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Enhancing the velocity of the oxidation-reduction cycle is crucial for improving the catalytic efficiency of Fenton processes. Therefore, the development of an effective strategy for wastewater degradation at low temperatures is essential. In this context, we present the preparation of an NH2-MIL-88B (Fe)/CuInS2 S-scheme heterojunction. Specifically, CuInS2 nanoparticles are introduced onto the Ferro-organic skeleton, resulting in the exposure of a significant number of active surface sites. Furthermore, NH2-MIL-88B (Fe)/CuInS2 demonstrates an extended photoresponse into the long-wavelength region, which contributes to its excellent photothermal properties. Notably, the degradation rate of tetracycline in low-temperature aqueous environments reaches as high as 99.7â¯%, several times higher than that of the original sample. Additionally, the hydrogen production of NH2-MIL-88B (Fe)/CuInS2 is 2.23 times that of single NH2-MIL-88B (Fe) and 3.46 times that of single CuInS2. Moreover, the system exhibits good H2O2 evolution performance, forming an efficient photo-Fenton system. The charge transfer process in S-scheme heterojunction is confirmed using in-situ X-ray photoelectron spectroscopy and electron paramagnetic resonance. Both transient photoluminescence and photo electrochemical tests further validate the enhanced photoelectrochemical properties of the NH2-MIL-88B (Fe)/CuInS2 S-scheme heterojunction. The exceptional performance of this system can be attributed to the synergistic effects of the S-scheme heterojunction and the bimetallic codoped photo-Fenton system. This research presents a novel approach for the breakdown of low-temperature wastewater using an improved photocatalytic Fenton system.
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Gastric cancer has become a great challenge to human health in the world. We studied the expression and role of the circular RNA 0001438 (circ_0001438) with the aim of finding a biomarker to assess the prognosis of gastric cancer. Through a polymerase chain reaction, circ_0001438 expression in gastric cancer was detected. Chi-square test, multi-factor Cox regression, and Kaplan-Meier analyses were used to determine the association between circ_0001438 and the patients' clinical condition and prognosis. Using the luciferase reporter gene system, the interaction between circ_0001438 and miR-1290 was analyzed, and the regulatory impact of circ_0001438/miR-1290 on the activity of gastric cancer cells was examined flowing the Transwell assay and CCK8 assay. In gastric cancer tissues and cells, circ_0001438 expression was downregulated, and miR-1290 expression was upregulated and the two were negatively correlated. miR-1290 inhibitors were transfected and significantly increased the activity of circ_0001438 luciferase, while miR-1290 mimics decreased the activity. Overexpression of circ_0001438 decreased miR-1290 expression and inhibited the proliferation and metastasis of gastric cancer cells, which was reversed when miR-1290 mimics were transfected. Additionally, there was a correlation between circ_0001438 expression and lymph node metastases, tumor size, and TNM stage of gastric cancer. Low circ_0001438 expression predicts poor prognosis of gastric cancer patients. circ_0001438 is a biomarker for tumor development and clinical prognosis in gastric cancer. It works by downregulating miR-1290 to control the activity of gastric cancer cells.
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MicroARNs , ARN Circular , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Línea Celular Tumoral , MicroARNs/genética , Masculino , Femenino , Persona de Mediana Edad , Proliferación Celular/genética , Pronóstico , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismoRESUMEN
BACKGROUND: Early dissemination to distant organs accounts for the dismal prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). Chronic, dysregulated, persistent and unresolved inflammation provides a preferred tumor microenvironment (TME) for tumorigenesis, development, and metastasis. A better understanding of the key regulators that maintain inflammatory TME and the development of predictive biomarkers to identify patients who are most likely to benefit from specific inflammatory-targeted therapies is crucial for advancing personalized cancer treatment. METHODS: This study identified cell-specific expression of CALB2 in human PDAC through single-cell RNA sequencing analysis and assessed its clinicopathological correlations in tissue microarray using multi-color immunofluorescence. Co-culture systems containing cancer-associated fibroblasts (CAFs) and patient-derived organoids (PDOs) in vitro and in vivo were employed to elucidate the effects of CALB2-activated CAFs on PDAC malignancy. Furthermore, CUT&RUN assays, luciferase reporter assays, RNA sequencing, and gain- or loss-of-function assays were used to unravel the molecular mechanisms of CALB2-mediated inflammatory reprogramming and metastasis. Additionally, immunocompetent KPC organoid allograft models were constructed to evaluate CALB2-induced immunosuppression and PDAC metastasis, as well as the efficacy of inflammation-targeted therapy. RESULTS: CALB2 was highly expressed both in CAFs and cancer cells and correlated with an unfavorable prognosis and immunosuppressive TME in PDAC patients. CALB2 collaborated with hypoxia to activate an inflammatory fibroblast phenotype, which promoted PDAC cell migration and PDO growth in vitro and in vivo. In turn, CALB2-activated CAFs upregulated CALB2 expression in cancer cells through IL6-STAT3 signaling-mediated direct transcription. In cancer cells, CALB2 further activated Ca2+-CXCL14 inflammatory axis to facilitate PDAC metastatic outgrowth and immunosuppression. Genetic or pharmaceutical inhibition of CXCL14 significantly suppressed CALB2-mediated metastatic colonization of PDAC cells in vivo and extended mouse survival. CONCLUSIONS: These findings identify CALB2 as a key regulator of inflammatory reprogramming to promote PDAC metastatic progression. Combination therapy with αCXCL14 monoclonal antibody and gemcitabine emerges as a promising strategy to suppress distant metastasis and improve survival outcomes in PDAC with CALB2 overexpression.
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Metástasis de la Neoplasia , Neoplasias Pancreáticas , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Ratones , Animales , Inflamación/patología , Inflamación/metabolismo , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Femenino , Masculino , PronósticoRESUMEN
In the original publication [...].
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Pancreatic cancer is an extremely malignant tumor. PVT1 and MYC signaling has been considered as a therapeutic target recently. Nonetheless, the prognostic values and critical regulatory networks of PVT1-MYC duet in pancreatic cancer remain unclear. Firstly, we identified PVT1-MYC duet-related genes using public databases. Then we analyzed our Hi-C and ChIP-seq data to confirm PVT1-MYC duet. We performed LASSO regression and multivariate Cox regression analysis to build a prognostic model whose effectiveness and robustness were validated by Cox regression, ROC analysis, calibration curve, and nomogram. Besides, we conducted functional enrichment analyses, mutation profiles analyses and the immune features analyses to compare low- and high-risk group. Functional enrichment analyses revealed that several terms associated with cancer progression were enriched in the high-risk group. Mutation profile analysis showed that high-risk group had higher tumor mutation burden, and immune analysis demonstrated high-risk group had more immunosuppressive tumor microenvironment. Finally, we detected PVT1 expression in pancreatic cancer and paracancer tissues from the PUMCH cohort, which showed that PVT1 was significantly upregulated in pancreatic cancer and associated with invasion, metastasis, and poor prognosis. We further performed transwell and proliferation assays and found that PVT1, CDC6, and COL17A1 could promote migration or proliferation of PDAC cells. This study constructed a prognostic model based on three PVT1-MYC duet-related genes, which had a significant potential in predicting the prognosis and tumor microenvironment of pancreatic cancer. These results suggested that targeting PVT1-MYC duet or its regulatory processes could be a therapeutic option with great interests.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Pancreáticas , Proteínas Proto-Oncogénicas c-myc , ARN Largo no Codificante , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/inmunología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , ARN Largo no Codificante/genética , Pronóstico , Proteínas Proto-Oncogénicas c-myc/genética , Biomarcadores de Tumor/genética , Nomogramas , Mutación , Masculino , FemeninoRESUMEN
Objective: The aim of this study was to investigate whether a potential moral cognitive impairment (failure in understanding moral rules) exists in patients with schizophrenia (SCZ) and to explore the effect of childhood trauma (CT) on moral cognition in a group of patients with SCZ. Methods: A total of 99 patients with SCZ and 102 healthy controls (HCs) were included in this study. The Childhood Trauma Questionnaire-Short Form (CTQ) was administered to assess childhood trauma experiences in both groups, while the Moral Identity Measure (MIM) and the Moral Foundations Questionnaire (MFQ) were applied for a comparative evaluation of moral cognition across the two groups. The Positive and Negative Syndrome Scale (PANSS) was administered to assess the psychopathology. Results: Patients with schizophrenia had significantly greater CTQ scores than HCs (42.77 ± 13.50 vs. 29.11 ± 4.25, t=9.697, p<0.001). The prevalence of childhood trauma (χ 2 = 58.452, p<0.001) and history of aggressive behaviors (χ 2 = 23.565, p=0.001) among patients with SCZ were greater than that among HCs. In addition, the scores of moral cognition (MIM: 61.82 ± 15.12 vs. 70.88 ± 8.87, p=0.001; MFQ: 87.24 ± 22.30 vs. 112.62 ± 23.42, p=0.045) in the SCZ group was lower than that in the HC group after controlling for the influence of CT covariates. The MFQ score was negatively correlated with the CTQ score, the emotional abuse (EA) score, the physical abuse (PA) score and the physical neglect (PN) score in SCZ patients. Among HCs, the MFQ score was positively correlated with the CTQ score, as well as with the dimensions of physical abuse (PA) and emotional Neglect (EN). Multiple linear regression analyses revealed that impaired moral cognition performance was significantly predicted by the CTQ score (beta=-0.235, p=0.034, 95% CI -0.743 to -0.031) in patients with SCZ but was significantly predicted by years of education (beta=-0.392, p<0.001, 95% CI -4.783 to -1.876), alcohol use (beta=0.210, p=0.023, 95% CI 2.191 to 29.399) and the CTQ score (beta=0.184, p=0.046, 95% CI 0.019 to 1.928) in HCs. CTQ moderated the effect of SCZ on MFQ (B = 0.516); Simple tests revealed that the group effect on the MFQ was B=12.306 at the lower level(-1SD) and B = 54.089 at the higher level(+1SD) of the CTQ scores. Conclusions: SCZ patients exhibit impaired moral cognition. The contribution of CT to the presence of moral cognitive impairments seems to be independent of psychopathology.
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Lignin has long been regarded as waste, readily separated and discarded from the pulp and paper industry. However, as the most abundant aromatic renewable biopolymer in nature, lignin can replace petroleum resources to prepare chemicals containing benzene rings. Therefore, the high-value transformation of lignin has attracted the interest of both academia and industry. Nitrogen-containing compounds and functionalized materials are a class of compounds that have wide applications in chemistry, materials science, energy storage, and other fields. Converting lignin into nitrogenous chemicals and materials is a high-value utilization pathway. Currently, there is a large amount of literature exploring the conversion of lignin. However, a comprehensive review of the transformation of lignin to nitrogenous compounds is lacking. The research progress of lignin conversion to nitrogenous chemicals and functional materials is reviewed in this article. This article provides an overview of the chemical structure and types of industrial lignin, methods of lignin modification, as well as nitrogen-containing chemicals and functional materials prepared from various types of lignin, including their applications in wastewater treatment, slow-release fertilizer, adhesive, coating, and biomedical fields. In addition, the challenges and limitations of nitrogenous lignin-based materials encountered during the development of applications are also discussed. It is believed that this review will act as a key reference and inspiration for researchers in the biomass and material field.
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This study evaluated the safety, tolerability, pharmacodynamics, and pharmacokinetics of recombinant neorudin (EPR-hirudin [EH]) in patients with acute coronary syndrome (ACS), providing a basis for further therapeutic research. This open-label, single-center, nonrandomized, nonblinded, and noncontrolled trial categorized 24 patients with nonprogressive ACS who met the screening criteria into 3 groups. They received an intravenous injection of neorudin (0.4 mg/kg), followed by an intravenous drip at doses of 0.15, 0.30, and 0.45 mg/kg/h for 3 days in the low-, medium-, and high-dose groups, respectively. The safety, tolerability, pharmacodynamics, and pharmacokinetics of EH were assessed after treatment, indicating that neorudin was safe and well tolerated in nonprogressive ACS. No serious adverse events or clinical composite end points were observed. The activated partial thromboplastin time and thrombin time increased significantly and dose dependently following EH administration across all groups compared to pretreatment values. Conversely, thrombin activity significantly decreased after drug administration but returned to baseline levels shortly after drug withdrawal. Within the administered dose range, neorudin exposure increased with the dose, and its half-life was approximately 2 hours. Neorudin was found to be safe and tolerable for treating patients with nonprogressive ACS, demonstrating therapeutic efficacy at doses up to 0.45 mg/kg/h over a 3-day period.
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Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.
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Pancreatic cancer, a highly fatal malignancy, is predicted to rank as the second leading cause of cancer-related death in the next decade. This highlights the urgent need for new insights into personalized diagnosis and treatment. Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics, few known molecular classifications are translated to guide clinical strategies and require a paradigm shift. Notably, chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics, proteomics, metabonomics, and metagenomics. Therefore, a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential therapeutic options. In this review, we recapitulated the molecular spectrum from different omics levels, discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact, and proposed some methodological and scientific challenges in store.
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OBJECTIVE: Rheumatoid arthritis (RA) is a systemic connective tissue autoimmune disease that can infiltrate arterial walls. The delay in diagnosis and treatment of rheumatoid vasculitis (RV) in patients with RA may lead to irreversible damage to the arterial walls of small-to-medium vessels, which has serious and devastating consequences, most notably lung and cardiac damage. In this work an ultrasound image-based biomarker was developed to detect precursory changes in RV. METHODS: The ground truth was initiated from a medical diagnosis of RA, with arterial wall thickening of the proximal dorsalis pedis artery (DPA) indicating precursory changes of RV identified with ultrasound scanning. Ultrasound images of the DPA from 49 healthy subjects in the control group and 46 patients in the RA group were obtained. In total, 187 texture features were extracted from the images, followed by principal component analysis and linear discriminant analysis. RESULTS: The proposed biomarker detected a significant difference between the two groups (p = 5.74 × 10-18) with an area under the receiver operating characteristic curve of 0.85. Ten major textural features contributing most heavily to the biomarker were identified, with these textures being consistent with clinical observations of RV identified in previous studies. Interscan reproducibility was assessed by computing the biomarker twice based on repeated scans of each ankle. High interscan reproducibility was demonstrated by a strong and significant Pearson's coefficient (r = 0.85, p < 0.01) between the two repeated measurements of the proposed biomarker. CONCLUSION: The proposed biomarker can discriminate image textural differences seen in images acquired from RA patients, demonstrating precursory changes in RV compared with healthy controls. The major discriminative features identified in this study may facilitate the early identification and treatment of RV.
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Vasculitis Reumatoide , Ultrasonografía , Humanos , Femenino , Persona de Mediana Edad , Masculino , Ultrasonografía/métodos , Vasculitis Reumatoide/diagnóstico por imagen , Adulto , Anciano , Arterias/diagnóstico por imagen , Pie/diagnóstico por imagen , Pie/irrigación sanguínea , Biomarcadores/sangre , Artritis Reumatoide/diagnóstico por imagenRESUMEN
BACKGROUND: There are limited data on the effect of different sutures and surgical approaches on the quality of pancreaticojejunostomy in minimally invasive pancreaticoduodenectomy (MIPD). This study compares the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) between the use of barbed sutures (BSs) and conventional sutures (CSs). METHODS: A retrospective cohort study was conducted on 253 consecutive patients who had undergone MIPD from July 2016 to April 2023. Patients were excluded if conversion to open surgery or open anastomosis was necessary. 220 patients were enrolled and divided into BS (n = 148) and CS (n = 72) groups. After 1:1 propensity score matching (PSM), 67 cases remained in each group. Univariate and multivariate analyses identified factors associated with CR-POPF. Comparisons were also made between laparoscopic (LPD) and robotic (RPD) pancreaticoduodenectomy. RESULTS: After PSM, BSs were associated with significantly lower rates of CR-POPF (7.5 vs. 22.4%, P = 0.015) and severe complications (Clavien-Dindo ≥ III) (7.5vs. 19.4%, P = 0.043). No significant differences were found in operative time, length of postoperative hospital stay, or other major morbidities. Multivariate analyses revealed BMI ≥ 22 kg/m2 (OR = 5.048, 95% CI: 1.256-20.287, P = 0.023) and the use of BSs (OR = 0.196, 95% CI: 0.059-0.653, P = 0.008) as the independent predictors of CR-POPF. There were no significant differences in postoperative outcomes between the LPD and RPD groups, but RPD was associated with significantly shorter operative time (402.8 min vs. 429.4 min, P = 0.015). CONCLUSIONS: In conclusion, using BSs for PJ during MIPD is feasible and has the potential to reduce CR-POPF and severe complications.
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Laparoscopía , Fístula Pancreática , Pancreaticoduodenectomía , Pancreatoyeyunostomía , Complicaciones Posoperatorias , Puntaje de Propensión , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados/métodos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Pancreatoyeyunostomía/métodos , Pancreatoyeyunostomía/efectos adversos , Persona de Mediana Edad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Fístula Pancreática/epidemiología , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Técnicas de Sutura , Suturas , Tempo Operativo , Neoplasias Pancreáticas/cirugía , Incidencia , AdultoRESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. It is important to discover new therapeutic regimens for treating CRC. Depression is known to be an important complication of cancer diseases. Repurposing antidepressants into anticancer drugs and exploring the combinational efficacy of antidepressants and chemotherapy are potentially good options for developing CRC treatment regimens. In this study, sertraline, an antidepressant drug, and paclitaxel, an anticancer drug, were chosen to study their antitumor effects in the treatment of colorectal cancer, alone or in combination, and to explore their underlying mechanisms. The data showed that sertraline exerted a dose-dependent cytotoxic effect on MC38 and CT26 colorectal cancer cell lines with IC50 values of 10.53 µM and 7.47 µM, respectively. Furthermore, sertraline synergistically sensitized chemotherapeutic agent paclitaxel efficacy in CRC cells with combination index (CI) values at various concentrations consistently lower than 1. Sertraline remarkably augmented paclitaxel-induced autophagy by increasing autophagosome formation indicated by elevated LC3-II/I ratio and promoting autophagic flux by degrading autophagy cargo receptor SQSTM1/p62, which may explain the synergistically cytotoxic effect of sertraline and paclitaxel combination therapy on CRC cells. This study provides important evidence to support repurposing sertraline as an anticancer agent and suggests a novel combinational regimen for effectively treating CRC as well as in the simultaneous treatment of CRC and depression.
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Antidepresivos , Autofagia , Neoplasias Colorrectales , Sinergismo Farmacológico , Paclitaxel , Sertralina , Sertralina/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Autofagia/efectos de los fármacos , Paclitaxel/farmacología , Humanos , Línea Celular Tumoral , Antidepresivos/farmacología , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , AnimalesRESUMEN
Thermoelectric materials that can convert thermal energy to electrical energy are stable and long-lasting and do not emit greenhouse gases; these properties render them useful in novel power generation devices that can conserve and utilize lost heat. SiC exhibits good mechanical properties, excellent corrosion resistance, high-temperature stability, non-toxicity, and environmental friendliness. It can withstand elevated temperatures and thermal shock and is well suited for thermoelectric conversions in high-temperature and harsh environments, such as supersonic vehicles and rockets. This paper reviews the potential of SiC as a high-temperature thermoelectric and third-generation wide-bandgap semiconductor material. Recent research on SiC thermoelectric materials is reviewed, and the principles and methods for optimizing the thermoelectric properties of SiC are discussed. Thus, this paper may contribute to increasing the application potential of SiC for thermoelectric energy conversion at high temperatures.
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The literature on polyvinyl alcohol (PVA) films is extensive, however, these methods often necessitate intricate synthesis processes or the addition of plasticizers to modify the strength and water solubility of the PVA material. A high-strength UV radiation-resistant composite film by chelating Fe3+ with lignin and PVA, which exhibits excellent hydrolysis resistance is developed. This composite film is prepared simply by incorporating a small amount of dealkalized lignin (APPL) and ferric chloride (FeCl3) into PVA through a straightforward composite process. During the scanning test, it is noted that the film exhibits a high density of uniformly dispersed particles, endowing it with efficient ultraviolet absorption capabilities. The infrared and anti-dissolution tests reveal that the coordination of Fe3+ with lignin imparts an outstanding hydrolysis resistance to the film, obviating the need for any extender, curing agent, acid or base. The tensile fracture strength reaches an impressive 187.81Mpa in the tensile test. UV and indicator card tests unequivocally demonstrate that the film achieves a remarkable 100% anti-UV efficiency. This Fe3+ chelated lignin/PVA composite film, with its facile preparation, environmental sustainability, high strength, and outstanding anti-ultraviolet efficiency, can be deployed across diverse applications requiring robust protection against ultraviolet radiation.
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Medical Visual Question Answering (VQA-Med) is a challenging task that involves answering clinical questions related to medical images. However, most current VQA-Med methods ignore the causal correlation between specific lesion or abnormality features and answers, while also failing to provide accurate explanations for their decisions. To explore the interpretability of VQA-Med, this paper proposes a novel CCIS-MVQA model for VQA-Med based on a counterfactual causal-effect intervention strategy. This model consists of the modified ResNet for image feature extraction, a GloVe decoder for question feature extraction, a bilinear attention network for vision and language feature fusion, and an interpretability generator for producing the interpretability and prediction results. The proposed CCIS-MVQA introduces a layer-wise relevance propagation method to automatically generate counterfactual samples. Additionally, CCIS-MVQA applies counterfactual causal reasoning throughout the training phase to enhance interpretability and generalization. Extensive experiments on three benchmark datasets show that the proposed CCIS-MVQA model outperforms the state-of-the-art methods. Enough visualization results are produced to analyze the interpretability and performance of CCIS-MVQA.
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Tetrandrine (TET) is a natural bis-benzylisoquinoline alkaloid isolated from Stephania species with a wide range of biological and pharmacologic activities; it mainly serves as an anti-inflammatory agent or antitumor adjuvant in clinical applications. However, limitations such as prominent hydrophobicity, severe off-target toxicity, and low absorption result in suboptimal therapeutic outcomes preventing its widespread adoption. Nanoparticles have proven to be efficient devices for targeted drug delivery since drug-carrying nanoparticles can be passively transported to the tumor site by the enhanced permeability and retention (EPR) effects, thus securing a niche in cancer therapies. Great progress has been made in nanocarrier construction for TET delivery due to their outstanding advantages such as increased water-solubility, improved biodistribution and blood circulation, reduced off-target irritation, and combinational therapy. Herein, we systematically reviewed the latest advancements in TET-loaded nanoparticles and their respective features with the expectation of providing perspective and guidelines for future research and potential applications of TET.
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Bencilisoquinolinas , Disponibilidad Biológica , Nanopartículas , Solubilidad , Bencilisoquinolinas/química , Bencilisoquinolinas/administración & dosificación , Bencilisoquinolinas/farmacología , Bencilisoquinolinas/farmacocinética , Humanos , Nanopartículas/química , Animales , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Distribución Tisular , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/administración & dosificaciónRESUMEN
Amino acid metabolism plays a pivotal role in tumor microenvironment, influencing various aspects of cancer progression. The metabolic reprogramming of amino acids in tumor cells is intricately linked to protein synthesis, nucleotide synthesis, modulation of signaling pathways, regulation of tumor cell metabolism, maintenance of oxidative stress homeostasis, and epigenetic modifications. Furthermore, the dysregulation of amino acid metabolism also impacts tumor microenvironment and tumor immunity. Amino acids can act as signaling molecules that modulate immune cell function and immune tolerance within the tumor microenvironment, reshaping the anti-tumor immune response and promoting immune evasion by cancer cells. Moreover, amino acid metabolism can influence the behavior of stromal cells, such as cancer-associated fibroblasts, regulate ECM remodeling and promote angiogenesis, thereby facilitating tumor growth and metastasis. Understanding the intricate interplay between amino acid metabolism and the tumor microenvironment is of crucial significance. Expanding our knowledge of the multifaceted roles of amino acid metabolism in tumor microenvironment holds significant promise for the development of more effective cancer therapies aimed at disrupting the metabolic dependencies of cancer cells and modulating the tumor microenvironment to enhance anti-tumor immune responses and inhibit tumor progression.
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Aminoácidos , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/metabolismo , Neoplasias/patología , Aminoácidos/metabolismo , Animales , Reprogramación Celular , Reprogramación MetabólicaRESUMEN
Cysteine (Cys) not only plays an indispensable role in maintaining the redox balance in organisms, but is also an important nutrient in the food industry. Fluorescence-based detection systems have emerged as an effective method to track the locations and concentrations of different species. To achieve efficient monitoring of Cys in both food samples and biological systems, a novel lipid droplet (LD) targeted fluorescent probe (namely NIT-Cys) was constructed for the turn-on detection of Cys, characterized by a large Stokes shift (142 nm), a short response time (<8 min), and a low Cys detection limit (39 nM). Furthermore, the NIT-Cys probe has been successfully used not only to quantify the amounts of Cys in selected food samples, but also to enable the visualization of endogenous Cys in acetaminophen (APAP)-induced drug-induced liver injury cells, zebrafish larvae and mice models. Consequently, the work presented here provides an efficient tool for monitoring Cys.