470397

RÉSUMÉ

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction.


Sujet(s)
Immunité des plantes , Transduction du signal , Récepteurs de reconnaissance de motifs moléculaires/métabolisme , Récepteurs de reconnaissance de motifs moléculaires/immunologie , Maladies des plantes/immunologie , Maladies des plantes/microbiologie , Plantes/immunologie , Plantes/métabolisme , Résistance à la maladie/immunologie
16.
Cancer Lett ; 588: 216747, 2024 Apr 28.
Article de Anglais | MEDLINE | ID: mdl-38403110

RÉSUMÉ

Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) have rapidly received Food and Drug Administration (FDA) approval as a new type of therapy for patients with advanced hormone receptor-positive breast cancer. However, with the widespread application of CDK4/6i, drug resistance has become a new challenge for clinical practice and has greatly limited the treatment effect. Here, the whole microenvironment landscape of ER+ breast cancer tumors was revealed through single-cell RNA sequencing, and a specific subset of cancer-associated fibroblasts (CD63+ CAFs) was identified as highly enriched in CDK4/6i resistant tumor tissues. Then, we found that CD63+ CAFs can distinctly promote resistance to CDK4/6i in breast cancer cells and tumor xenografts. In addition, it was discovered that miR-20 is markedly enriched in the CD63+ CAFs-derived exosomes, which are used to communicate with ER+ breast cancer cells, leading to CDK4/6i resistance. Furthermore, exosomal miR-20 could directly target the RB1 mRNA 3'UTR and negatively regulate RB1 expression to decrease CDK4/6i sensitivity in breast cancer cells. Most importantly, we designed and synthesized cRGD-miR-20 sponge nanoparticles and found that they can enhance the therapeutic effect of CDK4/6i in breast cancer. In summary, our findings reveal that CD63+ CAFs can promote CDK4/6i resistance via exosomal miR-20, which induces the downregulation of RB1 in breast cancer cells, and suggest that CD63+ CAFs may be a novel therapeutic target to enhance CDK4/6i sensitivity.


Sujet(s)
Tumeurs du sein , Fibroblastes associés au cancer , microARN , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/génétique , Tumeurs du sein/anatomopathologie , Fibroblastes associés au cancer/métabolisme , Kinase-4 cycline-dépendante , Prolifération cellulaire , microARN/métabolisme , Kinase-6 cycline-dépendante , Microenvironnement tumoral , Antigène CD63/métabolisme
17.
J Pathol ; 263(1): 99-112, 2024 05.
Article de Anglais | MEDLINE | ID: mdl-38411280

RÉSUMÉ

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.


Sujet(s)
Tumeurs de l'oesophage , Carcinome épidermoïde de l'oesophage , Humains , Carcinome épidermoïde de l'oesophage/métabolisme , Phosphorylation , Protein kinase D2 , Tumeurs de l'oesophage/anatomopathologie , Lignée cellulaire tumorale , Prolifération cellulaire/physiologie , Sérine , Mouvement cellulaire/physiologie , Régulation de l'expression des gènes tumoraux , Desmogléine-2/génétique , Desmogléine-2/métabolisme
18.
Sci Total Environ ; 919: 170832, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38346653

RÉSUMÉ

Biomass power plant with carbon capture facility has great carbon emission reduction potential due to biomass's carbon neutrality characteristic, but it has been long-time suffered from undesirable system efficiency. This paper explored the life cycle carbon emission of a high-efficient biomass power generation system, which was comprised by the semi-closed supercritical CO2 cycle and chemical looping air separation sub-units. This system was proved to be environmentally superior with the life cycle warming impact value at 97.69 kg CO2 eq./MWh, the life cycle carbon emission reduction rate was 49.61 % and 45.46 % compared with traditional biomass gasification combined cycle system and biomass chemical looping gasification combined cycle system, respectively. The fuel and materials preparation stage should receive improvement attention due to its largest emission share of 76 %. In addition, the effects of key parameters, such as CO2 to biomass ratio (CO2/C), biomass gasification temperature, oxygen carrier and biomass types on environmental performance were investigated to further reveal this system's carbon emission reduction potential. The biomass/coal co-fired system showed net zero carbon emission was achieved when biomass share exceeded only around 10 %.

19.
J Stroke Cerebrovasc Dis ; 33(4): 107579, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38325032

RÉSUMÉ

OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.


Sujet(s)
Encéphalopathie ischémique , Hémorragie meningée , Humains , Hémorragie meningée/complications , Hémorragie meningée/diagnostic , Études rétrospectives , Chlorures , Infarctus cérébral/étiologie , Infarctus cérébral/complications , Encéphalopathie ischémique/diagnostic , Encéphalopathie ischémique/étiologie
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