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2.
Mater Horiz ; 2024 Sep 23.
Article de Anglais | MEDLINE | ID: mdl-39311412

RÉSUMÉ

Dielectric capacitors are pivotal elements in advanced pulsed power devices and high-voltage, high-capacity power electronic converters, crucial for efficient energy storage. However, a major challenge remains the significant reduction in energy density and charge-discharged efficiency of dielectric polymers under high temperatures, primarily due to heightened electrical conduction losses. This study introduces a universal approach of heterojunction interface engineering in polyethersulfone (PESU) composites, aimed at improving capacitive performance across a broad temperature range. The introduction of one-dimensional heterojunction BaTiO3@Al2O3 nanofibers with large aspect ratios could enhance both the dielectric constant (εr) and breakdown strength (Eb). Specifically, the creation of hierarchical interfaces increases the trap density and energy levels for mobile charges, effectively reducing conduction losses and improving Eb under high-temperature conditions. Consequently, the PESU-3 vol% BaTiO3@Al2O3 nanocomposite achieves an excellent energy density of 7.3 J cm-3 with over 90% retention at 150 °C and 550 MV m-1. Finite element simulations further confirm that the heterojunction structure of BaTiO3@Al2O3 nanofibers effectively inhibits the growth of breakdown paths. This work demonstrates that hierarchical interface engineering offers a powerful strategy to enhance capacitive performance in dielectric polymer composites under harsh conditions.

3.
Cell Rep ; 43(9): 114731, 2024 Sep 12.
Article de Anglais | MEDLINE | ID: mdl-39269901

RÉSUMÉ

The Arabidopsis thaliana aluminum-activated malate transporter 9 (AtALMT9) functions as a vacuolar chloride channel that regulates the stomatal aperture. Here, we present the cryoelectron microscopy (cryo-EM) structures of AtALMT9 in three distinct states. AtALMT9 forms a dimer, and the pore is lined with four positively charged rings. The apo-AtALMT9 state shows a putative endogenous citrate obstructing the pore, where two W120 constriction residues enclose a gate with a pore radius of approximately 1.8 Å, representing an open state. Interestingly, channel closure is solely controlled by W120. Compared to wild-type plants, the W120A mutant exhibits more sensitivity to drought stress and is unable to restore the visual phenotype on leaves upon water recovery, reflecting persistent stomatal opening. Furthermore, notable variations are noted in channel gating and substrate recognition of Glycine max ALMT12, AtALMT9, and AtALMT1. In summary, our investigation enhances comprehension of the interplay between structure and function within the ALMT family.

6.
Langmuir ; 40(37): 19689-19700, 2024 Sep 17.
Article de Anglais | MEDLINE | ID: mdl-39235286

RÉSUMÉ

Matrine (MT) is a kind of alkaloid extracted from Sophora and is a promising substitute for chemical nematicides and botanical pesticides. The present study utilized sodium alginate (SA), zeolite imidazole salt skeleton (ZIF), and MT as raw materials to prepare a pH-response-release nematicide through the electrostatic spray technique. Zinc metal-organic framework (ZIF-8) was initially synthesized, followed by the successful loading of MT. Subsequently, the electrostatic spray process was employed to encapsulate it in SA, resulting in the formation of MT/ZIF-8@SA microcapsules. The efficiency of encapsulation and drug loadings can reach 79.93 and 26.83%, respectively. Soybean cyst nematode (SCN) is one of the important pests that harm crops; acetic acid produced by plant roots and CO2 produced by root respiration causing a decrease in the pH of the surrounding environment, which is most attractive to the SCN when the pH is between 4.5 and 5.4. MT/ZIF-8@SA releases the loaded MT in response to acetic acid produced by roots and acidic oxides produced by root respiration. The rate of release was 37.67% higher at pH 5.25 compared with pH 8.60. The control efficiency can reach 89.08% under greenhouse conditions. The above results demonstrate that the prepared MT/ZIF-8@SA not only exhibited excellent efficacy but also demonstrated a pH-responsive release of the nematicide.


Sujet(s)
Alginates , Alcaloïdes , Capsules , Glycine max , , Quinolizines , Électricité statique , Alginates/composition chimique , Alcaloïdes/composition chimique , Alcaloïdes/pharmacologie , Animaux , Concentration en ions d'hydrogène , Quinolizines/composition chimique , Glycine max/composition chimique , Glycine max/parasitologie , Capsules/composition chimique , Réseaux organométalliques/composition chimique , Réseaux organométalliques/pharmacologie , Antihelminthiques antinématodes/composition chimique , Antihelminthiques antinématodes/pharmacologie , Nematoda/effets des médicaments et des substances chimiques , Libération de médicament , Acide glucuronique/composition chimique , Acides hexuroniques/composition chimique
7.
Small ; : e2405786, 2024 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-39291954

RÉSUMÉ

Multilayer-structured nanocomposites are recognized as a prominent strategy for overcoming the paradox between the breakdown strength (Eb) and polarization (P) to achieve superior energy storage performance. However, current multilayer-structured nanocomposites involving substantial quantities of nanofillers (>10 vol.%) for high dielectric constant as polarization layer will inevitably deteriorate mechanical properties and breakdown strength. Herein, an innovative approach is reported to breaking conventional rules by designing a multilayered polymer composite with ultralow loading of Al2O3 nanoparticles, i.e., 0.3 vol.% for polarization layers and 2 vol.% for insulation layers. By modulating the spatial distribution of Al2O3 nanoparticles in polymer, a significantly increased interfacial dipole response is induced, and deep interfacial traps are constructed to capture the mobile charges, thereby suppressing high-temperature conduction loss. The resulting multilayered polymer composite exhibits an unparalleled discharged energy density of 7.8 J cm-3 with a charging/discharging efficiency exceeding 90% at 150 °C. This work provides valuable insights into achieving superior capacitive performance in multilayer composite films operating under extreme conditions.

8.
Inorg Chem ; 63(36): 16676-16687, 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39198180

RÉSUMÉ

To address the unsatisfactory photodegradation capacities of photocatalysts, Er3+/Yb3+-codoped Bi2WO6 (Bi2WO6:Er3+/xYb3+) nanoparticles (NPs) with polychromatic upconversion (UC) emission and boosted visible-light-triggered photocatalytic abilities were designed. First-principles density functional theory was employed to study the impact of Er3+ and Yb3+ codoping on the electronic structure of Bi2WO6. Upon 980 nm excitation, the resultant NPs emitted polychromatic UC emissions caused by energy back transfer from Er3+ to Yb3+. Moreover, the involved UC emission mechanism was clarified through examining the pump power related to UC emission spectra. By investigating the visible-light-induced tetracycline (TC) decomposition, the photocatalytic activities of developed NPs were explored, where Bi2WO6:Er3+/0.07Yb3+ NP can degrade 81.76% of TC within 30 min, with a k value of 0.0552 min-1. Both the theoretical calculation and trapping results reveal that the •O2-, h+, and •OH were formed during the pollutant removal process. Additionally, the toxic TC can be photodegraded to nontoxic products via the synthesized photocatalysts, leading to wastewater purification. These achievements manifest that Bi2WO6:Er3+/xYb3+ NPs are promising visible-light-triggered photocatalysts to degrade pollutants, and our findings also propose a facile approach to regulate the photocatalytic activities of photocatalysts via utilizing doping and UC emission strategies.

9.
Arthroscopy ; 2024 Aug 10.
Article de Anglais | MEDLINE | ID: mdl-39128679

RÉSUMÉ

PURPOSE: To enhance the understanding of histologic healing after repairing medial meniscal posterior root tears (MMPRTs) at an early stage, utilizing a goat model. METHODS: Eighteen adult goats, totaling 36 knee joints, were allocated into 3 groups (n = 12): sham group (Sham), root tear group (RT), and root tear with transosseous suture group (RTS). At 12- and 24-week intervals postsurgery, all the knees were harvested for imaging, macroscopic, histologic, and biomechanical assessments. RESULTS: The intact root served as a meniscus-bone interface that connected the tibial and circular fibers of the meniscus with a bony insertion and a root-meniscus transition. A direct fibrous connection was displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs 0.19 ± 0.02, P = .0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = .0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions. CONCLUSIONS: The incomplete healing may be attributed to the histologic factors underlying the low healing rate and persistent medial meniscal extrusion. Notably, the region attached to the posterior cruciate ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process. CLINICAL RELEVANCE: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to enhance the healing of the root-meniscus transition.

10.
Front Cell Dev Biol ; 12: 1391873, 2024.
Article de Anglais | MEDLINE | ID: mdl-39170916

RÉSUMÉ

Background: Prion protein gene (PRNP) is widely expressed in a variety of tissues. Although the roles of PRNP in several cancers have been investigated, no pan-cancer analysis has revealed its relationship with tumorigenesis and immunity. Methods: Comprehensive analyses were conducted on The Cancer Genome Atlas (TCGA) Pan-Cancer dataset from the University of California Santa Cruz (UCSC) database to determine the expression of PRNP and its potential prognostic implications. Immune infiltration and enrichment analysis methods were used to ascertain correlations between PRNP expression levels, tumor immunity, and immunotherapy. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were employed to examine possible signaling pathways involving PRNP. In vitro experiments using CCK-8 assay, Wound healing assay, and Transwell assay to detect the effect of Cellular prion protein (PrPC) on proliferation, migration, and invasion in colorectal cancer (CRC) cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, E-cadherin, Vimentin and Snail) were detected by western blot. Results: Among most cancer types, PRNP is expressed at high levels, which is linked to the prognosis of patients. PRNP expression is strongly associated with immune infiltrating cells, immunosuppressive cell infiltration and immune checkpoint molecules. In addition to tumor mutation burden (TMB), substantial correlations are detected between PRNP expression and microsatellite instability (MSI) in several cancers. In vitro cell studies inferred that PrPC enhanced the proliferation, migration, invasion, and EMT of CRC cells. Conclusion: PRNP serves as an immune-related prognostic marker that holds promise for predicting outcomes related to CRC immunotherapy while simultaneously promoting cell proliferation, migration, and invasion activities. Furthermore, it potentially plays a role in governing EMT regulation within CRC.

11.
Zhonghua Nan Ke Xue ; 30(2): 180-183, 2024 Feb.
Article de Chinois | MEDLINE | ID: mdl-39177354

RÉSUMÉ

Pyroptosis, as a new programmed death mode, plays an important role in the development and progression of prostate cancer, and the drugs targeting the pyroptosis pathway, as a new therapeutic strategy, may produce a significant influence on the treatment of prostate cancer . However, the precise mechanism of cellular pyroptosis remains unclear, necessitating further investigation. This paper presents a summary of the role of cellular pyroptosis in prostate cancer over recent years. It includes a discussion of the mechanism of pyroptosis, its role in prostate cancer development, and its clinical applications. This will provide clinicians with a new strategy for treatment and drug development.


Sujet(s)
Évolution de la maladie , Tumeurs de la prostate , Pyroptose , Humains , Tumeurs de la prostate/anatomopathologie , Mâle
12.
Front Endocrinol (Lausanne) ; 15: 1387845, 2024.
Article de Anglais | MEDLINE | ID: mdl-39157680

RÉSUMÉ

Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.


Sujet(s)
, Coagulation sanguine , Hormones thyroïdiennes , Humains , Mâle , Femelle , Pronostic , Études rétrospectives , Adulte d'âge moyen , Hormones thyroïdiennes/sang , Coagulation sanguine/physiologie , /sang , /physiopathologie , Rein/physiopathologie , Sujet âgé , Marqueurs biologiques/sang , Mortalité hospitalière , Adulte , Maladie aigüe
13.
Arch Med Res ; 56(1): 103072, 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39208548

RÉSUMÉ

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs. METHODS: RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs. RESULTS: 1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response. DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p < 0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis. CONCLUSIONS: This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.

14.
Transl Cancer Res ; 13(6): 2721-2734, 2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-38988914

RÉSUMÉ

Background: Breast cancer (BC) has the highest incidence rate among female malignant tumors. Adjuvant chemotherapy is commonly used to reduce micrometastasis in postoperative patients. However, monitoring the efficacy of chemotherapy in BC is a major challenge in clinical practice. In this study, 1H nuclear magnetic resonance (NMR) metabonomics was performed to explore the serum metabolic characteristics of BC patients before and after adjuvant chemotherapy. Methods: In this study, we collected serum samples from 51 healthy controls and 61 BC patients before and after chemotherapy for 1H NMR metabolomic analysis, and tested the performance of each metabolite and combination segment by the receiver operating characteristic (ROC) curves. Results: Nine metabolites, namely glutamine, citrate, creatine, glycerophosphatidylcholine/phosphatidylcholine, glycine, 1-methylhistidine, lactate, pyruvate and formate had significant changes in BC patients before chemotherapy compared with healthy controls. Lactate, pyruvate, 1-methylhistidine and formate were found to be inversely regulated by chemotherapy. ROC analysis showed that a combination of the four metabolites had good prediction for chemotherapy efficacy with area under the curve of 0.958, sensitivity of 98.36% and specificity of 91.30%. There was no significant correlation between chemotherapy-related metabolites and clinical indicators of cancer patients, indicating that they can be used to evaluate the chemotherapy efficacy of patients with different clinical indicators. Conclusions: Effectively, dynamic and non-invasive metabolic markers for the evaluation of the efficacy of chemotherapy were identified in this study.

15.
Angew Chem Int Ed Engl ; : e202410392, 2024 Jul 30.
Article de Anglais | MEDLINE | ID: mdl-39078407

RÉSUMÉ

The poor electrochemical stability window and low ionic conductivity in solid-state electrolytes hinder the development of safe, high-voltage, and energy-dense lithium metal batteries. Herein, taking advantage of the unique electronic effect of nitrile groups, we designed a novel azanide-based single-ion covalent organic framework (CN-iCOF) structure that possesses effective Li+ transport and high-voltage stability in lithium metal batteries. Density functional theory (DFT) calculations and molecular dynamics (MD) revealed that electron-withdrawing nitrile groups not only resulted in an ultralow HOMO energy orbital but also enhanced Li+ dissociation through charge delocalization, leading to a high tLi+ of 0.93 and remarkable oxidative stability up to 5.6 V (vs. Li+/Li) simultaneously. Moreover, cyanation leveraging Strecker reaction transformed reversible imine-linkage to a stable sp3-carbon-containing azanide anion, which facilitated contorted alignment of transport "ladders" along the one-dimensional anionic channels and the ionic conductivity could reach 1.33 × 10-5 S cm-1 at ambient temperature without any additives. As a result, CN-iCOF allowed operation of solid-state lithium metal batteries with high-voltage cathodes such as LiNi0.8Mn0.1Co0.1O2 (NCM811), demonstrating stable lithium deposition up to 1,100 h and reversible battery cycling at ambient temperature up to 4.5 V, shedding light on the importance of discovering new functionality for forthcoming high-performance batteries.

16.
Huan Jing Ke Xue ; 45(6): 3661-3670, 2024 Jun 08.
Article de Chinois | MEDLINE | ID: mdl-38897785

RÉSUMÉ

The impact of microplastics (MPs) as a new type of pollutant on water pollution has become a research hotspot. To explore the response relationship between the abundance of MPs and nitrogen metabolism function in a freshwater environment, Lake Ulansuhai was used as the research object; the abundance of MPs in the water was detected using a Zeiss microscope, and the distribution characteristics of nitrogen metabolism functional bacteria and functional genes in the water were analyzed using metagenomics sequencing. The correlation analysis method was used to explore the relationship between the abundance of MPs and nitrogen metabolism functional microorganisms and nitrogen metabolism functional genes. The results showed that the presence of MPs in freshwater environments had a higher impact on Cyanobacteria and Firmicutes as the dominant phyla, and the presence of MPs promoted their enrichment and growth. Among the dominant bacterial genera, MPs promoted the growth of Mycobacterium and inhibited Candidatus_Planktopila more significantly, further indicating that in freshwater environments, MPs affected normal nitrogen metabolism by affecting microbial communities, and pathways such as carbon and nitrogen fixation and denitrification were important pathways for MPs to affect nitrogen metabolism. From the perspective of nitrogen metabolism functional genes, it was found that the abundance of MPs significantly affected some functional genes during nitrification (pmoA-amoA, pmoB-amoB, and pmoC-amoC), denitrification (nirK and napA), and dissimilatory nitrate reduction (nrfA) processes (P < 0.05). Moreover, the influence of MPs abundance on different functional genes in the same pathway of nitrogen metabolism varied, making the impact of MPs on aquatic environments very complex; thus, its harm to the water environment cannot be underestimated.


Sujet(s)
Bactéries , Microplastiques , Azote , Polluants chimiques de l'eau , Azote/métabolisme , Polluants chimiques de l'eau/métabolisme , Bactéries/métabolisme , Bactéries/génétique , Bactéries/classification , Microbiologie de l'eau , Cyanobactéries/métabolisme , Cyanobactéries/génétique , Lacs/microbiologie , Chine , Eau douce , Surveillance de l'environnement
17.
ACS Appl Mater Interfaces ; 16(24): 31709-31718, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38836706

RÉSUMÉ

Air-processed perovskite solar cells (PSCs) with high photoelectric conversion efficiency (PCE) can not only further reduce the production cost but also promote its industrialization. During the preparation of the PSCs in ambient air, the contact of the buried interface not only affects the crystallization of the perovskite film but also affects the interface carrier transport, which is directly related to the performance of the device. Here, we optimize the buried interface by introducing 3-mercaptopropyltrimethoxysilane (MPTMS, (CH3O)3Si(CH2)3SH) on the nickel oxide (NiOx) surface. The crystallization of the perovskite film is improved by enhancing surface hydrophobicity; besides, the SH-based functional group of MPTMS passivates the uncoordinated lead at the interface, which effectively reduces the defects at the bottom interface of perovskite and inhibits the nonradiative recombination at the interface. Moreover, the energy level between the NiOx layer and the perovskite layer is better matched. Based on multiple functions of MPTMS modification, the open circuit voltage of the device is obviously improved, and efficient air-processed methylamine-free (MA-free) PSCs are realized with PCE reaching 21.0%. The device still maintains the initial PCE of 85% after 1000 h aging in the glovebox. This work highlights interface modification in air-processed MA-free PSCs to promote the industrialization of PSCs.

18.
Front Microbiol ; 15: 1390331, 2024.
Article de Anglais | MEDLINE | ID: mdl-38841064

RÉSUMÉ

This study investigated the effect of nitrogen application on the rhizosphere soil microenvironment of sunflower and clarified the relationship between ammonium assimilation and the microenvironment. In a field experiment high (HN, 190 kg/hm2), medium (MN, 120 kg/hm2) and low nitrogen (CK, 50 kg/hm2) treatments were made to replicate plots of sunflowers using drip irrigation. Metagenomic sequencing was used to analyze the community structure and functional genes involved in the ammonium assimilation pathway in rhizosphere soil. The findings indicated that glnA and gltB played a crucial role in the ammonium assimilation pathway in sunflower rhizosphere soil, with Actinobacteria and Proteobacteria being the primary contributors. Compared with CK treatment, the relative abundance of Actinobacteria increased by 15.57% under MN treatment, while the relative abundance decreased at flowering and maturation stages. Conversely, the relative abundance of Proteobacteria was 28.57 and 61.26% higher in the MN treatment during anthesis and maturation period, respectively, compared with the CK. Furthermore, during the bud stage and anthesis, the abundance of Actinobacteria, Proteobacteria, and their dominant species were influenced mainly by rhizosphere soil EC, ammonium nitrogen (NH4+-N), and nitrate nitrogen (NO3--N), whereas, at maturity, soil pH and NO3--N played a more significant role in shaping the community of ammonium-assimilating microorganisms. The MN treatment increased the root length density, surface area density, and root volume density of sunflower at the bud, flowering, and maturity stages compared to the CK. Moreover, root exudates such as oxalate and malate were positively correlated with the dominant species of Actinobacteria and Proteobacteria during anthesis and the maturation period. Under drip irrigation, applying 120 kg/hm2 of nitrogen to sunflowers effectively promoted the community structure of ammonium-assimilating microorganisms in rhizosphere soil and had a positive influence on the rhizosphere soil microenvironment and sunflower root growth.

19.
Sci Rep ; 14(1): 13432, 2024 06 11.
Article de Anglais | MEDLINE | ID: mdl-38862586

RÉSUMÉ

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.


Sujet(s)
Tumeurs du sein , Cyclophosphamide , Lymphocytes T régulateurs , Humains , Cyclophosphamide/administration et posologie , Cyclophosphamide/usage thérapeutique , Lymphocytes T régulateurs/immunologie , Lymphocytes T régulateurs/effets des médicaments et des substances chimiques , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/immunologie , Tumeurs du sein/mortalité , Sujet âgé , Études rétrospectives , Administration par voie orale , Adulte d'âge moyen , Sujet âgé de 80 ans ou plus , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Métastase tumorale , Résultat thérapeutique
20.
Regen Biomater ; 11: rbae050, 2024.
Article de Anglais | MEDLINE | ID: mdl-38872841

RÉSUMÉ

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

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