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The synthesis of zirconium MOFs with zeolite net is quite challenging due to the high connectivity of Zr6 clusters, which is far from tetrahedral connection, a requisite for zeolite net. In this work, we demonstrate a six-membered ring (6MR) strategy through mimicking of mineral zeolites with mixed ditopic and tritopic carboxylate linkers. With this strategy, the ditopic linker cross-links Zr6 clusters to form 4-connected zeolite-like nets, while the tritopic one is used to direct the formation of 6MR and simultaneously consumes extra coordination sites on the cluster. The feasibility of this strategy is shown by one zeolitic metal-organic framework (NNM-5) and this strategy has also led to the synthesis of the other dia-type zirconium MOF (NNM-6). Interestingly, as the tritopic linker not only directs the formation of 6-MR but also partitions 6-MR into small segments, NNM-5 with SOD topology shows a structural feature of small aperture and big cage, which has led to efficient separation of hexane isomers. With both exceptionally high n-hexane uptake (65.9 cm3·g-1) and size-exclusion selectivity, an exceptional separation capability is verified by breakthrough experiments. Calculation results demonstrate that the large difference of diffusion energy barrier due to the small aperture accounts for the underlying separation mechanism.
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Objective: This study aimed to investigate the expression of GPRC5A in pan-cancer and its correlation with clinical outcomes, tumor immune microenvironment, and biological functions. Methods: The expression of GPRC5A was analyzed using 33 tumor datasets from the TCGA, GTEx and TCGA databases. Immunohistochemical images from the HPA database were also examined. Kaplan-Meier survival analysis was conducted to assess the prognostic value of GPRC5A. Correlations between GPRC5A expression and clinical parameters were investigated. Nomogram models were developed to predict survival probabilities. The correlation between GPRC5A expression and tumor immune microenvironment was analyzed using the GEPIA2 database. Functional enrichment analysis and Gene Set Enrichment Analysis were performed to explore the biological functions associated with GPRC5A. Results: GPRC5A exhibited varying expression levels across different types of tumors, with high expression observed in 11 types of cancer tissues. Aberrant GPRC5A expression was correlated with overall survival, disease-specific survival, and progression-free interval in specific cancers. Specific clinicopathological features were found to be associated with GPRC5A expression in six tumors. Nomogram models incorporating GPRC5A expression demonstrated significant clinical utility in predicting survival probabilities for patients with ACC, KIRC, LGG, and PAAD. GPRC5A was also found to be associated with the tumor immune microenvironment. Functional enrichment analysis revealed the involvement of GPRC5A-related genes in various biological processes and functions. Conclusion: This study highlights the differential expression of GPRC5A in pan-cancer and its correlation with clinical outcomes. GPRC5A shows potential as a prognostic biomarker and therapeutic target in specific cancers. Moreover, its association with the tumor immune microenvironment suggests its involvement in the tumor immune response. The findings provide valuable insights into the biological roles of GPRC5A in tumors and contribute to our understanding of its clinical implications.
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Potassium-ion batteries (PIBs) have been widely studied owing to the abundant reserves, widespread distribution, and easy extraction of potassium (K) resources. Molybdenum disulfide (MoS2) has received a great deal of attention as a key anode material for PIBs owing to its two-dimensional diffusion channels for K+ ions. However, due to its poor electronic conductivity and the huge influence of embedded K+ ions (with a large ionic radius of 3.6 Å) on MoS2 layer, MoS2 anodes exhibit a poor rate performance and easily collapsed structure. To address these issues, the common strategies are enlarging the interlayer spacing to reduce the mechanical strain and increasing the electronic conductivity by adding conductive agents. However, simultaneous implementation of the above strategies by simple methods is currently still a challenge. Herein, MoS2 anodes on reduced graphene oxide (MoS2/rGO) composite were prepared using one-step hydrothermal methods. Owing to the presence of rGO in the synthesis process, MoS2 possesses a unique scaled structure with large layer spacing, and the intrinsic conductivity of MoS2 is proved. As a result, MoS2/rGO composite anodes exhibit a larger rate performance and better cycle stability than that of anodes based on pure MoS2, and the direct mixtures of MoS2 and graphene oxide (MoS2-GO). This work suggests that the composite material of MoS2/rGO has infinite possibilities as a high-quality anode material for PIBs.
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BACKGROUND: Chemotherapeutic agents including cisplatin, gemcitabine, and pemetrexed, significantly enhance the efficacy of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) by increasing PD-L1 expression and potentiating T cell cytotoxicity. However, the low response rate and adverse effects limit the application of chemotherapy/ICI combinations in patients. METHODS: We screened for medicinal herbs that could perturb PD-L1 expression and enhance T cell cytotoxicity in the presence of anti-PD-L1 antibody, and investigated the underlying mechanisms. RESULTS: We found that the aqueous extracts of Centipeda minima (CM) significantly enhanced the cancer cell-killing activity and granzyme B expression level of CD8+ T cells, in the presence of anti-PD-L1 antibody. Both CM and its active component 6-O-angeloylplenolin (6-OAP) upregulated PD-L1 expression by suppressing GSK-3ß-ß-TRCP-mediated ubiquitination and degradation. CM and 6-OAP significantly enhanced ICI-induced reduction of tumor burden and prolongation of overall survival of mice bearing NSCLC cells, accompanied by upregulation of PD-L1 and increase of CD8+ T cell infiltration. CM also exhibited anti-NSCLC activity in cells and in a patient-derived xenograft mouse model. CONCLUSIONS: These data demonstrated that the induced expression of PD-L1 and enhancement of CD8+ T cell cytotoxicity underlay the beneficial effects of 6-OAP-rich CM in NSCLCs, providing a clinically available and safe medicinal herb for combined use with ICIs to treat this deadly disease.
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Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Antígeno B7-H1/metabolismo , Línea Celular Tumoral , Linfocitos T CD8-positivos/efectos de los fármacos , Ratones , Extractos Vegetales/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto , FemeninoRESUMEN
To reduce the bitterness of florfenicol, avoid its degradation by gastric acid, and enhance its antibacterial activity against Escherichia coli by targeting and slowly releasing drugs at the site of intestinal infection, with pectin as an anion carrier and chitosan oligosaccharides (COS) as a cationic carrier, florfenicol-loaded COS@pectin core nanogels were self-assembled by electrostatic interaction and then encapsulated in sodium carboxymethylcellulose (CMCNa) shell nanogels through the complexation of CMCNa and Ca2+ to prepare florfenicol core-shell composite nanogels in this study. The florfenicol core-shell composite nanogels were investigated for their formula choice, physicochemical characterization, pH-responsive performances, antibacterial activity, therapeutic efficacy, and in vitro and in vivo biosafety studies. The results indicated that the optimized formula was 0.6 g florfenicol, 0.79 g CMCNa, 0.30 g CaCl2, 0.05 g COS, and 0.10 g pectin, respectively. In addition, the mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 124.0 ± 7.2 nm, -22.9 ± 2.5 mV, 0.42 ± 0.03, 43.4 % ± 3.1 %, and 80.5 % ± 3.4 %, respectively. The appearance, lyophilized mass, resolvability, scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and fourier transform infrared (FTIR) showed that the florfenicol core-shell composite nanogels were successfully prepared. Florfenicol core-shell composite nanogels had satisfactory stability, rheology, and pH-responsiveness, which were conducive to avoid degradation by gastric acid and achieve targeted and slow release at intestinal infection sites. More importantly, florfenicol core-shell composite nanogels had excellent antibacterial activity against Escherichia coli, a satisfactory therapeutic effect, and good palatability. In vitro and in vivo biosafety studies suggested the great promise of florfenicol core-shell composite nanogels. Therefore, the prepared florfenicol core-shell composite nanogels may be helpful for the treatment of bacterial enteritis as a biocompatible oral administration.
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Antibacterianos , Quitosano , Escherichia coli , Pectinas , Tianfenicol , Tianfenicol/análogos & derivados , Tianfenicol/administración & dosificación , Tianfenicol/química , Tianfenicol/farmacología , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Quitosano/química , Quitosano/administración & dosificación , Animales , Escherichia coli/efectos de los fármacos , Pectinas/química , Administración Oral , Portadores de Fármacos/química , Liberación de Fármacos , Nanogeles/química , Carboximetilcelulosa de Sodio/química , Masculino , Concentración de Iones de Hidrógeno , Ratones , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Tamaño de la Partícula , Polietilenglicoles/química , Polietilenglicoles/administración & dosificación , Nanopartículas/químicaRESUMEN
OBJECTIVES: Aneurysm wall enhancement (AWE) on high-resolution contrast-enhanced vessel wall MRI (VWMRI) is an emerging biomarker for intracranial aneurysms (IAs) stability. Quantification methods of AWE in the literature, however, are variable. We aimed to determine the optimal post-contrast timing to quantify AWE in both saccular and fusiform IAs. MATERIALS AND METHODS: Consecutive patients with unruptured IAs were prospectively recruited. VWMRI was acquired on 1 pre-contrast and 4 consecutive post-contrast phases (each phase was 9 min). Signal intensity values of cerebrospinal fluid (CSF) and aneurysm wall on pre- and 4 post-contrast phases were measured to determine the aneurysm wall enhancement index (WEI). AWE was also qualitatively analyzed on post-contrast images using previous grading criteria. The dynamic changes of AWE grade and WEI were analyzed for both saccular and fusiform IAs. RESULTS: Thirty-four patients with 42 IAs (27 saccular IAs and 15 fusiform IAs) were included. The changes in AWE grade occurred in 8 (30%) saccular IAs and 6 (40%) in fusiform IAs during the 4 post-contrast phases. The WEI of fusiform IAs decreased 22.0% over time after contrast enhancement (p = 0.009), while the WEI of saccular IAs kept constant during the 4 post-contrast phases (p > 0.05). CONCLUSIONS: When performing quantitative analysis of AWE, acquiring post-contrast VWMRI immediately after contrast injection achieves the strongest AWE for fusiform IAs. While the AWE degree is stable for 36 min after contrast injection for saccular IAs. CLINICAL RELEVANCE STATEMENT: The standardization of imaging protocols and analysis methods for AWE will be helpful for imaging surveillance and further treatment decisions of patients with unruptured IAs. KEY POINTS: Imaging protocols and measurements of intracranial aneurysm wall enhancement are reported heterogeneously. Aneurysm wall enhancement for fusiform intracranial aneurysms (IAs) is strongest immediately post-contrast, and stable for 36 min for saccular IAs. Future multi-center studies should investigate aneurysm wall enhancement as an emerging marker of aneurysm growth and rupture.
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Aqueous aluminum-ion batteries have many advantages such as their safety, environmental friendliness, low cost, high reserves and the high theoretical specific capacity of aluminum. So aqueous aluminum-ion batteries are potential substitute for lithium-ion batteries. In this paper, the current research status and development trends of cathode and anode materials and electrolytes for aqueous aluminum-ion batteries are described. Aiming at the problem of passivation, corrosion and hydrogen evolution reaction of aluminum anode and dissolution and irreversible change of cathode after cycling in aqueous aluminum-ion batteries. Solutions of different research routes such as ASEI (artificial solid electrolyte interphase), alloying, amorphization, elemental doping, electrolyte regulation, etc and different transformation mechanisms of anode and cathode materials during cycling have been summarized. Moreover, it looks forward to the possible research directions of aqueous aluminum-ion batteries in the future. We hope that this review can provide some insights and support for the design of more suitable electrode materials and electrolytes for aqueous aluminum-ion batteries.
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Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.
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Proliferación Celular , ADN Helicasas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Daño del ADN , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Reparación del ADN/efectos de los fármacosRESUMEN
Ethylene-vinyl acetate copolymer (EVA) is widely used in various applications; however, its flammability limits its application in wire and cable industries. In this study, 3-methacryloxypropyltrimethoxysilane (KH570) was successfully grafted onto the surface of anhydrous magnesium carbonate (AMC) by alkali activation treatment. The KH570 modified AMC (AMC@KH570) was then introduced into the EVA matrix along with hexaphenoxycyclotriphosphazene (HPCTP) to assess their effects on the flame retardancy and mechanical properties of EVA composites. The results illustrate a significant synergistic effect in enhancing the flame retardancy of EVA composites by using AMC@KH570 and HPCTP, and the limiting oxygen index (LOI) and vertical burning test (UL-94) of EVA filled with 5 wt% HPCTP and 45 wt% AMC@KH570 (mAMC/H-45-5) reached 27.6% and V-0, respectively. The flame retardant mechanism was investigated by thermogravimetric/infrared (TG-IR) spectroscopy and residual carbon composition analysis. The results show that the thermal decomposition of AMC@KH570 and HPCTP consists of gas dilution, free radical quenching, and catalytic carbonization. Furthermore, KH570 works as a bridge to improve the compatibility of AMC and EVA matrix, which offsets the mechanical loss of EVA to some extent. The present research provides a new path to modify AMC and fabricate EVA composites with excellent flame retardant properties.
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Aluminium is one of the most abundant metals in the universe and impacts the evolution of various astrophysical environments. Currently detected Al-bearing molecules represent only a small fraction of the aluminium budget, suggesting that aluminium may reside in other species. AlO and AlOH molecules are abundant in the oxygen-rich supergiant stars such as VY Canis Majoris, a stellar molecular factory with 60+ molecules including the prebiotic NC-bearing species. Additional Al-bearing molecules with N, C, O, and H may form in O-rich environments with radiation-accelerated chemistry. Here, we present spectroscopic identification of novel aluminium-bearing molecules composed of [Al, N, C, O, H] and [Al, N, C, O] from the reactions of Al atoms and HNCO in solid argon matrix, which are potential Al-bearing molecules in space. Photoinduced transformations among six [Al, N, C, O, H] isomers and three [Al, N, C, O] isomers, along with their dissociation reactions forming the known interstellar species, have been disclosed. These results provide new insight into the chemical network of astronomically detected Al-bearing species in space.
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BACKGROUND: Biofilms, such as those from Staphylococcus epidermidis, are generally insensitive to traditional antimicrobial agents, making it difficult to inhibit their formation. Although quercetin has excellent antibiofilm effects, its clinical applications are limited by the lack of sustained and targeted release at the site of S. epidermidis infection. OBJECTIVES: Polyethylene glycol-quercetin nanoparticles (PQ-NPs)-loaded gelatin-N,O-carboxymethyl chitosan (N,O-CMCS) composite nanogels were prepared and assessed for the on-demand release potential for reducing S. epidermidis biofilm formation. METHODS: The formation mechanism, physicochemical characterization, and antibiofilm activity of PQ-nanogels against S. epidermidis were studied. RESULTS: Physicochemical characterization confirmed that PQ-nanogels had been prepared by the electrostatic interactions between gelatin and N,O-CMCS with sodium tripolyphosphate. The PQ-nanogels exhibited obvious pH and gelatinase-responsive to achieve on-demand release in the micro-environment (pH 5.5 and gelatinase) of S. epidermidis. In addition, PQ-nanogels had excellent antibiofilm activity, and the potential antibiofilm mechanism may enhance its antibiofilm activity by reducing its relative biofilm formation, surface hydrophobicity, exopolysaccharides production, and eDNA production. CONCLUSIONS: This study will guide the development of the dual responsiveness (pH and gelatinase) of nanogels to achieve on-demand release for reducing S. epidermidis biofilm formation.
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Quitosano , Nanopartículas , Animales , Staphylococcus epidermidis/genética , Nanogeles , Gelatina/farmacología , Quercetina/farmacología , Biopelículas , Quitosano/farmacología , Quitosano/química , Gelatinasas/farmacología , Antibacterianos/farmacologíaRESUMEN
The antitumor effect of norcantharidin (NCTD) has been widely reported. However, whether NCTD can inhibit cervical cancer remains unknown. In the present study, it was shown that NCTD inhibited the viability of cervical cancer cells and caused cell cycle arrest in a concentrationdependent manner. Further analysis revealed that the NCTDinduced reduction in cell viability could be reversed by the inhibitor of apoptosis zVADFMK and by the inhibitor of endoplasmic reticulum (ER) stress, 4phenylbutyric acid (4PBA). Additionally, NCTD led to the accumulation of reactive oxygen species as well as a decrease in the mitochondrial membrane potential in cervical cancer cells, whereas 4PBA pretreatment attenuated these alterations. In addition, NCTD increased the expression of the apoptosisrelated proteins Bip, activating transcription factor (ATF) 4 and C/EBP homologous protein in a concentrationdependent manner. Moreover, NCTD significantly increased the expression of the ER stressrelated signaling molecules protein kinase Rlike ER kinase, inositolrequiring enzyme 1 and ATF6, but 4PBA abolished these effects. In vivo experiments showed that NCTD significantly inhibited the growth of subcutaneous tumors in mice. Additionally, the expression of ER stressrelated molecules and apoptosisrelated proteins increased significantly after NCTD treatment. In conclusion, NCTD induces apoptosis by activating ER stress and ultimately curtails the progression of cervical cancer.
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Compuestos Bicíclicos Heterocíclicos con Puentes , Butilaminas , Neoplasias del Cuello Uterino , Humanos , Femenino , Ratones , Animales , Neoplasias del Cuello Uterino/tratamiento farmacológico , Apoptosis , Estrés del Retículo Endoplásmico , Proliferación Celular , Línea Celular TumoralRESUMEN
BACKGROUND AND PURPOSE: Intracranial plaque enhancement (IPE) identified by contrast-enhanced vessel wall MR imaging (VW-MR imaging) is an emerging marker of plaque instability related to stroke risk, but there was no standardized timing for postcontrast acquisition. We aim to explore the optimal postcontrast timing by using multiphase contrast-enhanced VW-MR imaging and to test its performance in differentiating culprit and nonculprit lesions. MATERIALS AND METHODS: Patients with acute ischemic stroke due to intracranial plaque were prospectively recruited to undergo VW-MR imaging with 1 precontrast phase and 4 consecutive postcontrast phases (9 minutes and 13 seconds for each phase). The signal intensity (SI) values of the CSF and intracranial plaque were measured on 1 precontrast and 4 postcontrast phases to determine the intracranial plaque enhancement index (PEI). The dynamic changes of the PEI were compared between culprit and nonculprit plaques on the postcontrast acquisitions. RESULTS: Thirty patients with acute stroke (aged 59 ± 10 years, 18 [60%] men) with 113 intracranial plaques were included. The average PEI of all intracranial plaques significantly increased (up to 14%) over the 4 phases. There was significantly increased PEI over the 4 phases for culprit plaques (an average increase of 23%), but this was not observed for nonculprit plaques. For differentiating culprit and nonculprit plaques, we observed that the performance of IPE in the second postcontrast phase (cutoff = 0.83, AUC = 0.829 [0.746-0.893]) exhibited superior accuracy when compared with PEI in the first postcontrast phase (cutoff = 0.48; AUC = 0.768 [0.680-0.843]) (P = .022). CONCLUSIONS: A 9-minute delay of postcontrast acquisition can maximize plaque enhancement and better differentiate between culprit and nonculprit plaques. In addition, culprit and nonculprit plaques have different enhancement temporal patterns, which should be evaluated in future studies.
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Arteriosclerosis Intracraneal , Accidente Cerebrovascular Isquémico , Placa Aterosclerótica , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Arteriosclerosis Intracraneal/patología , Imagen por Resonancia Magnética/métodos , Placa Aterosclerótica/patologíaRESUMEN
This research explores the potential of multimodal fusion for the differential diagnosis of early-stage lung adenocarcinoma (LUAD) (tumor sizes < 2 cm). It combines liquid biopsy biomarkers, specifically extracellular vesicle long RNA (evlRNA) and the computed tomography (CT) attributes. The fusion model achieves an impressive area under receiver operating characteristic curve (AUC) of 91.9% for the four-classification of adenocarcinoma, along with a benign-malignant AUC of 94.8% (sensitivity: 89.1%, specificity: 94.3%). These outcomes outperform the diagnostic capabilities of the single-modal models and human experts. A comprehensive SHapley Additive exPlanations (SHAP) is provided to offer deep insights into model predictions. Our findings reveal the complementary interplay between evlRNA and image-based characteristics, underscoring the significance of integrating diverse modalities in diagnosing early-stage LUAD.
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Tumor cells are usually considered defective in mitochondrial respiration, but human non-small cell lung cancer (NSCLC) tumor tissues are shown to have enhanced glucose oxidation relative to adjacent benign lung. Here, we reported that oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) inhibited glycolysis and promoted oxidative metabolism in NSCLC cells. CIP2A bound to pyruvate kinase M2 (PKM2) and induced the formation of PKM2 tetramer, with serine 287 as a novel phosphorylation site essential for PKM2 dimer-tetramer switching. CIP2A redirected PKM2 to mitochondrion, leading to upregulation of Bcl2 via phosphorylating Bcl2 at threonine 69. Clinically, CIP2A level in tumor tissues was positively correlated with the level of phosphorylated PKM2 S287. CIP2A-targeting compounds synergized with glycolysis inhibitor in suppressing cell proliferation in vitro and in vivo. These results indicated that CIP2A facilitates oxidative phosphorylation by promoting tetrameric PKM2 formation, and targeting CIP2A and glycolysis exhibits therapeutic potentials in NSCLC.
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OBJECTIVES: Significant atherosclerotic stenosis or occlusion in the distal internal carotid artery (ICA) may induce diffuse wall thickening (DWT) in the upstream arterial wall. This study aimed to assess the association of atherosclerotic steno-occlusive diseases in the distal ICA with DWT in the upstream ipsilateral ICA. METHODS: Individuals with atherosclerotic stenosis in the distal ICA, detected by carotid MR vessel wall imaging using 3D pre- and post-contrast T1 volume isotropic turbo spin-echo acquisition (T1-VISTA) sequence, were enrolled. The associations of vessel wall thickening, the longitudinal extent of DWT, enhancement of the upstream ipsilateral ICA, and stenosis degree in the distal ICA were examined. RESULTS: Totally 64 arteries in 55 patients with atherosclerotic steno-occlusive distal ICAs were included. Significant correlations were found between distal ICA stenosis and DWT in the petrous ICA (r = 0.422, p = 0.001), DWT severity (r = 0.474, p < 0.001), the longitudinal extent of DWT in the ICA (r = 0.671, p < 0.001), enhancement in the petrous ICA (r = 0.409, p = 0.001), and enhancement degree (r = 0.651, p < 0.001). In addition, high degree of enhancement was correlated with both increased wall thickness and increased prevalence of DWT in the petrous ICA (both p < 0.001). CONCLUSIONS: DWT of the petrous ICA is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal ICA. The degree of stenosis in the distal ICA is associated with wall thickening and its longitudinal extent in the upstream segments. CLINICAL RELEVANCE STATEMENT: Diffuse wall thickening is a common secondary change in atherosclerotic steno-occlusive disease in the intracranial carotid. This phenomenon constitutes a confounding factor in the distinction between atherosclerosis and inflammatory vasculopathies, and could be reversed after alleviated atherosclerotic stenosis. KEY POINTS: ⢠Diffuse wall thickening of the petrous internal carotid artery is commonly detected in patients with atherosclerotic steno-occlusive disease in the distal internal carotid artery. ⢠The phenomenon of diffuse wall thickening could be reversed after stenosis alleviation. ⢠Carotid artery atherosclerosis with diffuse wall thickening should warrant a differential diagnosis from other steno-occlusive diseases, including moyamoya diseases and Takayasu aortitis.
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Arteria Carótida Interna , Estenosis Carotídea , Humanos , Femenino , Masculino , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/complicaciones , Persona de Mediana Edad , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/patología , Anciano , Angiografía por Resonancia Magnética/métodos , Adulto , Imagenología Tridimensional/métodos , Anciano de 80 o más AñosRESUMEN
Acetylshikonin (AS) is an active component of Lithospermum erythrorhizon Sieb. et Zucc that exhibits activity against various cancers; however, the underlying mechanisms of AS against oesophageal squamous carcinoma (ESCC) need to be elusive. The research explores the anti-cancer role and potential mechanism of AS on ESCC in vitro and in vivo, providing evidences for AS treatment against ESCC. In this study, we firstly demonstrated that AS treatment effectively inhibits cell viability and proliferation of ESCC cells. In addition, AS significantly induces G1/S phage arrest and promotes apoptosis in ESCC cell lines. Further studies reveal that AS induces ER stress, as observed by dose- and time-dependently increased expression of BIP, PDI, PERK, phosphorylation of eIF2α , CHOP and splicing of XBP1. CHOP knockdown or PERK inhibition markedly rescue cell apoptosis induced by AS. Moreover, AS treatment significantly inhibits ESCC xenograft growth in nude mice. Elevated expression of BIP and CHOP is also observed in xenograft tumours. Taken together, AS inhibits proliferation and induces apoptosis through ER stress-activated PERK/eIF2α /CHOP pathway in ESCC, which indicates AS represents a promising candidate for ESCC treatment.
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Antraquinonas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Ratones , Animales , Humanos , eIF-2 Quinasa/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Ratones Desnudos , Estrés del Retículo Endoplásmico , Apoptosis , Factor de Transcripción CHOP/metabolismoRESUMEN
AIMS: Interleukin-34 (IL-34) and macrophage colony-stimulating factor (CSF-1) have similar functions, such as promoting the formation of liver fibrosis. This study aimed to evaluate and compare the diagnostic value of serum IL-34 and CSF-1 for significant liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: A total of 369 CHB patients, consisting of 208 HBeAg-negative patients and 161 HBeAg-positive patients, were enrolled in this study. Additionally, 72 healthy individuals served as healthy controls (HCs). Serum levels of IL-34 and CSF-1 were measured using the enzyme-linked immunosorbent assay method. Liver fibrosis grades were assessed using the modified Scheuer scoring system. RESULTS: Serum IL-34 and CSF-1 levels exhibited significant elevation in both HBeAg-negative and HBeAg-positive patients in comparison to HCs (p < 0.001). IL-34 emerged as an independent factor linked to significant liver fibrosis, whereas CSF-1 did not exhibit such an association. Receiver operating characteristic (ROC) analysis indicated higher areas under the curves (AUCs) for IL-34 (0.814, p < 0.001 and 0.673, p < 0.001) when diagnosing significant liver fibrosis in HBeAg-negative and HBeAg-positive patients, respectively, as opposed to CSF-1 (0.602, p < 0.001; 0.619, p = 0.385). Within the HBeAg-negative patient subgroup, the AUC for IL-34 surpassed that of FIB-4 (p = 0.009) and APRI (p = 0.045). CONCLUSION: Serum IL-34 has the potential to be a straightforward and practical biomarker that demonstrates superior performance to serum CSF-1 in the diagnosis of significant liver fibrosis in CHB patients, especially within the HBeAg-negative patients.