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1.
Foods ; 13(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38731788

RESUMO

Cardiovascular disease (CVD) represents a substantial global health challenge, with its impact on mortality and morbidity rates surpassing that of cancer. The present study was designed to explore the cardioprotective properties of anthocyanin (ACN), a compound derived from black barley, against oxidative stress-induced damage in myocardial cells and to uncover the molecular mechanisms at play. Utilizing both in vitro and in vivo experimental models, our findings indicate that ACN notably reduced cell damage caused by oxidative stress and effectively prevented apoptosis. High-throughput RNA sequencing analysis has shed light on the mechanism by which ACN achieves its antioxidative stress effects, implicating the PTEN-Akt signaling pathway. ACN was found to modulate PTEN expression levels, which in turn influences the Akt pathway, leading to a reduction in apoptotic processes. This novel insight lays the groundwork for the potential clinical utilization of ACN in the management of CVD. While this study has shed light on some of the functions of ACN, it is important to recognize that natural compounds often interact with multiple molecular targets and engage in intricate signaling cascades. Future research endeavors will concentrate on further elucidating the regulatory mechanisms by which ACN influences PTEN expression, with the goal of enhancing our comprehension and expanding the therapeutic potential of ACN in the treatment of cardiovascular conditions.

2.
JACS Au ; 4(3): 985-991, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38559740

RESUMO

Often, trace impurities in a feed stream will cause failures in industrial applications. The efficient removal of such a trace impurity from industrial steams, however, is a daunting challenge due to the extremely small driving force for mass transfer. The issue lies in an activity-stability dilemma, that is, an ultrafine adsorbent that offers a high exposure of active sites is favorable for capturing species of a low concentration, but free-standing adsorptive species are susceptible to rapidly aggregating in working conditions, thus losing their intrinsic high activity. Confining ultrafine adsorbents in a porous matrix is a feasible solution to address this activity-stability dilemma. We herein demonstrate a proof of concept by encapsulating ZnO nanoclusters into a pure-silica MFI zeolite (ZnO@silicalite-1) for the ultradeep removal of H2S, a critical need in the purification of hydrogen for fuel cells. The Zn species and their interaction with silicalite-1 were thoroughly investigated by a collection of characterization techniques such as HADDF-STEM, UV-visible spectroscopy, DRIFTS, and 1H MAS NMR. The results show that the zeolite offers rich silanol defects, which enable the guest nanoclusters to be highly dispersed and anchored in the silicious matrix. The nanoclusters are present in two forms, Zn(OH)+ and ZnO, depending on the varying degrees of interaction with the silanol defects. The ultrafine nanoclusters exhibit an excellent desulfurization performance in terms of the adsorption rate and utilization. Furthermore, the ZnO@silicalite-1 adsorbents are remarkably stable against sintering at high temperatures, thus maintaining a high activity in multiple adsorption-regeneration cycles. The results demonstrate that the encapsulation of active metal oxide species into zeolite is a promising strategy to develop fast responsive and highly stable adsorbents for the ultradeep removal of trace impurities.

3.
Hellenic J Cardiol ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582140

RESUMO

BACKGROUND: Sacubitril/valsartan (S/V) has been shown to be an effective antihypertensive drug combination. However, its therapeutic effects on blood pressure (BP), hemodynamics, and left ventricular (LV) remodeling in resistant hypertension (RHTN) remain unclear. METHODS: Eighty-six patients completed this self-control study, during which olmesartan was administered within the first 8 weeks (phase 1), followed by S/V within the second 8 weeks (phase 2), with nifedipine and hydrochlorothiazide taken as background medications. Office BP, echocardiography, and hemodynamics assessment using impedance cardiography were performed at baseline and at the eighth and sixteenth weeks. RESULTS: The reduction in office BP was larger in phase 2 than in phase 1 (19.59/11.66 mmHg vs. 2.88/1.15 mmHg). Furthermore, the treatment in phase 2 provided greater reductions in systemic vascular resistance index (SVRI) and thoracic blood saturation ratio (TBR), with differences between the two phases of -226.59 (-1212.80 to 509.55) dyn·s/cm5/m2 and -0.02 (-0.04 to 0.02). Switching from olmesartan to S/V also significantly reduced E/E', LV mass index, LV end-diastolic volume index, and LV end-systolic volume index (all P < 0.05). Decreases in arterial stiffness, SVRI, and TBR were correlated with changes in indicators of LV remodeling (all P < 0.05). This correlation persisted even after adjusting for confounders including changes in BP. CONCLUSIONS: Switching from olmesartan to S/V effectively lowered BP and reversed ventricular remodeling in RHTN. In addition, hemodynamic improvement was also observed. Changes in hemodynamics played an important role in reversing LV remodeling of S/V, and were independent of its antihypertensive effect.

4.
Aging (Albany NY) ; 16(7): 6188-6211, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38552216

RESUMO

BACKGROUND: REEP4 is involved in the regulation of the biological process of mitosis. Lower grade glioma (LGG), as a malignant tumor, is accompanied by abnormalities in mitosis, but there have been no reports of REEP4 so far. METHODS: We collected transcriptome data, DNA methylation data and the clinical characteristics of thousands of patients with LGG. Various big data analysis methods and molecular biology experiments were employed to reveal the impact of REEP4 on the pathological process of LGG. RESULTS: It was found that the expression of REEP4 was significantly elevated and negatively regulated by its methylation site. Therefore, both the high expression of REEP4 and low methylation state of cg16311504 showed that the patients are correlated with lower patient survival rate. In addition, high REEP4 expression participates in the regulation of various cancer-related cellular signaling pathways, such as the cell cycle, MAPK signaling pathway, NOD-like receptor signaling pathway, etc. More importantly, the level of immune cell infiltration significantly increased in the high expression group of REEP4 in the LGG tumor microenvironment and REEP4 has a high positive correlation with PD-L1 and other immune checkpoints. CONCLUSIONS: In brief, this study is the first to introduce REEP4 in malignant tumors, which can be used as an independent risk factor that participates in the malignant process of LGG. More importantly, REEP4 has the potential to become a new star in the field of anti-tumor treatment.


Assuntos
Neoplasias Encefálicas , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Glioma , Humanos , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Glioma/mortalidade , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Microambiente Tumoral/genética , Gradação de Tumores , Transcriptoma , Feminino
5.
Adv Sci (Weinh) ; 11(15): e2308546, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38342609

RESUMO

In order to establish a set of perfect heterojunction designs and characterization schemes, step-scheme (S-scheme) BiOBr@Bi2S3 nanoheterojunctions that enable the charge separation and expand the scope of catalytic reactions, aiming to promote the development and improvement of heterojunction engineering is developed. In this kind of heterojunction system, the Fermi levels mediate the formation of the internal electric field at the interface and guide the recombination of the weak redox carriers, while the strong redox carriers are retained. Thus, these high-energy electrons and holes are able to catalyze a variety of substrates in the tumor microenvironment, such as the reduction of oxygen and carbon dioxide to superoxide radicals and carbon monoxide (CO), and the oxidation of H2O to hydroxyl radicals, thus achieving sonodynamic therapy and CO combined therapy. Mechanistically, the generated reactive oxygen species and CO damage DNA and inhibit cancer cell energy levels, respectively, to synergistically induce tumor cell apoptosis. This study provides new insights into the realization of high efficiency and low toxicity in catalytic therapy from a unique perspective of materials design. It is anticipated that this catalytic therapeutic method will garner significant interest in the sonocatalytic nanomedicine field.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Apoptose , Monóxido de Carbono , Catálise , Dano ao DNA , Neoplasias/terapia , Microambiente Tumoral
6.
Adv Sci (Weinh) ; 11(14): e2307674, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38308139

RESUMO

Erionite (ERI) zeolite has recently attracted considerable attention for its application prospect in the selective catalytic reduction of NOx with NH3 (NH3-SCR), provided that the high-silica (Si/Al > 5.5) analog with improved hydrothermal stability can be facilely synthesized. In this work, ERI zeolites with different Si/Al ratios (4.6, 6.4, and 9.1) are synthesized through an ultrafast route, and in particular, a high-silica ERI zeolite with a Si/Al ratio of 9.1 is obtained by using faujasite (FAU) as a starting material. The solid-state 29Si MAS NMR spectroscopic study in combination with a computational simulation allows for figuring out the atomic configurations of the Al species in the three ERI zeolites. It is revealed that the ERI zeolite with the highest Si/Al ratio (ERI-9.1, where the number indicates the Si/Al ratio) exhibits a biased Al occupancy at T1 site, which is possibly due to the presence of a higher fraction of the residual potassium cations in the can cages. In contrast, the Al siting in ERI-4.6 and ERI-6.4 proves to be relatively random.

7.
Food Chem X ; 21: 101166, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38322764

RESUMO

Efficient and comprehensive analysis of lipid profiles in yak ghee samples collected from different elevations is crucial for optimal utilization of these resources. Unfortunately, such research is relatively rare. Yak ghee collected from three locations at different altitudes (S2: 2986 m; S5: 3671 m; S6: 4508 m) were analyzed by quantitative lipidomic. Our analysis identified a total of 176 lipids, and 147 s lipid of them were upregulated and 29 lipids were downregulated. These lipids have the potential to serve as biomarkers for distinguishing yak ghee from different altitudes. Notably, S2 exhibited higher levels of fatty acids (21:1) and branched fatty acid esters of hydroxy fatty acids (14:0/18:0), while S5 showed increased levels of phosphatidylserine (O-20:0/19:1) and glycerophosphoric acid (19:0/22:1). S6 displayed higher levels of triacylglycerol (17:0/20:5/22:3), ceramide alpha-hydroxy fatty acid-sphingosine (d17:3/34:2), and acyl glucosylceramides (16:0-18:0-18:1). Yak ghee exhibited a high content of neutralizing glycerophospholipids and various functional lipids, including sphingolipids and 21 newly discovered functional lipids. Our findings provide insights into quantitative changes in yak ghee lipids during different altitudes, development of yak ghee products, and screening of potential biomarkers.

8.
Foods ; 13(2)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38254494

RESUMO

Dairy products are susceptible to modifications in protein oxidation during heat processing, which can lead to changes in protein function, subsequently affecting intestinal health. Despite being a unique nutritional source, yak milk has not been thoroughly examined for the effects of its oxidized proteins on intestinal microbiota and metabolism. Hence, this study employed different heat treatment methods (low-temperature pasteurization, high-temperature pasteurization, and high-temperature sterilization) to induce oxidation in yak milk proteins. The study then assessed the degree of oxidation in these proteins and utilized mice as research subjects. Using metagenomics and metabolomics methods, this study examined the structure of intestinal microbial communities and metabolic products in mice consuming oxidized yak milk. The results showed a decrease in carbonyl and total thiol contents of yak milk proteins after different heat treatments, indicating that heat treatment causes oxidation in yak milk proteins. Metagenomic analysis of mouse intestinal microbiota revealed significant changes in 66 genera. In the high-temperature sterilization group (H), key differential genera included Verrucomicrobiales, Verrucomicrobiae, Akkermansiaceae, and 28 others. The high-temperature pasteurization group (M) mainly consisted of Latilactobacillus, Bacillus, and Romboutsia. The low-temperature pasteurization group (L) primarily comprised of Faecalibacterium, Chaetomium, Paenibacillaceae, Eggerthella, Sordariales, and 33 others. Functionally, compared to the control group (C), the H group upregulated translation and energy metabolism functions, the L group the M group significantly upregulated metabolism of other amino acids, translation, and cell replication and repair functions. Based on metabolomic analysis, differential changes in mouse metabolites could affect multiple metabolic pathways in the body. The most significantly affected metabolic pathways were phenylalanine metabolism, vitamin B6 metabolism, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. The changes were similar to the functional pathway analysis of mouse metagenomics, affecting amino acid and energy metabolism in mice. In summary, moderate oxidation of yak milk proteins exhibits a positive effect on mouse intestinal microbiota and metabolism. In conclusion, yak milk has a positive effect on mouse intestinal microflora and metabolism, and this study provides a scientific basis for optimizing dairy processing technology and further developing and applying yak milk.

9.
Eur J Med Res ; 29(1): 13, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173030

RESUMO

BACKGROUND: The WD40 repeat (WDR) domain provides scaffolds for numerous protein-protein interactions in multiple biological processes. WDR domain 76 (WDR76) has complex functionality owing to its diversified interactions; however, its mechanism in LGG has not yet been reported. METHODS: Transcriptomic data from public databases were multifariously analyzed to explore the role of WDR76 in LGG pathology and tumor immunity. Laboratory experiments were conducted to confirm these results. RESULTS: The results first confirmed that high expression of WDR76 in LGG was not only positively associated with clinical and molecular features of malignant LGG, but also served as an independent prognostic factor that predicted shorter survival in patients with LGG. Furthermore, high expression of WDR76 resulted in the upregulation of oncogenes, such as PRC1 and NUSAP1, and the activation of oncogenic mechanisms, such as the cell cycle and Notch signaling pathway. Finally, WDR76 was shown to be involved in LGG tumor immunity by promoting the infiltration of immune cells, such as M2 macrophages, and the expression of immune checkpoints, such as PDCD1 (encoding PD-1). CONCLUSIONS: This study shows for the first time the diagnostic and prognostic value of WDR76 in LGG and provides a novel personalized biomarker for future targeted therapy and immunotherapy. Thus, WDR76 may significantly improve the prognosis of patients with LGG.


Assuntos
Glioma , Repetições WD40 , Humanos , Imunoterapia , Ciclo Celular , Perfilação da Expressão Gênica , Glioma/genética , Glioma/terapia , Prognóstico , Proteínas de Ligação a DNA , Proteínas de Ciclo Celular
10.
Neural Netw ; 172: 106091, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38266475

RESUMO

As the deployment of artificial intelligence (AI) models in real-world settings grows, their open-environment robustness becomes increasingly critical. This study aims to dissect the robustness of deep learning models, particularly comparing transformer-based models against CNN-based models. We focus on unraveling the sources of robustness from two key perspectives: structural and process robustness. Our findings suggest that transformer-based models generally outperform convolution-based models in robustness across multiple metrics. However, we contend that these metrics may not wholly represent true model robustness, such as the mean of corruption error. To better understand the underpinnings of this robustness advantage, we analyze models through the lens of Fourier transform and game interaction. From our insights, we propose a calibrated evaluation metric for robustness against real-world data, and a blur-based method to enhance robustness performance. Our approach achieves state-of-the-art results, with mCE scores of 2.1% on CIFAR-10-C, 12.4% on CIFAR-100-C, and 24.9% on TinyImageNet-C.


Assuntos
Inteligência Artificial , Benchmarking
11.
Orthop Surg ; 16(2): 462-470, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38086608

RESUMO

OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.


Assuntos
Neoplasias Ósseas , Medicamentos de Ervas Chinesas , Ginsenosídeos , Osteossarcoma , Humanos , Simulação de Acoplamento Molecular , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológico
12.
Liver Int ; 44(1): 155-168, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37804070

RESUMO

BACKGROUND AND AIMS: Sarcopenia is associated with poor prognosis, but its role in older patients with intrahepatic cholangiocarcinoma (ICC) is unclear. We aimed to evaluate the impact of sarcopenia on the prognosis of older patients with ICC undergoing hepatectomy. METHODS: A total of 363 patients with ICC following hepatectomy from 2015 to 2021 were retrospectively reviewed at five institutions. Sarcopenia was evaluated using skeletal muscle index by computed tomography images. Patients were divided into four subgroups according to sarcopenia and age. Postoperative outcomes including complication, overall survival (OS) and recurrence-free survival (RFS) were evaluated. Risk factors were identified through univariate and multivariate Cox regression analyses. RESULTS: 302 patients were included in the analysis. The median age was 63 years and there were 128 patients (42.4%) aged over 65 years. 192 patients (63.6%) were diagnosed with sarcopenia, while 180 patients (59.6%) experienced myosteatosis. Older patients experienced a higher incidence of sarcopenia and myosteatosis, and worse postoperative outcomes than younger patients. In the subgroup of patients with sarcopenia, older patients experienced a significant shorter OS than younger patients, which was not observed in patients without sarcopenia. According to the multivariate Cox regression analysis, lymphatic metastasis (p < .001), blood transfusion (p = .004), low serum albumin (p = .051), sarcopenia (p = .024), and myosteatosis (p = .004) were identified as independent risk factors of OS in older patients, meanwhile tumour size (p = .013) and lymphatic metastasis (p < .001) were independent risk factors of RFS. CONCLUSIONS: Sarcopenia and myosteatosis have a significant adverse impact on postoperative outcomes in older patients with ICC undergoing hepatectomy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Sarcopenia , Humanos , Idoso , Pessoa de Meia-Idade , Hepatectomia/efeitos adversos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Metástase Linfática/patologia , Colangiocarcinoma/patologia , Prognóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia
13.
Small ; 20(4): e2305841, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37712105

RESUMO

Pitch-derived carbon (PC) anode features the merits of low-cost, rich edge-defect sites, and tunable crystallization degree for potassium ion batteries (PIBs). However, gaining the PC anode with both rich edge-defect sites and robust structure remains challenging. Herein, micro-sized and robust PC/expanded-graphite (EG) composites (EGC) with rich edge-defect sites are massively synthesized via melting impregnation and confined pyrolysis. The PC is in situ encapsulated in micro-sized EG skeleton with robust chemical bonds between PC and EG after thermal treatment, endowing the structural stability as micro-sized carbon-carbon composites. The confinement effect originating from EG skeleton could suppress the crystallization degree of the PC and contribute rich edge-defect sites in EGC composites. Additionally, the EG skeleton inside EGC could form continuous electronic conduction nets and establish low-tortuosity carbonaceous electrodes, facilitating rapid electron/ion migration. While applied in PIBs, the EGC anode delivers a reversible capacity that up to 338.5 mAh g-1 at 0.1 A g-1 , superior rate performance of 127.5 mAh g-1 at 5.0 A g-1 , and long-term stability with 204.8 mAh g-1 retain after 700 cycles at 1.0 A g-1 . This novel strategy highlights an interesting category of heterogeneous carbon-carbon composite materials to keep pace with the demand for the future PIBs industry.

14.
J Sci Food Agric ; 104(4): 2449-2457, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37961839

RESUMO

BACKGROUND: The shortage of water resources and the increase of greenhouse gas emissions from soil seriously restrict the sustainable development of agriculture. Under the premise of ensuring a stable yield of winter wheat through a reasonable irrigation scenario, identifying a suitable straw returning method will have a positive effect on agricultural carbon sequestration and emission reduction in North China Plain. RESULTS: Straw burying (SR) and straw mulching (SM) were adopted based on traditional tillage under in the winter wheat growing season of 2020-2021 and 2021-2022. Three irrigation scenarios were used for each straw returning method: no irrigation (I0), irrigation 60 mm at jointing stage (I1), and irrigation of 60 mm each at the jointing and heading stages (I2). Soil moisture, soil respiration rate, cumulative soil CO2 emissions, yield, water use efficiency (WUE) and soil CO2 emission efficiency (CEE) were mainly studied. The results showed that, compared to SM, SR improved the utilization of soil water and enhanced soil carbon sequestration. SR reduced soil respiration rate and cumulative soil CO2 emissions in two winter wheat growing seasons, and increased yield by increasing spike numbers. In addition, with an increase in the amount of irrigation, soil CO2 emissions and yield increased. Under SR-I1 treatment, WUE and CEE were the highest. SR-I1 increases crop yields at the same time as reducing soil CO2 emissions. CONCLUSION: The combination of SR and irrigation 60 mm at jointing stage is a suitable straw returning irrigation scenario, which can improve water use and reduce soil CO2 emission in NCP. © 2023 Society of Chemical Industry.


Assuntos
Solo , Triticum , Estações do Ano , Dióxido de Carbono/análise , Água , Carbono , Agricultura/métodos , China
15.
Adv Mater ; 36(5): e2308774, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37917791

RESUMO

Near-infrared (NIR) laser-induced photoimmunotherapy has aroused great interest due to its intrinsic noninvasiveness and spatiotemporal precision, while immune evasion evoked by lactic acid (LA) accumulation severely limits its clinical outcomes. Although several metabolic interventions have been devoted to ameliorate immunosuppression, intracellular residual LA still remains a potential energy source for oncocyte proliferation. Herein, an immunomodulatory nanoadjuvant based on a yolk-shell CoP/NiCoP (CNCP) heterostructure loaded with the monocarboxylate transporter 4 inhibitor fluvastatin sodium (Flu) is constructed to concurrently relieve immunosuppression and elicit robust antitumor immunity. Under NIR irradiation, CNCP heterojunctions exhibit superior photothermal performance and photocatalytic production of reactive oxygen species and hydrogen. The continuous heat then facilitates Flu release to restrain LA exudation from tumor cells, whereas cumulative LA can be depleted as a hole scavenger to improve photocatalytic efficiency. Subsequently, potentiated photocatalytic therapy can not only initiate systematic immunoreaction, but also provoke severe mitochondrial dysfunction and disrupt the energy supply for heat shock protein synthesis, in turn realizing mild photothermal therapy. Consequently, LA metabolic remodeling endows an intensive cascade treatment with an optimal safety profile to effectually suppress tumor proliferation and metastasis, which offers a new paradigm for the development of metabolism-regulated immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Fototerapia , Luz , Neoplasias/tratamento farmacológico , Imunoterapia , Lactatos/uso terapêutico , Linhagem Celular Tumoral , Nanopartículas/química
16.
Front Oncol ; 13: 1210910, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074636

RESUMO

Background: Tumor Protein D52-Like 2 (TPD52L2) is a tumor-associated protein that participates in B-cell differentiation. However, the role of TPD52L2 in the pathological process of clear cell renal cell carcinoma (ccRCC) is unclear. Methods: Multiple omics data of ccRCC samples were obtained from public databases, and 5 pairs of ccRCC tissue samples were collected from the operating room. Wilcox, chi-square test, Kaplan-Meier method, receiver operating characteristic curve, regression analysis, meta-analysis, and correlation analysis were used to clarify the relationship of TPD52L2 with clinical features, prognosis, and immune microenvironment. Functional enrichment analysis was performed to reveal the potential pathways in which TPD52L2 participates in the progression of ccRCC. The siRNA technique was used to knockdown in the expression level of TPD52L2 in 786-O cells to verify its effect on ccRCC progression. Results: First, TPD52L2 was found to be upregulated in ccRCC at both mRNA and protein levels. Second, TPD52L2 was significantly associated with poor prognosis and served as an independent prognostic factor. Moreover, TPD52L2 expression was regulated by DNA methylation, and some methylation sites were associated with ccRCC prognosis. Third, TPD52L2 overexpression may participate in the pathological process through various signaling pathways such as cytokine-cytokine receptor interactions, PI3K-Akt, IL-17, Wnt, Hippo signaling pathway, and ECM-receptor interactions. Interestingly, TPD52L2 expression level was also closely related to the abundance of various immune cells, immune checkpoint expression, and TMB. Finally, in vitro experiments confirmed that knocking down TPD52L2 can inhibit the proliferation, migration, and invasion abilities of ccRCC cells. Conclusion: This study for the first time revealed the upregulation of TPD52L2 expression in ccRCC, which is closely associated with poor prognosis of patients and is a potentially valuable therapeutic and efficacy assessment target for immunotherapy.

17.
Hortic Res ; 10(12): uhad226, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38077492

RESUMO

Berry texture is a noteworthy economic trait for grape; however, the genetic bases and the complex gene expression and regulatory mechanism for the diverse changes in berry texture are still poorly understood. In this study, the results suggest that it is difficult to obtain high-mesocarp firmness (MesF) and high-pericarp puncture hardness (PPH) grape cultivars with high pericarp brittleness (PerB). The high-density linkage map was constructed using whole-genome resequencing based on 151 F1 individuals originating from intraspecific hybridization between the firm-flesh cultivar 'Red Globe' and soft-flesh cultivar 'Muscat Hamburg'. The total length of the consensus map was 1613.17 cM, with a mean genetic distance between adjacent bin markers of 0.59 cM. Twenty-seven quantitative trait loci (QTLs) for berry MesF, PPH, and PerB were identified in linkage groups (LGs) 1, 3, 4, 6, 8, 9, 10, 11, 14, 16, and 17, including twelve QTLs that were firstly detected in LGs 6, 11, and 14. Fourteen promising candidate genes were identified from the stable QTL regions in LGs 10, 11, 14, and 17. In particular, VvWARK2 and VvWARK8 refer to chromosome 17 and are two promising candidate genes for MesF and PPH, as the VvWARK8 gene may increase pectin residue binding with WARK for high berry firmness maintenance and the allele for VvWARK2 carrying the 'CC' and 'GA' genotypes at Chr17:1836764 and Chr17:1836770 may be associated with non-hard texture grape cultivars. In addition, real-time quantitative polymerase chain reaction (RT-qPCR) verification revealed that the promising candidate transcription factor genes VvMYB4-like, VvERF113, VvWRKY31, VvWRKY1, and VvNAC83 may regulate cell wall metabolism candidate gene expression for grape berry texture changes.

18.
Phys Chem Chem Phys ; 26(1): 116-122, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38059533

RESUMO

Alkaline earth metal cations are ubiquitously present in natural zeolites but less exploited in synthetic zeolites due to their low solubility in water, and hence it remains elusive how they contribute to zeolite formation. Herein, harmotome, a PHI-type zeolite with Ba2+, is readily synthesized from a Ba-containing aluminosilicate glass. This glass-to-zeolite transformation process, in particular the structure-regulating role of Ba2+, is investigated by anomalous X-ray scattering and high-energy X-ray total scattering techniques. The results demonstrate that the steady Ba2+-aluminosilicate interactions not only help prevent the precipitation of barium species under alkaline synthetic conditions, but also dictate the local structures with distinct interatomic distances between the Ba2+ and the surrounding aluminosilicate species throughout the transformation process, which lead to the successful formation of harmotome without detectable impurities. This study highlights the usefulness of the comprehensive X-ray scattering techniques in revealing the formation scheme of the zeolites containing specific metal species. In addition, a promising alternative approach to design and synthesize zeolites with unique compositions and topologies by using well-crafted glasses with suitable metal cation dopants is demonstrated.

19.
Artigo em Inglês | MEDLINE | ID: mdl-37878539

RESUMO

A piezoresistive material consisting of internal vertically aligned carbon nanotubes acting in concert with an external microdome structure is prepared to obtain a flexible piezoresistive sensor with high anisotropy. Here, we first obtained flexible piezoresistive composites (VCP) with anisotropic properties by inducing the vertical alignment of multiwalled carbon nanotubes in the pressure direction under a weak magnetic field of 0.6 T. Then, the composite with a microdome structure on the surface (m-VCP) was fabricated by a mold with a microstructure to further increase the anisotropy of the composite. The m-VCP microstructure was docked with VCP and placed between two layers of copper foil. With the synergistic effect of vertically aligned carbon nanotubes and the microdome structure, the sensitivity of the flexible sensor in the pressure direction was dramatically increased. In the low-strain range (0-6%), the sensitivity of m-VCP (GF = 9.208) is improved by 49% compared to m-CP and by 86% compared to VCP. The sensor has high anisotropy in the piezoresistive direction and retains good fatigue resistance under fatigue testing for 2000 cycles. This means that the sensor can be used in emerging fields such as human health monitoring, wearable electronics, and intelligent human-computer interaction.

20.
Cancer Manag Res ; 15: 1097-1110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818334

RESUMO

Purpose: Colon adenocarcinoma (COAD) is the second leading cause of death in the world, and the new incidence rate ranks third among all cancers. Abnormal DNA methylation is related to the occurrence and development of tumors. In this study, we aimed to identify genes associated with abnormal methylation in COAD. Methods: COAD transcriptome data, methylation data and clinical information were downloaded from the TCGA database and GEO database. The differentially expressed genes (DEGs) and methylated genes (DMGs) were analyzed and identified in COAD. PCA analysis was applied to divide COAD into subtypes, and the survival and immune cell infiltration of each subtype were evaluated. Cox and LASSO analyses were performed to construct COAD risk model. GSEA was used to evaluate the enrichment pathways. The Kaplan-Meier was used to analyze the difference in survival. ROC curve was plotted to evaluate the accuracy of the model, and GSE17536 was used to verify the accuracy of the risk model. The risk model is combined with the clinicopathological characteristics of COAD patients to perform multivariate Cox regression analysis to obtain independent risk factors and draw nomograms. Results: In total, 4564 DEGs and 1093 DMGs were screened, among which 298 were found to be overlapping genes. For 220 of these overlapping genes, the methylation was significantly negatively correlated to expression levels. An optimal signature from 4 methylated biomarkers was identified to construct the prognostic model. Conclusion: Our study identified 4 methylated biomarkers in the COAD. Then, we constructed the risk model to provide a theoretical basis and reference value for the research and treatment of COAD.

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