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1.
Adv Mater ; : e2313393, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573779

RESUMO

The meta-stable active layer morphology of organic solar cells (OSCs) has been identified as the main cause of the rapid burn-in loss of power conversion efficiency (PCE) during long-term device operation. However, effective strategies to eliminate the associated loss mechanisms from the initial stage of device operation are still lacking, especially for high-efficiency material systems. Herein, we report the introduction of molecularly engineered dimer acceptors with adjustable thermal transition properties into the active layer of OSCs to serve as supramolecular stabilizers for regulating the thermal transitions and optimizing the crystallization of the absorber composites. By establishing intimate π-π interactions with small-molecule acceptors, these stabilizers can effectively reduce the trap-state density (Nt) in the devices to achieve excellent PCEs over 19%. More importantly, the low Nt associated with an initially optimized morphology can be maintained under external stresses to significantly reduce the PCE burn-in loss in devices. Our research reveals a judicious approach to improving OPV stability by establishing a comprehensive correlation between material properties, active-layer morphology, and device performance, for developing burn-in-free OSCs. This article is protected by copyright. All rights reserved.

2.
Sci Adv ; 10(14): eadk0647, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38569023

RESUMO

Conjugated polymers have demonstrated promising optoelectronic properties, but their brittleness and poor mechanical characteristics have hindered their fabrication into durable fibers and textiles. Here, we report a universal approach to continuously producing highly strong, ultratough conjugated polymer fibers using a flow-enhanced crystallization (FLEX) method. These fibers exhibit one order of magnitude higher tensile strength (>200 megapascals) and toughness (>80 megajoules per cubic meter) than traditional semiconducting polymer fibers and films, outperforming many synthetic fibers, ready for scalable production. These fibers also exhibit unique strain-enhanced electronic properties and exceptional performance when used as stretchable conductors, thermoelectrics, transistors, and sensors. This work not only highlights the influence of fluid mechanical effects on the crystallization and mechanical properties of conjugated polymers but also opens up exciting possibilities for integrating these functional fibers into wearable electronics.

3.
World J Gastrointest Surg ; 16(3): 700-709, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38577087

RESUMO

BACKGROUND: Gastric cancer (GC) is the fifth most common type of cancer and has the fourth highest death rate among all cancers. There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC. AIM: To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC. METHODS: This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023. The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method. The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases. RESULTS: The analysis comprised 48 patients diagnosed with advanced GC, who were categorized into two groups: A liver metastasis cohort (n = 20) and a non-liver metastatic cohort (n = 28). Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis. The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0% and 35.7% (P > 0.05), respectively. Similarly, the disease control rates in these two cohorts were 65.0% and 82.1% (P > 0.05), respectively. The median progression-free survival was 5.0 months in one group and 11.2 months in the other group, with a hazard ratio of 0.40 and a significance level (P) less than 0.05. The median overall survival was 12.0 months in one group and 19.0 months in the other group, with a significance level (P) greater than 0.05. CONCLUSION: Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

4.
BMC Gastroenterol ; 24(1): 129, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589828

RESUMO

BACKGROUND: The HAP, Six-and-Twelve, Up to Seven, and ALBI scores have been substantiated as reliable prognostic markers in patients presenting with intermediate and advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) treatment. Given this premise, our research aims to assess the predictive efficacy of these models in patients with intermediate and advanced HCC receiving a combination of TACE and Apatinib. Additionally, we have conducted a meticulous comparative analysis of these four scoring systems to discern their respective predictive capacities and efficacies in combined therapy. METHODS: Performing a retrospective analysis on the clinical data from 200 patients with intermediate and advanced HCC, we studied those who received TACE combined with Apatinib at the First Affiliated Hospital of the University of Science and Technology of China between June 2018 and December 2022. To identify the factors affecting survival, the study performed univariate and multivariate Cox regression analyses, with calculations of four different scores: HAP, Six-and-Twelve, Up to Seven, and ALBI. Lastly, Harrell's C-index was employed to compare the prognostic abilities of these scores. RESULTS: Cox proportional hazards model results revealed that the ALBI score, presence of portal vein tumor thrombus (PVTT, )and tumor size are independent determinants of prognostic survival. The Kaplan-Meier analyses showed significant differences in survival rates among patients classified by the HAP, Six-and-Twelve, Up to Seven, and ALBI scoring methods. Of the evaluated systems, the HAP scoring demonstrated greater prognostic precision, with a Harrell's C-index of 0.742, surpassing the alternative models (P < 0.05). In addition, an analysis of the area under the AU-ROC curve confirms the remarkable superiority of the HAP score in predicting short-term survival outcomes. CONCLUSION: Our study confirms the predictive value of HAP, Six-and-Twelve, Up to Seven, and ALBI scores in intermediate to advanced Hepatocellular Carcinoma (HCC) patients receiving combined Transarterial Chemoembolization (TACE) and Apatinib therapy. Notably, the HAP model excels in predicting outcomes for this specific HCC subgroup.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Piridinas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/métodos , Estudos Retrospectivos , Prognóstico
5.
Adv Sci (Weinh) ; : e2309871, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572674

RESUMO

The rapid development of the Internet of Things has triggered a huge demand for self-sustained technology that can provide a continuous electricity supply for low-power electronics. Here, a self-sustained power supply solution is demonstrated that can produce a 24 h continuous and unipolar electricity output based on thermoelectric devices by harvesting the environmental temperature difference, which is ingeniously established utilizing radiation cooling and selective photothermal conversion. The developed prototype system can stably maintain a large temperature difference of about 1.8 K for a full day despite the real-time changes in environmental temperature and solar radiation, thereby driving continuous electricity output using the built-in thermoelectric device. Specifically, the large output voltage of >102 mV and the power density of >4.4 mW m-2 could be achieved for a full day, which are outstanding among the 24 h self-sustained thermoelectric devices and far higher than the start-up values of the wireless temperature sensor and also the light-emitting diode, enabling the 24 h remote data transmission and lighting, respectively. This work highlights the application prospects of self-sustained thermoelectric devices for low-power electronics.

6.
Pestic Biochem Physiol ; 200: 105817, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582587

RESUMO

Thiram is a kind of organic compound, which is commonly used for sterilization, insecticidal and deodorization in daily life. Its toxicology has been broadly studied. Recently, more and more microRNAs have been shown to participate in the regulation of cartilage development. However, the potential mechanism by which microRNA regulates chondrocyte growth is still unclear. Our experiments have demonstrated that thiram can hamper chondrocytes development and cause a significant increase in miR-203a content in vitro and in vivo trials. miR-203a mimic significantly decrease in mRNA and protein expression of Wnt4, Runx2, COL2A1, ß-catenin and ALP, and significantly enhance the mRNA and protein levels of GSK-3ß. It has been observed that overexpression of miR-203a hindered chondrocytes development. In addition, Runx2 was confirmed to be a direct target of miR-203a by dual luciferase report gene assay. Transfection of si-Runx2 into chondrocytes reveals that significant downregulation of genes is associated with cartilage development. Overall, these results suggest that overexpression of miR-203a inhibits the expression of Runx2. These findings are conducive to elucidate the mechanism of chondrocytes dysplasia induced by thiram and provide new research ideas for the toxicology of thiram.


Assuntos
Condrócitos , MicroRNAs , Condrócitos/metabolismo , Tiram , Glicogênio Sintase Quinase 3 beta/metabolismo , MicroRNAs/genética , RNA Mensageiro/genética
7.
Nat Prod Res ; : 1-6, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38586959

RESUMO

A new natural product olimycin E (1), together with two known compounds of divergolide R (2) and olimycin B (3), were obtained from the marine-derived Streptomyces sp. 11695. The structures of 1-3 were established on the basis of HRESIMS as well as 1D and 2D NMR datasets. The absolute configuration of 1 is identified as 4 R, 6S, 7S, 10 R by comparison the experiment ECD with that of the theoretical ECD. Antibacterial results showed that compound 2 have antibacterial activities against Staphylococcus aureus and MRSA with the MIC values of 32 µg/mL, respectively.

8.
JAMA Pediatr ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587862
9.
Orphanet J Rare Dis ; 19(1): 144, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575988

RESUMO

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. RESULTS: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density. CONCLUSIONS: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.


Assuntos
Doença de Gaucher , Osteoporose , Humanos , Glucosilceramidase/uso terapêutico , Doença de Gaucher/tratamento farmacológico , Inflamassomos , Osteoporose/genética , Osteoporose/tratamento farmacológico , Densidade Óssea/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-38568768

RESUMO

In biomedical literature, biological pathways are commonly described through a combination of images and text. These pathways contain valuable information, including genes and their relationships, which provide insight into biological mechanisms and precision medicine. Curating pathway information across the literature enables the integration of this information to build a comprehensive knowledge base. While some studies have extracted pathway information from images and text independently, they often overlook the correspondence between the two modalities. In this paper, we present a pathway figure curation system named pathCLIP for identifying genes and gene relations from pathway figures. Our key innovation is the use of an image-text contrastive learning model to learn coordinated embeddings of image snippets and text descriptions of genes and gene relations, thereby improving curation. Our validation results, using pathway figures from PubMed, showed that our multimodal model outperforms models using only a single modality. Additionally, our system effectively curates genes and gene relations from multiple literature sources. Two case studies on extracting pathway information from literature of non-small cell lung cancer and Alzheimer's disease further demonstrate the usefulness of our curated pathway information in enhancing related pathways in the KEGG database.

11.
Dev Cell ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569547

RESUMO

The ability of cells to perceive and respond to mechanical cues is essential for numerous biological activities. Emerging evidence indicates important contributions of organelles to cellular mechanosensitivity and mechanotransduction. However, whether and how the endoplasmic reticulum (ER) senses and reacts to mechanical forces remains elusive. To fill the knowledge gap, after developing a light-inducible ER-specific mechanostimulator (LIMER), we identify that mechanostimulation of ER elicits a transient, rapid efflux of Ca2+ from ER in monkey kidney COS-7 cells, which is dependent on the cation channels transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and polycystin-2 (PKD2) in an additive manner. This ER Ca2+ release can be repeatedly stimulated and tuned by varying the intensity and duration of force application. Moreover, ER-specific mechanostimulation inhibits ER-to-Golgi trafficking. Sustained mechanostimuli increase the levels of binding-immunoglobulin protein (BiP) expression and phosphorylated eIF2α, two markers for ER stress. Our results provide direct evidence for ER mechanosensitivity and tight mechanoregulation of ER functions, placing ER as an important player on the intricate map of cellular mechanotransduction.

12.
Clin Otolaryngol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558499

RESUMO

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38565964

RESUMO

Graft failure is a fatal complication following allogeneic stem cell transplantation where a second transplantation is usually required for salvage. However, there are no recommended regimens for second transplantations for graft failure, especially in the haploidentical transplant setting. We recently reported encouraging outcomes using a novel method (haploidentical transplantation from a different donor after conditioning with fludarabine and cyclophosphamide). Herein, we report updated outcomes in 30 patients using this method. The median time of the second transplantation was 96.5 (33-215) days after the first transplantation. Except for one patient who died at +19d and before engraftment, neutrophil engraftments were achieved in all patients at 11 (8-24) days, while platelet engraftments were achieved in 22 (75.8%) patients at 17.5 (9-140) days. The 1-year OS and DFS were 60% and 53.3%, and CIR and TRM was 6.7% and 33.3%, respectively. Compared with the historical group, neutrophil engraftment (100% versus 58.5%, p < 0.001) and platelet engraftment (75.8% versus 32.3%, p < 0.001) were better in the novel regimen group, and OS was also improved (60.0% versus 26.4%, p = 0.011). In conclusion, salvage haploidentical transplantation from a different donor using the novel regimen represents a promising option to rescue patients with graft failure after the first haploidentical transplantation.

14.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38555476

RESUMO

Antigen presentation on MHC class II (pMHCII presentation) plays an essential role in the adaptive immune response to extracellular pathogens and cancerous cells. But it can also reduce the efficacy of large-molecule drugs by triggering an anti-drug response. Significant progress has been made in pMHCII presentation modeling due to the collection of large-scale pMHC mass spectrometry datasets (ligandomes) and advances in machine learning. Here, we develop graph-pMHC, a graph neural network approach to predict pMHCII presentation. We derive adjacency matrices for pMHCII using Alphafold2-multimer and address the peptide-MHC binding groove alignment problem with a simple graph enumeration strategy. We demonstrate that graph-pMHC dramatically outperforms methods with suboptimal inductive biases, such as the multilayer-perceptron-based NetMHCIIpan-4.0 (+20.17% absolute average precision). Finally, we create an antibody drug immunogenicity dataset from clinical trial data and develop a method for measuring anti-antibody immunogenicity risk using pMHCII presentation models. Our model increases receiver operating characteristic curve (ROC)-area under the ROC curve (AUC) by 2.57% compared to just filtering peptides by hits in OASis alone for predicting antibody drug immunogenicity.


Assuntos
Antígenos de Histocompatibilidade Classe II , Peptídeos , Antígenos de Histocompatibilidade Classe II/química , Peptídeos/química , Apresentação de Antígeno , Redes Neurais de Computação
15.
Respir Res ; 25(1): 143, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553757

RESUMO

BACKGROUND: Although ROX index is frequently used to assess the efficacy of high-flow nasal cannula treatment in acute hypoxemic respiratory failure (AHRF) patients, the relationship between the ROX index and the mortality remains unclear. Therefore, a retrospective cohort study was conducted to evaluate the ability of the ROX index to predict mortality risk in patients with AHRF. METHOD: Patients diagnosed with AHRF were extracted from the MIMIC-IV database and divided into four groups based on the ROX index quartiles. The primary outcome was 28-day mortality, while in-hospital mortality and follow-up mortality were secondary outcomes. To investigate the association between ROX index and mortality in AHRF patients, restricted cubic spline curve and COX proportional risk regression were utilized. RESULT: A non-linear association (L-shaped) has been observed between the ROX index and mortality rate. When the ROX index is below 8.28, there is a notable decline in the 28-day mortality risk of patients as the ROX index increases (HR per SD, 0.858 [95%CI 0.794-0.928] P < 0.001). When the ROX index is above 8.28, no significant association was found between the ROX index and 28-day mortality. In contrast to the Q1 group, the mortality rates in the Q2, Q3, and Q4 groups had a substantial reduction (Q1 vs. Q2: HR, 0.749 [0.590-0.950] P = 0.017; Q3: HR, 0.711 [0.558-0.906] P = 0.006; Q4: HR, 0.641 [0.495-0.830] P < 0.001). CONCLUSION: The ROX index serves as a valuable predictor of mortality risk in adult patients with AHRF, and that a lower ROX index is substantially associated with an increase in mortality.


Assuntos
Cânula , Insuficiência Respiratória , Adulto , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Administração Intranasal , Bases de Dados Factuais , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/terapia , Oxigenoterapia
16.
Angew Chem Int Ed Engl ; : e202316717, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477147

RESUMO

The electrolytes for lithium metal batteries (LMBs) are plagued by a low Li+ transference number (T+) of conventional lithium salts and inability to form a stable solid electrolyte interphase (SEI). Here, we synthesized a self-folded lithium salt, lithium 2-[2-(2-methoxy ethoxy)ethoxy]ethanesulfonyl(trifluoromethanesulfonyl) imide (LiETFSI), and comparatively studied with its structure analogue, lithium 1,1,1-trifluoro-N-[2-[2-(2-methoxyethoxy)ethoxy)]ethyl]methanesulfonamide (LiFEA). The special anion chemistry imparts the following new characteristics: i) In both LiFEA and LiETFSI, the ethylene oxide moiety efficiently captures Li+, resulting in a self-folded structure and high T+ around 0.8. ii) For LiFEA, a Li-N bond (2.069 Å) is revealed by single crystal X-ray diffraction, indicating that the FEA anion possesses a high donor number (DN) and thus an intensive interphase "self-cleaning" function for an ultra-thin and compact SEI. iii) Starting from LiFEA, an electron-withdrawing sulfone group is introduced near the N atom. The distance of Li-N is tuned from 2.069 Šin LiFEA to 4.367 Šin LiETFSI. This alteration enhances ionic separation, achieves a more balanced DN, and tunes the self-cleaning intensity for a reinforced SEI. Consequently, the fast charging/discharging capability of LMBs is progressively improved. This rationally tuned anion chemistry reshapes the interactions among Li+, anions, and solvents, presenting new prospects for advanced LMBs.

17.
J Gastroenterol ; 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38461467

RESUMO

BACKGROUND: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. METHODS: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. RESULTS: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. CONCLUSION: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC.

18.
Sensors (Basel) ; 24(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38474962

RESUMO

To evaluate the lifetime and reliability of long-life, high-reliability products under limited resources, accelerated degradation testing (ADT) technology has been widely applied. Furthermore, the Bayesian evaluation method for ADT can comprehensively utilize historical information and overcome the limitations caused by small sample sizes, garnering significant attention from scholars. However, the traditional ADT Bayesian evaluation method has inherent shortcomings and limitations. Due to the constraints of small samples and an incomplete understanding of degradation mechanisms or accelerated mechanisms, the selected evaluation model may be inaccurate, leading to potentially inaccurate evaluation results. Therefore, describing and quantifying the impact of model uncertainty on evaluation results is a challenging issue that urgently needs resolution in the theoretical research of ADT Bayesian methods. This article addresses the issue of model uncertainty in the ADT Bayesian evaluation process. It analyzes the modeling process of ADT Bayesian and proposes a new model averaging evaluation method for ADT Bayesian based on relative entropy, which, to a certain extent, can resolve the issue of evaluation inaccuracy caused by model selection uncertainty. This study holds certain theoretical and engineering application value for conducting ADT Bayesian evaluation under model uncertainty.

19.
Adv Sci (Weinh) ; : e2401611, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509850

RESUMO

Cell mechanotransduction signals are important targets for physical therapy. However, current physiotherapy heavily relies on ultrasound, which is generated by high-power equipment or amplified by auxiliary drugs, potentially causing undesired side effects. To address current limitations, a robotic actuation-mediated therapy is developed that utilizes gentle mechanical loads to activate mechanosensitive ion channels. The resulting calcium influx precisely regulated the expression of recombinant tumor suppressor protein and death-associated protein kinase, leading to programmed apoptosis of cancer cell line through caspase-dependent pathway. In stark contrast to traditional gene therapy, the complete elimination of early- and middle-stage tumors (volume ≤ 100 mm3) and significant growth inhibition of late-stage tumor (500 mm3) are realized in tumor-bearing mice by transfecting mechanogenetic circuits and treating daily with quantitative robotic actuation in a form of 5 min treatment over the course of 14 days. Thus, this massage-derived therapy represents a quantitative strategy for cancer treatment.

20.
Nat Commun ; 15(1): 2365, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491012

RESUMO

It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Luminescência
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