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1.
J Am Chem Soc ; 146(38): 26534-26542, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39255449

RESUMEN

Dynamic twisting crystals, combining the features of dynamic crystals and twisting crystals, promise advanced applications in targeted drug delivery, biosensors, microrobots, and spiral optoelectronics. However, the determination of dynamic twisting crystals with specific directions remains a formidable challenge in practical applications. Herein, based on organic-inorganic hybrid metal halide (OIHMH) single crystals, we have realized the chirality-induced macroscopic twisting of single crystals driven by a thermo-induced topochemical dehydration reaction. These crystals exhibit molecular-chirality-induced twisting upon heating, along with reversals in their linear chiroptical circular dichroism and nonlinear chiroptical second harmonic generation circular dichroism. Such an induced twisting has been attributed to the alteration of the helical arrangement of chiral cation post-topochemical dehydration. The feasibility of tuning the macroscopic twisting of OIHMH single crystals and the switching in their linear and nonlinear chiroptical properties might open up new avenues for developing dynamic crystals for microactuating and optoelectronic applications.

2.
Cancer Lett ; : 217271, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39306229

RESUMEN

Metabolic remodeling is a pivotal feature of cancer, with cancer stem cells frequently showcasing distinctive metabolic behaviors. Nonetheless, understanding the metabolic intricacies of triple-negative breast cancer (TNBC) and breast cancer stem cells (BCSCs) has remained elusive. In this study, we meticulously characterized the metabolic profiles of TNBC and BCSCs and delved into their potential implications for TNBC treatment. Our findings illuminated the robust lipid metabolism activity within TNBC tumors, especially in BCSCs. Furthermore, we discovered that Fabp4, through its mediation of fatty acid uptake, plays a crucial role in regulating TNBC lipid metabolism. Knocking down Fabp4 or inhibiting its activity significantly suppressed TNBC tumor progression in both the MMTV-Wnt1 spontaneous TNBC model and the TNBC patient-derived xenograft model. Mechanistically, Fabp4's influence on TNBC tumor progression was linked to its regulation of mitochondrial stability, the CPT1-mediated fatty acid oxidation process, and ROS production. Notably, in a high-fat diet model, Fabp4 deficiency proved to be a substantial inhibitor of obesity-accelerated TNBC progression. Collectively, these findings shed light on the unique metabolic patterns of TNBC and BCSCs, underscore the biological significance of Fabp4-mediated fatty acid metabolism in governing TNBC progression, and offer a solid theoretical foundation for considering metabolic interventions in breast cancer treatment. SIGNIFICANCE: Triple-negative breast cancer progression and breast cancer stem cell activity can be restricted by targeting a critical regulator of lipid responses, FABP4.

3.
Int J Biol Sci ; 20(11): 4424-4437, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247809

RESUMEN

Prostate cancer presents as an immunologically "cold" malignancy, characterized by a lack of response to immunotherapy in the majority of patients. The dysfunction of prostate tumor metabolism is recognized as a critical factor in immune evasion, resulting in reduced effectiveness of immunotherapeutic interventions. Despite this awareness, the precise molecular mechanisms underpinning metabolic dysregulation in prostate cancer and its intricate relationship with immune evasion remain incompletely elucidated. In this study, we introduce the multi-drug resistance protein ABCC4/MRP4 as a key player prominently expressed in prostate cancer, exerting a pivotal role in suppressing the activity of intratumoral CD8+ T cells. Depletion of ABCC4 in prostate cancer cells halts the release of prostaglandin E2 (PGE2), a molecule that diminishes the population of CD8+ T cells and curtails their cytotoxic capabilities. Conversely, constraining the activation of PGE2 signaling in CD8+ T cells effectively improved the efficacy of prostate cancer treatment with PD-1 blockade. During this process, downregulation of the JAK1-STAT3 pathway and depolarization of mitochondria emerge as crucial factors contributing to T cell anergy. Collectively, our research identifies the ABCC4-PGE2 axis as a promising target for reversing dysfunction within tumor-infiltrating lymphocytes (TILs) and augmenting the suboptimal responsiveness to immunotherapy in prostate cancer.


Asunto(s)
Linfocitos T CD8-positivos , Dinoprostona , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Neoplasias de la Próstata , Masculino , Neoplasias de la Próstata/metabolismo , Linfocitos T CD8-positivos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Dinoprostona/metabolismo , Humanos , Receptor de Muerte Celular Programada 1/metabolismo , Línea Celular Tumoral , Animales , Ratones
4.
Angew Chem Int Ed Engl ; : e202416856, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291894

RESUMEN

Flexible crystals with unique mechanical properties have presented enormous applications in optoelectronics, soft robotics and sensors. However, there have been no reports of low-temperature-resistant flexible crystals with second-order nonlinear optical properties (NLO). Here, we report the flexible chiral Schiff-base crystals capable of efficient second harmonic generation (SHG). Both enantiomers and racemic modifications of these crystals are mechanically flexible in two directions at both room temperature and at -196 °C, although their mechanical responses differ. The enantiomers display SHG with an intensity of up to 12 times that of potassium dihydrogenphosphate (KDP) when pumped at 980 nm, and they also have high laser-induced damage thresholds (LDT). Even when bent, the crystals retain strong second harmonic generation, although with a different intensity distribution depending on the polarization, compared to when they are straight. This work describes the first instance of flexible organic crystal with NLO properties and lays the foundation for the development of mechanically flexible organic NLO materials.

5.
J Cancer ; 15(16): 5477-5491, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247595

RESUMEN

Background: ATP11A, a P-type ATPase, functions as flippases at the plasma membrane to maintain cellular function and vitality in several cancers. However, the role of ATP11A in gastric cancer remains unknown. This study aimed to identify ATP11A related to the biological behavior of gastric cancer, and elucidate the underlying mechanism. Methods: The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were used to analyze the expression and prognosis of ATP11A. The biofunctions of ATP11A were explored through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). The expression of ATP11A were validated by immunohistochemistry (IHC), qRT-PCR and Western blotting. Transwell, wound healing, CCK8 and colony-formation were to detected the migration, invasion and proliferation of gastric cancer cells. The epithelial-mesenchymal transition (EMT) and Hippo pathway markers were examined by Western blotting. Results: The expression of ATP11A was higher in gastric cancer tissues than in normal tissues, and high ATP11A levels were related to worse prognosis of gastric cancer patients. Additionally, we proved that ATP11A promoted the migration, invasion and proliferation in gastric cancer cells. Furthermore, ATP11A was found to promote EMT by devitalizing the Hippo pathway. Conclusion: ATP11A promoted migration, invasion, proliferation and EMT via Hippo signaling devitalization in gastric cancer cells.

6.
Cell Mol Biol Lett ; 29(1): 118, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237880

RESUMEN

BACKGROUND: Vasculogenic mimicry (VM) is a potential cause of resistance to antiangiogenic therapy and is closely related to the malignant progression of tumors. It has been shown that noncoding RNAs play an important role in the formation of VM in malignant tumors. However, the role of circRNAs in VM of bladder cancer and the regulatory mechanisms are unclear. METHODS: Firstly, hsa_circ_0000520 was identified to have circular character by Sanger sequencing and Rnase R assays. Secondly, the potential clinical value of hsa_circ_0000520 was explored by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) of clinical specimens. Thirdly, the role of hsa_circ_0000520 in bladder cancer invasion, migration, and VM formation was examined by in vivo and in vitro experiments. Finally, the regulatory mechanisms of hsa_circ_0000520 in the malignant progression of bladder cancer were elucidated by RNA binding protein immunoprecipitation (RIP), RNA pulldown, co-immunoprecipitation (co-IP), qRT-PCR, Western blot (WB), and fluorescence co-localization. RESULTS: Hsa_circ_0000520 was characterized as a circular RNA and was lowly expressed in bladder cancer compared with the paracancer. Bladder cancer patients with high expression of hsa_circ_0000520 had better survival prognosis. Functionally, hsa_circ_0000520 inhibited bladder cancer invasion, migration, and VM formation. Mechanistically, hsa_circ_0000520 acted as a scaffold to promote binding of UBE2V1/UBC13 to Lin28a, further promoting the ubiquitous degradation of Lin28a, improving PTEN mRNA stability, and inhibiting the phosphorylation of the PI3K/AKT pathway. The formation of hsa_circ_0000520 in bladder cancer was regulated by RNA binding protein QKI. CONCLUSIONS: Hsa_circ_0000520 inhibits metastasis and VM formation in bladder cancer and is a potential target for bladder cancer diagnosis and treatment.


Asunto(s)
Movimiento Celular , Fosfohidrolasa PTEN , Fosfatidilinositol 3-Quinasas , ARN Circular , Proteínas de Unión al ARN , Transducción de Señal , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Transducción de Señal/genética , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Movimiento Celular/genética , Masculino , Animales , Regulación Neoplásica de la Expresión Génica , Metástasis de la Neoplasia , Femenino , Neovascularización Patológica/genética , Ratones Desnudos , Ratones , Persona de Mediana Edad , Ratones Endogámicos BALB C
7.
Artículo en Inglés | MEDLINE | ID: mdl-39226206

RESUMEN

Ultrasound image super-resolution (SR) aims to transform low-resolution images into high-resolution ones, thereby restoring intricate details crucial for improved diagnostic accuracy. However, prevailing methods relying solely on image modality guidance and pixel-wise loss functions struggle to capture the distinct characteristics of medical images, such as unique texture patterns and specific colors harboring critical diagnostic information. To overcome these challenges, this paper introduces the Multi-Modal Regularized Coarse-to-fine Transformer (M2Trans) for Ultrasound Image SR. By integrating the text modality, we establish joint image-text guidance during training, leveraging the medical CLIP model to incorporate richer priors from text descriptions into the SR optimization process, enhancing detail, structure, and semantic recovery. Furthermore, we propose a novel coarse-to-fine transformer comprising multiple branches infused with self-attention and frequency transforms to efficiently capture signal dependencies across different scales. Extensive experimental results demonstrate significant improvements over state-of-the-art methods on benchmark datasets, including CCA-US, US-CASE, and our newly created dataset MMUS1K, with a minimum improvement of 0.17dB, 0.30dB, and 0.28dB in terms of PSNR. Our code and dataset will be available at: https://github.com/eezkni/M2Trans.

8.
Int J Biol Macromol ; 277(Pt 4): 134636, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128752

RESUMEN

To mitigate environmental impacts in food preservation, the development of a multifunctional membrane for packaging is of importance. In this study, we have successfully fabricated a nanofibrous membrane using an eco-friendly electrospinning technique, comprising polyvinyl alcohol (PVA), chitosan (CS), and tannic acid (TA). The resulting nanofibrous membranes were crosslinked with glutaraldehyde (GA) and surface modified with ZnO. Our findings demonstrate that the crosslinking process enhances water resistance, reduces water vapor permeability, improves tensile strength (from 3 to 18 MPa), and enhances thermal stability (increasing decomposition temperature from 225 °C to 310 °C). Furthermore, the incorporation of TA and ZnO provides antioxidant properties to the membrane, effectively preventing food decomposition caused by UV-induced oxidation. Additionally, CS, TA, and ZnO synergistically exhibit a remarkable antibacterial effect with a bacteriostasis rate exceeding 99.9 %. The strawberry fresh-keeping experiment further confirms that our developed membrane significantly extends shelf life by up to 6 days. Moreover, cytotoxicity assays confirm the non-toxic nature of these membranes. The innovative significance of this study lies in proposing a robust GA-PVA/CS/TA@ZnO nanofibrous membrane with excellent mechanical properties, biocompatibility, and multiple functionalities including antibacterial, anti-ultraviolet, and anti-oxidation capabilities. It has tremendous potential for applications in active food packaging materials.


Asunto(s)
Quitosano , Embalaje de Alimentos , Conservación de Alimentos , Frutas , Membranas Artificiales , Alcohol Polivinílico , Quitosano/química , Alcohol Polivinílico/química , Embalaje de Alimentos/métodos , Conservación de Alimentos/métodos , Frutas/química , Antioxidantes/química , Antioxidantes/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Taninos/química , Resistencia a la Tracción , Nanofibras/química , Permeabilidad , Vapor , Óxido de Zinc/química , Óxido de Zinc/farmacología , Fragaria/química
9.
Chemosphere ; 364: 143001, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39121961

RESUMEN

Three novel coordination polymers (CPs), namely [Cu(µ-1κO,2κN-L)2]n (1), [Zn (µ-1κO,2κN-L)2(H2O)2]n (2) and [Cd (µ-1κOO',2κN-L)2]n (3) [where HL = 4-(pyrimidin-5-ylcarbamoyl)benzoic acid], were synthesized and characterized by elemental analysis, ATR-IR, TGA, XPS and single-crystal X-ray diffraction. Despite having the same organic ligand, the various metal cations had an impact in the subsequent frameworks. Hirshfeld surface analysis was performed to investigate the intermolecular interactions and to examine the stability of the crystal structures of the three polymers. Their catalytic performances were screened for the peroxidative oxidation of Volatile Organic Compounds (VOCs), with toluene and p-xylene selected as model substrates. Tert-butyl hydroperoxide (t-BuOOH or TBHP) (aq. 70 %) was employed as the oxidant. The catalytic oxidation of toluene yielded benzyl alcohol, benzaldehyde and benzoic acid. The copper CP 1 exhibited the highest total yield for toluene oxidation, reaching approximately 36% in an aqueous medium. For p-xylene oxidation, tolualdehyde, methylbenzyl alcohol, and toluic acid were produced as the primary products, accompanied by minor ones. The experiments were conducted under diverse conditions, manipulating key parameters such as the choice of solvent (water or acetonitrile), type of oxidant (t-BuOOH or H2O2), the concentration of the oxidant and reaction temperature. In the presence of catalyst 1, a maximum total yield of ca. 80% was achieved for p-xylene oxidation.


Asunto(s)
Cobre , Oxidación-Reducción , Polímeros , Compuestos Orgánicos Volátiles , Cobre/química , Catálisis , Polímeros/química , Compuestos Orgánicos Volátiles/química , Complejos de Coordinación/química , Tolueno/química
10.
Transl Androl Urol ; 13(7): 1219-1227, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39100834

RESUMEN

Background: Multiparametric magnetic resonance imaging (mpMRI) is a commonly used method to diagnose pelvic lymph node metastasis (PLNM) in prostate cancer (PCa) patients, but there are few comparative studies on mpMRI and 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in locally advanced PCa (LAPC) patients. Therefore, we designed a retrospective study to compare the diagnostic value of 68Ga-PSMA PET/CT and mpMRI for PLNM of LAPC. Methods: A retrospective study was performed on 50 patients with LAPC who underwent radical prostatectomy (RP) in Tongji Hospital from 2021 to 2023. All patients underwent PET/CT and mpMRI examination, and were diagnosed as LAPC before surgery, followed by robot-assisted laparoscopic prostatectomy or laparoscopic RP and extended pelvic lymph node dissection (ePLND). Routine postoperative pathological examination was performed. According to the results, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT and mpMRI for the diagnosis of PLNM of LAPC were compared. Results: Among the 50 patients, the mean age was 65.5±10.3 years, the preoperative total serum prostate-specific antigen (PSA) was 30.7±12.3 ng/mL, and the Gleason score was 7 [7, 8]. The difference in diagnostic efficacy between 68Ga-PSMA PET/CT and mpMRI in the preoperative diagnosis of PLNM of PCa was determined by postoperative pathological results. Based on the number of patients who developed PLNM, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were as follows: 93.75%, 100.00%, 100.00%, 97.14%, and 68.75%, 97.06%, 91.67%, 86.84% for mpMRI, respectively. Based on the number of pelvic metastatic lymph nodes, the sensitivity, specificity, positive predictive value, and negative predictive value of 68Ga-PSMA PET/CT were 95.24%, 100.00%, 100.00%, 99.48%, and 65.08%, 99.13%, 89.13%, 96.30% for mpMRI, respectively. It turned out that PET/CT was more sensitive than mpMRI in detecting PLNM of PCa, and the difference was statistically significant. Conclusions: 68Ga-PSMA PET/CT is more sensitive than mpMRI in the detection of PLNM in patients with LAPC. It is a promising method in the diagnosis and preoperative assessment of PLNM in LAPC.

11.
Angew Chem Int Ed Engl ; : e202414231, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136326

RESUMEN

Integration of spirocycles with buckybowls is a promising strategy to construct three-dimensional (3D) curved π-systems and to endow distinctive physicochemical features arising from buckybowls. Herein, a series of carbon-bridged spiro-type heterosumanenes (spiro-HSEs) were synthesized by combining 9,9'-spirobifluorene and dichalcogenasumanenes (DCSs). It is found that spiro-conjugation plays an important role in the geometric and electronic structures of spiro-HSEs. The bowl depth of DCSs moiety becomes larger in the spiro-HSEs. Owing to the Jahn-Teller (J-T) effect, two DCSs segments of spiro-HSEs have different bowl depths accompanied with the unequal distribution of charge in radical cation state. Taking advantage of the typical reactions of DCSs, selective transformations of spiro-HSEs have been adopted in accordance to the nature of chalcogen atoms (S, Se, Te) to bestow the value-added functionalities. The emissive property is enhanced by converting the thiophene rings of S-doped spiro-HSE into thiophene S,S-dioxides. A chiroptical polycycle could be produced by ring-opening of the edge benzene of Se-doped spiro-HSE. The covalent adduct of Te-doped spiro-HSE with Br2 forms non-centrosymmetric halogen-bonded networks, resulting in the high performance second-order nonlinear optics (NLO).

12.
J Ethnopharmacol ; 337(Pt 1): 118708, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39197804

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Jizhi syrup (JZTJ) is composed of eight medicinal herbs, including Houttuynia cordata, Fagopyrum dibotrys, Ilex chinensis, Ephedra sinica, Aster tataricus, Peucedanum praeruptorum, Citrus aurantium and Glycyrrhiza uralensis. It is mainly used for coughing caused by exogenous wind heat. Symptoms include fever, aversion to cold, chest and diaphragm tightness, cough and sore throat; and acute bronchitis and acute exacerbation of chronic bronchitis with the above symptoms. PURPOSE: This study aimed to preliminary analyse the chemical components in the liposoluble part of JZTJ, evaluate the anti-inflammatory effect of JZTJ by using six animal and cell models and predict the target and mechanism of acute bronchitis prevention and treatment with JZTJ. METHODS: The chemical components in the liposoluble fraction of JZTJ (extracted by cyclohexane) were quantitatively analysed using gas chromatography-mass spectrometry (GC-MS). Classic non-specific inflammation models and acute bronchitis models were established to systematically evaluate the anti-inflammatory effect of JZTJ. The anti-inflammatory intensity and characteristics of three doses of JZTJ were comprehensively compared on the basis of principal component analysis method at the cellular and overall animal levels. By using lipopolysaccharides (LPSs) as modelling factors, a RAW264.7 macrophage inflammatory response model and a rat acute bronchitis model were created to study the effect of JZTJ on the in-vitro and - vivo LPS-iNOS-inflammatory mediators' inflammatory signalling pathway to reveal the mechanism of acute bronchitis prevention and treatment by JZTJ at the levels of genes, proteins, and inflammatory mediators. RESULTS: Seventeen alkane and ester compounds were preliminarily qualitatively identified from the lipid soluble fraction of JZTJ: dibutyl phthalate, tetradecane, ridecane, n-hexadecanoic acid, pentadecane, n-decanoic acid, 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(all-E)-; phenol, 2,2'-methylenebis[6-(1,1-dimethylethyl)-4-methyl-; hexadecane. JZTJ has a significant inhibitory effect on acute non-specific inflammation, specifically inhibiting 'xylene-induced ear swelling in mice', 'acetic acid-induced increased permeability of abdominal capillaries in mice' and 'egg white-induced foot swelling in rats'. The above effects are most evident in high doses, followed by medium doses, whereas low doses have poorer or no effects. JZTJ can prevent and treat acute bronchitis induced by LPS in mice and rats, significantly improve the pathological changes in patchy interstitial and alveolar bleeding with excessive neutrophil infiltration and inhibit the release of inflammatory mediators by LPS-induced RAW264.7 macrophages. Its mechanism of action may be by downregulating the phosphorylation level of p-ERK1/2 protein, thereby inhibiting inducible nitric oxide synthase (iNOS) mRNA, tumour necrosis factor (TNF)-α mRNA and IL-1ß. The expression levels of genes, such as mRNA and IL-6 mRNA, thereby reducing iNOS, TNF-α and IL-1ß. The expression of proteins in the cytoplasm of lung and bronchial tissue cells reduced the release of downstream inflammatory mediators NO and IL-6. CONCLUSION: Preliminary analysis of the chemical components in the lipid soluble fraction of JZTJ can lay the foundation for subsequent research on its effective components. Evaluating the anti-inflammatory effect of JZTJ is helpful for further research on its mechanism of action. The anti-inflammatory effects are exerted by regulating the inflammatory signalling pathway of LPS-iNOS inflammatory mediators, providing a scientific basis for their clinical application.

13.
Small ; : e2403271, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39039981

RESUMEN

2D transition metal carbides and nitrides, i.e., MXene, are recently attracting wide attentions and presenting competitive performances as adsorbents used in hemoperfusion. Nonetheless, the nonporous texture and easily restacking feature limit the efficient adsorption of toxin molecules inside MXene and between layers. To circumvent this concern, here a plerogyra sinuosa biomimetic porous titanium carbide MXene (P-Ti3C2) is reported. The hollow and hierarchically porous structure with large surface area benefits the maximum access of toxins as well as trapping them inside the spherical cavity. The cambered surface of P-Ti3C2 prevents layers restacking, thus affording better interlaminar adsorption. In addition to enhanced toxin removal ability, the P-Ti3C2 is found to selectively adsorb more middle and large toxin molecules than small toxin molecules. It possibly originates from the rich Ti-deficient vacancies in the P-MXene lattice that increases the affinity with middle/large toxin molecules. Also, the vacancies as active sites facilitate the production of reactive oxygen under NIR irradiation to promote the photodynamic antibacterial performance. Then, the versatility of P-MXene is validated by extension to niobium carbide (P-Nb2C). And the simulated hemoperfusion proves the practicability of the P-MXene as polymeric adhesives-free adsorbents to eliminate the broad-spectrum toxins.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38959943

RESUMEN

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive form of brain cancer. This study investigated the clinical predictive value of heat shock protein ß1 (HSPB1) in patients with GBM. METHODS: A correlation was established between HSPB1 expression and GBM progression using data from The Cancer Genome Atlas (TCGA) dataset, Chinese Glioma Genome Atlas dataset, Gene Expression Omnibus dataset, and Human Protein Atlas database. A survival analysis was conducted and an HSPB1-based nomogram was constructed to evaluate the prognostic value of HSPB1 in patients with GBM. RESULTS: Based on TCGA data mining, we discovered that HSPB1 was significantly elevated in patients with GBM and may reflect their response to immunotherapy. In survival analysis, it appeared to have a predictive role in the prognosis of patients with GBM. Five signaling pathways were significantly enriched in the high HSPB1 expression phenotype according to the gene set enrichment analysis. In addition, a significant association was found between HSPB1 expression and immune checkpoints, tumor immune infiltration, tumor immune microenvironment, and immune cell markers in glioma. Overall, our results suggest that HSPB1 may regulate the function of immune cells, serve as a new immunotherapy target, and predict the response to immunotherapy in patients with GBM. CONCLUSION: HSPB1 appears to serve as a potential predictor of the clinical prognosis and response to immunotherapy in patients with GBM. It may be possible to identify patients who are likely to benefit from immunotherapy by assessing the expression level of HSPB1.

15.
Inorg Chem ; 63(29): 13321-13337, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38987901

RESUMEN

Two new porous three-dimensional cadmium(II) metal-organic frameworks (MOFs) containing thiophene-appended carboxylate acid ligands, formulated as [Cd(L1)(4,4'-Bipy)]n.2n(DMF) (1) and [Cd(L2)(4,4'-Bipy)]n.2n(DMF) (2) [where L1 = 5-{(thiophen-2-ylmethyl)amino}isophthalate, L2 = 5-{(thiophen-3-ylmethyl)amino}isophthalate, 4,4'-Bipy = 4,4'-bipyridine, and DMF = N,N'-dimethylformamide] have been synthesized and structurally characterized. The gas adsorption analysis of the activated MOFs shows that they specifically capture CO2 (uptake amount 4.36 mmol/g under 1 bar at 195 K) over N2 and CH4. Moreover, both MOFs show a gate-opening-closing phenomenon, which features the S-shaped isotherms with impressive hysteretic desorption during the CO2 adsorption-desorption process at 195 K. Ideal adsorbed solution theory (IAST) calculations of these MOFs displayed that the obtained selectivity values for CO2/CH4 (50:50) and CO2/N2 (15:85) are approximately 8.6-23 and 93-565, respectively. Configurational bias Monte Carlo simulation was performed to understand the mechanism behind the better CO2 adsorption by these MOFs. Catalytic activity of the MOFs for the CO2 fixation reactions with different epoxides to form cyclic carbonates were tested. These MOFs demonstrated a significantly high conversion (94-99%) of epichlorohydrin to the corresponding cyclic carbonate within 8 h of reaction time at 1 bar of CO2 pressure, at 70 °C, and they can be reused up to five cycles without losing considerably their activity.

16.
Angew Chem Int Ed Engl ; : e202410823, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39034916

RESUMEN

Improving the slow redox kinetics of sulfur species and shuttling issues of soluble intermediates induced from the multiphase sulfur redox reactions are crucial factors for developing the next-generation high-energy-density lithium-sulfur (Li-S) batteries. In this study, we successfully constructed a novel molecular electrocatalyst through in situ polymerization of bis(3,4-dibromobenzene)-18-crown-6 (BD18C6) with polysulfide anions on the cathode interface. The crown ether (CE)-based polymer acts as a spatial "fence" to precisely control the unique redox characteristics of sulfur species, which could confine sulfur substance within its interior and interact with lithium polysulfides (LiPSs) to optimize the reaction barrier of sulfur species. The "fence" structure and the double-sided Li+ penetrability of the CE molecule may also prevent the CE catalytic sites from being covered by sulfur during cycling. This new fence-type electrocatalyst mitigates the "shuttle effect", enhances the redox activity of sulfur species, and promotes the formation of three-dimensional stacked lithium sulfide (Li2S) simultaneously. It thus enables lithium-sulfur batteries to exhibit superior rate performance and cycle stability, which may also inspire development facing analogous multiphase electrochemical energy-efficient conversion process.

17.
Int J Neural Syst ; 34(10): 2450054, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38984421

RESUMEN

The quality of medical images is crucial for accurately diagnosing and treating various diseases. However, current automated methods for assessing image quality are based on neural networks, which often focus solely on pixel distortion and overlook the significance of complex structures within the images. This study introduces a novel neural network model designed explicitly for automated image quality assessment that addresses pixel and semantic distortion. The model introduces an adaptive ranking mechanism enhanced with contrast sensitivity weighting to refine the detection of minor variances in similar images for pixel distortion assessment. More significantly, the model integrates a structure-aware learning module employing graph neural networks. This module is adept at deciphering the intricate relationships between an image's semantic structure and quality. When evaluated on two ultrasound imaging datasets, the proposed method outshines existing leading models in performance. Additionally, it boasts seamless integration into clinical workflows, enabling real-time image quality assessment, crucial for precise disease diagnosis and treatment.


Asunto(s)
Ecocardiografía , Redes Neurales de la Computación , Humanos , Ecocardiografía/normas , Ecocardiografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Aprendizaje Automático
18.
Acta Pharmacol Sin ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886550

RESUMEN

Urolithin A (UroA), a dietary phytochemical, is produced by gut bacteria from fruits rich in natural polyphenols ellagitannins (ETs). The efficiency of ETs metabolism to UroA in humans depends on gut microbiota. UroA has shown a variety of pharmacological activities. In this study we investigated the effects of UroA on atherosclerotic lesion development and stability. Apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for 3 months to establish atherosclerosis model. Meanwhile the mice were administered UroA (50 mg·kg-1·d-1, i.g.). We showed that UroA administration significantly decreased diet-induced atherosclerotic lesions in brachiocephalic arteries, macrophage content in plaques, expression of endothelial adhesion molecules, intraplaque hemorrhage and size of necrotic core, while increased the expression of smooth muscle actin and the thickness of fibrous cap, implying features of plaque stabilization. The underlying mechanisms were elucidated using TNF-α-stimulated human endothelial cells. Pretreatment with UroA (10, 25, 50 µM) dose-dependently inhibited TNF-α-induced endothelial cell activation and monocyte adhesion. However, the anti-inflammatory effects of UroA in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) were independent of NF-κB p65 pathway. We conducted RNA-sequencing profiling analysis to identify the differential expression of genes (DEGs) associated with vascular function, inflammatory responses, cell adhesion and thrombosis in UroA-pretreated HUVECs. Human disease enrichment analysis revealed that the DEGs were significantly correlated with cardiovascular diseases. We demonstrated that UroA pretreatment mitigated endothelial inflammation by promoting NO production and decreasing YAP/TAZ protein expression and TEAD transcriptional activity in TNF-α-stimulated HUVECs. On the other hand, we found that UroA administration modulated the transcription and cleavage of lipogenic transcription factors SREBP1/2 in the liver to ameliorate cholesterol metabolism in ApoE-/- mice. This study provides an experimental basis for new dietary therapeutic option to prevent atherosclerosis.

19.
J Med Case Rep ; 18(1): 276, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38863038

RESUMEN

BACKGROUND: Currently, there is a scarcity of cases and diagnostic data regarding ectopic adrenocortical adenomas, particularly in relation to their impact on gonadal function and localization diagnostic techniques. We report a typical case of ectopic adrenocortical adenomas and the data of treatment follow-up, and review the literature of 31 available cases of ectopic adrenocortical adenomas. CASE PRESENTATION: A 27-year-old Chinese female patient was admitted to our hospital for hypertension, hyperglycaemia and primary amenorrhea. The patient was functionally diagnosed with ACTH-independent CS and hypogonadotropic hypogonadism. Radiological evaluations, including Computed Tomography (CT) and functional imaging, identified a mass at the left renal hilum. Histological assessments post-surgical excision confirmed the mass to be an ectopic adrenocortical adenoma. A subsequent 3-month follow-up showed no signs of disease recurrence, a swift recovery of the cortisol axis was observed, with a partial recuperation of the gonadal axis. REVIEW: Our literature review shows that the most common ectopic areas of cortisol adenomas are renal hilum and hepatic region. The most positive biomarker is Melan A, and only a few cases have been diagnosed with functional localization. CONCLUSION: Ectopic adrenocortical adenomas may be asymptomatic in the early stage and can impact gonadal function. Physicians who treat hypogonadism must be aware of the need to test cortisol levels and perform functional localization in patients with lumps present.


Asunto(s)
Neoplasias de la Corteza Suprarrenal , Adenoma Corticosuprarrenal , Hipogonadismo , Humanos , Femenino , Adulto , Adenoma Corticosuprarrenal/cirugía , Adenoma Corticosuprarrenal/patología , Adenoma Corticosuprarrenal/complicaciones , Neoplasias de la Corteza Suprarrenal/cirugía , Neoplasias de la Corteza Suprarrenal/patología , Neoplasias de la Corteza Suprarrenal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Hidrocortisona
20.
Materials (Basel) ; 17(11)2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38893942

RESUMEN

Grain boundary (GB) precipitation-induced cracking is a significant issue for S31254 super austenitic stainless steel during hot working. Investigating the deformation behavior based on precipitate morphology and distribution is essential. In this study, continuous smaller and intermittent larger precipitates were obtained through heat treatments at 950 °C and 1050 °C. The microstructure evolution and mechanical properties influenced by precipitates were experimentally investigated using an in situ tensile stage inside a scanning electron microscope (SEM) combined with electron backscatter diffraction (EBSD). The results showed that continuous precipitates at 950 °C had a stronger pinning effect on the GB, making grain rotation difficult and promoting slip deformation in the plastic interval. Continuous precipitates caused severe stress concentration near GB and reduced coordinated deformation ability. Additionally, the crack propagation path changed from transcrystalline to intercrystalline. Furthermore, internal precipitates were a crucial factor affecting the initial crack nucleation position. Interconnected precipitates led to an intergranular fracture tendency and severe deterioration of the material's plasticity, as observed in fracture morphology.

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