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Abstract\nHighlightsThis research investigates the fatigue behavior of multi-row film cooling holes produced by lasers with diverse pulse widths amid intricate thermal environments. Through laser drilling experiments, conjugate heat transfer simulations, and crystal plasticity finite element analyses, it explores the interplay of temperature and stress fields among multiple holes in these structures, and factors influencing fatigue damage and its severity. Additionally, it anticipates the fatigue fracture paths of multi-row film cooling hole structures. Findings reveal that while the drilling process and aerodynamic parameters significantly impact cooling effectiveness, their influence on cooling distribution is negligible. Fatigue damage distribution is shaped by structural imperfections from different processes, stress field interference among multiple holes, and material property alterations due to temperature changes. The extent of damage is primarily dictated by roundness errors resulting from the drilling process, with taper playing a minor role. Nonetheless, stress interference among multiple holes notably exacerbates stress concentration at the interference zone, leading to increased damage levels in film cooling holes crafted by picosecond lasers with minimal roundness errors. Moreover, in complex thermal environments, fatigue fracture paths of multi-row film cooling holes migrate and evolve contingent on temperature-induced shifts in material properties.Through laser drilling experiments, conjugate heat transfer simulation, and finite element analysis of crystal plasticity, an innovative combination of drilling process, real flow field, temperature field, and hole arrangement under actual working conditions was achieved. The fatigue behavior of multi-row film cooling holes manufactured by lasers with different pulse widths under complex temperature fields were analyzed.Explored the fatigue damage factors of multi-row film cooling holes manufactured by lasers with different pulse widths under complex temperature fields, revealing the influence of the thermo-mechanical coupling mechanism on the fatigue behavior of the film cooling holes.Analyzed the interference between temperature field and structural field, and predicted the fatigue fracture paths of multi-row film cooling holes manufactured by lasers with different pulse widths under complex temperature fields. [ABSTRACT FROM AUTHOR]

Background: Metformin, a first-line antidiabetic drug, has recently been reported with anticancer activities in various cancers; however, the underlying mechanisms remain elusive. The aim of the present study was to investigate the role of cellular FADD-like IL-1β-converting enzyme (FLICE)-inhibitory protein large (c-FLIPL) in metformin-induced anticancer activity in non-small cell lung cancer (NSCLC) in vitro. Materials and methods: Cell viability was measured by MTT assay. Quantitative real-time PCR was carried out to detect the level of mRNA of related genes. The expression of related proteins was detected by Western blot. siRNA was used to silence the expression of targeted proteins. Results: Metformin significantly suppressed proliferation of both A549 and H460 cells in a dose-dependent manner. Mechanistic studies suggested that metformin killed NSCLC cells by inducing apoptotic cell death. Moreover, metformin greatly inhibited c-FLIPL expression and then promoted its degradation. Furthermore, metformin significantly activated Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3β), block the expression of AMPK, and GSK-3β with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIPL in lung cancer cells. Metformin also suppressed the activity of AMPK downstream protein kinase A (PKA), PKA activators, both 8-Br-cAMP and forskolin, greatly increased c-FLIPL expression in NSCLC cells. Conclusion: This study provided evidence that metformin killed NSCLC cells through AMPK/PKA/GSK-3β axis-mediated c-FLIPL degradation. [ABSTRACT FROM AUTHOR]

Background CRTC2 is highly expressed in lung cancer and contributes to lung cancer pathogenesis; however, whether CRTC2 promotes lung cancer metastasis remains unknown. In the present study, we investigated the role of CRTC2 in lung cancer metastasis in vitro. Methods CRTC2 stable knockdown of lung cancer cell A549 was generated with small hairpin RNA and confirmed by quantitative reverse transcription-PCR and Western blot. Wound healing and invasion transwell assays were performed to explore migration and invasion activity, and Western blot was conducted to detect the expression of related proteins. Results Suppression of CRTC2 significantly inhibited A549 cell migration and invasion in vitro. Mechanistic studies showed that knockdown of CRTC2 greatly downregulated MMP2 and MMP9 expression. CRTC2 silencing remarkably suppressed epithelial-mesenchymal transition by modulating the expression of E-cadherin and vimentin. Furthermore, suppression of CRTC2 expression significantly reduced MAPK/c-Jun N-terminal kinase activity. Conclusion CRTC2 may promote A549 migration and invasion by modulation of c-Jun N-terminal kinase-mediated epithelial-mesenchymal transition and matrix metalloproteinase expression. [ABSTRACT FROM AUTHOR]

Background: Some studies have found that the application of traditional Chinese medicine in the treatment of lung cancer has achieved satisfying results. Polyphyllin Ⅲ (PP Ⅲ) is a natural steroid saponin from P. polyphylla var. yunnanensis, and its analogs have played a wide role in anticancer research. This study aimed to investigate the effect of PP Ⅲ on the development of lung cancer and its molecular mechanism., Methods: A549 and NCI-H1299 cell lines were treated with PP Ⅲ in gradient concentration to detect the IC50 of the cells, and the optimal concentration was selected for subsequent experiments. The effects of PP III treatment on lung cancer were investigated in vitro and in vivo., Results: In vitro experiments, it was found that the proliferation, invasion, migration, and colony formation ability of cancer cells were significantly reduced after PP III treatment, while accompanied by a large number of cell apoptosis. Further detection showed that N-cadherin was significantly decreased, E-cadherin was increased, and Snail and Twist were decreased in A549 cells and NCI-H1299 cells, respectively. In addition, GSK-3β expression was increased, while β-catenin expression was reduced with PP III treatment. In the mouse model, it was demonstrated that the volume of transplanted tumors was significantly reduced after PP Ⅲ treatment., Conclusions: PP Ⅲ has the capacity to inhibit the progression of lung cancer and regulate epithelial-mesenchymal transition through the GSK-3β/β-catenin pathway to suppress the malignant behavior of cancer cells. The application of PP Ⅲ is expected to be an effective method for the treatment of lung cancer., Competing Interests: The authors declare that there is no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Two-dimensional transition metal dichalcogenides exhibit promising potential and attract the attention of the world in the application of optoelectronic devices owing to their distinctive physical and chemical properties. The real-time control of light-matter interactions in semiconductor devices through an external optical resonant cavity is crucial for designing next-generation optoelectronic devices. Here, we report the spectroscopic identification of trion binding energy in monolayer MoS 2 field-effect transistors with plasmonic nanoresonators. In consequence, the binding energy could be regulated dynamically through an external electric field. In addition, after increasing the carrier injection, the evidence of the enhanced trion binding energy can also be observed, which can be utilized for researching magneto-plasmons. The ability to dynamically control the optical properties by electrostatic doping opens a platform for designing next-generation optoelectronic and valleytronic applications in two-dimensional crystals with accurate and precise tailored responses.

The purpose of this study was to evaluate the effects of intraverbal prompts on response diversity and novelty in intraverbals posed to children with autism spectrum disorder (ASD). The intraverbal prompts involving function, feature, and class (FFC) of an item were used in the training of three questions requiring multiple responses. Two Chinese boys with ASD (aged 5-6 years) served as participants. A multiple-probe across three behaviors design was employed. The results indicated that the intraverbal prompts effectively increased the number of divergent responses to all three questions. Novel responses emerged at a low level while generalization to similar questions was not observed following the training.

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Metformin, a first-line antidiabetic drug, has recently been reported with anticancer activities in various cancers; however, the underlying mechanisms remain elusive. The aim of the present study was to investigate the role of cellular FADD-like IL-1β-converting enzyme (FLICE)-inhibitory protein large (c-FLIP L ) in metformin-induced anticancer activity in non-small cell lung cancer (NSCLC) in vitro., Materials and Methods: Cell viability was measured by MTT assay. Quantitative real-time PCR was carried out to detect the level of mRNA of related genes. The expression of related proteins was detected by Western blot. siRNA was used to silence the expression of targeted proteins., Results: Metformin significantly suppressed proliferation of both A549 and H460 cells in a dose-dependent manner. Mechanistic studies suggested that metformin killed NSCLC cells by inducing apoptotic cell death. Moreover, metformin greatly inhibited c-FLIP L expression and then promoted its degradation. Furthermore, metformin significantly activated Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and its downstream glycogen synthase kinase 3beta (GSK-3β), block the expression of AMPK, and GSK-3β with siRNA partially reversed metformin-induced cytotoxicity and restored the expression of c-FLIP L in lung cancer cells. Metformin also suppressed the activity of AMPK downstream protein kinase A (PKA), PKA activators, both 8-Br-cAMP and forskolin, greatly increased c-FLIP L expression in NSCLC cells., Conclusion: This study provided evidence that metformin killed NSCLC cells through AMPK/PKA/GSK-3β axis-mediated c-FLIP L degradation., Competing Interests: Disclosure This study was supported in part by National Natural Science Foundation of China (No. 81860412) to S. Shi, Yunnan Natural Science Foundation of China (2017FE468 [−151] to S. Shi, 2017FE468[−200] to Z. Luo, 2018FE001 [−031] to C. Wang), Yunnan Provincial Fund for High Level Reserve Talents in Health Science (H2017063) to Z. Luo and also partly supported by 100 young and middle-aged academic and technical backbone of Kunming Medical University (60117190451 to S. Shi, 60117190423 to Z. Luo). The authors report no other conflicts of interest in this work.

Background: Expression of estrogen receptor beta (ERβ) is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of ERβ has been reported to correlate with better prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between ERβ expression and prognosis in NSCLC., Materials and Methods: We performed a final analysis of 2279 patients from 14 evaluable studies for Prognostic Value of overexpression ERβ (up to October 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) were calculated., Results: Our study shows that the pooled hazard ratio (HR) of overexpression ERβ for overall survival in NSCLC was 0.78 [95% confidence interval (CI): 0.62-0.98] by univariate analysis and 1.06 (95% CI: 0.70-1.61) by multivariate analysis. Pooled HR in American and Japan was 1.09 (95% CI: 0.95-1.25, P=0.239) from 6 studies reported, however, pooled HR was 0.57 (95% CI: 0.46-0.70) outside of American and Japan from 8 studies reported. Pooled HR was 0.75 (95% CI: 0.60-0.94) from 6 studies reported for N-ERβ and 0.76 (95% CI: 0.51-1.12) from 6 Studies reported for C-ERβ., Conclusion: Our results suggested ERβ was significant associated with good overall survival in patients with NSCLC on univariate analysis but not multivariate analysis. ERβ expression is a good prognostic outcome outside of American and Japan. Overexpression of N-ERβ NSCLC patients had better survival. Large prospective studies are now needed to confirm the clinical utility of ERβ as an independent prognostic marker.

Background: CD44 is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). Although the expression of CD44 has been reported to correlate with poor prognosis of NSCLC in most literatures, some controversies still exist. Since the limited patient numbers within independent studies, here we performed a meta-analysis to clarify the correlations between CD44 expression and prognosis and clinicopathological features in NSCLC., Methods: Relevant literatures were identified using PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases (up to February 2014). Data from eligible studies were extracted and included into meta-analysis using a random effects model. Studies were pooled. Summary hazard ratios (HR) and clinical parameters were calculated., Results: We performed a final analysis of 1772 patients from 23 evaluable studies for Prognostic Value and 2167 patients from 28 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD44-V6 for overall survival in NSCLC was 1.63 [95% confidence interval (CI): 1.20-2.21] by univariate analysis and 1.29 (95% CI: 0.71-2.37) by multivariate analysis.The pooled HR of overexprssion panCD44 for overall survival in NSCLC was 1.53 (95% CI: 0.58-4.04) by univariate analysis and 3.00 (95% CI: 1.53-5.87) by multivariate analysis. Overexpression of CD44-V6 is associated with tumor differentiation (poor differentiation, OR = 1.66, 95% CI: 1.12-2.45), tumor histological type [squamous cell carcinomas (SCC), OR = 2.6, 95% CI: 1.63-5.02], clinical TMN stage (TMN stage III, OR = 2.22, 95% CI: 1.44-3.43) and lymph node metastasis (N1-3, 3.52, 95% CI: 2.08-5.93) in patients with NSCLC. However, there was no significant association between CD44-V6 and tumor size [T category, OR = 1.42, 95% CI: 0.73-2.78]., Conclusion: Our meta-analysis showed that CD44-V6 is an efficient prognostic factor for NSCLC. Overexpression of CD44-V6 was significantly associated with tumor differentiation, tumor histological type, clinical TMN stage and lymph node metastasis. However, there was no significant association between CD44-V6 and tumor size. Large prospective studies are now needed to confirm the clinical utility of CD44 as an independent prognostic marker.

Background: The plasma concentration of paraquat is closely related to the prognosis of patients with paraquat toxication, and the most common cause of death from paraquat poisoning is multiple organ failure (MOF). This study aimed to evaluate therapeutic effect of smecta on the plasma concentrations of paraquat and multi-organ injury induced by paraquat intoxication in rats., Methods: A total of 76 healthy adult SD rats were randomly divided into group A (control group, n=6), group B (poisoned group, n=30) and group C (smecta-treated group, n=30). Rats in groups B and C were treated intragastrically with PQ at 50 mg/kg, and rats in group A was treated intragastrically with saline (1 mL). Rats in group C were given intragastrically smecta at 400 mg/kg 10 minutes after administration of PQ, while rats in other two groups were treated intragastrically with 1 mL saline at the same time. Live rats in groups B and C were sacrificed at 2, 6, 24, 48, 72 hours after administration of PQ for the determination of paraquat plasma concentrations and for HE staining of the lung, stomach and jejunum. The rats were executed at the end of trial by the same way in group A., Results: The plasma concentration of paraquat (ng/mL) ranged from 440.314±49.776 to 4320.6150±413.947. Distinctive pathological changes were seen in the lung, stomach and jejunum in group B. Lung injuries deteriorated gradually, edema, leukocyte infiltration, pneumorrhagia, incrassated septa and lung consolidation were observed. Abruption of mucosa, hyperemic gastric mucosa and leukocyte infiltration were obvious in the stomach. The hemorrhage of jejunum mucosa, the abruption of villus, the gland damage with the addition of inflammatory cell infiltration were found. Compared to group B, the plasma concentration of paraquat reduced (P<0.01) and the pathological changes mentioned above were obviously alleviated in group C (P<0.05, P<0.01)., Conclusion: Smecta reduced the plasma concentration of paraquat and alleviated pathologic injury of rats with PQ poisoning.