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1.
J Magn Reson Imaging ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38647041

RESUMEN

BACKGROUND: Proliferative hepatocellular carcinoma (HCC), aggressive with poor prognosis, and lacks reliable MRI diagnosis. PURPOSE: To develop a diagnostic model for proliferative HCC using liver imaging reporting and data system (LI-RADS) and assess its prognostic value. STUDY TYPE: Retrospective. POPULATION: 241 HCC patients underwent hepatectomy (90 proliferative HCCs: 151 nonproliferative HCCs), divided into the training (N = 167) and validation (N = 74) sets. 57 HCC patients received combination therapy with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). FIELD STRENGTH/SEQUENCE: 3.0 T, T1- and T2-weighted, diffusion-weighted, in- and out-phase, T1 high resolution isotropic volume excitation and dynamic gadoxetic acid-enhanced imaging. ASSESSMENT: LI-RADS v2018 and other MRI features (intratumoral artery, substantial hypoenhancing component, hepatobiliary phase peritumoral hypointensity, and irregular tumor margin) were assessed. A diagnostic model for proliferative HCC was established, stratifying patients into high- and low-risk groups. Follow-up occurred every 3-6 months, and recurrence-free survival (RFS), progression-free survival (PFS) and overall survival (OS) in different groups were compared. STATISTICAL TESTS: Fisher's test or chi-square test, t-test or Mann-Whitney test, logistic regression, Harrell's concordance index (C-index), Kaplan-Meier curves, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: The diagnostic model, incorporating corona enhancement, rim arterial phase hyperenhancement, infiltrative appearance, intratumoral artery, and substantial hypoenhancing component, achieved a C-index of 0.823 (training set) and 0.804 (validation set). Median follow-up was 32.5 months (interquartile range [IQR], 25.1 months) for postsurgery patients, and 16.8 months (IQR: 13.2 months) for combination-treated patients. 99 patients experienced recurrence, and 30 demonstrated tumor nonresponse. Differences were significant in RFS and OS rates between high-risk and low-risk groups post-surgery (40.3% vs. 65.8%, 62.3% vs. 90.1%, at 5 years). In combination-treated patients, PFS rates differed significantly (80.6% vs. 7.7% at 2 years). DATA CONCLUSION: The MR-based model could pre-treatment identify proliferative HCC and assist in prognosis evaluation. TECHNICAL EFFICACY: Stage 2.

2.
Cancer Cell Int ; 24(1): 83, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38402402

RESUMEN

Apatinib was the first anti-angiogenic agent approved for treatment of metastatic gastric cancer (GC). However, the emergence of resistance was inevitable. Thus investigating new and valuable off-target effect of apatinib directly against cancer cells is of great significance. Here, we identified extra spindle pole bodies-like 1 (ESPL1) was responsible for apatinib resistance in GC cells through CRISPR genome-wide gain-of-function screening. Loss of function studies further showed that ESPL1 inhibition suppressed cell proliferation, migration and promoted apoptosis in vitro, and accordingly ESPL1 knockdown sensitized GC cells to apatinib. In addition, we found ESPL1 interacted with mouse double minute 2 (MDM2), a E3 ubiquitin protein ligase, and the combination of MDM2 siRNA with apatinib synergistically ameliorated the resistance induced by ESPL1 overexpression. In summary, our study indicated that ESPL1 played a critical role in apatinib resistance in GC cells. Inhibition of MDM2 could rescue the sensitivity of GC cells to apatinib and reverse ESPL1-mediated resistance.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38299401

RESUMEN

BACKGROUND: Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. OBJECTIVE: Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. METHODS: RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. RESULTS: Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. CONCLUSION: Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

4.
Artículo en Inglés | MEDLINE | ID: mdl-37933535

RESUMEN

Technologies for human-machine interactions are booming now. In order to achieve multifunctional sensing abilities of electronic skins, further developments of various sensors are in urgent demand. Herein, a dual-mode proximity sensor based on an oxide thin-film transistor (TFT) is reported. Although InSnO (ITO) is featured with high mobility, the inherent high carrier concentration limits its use as a channel material for thin-film transistors. Herein, the tungsten element was introduced as a carrier suppressor to develop ITO-based semiconducting materials and devices. TFTs with amorphous tungsten-doped ITO (ITWO) channel layers were fabricated. As for a flat panel display application, the TFT device from 250 °C-annealed ITWO layer with an atomic ratio of In/Sn/W = 86:9:5 presented the optimal device performance with carrier mobility of 11.53 cm2 V-1 s-1, swing subthreshold of 0.66 V dec-1, threshold voltage of -2.18 V, and Ion/Ioff ratio of 3.33 × 107 and much small hysteresis of transfer characteristic. ITWO TFT devices were further developed as dual-mode proximity sensors that could work with both extended-gate and compact configurations, where the drain current was directly related to the surface potential of a charged object and the distance between the sensing end and the object, enabling the proximity sensing of charged stimuli. For extended-gate-configured proximity sensing, a charged object modulated the formation of a conductive channel at the semiconductor/SiO2 interface, while this conductive channel occurred at the semiconductor/air interface for compact-configured sensing. Formation of the conductive channel of the compact transistor was modulated by the electric field component in the direction perpendicular to the interface, and the drain current was sensitive to the orientation of the approaching object, which implied the capacity of angle sensing to the approach of a charged object. This work further emphasizes that the basic device performance should be optimized according to its specific application scenarios rather than only considering the requirements of the panel display.

5.
J Med Chem ; 66(19): 13501-13515, 2023 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-37766386

RESUMEN

Excessive fructose absorption and its subsequent metabolisms are implicated in nonalcoholic fatty liver disease, obesity, and insulin resistance in humans. Ketohexokinase (KHK) is a primary enzyme involved in fructose metabolism via the conversion of fructose to fructose-1-phosphate. KHK inhibition might be a potential approach for the treatment of metabolic disorders. Herein, a series of novel KHK inhibitors were designed, synthesized, and evaluated. Among them, compound 14 exhibited more potent activity than PF-06835919 based on the rat KHK inhibition assay in vivo, and higher drug distribution concentration in the liver. Its good absorption, distribution, metabolism, and excretion and pharmacokinetic properties make it a promising clinical candidate.


Asunto(s)
Resistencia a la Insulina , Enfermedades Metabólicas , Animales , Humanos , Ratas , Fructoquinasas/antagonistas & inhibidores , Fructosa , Hígado/metabolismo , Enfermedades Metabólicas/tratamiento farmacológico
6.
J Lipid Res ; 64(11): 100449, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37734559

RESUMEN

Activation of brown adipose tissue (BAT) contributes to energy dissipation and metabolic health. Although mineralocorticoid receptor (MR) antagonists have been demonstrated to improve metabolism under obesity, the underlying mechanisms remain incompletely understood. We aimed to evaluate the role of BAT MR in metabolic regulation. After 8 weeks of high-fat diet (HFD) feeding, BAT MR KO (BMRKO) mice manifested significantly increased bodyweight, fat mass, serum fasting glucose, and impaired glucose homeostasis compared with littermate control (LC) mice, although insulin resistance and fasting serum insulin were not significantly changed. Metabolic cage experiments showed no change in O2 consumption, CO2 production, or energy expenditure in obese BMRKO mice. RNA sequencing analysis revealed downregulation of genes related to fatty acid metabolism in BAT of BMRKO-HFD mice compared with LC-HFD mice. Moreover, H&E and immunohistochemical staining demonstrated that BMRKO exacerbated HFD-induced macrophage infiltration and proinflammatory genes in epididymal white adipose tissue (eWAT). BMRKO-HFD mice also manifested significantly increased liver weights and hepatic lipid accumulation, an increasing trend of genes related to lipogenesis and lipid uptake, and significantly decreased genes related to lipolytic and fatty acid oxidation in the liver. Finally, the level of insulin-induced AKT phosphorylation was substantially blunted in eWAT but not liver or skeletal muscle of BMRKO-HFD mice compared with LC-HFD mice. These data suggest that BAT MR is required to maintain metabolic homeostasis, likely through its regulation of fatty acid metabolism in BAT and impacts on eWAT and liver.


Asunto(s)
Adipocitos Marrones , Metabolismo Energético , Receptores de Mineralocorticoides , Animales , Ratones , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos/metabolismo , Glucosa/metabolismo , Insulina/metabolismo , Resistencia a la Insulina/fisiología , Lípidos , Ratones Endogámicos C57BL , Ratones Obesos , Receptores de Mineralocorticoides/genética , Receptores de Mineralocorticoides/metabolismo , Metabolismo Energético/genética
7.
Int J Mol Sci ; 24(15)2023 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-37569676

RESUMEN

Forkhead box protein P3 (FoxP3) primarily functions as the master regulator in regulatory T cells (Tregs) differentiation, but its high level of expression has also been found in tumor cells recently. The aim of our study was to clarify the role of FoxP3 in renal cell carcinoma (RCC) progression and metastasis. We verified the FoxP3 characteristic clinicopathological data from The Cancer Genome Atlas (TCGA) database using bioinformatics tools. Meanwhile, RNA sequencing was performed to determine the FoxP3 biofunction in RCC progression. Our results showed that high expression of FoxP3 was found in BAP1- or SETD2-mutant patients with RCC, and a higher FoxP3 expression was related to worse prognosis. However, there was no statistically significant relationship between the FoxP3 IHC score and RCC malignant progression owning to the limited number of patients in our tissue microarray. Using in vitro FoxP3 loss-of-function assays, we verified that silencing FoxP3 in 786-O and ACHN cells could inhibit the cell migration/invasion capability, which was consistent with the data from RNA sequencing in 786-O cells and from the TCGA datasets. Using an in vivo nude mice orthotopic kidney cancer model, we found that silencing FoxP3 could inhibit tumor growth. In conclusion, our study demonstrated that BAP1 or SEDT2 mutation could lead to higher expression of FoxP3 in RCC patients, and FoxP3 could eventually stimulate RCC cells' invasion and metastasis, which might indicate that FoxP3 could function as a potential oncogene in RCC progression.


Asunto(s)
Carcinoma de Células Renales , Histona Metiltransferasas , Neoplasias Renales , Animales , Humanos , Ratones , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Neoplasias Renales/metabolismo , Ratones Desnudos , Mutación , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Ubiquitina Tiolesterasa/genética , Histona Metiltransferasas/metabolismo
8.
Curr Issues Mol Biol ; 45(6): 4763-4777, 2023 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-37367052

RESUMEN

Kidney tumors comprise a broad spectrum of different histopathological entities, with more than 0.4 million newly diagnosed cases each year, mostly in middle-aged and older men. Based on the description of the 2022 World Health Organization (WHO) classification of renal cell carcinoma (RCC), some new categories of tumor types have been added according to their specific molecular typing. However, studies on these types of RCC are still superficial, many types of these RCC currently lack accurate diagnostic standards in the clinic, and treatment protocols are largely consistent with the treatment guidelines for clear cell RCC (ccRCC), which might result in worse treatment outcomes for patients with these types of molecularly defined RCC. In this article, we conduct a narrative review of the literature published in the last 15 years on molecularly defined RCC. The purpose of this review is to summarize the clinical features and the current status of research on the detection and treatment of molecularly defined RCC.

9.
Nat Aging ; 3(4): 418-435, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37117789

RESUMEN

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adulto Joven , Humanos , Anciano , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunidad Celular , Células Clonales , Epítopos , Vacunas de Productos Inactivados
10.
Influenza Other Respir Viruses ; 17(3): e13112, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36875207

RESUMEN

Background: Influenza virus causes significant morbidity and mortality with pandemic threat. Oleaceae Fructus Forsythiae is a medicinal herb. This study aimed to investigate antiviral effect of Phillyrin, a purified bioactive compound from this herb, and its reformulated preparation FS21 against influenza and its mechanism. Methods: Madin-Darby Canine Kidney (MDCK) cells were infected by one of six influenza viruses: five influenza A viruses (IAVs: three H1N1 and two H3N2) and one influenza B virus (IBV). Virus-induced cytopathic effects were observed and recorded under microscope. Viral replication and mRNA transcription were evaluated by quantitative polymerase chain reaction (qPCR) and protein expression by Western blot. Infectious virus production was assessed using TCID50 assay, and IC50 was calculated accordingly. Pretreatment and time-of-addition experiments with Phillyrin or FS21 added 1 h before or in early (0-3 h), mid (3-6 h), or late (6-9 h) stages of viral infection were performed to assess their antiviral effects. Mechanistic studies included hemagglutination and neuraminidase inhibition, viral binding and entry, endosomal acidification, and plasmid-based influenza RNA polymerase activity. Results: Phillyrin and FS21 had potent antiviral effects against all six IAV and IBV in a dose-dependent manner. Mechanistic studies showed that both suppressed influenza viral RNA polymerase with no effect on virus-mediated hemagglutination inhibition, viral binding or entry, endosomal acidification, or neuraminidase activity. Conclusions: Phillyrin and FS21 have broad and potent antiviral effects against influenza viruses with inhibition of viral RNA polymerase as the distinct antiviral mechanism.


Asunto(s)
Antivirales , Glucósidos , Infecciones por Orthomyxoviridae , Animales , Perros , Humanos , Antivirales/farmacología , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Virus de la Influenza B , Neuraminidasa , Proteinas del Complejo de Replicasa Viral , Células de Riñón Canino Madin Darby , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Glucósidos/farmacología
11.
Diagnostics (Basel) ; 13(5)2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36900148

RESUMEN

Upper tract urothelial carcinoma (UTUC) is a relatively rare, but highly malignant, disease with an estimated annual incidence of 2 cases per 100,000 people. The main surgical treatment modalities for UTUC are radical nephroureterectomy (RNU) with bladder cuff resection. After surgery, intravesical recurrence (IVR) can occur in up to 47% of patients, and 75% of them present with non-muscle invasive bladder cancer (NMIBC). However, there are few studies focused on the diagnosis and treatment of postoperatively recurrent bladder cancer for patients with previous UTUC history (UTUC-BC), and many of the influencing factors are still controversial. In this article, we performed a narrative review of the recent literature, mainly summarizing the factors influencing postoperative IVR in patients with UTUC and discussing the subsequent prevention, monitoring, and treatment tools for it.

12.
iScience ; 26(3): 106099, 2023 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-36843840

RESUMEN

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. Here we described a genome-wide screen by CRISPR activation (CRISPRa) library in vivo for drivers of HCC growth and metastasis. Pathological results showed the cell population formed highly metastatic tumors in lung after being mutagenized with CRISPRa. In vitro validation indicated overexpression of XAGE1B, PLK4, LMO1 and MYADML2 promoted cells proliferation and invasion, and the inhibition suppressed HCC progress. In addition, we reported high MYADML2 protein level exhibited worse overall survival in HCC, which increased significantly in patients over 60 years. Moreover, high MYADML2 reduced the sensitivity to chemotherapeutic drugs. Interestingly, immune cell infiltration analysis showed that the dendritic cells, macrophages, and so forth might play important role in HCC progress. In brief, we provides a roadmap for screening functional genes related to HCC invasion and metastasis in vivo, which may provide new potential targets for the treatment of HCC.

13.
Pestic Biochem Physiol ; 190: 105338, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36740337

RESUMEN

Bradysia odoriphaga and Bradysia difformis are destructive root maggots that cause severe losses to vegetables, flowers and edible fungi. Due to the long-term dependence on single pesticides, Bradysia resistance to insecticides has increased, and field control efficacy has decreased obviously. To screen alternative insecticides, and compare the insecticide susceptibility of these two species, we tested the toxicity of eight insecticides to B. odoriphaga and B. difformis, and measured the sublethal effects of Dinotefuran and Lufenuron on life-history parameters and detoxification enzyme activities. Bioassay results indicated that Dinotefuran and Lufenuron had relatively higher toxicity to B. odoriphaga and B. difformis compared to other neonicotinoid and insect growth regulator insecticides, respectively. Significant adverse impacts caused by sublethal concentrations (LC20) of Dinotefuran and Lufenuron on the life-history parameters of F0 and F1 generations of B. odoriphaga and B. difformis were observed. These included reduced survival, prolonged larval development and reduced adult longevity and fecundity. B. odoriphaga had greater resistance and adaptation to insecticides than B. difformis, and an LC20 concentration of Dinotefuran stimulated the reproduction of B. odoriphaga F1 generation and increased the life table parameters. Detoxifying enzymes (CarE and GSTs) and P450 activities fluctuated after a sublethal concentration (Dinotefuran and Lufenuron) treatment, and at the peak value of enzyme activities, the enhancement of detoxifying enzymes of B. odoriphaga was significantly higher than that of B. difformis. These results indicated that Dinotefuran and Lufenuron should be considered as alternatives to other insecticides for control of root maggots. B. odoriphaga exhibited stronger adaptation to insecticides than B. difformis. These data provide guidance for control of root maggots, and the basic information presented here can help reveal the differences in adaptive mechanisms between B. odoriphaga and B. difformis.


Asunto(s)
Dípteros , Insecticidas , Animales , Insecticidas/toxicidad , Neonicotinoides/toxicidad , Larva
14.
Insects ; 14(2)2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36835731

RESUMEN

Mucor hiemalis BO-1 is an entomopathogenic fungus that infects Bradysia odoriphaga, a destructive root maggot. M. hiemalis BO-1 possesses stronger pathogenicity to the larvae than to other stages of B. odoriphaga, and provides satisfactory field control. However, the physiological response of B. odoriphaga larvae to infection and the infection mechanism of M. hiemalis are unknown. We detected some physiological indicators of diseased B. odoriphaga larvae infected by M. hiemalis BO-1. These included changes in consumption, nutrient contents, and digestive and antioxidant enzymes. We performed transcriptome analysis of diseased B. odoriphaga larvae, and found that M. hiemalis BO-1 showed acute toxicity to B. odoriphaga larvae and was as toxic as some chemical pesticides. The food consumption of diseased B. odoriphaga after inoculation with M. hiemalis spores decreased significantly, and there was a significant decrease in total protein, lipid, and carbohydrates in diseased larvae. Key digestive enzymes (protease, α-amylase, lipase, and cellulase) were significantly inhibited during infection. Peroxidase maintained high activity, and the activity of other antioxidant enzymes (catalase, superoxide dismutase, and glutathione S-transferases) first increased and then decreased. Combined with the transcriptional signatures of diseased B. odoriphaga larvae, M. hiemalis BO-1 infection resulted in decreased food consumption, reduced digestive enzyme activity, and altered energy metabolism and material accumulation. Infection was also accompanied by fluctuations in immune function, such as cytochrome P450 and the Toll pathway. Therefore, our results laid a basis for the further study of the interactions between M. hiemalis BO-1 and B. odoriphaga and promoted the genetic improvement of entomopathogenic fungi.

15.
Opt Express ; 30(26): 46552-46559, 2022 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-36558606

RESUMEN

Featuring with ultracompactness and subwavelength resolution, metasurface-assisted nanoprinting has been widely researched as an optical device for image display. It also provides a platform for information multiplexing, and a series of multiplexed works based on incident polarizations, operating wavelengths and observation angles have emerged. However, the angular-multiplexing nanoprinting is realized at the cost of image resolution reduction or the increase of fabrication difficulty, hindering its practical applications. Here, inspired by the Jacobi-Anger expansion, a phase-assisted design paradigm, called Bessel metasurface, was proposed for angular multiplexing nanoprinting. By elaborately designing the phase distribution of the Bessel metasurface, the target images can be encoded into the desired observation angles, reaching angular multiplexing. With the merits of ultracompactness and easy fabrication, we believe that our design strategy would be attractive in the real-world applications, including optical information storage, encryption/concealment, multifunctional switchable optical devices, and 3D stereoscopic displays, etc.

16.
Ann Transl Med ; 10(22): 1240, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36544660

RESUMEN

Background: Recent research suggests that dihydrolipoamide acetyltransferase (DLAT), which is a copper-induced cell death-related gene, is involved in multiple biological events in tumors. This study sought to investigate the relationship between DLAT and hepatocellular carcinoma (HCC). Methods: In the Cancer Genome Atlas (TCGA) database, we first identified the differentially expressed gene (i.e., DLAT), then confirmed DLAT expression, and found a link between it and the prognosis of HCC patients. An internal validation nomogram was built based on a multivariate Cox regression analysis. Data from the Tumor Immune Estimation Resource (TIMER) database was used to examine the association between DLT and immunological cells. A gene set enrichment analysis (GSEA) was conducted to investigate the probable mechanism of action. Finally, in vitro cytological research was conducted to further examin the involvement of DLAT in HCC-related unfavorable biological events. Results: The database screenings showed that DLAT was a differentially expressed molecule; that is, DLAT was more highly expressed in the cancer tissues than normal tissues. TCGA results and Kaplan-Meier-plotter data sets showed that HCC patients with reduced DLAT expression had greater disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI). The prediction model had a concordance index of 0.659 (0.614-0.704), which indicates high accuracy. According to the TIMER database, tumor cells in the HCC microenvironment may be able to bypass the immune system due to the expression of DLAT. The in vitro cytological tests showed that DLAT knockdown significantly decreased the proliferation and invasion of the HCC cells. It also inhibited the activity of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) and Wnt/ß-catenin signaling pathways. Conclusions: Decreased DLAT expression significantly prolongs the OS, PFI, and DSS of HCC patients. DLAT may be employed as a new predictive biomarker for HCC, and may be linked to the immune system in HCC patients. The tumor microenvironment (TME) may have a significant effect on the ability of tumor cells to evade the immune system. The PI3K/Akt and Wnt/ß-catenin signaling pathways may affect the prognosis of HCC by interfering with DLAT. Given these findings, HCC may be an ideal target for the development of anti-cancer therapies.

17.
Int J Genomics ; 2022: 6465760, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36419652

RESUMEN

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

18.
BMC Surg ; 22(1): 377, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36333708

RESUMEN

BACKGROUND: We aimed to compare the oncological outcomes between the oblique occlusion technique and the traditional technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) thrombectomy, and to explore the safety and effectiveness of the oblique occlusion technique. METHODS: Overall, 21 patients with renal cell carcinoma (RCC) and IVC tumor thrombus (TT) were admitted to our hospital from August 2019 to June 2020. All the patients underwent RARN with IVC thrombectomy, of which the IVC oblique occlusion technique was used in 11 patients and traditional occlusion technique was used in 10 patients. The oblique occlusion technique refers to oblique blocking from the upper corner of the right renal vein to the lower corner of the left renal vein using a vessel tourniquet or a vessel clamp (left RCC with IVCTT as an example). RESULTS: Compared with patients in the traditional group, those in the oblique group had lower serum creatinine at follow-up (3 month) (95 ± 21.1 vs. 131 ± 30.7 µmol/L, P = 0.03). There was no significant difference in operation time [149 (IQR 143-245) min vs. 148 (IQR 108-261) min, p = 0.86], IVC clamping time [18 (IQR 12-20) min vs. 20 (IQR 14-23) min, p = 0.41], and estimated intraoperative blood loss [300 (IQR 100-800) mL vs. 500 (IQR 175-738) mL, p = 0.51] between both groups. During a 16-month (range, 15-23 months) follow-up period, two cases progressed in the oblique group and three cases progressed in the traditional group. CONCLUSIONS: The modified IVC oblique occlusion technique procedure is relatively safe and effective in RARN with IVC thrombectomy. The IVC oblique occlusion technique may play a role in the protection of renal function.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Robótica , Trombosis de la Vena , Humanos , Vena Cava Inferior/cirugía , Vena Cava Inferior/patología , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Trombectomía/métodos , Nefrectomía/métodos , Trombosis de la Vena/cirugía , Trombosis de la Vena/patología , Estudios Retrospectivos
19.
Opt Express ; 30(19): 33574-33587, 2022 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-36242389

RESUMEN

Metasurface-based structural-colors are usually implemented by changing the dimensions of nanostructures to produce different spectral responses. Therefore, a single-size nanostructured metasurface usually cannot display structural-colors since it has only one design degree of freedom (DOF), i.e., the orientation angles of nanostructures. Here, we show structural-color nanoprinting images can be generated with a single-size nanostructured metasurface, enabled by designing the anisotropic nanostructure with different spectral responses along its long- and short-axis directions, respectively. More interestingly, the concept of orientation degeneracy of nanostructures can be applied in the metasurface design, which shows two spectral modulations can be implemented under different polarization directions of output light, thus extending the color-nanoprinting from single-channel to dual-channel. The proposed dual-channel metasurface used for anticounterfeiting color-nanoprinting has presented the advantages of ultra-compactness, high information capacity, and vivid colors, which can develop broad applications in fields such as high-end anticounterfeiting, high-density information storage, optical encryption, etc.

20.
Phys Chem Chem Phys ; 24(39): 24394-24403, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36189674

RESUMEN

Precise prediction of the hindered diffusion behavior of electroneutral particles in fibrous media plays a critical role in the development of drugs, polymer membranes, and porous electrodes. However, the random microstructure and unknown coupling relationship of multiple resistance mechanisms lead to the lack of a universal prediction model. In this work, a dual-resistance model is proposed by reconstructed pore-scale simulations, which presents the coexistence of steric and hydrodynamic resistances in the multiplication form. The simulation results show that the relationship between steric resistance and structural parameters (porosity, fiber radius, and particle radius) is exponential, while that for hydrodynamic resistance is polynomial. The dominant diffusion resistance is found to change from hydrodynamic to steric resistance with a decrease in porosity. The fluorescent polystyrene microsphere diffusivity in a series of SiO2 fibrous media is determined by single-particle tracking experiments, quantitatively confirming the dual-resistance model. The present model can be used for rapid diffusivity prediction and fibrous membrane and drug design.


Asunto(s)
Hidrodinámica , Nanopartículas , Difusión , Poliestirenos , Porosidad , Dióxido de Silicio
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