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1.
Angew Chem Int Ed Engl ; : e202414712, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226119

RESUMO

The asymmetric rearrangement of allylic sulfilimines is an effective route to synthetic attractive targets such as allylic sulfenamides and others. The current methods are limited to chirality transfer from chiral allylic sulfilimine precursors. Herein, we report a general and fundamentally new rearrangement route accessing optically enriched allylic sulfenamides and their derivatives. The process involves a S-alkylation and an unusual S-to-N rearrangement step. The chiral nickel complex enables the transformation of a broad scope of sulfenamides and vinyl α-diazo pyrazoleamides under mild conditions. Various allylic sulfenamides have been synthesized with excellent γ-regioselectivity and enantioselectivity, which can be efficiently converted to sulfinamide and 4-aminobutenoic acid derivatives. In addition, DFT calculations demonstrate the connection between the spin state and conformation of nickel vinyl carbenoid, as well as an unknown rearrangement process.

2.
J Am Chem Soc ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223083

RESUMO

Our knowledge about endohedral metallofullerenes (EMFs) is restricted to the structures with sufficient kinetic stability to be extracted from the arc-discharge soot and processed by chromatographic and structural techniques. For the most abundant rare-earth monometallofullerene MIII@C82, experimental studies repeatedly demonstrated C2v(9) and Cs(6) carbon cage isomers, while computations predicted equal stability of the "missing" C3v(8) isomer. Here we report that this isomer is indeed formed but has not been recovered from soot using standard protocols. Using a combination of redox extraction and subsequent benzylation and trifluoromethylation with single-crystal XRD analysis of CF3 adduct, we prove that Dy@C3v(8)-C82 is one of the most abundantly produced metallofullerenes, which was not identified in earlier studies because of the low kinetic stability. Further, using the Dy@C3v(8)-C82(CF3) and Dy@C3v(8)-C82(CH2Ph) monoadducts for the case study, we analyzed the role of metal-fullerene bonding on the single-ion magnetic anisotropy of Dy in EMFs. The multitechnique approach, combining ab initio calculations, EPR spectroscopy, and SQUID magnetometry, demonstrated that coordination of the Dy ion to the fullerene cage induces moderate, nonaxial, and very fluid magnetic anisotropy, which strongly varies with small alterations in the Dy-fullerene coordination geometry. As a result, Dy@C3v(8)-C82(CH2Ph) is a weak field-induced single-molecule magnet (SMM), whose signatures of magnetic relaxation are detectable only below 3 K. Our results demonstrate that metal-cage interactions should have a detrimental effect on the SMM performance of EMFs. At the same time, the strong variability of the magnetic anisotropy with metal position suggests tunability and offers strategies for future progress.

3.
Nanoscale ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225229

RESUMO

Theoretically determining the lowest-energy structure of a cluster has been a persistent challenge due to the inherent difficulty in accurate description of its potential energy surface (PES) and the exponentially increasing number of local minima on the PES with the cluster size. In this work, density-functional theory (DFT) calculations of Co clusters were performed to construct a dataset for training deep neural networks to deduce a deep potential (DP) model with near-DFT accuracy while significantly reducing computational consumption comparable to classic empirical potentials. Leveraging the DP model, a high-efficiency hybrid differential evolution (HDE) algorithm was employed to search for the lowest-energy structures of CoN (N = 11-50) clusters. Our results revealed 38 of these clusters superior to those recorded in the Cambridge Cluster Database and identified diverse architectures of the clusters, evolving from layered structures for N = 11-27 to Marks decahedron-like structures for N = 28-42 and to icosahedron-like structures for N = 43-50. Subsequent analyses of the atomic arrangement, structural similarity, and growth pattern further verified their hierarchical structures. Meanwhile, several highly stable clusters, i.e., Co13, Co19, Co22, Co39, and Co43, were discovered by the energetic analyses. Furthermore, the magnetic stability of the clusters was verified, and a competition between the coordination number and bond length in affecting the magnetic moment was observed. Our study provides high-accuracy and high-efficiency prediction of the optimal structures of clusters and sheds light on the growth trend of Co clusters containing tens of atoms, contributing to advancing the global optimization algorithms for effective determination of cluster structures.

4.
Adv Sci (Weinh) ; : e2405729, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225346

RESUMO

The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al) or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS-H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen-specific T cells. MANS-H demonstrates even greater effectiveness in the production of antigen-specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS-H evokes high frequencies of antigen-specific Th1 and CD8+ cell immunity, which are comparable with Quil-A that is widely used in veterinary vaccines. Immunized mice with MANS-H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.

5.
J Neurooncol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225955

RESUMO

OBJECTIVE: This study aimed to develop a predictive model for cerebellar mutism syndrome (CMS) in pediatric patients with posterior fossa tumors, integrating lesion-symptom mapping (LSM) data with clinical factors, and to assess the model's performance. METHODS: A cohort of pediatric patients diagnosed with posterior fossa tumors and undergoing surgery at Beijing Children's Hospital from July 2013 to December 2023 was analyzed. Clinical variables gender, age at surgery, tumor characteristics, hydrocephalus, surgical route and pathology were collected. LSM was used to link tumor locations with CMS outcomes. Lasso regression and logistic regression were employed for feature selection and model construction, respectively. Model performance was assessed using area under the curve (AUC) and accuracy metrics. RESULTS: The study included 197 patients in total, with CMS rates consistent across training, validation, and prospective groups. Significant associations were found between CMS and gender, tumor type, hydrocephalus, paraventricular edema, surgical route, and pathology. A predictive model combining voxel location data from LSM with clinical factors achieved high predictive performance (C-index: training 0.956, validation 0.933, prospective 0.892). Gender, pathology, and voxel location were identified as key predictors for CMS. CONCLUSION: The study established an effective predictive model for CMS in pediatric posterior fossa tumor patients, leveraging LSM data and clinical factors. The model's accuracy and robustness suggest its potential utility in clinical practice for early CMS risk assessment and intervention planning.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39230249

RESUMO

Porous spindle-knot structures have been found in many creatures, such as spider silk and the root of the soybean plant, which show interesting functions such as droplet collection or biotransformation. However, continuous fabrication of precisely controlled porous spindle-knots presents a big challenge, particularly in striking a balance among good structural controllability, low-cost, and functions. Here, we propose a concept of a fiber-microfluidics phase separation (FMF-PS) strategy to address the above challenge. This FMF-PS combines the advantages of a microchannel regulated Rayleigh instability of polymer solution coated onto a fiber with the nonsolvent-induced phase separation of the polymer solution, which enables continuous and cost-effective production of porous spindle-knot fiber (PSKF) with well-controlled size and porous structures. The critical factors controlling the geometry and the porous structures of the spindle-knot by FMF-PS have been systematically investigated. For applications, the PSKF exhibited faster water droplet nucleation, growth, and maximum water collection capability, compared to the control samples, as revealed by in situ water collection growth curves. Furthermore, high-level fabrics of the PSKFs, including a two-dimensional network and three-dimensional architecture, have been demonstrated for both large-scale water collection and art performance. Finally, the PSKF is demonstrated as a programmable building block for surface nanopatterning.

7.
Plant Cell Environ ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248548

RESUMO

The freezing temperature greatly limits the growth, development and productivity of plants. The C-repeat/DRE binding factor (CBF) plays a major role in cold acclimation, enabling plants to increase their freezing tolerance. Notably, the INDUCER OF CBF EXPRESSION1 (ICE1) protein has garnered attention for its pivotal role in bolstering plants' resilience against freezing through transcriptional upregulation of DREB1A/CBF3. However, the research on the interaction between ICE1 and other transcription factors and its function in regulating cold stress tolerance is largely inadequate. In this study, we found that a R2R3 MYB transcription factor CDC5 interacts with ICE1 and regulates the expression of CBF3 by recruiting RNA polymerase II, overexpression of ICE1 can complements the freezing deficient phenotype of cdc5 mutant. CDC5 increases the expression of CBF3 in response to freezing. Furthermore, CDC5 influences the expression of CBF3 by altering the chromatin status through H3K4me3 and H3K27me3 modifications. Our work identified a novel component that regulates CBF3 transcription in both ICE1-dependent and ICE1-independent manner, improving the understanding of the freezing signal transduction in plants.

8.
Stat Med ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248697

RESUMO

Clustering functional data aims to identify unique functional patterns in the entire domain, but this can be challenging due to phase variability that distorts the observed patterns. Curve registration can be used to remove this variability, but determining the appropriate level of warping flexibility can be complicated. Curve registration also requires a target to which a functional object is aligned, typically the cross-sectional mean of functional objects within the same cluster. However, this mean is unknown prior to clustering. Furthermore, there is a trade-off between flexible warping and the number of resulting clusters. Removing more phase variability through curve registration can lead to fewer remaining variations in the functional data, resulting in a smaller number of clusters. Thus, the optimal number of clusters and warping flexibility cannot be uniquely identified. We propose to use external information to solve the identification issue. We define a cross validated Kullback-Leibler information criterion to select the number of clusters and the warping penalty. The criterion is derived from the predictive classification likelihood considering the joint distribution of both the functional data and external variable and penalizes the uncertainty in the cluster membership. We evaluate our method through simulation and apply it to electrocardiographic data collected in the Chronic Renal Insufficiency Cohort study. We identify two distinct clusters of electrocardiogram (ECG) profiles, with the second cluster exhibiting ST segment depression, an indication of cardiac ischemia, compared to the normal ECG profiles in the first cluster.

9.
bioRxiv ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39229160

RESUMO

Extracellular vesicles (EVs) are heterogenous in size, biogenesis, cargo and function. Beside small EVs, aggressive tumor cells release a population of particularly large EVs, namely large oncosomes (LO). This study provides the first resource of label-free quantitative proteomics of LO and small EVs obtained from distinct cancer cell types (prostate, breast, and glioma). This dataset was integrated with a SWATH Proteomic assay on LO, rigorously isolated from the plasma of patients with metastatic prostate cancer (PC). Proteins enriched in LO, which were identified also at the RNA level, and found in plasma LO significantly correlated with PC progression. Single EV RNA-Seq of the PC cell-derived LO confirmed some of the main findings from the bulk RNA-Seq, providing first evidence that single cell technologies can be successfully applied to EVs. This multiomics resource of cancer EVs can be leveraged for developing a multi-analyte approach for liquid biopsy.

10.
Heliyon ; 10(16): e35528, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39229502

RESUMO

Rationale and objectives: We constructed a dual-energy computed tomography (DECT)-based model to assess cervical lymph node metastasis (LNM) in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods: We retrospectively analysed 164 patients with LSCC who underwent preoperative DECT from May 2019 to May 2023. The patients were randomly divided into training (n = 115) and validation (n = 49) cohorts. Quantitative DECT parameters of the primary tumours and their clinical characteristics were collected. A logistic regression model was used to determine independent predictors of LNM, and a nomogram was constructed along with a corresponding online model. Model performance was assessed using the area under the curve (AUC) and the calibration curve, and the clinical value was evaluated using decision curve analysis (DCA). Results: In total, 64/164 (39.0 %) patients with LSCC had cervical LNM. Independent predictors of LNM included normalized iodine concentration in the arterial phase (odds ratio [OR]: 8.332, 95 % confidence interval [CI]: 2.813-24.678, P < 0.001), normalized effective atomic number in the arterial phase (OR: 5.518, 95 % CI: 1.095-27.818, P = 0.002), clinical T3-4 stage (OR: 5.684, 95 % CI: 1.701-18.989, P = 0.005), and poor histological grade (OR: 5.011, 95 % CI: 1.003-25.026, P = 0.049). These predictors were incorporated into the DECT-based nomogram and the corresponding online model, showing good calibration and favourable performance (training AUC: 0.910, validation AUC: 0.918). The DCA indicated a significant clinical benefit of the nomogram for estimating LNM. Conclusions: DECT parameters may be useful independent predictors of LNM in patients with LSCC, and a DECT-based nomogram may be helpful in clinical decision-making.

11.
Int Immunopharmacol ; 142(Pt A): 113042, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39236453

RESUMO

BACKGROUND: Germ cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. METHODS: This retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. RESULTS: The study included 37 male patients with a median age of 26 years (range: 18-65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. CONCLUSIONS: Immunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

12.
BMC Microbiol ; 24(1): 321, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232659

RESUMO

With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In this study, we isolated a series of LDPE-degrading fungi from landfill sites and carried out LDPE degradation experiments by combining highly efficient degrading fungi in pairs. The results showed that the mixed microorganisms composed of Alternaria sp. CPEF-1 and Trametes sp. PE2F-4 (H-3 group) had a greater degradation effect on heat-treated LDPE (T-LDPE). After 30 days of inoculation with combination strain H-3, the weight loss rate of the T-LDPE film was approximately 154% higher than that of the untreated LDPE (U-LDPE) film, and the weight loss rate reached 0.66 ± 0.06%. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) were used to further investigate the biodegradation impacts of T-LDPE, including the changes on the surface and depolymerization of the LDPE films during the fungal degradation process. Our findings revealed that the combined fungal treatment is more effective at degrading T-LDPE than the single strain treatment, and it is expected that properly altering the composition of the microbial community can help lessen the detrimental impact of plastics on the environment.


Assuntos
Alternaria , Biodegradação Ambiental , Polietileno , Trametes , Alternaria/metabolismo , Polietileno/metabolismo , Trametes/metabolismo , Instalações de Eliminação de Resíduos , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Filogenia , Microbiologia do Solo
13.
BMC Geriatr ; 24(1): 730, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227765

RESUMO

BACKGROUND: Formal home and community-based care are often considered as the preferable option to institutional care, offering older individuals the convenience of receiving care in their homes. Although research has found that these services may alleviate the burden on informal caregivers, there is a lack of research on which specific types of formal home and community-based care influence informal care provision. METHODS: Employing fixed-effects and quantile regression models, this study seeks to explore the effects that various formal home and community-based care services have on reducing the burden of informal care. This study draws data from the Chinese Longitudinal Healthy Longevity Survey 2005, 2008, 2011, 2014, and 2018. RESULTS: Our findings indicate that two types of formal care substantially influence the provision of informal care. The availability of daily living assistance services correlates with reduced informal caregiving hours, especially for those with extensive care needs. The availability of community-based health care services is linked to a reduction in the direct expenses incurred from informal caregiving, especially for those incurring greater direct caregiving costs. These effects are more prominent among urban residents. Other services, such as mental health support and legal advice services, do not demonstrate significant effects on reducing informal care hours and costs. CONCLUSIONS: Daily living assistance and community-based health care services play a crucial role in benefiting informal caregivers. It is important to prioritize the expansion of these services, especially among those with greater care needs.


Assuntos
Cuidadores , Serviços de Saúde Comunitária , Serviços de Assistência Domiciliar , Humanos , Masculino , Feminino , Estudos Longitudinais , Idoso , China/epidemiologia , Serviços de Saúde Comunitária/economia , Idoso de 80 Anos ou mais , Longevidade , Pessoa de Meia-Idade , População do Leste Asiático
14.
Biomater Sci ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39233608

RESUMO

Bacterial keratitis is a common form of inflammation caused by the bacterial invasion of the corneal stroma after trauma. In extreme cases, it can lead to severe visual impairment or even blindness; therefore, timely medical intervention is imperative. Unfortunately, widespread misuse of antibiotics has led to the development of drug resistance. In recent years, organ-on-chips that integrate multiple cell co-cultures have extensive applications in fundamental research and drug screening. In this study, immortalized human corneal epithelial cells and primary human corneal fibroblasts were co-cultured on a porous polydimethylsiloxane membrane to create a cornea-on-a-chip model. The developed multilayer epithelium closely mimicked clinical conditions, demonstrating high structural resemblance and repeatability. By introducing a consistently defective epithelium and bacterial infection using the space-occupying method, we successfully established an in vitro model of bacterial keratitis using S. aureus. We validate this model by evaluating the efficacy of antibiotics, such as levofloxacin, tobramycin, and chloramphenicol, through simultaneously observing the reactions of bacteria and the two cell types to these antibiotics. Our study has revealed the barrier function of epithelium of the model and differentiated efficacy of three drugs in terms of bactericidal activity, reducing cellular apoptosis, and mitigating scar formation. Altogether, the cornea on chip enables the assessment of ocular antibiotics, distinguishing the impact on corneal cells and structural integrity. This study introduced a biomimetic in vitro disease model to evaluate drug efficacy and provided significant insights into the extensive effects of antibiotics on diverse cell populations within the cornea.

15.
Haematologica ; 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234866

RESUMO

Patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Loncastuximab tesirine (Lonca), an antibody conjugate targeting CD19, has demonstrated significant clinical benefit in R/R DLBCL in a global phase 2 LOTIS-2 study. In the China bridging pivotal phase 2 OL-ADCT-402-001 study, eligible patients aged ≥18 years with R/R DLBCL who had failed ≥ 2 lines of systemic therapies were enrolled and treated with Lonca every 3 week with 150 µg/kg for 2 cycles; then 75 µg/kg for subsequent cycles (up to 1 year). The primary endpoint was overall response rate (ORR) assessed by independent review committee. Primary analyses for efficacy and safety were performed on the patients who received at least one treatment and had at least 6 months of follow-up following an initial documented response. As of data-cutoff, 64 patients received Lonca (median: 4.0 cycles [range: 1 to 17]). The median number of prior lines of therapies was 3.0 (range: 2 to 12). The ORR was 51.6% (95% CI: 38.7% to 64.2%), and the complete response rate was 23.4%. Hematological events accounted for the majority of the most common (≥15%) Grade ≥3 treatment-emergent adverse events (TEAEs), in which increased gamma glutamyltransferase (25.0%), and hypokalaemia (18.8%) also were reported. Serious TEAEs were reported in 35 of 64 patients with 4 fatal TEAEs. In conclusion, Lonca monotherapy demonstrated clinically meaningful efficacy and was well-tolerated in heavily pretreated Chinese patients with R/R DLBCL, which was consistent with the results of the LOTIS-2 study in Caucasian patients.

16.
Cell Metab ; 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39243758

RESUMO

During the progression of metabolic dysfunction-associated steatohepatitis (MASH), the accumulation of auto-aggressive CD8+ T cells significantly contributes to liver injury and inflammation. Empagliflozin (EMPA), a highly selective inhibitor of sodium-glucose co-transporter 2 (SGLT2), exhibits potential therapeutic benefits for liver steatosis; however, the underlying mechanism remains incompletely elucidated. Here, we found that EMPA significantly reduced the hepatic accumulation of auto-aggressive CD8+ T cells and lowered granzyme B levels in mice with MASH. Mechanistically, EMPA increased ß-hydroxybutyric acid by promoting the ketogenesis of CD8+ T cells via elevating 3-hydroxybutyrate dehydrogenase 1 (Bdh1) expression. The ß-hydroxybutyric acid subsequently inhibited interferon regulatory factor 4 (Irf4), which is crucial for CD8+ T cell activation. Furthermore, the ablation of Bdh1 in T cells aggravated the manifestation of MASH and hindered the therapeutic efficacy of EMPA. Moreover, a case-control study also showed that SGLT2 inhibitor treatment repressed CD8+ T cell infiltration and improved liver injury in patients with MASH. In summary, our study indicates that SGLT2 inhibitors can target CD8+ T cells and may be an effective strategy for treating MASH.

17.
J Stomatol Oral Maxillofac Surg ; : 102042, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39244031

RESUMO

OBJECTIVE: To explore the risk factors of radiation-induced oral mucositis (RIOM) in patients with head and neck tumors undergoing radiotherapy. METHODS: A retrospective collection was conducted on patients with head and neck tumors who underwent radiotherapy and chemotherapy in our hospital from April 1, 2015 to April 1, 2019. They were divided into an incidence group (n=48) and a non-incidence group (n=76) based on whether RIOM occurred, and relevant data was collected for comparison. RESULTS: There were statistically significant differences between the two groups of patients in terms of tumor type, smoking percentage, education level percentage, tumor stage, oral mucosal inflammation stage, radiotherapy dose, mucosal protectants, and oral hygiene condition(P<0.05); The regression analysis results showed that smoking (OR=1.274, 95% CI: 1.095-2.007), high-dose radiotherapy (OR=1.223, 95% CI: 1.098-2.077), and poor oral hygiene (OR=1.367, 95% CI: 1.024-2.890) were risk factors for RIOM. CONCLUSION: Smoking, high-dose radiotherapy, and poor oral hygiene were risk factors for RIOM in head and neck patients after radiotherapy and chemotherapy.

18.
J Nanobiotechnology ; 22(1): 533, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39223666

RESUMO

The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Ferroptose , Neoplasias Hepáticas , Nanomedicina , Peptídeos , Sorafenibe , Ferroptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanomedicina/métodos , Sorafenibe/farmacologia , Sorafenibe/química , Linhagem Celular Tumoral , Animais , Peptídeos/química , Peptídeos/farmacologia , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Sinergismo Farmacológico , Sistema y+ de Transporte de Aminoácidos/metabolismo , Camundongos Nus , RNA Interferente Pequeno , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos
19.
Sci Rep ; 14(1): 20347, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223188

RESUMO

The study of hydrogen concentration distribution law of hydrogen-doped methane pipeline is directly related to the safety and stability of hydrogen-doped methane pipeline network. Based on the theory of fluid dynamics, this paper established a model of hydrogen-doped methane pipeline and simulated the operation and shutdown status of hydrogen-doped methane pipeline by adopting the computational fluid dynamics method and selecting the mixture multiphase model and standard k - ε turbulence model. This paper investigates the hydrogen concentration distribution law in hydrogen-doped methane pipelines as well as the influence law of different hydrogen-doping ratios, operating flow velocities, operating pressures, shutdown time and gas usage on the hydrogen concentration distribution in gas pipeline. The results show that: under the operation condition, there is a weak uneven distribution of hydrogen in the pipeline, the hydrogen-doping ratio, flow velocity, pressure on the hydrogen volume fraction of the change in the 0.9% or less, the effect can be ignored; in the shutdown status, there is a clear stratification phenomenon, the hydrogen-doping ratio increased from 10 to 25%, the change in the volume fraction of hydrogen in the 11.2% or less, a positive correlation; with the extension of the shutdown time to 900s, the pipeline firstly appeared obvious stratification phenomenon in the branch pipe, the thickness of the gas with hydrogen volume fraction above 40% on the upper wall surface of the branch pipe increased to 0.7 mm, and after the shutdown time was extended to 10 h, obvious stratification phenomenon appeared in the main pipeline, and the volume fraction of hydrogen near the top of the main pipe of about 16.5 mm was above 30%, which was positively correlated; In the shutdown status, the shutdown time has the greatest effect on the stratification phenomenon in the pipe, followed by the hydrogen-doping ratio, and the gas usage has the least effect.

20.
Small ; : e2404893, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105465

RESUMO

Vanadium-based compounds have attracted significant attention as cathodes for aqueous zinc metal batteries (AZMBs) because of their remarkable advantages in specific capacities. However, their low diffusion coefficient for zinc ions and structural collapse problems lead to poor rate capability and cycle stability. In this work, bilayered Sr0.25V2O5·0.8H2O (SVOH) nanowires are first reported as a highly stable cathode material for rechargeable AZMBs. The synergistic pillaring effect of strontium ions and water molecules improves the structural stability and ion transport dynamics of vanadium-based compounds. Consequently, the SVOH cathode exhibits a high capacity of 325.6 mAh g-1 at 50 mA g-1, with a capacity retention rate of 72.6% relative to the maximum specific capacity at 3.0 A g-1 after 3000 cycles. Significantly, a unique single-nanowire device is utilized to demonstrate the excellent conductivity of the SVOH cathode directly. Additionally, the energy storage mechanism of zinc insertion and extraction is investigated using a variety of advanced in situ and ex situ analysis techniques. This method of ion intercalation to improve electrochemical performance will further promote the development of AZMBs in large-scale applications.

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