Evolution mechanism of surface roughness during ion beam sputtering of fused silica.

Ultrasmooth surfaces with sub-nanometer roughness and low damage are a great challenge for optical fabrication. Ion beam sputtering (IBS) has obvious advantages on the improvement of surface quality and the removal of surface defects. However, surface defects with different properties and structures display different evolution laws during the IBS process, which affects the roughness change and needs classification studies. In this paper, classification experiments are carried out to study the surface topography evolution of plastic scratches, brittle scratches, and micro-particles during the IBS process. The plastic scratches and micro-particles can be removed, while the brittle scratches can be passivated, so that surface defects can be reduced and surface quality improved. The corresponding evolution mechanisms are discussed in depth, and we show that micro-topography characteristics and material properties are important factors affecting the evolution of surface topography. Through the summary of evolution laws of different surface states, the Gaussian distribution law of surface roughness is established. The evolution regularity and mechanism of surface roughness during the IBS process are expounded upon from the perspective of microscopic morphology, which lays a foundation for ultra-smooth surface manufacturing with low damage.

Fabrication of continuous phase plates with small structures based on recursive frequency filtered ion beam figuring.

Large surface gradient and extensive mid-to-high spatial frequency in continuous phase plates (CPPs) with small structures make it difficult to achieve high-precision fabrication. An ion beam figuring (IBF) technology to fabricate CPPs with such characteristics is proposed in this paper. In order to imprint CPP microstructures with smaller spatial periods even down to 1mm in shorter time, we present a multi-pass IBF approach with different ion beam sizes based on the frequency filtering method. We discuss the selection principle and when to reduce ion beam sizes for different procedures to control dwell time and adequately exert the corrective capability in detail. This filtering method can obtains better surface quality in a faster way compared to the non filtering traditional IBF method. The experimental results verify this optimized method can effectively imprint complex microstructures with spatial period as small as 0.7 mm, surface peak-to-valleys (PV) smaller than 200nm and surface gradient as large as 1.8µm/cm to within 10 nm root-mean-square (RMS) of design specifications, which displays the advantages of our fabrication method.

Optimization technique for rolled edge control process based on the acentric tool influence functions.

In the process of computer controlled optical surfacing (CCOS), the uncontrollable rolled edge restricts further improvements of the machining accuracy and efficiency. Two reasons are responsible for the rolled edge problem during small tool polishing. One is that the edge areas cannot be processed because of the orbit movement. The other is that changing the tool influence function (TIF) is difficult to compensate for in algorithms, since pressure step appears in the local pressure distribution at the surface edge. In this paper, an acentric tool influence function (A-TIF) is designed to remove the rolled edge after CCOS polishing. The model of A-TIF is analyzed theoretically, and a control point translation dwell time algorithm is used to verify that the full aperture of the workpiece can be covered by the peak removal point of the tool influence functions. Thus, surface residual error in the full aperture can be effectively corrected. Finally, the experiments are carried out. Two fused silica glass samples of 100 mm×100 mm are polished by traditional CCOS and the A-TIF method, respectively. The rolled edge was clearly produced in the sample polished by the traditional CCOS, while residual errors do not show this problem the sample polished by the A-TIF method. Therefore, the rolled edge caused by the traditional CCOS process is successfully suppressed during the A-TIF process. The ability to suppress the rolled edge of the designed A-TIF has been confirmed.

Detailed subsurface damage measurement and efficient damage-free fabrication of fused silica optics assisted by ion beam sputtering.

Formation of subsurface damage has an inseparable relationship with microscopic material behaviors. In this work, our research results indicate that the formation process of subsurface damage often accompanies with the local densification effect of fused silica material, which seriously influences microscopic material properties. Interestingly, we find ion beam sputtering (IBS) is very sensitive to the local densification, and this microscopic phenomenon makes IBS as a promising technique for the detection of nanoscale subsurface damages. Additionally, to control the densification effect and subsurface damage during the fabrication of high-performance optical components, a combined polishing technology integrating chemical-mechanical polishing (CMP) and ion beam figuring (IBF) is proposed. With this combined technology, fused silica without subsurface damage is obtained through the final experimental investigation, which demonstrates the feasibility of our proposed method.

Investigation of surface damage precursor evolutions and laser-induced damage threshold improvement mechanism during Ion beam etching of fused silica.

Surface damage precursor evolution has great influence on laser-induced damage threshold improvement of fused silica surface during Ion beam etching. In this work, a series of ion sputtering experiment are carried out to obtain the evolutions of damage precursors (dot-form microstructures, Polishing-Induced Contamination, Hertz scratches, and roughness). Based on ion sputtering theory, surface damage precursor evolutions are analyzed. The results show that the dot-form microstructures will appear during ion beam etching. But as the ion beam etching depth goes up, the dot-form microstructures can be mitigated. And ion-beam etching can broaden and passivate the Hertz scratches without increasing roughness value. A super-smooth surface (0.238nm RMS) can be obtained finally. The relative content of Fe and Ce impurities both significantly reduce after ion beam etching. The laser-induced damage threshold of fused silica is improved by 34% after ion beam etching for 800nm. Research results can be a reference on using ion beam etching process technology to improve laser-induced damage threshold of fused silica optics.

Structure optimization and fabricating capability analysis of an ion-beam machine for a subnanometer optical surface.

Ultraprecise and ultrasmooth surfaces become critical requirements for some high-performance optical systems. Ion-beam figuring (IBF) is a good and highly deterministic method for the final precision optical figuring. However, the uniform convergences of all spatial frequency surface errors are strongly dependent on the dynamic performance and ion-beam stability of the IBF machine. In this paper, only the dynamic performance is discussed, which is limited by the acceleration and velocity of the motion system. So we discuss these problems and their influences on figuring optical surfaces in detail. The structure optimization principle is based on the fabricating capability of ultraprecise surface errors in all spatial frequency ranges. With this requirement, the structure optimization of a quick-response platform is performed to improve its dynamic performance. Manufacturing experiments on a fused silica spherical concave surface (Φ135.7 mm, radius of curvature 340.5 mm) are accomplished, and the IBF machine can effectively correct the figure errors and improve the surface quality simultaneously. The IBF process realizes the uniform convergence of surface errors in all spatial frequency ranges, which is reduced down to 0.368 nm RMS, 0.204 nm RMS, and 0.087 nm RMS, respectively. The final results indicate that the performance of the new designed IBF machine meets the requirements well for the fabrication of a subnanometer optical surface.

Propagation thresholds and driving mechanism detection of karst meteorological- agricultural drought: A case study in Guizhou Province.

It is significant to systematically quantify the propagation thresholds of meteorological drought to different levels of agricultural drought in karst areas, and revealit's the propagation driving mechanisms. This can guide early warning and fine management of agricultural drought. In this study,we selected Guizhou Province as an example. The standardized precipitation evapotranspiration index (SPEI) and standardized soil moisture index (SSI) were used to characterize meteorological and agricultural drought. The run theory was used to identify, merge and eliminate drought events. The maximum correlation coefficient was used to capture the propagation time of meteorological-agricultural drought. The regression models were used to quantify the propagation intensity threshold from meteorological drought to different levels of agricultural drought. Finally, the propagation threshold driving mechanism was explored using geographical detectors. The results show that: (1) in terms of temporal variations during the past 21 years, regional meteorological drought had a shorter duration and a higher intensity than agricultural drought, Particularly, 2011 was a year of severe drought, and agricultural drought was significantly alleviated after 2014. (2) In terms of spatial variations, the "long duration area" of meteorological drought duration showed an "S" shaped distribution in the northeast, and the "short duration area" showed a point-like distribution. The overall duration of agricultural drought showed a spatial distribution of northeast to "medium-high in the northeast and low in the southwest. (3) The drought propagation time showed an alternating distribution of "valley-peak-valley-peak" from southeast to northwest. In terms of propagation intensity thresholds, light drought showed an overall spatial distribution of high in the east and low in the west. Moderate, severe, and extreme droughts showed a spatial distribution of low in the center north of southern Guizhou) and high in the borders. (4) There was a strong spatial coupling relationship between karst development intensity, altitude and meteorological-agricultural drought propagation thresholds. The interaction of different factors exhibited a two-factor enhancement and nonlinear enhancement on the propagation threshold. This indicates that synergistic effects of different factors on the propagation threshold were larger than single-factor effects.

Agricultural drought-driven mechanism of coupled climate and human activities in the karst basin of southern China.

Timely and accurate agricultural drought monitoring and drought-driven mechanism analysis in karst basins in the context of global warming are highly important for drought disaster monitoring and sustainable ecological development in a basin. In this study, based on MODIS data, meteorological and topographic data and land use data from 2001 to 2020, we used the Sen slope, the Mann-Kendall test and a geographic detector to explore the driving mechanisms of agricultural drought caused by climate change and human activities in the karst basin of southern China from 2001 to 2020. The results showed that (1) the spatial distribution of the TVDI in the karst basin in southern China has obvious regional characteristics, showing a decreasing trend from west to east. (2) According to the interannual trend of drought, the degree of drought in the South China karst basin exhibited a weakening trend over the last 20 years, with the most severe drought occurring in 2003. Regarding the seasonal change in the TVDI, drought in spring, summer and autumn exhibited a decreasing trend, while that in winter exhibited an increasing trend, and the drought intensity decreased in the following order: spring (0.58) > autumn (0.53) > summer (0.5) > winter (0.48). (3) Single-factor detection the results showed that rainfall, temperature and elevation were the main factors driving aridification in the study area; multifactor coupling (mean) drove drought in descending order: rainfall (q = 0.424) > temperature (q = 0.340) > elevation (q = 0.219) > land use (q = 0.188) > population density (q = 0.061) > slope (q = 0.057). Therefore, revealing the mechanism of agricultural drought in karst basins through the study of this paper has important theoretical significance and provides technical guidance for drought relief in karst areas.

PiR-hsa-23533 promotes malignancy in head and neck squamous cell carcinoma via USP7.

BACKGROUND: With regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. METHODS: Differentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. RESULTS: piR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. CONCLUSIONS: These findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

Study on the driving mechanism of lagged effects based on different time scales in a karst drainage basin in South China.

Compared to earthquakes and volcanoes, drought is one of the most damaging natural disasters and is mainly affected by rainfall losses, especially by the runoff regulation ability of the underlying watershed surface. Based on monthly rainfall runoff data recorded from 1980 to 2020, in this study, the distributed lag regression model is used to simulate the rainfall-runoff process in the karst distribution region of South China, and a time series of watershed lagged-flow volumes is calculated. The watershed lagged effect is analyzed by four distribution models, and the joint probability between the lagged intensity and frequency is simulated by the copula function family. The results show that (1) the watershed lagged effects simulated by the normal, log-normal, P-III and log-logistic distribution models in the karst drainage basin are particularly significant, with small mean square errors (MSEs) and significant time-scale characteristics. (2) Affected by spatiotemporal distribution differences in rainfall and the impacts of different basin media and structures, the lag response of runoff to rainfall differs significantly among different time scales. Especially at the 1-, 3- and 12-month scales, the coefficient of variation (Cv) of the watershed lagged intensity is greater than 1, while it is less than 1 at the 6- and 9-month scales. (3) The lagged frequencies simulated by the log-normal, P-III and log-logistic distribution models are relatively high (with medium, medium-high and high frequencies, respectively), while that simulated by the normal distribution is relatively low (medium-low and low frequencies). (4) There is a significant negative correlation (R < - 0.8, Sig. < 0.01) between the watershed lagged intensity and frequency. For the joint probability simulation, the fitting effect of the gumbel Copula is the best, followed by the Clayton and Frank-1 copulas, and while that of the Frank-2 copula is relatively weak. Consequently, the propagation mechanism from meteorological drought to agricultural or hydrological drought and the conversion mechanism between agricultural and hydrological drought are effectively revealed in this study, thereby providing a scientific basis for the rational utilization of water resources and drought resistance and disaster relief in karst areas.

Role of YES1 signaling in tumor therapy resistance.

YES proto-oncogene 1 (YES1) is an SRC family kinase (SFK) that plays a key role in cancer cell proliferation, adhesion, invasion, survival, and angiogenesis during tumorigenesis and tumor development. Reports suggest that YES1 amplification is associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors (TKIs) in human malignancies. However, the mechanisms of drug resistance have not been fully elucidated. In this article, we review the literature on YES1 and discuss the implications of YES1 signaling for targeted therapy and chemotherapy resistance in malignancies. Moreover, recent advances in targeted therapy for YES1-amplified malignancies are summarized. Finally, we conclude that targeting YES1 may reverse drug resistance and serve as a valuable tumor treatment strategy.

New advances into cisplatin resistance in head and neck squamous carcinoma: Mechanisms and therapeutic aspects.

Head and neck squamous cell carcinoma (HNSCC) arises from the interplay of multiple factors, such as smoking, alcohol consumption, and viral infections. Cisplatin-based concurrent radiotherapy regimens represent the first-line treatment for advanced HNSCC cases. However, cisplatin resistance significantly contributes to poor prognoses in HNSCC patients, making it crucial to unravel the underlying mechanisms to overcome this resistance. The complexity of cisplatin resistance in HNSCC involves cancer stem cells, autophagy, epithelial-mesenchymal transition, drug efflux, and metabolic reprogramming. Recent advances in nanodrug delivery systems, combined with existing small-molecule inhibitors and innovative genetic technologies, have opened new therapeutic avenues for addressing cisplatin resistance in HNSCC. This review systematically summarizes research progress from the past five years on cisplatin resistance in HNSCC, with a particular focus on the roles of cancer stem cells and autophagy. Additionally, potential future treatment strategies to overcome cisplatin resistance are discussed, including the targeting of cancer stem cells or autophagy through nanoparticle-based drug delivery systems. Furthermore, the review highlights the prospects and challenges associated with nanodelivery platforms in addressing cisplatin resistance in HNSCC.

Immunotherapy in SMARCB1 (INI-1)-deficient sinonasal carcinoma: Two case reports.

BACKGROUND: SMARCB1/INI-1 deficient sinonasal carcinoma (SDSC) is a rare subset of sinonasal undifferentiated carcinoma with a poor prognosis. Here, we present two case reports of SDSC patients. We also review the literature on this tumor. This is the first published report of SDSC treatment with immunotherapy. CASE SUMMARY: Here we present two patient cases of SDSC in which initial consultation and diagnosis were complicated but SDSC was ultimately diagnosed. One patient received a traditional treatment of surgery and adjuvant chemoradiotherapy, while the other patient received additional immunotherapy; the prognoses of these two patients differed. We review previous diagnostic literature reports and SDSC treatments and provide a unique perspective on this rare type of tumor. CONCLUSION: SDSC is a rare, diagnostically challenging carcinoma with a consistently poor prognosis, early distant metastases, and frequent recurrence. Timely diagnosis and intervention are critical for treatment, for which the standard of care is surgery followed by adjuvant chemoradiotherapy, though immunotherapy may be an effective new treatment for SDSC.

Identification of a six-gene signature to predict survival and immunotherapy effectiveness of gastric cancer.

Background: Gastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients. Methods: We studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature's performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Results: There were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model. Conclusion: In conclusion, we discovered a 6 gene signature to forecast GC patients' OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.

Identification of molecular subtypes and prognostic model to reveal immune infiltration and predict prognosis based on immunogenic cell death-related genes in lung adenocarcinoma.

Immunogenic cell death (ICD) has been increasingly indicated to be related to caners. However, ICD's role in Lung adenocarcinoma (LUAD) is still not well investigated. Clinical data along with associated mRNA expression profiles from LUAD cases were collected in TCGA and GEO databases. 13 ICD-related genes were identified. Relations of ICD-related genes expression with prognosis of patients, tumor immune microenvironment (TIME) was analyzed. Then, candidate genes were identified and the prognostic signature were constructed. Afterwards, one nomogram incorporating those chosen clinical data together with risk scores were built. Finally, the effect of HSP90AA1, one gene of the prognostic signature, on LUAD cell were analyzed. Two clusters were identified, which were designated as the ICD-high or -low subtype according to ICD-related genes levels. ICD-high subgroup showed good prognosis, high immune cell infiltration degrees, and enhanced immune response signaling activity compared with ICD-low subtype. Moreover, we established and verified the risk signature based on ICD-related genes. High risk group predicted poor prognosis of LUAD independently and presented negative association with immune score and immune status. Furthermore, nomogram contributed to the accurate prediction of LUAD prognostic outcome. Finally, HSP90AA1 levels were remarkably elevated within tumor cells in comparison with healthy pulmonary epithelial cells. HSP90α, HSP90AA1 protein product, promoted growth, migration, and invasion of LUAD cells. Molecular subtypes and prognostic model were identified by incorporating ICD-related genes, and it was related to TIME and might be adopted for the accurate prediction of LUAD prognosis.

Identification and Validation of a Four-Gene Ferroptosis Signature for Predicting Overall Survival of Lung Squamous Cell Carcinoma.

Background: Lung squamous cell carcinoma (LUSC) represents 30% of all non-small cell lung carcinoma. Targeted therapy is not sufficient for LUSC patients because of the low frequency of targeted-effective mutation in LUSC whereas immunotherapy offers more options for patients with LUSC. We explored a ferroptosis-related prognostic signature that can potentially assess the prognosis and immunotherapy efficacy of LUSC patients. Methods: A total of 502 LUSC patients were downloaded from The Cancer Genome Atlas (TCGA). The external validation data were obtained from the Gene Expression Omnibus (GEO): GSE73403. Then, we identified the candidate genes and constructed the prognostic signature through the Cox survival regression analyses and least absolute shrinkage and selection operator (LASSO). Risk score plot, Kaplan-Meier curve, and ROC curve were used to assess the prognostic power and performance of the model. The CIBERSORT algorithm estimated the fraction of immune cell types. TIDE was utilized to predict the response to immunotherapy. IMvigor210 was used to explore the association between the risk scores and immunotherapy outcomes. A nomogram combined selected clinical characteristics, and the risk scores were constructed. Results: We screened 132 differentially expressed ferroptosis-related genes. According to KEGG and GO pathway analyses, these genes were mainly engaged in the positive regulation of cytokine production, cytokine metabolic process, and oxidoreductase activity. We then constructed a prognostic model via LASSO regression. The proportions of CD8+ T cells, CD4+ activated T cells, and follicular helper T cells were significantly different between low-risk and high-risk groups. TIDE algorithm indicated that low-risk LUSC patients might profit more from immune checkpoint inhibitors. The predictive value of the ferroptosis gene model in immunotherapy response was further confirmed in IMvigor210. Finally, we combined the clinical characteristics with a LASSO regression model to construct a nomogram that could be easily applied in clinical practice. Conclusion: We identified a prognostic model that provides an accurate and objective basis for guiding individualized treatment decisions for LUSC.

Type IIA topoisomerase (TOP2A) triggers epithelial-mesenchymal transition and facilitates HCC progression by regulating Snail expression.

Type IIA topoisomerase (TOP2A) is upregulated in hepatocellular carcinoma (HCC) and its expression is positively correlated with poor prognosis. However, the underlying molecular mechanism of this connection are poorly understood. Hence, the present work aimed to examine the possible mechanisms which may be useful in identifying a potential therapeutic strategy. The differential expression of TOP2A mRNA in HCC as compared with adjacent normal tissue was analyzed using the Oncomine database. The expression levels of TOP2A in HCC specimens and cell lines were assessed by Western blot and RT-qPCR. Stable cell lines were generated to knockdown or overexpress TOP2A, and then cell growth, migration, and invasion were analyzed. Furthermore, this study examined epithelial-mesenchymal transition (EMT) as well as the activation of related pathways. Additionally, the correlation between TOP2A levels and E-cadherin/Snail expression was determined in 72 HCC specimens. Higher expression levels of TOP2A were observed in HCC in Oncomine datasets, and the results were verified using 40 pairs of HCC specimens and peritumoral tissues. TOP2A expression levels were remarkably elevated in cells with great metastatic capacity. In addition, HCC cell growth, migration, and invasion were suppressed after TOP2A knockdown in MHCC97H cells (MHCC97H-shRNA-TOP2A), while these capabilities were promoted in TOP2A-overexpressing Hep3B cells (Hep3B-TOP2A). Furthermore, EMT was inhibited in MHCC97H-shRNA-TOP2A cells, but induced in Hep3B-TOP2A cells. The induction of EMT by TOP2A was shown to be mediated by Snail, as TOP2A promoted Snail expression through the p-ERK1/2/p-SMAD2 signaling pathway. TOP2A level showed a negative correlation with E-cadherin, whereas a positive correlation with that of vimentin and Snail in human HCC specimens by immunohistochemistry analyses. Kaplan-Meier survival curves revealed that TOP2A upregulation showed a positive correlation with poor prognosis patients. Taken together, TOP2A possibly enhances the metastasis of HCC by promoting EMT through the mediation of the p-ERK1/2/p-SMAD2/Snail pathway. This indicates that TOP2A maybe a potential factor to predict the prognosis of HCC.

Apigenin, flavonoid component isolated from Gentiana veitchiorum flower suppresses the oxidative stress through LDLR-LCAT signaling pathway.

Flower of Gentiana veitchiorum has traditionally been used as an herbal medicine in Tibet for treatment of variola, respiratory infection, and pneumonia. However, the effective components contained in flower are not identified yet, and the underlying mechanisms for anti-inflammatory, antibacterial, and antioxidative activities remain to be elucidated. Here, we first extracted the flavonoid mixture from G. veitchiorum flower. The mixture was then further isolated and the within compounds was identified through the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The results showed that apigenin (4',5,7-trihydroxyflavone) was the most abundant flavonoid in G. veitchiorum flower. We next examined the antioxidative activity of the extracted apigenin using the ferric reducing/antioxidant power (FRAP), the 1,1-diphenyl-2-picrylhydrazyl (DPPH), and the 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assays and found that a positive correlation between apigenin concentration and reactive oxygen species (ROS) scavenging rate. The biochemical assays further revealed that the levels of total cholesterol (TC), triglyceride (TG), and malondialdehyde (MDA) were reduced, while the activity of superoxide dismutase (SOD) was increased after apigenin treatment in hyperlipidemic rats. Moreover, we performed histopathological investigations and found that the lipidic deposition patterns were recovered and the amount of lipid vacuoles was significantly reduced in apigenin-treated hyperlipidemic rat liver. Western blotting assay showed that the expression of low-density lipoprotein receptor (LDLR) and lecithin-cholesterol acyltransferase (LCAT) were up-regulated in the apigenin-treated samples. Overall, our results demonstrated that the apigenin isolated from G. veitchiorum flower exhibited radical scavenging activities, and reversed the high fat diet-induced oxidative damage in rats. Its antioxidative activities are probably achieved via LDLR-LCAT signaling pathway.

A Pilot Study: Changes of Intestinal Microbiota of Patients With Non-small Cell Lung Cancer in Response to Osimertinib Therapy.

Osimertinib contributes to the higher efficacy and few intestinal side effects in non-small cell lung cancer (NSCLC) patients with T790M mutation. Previous studies has reported that intestinal microbiota play important roles in drug efficacy and toxicity. However, we have known less about the changes of intestinal microbiota in response to osimertinib therapy. In this pilot study, we used longitudinal sampling with 6 weeks sampling collection intervals for about 1 year to model intestinal microbial changes based on the 16S rRNA genes sequencing in fecal samples from NSCLC patients in response to osimertinib therapy. The results showed that there was no significantly different on the intestinal microbial composition at the phylum, family, and genus level among NSCLC patients with different treatment cycles (P > 0.05). There were no significant differences in alpha diversity characterized by the richness, Shannon diversity, and phylogenetic diversity based on the Welch's t-test among NSCLC patients in response to osimertinib therapy (P > 0.05). However, the dissimilarity test and principal coordination analysis showed a few differences among NSCLC patients. The intestinal microbial markers were changed in post-therapy (Sutterella, Peptoniphilus, and Anaeroglobus) compared to that in pre-therapy (Clostridium XIVa). Furthermore, the phylogenetic molecular ecological networks (MENs) were influenced by osimertinib therapy based on the module number, link number, and module taxa composition of the first six groups. Overall, it indicated that osimertinib therapy changed the intestinal microbiota to some extent, though not completely. In all, this pilot study provides an understanding of changes of intestinal microbiota from NSCLC patients in response to osimertinib therapy. No complete changes in intestinal microbiota seem to be closely linked with the few intestinal side effects and higher efficacy in response to osimertinib therapy.