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Superhydrophobic coatings have broad applications in a variety of industries. By using a low-surface-energy material and creating nanoscale roughness, a superhydrophobic surface can be produced. To overcome the health and environmental concerns of fluorine-based materials and the limitations of large-scale rough microstructure fabrication, a poly(dimethylsiloxane) (PDMS)-based hierarchical superhydrophobic fabric coating prepared by simple thermal treatment and electrostatic flocking technology was introduced in this study. High-temperature thermal treatment is employed to create PDMS nanoparticle-decorated carbon fibers, which are further vertically implanted onto the surface of cotton fabric via electrostatic flocking technology. The environmentally friendly PDMS nanoparticles were adopted as low-surface-energy materials, and the electrostatic flocking technology was utilized to generate a vertically aligned carbon fiber array coating, mimicking a lotus leaf-like superhydrophobic surface microstructure. Therefore, an ultrahigh water contact angle of 173.9 ± 2.8° and a low sliding angle of 1 ± 0.5° can be obtained by the fabric coating with a PDMS-to-carbon fiber ratio of 20:1. The prepared superhydrophobic fabric also exhibits an excellent self-cleaning property and great durability after 60 cycles of washing. Through commercially available thermal treatment and electrostatic flocking processes, this strategy for fabricating fluorine-free superhydrophobic fabric can be easily scaled up for commercial manufacturing and promotes the design of superhydrophobic coatings for other substrates.
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Cancer stem cells (CSCs) play a substantial role in cancer onset and recurrence. Anomalous iron and lipid metabolism have been documented in CSCs, suggesting that ferroptosis, a recently discovered form of regulated cell death characterised by lipid peroxidation, could potentially exert a significant influence on CSCs. However, the precise role of ferroptosis in gastric cancer stem cells (GCSCs) remains unknown. To address this gap, we screened ferroptosis-related genes in GCSCs using The Cancer Genome Atlas and corroborated our findings through quantitative polymerase chain reaction and western blotting. These results indicate that stearoyl-CoA desaturase (SCD1) is a key player in the regulation of ferroptosis in GCSCs. This study provides evidence that SCD1 positively regulates the transcription of squalene epoxidase (SQLE) by eliminating transcriptional inhibition of P53. This mechanism increases the cholesterol content and the elevated cholesterol regulated by SCD1 inhibits ferroptosis via the mTOR signalling pathway. Furthermore, our in vivo studies showed that SCD1 knockdown or regulation of cholesterol intake affects the stemness of GCSCs and their sensitivity to ferroptosis inducers. Thus, targeting the SCD1/squalene epoxidase/cholesterol signalling axis in conjunction with ferroptosis inducers may represent a promising therapeutic approach for the treatment of gastric cancer based on GCSCs.
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Colesterol , Ferroptosis , Células Madre Neoplásicas , Transducción de Señal , Escualeno-Monooxigenasa , Estearoil-CoA Desaturasa , Neoplasias Gástricas , Serina-Treonina Quinasas TOR , Ferroptosis/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Estearoil-CoA Desaturasa/metabolismo , Estearoil-CoA Desaturasa/genética , Serina-Treonina Quinasas TOR/metabolismo , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Humanos , Escualeno-Monooxigenasa/metabolismo , Escualeno-Monooxigenasa/genética , Colesterol/metabolismo , Línea Celular Tumoral , Animales , Ratones , Regulación Neoplásica de la Expresión GénicaRESUMEN
Gastrointestinal cancer is among the most common cancers worldwide. Immune checkpoint inhibitor-based cancer immunotherapy has become an innovative approach in cancer treatment; however, its efficacy in gastrointestinal cancer is limited by the absence of infiltration of immune cells within the tumor microenvironment. Therefore, it is therefore urgent to develop a novel therapeutic drug to enhance immunotherapy. In this study, we describe a previously unreported potentiating effect of Icariside I (ICA I, GH01), the main bioactive compound isolated from the Epimedium species, on anti-tumor immune responses. Mechanistically, molecular docking and SPR assay result show that ICA I binding with TRPV4. ICA I induced intracellular Ca2+ increasing and mitochondrial DNA release by targeting TRPV4, which triggered cytosolic ox-mitoDNA release. Importantly, these intracellular ox-mitoDNA fragments were taken up by immune cells in the tumor microenvironment, which amplified the immune response. Moreover, our study shows the remarkable efficacy of sequential administration of ICA I and anti-α-PD-1 mAb in advanced tumors and provides a strong scientific rationale for recommending such a combination therapy for clinical trials. ICA I enhanced the anti-tumor effects with PD-1 inhibitors by regulating the TRPV4/Ca2+/Ox-mitoDNA/cGAS/STING axis. We expect that these findings will be translated into clinical therapies, which will benefit more patients with cancer in the near future.
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Flavonoides , Neoplasias Gastrointestinales , Inmunoterapia , Proteínas de la Membrana , Canales Catiónicos TRPV , Humanos , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Animales , Inmunoterapia/métodos , Línea Celular Tumoral , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/inmunología , Neoplasias Gastrointestinales/patología , Flavonoides/farmacología , Microambiente Tumoral/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones , Sinergismo Farmacológico , Inhibidores de Puntos de Control Inmunológico/farmacología , Femenino , Ratones Endogámicos BALB C , ADN Mitocondrial , Simulación del Acoplamiento MolecularRESUMEN
Targeted imaging of cancer lymphatic metastasis remains challenging due to its highly heterogeneous molecular and phenotypic diversity. Herein, triple-targeted protein nanoprobes capable of specifically binding to three targets for imaging cancer lymphatic metastasis, through a data-driven design approach combined with a synthetic biology-based assembly strategy, are introduced. Specifically, to address the diversity of metastatic lymph nodes (LNs), a combination of three targets, including C-X-C motif chemokine receptor 4 (CXCR4), transferrin receptor protein 1 (TfR1), and vascular endothelial growth factor receptor 3 (VEGFR3) is identified, leveraging machine leaning-based bioinformatics analysis and examination of LN tissues from patients with gastric cancer. Using this identified target combination, ferritin nanocage-based nanoprobes capable of specifically binding to all three targets are designed through the self-assembly of genetically engineered ferritin subunits using a synthetic biology approach. Using these nanoprobes, multiplexed imaging of heterogeneous metastatic LNs is successfully achieved in a polyclonal lymphatic metastasis animal model. In 19 freshly resected human gastric specimens, the signal from the triple-targeted nanoprobes significantly differentiates metastatic LNs from benign LNs. This study not only provides an effective nanoprobe for imaging highly heterogeneous lymphatic metastasis but also proposes a potential strategy for guiding the design of targeted nanomedicines for cancer lymphatic metastasis.
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Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown. In vitro, we showed that cell viability and migration was largely reduced in Nogo-B knockout or knockdown cells, while enhanced by Nogo-B overexpression. Consistently, orthotopic tumor and metastasis was reduced in global Nogo knockout mice. Furthermore, we indicated that glucose enhanced cell proliferation was associated to the elevation expression of Nogo-B and nuclear factor κB (NF-κB). While, NF-κB, glucose transporter type 1 (GLUT1) and sterol regulatory element-binding protein 1 (SREBP1) expression was reduced in Nogo-B deficiency cells. In addition, we showed that GLUT1 and SREBP1 was downstream target of NF-κB. Therefore, we demonstrated that Nogo deficiency inhibited PC progression is regulated by the NF-κB/GLUT1 and SREBP1 pathways, and suggested that Nogo-B may be a target for PC therapy.
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The room temperature metal-free cascade electrophilic addition/cyclization/oxidation reactions of (3-phenoxyprop-1-yn-1-yl)benzenes to divergently synthesize various brominated benzopyran derivatives (3-bromo-2H-chromenes, 3-bromo-2H-chromen-2-ols and 3-bromo coumarins) by tuning the amount of Br2 and H2O have been developed. The method exhibited high selectivity, mild reaction conditions, broad substrate scope, high efficiency, and the applicability for derivatization of the brominated products. The importance of the strategies provides a great advantage for selective synthesis of brominated benzopyran derivatives.
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BACKGROUND: This study aimed to assess the radiological and clinical outcomes of treatment using the ankle dislocation method for posterior malleolar malunion. METHOD: Thirty-one patients with posterior malleolar malunion who underwent treatment using the ankle dislocation method from May 2015 to October 2021 were retrospectively analyzed. Key outcome measures were radiographic parameters (articular step-off, tibiofibular clear space, fibular length, tibial lateral surface angle, and ankle osteoarthritis), clinical scores (American Orthopaedic Foot and Ankle Society ankle-hindfoot scale and Visual Analogue Scale), and patient satisfaction rate. RESULT: Preoperative computed tomography revealed that Bartoní cek types 3 and 4 accounted for 64.5 % (n = 20) of total cases. Most posterior malleolar malunions were accompanied by depressed intercalary fragments (61.2 % [n = 19]). At the final follow-up, radiographic parameters and clinical scores showed significant improvements postoperatively (P < 0.05), with a high patient satisfaction rate of 77.4 %. Subgroup analysis revealed that the posterior malleolar fracture morphology significantly affected postoperative pain, particularly in more complex fractures (P < 0.001). CONCLUSION: The ankle dislocation method effectively exposes the distal tibial articular surface and facilitates the anatomical restoration of joint congruity under direct vision. This approach substantially improves the clinical and imaging outcomes in patients with complex posterior malleolar malunion. LEVELS OF EVIDENCE: Level IV, retrospective case series.
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Microwave irradiation (MW) and ionic liquids (ILs) are two of the most promising relatively greener synthetic approaches to preparing value-added chemicals. Herein, a series of 2-acylbenzothiazole derivatives were synthesized for the first time from commercially available α-bromoacetophenones and disulfane-diyl-dianilines through the cooperation of ionic liquids and microwave irradiation under metal- and extra-additives-free conditions. A plausible mechanism involving the successive IL-induced enolation has been proposed.
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Objective: To compare the effectiveness of talonavicular-cuneiform joint fusion with iliac bone grafting and without bone grafting in the treatment of Müller-Weiss diseases (MWD). Methods: The clinical data of 44 patients (44 feet) with MWD who received talonavicular-cuneiform joint fusion between January 2017 and November 2022 and met the selection criteria was retrospectively analyzed. Among them, 25 patients were treated with structural iliac bone grafting (bone grafting group) and 19 patients without bone grafting (non-bone grafting group). There was no significant difference ( P>0.05) in age, gender composition, body mass index, disease duration, affected side, Maceira stage, and preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) score, anteroposterior/lateral Meary angle, and Pitch angle between the two groups. Operation time, operation cost, and postoperative complications were recorded in the two groups. AOFAS and VAS scores were used to evaluate the function and pain degree of the affected foot. Meary angle and Pitch angle were measured on the X-ray film, and the joint fusion was observed after operation. The difference (change value) of the above indexes before and after operation was calculated for comparison between groups to evaluate the difference in effectiveness. Results: The operation was successfully completed in both groups, and the incisions in the two groups healed by first intention. The operation time and cost in the bone grafting group were significantly more than those in the non-bone grafting group ( P<0.05). All patients were followed up. The median follow-up time was 41.0 months (range, 16-77 months) in the non-bone grafting group and 40.0 months (range, 16-80 months) in the bone grafting group. There was skin numbness of the medial dorsalis of the foot in 1 case, internal fixation stimulation in 2 cases, and pain at the iliac bone harvesting area in 1 case of the bone grafting group. There was skin numbness of the medial dorsalis of the foot in 1 case and muscle atrophy of the lower limb in 1 case of the non-bone grafting group. There was no significant difference in the incidence of complications between the two groups ( P>0.05). At last follow-up, the AOFAS scores of the two groups significantly improved when compared with those before operation, while the VAS scores significantly decreased, the anteroposterior/lateral Meary angle and Pitch angle significantly improved, and the differences were significant ( P<0.05). There was no significant difference in the change values of outcome indicators between the two groups ( P>0.05). There was no delayed bone union or bone nonunion in both groups, and joint fusion was achieved at last follow-up. Conclusion: In the treatment of MWD, there is no significant difference in effectiveness and imaging improvement of talonavicular-cuneiform joint fusion combined with or without bone grafting. However, non-bone grafting can shorten the operation time, reduce the cost, and may avoid the complications of bone donor site.
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Enfermedades Óseas , Enfermedades del Pie , Humanos , Trasplante Óseo , Enfermedades del Pie/cirugía , Hipoestesia , Dolor , Estudios Retrospectivos , Resultado del Tratamiento , Masculino , FemeninoRESUMEN
BACKGROUND: Midfoot arthrodesis is regarded as the main surgical approach for treating Müller-Weiss disease (MWD). This study aimed to investigate the incidence of postoperative pain during MWD treatment through midfoot reduction or malreduction during arthrodesis and to explore the factors influencing postoperative pain in patients with MWD. METHODS: A total of 67 patients with MWD were recruited and divided into two groups according to whether midfoot alignment was reduced: reduction group (n = 38) and malreduction group (n = 29). Demographic characteristics before the operation and at the last follow-up, as well as clinical and radiographic parameters, were compared between the two groups. Clinical parameters included the American Orthopaedic Foot & Ankle Society score and visual analog scale score, whereas radiographic parameters included the calcaneal pitch angle, lateral Meary's angle, talometatarsal-1 angle dorsoplantar (TMT1dp), talocalcaneal angle dorsoplantar (Kite angle), talonavicular coverage angle, and medial navicular pole extrusion. Postoperative complications and incidence of midfoot pain were evaluated at the last follow-up visit. RESULTS: The reduction group exhibited better clinical and radiological parameters, including the TMT1dp and medial navicular pole extrusion, than the malreduction group at the last follow-up (all P < .05). However, the calcaneal pitch angle, lateral Meary's angle, Kite angle, and talonavicular coverage angle did not significantly differ between the two groups (all P > .05). The overall incidence of midfoot pain was 26.4%. The reduction group showed a lower incidence of medial pain than the malreduction group (15.7% vs. 40.0%, P < .05). Regression analysis revealed that midfoot abduction, represented by the TMT1dp, was a critical factor for midfoot arthrodesis failure and that medial navicular pole extrusion was not correlated with postoperative midfoot pain. CONCLUSION: Midfoot reduction arthrodesis yields better clinical outcomes than malreduction arthrodesis. The TMT1dp, representing midfoot abduction, is a key factor for midfoot arthrodesis failure. The extruded medial navicular bone may not affect postoperative medial midfoot pain. LEVEL OF EVIDENCE: Level III, retrospective comparative study.
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Enfermedades Óseas , Enfermedades del Pie , Huesos Tarsianos , Humanos , Estudios Retrospectivos , Huesos Tarsianos/cirugía , Enfermedades del Pie/cirugía , Artrodesis , Dolor Postoperatorio , Resultado del TratamientoRESUMEN
The La(OTf)3-catalyzed [3+2] cycloaddition reactions for the synthesis of benzo[d]oxazoles/benzofurans via quinones and 1,2-di-tert-butyl-3-(cyanimino)diaziridine (1,3-di-tert-butyl-2-cyanoguanidine)/vinyl azides have been explored. A series of 5-hydroxybenzofuran-4-carboxylic acid derivatives and 5-hydroxybenzo[d]oxazole-4-carboxylic acid derivatives were conveniently obtained with high yields and good stereoselectivities, which could be used for further transformations to valuable compounds.
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The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A-/-mice resulted in fewer tumors and more IFN-γ+ CD8+ T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8+ T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.