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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125009, 2025 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-39178691

RESUMO

Fluoride ions (F-) are one of the essential trace elements for the human body and are widely existed in nature. In this study, we present a novel fluorescent probe (YF-SZ-F) designed and synthesized for the specific detection of F-. The probe exhibits high sensitivity, excellent selectivity, and low cytotoxicity, making it a promising tool for biomedical applications. Imaging experiments conducted on zebrafish and Arabidopsis roots demonstrate the probe's remarkable cellular permeability and biocompatibility, laying a solid foundation for its potential biomedical utility. Furthermore, the probe holds potential for practical applications in environmental monitoring and public health through its capability to detect fluoride ions in water samples and via mobile phone software. This multifaceted functionality underscores the broad applicability and significance of the fluorescent probe, not only in scientific research but also in real-world scenarios, contributing to the development of more convenient and precise methods for fluoride detection.


Assuntos
Benzotiazóis , Corantes Fluorescentes , Fluoretos , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Fluoretos/análise , Animais , Benzotiazóis/química , Humanos , Arabidopsis/química , Espectrometria de Fluorescência/métodos , Imagem Óptica
2.
Neurosci Bull ; 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39312108

RESUMO

Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.

3.
Methods ; 231: 70-77, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303774

RESUMO

Cancer classification is crucial for effective patient treatment, and recent years have seen various methods emerge based on protein expression levels. However, existing methods oversimplify by assuming uniform interaction strengths and neglecting intermediate influences among proteins. Addressing these limitations, GATDE employs a graph attention network enhanced with diffusion on protein-protein interactions. By constructing a weighted protein-protein interaction network, GATDE captures the diversity of these interactions and uses a diffusion process to assess multi-hop influences between proteins. This information is subsequently incorporated into the graph attention network, resulting in precise cancer classification. Experimental results on breast cancer and pan-cancer datasets demonstrate that GATDE surpasses current leading methods. Additionally, in-depth case studies further validate the effectiveness of the diffusion process and the attention mechanism, highlighting GATDE's robustness and potential for real-world applications.

4.
J Neuroinflammation ; 21(1): 237, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334416

RESUMO

BACKGROUND: Early severe cerebral edema and chronic hydrocephalus are the primary cause of poor prognosis in patients with subarachnoid hemorrhage (SAH). This study investigated the role of cerebrospinal fluid (CSF) inflammatory cytokines and coagulation factors in the development of severe cerebral edema and chronic hydrocephalus in patients with SAH. METHODS: Patients with SAH enrolled in this study were categorized into mild and severe cerebral edema groups based on the Subarachnoid Hemorrhage Early Brain Edema Score at admission. During long-term follow-up, patients were further classified into hydrocephalus and non-hydrocephalus groups. CSF samples were collected within 48 h post-SAH, and levels of inflammatory cytokines and coagulation factors were measured. Univariate and multivariate logistic regression analyses were performed to identify independent factors associated with severe cerebral edema and chronic hydrocephalus. The correlation between inflammatory cytokines and coagulation factors was further investigated and validated in a mouse model of SAH. RESULTS: Seventy-two patients were enrolled in the study. Factors from the extrinsic coagulation pathway and inflammatory cytokines were associated with both severe cerebral edema and chronic hydrocephalus. Coagulation products thrombin-antithrombin complexes (TAT) and fibrin, as well as inflammatory cytokines IL-1ß, IL-2, IL-5, IL-7, and IL-4, were independently associated with severe cerebral edema. Additionally, Factor VII, fibrin, IL-2, IL-5, IL-12, TNF-α, and CCL-4 were independently associated with chronic hydrocephalus. A positive correlation between extrinsic coagulation factors and inflammatory cytokines was observed. In the SAH mouse model, tissue plasminogen activator was shown to alleviate neuroinflammation and cerebral edema, potentially by restoring glymphatic-meningeal lymphatic function. CONCLUSIONS: Elevated levels of inflammatory cytokines and extrinsic coagulation pathway factors in the CSF are associated with the development of early severe cerebral edema and chronic hydrocephalus following SAH. These factors are interrelated and may contribute to post-SAH glymphatic-meningeal lymphatic dysfunction.


Assuntos
Biomarcadores , Edema Encefálico , Citocinas , Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Hidrocefalia/líquido cefalorraquidiano , Hidrocefalia/etiologia , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/complicações , Masculino , Feminino , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Citocinas/líquido cefalorraquidiano , Citocinas/sangue , Animais , Idoso , Camundongos , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/sangue , Doenças Neuroinflamatórias/líquido cefalorraquidiano , Doenças Neuroinflamatórias/etiologia , Adulto , Doença Crônica , Camundongos Endogâmicos C57BL , Coagulação Sanguínea/fisiologia
5.
J Chem Phys ; 161(11)2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39282841

RESUMO

Heterojunction catalysts in the field of hydrogen evolution reaction (HER) from electrocatalytic water splitting have recently become a hot research topic. In this paper, we systematically calculated the HER catalytic performance of a MoS2/CoS2 heterojunction for the first time, considering the effect of edge sites regulation, strain and electric field. The results indicate that the MoS2/CoS2 heterojunction exhibits synergistic catalytic performance compared to MoS2 and CoS2, the HER catalytic activity of which can be improved by exposing more edge sites or regulating the S content on the edges, with an optimized ratio of 25%. Surprisingly, applying strain has a slight effect on the catalytic activity of the edge, however, an obvious effect on the basal plane. For example, applying 2% tensile strain on the MoS2/CoS2 heterojunction can improve the edge catalytic performance by 13%, and for the basal plane, this value can reach 92%. In this case, the catalytic performance of the basal plane is better than that of the edge with 2% and without strain. Since the basal plane accounts for the majority of the two-dimensional catalysts, the catalytic performance of the basal plane is generally much lower than that of the edge. This discovery is of great significance, which means by adjusting strain, the catalytic performance of the heterojunction catalyst is likely to be improved by orders of magnitude. Moreover, considering the actual experimental process, we also calculated the effect of the electric field and found that 0.7 V/Å electric field can enhance the HER catalytic activity of the MoS2/CoS2 heterojunction by 23%.

6.
Sensors (Basel) ; 24(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39275372

RESUMO

Oil spill SAR images are characterized by high noise, low contrast, and irregular boundaries, which lead to the problems of overfitting and insufficient capturing of detailed features of the oil spill region in the current method when processing oil spill SAR images. An improved DeepLabV3+ model is proposed to address the above problems. First, the original backbone network Xception is replaced by the lightweight MobileNetV2, which significantly improves the generalization ability of the model while drastically reducing the number of model parameters and effectively addresses the overfitting problem. Further, the spatial and channel Squeeze and Excitation module (scSE) is introduced and the joint loss function of Bce + Dice is adopted to enhance the sensitivity of the model to the detailed parts of the oil spill area, which effectively solves the problem of insufficient capture of the detailed features of the oil spill area. The experimental results show that the mIOU and F1-score of the improved model in an oil spill region in the Gulf of Mexico reach 80.26% and 88.66%, respectively. In an oil spill region in the Persian Gulf, the mIOU and F1-score reach 81.34% and 89.62%, respectively, which are better than the metrics of the control model.

7.
Anal Methods ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39295462

RESUMO

This work presents the design and synthesis of a new fluorescent probe IF-Br-F for the specific detection of fluoride ions. The IF-Br-F probe has excellent fluorescence properties, and the mechanism of the probe response to fluoride ions was successfully verified via HRMS and DFT calculations. IF-Br-F has high sensitivity and low detection limit (5.82 × 10-7 mol L-1) and successfully detects fluoride ions in actual water samples. The probe can be applied to fluorescence imaging of zebrafish, cells, and Arabidopsis roots and exhibits low cytotoxicity and good biocompatibility.

8.
ACS Appl Mater Interfaces ; 16(38): 51089-51096, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39269784

RESUMO

In recent years, flexible UV photodetectors (PDs) with complex environmental adaptability and great wearability have attracted the attention of researchers worldwide. Wide bandgap inorganic semiconductor materials with excellent optoelectronic properties and mechanical stability are key functional materials for UV PD devices. However, the high temperature processing and inherent brittleness limit the further application of high-quality inorganic semiconductors in the field of flexible optoelectronics. In this work, we develop a specific flip-chip bonding fabrication technique that utilizes high-temperature treated inorganic semiconductor materials for high-performance flexible UV detection devices. Leveraging this technique, a 7 × 7 pixel flexible UV photodetector array (UV-FPDA) device based on a vertical architecture Mg-doped ZnO/NiO (Mg:ZnO/NiO) heterojunction transistor is built. The UV-FPDAs exhibit a high responsivity of 75.8 A/W and an outstanding detectivity of 8.5 × 1012 Jones. Besides, the UV-FPDAs also demonstrate excellent bending stability. Furthermore, the photoresponse characteristics of each pixel are trained and learned by an artificial neural network to achieve clear imaging of UV light information. Our results provide a new pathway for the application of inorganic semiconductors in the field of high-performance flexible UV photodetection.

9.
Front Oncol ; 14: 1434631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39328200

RESUMO

With the increasing incidence of lung cancer, the coexistence of pulmonary alveolar proteinosis (PAP) and lung cancer is becoming more common. However, the standard treatment protocols for patients with both conditions are still being explored. The conflict between the rapidly evolving therapeutic approaches for tumors and the limited treatment options for PAP presents a significant challenge for clinicians. Determining the optimal timing of treatment for both conditions to maximize patient benefit is a clinical conundrum. Here, we report a rare case of PAP complicated by lung adenocarcinoma, where interstitial lung changes worsened after neoadjuvant therapy but improved significantly following surgical resection of the lung adenocarcinoma. This case highlights the importance of prioritizing tumor treatment in patients with lung cancer complicated by PAP and examines the interplay between the two conditions, as well as potential therapeutic strategies.

10.
BMC Public Health ; 24(1): 2651, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333994

RESUMO

BACKGROUND: Premarital sexual behavior (PSB) is a controversial topic in China. However, in recent times, changes in attitudes have led to PSB being more common among college students. This study investigated the attitudes of Chinese undergraduates toward PSB to identify whether a typological classification exists among them. METHODS: A total of 278 undergraduate students from two public universities in Mainland China completed a 17-item survey that included five dimensions( emotions, responsiveness, sexual health, sexual freedom, and condemnation) on attitudes toward PSB. Data were collected online from April 2023 to July 2023. RESULTS: The PSB questionnaire demonstrated good reliability and construct validity in this study, with a Cronbach's α of 0.759 and a KMO value of 0.769. Meanwhile, a series of models were estimated specifying one through five latent classes and three typologies on the attitude were identified: "Affective,""Avoidant," and "Open." After the best fitting model was determined, multiple analysis of variance testing of different factors such as gender, year of study and where one came from were found to have significant effects on attitude complexity (p < .01). CONCLUSION: This research will contribute to the dissemination of information on PSB in China, which will be helpful in understanding relevant issues associated with PSB.


Assuntos
Comportamento Sexual , Estudantes , Humanos , China , Feminino , Masculino , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Comportamento Sexual/psicologia , Adulto Jovem , Universidades , Inquéritos e Questionários , Adolescente , Reprodutibilidade dos Testes , Atitude , Adulto , População do Leste Asiático
11.
Clin Interv Aging ; 19: 1479-1491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220855

RESUMO

Purpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.


Assuntos
Osteoartrite do Joelho , Músculo Quadríceps , Ultrassonografia , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiopatologia , Masculino , Feminino , Idoso , Fenômenos Biomecânicos , Pessoa de Meia-Idade , Estudos de Casos e Controles
12.
Mater Horiz ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264270

RESUMO

Efficient enrichment and accurate diagnosis of cancer cells from biological samples can guide effective treatment strategies. However, the accessibility and accuracy of rapid identification of tumor cells have been hampered due to the overlap of white blood cells (WBCs) and cancer cells in size. Therefore, a diagnosis system for the identification of tumor cells using reliable surface-enhanced Raman spectroscopy (SERS) bioprobes assisted with high-efficiency microfluidic chips for rapid enrichment of cancer cells was developed. According to this, a homogeneous flower-like Cu2O@Ag composite with high SERS performance was constructed. It showed a favorable spectral stability of 5.81% and can detect trace alizarin red (10-9 mol L-1). Finite-difference time-domain (FDTD) simulation of Cu2O, Ag and Cu2O@Ag, decreased the fluorescence lifetime of methylene blue after adsorption on Cu2O@Ag, and surface defects of Cu2O observed using a spherical aberration-corrected transmission electron microscope (AC-TEM) demonstrated that the combined effects of electromagnetic enhancement and promoted charge transfer endowed the Cu2O@Ag with good SERS activity. In addition, the modulation of the absorption properties of flower-like Cu2O@Ag composites significantly improved electromagnetic enhancement and charge transfer effects at 532 nm, providing a reliable basis for the label-free SERS detection. After the cancer cells in blood were separated by a spiral inertial microfluidic chip (purity >80%), machine learning-assisted linear discriminant analysis (LDA) successfully distinguished three types of cancer cells and WBCs with high accuracy (>90%). In conclusion, this study provides a profound reference for the rational design of SERS probes and the efficient diagnosis of malignant tumors.

13.
Sci Rep ; 14(1): 21084, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256515

RESUMO

The drying process of the lithium battery pole pieces makes extensive use of the suspension nozzle. It is of great significance to study the heat transfer and pressure steady-state characteristics of the suspension nozzle and to select the appropriate nozzle structure for the production of pole pieces. Based on the SST k - ω turbulence model, this article numerically simulates the impact jet process of suspension nozzles with slits, injection holes, and effusion holes. There is a qualitative and quantitative analysis of the distribution of their velocity field, temperature field, local Nusselt number, average Nusselt number, local pressure coefficient, and average pressure coefficient, and the comprehensive performance index of the nozzle is proposed. The results show that when the weight factor of heat transfer performance α is less than 21.61% and the weight factor of pressure performance ß is more than 78.39%, the comprehensive performance of the traditional suspension nozzle with double slits is the best. As the α is increasing, the ß is decreasing. The comprehensive performance of the suspension nozzle with effusion holes is the best. The turbulent intermittence, interaction between neighbouring jets, and edge effects affect the heat transfer and pressure uniformity of the suspension nozzle.

14.
Front Med (Lausanne) ; 11: 1391641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234036

RESUMO

Herein, we evaluated the optimal timing for implementing the BioFire® FilmArray® Pneumonia Panel (FA-PP) in the medical intensive care unit (MICU). Respiratory samples from 135 MICU-admitted patients with acute respiratory failure and severe pneumonia were examined using FA-PP. The cohort had an average age of 67.1 years, and 69.6% were male. Notably, 38.5% were smokers, and the mean acute physiology and chronic health evaluation-II (APACHE-II) score at initial MICU admission was 30.62, and the mean sequential organ failure assessment score (SOFA) was 11.23, indicating sever illness. Furthermore, 28.9, 52.6, and 43% of patients had a history of malignancy, hypertension, and diabetes mellitus, respectively. Community-acquired pneumonia accounted for 42.2% of cases, whereas hospital-acquired pneumonia accounted for 37%. The average time interval between pneumonia diagnosis and FA-PP implementation was 1.9 days, and the mean MICU length of stay was 19.42 days. The mortality rate was 50.4%. Multivariate logistic regression analysis identified two variables as significant independent predictors of mortality: APACHE-II score (p = 0.033, OR = 1.06, 95% CI 1.00-1.11), history of malignancy (OR = 3.89, 95% CI 1.64-9.26). The Kaplan-Meier survival analysis indicated that early FA-PP testing did not provide a survival benefit. The study suggested that the FA-PP test did not significantly impact the mortality rate of patients with severe pneumonia with acute respiratory failure. However, a history of cancer and a higher APACHE-II score remain important independent risk factors for mortality.

15.
Environ Sci Ecotechnol ; 22: 100478, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39280593

RESUMO

Urbanization is modifying aquatic ecosystems, with hydrodynamic and trophic variations altering biotic assemblages in rapidly expanding cities worldwide. Despite the fundamental bioenergetic role of food webs within these assemblages, their responding mechanism to the hydrodynamic and trophic variations remains largely unknown. Here we show that hydrodynamic and trophic loss, coupled with the weakening of cascade controls by key trophic guilds, leads to a significant decline in the structure, function and stability of macroinvertebrate food webs. Utilizing the allometric diet breadth model and biomass balance model, we established representative food webs for macroinvertebrate groups under varying hydrodynamic and trophic stresses. We found that such losses have reduced ∼75% trophic guild richness, ∼85% biomass flux, and ∼80% biomass storage. These reductions promote trophic guild specialization, further destabilizing food web, eroding interactive strength asymmetry, and diminishing the control of trophic guilds. Furthermore, macroinvertebrate food webs show divergent stability responses under similar stress levels, mainly driven by differences in the cascade controls exerted by key trophic guilds. Our results underscore the critical role of hydrodynamic and trophic variations in shaping urban aquatic ecosystems and highlight the significance of both external environmental revitalization and internal food web dynamics enhancement in restoring the ecological stability in urban settings.

16.
Acta Pharm Sin B ; 14(8): 3605-3623, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39220866

RESUMO

Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer. Herein, a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell. The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation, self-renewal, migration, and invasion of lung cancer cell lines at low micromolar concentrations. The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays. In the H460R231Q OE cell-derived xenograft (CDX) model, 37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks (TGI = 54.38%), without obvious toxicities. A pharmacokinetic study revealed that 37 possessed tolerable properties (t 1/2 = 1.93 ± 0.91 h, F = 97.2%) after intraperitoneal administration in rats. Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway. Moreover, analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the "Induced-fit" allosteric model in favor to the discovery of potent DOT1L candidates.

17.
Small ; : e2406160, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39240001

RESUMO

Simultaneously improving the strength and toughness of polymer-inorganic nanocomposites is highly desirable but remains technically challenging. Herein, a simple yet effective pathway to prepare polymer-inorganic nanocomposite films that exhibit excellent mechanical properties due to their unique composition and structure is demonstrated. Specifically, a series of poly(methacrylic acid)x-block-poly(benzyl methacrylate)y diblock copolymer nano-objects with differing dimensions and morphologies is prepared by polymerization-induced self-assembly (PISA) mediated by reversible addition-fragmentation chain transfer polymerization (RAFT). Such copolymer nano-objects and ultrasmall calcium phosphate oligomers (CPOs) are used as dual fillers for the preparation of polymer-inorganic composite films using sodium carboxymethyl cellulose (CMC) as a matrix. Impressively, the strength and toughness of such composite films are substantially reinforced as high as up to 202.5 ± 14.8 MPa and 62.3 ± 7.9 MJ m-3, respectively. Owing to the intimate interaction between the polymer-inorganic interphases at multiple scales, their mechanical performances are superior to most conventional polymer films and other nanocomposite films. This study demonstrates the combination of polymeric fillers and inorganic fillers to reinforce the mechanical properties of the resultant composite films, providing new insights into the design rules for the construction of novel hybrid films with excellent mechanical performances.

18.
Value Health ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39096963

RESUMO

OBJECTIVES: The BETAcc clinical trial demonstrated that chemotherapy combined with bevacizumab plus atezolizumab (CBA) significantly prolonged progression-free survival and overall survival in patients with metastatic, persistent, or recurrent cervical cancer. However, to the best of our knowledge, the economic value of using this new therapy for this indication is currently unknown. Therefore, our study aimed to evaluate the cost-effectiveness of CBA for the first-line treatment of metastatic, persistent, or recurrent cervical cancer from the United States healthcare payers perspective. METHODS: A state-transition Markov model over a 10-year lifetime horizon was developed to compare the cost and effectiveness of CBA with that of chemotherapy plus bevacizumab (CB). The primary outcomes of our study included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. RESULTS: CBA was associated with an additional 0.58 QALY at an extra cost of $172 495.90 compared with CB. The incremental cost-effectiveness ratio was $295 972.43/QALY, significantly higher than the willingness-to-pay threshold value of $150 000/QALY. One-way sensitivity analyses revealed that results were most sensitive to the progression-free disease utility, the unit cost of atezolizumab, and progressed disease utility. Probabilistic sensitivity analysis indicated that CBA achieved a 4.3% probability of cost-effectiveness at a $150 000/QALY threshold. To achieve cost-effectiveness, the unit price of atezolizumab must be reduced by approximately 56.6%. CONCLUSIONS: CBA treatment is unlikely to be a cost-effective option compared with CB for patients with persistent, recurrent, or metastatic cervical cancer in the United States.

19.
Bioconjug Chem ; 35(9): 1450-1458, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39213480

RESUMO

A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.


Assuntos
Ferroptose , Glutationa , Fotoquimioterapia , Porfirinas , Glutationa/metabolismo , Fotoquimioterapia/métodos , Porfirinas/química , Porfirinas/farmacologia , Ferroptose/efeitos dos fármacos , Humanos , Animais , Nanopartículas/química , Polímeros/química , Linhagem Celular Tumoral , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Ácido Hialurônico/química
20.
Biomolecules ; 14(8)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39199292

RESUMO

Gene delivery therapy has emerged as a popular approach for the treatment of various diseases. However, it still poses the challenges of accumulation in target sites and reducing off-target effects. Aerosol gene delivery for the treatment of pulmonary diseases has the advantages of high lung accumulation, specific targeting and fewer systemic side effects. However, the key challenge is selecting the appropriate formulation for aerosol gene delivery that can overcome physiological barriers. There are numerous existing gene carriers under study, including viral vectors and non-viral vectors. With the development of biomaterials, more biocompatible substances have applied gene delivery via inhalation. Furthermore, many types of genes can be delivered through aerosol inhalation, such as DNA, mRNA, siRNA and CRISPR/Cas9. Aerosol delivery of different types of genes has proven to be efficient in the treatment of many diseases such as SARS-CoV-2, cystic fibrosis and lung cancer. In this paper, we provide a comprehensive review of the ongoing research on aerosol gene delivery therapy, including the basic respiratory system, different types of gene carriers, different types of carried genes and clinical applications.


Assuntos
Aerossóis , Técnicas de Transferência de Genes , Terapia Genética , Pneumopatias , Humanos , Terapia Genética/métodos , Aerossóis/administração & dosagem , Administração por Inalação , Pneumopatias/terapia , Pneumopatias/genética , Vetores Genéticos/administração & dosagem , COVID-19/terapia , COVID-19/genética , SARS-CoV-2/genética , Animais
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