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Ultrasonic transducers with large output power have attracted extensive attentions due to their widespread applications in sonar, acoustic levitation, ultrasonic focusing, and so forth. However, the traditional transducer has almost no heat-dissipation capability itself, strictly relying on the assistant coolant system. Introducing high-performance heat-dissipation component is thus highly necessary. Herein, an embedded porcelain radiator component was designed by combining the excellent thermal conductivity of vertically oriented graphene (VG) with the outstanding heat-dissipation characteristics of thermosensitive ceramics, and a new-type transducer with an embedded VG/ceramic-hybrid radiator was constructed to show high heat-dissipation efficiency (up to â¼5 °C/min). Remarkably, prominent heat-dissipation effectiveness (temperature decline of â¼12 °C), enhanced amplitude and vibration uniformity were also achieved for the new-type transducer along with stabilized operating states. This research should pave ways for extending the applications of VG/ceramic hybrids to heat-dissipation scenarios and provide newfangled thoughts for the performance upgrade of multitudinous high-power devices.
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Direct growth of graphene on glass can bring an innovative revolution by coupling the complementary properties of traditional glass and modern graphene (such as transparency and conductivity), offering brand new daily-life related applications. However, preparation of high-quality graphene on nonmetallic glass is still challenging. Herein, the direct route of low sheet resistance graphene on glass is reported by using in situ-introduced water as a mild etchant and methane as a carbon precursor via chemical vapor deposition. The derived graphene features with large domain sizes and few amorphous carbon impurities. Intriguingly, the sheet resistance of graphene on glass is dramatically lowered down to ≈1170 Ω sq-1 at the optical transmittance ≈93%, ≈20% of that derived without the water etchant. Based on the highly conductive and optical transparent graphene on glass, a see-through thermochromic display is thus fabricated with transparent graphene glass as a heater. This work can motivate further investigations of the direct synthesis of high-quality graphene on functional glass and its versatile applications in transparent electronic devices or displays.
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Acute lung injury (ALI) is a life-threatening disease characterized by severe lung inflammation and intestinal microbiota disorder. The GPR18 receptor has been demonstrated to be a potential therapeutic target against ALI. Extracting Naringin dihydrochalcone (NDC) from the life-sustaining orange peel is known for its diverse anti-inflammatory properties, yet the specific action target remains uncertain. In the present study, we identified NDC as a potential agonist of the GPR18 receptor using virtual screening and investigated the pharmacological effects of NDC on sepsis-induced acute lung injury in rats and explored underlying mechanisms. In in vivo experiments, CLP-induced ALI model was established by cecum puncture and treated with NDC gavage one hour prior to drug administration, lung histopathology and inflammatory cytokines were evaluated, and feces were subjected to 16s rRNA sequencing and untargeted metabolomics analysis. In in vitro experiments, the anti-inflammatory properties were exerted by evaluating NDC targeting the GPR18 receptor to inhibit lipopolysaccharide (LPS)-induced secretion of TNF-α, IL-6, IL-1ß and activation of inflammatory signaling pathways in MH-S cells. Our findings showed that NDC significantly ameliorated lung damage and pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß) in both cells and lung tissues via inhibiting the activation of STAT3, NF-κB, and NLRP3 inflammatory signaling pathways through GRP18 receptor activation. In addition, NDC can also partly reverse the imbalance of gut microbiota composition caused by CLP via increasing the proportion of Firmicutes/Bacteroidetes and Lactobacillus and decreasing the relative abundance of Proteobacteria. Meanwhile, the fecal metabolites in the NDC treatment group also significantly were changed, including decreased secretion of Phenylalanin, Glycine, and bile secretion, and increased secretion of Lysine. In conclusion, these findings suggest that NDC can alleviate sepsis-induced ALI via improving gut microbial homeostasis and metabolism and mitigate inflammation via activating GPR18 receptor. In conclusion, the results indicate that NDC, derived from the typical orange peel of food, could significantly contribute to development by enhancing intestinal microbial balance and metabolic processes, and reducing inflammation by activating the GPR18 receptor, thus mitigating sepsis-induced ALI and expanding the range of functional foods.
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Lesão Pulmonar Aguda , Anti-Inflamatórios , Chalconas , Citocinas , Microbioma Gastrointestinal , Receptores Acoplados a Proteínas G , Sepse , Animais , Receptores Acoplados a Proteínas G/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/microbiologia , Lesão Pulmonar Aguda/metabolismo , Masculino , Sepse/tratamento farmacológico , Sepse/complicações , Citocinas/metabolismo , Ratos , Chalconas/farmacologia , Chalconas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Ratos Sprague-Dawley , Homeostase/efeitos dos fármacos , Linhagem Celular , Pulmão/patologia , Pulmão/efeitos dos fármacos , Modelos Animais de Doenças , Lipopolissacarídeos , Humanos , FlavanonasRESUMO
OBJECTIVE: To analyze the relationship between microRNA (miR)-21, miR-191 and clinical stage of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: 100 patients with DLBCL treated in Shanxi Fenyang Hospital from January 2019 to January 2021 were selected as the research subjects. All patients was divided into stage I, stage II, stage III and stage IV according to Ann-Arbor (Cotswolds) staging system at admission. The baseline data of patients at different clinical stages were counted and compared in detail. The relationship between the levels of miR-21 and miR-191 and the clinical stage of DLBCL patients was mainly analyzed. RESULTS: Among the 100 patients with DLBCL, there were 15 patients at stage I, 25 patients at stage II, 37 patients at stage III and 23 patients at stage IV. The levels of miR-21 and miR-191 in patients at stage â , â ¡, â ¢ and â £ were increased gradually, which showed statistically significant differences (P<0.05). According to Kendall's tau-b correlation analysis, it was found that the levels of miR-21 and miR-191 were positively correlated with the clinical stage of DLBCL patients (r=0.566, 0.636). Multiple logistic regression analysis showed that the overexpression of serum miR-21 and miR-191 was a risk factor for high clinical stage in patients with DLBCL (OR>1, P<0.05). Bivariate Pearson correlation analysis showed that there was a positive correlation between miR-21 and miR-191 levels in patients with DLBCL (r=0.339). CONCLUSION: The overexpression of miR-21 and miR-191 in patients with DLBCL is related to high clinical stage.
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Linfoma Difuso de Grandes Células B , MicroRNAs , Humanos , Prognóstico , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genéticaRESUMO
OBJECTIVE: To investigate the effect of Liangxue Huoxue decoction on intestinal flora, intestinal barrier and NOD-like receptor protein 3 (NLRP3)/caspase-1/gasdermin D (GSDMD) pyroptosis signaling pathway in mice model of sepsis-induced acute kidney injury (AKI). METHODS: The model of AKI was established by cecal ligation and perforation (CLP). Thirty male C57BL/6 mice were randomly divided into sham operation group (Sham group), sepsis group (CLP group) and sepsis+Liangxue Huoxue decoction (CLP+LXHX group), with 10 mice in each group. Mice in Sham group only underwent laparotomy. Two hours before model establishment, mice in CLP+LXHX group were treated with Liangxue Huoxue decoction (6 g/kg) by gavage; mice in Sham group and CLP group were given equal volume of normal saline by gavages. After 24 hours of modeling, all mice were sacrificed under anesthesia, and the colon and kidney tissues and fresh feces in the colon were taken. The pathological changes of kidney and colon were observed by hematoxylin-eosin (HE) staining under light microscope. Real-time polymerase chain reaction (RT-PCR) was used to detect inflammatory factors (interleukins, IL-1ß and IL-18) in renal tissue. The expressions of NLRP3, caspase-1 and GSDMD were detected by Western blotting. The changes of intestinal flora in mice were detected by 16S rDNA high-throughput sequencing. RESULTS: Compared with the Sham group, the inflammatory cell infiltration of the kidney tissue was increased and the kidney became vacuolated in CLP group, the mRNA expressions of IL-1ß, IL-18, and the protein expressions of NLRP3, caspase-1 and GSDMD were significantly increased in CLP group, the species richness of intestinal microflora decreased significantly, the relative abundance of Enterococcus and Escherichia-Shigella increased significantly, and the relative abundance of Ileibacterium, Alloprevotella, Lachnospiraceae, Klebsiella and Parasutterella increased significantly in CLP group. Compared with CLP group, Liangxue Huoxue decoction can significantly reduce the pathological changes of kidney and colon tissue, reduce the pathological score (1.75±0.43 vs. 3.50±0.50 for kidney tissue, 1.25±0.43 vs. 4.50±0.50 for colon tissue, both P < 0.05), improve the composition of intestinal flora, reduce the relative abundance of Enterococcus and Escherichia-Shigella, and significantly increase the relative abundance of Lactobacillus and Akkermansia. In addition, Liangxue Huoxue decoction can significantly reduce mRNA expressions of IL-1ß and IL-18 in kidney tissue [IL-1ß mRNA (2-ΔΔCt): 1.59±0.05 vs. 4.61±0.88, IL-18 mRNA (2-ΔΔCt): 1.69±0.17 vs. 2.86±0.63, both P < 0.05] and the protein expressions of NLRP3, caspase-1 and GSDMD (NLRP3/GAPDH: 0.71±0.04 vs. 0.89±0.01, caspase-1/GAPDH: 1.04±0.04 vs. 1.48±0.04, GSDMD/GAPDH: 0.90±0.01 vs. 1.41±0.02, all P < 0.05). CONCLUSIONS: Liangxue Huoxue decoction has obvious protective effect on AKI induced by sepsis. It can improve intestinal barrier by regulating intestinal flora, thereby inhibiting the activation of NLRP3/caspase-1/GSDMD signaling pathway in kidney tissue and reducing the expression of proptosis-related inflammatory factors.
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Injúria Renal Aguda , Microbioma Gastrointestinal , Sepse , Camundongos , Masculino , Animais , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Caspase 1/metabolismo , Camundongos Endogâmicos C57BL , Injúria Renal Aguda/tratamento farmacológico , Transdução de Sinais , RNA Mensageiro , Sepse/complicações , Sepse/metabolismoRESUMO
OBJECTIVE: To analyze the composition and metabolites of gut microbiota in septic rats by fecal 16s rRNA sequencing and untargeted metabolomics, and to preliminarily explore the effect and potential mechanism of gut microbiota and its metabolites on inflammatory response and multiple organ damage in sepsis. METHODS: Ten males healthy male Wistar rats were randomly divided into a sham operated group (Sham group) and sepsis model group (CLP group) using a random number table method, with 5 rats in each group. A rat sepsis model was established by cecal ligation and perforation (CLP) method. The animals were sacrificed 24 hours after modeling, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in peripheral blood were detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung and kidney tissues, and the pathological scores were evaluated. Fecal samples were collected, and 16s rRNA high-throughput sequencing and non-targeted metabolomics were used to screen microbiota, metabolites and potential signal pathways that may play an important role in disease outcomes. Spearman correlation analysis was conducted to jointly analyze the gut microbiota and non-targeted metabolism. RESULTS: Compared with the Sham group, the degree of pathological damage to lung and kidney tissues in the CLP group was significantly increased (lung tissue score: 3.60±0.80 vs. 0.00±0.00, kidney tissue score: 2.40±0.80 vs. 0.00±0.00, both P < 0.01), the level of IL-6 and TNF-α in peripheral blood significantly increased [TNF-α (ng/L): 248.12±55.98 vs. 143.28±36.57, IL-6 (ng/L): 260.26±39.47 vs. 116.01±26.43, both P < 0.05], the species diversity of intestinal flora of rats in the CLP group was significantly reduced, the relative abundance of Morganella, Bacteroides and Escherichia-Shigella were significantly increased, and the relative abundance of Lachnospiraceae NK4A136, Ruminococcus, Romboutsia and Roseburia were significantly reduced. In addition, the biosynthesis and bile secretion of phenylalanine, tyrosine, and tryptophan in the gut microbiota of the CLP group were significantly increased, while the biosynthesis of secondary bile acids was significantly reduced. There was a significant correlation between differential metabolites and differential microbiota. CONCLUSIONS: Sepsis can cause significant changes in the characteristics of gut microbiota and fecal metabolites in rats, which provides a basis for translational research to seek new targets for the treatment of sepsis.
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Microbioma Gastrointestinal , Sepse , Ratos , Masculino , Animais , Fator de Necrose Tumoral alfa , RNA Ribossômico 16S , Interleucina-6 , Ratos WistarRESUMO
The primary objectives of this research were to investigate the protective effects of liriodendrin against IgG immune complex (IgG-IC)-induced acute lung injury (ALI) and to elucidate the underlying mechanisms. This study employed a mouse and cell model of IgG-IC-induced acute lung injury. Lung tissue was stained with hematoxylin-eosin to observe pathological alterations and arterial blood gas analysis was tested. Inflammatory cytokines, including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-alpha (TNF-α), were measured using ELISA. The mRNA expression of inflammatory cytokines was assessed via RT-qPCR. Molecular docking and enrichment analysis were combined to identify the most potential signaling pathways modulated by liriodendrin, which were then verified using western blot analysis in IgG-IC-induced ALI models. We identified 253 shared targets between liriodendrin and IgG-IC-induced acute lung injury from the database. Through network pharmacology, enrichment analysis, and molecular docking, SRC was determined to be the most closely associated target of liriodendrin in IgG-IC-induced ALI. Pretreatment with liriodendrin notably reduced the increased cytokine secretion of IL-1ß, IL-6, and TNF-α. Histopathological analysis of lung tissue demonstrated a protective effect of liriodendrin on IgG-IC-induced acute lung injury in mice. Arterial blood gas analysis showed liriodendrin ameliorated acidosis and hypoxemia efficiently. Further studies revealed that liriodendrin pretreatment substantially attenuated the elevated phosphorylation levels of SRC's downstream components (JNK, P38, and STAT3), suggesting that liriodendrin may protect against IgG-IC-induced ALI via the SRC/STAT3/MAPK pathway. Our findings indicate that liriodendrin protects against IgG-IC-induced acute lung injury by inhibiting the SRC/STAT3/MAPK signaling pathway, suggesting that liriodendrin may serve as a potential treatment for acute lung injury caused by IgG-IC.
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Lesão Pulmonar Aguda , Complexo Antígeno-Anticorpo , Camundongos , Animais , Complexo Antígeno-Anticorpo/farmacologia , Complexo Antígeno-Anticorpo/uso terapêutico , Interleucina-6 , Fator de Necrose Tumoral alfa/farmacologia , Simulação de Acoplamento Molecular , Farmacologia em Rede , Transdução de Sinais , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/etiologia , Pulmão/patologia , Citocinas/metabolismo , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Lipopolissacarídeos/farmacologiaRESUMO
Acute lung injury (ALI) is a life-threatening condition characterized by severe lung inflammation and tissue damage. In this study, we investigate the potential therapeutic efficacy of (+)-Syringaresinol (SYG), a natural compound known for its antioxidant and anti-inflammatory properties, in alleviating ALI induced by IgG immune complexes (IgG-IC). Using MH-S cells as a model, we explore SYG's ability to target peroxisome proliferator-activated receptor gamma (PPARγ) and its anti-inflammatory properties. Our comprehensive investigation aims to elucidate the specific molecular mechanisms underlying SYG's effects against pyroptosis, as revealed through transcriptomic analysis. Validation in C57BL/6 mice provides in vivo support. Our findings indicate that SYG effectively mitigates IgG-IC-induced lung damage, as evidenced by a significant reduction in lung inflammation and tissue injury. SYG treatment notably decreases pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1ß) in both lung tissue and cells. Molecular docking analysis reveals SYG's robust binding to PPARγ, leading to the inhibition of IgG-IC-induced inflammatory signaling pathways. Additionally, transcriptomic analysis unveils SYG's potential in suppressing macrophage pyroptosis, potentially through the downregulation of key inflammatory mediators (NLRP3, GSDMD, Caspase-1). In summary, our study presents compelling evidence supporting SYG as an effective therapeutic agent for ALI. SYG's activation of PPARγ contributes to the suppression of NF-κB and C/EBPs expression, thereby mitigating inflammation. Moreover, SYG demonstrates the ability to inhibit macrophage pyroptosis by targeting the NLRP3/GSDMD/caspase-1 axis.
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Lesão Pulmonar Aguda , Pneumonia , Camundongos , Animais , Camundongos Endogâmicos C57BL , Piroptose , PPAR gama , Complexo Antígeno-Anticorpo , Simulação de Acoplamento Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Lesão Pulmonar Aguda/tratamento farmacológico , Caspase 1 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Imunoglobulina G , NF-kappa B , LipopolissacarídeosRESUMO
Induction of cancer cell death is an established treatment strategy, but chemotherapy drug-mediated apoptosis can be evaded by many tumors. Pyroptosis is a type of inflammatory programmed cell death (PCD) that is important for organism immunity. Tubeimoside-I (TBMS1) is a plant-derived component that exhibits antitumor activity. However, it is unclear how TBMS1 induces pyroptosis to inhibit colorectal cancer (CRC). In this study, we demonstrated that TBMS1 is able to induce pyroptosis in murine CRC cells and releases pro-inflammatory cytokines. Mechanistically, we found that TBMS1 inhibits CRC cell proliferation and migration and induces pyroptosis by activating caspase-3 and cleaving gasdermin E (GSDME) through the inhibition of PKM2. In the animal experiments, TBMS1 attenuated the weight of solid tumors, increased the proportion of CD8+ cytotoxic T cells, and reduced the content of M2-type macrophages in the spleen of tumor-bearing mice. Furthermore, TBMS1 inhibited M2-type polarization by blocking STAT6 pathway activation in RAW 264.7 cells. To sum up, our findings suggest that TBMS1 triggers pyroptosis in CRC by acting on the PKM2/caspase-3/GSDME signaling pathway. Additionally, it modulates the antitumor immune response in CRC murine models. This study provides a promising basis for the potential use of TBMS1 in treating CRC.
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An all-optical non-resonant photoacoustic spectroscopy system for multicomponent gas detection based on a silicon cantilever optical microphone (SCOM) and an aseismic photoacoustic cell is proposed and demonstrated. The SCOM has a high sensitivity of over 96.25 rad/Pa with sensitivity fluctuation less than ± 1.56 dB between 5 Hz and 250 Hz. Besides, the minimal detectable pressure (MDP) of the sensor is 0.55 µPa·Hz-1/2 at 200 Hz, which indicates that the fabricated sensor has high sensitivity and low noise level. Six different gases of CO2, CO, CH4, C2H6, C2H4, C2H2 are detected at the frequency of 10 Hz, whose detection limits (3σ) are 62.66 ppb, 929.11 ppb, 1494.97 ppb, 212.94 ppb, 1153.36 ppb and 417.61 ppb, respectively. The system achieves high sensitivity and low detection limits for trace gas detection. In addition, the system exhibits seismic performance with suppressing vibration noise by 4.5 times, and achieves long-term stable operation. The proposed non-resonant all-optical PAS multi-component gas detection system exhibits the advantages of anti-vibration performance, low gas consumption and long term stability, which provides a solution for working in complex environments with inherently safe.
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Coronavirus is one of the RNA viruses with the largest genome; It is a group of viruses known to infect humans very little until the end of the 20th century, generally causing infection in animals (bird, cat, pig, mouse, horse, bat). It is the causative agent of 15-30% of seasonal lower and upper respiratory tract infections, and may rarely cause gastrointestinal and nervous system infections. We have obtained results for the collagenase and elastase enzymes were at the micromolar level. We obtained IC50 results for the collagenase enzyme for 6-hydroxy-4-methylcoumarin 257.22 ± 34.07 µM and for 2,5-dihydroxyacetophenone 74.46 ± 8.61 µM. 6-Hydroxy-4-methylcoumarin and 2,5-dihydroxyacetophenone were considered good inhibitors for elastase enzyme. Additionally, these compounds significantly decreased human pancreatic cancer cell viability from low doses. In addition, 100 µM dose of all compounds caused significant reductions in human pancreatic cancer cell viability. IC50 results (IC50: 10-50 µM) were better than control. In the otherwords, the docking results suggest that both compounds tend to have lower efficacy on the main protease targets of SARS-CoV-2 than standard compounds, (NL-1 and NL-2). The reason for this is that the standard compounds interact strongly and more frequently with the target proteins, and the surface areas they cover on the active surface are much larger than the small ligand molecules studied.
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Tratamento Farmacológico da COVID-19 , Neoplasias Pancreáticas , Acetofenonas , Animais , Colagenases , Flavonoides , Cavalos , Camundongos , Elastase Pancreática , Neoplasias Pancreáticas/tratamento farmacológico , SARS-CoV-2 , SuínosRESUMO
The bipolar plate (BP) serves as one of the crucial components in proton exchange membrane fuel cells (PEMFCs). Among BP materials, metallic BPs are widely employed due to their outstanding comprehensive properties. However, the interfacial contact resistance (ICR) between BP and gas diffusion layer together with corrosion of metallic BP under acidic operating conditions degrades the performance and stability of PEMFCs. Herein, an approach is proposed for the surface reinforcement of titanium (Ti) alloy BPs, relying on a directly grown vertical graphene (VG) coating via the plasma-enhanced chemical vapor deposition method. Compared with bare Ti alloy, the corrosion rate of VG-coated Ti alloy reduces by 1-2 orders of magnitude in the simulated PEMFC operating environments and ICR decreases by ≈100 times, while its thermal conductivity improves by ≈20% and water contact angle increases by 68.1°. The results can be interpreted that the unique structure of VG enables excellent electrical and thermal conduction in PEMFCs, and the highly hydrophobic VG coating suppresses the penetration of corrosive liquid as well as contributing to water management. This study opens a new opportunity to reinforce metallic surfaces by the robust and versatile VG coating for high-performance electrodes used in energy and catalyst applications.
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Background: Advanced gastric cancer is the fifth leading cause of cancer-related deaths. Patients with metastatic advanced gastric cancer commonly develop a gastric outlet obstruction that considerably worsens their quality of life. Surgical interventions such as gastrojejunostomy and palliative gastrectomy are commonly administered to alleviate this obstruction. However, whether one intervention is better than another at improving morbidity- and mortality-related outcomes is unclear. Thus, in this meta-analysis, we compare outcomes of palliative gastrectomy and gastrojejunostomy (overall hospital stay length, time to oral intake, survival, and complication rates) in patients with metastatic advanced gastric cancer to identify the best procedure. Objective: To compare morbidity and mortality outcomes of palliative gastrectomy and gastrojejunostomy in patients with metastatic advanced gastric cancer. Methods: We followed the PRISMA guidelines to systematically search Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE for relevant studies. We conducted a random-effects meta-analysis to find differential outcomes between palliative gastrectomy and gastrojejunostomy among variables such as time to oral intake, overall hospital stay length, complication rates, and survival in patients with metastatic advanced gastric cancer. Results: From 963 studies, we found 7 eligible studies with 642 patients (70.3 ± 4.7 years) who had undergone palliative gastrectomy or gastrojejunostomy. Our meta-analysis revealed an insignificant (p > 0.05) differences in terms of overall survival duration (Hedge's g, 1.22), complication risks (odds ratio, 1.35), and time to oral intake (g, 0.62) and hospital stay length (g, 0.12) between patients undergoing gastrojejunostomy and palliative gastrectomy. Conclusion: In this present study we observed no statistically significant differences in terms of morbidity and mortality outcomes after palliative gastrectomy and gastrojejunostomy in patients with metastatic advanced gastric cancer. Therefore, no conclusions can be drawn for the variables evaluated. This study provides a preliminary overview of the risks associated with gastrojejunostomy and palliative gastrectomy to help gastroenterologists manage patients with metastatic advanced-stage gastric cancer.
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PURPOSE: This study was designed to investigate the correlation between the expression of human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), and clinicopathological parameters and serum tumor markers in a total of 522 resection samples materials from colorectal cancer (CRC) patients. These data were also used to determine the links between HER2 and MMR expression and prognosis. METHODS: We conducted a retrospective analysis of the clinical data from 522 CRC patients. Immunohistochemistry (IHC) was used to detect HER2 overexpression and MMR deficiency (dMMR) in tumor specimens which were then correlated with various clinicopathological parameters. Prognostic value for HER2 and MMR expression was then evaluated using the data from 105 CRC patients. RESULTS: HER2 overexpression was identified in 35.63% of the samples evaluated in this study, while the total dMMR rate was 12.64%. Expression of HER2 and several, MMR proteins (MLH1, MSH-2, MSH-6, and PMS-2) were then correlated with tumor location. HER2 overexpression is significantly associated with increased depth of tumor invasion, lymph node metastasis, distant metastases, pTNM staging, vascular invasion, nerve infiltration, and serum carcinoembryonic antigen (CEA) levels. HER2 overexpression and dMMR increased with advancing clinical stage. In addition, deficiencies in MLH1 and PMS2 correlated with HER2 overexpression. Finally, the prognostic evaluations revealed that HER2 overexpression was closely associated with poorer clinical outcomes. CONCLUSION: HER2 overexpression is significantly correlated with multiple clinicopathological parameters resulting in a poorer prognosis. Moreover, the prognosis of patients with HER2 overexpression was worse, confirming its significance during disease assessment. In clinical practice, clinicians should pay close attention to the HER2 profile of patients as they may require more extensive clinical intervention. In addition, deficiencies in MLH1, MSH-2, MSH-6, or PMS-2 correlate with tumor location, and MLH1 and PMS2 expression is associated with lymph node metastasis and pTNM stage, suggesting that these may be additional markers in CRC risk assessments.
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Objective: To investigate the synergistic effects of magnolol and gefitinib on non-small cell lung cancer A549 cells. Methods: A549 cells were treated with Magnolol (6.25ï½500 µmol/L) or gefitinib (6.25ï½500 µmol/L) for 24 h, respectively, and the cell viability was detected by cell counting Kit-8 (CCK-8) experiment (n=3). Magnolol 100 µmol/L and gefitinib 5 µmol/L were selected in the following experiments (n=3, 24 h). Control group, magnolol group, gefitinib group and magnolol+gefitinib group were set up for factorial analysis. Colony formation experiment was applied to detect the cell proliferation. Western blot was used to detect protein expressions. Flow cytometry was applied to test cell apoptosis and sorting CD44+ and CD133+ cells. Results: Compared with the control group, the colony formation rate of Magnolol or Gefitinib groups was decreased significantly (Pï¼0.05); the apoptosis rate was increased significantly (Pï¼0.05); the number of CD44+ and CD133+ cells was reduced significantly (Pï¼0.05); the expressions of Ki67, PCNA, and stem cell marker proteins SOX2 and OCT4 were down-regulated (Pï¼0.05); and the ratio of Bax/Bcl-2 was increased significantly (Pï¼0.05). Compared with the Magnolol group or Gefitinib group, the Magnolol+Gefitinib group further promoted the above changes (Pï¼0.05), and the apoptosis rate, the ratio of Bax/Bcl-2, SOX2 and OCT4 all showed interactions between magnolol and gefitinib (Pï¼0.05). Conclusion: Magnolol and gefitinib promote the apoptosis of A549 cells and inhibit its stem cell-like properties, and the effect of the two combined is better than separated administration. Magnolol and gefitinib have interactive effects on A549 cells.
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Compostos de Bifenilo/farmacologia , Carcinoma Pulmonar de Células não Pequenas , Gefitinibe , Lignanas/farmacologia , Neoplasias Pulmonares , Células A549 , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Gefitinibe/farmacologia , Humanos , Neoplasias Pulmonares/patologiaRESUMO
Improving the adhesion property of graphene directly grown on an insulating substrate is essential for promoting the reliability and durability of the related applications. However, effective approaches have rarely been reported, especially for vertically oriented graphene (VG) films grown on insulating templates. To tackle this, we have developed a facile synthetic strategy by introducing an ultrathin (10 nm-thick) titanium (Ti) film on a quartz glass substrate as the adhesion layer, for plasma-enhanced chemical vapor deposition (PECVD) growth of VG films. This synthetic process induces the formation of Ti, oxygen (O), carbon (C)-containing adhesion layer (Ti (O, C)), offering improved interfacial adhesion due to the formation of chemical bonds among Ti and C atoms. Dramatically improved surface and interface stabilities have been achieved, with regard to its counterpart without a Ti adhesion layer. Moreover, we have also realized precise controls of the transparent/conductive property, surface roughness, and hydrophobicity, etc., by varying the VG film growth time. We have also demonstrated the very intriguing application potentials of the hybrids in light-dimming related fields, that is, electro-heating defogging lenses and neutral density filters toward medical endoscope defogging and camera photography.
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BACKGROUND: In recent years, targeted therapy and immunotherapy have become important treatment strategies for patients with non-small cell lung cancer (NSCLC). However, the clinical evidence for successful off-label use of targeted drugs for patients with NSCLC following progression on multiple lines of treatment is still lacking. CASE SUMMARY: We describe a 62-year-old male patient with a right lung adenocarcinoma who harbored an EGFR exon 19 deletion mutation. He received gefitinib combined with six cycles of vinorelbine, cisplatin, and recombinant human endostatin as the first-line therapy. Then gefitinib was administered in combination with recombinant human endostatin as maintenance therapy, resulting in a progression-free survival (PFS) of 14 mo. Chemoradiotherapy was added following progression (enlarged brain metastases) on maintenance treatment. Unfortunately, the brain lesions were highly refractory and progressed again after 15 mo, at which time next-generation sequencing (NGS) of 1021 cancer-related genes was performed using peripheral blood to identify potential actionable mutations. NGS revealed that the patient harbored a BRCA2 germline mutation, the EGFR exon 19 deletion mutation disappeared, and no additional targetable genetic variant was detected. Therefore, the patient received olaparib combined with gefitinib and recombinant human endostatin, with a rapid and long-lasting clinical response (PFS = 13.5 mo). CONCLUSION: This is a rare case of lung adenocarcinoma in a patient with a BRCA2 germline mutation who had long-term benefit from olaparib combination treatment, suggesting that NGS-based genetic testing may render the possibility of long-term survival in NSCLC patients after disease progression.
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Direct growth of vertically oriented graphene (VG) nanowalls on soda-lime glass has practical significance in extending the application of graphene to daily-life-related areas, such as gas sensors and conductive electrodes, via combining their complementary properties and applications. However, VG films derived by low-temperature deposition (e.g., on glass) usually present relatively low conductivity and optical transparency. To tackle this issue, an ethanol-precursor-based, radio-frequency plasma-enhanced chemical vapor deposition (rf-PECVD) route for the synthesis of VG nanowalls is developed in this research, at around the softening temperature of soda-lime glass (â¼600 °C) templates. The average sheet resistance, i.e., â¼2.4 kΩ·sq-1 (at transmittance â¼81.6%), is only one-half of that achieved by a traditional methane-precursor-based PECVD route. Based on the highly conductive and optically transparent VG/glass, as well as its scalable size up to 25 in. scale, high-performance reversible thermochromic devices were successfully constructed using VG/glass as transparent heaters. Hereby, this work should propel the scalable synthesis and applications of highly conductive VG films on glass in next-generation transparent electronics and switchable windows.
RESUMO
The direct growth of vertically oriented graphene (VG) on low-priced, easily accessible soda-lime glass can propel its applications in transparent electrodes and energy-relevant areas. However, graphene deposited at low temperature (â¼600 °C) on the catalysis-free insulating substrates usually presents high defect density, poor crystalline quality, and unsatisfactory electrical conductivity. To tackle this issue, we select high borosilicate glass as the growth substrate (softening point â¼850 °C), which can resist higher growth temperature and thus afford higher graphene crystalline quality, by using a radio-frequency plasma-enhanced chemical vapor deposition (rf-PECVD) route. A nitrogen doping strategy is also combined to tailor the carrier concentration through a methane/acetonitrile-precursor-based synthetic strategy. The sheet resistance of as-grown nitrogen-doped (N-doped) VG films on high borosilicate glass can thus be lowered down to â¼2.3 kΩ·sq-1 at a transmittance of 88%, less than half of the methane-precursor-based PECVD product. Significantly, this synthetic route allows the achievement of 30-inch-scale uniform N-doped graphene glass, thus promoting its applications as excellent electrodes in high-performance switchable windows. Additionally, such N-doped VG films were also employed as efficient electrocatalysts for electrocatalytic hydrogen evolution reaction.
RESUMO
Transparent heating devices are widely used in daily life-related applications that can be achieved by various heating materials with suitable resistances. Herein, high-performance vertically-oriented graphene (VG) films are directly grown on soda-lime glass by a radio-frequency (rf) plasma-enhanced chemical vapor deposition (PECVD) method, giving reasonable resistances for electrothermal heating. The optical and electrical properties of VG films are found to be tunable by optimizing the growth parameters such as growth time, carrier gas flow, etc. The electrothermal performances of the derived materials with different resistances are thus studied systematically. Specifically, the VG film on glass with a transmittance of ~73% at 550 nm and a sheet resistance of ~3.9 KΩ/â¡ is fabricated into a heating device, presenting a saturated temperature up to 55 °C by applying 80 V for 3 min. The VG film on the glass at a transmittance of ~43% and a sheet resistance of 0.76 KΩ/â¡ exhibits a highly steady temperature increase up to ~108 °C with a maximum heating rate of ~2.6 °C/s under a voltage of 60 V. Briefly, the tunable sheet resistance, good adhesion of VG to the growth substrate, relative high heating efficiency, and large heating temperature range make VG films on glass decent candidates for electrothermal related applications in defrosting and defogging devices.