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1.
Artigo em Inglês | MEDLINE | ID: mdl-38652626

RESUMO

Contrastive learning (CL) has emerged as a powerful approach for self-supervised learning. However, it suffers from sampling bias, which hinders its performance. While the mainstream solutions, hard negative mining (HNM) and supervised CL (SCL), have been proposed to mitigate this critical issue, they do not effectively address graph CL (GCL). To address it, we propose graph positive sampling (GPS) and three contrastive objectives. The former is a novel learning paradigm designed to leverage the inherent properties of graphs for improved GCL models, which utilizes four complementary similarity measurements, including node centrality, topological distance, neighborhood overlapping, and semantic distance, to select positive counterparts for each node. Notably, GPS operates without relying on true labels and enables preprocessing applications. The latter aims to fuse positive samples and enhance representative selection in the semantic space. We release three node-level models with GPS and conduct extensive experiments on public datasets. The results demonstrate the superiority of GPS over state-of-the-art (SOTA) baselines and debiasing methods. In addition, the GPS has also been proven to be versatile, adaptive, and flexible.

2.
RSC Adv ; 14(18): 12911-12922, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38650688

RESUMO

Thermal insulation materials with good flame-retardant properties have attracted widespread attention because of their huge application potential. Traditional petrochemical-based polymer insulation materials are flammable and have problems with environmental pollution. The microtubule structure is a perfect microstructure with excellent thermal insulation performance. In addition, the microtubule structure also has low density and high elasticity. Therefore, the microtubule structure is an important reference microstructure for the development of efficient thermal insulation materials. In this paper, a cellulose/SiO2 composite microtube thermal insulation superfoam has been successfully prepared. Cellulose microtubules were successfully prepared from poplar sawdust by chemical methods. The SiO2 aerogel precursor solution can be quickly adsorbed by the delignified cellulose microtubes. The SiO2 aerogel shells are evenly distributed only on the inner and outer walls of the delignified cellulose microtubes. The cellulose/SiO2 microtube composite (CSMC) superfoam exhibits low density, good mechanical properties, and low thermal conductivity (as low as 0.042 ± 0.0018 W m-1 K-1). The CSMC superfoam exhibits excellent self-extinguishing and flame-retardant properties. After being burned by a butane flame, the superfoam still has certain mechanical properties. The thermal conductivity of the B-CSMC superfoam (the CSMC superfoam burned by a butane flame) is about 0.050 W m-1 K-1. The B-CSMC superfoam remained almost unchanged after being continuously ablated by a butane flame for 3600 seconds.

3.
Orthop Surg ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38650179

RESUMO

OBJECTIVE: Peroneus Longus Tendon (PLT), a viable anterior cruciate ligament (ACL) graft, shares similar biomechanics, making it suitable for reconstruction. Controversy exists over whether PLT transplants affects the donor ankle joint. The purpose of this study was to examine the recovery of knee joint function following arthroscopic ACL restoration using autologous PLT and its influence on the donor ankle joint. METHODS: A retrospective analysis was conducted on 65 patients with ACL rupture who underwent PLT graft reconstruction in our hospital from January 2016 to December 2021. A three-dimensional gait analysis of the bilateral knee and ankle joints was performed postoperatively using an Opti_Knee three-dimensional motion measurement and analysis system-Yidong Medical Infrared Motion Gait Analyzer. Knee function scores and changes in the range of motion of the bilateral knee and ankle joints were collected. The analysis of preoperative and postoperative joint function scores, bilateral knee and ankle mobility was performed by t-tests. RESULTS: One year after surgery, the patients' International Knee Documentation Committee (IKDC) scores, Knee Injury and Osteoarthritis Outcome Scores (KOOSs), and Lysholm scores were significantly improved compared to preoperative scores, with statistically significant differences (p < 0.05). There was no statistical difference in the American Orthopedic Foot and Ankle Society (AOFAS) score of the donor ankle joint before and after surgery (p > 0.05). During different gait cycles, there was no statistical difference in knee joint mobility between the affected and healthy sides (p > 0.05), but there was a statistical difference in the inversion and eversion angle of the donor ankle joint during the support phase (p < 0.05). CONCLUSION: ACL reconstruction using the PLT can yield satisfactory knee joint function. However, it does affect inversion and eversion in the donor ankle joint, necessitating postoperative exercises. Similar subjective function ratings for both operated and non-operated feet, despite increased inversion-eversion motion in the operated foot, may be influenced by the subjective nature and margin of error in the AOFAS Ankle-hindfoot score, along with the relatively small variation in ankle inversion-eversion angles.

4.
ACS Nano ; 18(16): 10902-10911, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38606667

RESUMO

The practical application of high-energy density lithium-oxygen (Li-O2) batteries is severely impeded by the notorious cycling stability and safety, which mainly comes from slow kinetics of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) at cathodes, causing inferior redox overpotentials and reactive lithium metal in flammable liquid electrolyte. Herein, a bifunctional electrode, a safe gel polymer electrolyte (GPE), and a robust lithium anode are proposed to alleviate above problems. The bifunctional electrode is composed of N-doped carbon nanotubes (N-CNTs) and Co4N by in situ chemical vapor deposition self-catalyzed growth on carbon cloth (N-CNTs@Co4N@CC). The self-supporting, binder-free N-CNTs@Co4N@CC electrode has a strong and stable three-dimensional (3D) interconnected conductive structure, which provides interconnectivity between the active sites and the electrode to promote the transfer of electrons. Furthermore, the N-CNT-intertwined Co4N ensures efficient catalytic activity. Hence, the electrode demonstrates improved electrochemical properties even under a large current density (2000 mA g-1) and long cycling operation (250 cycles). Moreover, a highly safe and flexible rechargeable cell using the 3D N-CNTs@Co4N@CC electrode, GPE, and robust lithium anode design has been explored. The open circuit voltage is stable at ∼3.0 V even after 9800 cycles, which proves the mechanical durability of the integrated GPE cell. The stable cable-type Li-air battery was demonstrated to stably drive the light-emitting diodes (LEDs), highlighting the reliability for practical use.

5.
Materials (Basel) ; 17(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38541510

RESUMO

Thermally induced pores (TIPs) are generally the source of fatigue crack initiation in the powder metallurgy (PM) Ni-based FGH96 superalloy. The effect of TIPs on fatigue crack initiation on the surface of the FGH96 superalloy was detected using scanning electron microscopy (SEM). The cause of fatigue crack deflection was studied using electron backscatter diffraction (EBSD) analysis. The results indicated that there are two states of TIPs including isolated TIPs and clustered TIPs located at the grain boundary. The investigation of crack initiation and propagation around TIPs was conducted in detail through the comprehensive integration of experimental findings and computational results. For cracks initiated by isolated TIPs, the maximum equivalent size and the ratio of the vertical-parallel axis to the loading direction of the TIPs reveal a linear relationship, and both of them determine crack initiation. Regarding clustered TIPs, the constituent pores of the clustered TIPs will compete to initiate cracks based on the experimental results, and the largest pore will be more likely to initiate cracking. Moreover, the results showed that fatigue crack propagation can be hindered by hard-orientation grains and twins with a low Schmid factor (SF). Large-angle crack deflection due to twins with a low SF can significantly increase crack length and resistance to crack propagation.

6.
J Neuroinflammation ; 21(1): 73, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528529

RESUMO

BACKGROUND: Guillain-Barré syndrome (GBS), a post-infectious, immune-mediated, acute demyelinating disease of the peripheral nerves and nerve roots, represents the most prevalent and severe acute paralyzing neuropathy. Purinergic P2X7 receptors (P2X7R) play a crucial role in central nervous system inflammation. However, little is known about their role in the immune-inflammatory response within the peripheral nervous system. METHODS: Initially, we assessed the expression of purinergic P2X7R in the peripheral blood of patients with GBS using flow cytometry and qRT-PCR. Next, we explored the expression of P2 X7R in CD4+ T cells, CD8+ T cells, and macrophages within the sciatic nerves and spleens of rats using immunofluorescence labeling and flow cytometry. The P2X7R antagonist brilliant blue G (BBG) was employed to examine its therapeutic impact on rats with experimental autoimmune neuritis (EAN) induced by immunization with the P0180 - 199 peptide. We analyzed CD4+ T cell differentiation in splenic mononuclear cells using flow cytometry, assessed Th17 cell differentiation in the sciatic nerve through immunofluorescence staining, and examined the expression of pro-inflammatory cytokine mRNA using RT-PCR. Additionally, we performed protein blotting to assess the expression of P2X7R and NLRP3-related inflammatory proteins within the sciatic nerve. Lastly, we utilized flow cytometry and immunofluorescence labeling to examine the expression of NLRP3 on CD4+ T cells in rats with EAN. RESULTS: P2X7R expression was elevated not only in the peripheral blood of patients with GBS but also in rats with EAN. In rats with EAN, inhibiting P2X7R with BBG alleviated neurological symptoms, reduced demyelination, decreased inflammatory cell infiltration of the peripheral nerves, and improved nerve conduction. BBG also limited the production of pro-inflammatory molecules, down-regulated the expression of P2X7R and NLRP3, and suppressed the differentiation of Th1 and Th17 cells, thus protecting against EAN. These effects collectively contribute to modifying the inflammatory environment and enhancing outcomes in EAN rats. CONCLUSIONS: Suppression of P2X7R relieved EAN manifestation by regulating CD4+ T cell differentiation and NLRP3 inflammasome activation. This finding underscores the potential significance of P2X7R as a target for anti-inflammatory treatments, advancing research and management of GBS.


Assuntos
Síndrome de Guillain-Barré , Neurite Autoimune Experimental , Antagonistas do Receptor Purinérgico P2X , Animais , Humanos , Ratos , Linfócitos T CD8-Positivos , Diferenciação Celular/efeitos dos fármacos , Síndrome de Guillain-Barré/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Antagonistas do Receptor Purinérgico P2X/farmacologia , Antagonistas do Receptor Purinérgico P2X/uso terapêutico , Nervo Isquiático/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Células Th1/efeitos dos fármacos , Células Th1/metabolismo
7.
RSC Adv ; 14(11): 7350-7358, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38433938

RESUMO

High-performance thermal insulation materials with broad application prospects have attracted great attention. The introduction of new microstructures into thermal protection materials can significantly improve the thermal insulation performance. The tubular microstructure has obvious advantages such as thermal insulation, lightweight, mechanical, and other properties. Therefore, the microtubular structure has become an important reference microstructure for the development of high-performance thermal insulation materials. In this paper, the carbon/ZrO2 aerogel composite microtube superfoams with excellent thermal protection properties were prepared by a vacuum filtration and high-temperature carbonization method. The ZrO2 aerogel precursor solution can be quickly and uniformly adsorbed on the inner and outer walls of cellulose microtubules. These adsorbed ZrO2 aerogel precursor solution films can be converted into ZrO2 alcohol gel shells under the acceleration and promotion effect of citric acid at 65 °C. The micromorphology of the ZrO2 aerogel shell on the inner and outer walls of the composite microtubes can be efficiently controlled by the concentration of the ZrO2 aerogel precursor solution and the carbonization temperature. The carbon/ZrO2 aerogel composite microtube superfoam exhibits a lower thermal conductivity, lower density, good mechanical properties, and high ablation resistance. The thermal conductivity of the carbon/ZrO2 aerogel composite microtube superfoam is as low as 0.040 ± 0.001 W m-1 K-1. The residual rate of the carbon/ZrO2 aerogel composite microtube superfoam is still as high as 84.33% after butane flame ablation for up to 3600 seconds.

8.
ACS Appl Mater Interfaces ; 16(10): 12924-12938, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426939

RESUMO

The commercialization of alloy-type anodes has been hindered by rapid capacity degradation due to volume fluctuations. To address this issue, stress-relief engineering is proposed for Si anodes that combines hierarchical nanoporous structures and modified layers, inspired by the phenomenon in which structures with continuous changes in curvature can reduce stress concentration. The N-doped C-modified hierarchical nanoporous Si anode with a microcurved pore wall (N-C@m-HNP Si) is prepared from inexpensive Mg-55Si alloys using a simple chemical etching and heat treatment process. When used as the anode for lithium-ion batteries, the N-C@m-HNP Si anode exhibits initial charge/discharge specific capacities of 1092.93 and 2636.32 mAh g-1 at 0.1 C (1 C = 3579 mA g-1), respectively, and a stable reversible specific capacity of 1071.84 mAh g-1 after 200 cycles. The synergy of the hierarchical porous structure with a microcurved pore wall and the N-doped C-modified layer effectively improves the electrochemical performance of N-C@m-HNP Si, and the effectiveness of stress-relief engineering is quantitatively analyzed through the theory of elastic bending of thin plates. Moreover, the formation process of Li15Si4 crystals, which causes substantial mechanical stress, is investigated using first-principles molecular dynamic simulations to reveal their tendency to occur at different scales. The results demonstrate that the hierarchical nanoporous structure helps to inhibit the transformation of amorphous LixSi into metastable Li15Si4 crystals during lithiation.

9.
Artif Intell Med ; 149: 102778, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462280

RESUMO

Many computational methods have been proposed to identify potential drug-target interactions (DTIs) to expedite drug development. Graph neural network (GNN) methods are considered to be one of the most effective approaches. However, shallow GNN methods can only aggregate local information from nodes. Also, deep GNN methods may result in over-smoothing while obtaining long-distance neighbourhood information. As a result, existing GNN methods struggle to extract the complete features of the graph. Additionally, the number of known DTIs is insufficient, and there are far more unknown drug-target pairs than known DTIs, leading to class imbalance. This article proposes a model that combines graph autoencoder and self-supervised learning to accurately encode multilevel features of graphs using only a small number of labelled samples. We introduce a positive sample compensation coefficient to the objective function to mitigate the impact of class imbalance. Experiments on two datasets demonstrated that our model outperforms the four baseline methods, and the new DTIs predicted by the SSLDTI model were verified by the DrugBank database.


Assuntos
Desenvolvimento de Medicamentos , Redes Neurais de Computação , Bases de Dados Factuais , Aprendizado de Máquina Supervisionado
10.
Med Phys ; 51(4): 3076-3092, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38408025

RESUMO

BACKGROUND: The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. PURPOSE: The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. METHODS: Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS-nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. RESULTS: Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and ß, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter M 1 C 2 $M_1^{{{\mathrm{C}}}_2}$ effectively captures the fluctuations in model coefficients α and RBE. CONCLUSION: Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning.


Assuntos
Terapia por Captura de Nêutron de Boro , Modelos Biológicos , Eficiência Biológica Relativa , Radiobiologia , Método de Monte Carlo
11.
Eur J Pharmacol ; 969: 176457, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38395375

RESUMO

Neuropeptide FF (NPFF) plays a critical role in various physiological processes through the activation of neuropeptide FF receptor 1 and 2 (NPFFR1 and NPFFR2). Numerous evidence has indicated that NPFF exhibits opposite opioid-modulating effects on opioid-induced analgesia after supraspinal and spinal administrations, while the detailed role of NPFFR1 and NPFFR2 remains unclear. In this study, we employed pharmacological and genetic inhibition of NPFFR to investigate the modulating roles of central NPFFR1 and NPFFR2 in opioid-induced analgesia and hyperalgesia, using a male mouse model of acute fentanyl-induced analgesia and secondary hyperalgesia. Our findings revealed that intrathecal (i.t.) injection of the nonselective NPFFR antagonist RF9 significantly enhanced fentanyl-induced analgesia, whereas intracerebroventricular (i.c.v.) injection did not show the same effect. Moreover, NPFFR2 deficient (npffr2-/-) mice exhibited stronger analgesic responses to fentanyl compared to wild type (WT) or NPFFR1 knockout (npffr1-/-) mice. Intrathecal injection of RF9 in npffr1-/- mice also significantly enhanced fentanyl-induced analgesia. These results indicate a crucial role of spinal NPFFR2 in the enhancement of opioid analgesia. Contrastingly, hyperalgesia induced by fentanyl was markedly reversed in npffr1-/- mice but remained unaffected in npffr2-/- mice. Similarly, i.c.v. injection of the selective NPFFR1 antagonist RF3286 effectively prevented fentanyl-induced hyperalgesia in WT or npffr2-/- mice. Notably, co-administration of i.c.v. RF3286 and i.t. RF9 augmented fentanyl-induced analgesia while reducing hyperalgesia. Collectively, these findings highlight the modulating effects of blocking spinal NPFFR2 and supraspinal NPFFR1 on fentanyl-induced analgesia and hyperalgesia, respectively, which shed a light on understanding the pharmacological function of NPFF system in future studies.


Assuntos
Analgesia , Hiperalgesia , Camundongos , Masculino , Animais , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Fentanila/farmacologia , Analgésicos Opioides/farmacologia , Dor , Receptores de Neuropeptídeos/genética
12.
BMC Cancer ; 24(1): 276, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38424484

RESUMO

BACKGROUND: Adenosine monophosphate-activated protein kinase (AMPK) is associated with the development of liver hepatocellular carcinoma (LIHC). AMPKα2, an α2 subunit of AMPK, is encoded by PRKAA2, and functions as the catalytic core of AMPK. However, the role of AMPKα2 in the LIHC tumor immune environment is unclear. METHODS: RNA-seq data were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression databases. Using the single-cell RNA-sequencing dataset for LIHC obtained from the China National Genebank Database, the communication between malignant cells and T cells in response to different PRKAA2 expression patterns was evaluated. In addition, the association between PRKAA2 expression and T-cell evolution during tumor progression was explored using Pseudotime analysis, and the role of PRKAA2 in metabolic reprogramming was explored using the R "scMetabolis" package. Functional experiments were performed in LIHC HepG2 cells. RESULTS: AMPK subunits were expressed in tissue-specific and substrate-specific patterns. PRKAA2 was highly expressed in LIHC tissues and was associated with poor patient prognosis. Tumors with high PRKAA2 expression displayed an immune cold phenotype. High PRKAA2 expression significantly promoted LIHC immune escape. This result is supported by the following evidence: 1) the inhibition of major histocompatibility complex class I (MHC-I) expression through the regulation of interferon-gamma activity in malignant cells; 2) the promotion of CD8+ T-cell exhaustion and the formation of CD4+ Treg cells in T cells; 3) altered interactions between malignant cells and T cells in the tumor immune environment; and 4) induction of metabolic reprogramming in malignant cells. CONCLUSIONS: Our study indicate that PRKAA2 may contribute to LIHC progression by promoting metabolic reprogramming and tumor immune escape through theoretical analysis, which offers a theoretical foundation for developing PRKAA2-based strategies for personalized LIHC treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteínas Quinases Ativadas por AMP , Carcinoma Hepatocelular/genética , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Neoplasias Hepáticas/genética , Exaustão das Células T , Linfócitos T Reguladores , Evasão Tumoral
13.
Small ; : e2311827, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381114

RESUMO

The expeditious growth of wearable electronic devices has boomed the development of versatile smart textiles for personal health-related applications. In practice, integrated high-performance systems still face challenges of compromised breathability, high cost, and complicated manufacturing processes. Herein, a breathable fibrous membrane with dual-driven heating and electromagnetic interference (EMI) shielding performance is developed through a facile process of electrospinning followed by targeted conformal deposition. The approach constructs a robust hierarchically coaxial heterostructure consisting of elastic polymers as supportive "core" and dual-conductive components of polypyrrole and copper sulfide (CuS) nanosheets as continuous "sheath" at the fiber level. The CuS nanosheets with metal-like electrical conductivity demonstrate the promising potential to substitute the expensive conductive nano-materials with a complex fabricating process. The as-prepared fibrous membrane exhibits high electrical conductivity (70.38 S cm-1 ), exceptional active heating effects, including solar heating (saturation temperature of 69.7 °C at 1 sun) and Joule heating (75.2 °C at 2.9 V), and impressive EMI shielding performance (50.11 dB in the X-band), coupled with favorable air permeability (161.4 mm s-1 at 200 Pa) and efficient water vapor transmittance (118.9 g m-2 h). This work opens up a new avenue to fabricate versatile wearable devices for personal thermal management and health protection.

14.
J Biophotonics ; 17(4): e202300417, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221649

RESUMO

Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion that has the potential to progress to invasive pancreatic cancer, and early and rapid detection may offer patients a chance for treatment before the development of invasive carcinoma. Therefore, the identification of PanIN holds significant clinical importance. In this study, we first used multiphoton microscopy (MPM) combining two-photon excitation fluorescence and second-harmonic generation imaging to label-free detect PanIN and attempted to differentiate between normal pancreatic ducts and different grades of PanIN. Then, we also developed an automatic image processing strategy to extract eight morphological features of collagen fibers from MPM images to quantify the changes in collagen fibers surrounding the ducts. Experimental results demonstrate that the combination of MPM and quantitative information can accurately identify normal pancreatic ducts and different grades of PanIN. This study may contribute to the rapid diagnosis of pancreatic diseases and may lay the foundation for further clinical application of MPM.


Assuntos
Microscopia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Pâncreas , Colágeno , Microscopia de Fluorescência por Excitação Multifotônica/métodos
15.
Mol Cancer ; 23(1): 11, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200551

RESUMO

Dysregulation of R-loop homeostasis is closely related to various human diseases, including cancer. However, the causality of aberrant R-loops in tumor progression remains unclear. In this study, using single-cell RNA-sequencing datasets from lung adenocarcinoma (LUAD), we constructed an R-loop scoring model to characterize the R-loop state according to the identified R-loop regulators related to EGFR mutations, tissue origins, and TNM stage. We then evaluated the relationships of the R-loop score with the tumor microenvironment (TME) and treatment response. Furthermore, the potential roles of FANCI-mediated R-loops in LUAD were explored using a series of in vitro experiments. Results showed that malignant cells with low R-loop scores displayed glycolysis and epithelial-mesenchymal transition pathway activation and immune escape promotion, thereby hampering the antitumor therapeutic effects. Cell communication analysis suggested that low R-loop scores contributed to T cell exhaustion. We subsequently validated the prognostic value of R-loop scores by using bulk transcriptome datasets across 33 tumor types. The R-loop scoring model well predicted patients' therapeutic response to targeted therapy, chemotherapy, or immunotherapy in 32 independent cohorts. Remarkably, changes in R-loop distribution mediated by FANCI deficiency blocked the activity of Ras signaling pathway, suppressing tumor-cell proliferation and dissemination. In conclusion, this study reveals the underlying molecular mechanism of metabolic reprogramming and T cell exhaustion under R-loop score patterns, and the changes in R-loops mediated by R-loop regulators resulting in tumor progression. Therefore, incorporating anticancer methods based on R-loop or R-loop regulators into the treatment schemes of precision medicine may be beneficial.


Assuntos
Adenocarcinoma de Pulmão , Anemia de Fanconi , Neoplasias Pulmonares , Humanos , Estruturas R-Loop , 60645 , Evasão da Resposta Imune , Adenocarcinoma de Pulmão/genética , Comunicação Celular , Análise de Célula Única , Neoplasias Pulmonares/genética , Microambiente Tumoral/genética
16.
Biomater Sci ; 12(4): 949-963, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38221844

RESUMO

The shortage of face masks and the lack of antipathogenic functions has been significant since the recent pandemic's inception. Moreover, the disposal of an enormous number of contaminated face masks not only carries a significant environmental impact but also escalates the risk of cross-contamination. This study proposes a strategy to upgrade available surgical masks into antibacterial masks with enhanced particle and bacterial filtration. Plasmonic nanoparticles can provide photodynamic and photothermal functionalities for surgical masks. For this purpose, gold nanorods act as on-demand agents to eliminate pathogens on the surface of the masks upon near-infrared light irradiation. Additionally, the modified masks are furnished with polymer electrospun nanofibrous layers. These electrospun layers can enhance the particle and bacterial filtration efficiency, not at the cost of the pressure drop of the mask. Consequently, fabricating these prototype masks could be a practical approach to upgrading the available masks to alleviate the environmental toll of disposable face masks.


Assuntos
Nanofibras , Nanopartículas , Nanotubos , Máscaras , Filtração
17.
Int J Cancer ; 154(10): 1802-1813, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38268429

RESUMO

Ductal carcinoma in situ with microinvasion (DCISM) is a challenging subtype of breast cancer with controversial invasiveness and prognosis. Accurate diagnosis of DCISM from ductal carcinoma in situ (DCIS) is crucial for optimal treatment and improved clinical outcomes. However, there are often some suspicious small cancer nests in DCIS, and it is difficult to diagnose the presence of intact myoepithelium by conventional hematoxylin and eosin (H&E) stained images. Although a variety of biomarkers are available for immunohistochemical (IHC) staining of myoepithelial cells, no single biomarker is consistently sensitive to all tumor lesions. Here, we introduced a new diagnostic method that provides rapid and accurate diagnosis of DCISM using multiphoton microscopy (MPM). Suspicious foci in H&E-stained images were labeled as regions of interest (ROIs), and the nuclei within these ROIs were segmented using a deep learning model. MPM was used to capture images of the ROIs in H&E-stained sections. The intensity of two-photon excitation fluorescence (TPEF) in the myoepithelium was significantly different from that in tumor parenchyma and tumor stroma. Through the use of MPM, the myoepithelium and basement membrane can be easily observed via TPEF and second-harmonic generation (SHG), respectively. By fusing the nuclei in H&E-stained images with MPM images, DCISM can be differentiated from suspicious small cancer clusters in DCIS. The proposed method demonstrated good consistency with the cytokeratin 5/6 (CK5/6) myoepithelial staining method (kappa coefficient = 0.818).


Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/patologia , Imuno-Histoquímica , Microscopia , Neoplasias da Mama/patologia , Coloração e Rotulagem , Invasividade Neoplásica
18.
Adv Sci (Weinh) ; 11(7): e2307052, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063837

RESUMO

Aqueous zinc (Zn) ion batteries (AZIBs) have not yet fulfilled their talent of high safety and low cost since the anode/electrolyte interface (AEI) has long been impeded by hydrogen evolution, surface corrosion, dendritic growth, and by-product accumulation. Here, the hydrolysis of solid buffers is elaborately proposed to comprehensively and enduringly handle these issues. Take 2D layered black phosphorus (BP) as a hydrolytic subject. It is reported that the phosphoric acid generated by hydrolysis in an aqueous electrolyte produces a zinc phosphate (ZPO) rich solid electrolyte interphase (SEI) layer, which largely inhibits the dendrite growth, surface corrosion, and hydrogen evolution. Meanwhile, the hydrolytic phosphoric acid stabilizes the pH value near AEI, avoiding the accumulation of alkaline by-products. Notably, compared with the disposable ZPO engineerings of anodic SEI pre-construction and electrolyte additive, the hydrolysis strategy of BP can realize a dramatically prolonged protective effect. As a result, these multiple merits endow BP modified separator to achieve improved stripping/plating stability toward Zn anode with more than ten times lifespan enhancement in Zn||Zn symmetrical cell. More encouragingly, when coupled with a V2 O5 ·nH2 O cathode with ultra-high loadings (34.1 and 28.7 mg cm-2 ), the cumulative capacities are remarkably promoted for both coin and pouch cells.

19.
Adv Sci (Weinh) ; 11(8): e2305061, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37939285

RESUMO

Aqueous zinc-halogen batteries (AZHBs) have emerged as promising candidates for energy storage applications due to their high security features and low cost. However, several challenges including natural subliming, sluggish reaction kinetics, and shuttle effect of halogens, as well as dendrite growth of the zinc (Zn) anode, have hindered their large-scale commercialization. In this review, first the fundamental mechanisms and scientific issues associated with AZHBs are summarized. Then the research issues and progresses related to the cathode, separator, anode, and electrolyte are discussed. Additionally, emerging research opportunities in this field is explored. Finally, ideas and prospects for the future development of AZHBs are presented. The objective of this review is to stimulate further exploration, foster the advancement of AZHBs, and contribute to the diversified development of electrochemical energy storage.

20.
Int J Infect Dis ; 139: 101-108, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065317

RESUMO

OBJECTIVES: To explore the effects of perioperative SARS-CoV-2 Omicron infection on postoperative complications in patients with liver cancer. METHODS: A propensity-matched study was conducted, which included patients with primary liver cancer who underwent hepatectomy from September 01, 2022 to January 20, 2023. Patients who infected SARS-CoV-2 Omicron during the perioperative period (7 days before to 30 days after surgery) were matched 1:1 with noninfected patients. The primary outcomes, which were COVID-19-related major complications and liver resection-specific complications, were analyzed using multivariate logistic regression. RESULTS: A total of 243 patients were included, with 63 cases of perioperative infections, of which 62 were postoperative infections. The overall 30-day postoperative mortality rate was 1.6% (4/243). Compared to noninfected patients, those with perioperative infections showed no significant difference in the occurrence of adverse postoperative outcomes. However, they had a higher rate of 30-day readmission after surgery (11.1% vs 0%, P = 0.013). Perioperative SARS-CoV-2 infection was not associated with "major cardiorespiratory complications" or "liver resection-specific complications", but age, pre-existing comorbidities, and tumor type were related to these outcomes. CONCLUSION: Perioperative SARS-CoV-2 Omicron infection did not increase the incidence of postoperative complications in patients with liver cancer. However, those patients had a higher rate of 30-day readmission after surgery.


Assuntos
COVID-19 , Neoplasias Hepáticas , Humanos , Hepatectomia/efeitos adversos , COVID-19/complicações , SARS-CoV-2 , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
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