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1.
J Mater Chem B ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109473

RESUMO

Conjugated polymers (CPs), which emit in the second near-infrared window (NIR-II, 1000-1700 nm), are used as biomaterials for NIR-II fluorescence imaging because of their adjustable photophysical properties and high optical stability. However, the fluorescence signal of conventional CPs is quenched in an aggregated state due to strong π-π stacking, which results in the closure of the radiation attenuation pathway. To solve this problem, the aggregation-induced emission effect is considered a reasonable strategy for enhancing the aggregative fluorescence of IR-II emitters. We herein report NIR-II conjugated polymers with typical AIE characteristics (αAIE > 3) by changing the side chain structure of receptor units and the conjugation degree of donors. Conjugated polymer nanoparticles (PoBVT NPs) exhibit outstanding performance in NIR-II fluorescence imaging (QY = 1.94%) and highly effective photothermal therapy (η = 45%). In vivo studies have shown that the location of tumors can be accurately obtained by NIR-II FL/NIR-II PA imaging, and there is a significant anti-tumor effect after laser irradiation. This work offers prospects for the design of multifunctional conjugated polymers for NIR-II FL/PA imaging to guide NIR-II PTT applications.

2.
Nat Commun ; 15(1): 6781, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117642

RESUMO

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

3.
Ultrasonics ; 143: 107406, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39047350

RESUMO

Early ultrasound screening for breast cancer reduces mortality significantly. The main evaluation criterion for breast ultrasound screening is the Breast Imaging-Reporting and Data System (BI-RADS), which categorizes breast lesions into categories 0-6 based on ultrasound grayscale images. Due to the limitations of ultrasound grayscale imaging, lesions with categories 4 and 5 necessitate additional biopsy for the confirmation of benign or malignant status. In this paper, the SAE-Net was proposed to combine the tissue microstructure information with the morphological information, thus improving the identification of high-grade breast lesions. The SAE-Net consists of a grayscale image branch and a spectral pattern branch. The grayscale image branch used the classical deep learning backbone model to learn the image morphological features from grayscale images, while the spectral pattern branch is designed to learn the microstructure features from ultrasound radio frequency (RF) signals. Our experimental results show that the best SAE-Net model has an area under the receiver operating characteristic curve (AUROC) of 12% higher and a Youden index of 19% higher than the single backbone model. These results demonstrate the effectiveness of our method, which potentially optimizes biopsy exemption and diagnostic efficiency.

4.
J Bone Oncol ; 47: 100614, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38975332

RESUMO

Objective: To develop a model combining clinical and radiomics features from CT scans for a preoperative noninvasive evaluation of Huvos grading of neoadjuvant chemotherapy in patients with HOS. Methods: 183 patients from center A and 42 from center B were categorized into training and validation sets. Features derived from radiomics were obtained from unenhanced CT scans.Following dimensionality reduction, the most optimal features were selected and utilized in creating a radiomics model through logistic regression analysis. Integrating clinical features, a composite clinical radiomics model was developed, and a nomogram was constructed. Predictive performance of the model was evaluated using ROC curves and calibration curves. Additionally, decision curve analysis was conducted to assess practical utility of nomogram in clinical settings. Results: LASSO LR analysis was performed, and finally, three selected image omics features were obtained.Radiomics model yielded AUC values with a good diagnostic effect for both patient sets (AUCs: 0.69 and 0.68, respectively). Clinical models (including sex, age, pre-chemotherapy ALP and LDH levels, new lung metastases within 1 year after surgery, and incidence) performed well in terms of Huvos grade prediction, with an AUC of 0.74 for training set. The AUC for independent validation set stood at 0.70. Notably, the amalgamation of radiomics and clinical features exhibited commendable predictive prowess in training set, registering an AUC of 0.78. This robust performance was subsequently validated in the independent validation set, where the AUC remained high at 0.75. Calibration curves of nomogram showed that the predictions were in good agreement with actual observations. Conclusion: Combined model can be used for Huvos grading in patients with HOS after preoperative chemotherapy, which is helpful for adjuvant treatment decisions.

5.
J Nanobiotechnology ; 22(1): 451, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080708

RESUMO

The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000-1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo.


Assuntos
Cátions , Nanopartículas , Terapia Fototérmica , Polímeros , Animais , Camundongos , Polímeros/química , Terapia Fototérmica/métodos , Humanos , Nanopartículas/química , Cátions/química , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Fluorescência , Técnicas Fotoacústicas/métodos , Camundongos Nus , Feminino , Nanomedicina Teranóstica/métodos
6.
Adv Sci (Weinh) ; 11(30): e2309446, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38885368

RESUMO

Multidrug resistance to clinical chemotherapeutic drugs severely limits antitumor efficacy and patient survival. The integration of chemotherapy with photothermal therapy (PTT) and reactive nitrogen species has become a major strategy to enhance cancer treatment efficacy. Herein, a multifunctional peroxynitrite (ONOO-) nanogenerator (PBT/NO/Pt) for NIR-II fluorescence (NIR-II FL)/NIR-II photoacoustic (NIR-II PA) imaging-guided chemo/NIR-II PTT/ONOO- combination therapy is reported. The multifunction nanogenerator is developed by co-loading a pH-sensitive nitric oxide donor (DETA NONOate) and nicotinamide adenine dinucleotide phosphate oxidases trigger superoxide (O2 •-) generator chemotherapy drug (CDDP) to an NIR-II excitation-conjugated polyelectrolyte (PNC11BA). PNC11BA has non-conjugated alkyl chain segments in the polymer backbone and abundant positively charged phenylboronic acid in its side chains, which support the anti-quenching of NIR-II FL and the integration of DETA NONOate and CDDP into PBT/NO/Pt. In the acidic tumor microenvironment, the coordination bonds between CDDP and PNC11BA are cleaved, releasing CDDP for chemotherapeutic activity. The simultaneous release of nitric oxide (NO) and O2 •- rapidly leads to the in situ generation of the more cytotoxic reactive physiological nitrogen species ONOO-. In vitro and in vivo results prove that PBT/NO/Pt exhibited a markedly ONOO- enhanced chemo-photothermal synergistic therapy for SKOV3/DDP tumor by downregulating the intracellular glutathione and increasing CDDP-DNA adducts.


Assuntos
Ácidos Borônicos , Ácido Peroxinitroso , Terapia Fototérmica , Ácido Peroxinitroso/química , Terapia Fototérmica/métodos , Animais , Camundongos , Ácidos Borônicos/química , Polieletrólitos/química , Modelos Animais de Doenças , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral
7.
Sci Rep ; 14(1): 10191, 2024 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702362

RESUMO

The main objective of this study was to investigate the incidence and characteristics of electrocardiographic abnormalities in patients with microtia, and to explore cardiac maldevelopment associated with microtia. This retrospective study analyzed a large cohort of microtia patients admitted to Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from September 2017 to August 2022. The routine electrocardiographic reports of these patients were reviewed to assess the incidence and characteristics of abnormalities. The study included a total of 10,151 patients (5598 in the microtia group and 4553 in the control group) who were admitted to the Plastic Surgery Hospital of Peking Union Medical College. The microtia group had a significantly higher incidence of abnormal electrocardiographies compared to the control group (18.3% vs. 13.6%, P < 0.01), even when excluding sinus irregularity (6.1% vs. 4.4%, P < 0.01). Among the 1025 cases of abnormal electrocardiographies in the microtia group, 686 cases were reported with simple sinus irregularity. After excluding sinus irregularity as abnormal, the most prevalent abnormalities was right bundle branch block (37.5%), followed by sinus bradycardia (17.4%), ST-T wave abnormalities (13.3%), atrial rhythm (9.1%), sinus tachycardia (8.3%), and ventricular high voltage (4.7%). Less common ECG abnormalities included atrial tachycardia (2.1%), ventricular premature contraction (2.4%), and ectopic atrial rhythm (1.8%). atrioventricular block and junctional rhythm were present in 1.2% and 0.9% of the cases, respectively. Wolff Parkinson White syndrome and dextrocardia had a lower prevalence, at 0.6% and 0.9%, respectively. The occurrence of electrocardiographic abnormalities in microtia patients was found to be higher compared to the control group. These findings highlight the potential congenital defect in cardiac electrophysiology beyond the presence of congenital heart defect that coincide with microtia.


Assuntos
Microtia Congênita , Eletrocardiografia , Humanos , Microtia Congênita/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Adolescente , Criança , Adulto , Adulto Jovem , Incidência , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/fisiopatologia , China/epidemiologia
8.
Cardiovasc Diagn Ther ; 14(2): 240-250, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38716315

RESUMO

Background: Data on the associations of triglyceride (TG) levels with cardiovascular disease (CVD) and all-cause mortality mainly focused on the middle-aged or elderly population, with limited information available for younger adults. This study aimed to identify such associations among Chinese young adults. Methods: This study included Chinese adults younger than 40 years free of CVD, cancer, and lipid-lowering agents at baseline in the Kailuan study who were enrolled during 2006 through 2016. All participants were biennially followed up till December 2020. The enzymatic colorimetric method was used to measure baseline fasting TG. Participants were categorized into four groups by quartiles of TG, with the lowest quartile (Q1) as the reference group. The primary outcomes were CVD [composite of myocardial infarction (MI) and ischemic stroke] and all-cause mortality. CVD and mortality risks were estimated with Cox regression models. Results: A total of 43,882 participants were included. Their mean age was 30.6±5.56 years, and 80.2% were males. During a median follow-up of 11.2 years, 298 CVD events and 345 deaths occurred. The incidences of CVD and all-cause mortality were 0.67 and 0.76 per 1,000 person-years, respectively. Compared with individuals in the lowest quartile (Q1), participants in the highest quartile (Q4) showed a 126% higher risk of developing CVD [adjusted hazard ratio (HR) 2.26; 95% confidence interval (CI): 1.56 to 3.29; P=0.001] and a 61% higher risk of all-cause mortality (adjusted HR 1.61; 95% CI: 1.14 to 2.28; P=0.007). In addition, analyses of CVD subtypes showed that adjusted HRs (Q4 vs. Q1) were 3.25 (95% CI: 1.33 to 7.97; P=0.01) for MI, and 1.88 (95% CI: 1.16 to 3.04; P=0.01) for ischemic stroke. Conclusions: Among Chinese young adults, elevated fasting TG levels were associated with increased CVD and all-cause mortality risks.

9.
Nat Commun ; 15(1): 3260, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627377

RESUMO

Notable-HCC (NCT05185531) is a phase 1b trial, aiming to evaluate the safety and preliminary effectiveness of neoadjuvant PD-1 blockade plus stereotactic body radiotherapy (SBRT) in early-stage resectable hepatocellular carcinoma (HCC). Twenty patients with HCC of BCLC stage 0-A received 3 × Gy SBRT and two cycles of tislelizumab, an anti-PD-1 monoclonal antibody before the curative HCC resection. Primary endpoints were the surgery delay, radiographic and pathological tumor response after the neoadjuvant therapy, safety and tolerability. During the neoadjuvant therapy, treatment-related adverse events (TRAEs) of grade 1-2 occurred in all 20 patients (100%), eight patients (40%) had grade 3 TRAEs, no grade 4 to 5 TRAE occurred, and all resolved without corticosteroids treatment. Per mRECIST, the objective response rate was 63.2% (12/19), with 3 complete response; the disease control rate was 100%. Two (10.5%) patients achieved complete pathological response. No surgery delay occurred. The neoadjuvant therapy did not increase the surgical difficulty or the incidence of complications. Secondary endpoints of disease-free survival and overall survival were not mature at the time of the analysis. Our pilot trial shows that neoadjuvant therapy with anti-PD-1 + SBRT is safe and promotes tumor responses in early-stage resectable HCC.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Humanos , Terapia Neoadjuvante , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Radiocirurgia/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Adjuvantes Imunológicos
10.
BMC Cancer ; 24(1): 480, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627684

RESUMO

BACKGROUND: The treatment of hepatocellular carcinoma (HCC) patients exhibiting high-risk characteristics (Vp4, and/or bile duct invasion, and/or tumor occupancy ≥ 50%) lacks standardized approaches and yields unfavorable results. This study endeavors to evaluate the safety, efficacy, and prognostic impacts of employing hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and humanized programmed death receptor-1 (PD-1) in the treatment of high-risk HCC patients. METHODS: In this retrospective analysis, HCC patients with high-risk features were treated with either lenvatinib combined with PD-1 (LEN-PD1) or a combination of HAIC, lenvatinib, and PD-1 (HAIC-LEN-PD1). The study assessed the antitumor efficacy by calculating overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles. RESULTS: Between June 2019 and September 2022, a total of 61 patients were included in the LEN-PD1 group, while 103 patients were enrolled in the HAIC-LEN-PD1 group. The OS was 9.8 months in the LEN-PD1 group, whereas the HAIC-LEN-PD1 group exhibited a significantly longer median OS of 19.3 months (HR = 0.43, p < 0.001). Furthermore, PFS was notably extended in the HAIC-LEN-PD1 group compared to the LEN-PD1 group (9.6 months vs. 4.9 months, HR = 0.48, p < 0.001). Patients in the HAIC-LEN-PD1 group had a higher ORR and DCR according to the modified RECIST (76.7% vs. 23.0%, p < 0.001; 92.2% vs. 72.1%, p = 0.001). HAIC-LEN-HAIC group led to more adverse events than LEN-PD1 group, most of which were tolerable and controllable. CONCLUSION: Lenvatinib, HAIC and PD-1 showed safe and promising anti-tumor activity compared with lenvatinib alone for HCC with high-risk features.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico
11.
J Nanobiotechnology ; 22(1): 163, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600506

RESUMO

Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.


Assuntos
Indazóis , Nanopartículas , Neoplasias , Humanos , Fototerapia , Piroptose , Neoplasias/tratamento farmacológico , Imunoterapia , Linhagem Celular Tumoral
12.
Quant Imaging Med Surg ; 14(2): 1602-1615, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415150

RESUMO

Background: As artificial intelligence (AI) becomes increasingly prevalent in the medical field, the effectiveness of AI-generated medical reports in disease diagnosis remains to be evaluated. ChatGPT is a large language model developed by open AI with a notable capacity for text abstraction and comprehension. This study aimed to explore the capabilities, limitations, and potential of Generative Pre-trained Transformer (GPT)-4 in analyzing thyroid cancer ultrasound reports, providing diagnoses, and recommending treatment plans. Methods: Using 109 diverse thyroid cancer cases, we evaluated GPT-4's performance by comparing its generated reports to those from doctors with various levels of experience. We also conducted a Turing Test and a consistency analysis. To enhance the interpretability of the model, we applied the Chain of Thought (CoT) method to deconstruct the decision-making chain of the GPT model. Results: GPT-4 demonstrated proficiency in report structuring, professional terminology, and clarity of expression, but showed limitations in diagnostic accuracy. In addition, our consistency analysis highlighted certain discrepancies in the AI's performance. The CoT method effectively enhanced the interpretability of the AI's decision-making process. Conclusions: GPT-4 exhibits potential as a supplementary tool in healthcare, especially for generating thyroid gland diagnostic reports. Our proposed online platform, "ThyroAIGuide", alongside the CoT method, underscores the potential of AI to augment diagnostic processes, elevate healthcare accessibility, and advance patient education. However, the journey towards fully integrating AI into healthcare is ongoing, requiring continuous research, development, and careful monitoring by medical professionals to ensure patient safety and quality of care.

13.
Small Methods ; : e2301405, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168901

RESUMO

Currently, the copolymer of dopamine (DA) and pyrrole (PY) via chemical and electrochemical oxidation usually requires additional oxidants, and lacks flexibility in regulating the size and morphology, thereby limiting the broad applications of DA-PY copolymer in biomedicine. Herein, the semiquinone radicals produced by the self-oxidation of DA is ingeniously utilized as the oxidant to initiate the following copolymerization with PY, and a series of quinone-rich polydopamine-pyrrole copolymers (PDAm -nPY) with significantly enhanced absorption in near-infrared (NIR) region without any additional oxidant assistance is obtained. Moreover, the morphology and size of PDAm -nPY can be regulated by changing the concentration of DA and PY, thereby optimizing nanoscale PDA0.05 -0.15PY particles (≈ 150 nm) with excellent NIR absorption and surface modification activity are successfully synthesized. Such PDA0.05 -0.15PY particles show effective photoacoustic (PA) imaging and photothermal therapy (PTT) against 4T1 tumors in vivo. Furthermore, other catechol derivatives can also copolymerize with PY under the same conditions. This work by fully utilizing the semiquinone radical active intermediates produced through the self-oxidation of DA reduces the dependence on external oxidants in the synthesis of composite materials and predigests the preparation procedure, which provides a novel, simple, and green strategy for the synthesis of other newly catechol-based functional copolymers.

14.
Ultrasonics ; 138: 107233, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171228

RESUMO

Breast cancer has become the most common cancer worldwide, and early screening improves the patient's survival rate significantly. Although pathology with needle-based biopsy is the gold standard for breast cancer diagnosis, it is invasive, painful, and expensive. Meanwhile it makes patients suffer from misplacement of the needle, resulting in misdiagnosis and further assessment. Ultrasound imaging is non-invasive and real-time, however, benign and malignant tumors are hard to differentiate in grayscale B-mode images. We hypothesis that breast tumors exhibit characteristic properties, which generates distinctive spectral patterns not only in scattering, but also during propagation. In this paper, we propose a breast tumor classification method that evaluates the spectral pattern of the tissues both inside the tumor and beneath it. First, quantitative ultrasonic parameters of these spectral patterns were calculated as the representation of the corresponding tissues. Second, parameters were classified by the K-Nearest Neighbor machine learning model. This method was verified with an open access dataset as a reference, and applied to our own dataset to evaluate the potential for tumors assessment. With both datasets, the proposed method demonstrates accurate classification of the tumors, which potentially makes it unnecessary for certain patients to take the biopsy, reducing the rate of the painful and expensive procedure.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Ultrassonografia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mama , Biópsia , Biópsia por Agulha/métodos
15.
Chem Commun (Camb) ; 60(3): 332-335, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38073511

RESUMO

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

16.
J Med Chem ; 67(1): 467-478, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38147641

RESUMO

Subcellular organelle mitochondria are becoming a key player and a driver of cancer. Mitochondrial targeting phototheranostics has attracted increasing attention for precise cancer therapy. However, those phototheranostic systems still face great challenges, including complex and multiple components, light scattering, and insufficient therapeutic efficacy. Herein, a molecular fluorophore IR-TPP-1100 was tactfully designed by molecular engineering for mitochondria-targeted fluorescence imaging-guided phototherapy in the second near-infrared window (NIR-II). IR-TPP-1100 not only exhibited prominent photophysical properties and high photothermal conversion efficiency but also achieved excellent mitochondria-targeting ability. The mitochondria-targeting IR-TPP-1100 enabled NIR-II fluorescence and photoacoustic dual-modality imaging of mitochondria at the organism level. Moreover, it integrated photothermal and photodynamic therapy, obtaining remarkable tumor therapeutic efficacy by inducing mitochondrial apoptosis. These results indicate that IR-TPP-1100 has great potential for precise cancer therapy and provides a promising strategy for developing mitochondria-targeting NIR-II phototheranostic agents.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fototerapia/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Mitocôndrias , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral
17.
Bioorg Chem ; 143: 107047, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154387

RESUMO

Chemical protein synthesis offers a powerful way to access otherwise-difficult-to-obtain proteins such as mirror-image proteins. Although a large number of proteins have been chemically synthesized to date, the acquisition to proteins containing hydrophobic peptide fragments has proven challenging. Here, we describe an approach that combines the removable backbone modification strategy and the peptide hydrazide-based native chemical ligation for the chemical synthesis of a 28 kDa full-length PET degrading enzyme IGGC (a higher depolymerization efficiency of variant leaf-branch compost cutinase (LCC)) containing hydrophobic peptide segments. The synthetic ICCG exhibits the enzymatic activity and will be useful in establishing the corresponding mirror-image version of ICCG.


Assuntos
Polietilenotereftalatos , Hidrolases/química , Fragmentos de Peptídeos , Peptídeos/química , Polietilenotereftalatos/química
18.
J Nanobiotechnology ; 21(1): 446, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38001486

RESUMO

Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe2+ ions in DSPE-PEG2000. Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe2+ ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe2+ irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe2+ ions in the oxidative BME overexpressed with H2O2. Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs.


Assuntos
Infecções Bacterianas , Nanopartículas , Neoplasias , Humanos , Antibacterianos/farmacologia , Vancomicina/farmacologia , Terapia Fototérmica , Peróxido de Hidrogênio , Biofilmes , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Quant Imaging Med Surg ; 13(10): 6965-6978, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869307

RESUMO

Background: Prostate cancer rates have been steadily increasing in recent years. As high-precision radiation therapy methods, stereotactic body radiation therapy (SBRT) and carbon-ion radiation therapy (CIRT) have unique advantages. Analyzing the dosimetric differences between SBRT and CIRT in the treatment of localized prostate cancer can help provide patients with more accurate, individualized treatment plans. Methods: We selected computed tomography positioning images and the contours of target volumes of 16 patients with localized prostate cancer who received radiotherapy. We delineated the organs at risk (OARs) on the CyberKnife (CK) treatment planning system (TPS) MultiPlan4.0, which were imported into the CIRT uniform scanning TPS HIMM-1 ci-Plan. Two treatment plans, SBRT and CIRT, were designed for the same patient, and we used SPSS 22.0 for the statistical analysis of data. Results: Both SBRT and CIRT plans met the prescribed dose requirements. In terms of target volume exposure dose, D2 (P<0.001), D5 (P<0.001), D50 (P<0.001), D90 (P=0.029), D95 (P<0.001), D98 (P<0.001), and Dmean (P<0.001) under SBRT were significantly higher than those under CIRT; the conformity index (CI) under SBRT was significantly better than that under CIRT (P<0.001); the target volume coverage rate (V95%) and dose homogeneity index (HI) under CIRT were significantly better than those under SBRT (P<0.001). In terms of OAR exposure dosage, the Dmax of the bladder and rectum under SBRT was significantly lower than that under CIRT (P<0.001), but Dmean was in the other direction; the exposure dose of the intestinal tract under CIRT was significantly lower than that under SBRT (P<0.05); Dmax of the femoral head under CIRT was significantly lower than that under SBRT (P<0.05), and there was no statistical difference between them at other doses. Conclusions: In this study, we found that when CIRT was used for treating localized prostate cancer, the dose distribution in target volume was more homogeneous and the coverage rate was higher; the average dose of OARs was lower. SBRT had a better CI and higher dose in target volume; the dose hotspot was lower in OARs. It is important to comprehensively consider the dose relationship between local tumor and surrounding tissues when selecting treatment plans.

20.
Noncoding RNA Res ; 8(4): 593-601, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37680850

RESUMO

MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that typically consist of 19-25 nucleotides in length. These molecules function as essential regulators of gene expression by selectively binding to complementary target sequences within messenger RNA (mRNA) molecules, consequently exerting a negative impact on gene expression at the post-transcriptional level. By modulating the stability and translation efficiency of target mRNAs, miRNAs play pivotal roles in diverse biological processes, including the intricate orchestration of organ development. Among these processes, the development of the kidney has emerged as a key area of interest regarding miRNA function. Intriguingly, recent investigations have uncovered a subset of miRNAs that exhibit remarkably high expression levels in the kidney, signifying their close association with kidney development and diseases affecting this vital organ. This growing body of evidence strongly suggests that miRNAs serve as crucial regulators, actively shaping both the physiological processes governing kidney function and the pathological events leading to renal disorders. This comprehensive review aims to provide an up-to-date overview of the latest research progress regarding miRNAs and their involvement in kidney development. By examining the intricate interplay between miRNAs and the molecular pathways driving kidney development, this review seeks to elucidate the underlying mechanisms through which miRNAs exert their regulatory functions. Furthermore, an in-depth exploration of the role played by miRNAs in the occurrence and progression of renal dysplasia will be presented. Renal dysplasia represents a significant developmental anomaly characterized by abnormal kidney tissue formation, and miRNAs have emerged as key players in this pathological process. By shedding light on the intricate network of miRNA-mediated regulatory mechanisms involved in kidney dysplasia, this review aims to provide valuable insights for the diagnosis and research of diseases associated with aberrant kidney development.

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