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Abstract Background Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined. Methods Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter. Results Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566. Conclusions In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG.

Objectives: This study aims to investigate the risk factors for carbapenem-resistant Pseudomonas aeruginosa bloodstream infection (CRPA-BSI) and identify predictors of outcomes among patients with P. aeruginosa bloodstream infection (PA-BSI). Methods: A retrospective cohort study was conducted on patients with PA-BSI at Henan Cancer Hospital from 2013 to 2022. Results: Among the 503 incidences analysed, 15.1% of them were CRPA strains. Age, ANC < 100/mmc, receiving antifungal prophylaxis, exposure to carbapenems within the previous 90 days to onset of BSI, and allogeneic HSCT (allo-HSCT) were associated with the development of CRPA-BSI. CRPA-BSI patients experienced significantly higher 28-day mortality rates compared to those with carbapenem-susceptible P. aeruginosa bloodstream infection. Multivariate logistic regression analysis identified age at BSI, active stage of haematological disease, procalcitonin levels, prior corticosteroid treatment, isolation of CRPA, and septic shock as independent predictors of 28-day mortality. Conclusions: Risk factors for CRPA-BSI include age, ANC < 100/mmc, antifungal prophylaxis, exposure to carbapenems, and allo-HSCT. Additionally, age at BSI, active haematological disease, procalcitonin levels, prior corticosteroid treatment, CRPA isolation, and septic shock contribute to increased mortality rates among patients with PA-BSI.

Abstract. Background:. Whether the dynamic weight change is an independent risk factor for mortality remains controversial. This study aimed to examine the association between weight change and risk of all-cause and cause-specific mortality based on the Linxian Nutrition Intervention Trial (NIT) cohort. Methods:. Body weight of 21,028 healthy residents of Linxian, Henan province, aged 40–69 years was measured two times from 1986 to 1991. Outcome events were prospectively collected up to 2016. Weight maintenance group (weight change

In order to solve the problem of roof water inrush risk during the mining of No. 9 coal seam in Longfeng Coal Mine, an LDA-RBF neural network model for predicting the development height of water-conduction fracture zone was constructed by linear discriminant analysis (LDA), and a CRITIC-AHP comprehensive weighting method was established based on the improved CRITIC evaluation method combined with analytic hierarchy method (AHP) to evaluate the risk of roof cracking and the water richness level of the aquifer in the mining area. Through ArcGis geographic information processing technology, the cracking risk zone and the water-rich zone are superimposed to obtain a comprehensive zoning map of the water inrush risk of the roof of No.9 coal seam. The results show that the LDA-RBF neural network prediction model has a simple structure and higher fitting accuracy, and the development prediction height of the No.9 coal seam water-conducting fracture zone is 50.4 m, which has exceeded the bottom boundary level of most aquifers in the area, indicating that there is a high risk of cracking in most areas. The improved comprehensive weighting method avoids the problem of excessive subjectivity and objectivity of the evaluation results, and the water-rich zoning results are consistent with the actual water inflow of the borehole. Finally, the water inrush danger zone is mainly distributed in strips in the central and northern parts of the mining area, which is the result of the combined effect of strong water richness and high cracking risk of the aquifer in this area, indicating that the above areas should be paid attention to in actual mining.

Abstract The presence of random joints, cracks, and other defects significantly affects the meso-damage mechanism and macro-mechanical behavior of the rock. This study employed micro-CT scanning, digital image processing (DIP), and the rock failure process analysis system (RFPA3D) to reconstruct a genuine mesostructure, creating a three-dimensional (3D) numerical model of jointed sandstone. Under uniaxial stress, this model facilitated the meso-damage evolution process of prefabricated cracks in sandstone with varying dip angles. Additionally, the influence of jointed sandstone heterogeneity and prefabricated cracks with various dip angles on its failure mode and meso-damage mechanical properties were investigated. Utilizing the MATLAB platform, a 3D box dimension algorithm was developed to analyze the fractal characteristics of the mesodamage evolution in the sample. This algorithm enabled the quantitative characterization of the meso-damage evolution of sandstone. This study categorized three types of sandstone final failure modes: composite shear failure, shear failure along the joint surface, and tensile failure. Additionally, linear variations in the elastic modulus and compressive strength of the jointed sandstone were observed with increasing prefabricated fracture inclination, highlighting significant anisotropy. The presence of joints was found to induce and control the failure mode of sandstone. The meso-damage evolution process of sandstone was described in terms of the fractal dimension, indicating that more severe damage corresponded to a larger fractal dimension. This approach offers a novel statistical method for studying the progression of rock damage.

Background: Vascular cognitive impairment (VCI) is the second leading cause of dementia. Cognitive impairment is a common consequence of VCI. However, there is no effective treatment for VCI and the underlying mechanism of its pathogenesis remains unclear. This study to investigate whether artesunate (ART) can improve the learning and memory function in rats with VCI by down-regulating he level of autophagy in cerebral cortex neurons. Methods: The models for VCI were the rat bilateral common carotid artery occlusion (BACCO), which were randomized into three groups including the sham operation group (Sham), model + vehicle group (Model) and model + ART group (ART). Then the animal behaviors were recorded, as well as staining the results of cortical neurons. Western blot was performed to determine the protein expressions of LC3BⅡ/Ⅰ, p-AMPK, p-mTOR, and Beclin-1. Results: Behavioral outcomes and the protein expressions in Model group were supposedly affected by the induction of autophagy in cerebral cortex neurons. Compared to the Model group, ART improved memory impairment in VCI rats. And the expression of LC3BⅡ/Ⅰ, p-AMPK/AMPK, Beclin-1 is significant decreased in the ART group, while significant increases of p-mTOR/mTOR were showed. These results suggest that ART improved learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons. Conclusion: The results suggest that autophagy occurs in cerebral cortex neurons in rats with VCI. It is speculated that ART can improve learning and memory impairment in VCI rats by down-regulating the level of autophagy in cerebral cortex neurons.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

Abstract As a novel form of regulated cell death (RCD), disulfidptosis offering a significant opportunity in better understanding of tumor pathogenesis and therapeutic strategies. Long non-coding RNAs (lncRNAs) regulate the biology functions of tumor cells by engaging with a range of targets. However, the prognostic value of disulfidptosis-related lncRNAs (DRlncRNAs) in lung adenocarcinoma (LUAD) remains unclear. Therefore, our study aimed at establishing a prognostic model for LUAD patients based on DRlncRNAs. RNA-seq data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Subsequently, a prognostic model based on DRlncRNAs was constructed using LASSO and COX regression analysis. Patients were stratified into high- and low-risk groups based on their risk scores. Differences between the high-risk and low-risk groups were investigated in terms of overall survival (OS), functional enrichment, tumor immune microenvironment (TIME), somatic mutations, and drug sensitivity. Finally, the role of lncRNA GSEC in LUAD was validated through in vitro experiments. Using the prognostic model consists of 5 DRlncRNAs (AL365181.2, GSEC, AC093673.1, AC012615.1, AL606834.1), the low-risk group exhibited a markedly superior survival in comparison to the high-risk group. The significant differences were observed among patients from different risk groups in OS, immune cell infiltration, immune checkpoint expression, immunotherapy response, and mutation landscape. Experimental results from cellular studies demonstrate the knockdown of lncRNA GSEC leading to a significant reduction in the proliferation and migration abilities of LUAD cells. Our prognostic model, constructed using 5 DRlncRNAs, exhibited the capacity to independently predict the survival of LUAD patients, providing the potentially significant assistance in prognosis prediction, and treatment effects optimization. Moreover, our study established a foundation for further research on disulfidptosis in LUAD and proposed new perspectives for the treatment of LUAD.

Bacterial cellulose (BC) hydrogel spheroid plays a significant role in diverse fields due to its spatial 3D structure and properties. In the present work, a series of BC spheroids with controllable size and shape was obtained via an in situ biosynthesis. Crucial factors for fabricating BC spheroid including inoculum concentration of 1.35 × 103 CFU/mL, shaking speeds at 100 r/min, and 48–96 h incubation time during the biosynthetic process, were comprehensively established. An operable mechanism model for tuning the size of BC spheroids from 0.4 to 5.0 mm was proposed with a fresh feeding medium strategy of dynamic culture. The resulting BC spheroids exhibit an interactive 3D network of nanofibers, a crystallinity index of 72.3 %, a specific surface area of 91.2 m2/g, and good cytocompatibility. This study reinforces the understanding of BC spheroid formation and explores new horizons for the design of BC spheroids-derived functional matrix materials for medical care.

Abstract Objective To predict the appearance of early neurological deterioration (END) among patients with isolated acute pontine infarction (API) based on magnetic resonance imaging (MRI)-derived radiomics of the infarct site. Methods 544 patients with isolated API were recruited from two centers and divided into the training set (n = 344) and the verification set (n = 200). In total, 1702 radiomics characteristics were extracted from each patient. A support vector machine algorithm was used to construct a radiomics signature (rad-score). Subsequently, univariate and multivariate logistic regression (LR) analysis was adopted to filter clinical indicators and establish clinical models. Then, based on the LR algorithm, the rad-score and clinical indicators were integrated to construct the clinical-radiomics model, which was compared with other models. Results A clinical-radiomics model was established, including the 5 indicators rad-score, age, initial systolic blood pressure, initial National Institute of Health Stroke Scale, and triglyceride. A nomogram was then made based on the model. The nomogram had good predictive accuracy, with an area under the curve (AUC) of 0.966 (95% confidence interval [CI] 0.947–0.985) and 0.920 (95% [CI] 0.873–0.967) in the training and verification sets, respectively. According to the decision curve analysis, the clinical-radiomics model showed better clinical value than the other models. In addition, the calibration curves also showed that the model has excellent consistency. Conclusion The clinical-radiomics model combined MRI-derived radiomics and clinical metrics and may serve as a scoring tool for early prediction of END among patients with isolated API.

Abstract Background The involvement of centromere protein M (CENPM) in various types of cancer has been established, however, its impact on breast cancer and immune infiltration remains unknown. Methods We examined the expression of CENPM in different cancer types by utilizing the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression Pan-Cancer (GEO) databases. Using data from the TCGA, we examined the correlation between the expression of CENPM, the prognosis, and the clinicopathological features of individuals diagnosed with breast cancer. We conducted an enrichment analysis of CENPM using the clusterProfiler R software tool, utilizing data obtained from breast cancer patients and specimens at our institution. In addition to examining the correlation between CENPM expression and genes associated with immune checkpoints, the TIDE algorithm was employed to explore the potential of CENPM as a biomarker for immunotherapy in breast cancer. The impact of CENPM on the growth of breast cancer cells was evaluated through the utilization of the CCK8 test and the colony formation assay. The effect of CENPM on the migration of breast cancer cells was assessed using scratch and transwell assays. Results Research findings indicate that elevated levels of CENPM are linked to patient outcomes in breast cancer and various clinicopathological features. Furthermore, elevated levels of CENPM expression correlated with decreased levels of CD8 + T cells and mast cells, increased levels of Tregs and Th2, and reduced levels of CD8 + T cells. Additionally, the coexpression of CENPM with the majority of genes related to immune checkpoints indicates its potential to forecast the effectiveness of treatment in breast cancer. Suppression of CENPM hampers the growth and movement of breast tumor cells. Conclusions In summary, our study findings indicate that CENPM may serve as a cancer-causing gene in breast cancer and also as a biomarker for predicting the efficacy of immunotherapy. The oncogene CENPM is associated with breast cancer and is involved in cell proliferation and immune infiltration.

AimThe retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR).MethodsFifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP).ResultsSCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI.ConclusionsOptical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.

With the ultra-thin thickness and excellent performance, metalens are bi-dimensional optical elements composed of nanopatterned structures that demonstrate significant potential for various applications such as holography, planar imaging and tomography. However, the small size of metalens makes it challenging to precisely quantify their wavefront aberration, thus impeding their broader utilization. To address this challenge, we propose an innovative method for measuring wavefront aberration in metalens using phase-shift interferometry. Furthermore, we have developed the Small Aperture Interferometric Imaging Detection System with variable fields of view, specifically designed for metalens. This system can accurately measure the wavefront aberration of metalens with different fields of view with PV accuracy of 1/20λ, further enabling the acquisition of imaging performance parameters, including Modulation Transfer Function (MTF) and Point Spread Function (PSF). This innovative measurement approach not only enables quantitative evaluation of performance of metalens but also assists designers and manufacturers in optimizing process flows and identifying potential defects. As a result, this approach aids in promoting the industrial application of metalens.

Background: The study aimed to examine the bidirectional relationship between sarcopenia and depressive symptoms in a national, community-based cohort study, despite the unclear temporal sequence demonstrated previously. Methods: Data were derived from four waves (2011 baseline and 2013, 2015, and 2018 follow-ups) of the China Health and Retirement Longitudinal Study (CHARLS). A total of 17,708 participants aged 45 years or older who had baseline data on both sarcopenia status and depressive symptoms in 2011 were included in the study. For the two cohort analyses, a total of 8092 adults without depressive symptoms and 11,292 participants without sarcopenia in 2011 were included. Sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 (AWGS 2019) criteria. Depressive symptoms were defined as a score of 20 or higher on the 10-item Center for Epidemiologic Studies Depressive Scale (CES-D-10). Cox proportional hazard regression models were conducted to examine the risk of depressive symptoms and sarcopenia risk, while cross-lagged panel models were used to examine the temporal sequence between depressive symptoms and sarcopenia over time. Results: During a total of 48,305.1 person-years follow-up, 1262 cases of incident depressive symptoms were identified. Sarcopenia exhibited a dose–response relationship with a higher risk of depressive symptoms (HR = 1.7, 95%CI: 1.2–2.3 for sarcopenia, and HR = 1.5, 95%CI: 1.2–1.8 for possible sarcopenia, p trend < 0.001). In the second cohort analysis, 240 incident sarcopenia cases were identified over 39,621.1 person-years. Depressive symptoms (HR = 1.5, 95%CI: 1.2–2.0) are significantly associated with a higher risk of developing sarcopenia after multivariable adjustment (p < 0.001, Cross-lagged panel analyses demonstrated that depressive symptoms were associated with subsequent sarcopenia (β = 0.003, p < 0.001). Simultaneously, baseline sarcopenia was also associated with subsequent depressive symptoms (β = 0.428, p < 0.001). Conclusion: This study identified a bidirectional relationship between depressive symptoms and sarcopenia. It seems more probable that baseline sarcopenia is associated with subsequent depressive symptoms in a stronger pattern than the reverse pathway. The interlinkage indicated that maintaining normal muscle mass and strength may serve as a crucial intervention strategy for alleviating mood disorders.

To calculate the scattering impact of scratches on space-based telescope systems accurately, this study proposes fitting scratch scattering using an anisotropic scattering model based on actual test results. The stray light nonuniformity and total stray light of each mirror in a Cook-type off-axis three-mirror system was calculated. A scratch illuminated with unit radiation power can generate a maximum stray light level of 7 × 10-5 and can obscure dark targets with a brightness ratio of 1 × 10-5 to 8 × 10-5. Furthermore, as the wavelength decreases, the total stray light generated by this scratch can reach 5.7 × 10-4 when illuminated with unit radiation power in the 200 nm ultraviolet band. Such scratches on the mirrors of an off-axis three-mirror telescope cause 7–8 times higher nonuniformity of stray light than roughness scattering, decreasing signal-to-noise ratio and affecting target recognition and image processing.

Since the testing of convex mirrors often requires a compensator with a larger aperture than the mirror under test, this is undoubtedly a trade-off not worth pursuing. Moreover, for surfaces with higher levels of asphericity, it further escalates the challenges in testing. In this study, high-accuracy testing of large convex aspheric surfaces with rotary symmetry was achieved via a method that combines sub-aperture stitching and Computer-Generated Holograms (CGH) compensation testing. Applying the methodology outlined in this study, practical testing was conducted on a large-aperture convex aspheric mirror with a diameter of 538 mm. The outcomes demonstrated that the center testing data and the outer ring testing data were stitched by the stitching algorithm to obtain the surface error of the full-aperture. The results were compared to those of Luphoscan and compensation testing, with a residual Root Mean Square (RMS) less than λ/20 (λ = 632.8 nm). Finally, the error analysis of the entire testing process showed that the accuracy was better than λ/50. The results demonstrate that the method can achieve highly accurate test of large convex aspheric surfaces.

Abstract Background The Triglyceride and Glucose (TyG) index has been found to have a strong correlation with the recurrence of acute ischemic stroke (AIS) and poor patient outcomes. Nevertheless, the relationship between the TyG index and early neurological deterioration (END) has not been fully explored. Therefore, the present study aims to investigate the potential association between the TyG index and END. Methods A retrospective analysis of 2129 patients diagnosed with AIS between January 2019 and December 2022 at the Second Affiliated Hospital of Harbin Medical University. Patients were divided into END and non-END groups based on changes in National Institutes of Health Stroke Scale scores within 7 days of admission, and the differences in the indicators between the two groups were examined using univariate analysis. The patients were then divided into three groups based on the tertile of the TyG index (T1: TyG index

Abstract Wireless capsule endoscopy (WCE) is becoming more popular in clinical settings as a safe and painless gastrointestinal examination. Existing studies on automatic detection of lesions in WCE images have the problems of small dataset size and uneven distribution of numbers in terms of categories, which often leads to overfitting of the model and severely limits the performance improvement of the object detection network on WCE images. The traditional data enhancement methods such as flipping and local erasure have limitations and cannot achieve good generalization results. Therefore, a WCE‐DCGAN network was proposed in this paper to generate WCE images from existing WCE images. Using the images generated by this network and the original images as the input of the object detection network, there are different degrees of performance improvement on SSD, YOLOv5, and YOLOv4, and the average recognition accuracy of 97.25% can be achieved on SSD. Meanwhile, images generated by WCE‐DCGAN not only enlarge the size of the data set, but also have the characteristics of diversity, which makes the model have a good generalization effect.

AbstractConfronting the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), simple, fast and specific non-laboratory SARS-CoV-2 diagnostic tests are urgently required. However, the current nucleic acid assays generally rely on the diagnostic laboratory, trained staff and specialized equipment for execution and analysis, presenting clear limitations in the field detection. Here, we describe a portable and reliable immobilization-based loop-mediated isothermal amplification (LAMP) device which is mobile, without the requirement of any complicated instrument and appropriate for high-throughput testing. This device was constructed by utilizing the interaction between a carboxyl-tagged primer and an amino-tagged substrate, and capable of catching the target sequence in SARS-CoV-2 produced via the immobilization-based LAMP. In this study, the immobilization conditions and immobilized primer structure were explored and optimized. With this proposed device, the analysis result can be obtained rapidly in 30 min with excellent specificity, even if the template is extracted from a complex sample containing pharyngeal swab or human blood. In addition, the device can be applied to detect the nucleic acid of SARS-CoV-2 and various other pathogens, showing attractive potential for rapid and high-throughput detection at airports, railway stations, cold-chain transportations, community hospitals and so on. Therefore, we believe that the immobilization-based LAMP device is an advanced approach to developing a portable, specific, low-cost and high-throughput diagnostic platform.

Testing accuracy is an essential factor in determining the manufacturing accuracy of aspheric mirrors. Because of the complexity of the null compensation test, the coherent stray lights generated by multiple reflections and transmissions between optical elements and the crosstalk fringes generated by the multi-beam interference of the reference light, test light, and stray lights are superimposed on the interference fringes, resulting in reduced testing accuracy. Focusing on this problem, a simulation analysis method for crosstalk fringes based on ray-tracing and multi-beam interference in interference testing is proposed. The coordinates, amplitudes, and phases of the test light and stray lights on the transmission sphere are traced, and the crosstalk fringes and interference testing fringes and their positions, sizes, and intensity information are simulated via multi-beam interference. The influence of crosstalk fringes on interference fringes is determined. An experimental optical path is built to verify the correctness of the crosstalk fringe simulation method.

CIOMP report their progress in high-accuracy manufacturing of the world’s largest SiC aspheric mirror. The final surface figure error is 15.2 nm RMS and aerial density is less than 120 kg/m2.

The construction of heterojunction structure is an effective strategy for solving photogenerated electron-hole recombination. In this work, a kind of 1D/2D S-scheme BiPO4/BiOBr heterojunction film is designed and constructed by in-situ electrochemical-ion-exchange method on Bi plate. The S-scheme transfer path of photogenerated electrons of BiPO4/BiOBr film is collaboratively confirmed through DFT calculation and in-situ X-ray photoelectron spectra. As-prepared S-scheme BiPO4/BiOBr heterojunction film has the higher CO2 photoreduction activity (296.5 μmol·g−1) to CO, 1.9 times than pure BiOBr film, which should be mainly attributed to improved light utilization efficiency and effective separation/migration of photogenerated electron-hole pairs.

Background: Lung adenocarcinoma (LUAD) has emerged as one of the most aggressive lethal cancers. Anoikis serves as programmed apoptosis initiated by the detachment of cells from the extracel-lular matrix. Cuproptosis is distinct from traditional cell death modalities. The above two modes are both closely related to tumor progression, prognosis, and treatment. However, whether they have synergistic effects in LUAD deserves further investigation. Methods: The anoikis-related prognostic genes (ANRGs) co-expressed with cuproptosis-associated genes (CAGs) were screened using correlation analysis, analysis of variance, least absolute shrinkage, and selection operator (LASSO), and COX regression followed by functional analysis, and then LUAD risk score model was constructed. Using consensus clustering, the relationship between different subtypes and clinicopathological features, immune infiltration characteristics, and somatic mutations was analyzed. A nomogram was developed by incorporating clinical information, which provided a prediction of the survival of patients. Finally, a comprehensive analysis of ANRGs was performed and verified by the HPA database. Results: A total of 27 ANRGs associated with cuproptosis were obtained. On this basis, three distinct ANRGs subtypes were identified, and the differences between clinical prognosis and immune infiltration were observed. A risk score model has been constructed by incorporating seven ANRGs signatures (EIF2AK3, IKZF3, ITGAV, OGT, PLK1, TRAF2, XRCC5). A highly reliable nomogram was developed to help formulate treatment strategies based on risk score and the clinicopathological features of LUAD. The seven-gene signature was turned out to be strongly linked to immune cells and validated in single-cell data. Immunohistochemistry proved that all of them are highly expressed in LUAD tissues. Conclusion: This study reveals the potential relationship between cuproptosis-related ANRGs and clinicopathological features, tumor microenvironment (TME), and mutation characteristics, which can be applied for predicting the prognosis of LUAD and help develop individualized treatment strategies.

FeSiAl flakes were fabricated by vibrating ball milling the FeSiAl ribbons. And the microwave absorption properties of FeSiAl flakes were improved by doping the multi-wall carbon nanotubes (MWCNTs) with different mass concentrations. The results show that the FeSiAl/MWCNT composites exhibit significantly improved microwave absorption performance with advantages of strong and broadband absorption in the L-band and S-band. In particular, the reflection loss (RL) of the FeSiAl/MWCNT2 composite reaches −7.4 dB at 1.0 GHz, whereupon, through the electromagnetic simulation software CST Microwave Studio, FeSiAl/MWCNT2 all-dielectric metamaterial absorbers (ADMMAs) were macroscopically designed, achieving an ultra-wideband absorption (RL ≤ −10 dB) of 14.4 GHz (3.6~18.0 GHz). It is recognized that the standing wavelength resonance and diffraction effect are responsible for absorbing electromagnetic waves, and the broadband absorption is improved via dielectric dispersion; their synergistic effect makes the ADMMAs exhibit good microwave absorption performance. This work provides a useful method for designing microwave absorption materials with broadband absorption.

PurposeTo report a unique case of topiramate and hydrochlorothiazide associated with acute myopia and angle narrowing.Patients and methodsA 34-year-old Asian woman presented with prominent binocular visual acuity decrease 6 h after taking only one dose of 25 mg topiramate, 25 mg hydrochlorothiazide, and 22.4 mg fluoxetine to lose weight. She was subsequently diagnosed with acute bilateral myopia and angle narrowing and was started on topical therapy.ResultsInitial examination revealed a decreased visual acuity of 20/100 bilaterally, an elevated intraocular pressure of 23 mmHg in the right eye and 24 mmHg in the left eye, suprachoroidal effusions, and angle narrowing. After the discontinuation of these drugs and the use of IOP-lowering medication, the patient made full recovery.ConclusionWe speculate that there is a drug–drug interaction between topiramate and hydrochlorothiazide that may lead to the angle narrowing in a short time and at a low dose. Timely discontinuation of the drug usually leads to complete recovery within days to weeks.

Lung cancer has become the leading cause of cancer death all over the world. Nowadays, there is a consensus that the treatment of non-small cell lung cancer (NSCLC) prefers a combination of multidisciplinary comprehensive treatment and individualized treatment, which can significantly improve the prognosis of patients. Here, we report a female patient with recurrence-prone NSCLC. She had a decade-long disease course, during which the lesion recurred twice and finally cured with Multi-Disciplinary Treatment (MDT). An elderly female patient was admitted to the hospital after diagnosis of lung cancer, and treated with surgery and postoperative adjuvant chemotherapy. Five years later, suspicious lesions were found by computed tomography (CT) reexamination, and then confirmed tumor recurrence by puncture biopsy. Based on the genetic test results, gefitinib was used for subsequent targeted therapy, and the lesion gradually shrunk to disappear. However, the lesion appeared again two years later, after consultation the microwave ablation was adopted and the curative effect was excellent. At last, regular reexamination showed no abnormality, the patient has survived so far. The case proves the great benefit of multidisciplinary comprehensive treatment, especially microwave ablation for patient with recurrence-prone NSCLC. And the effect of systemic anti-tumor immune response induced by microwave ablation on lung cancer also needs to be further explored.

Abstract Background Many studies reporting that down-regulation of SOCS6 plays vital roles in promoting progression of malignant tumors have been published. The present study was performed to evaluate whether SOCS6 was significantly associated with prognosis of GIST patients. Methods Immunohistochemical staining was accomplished to evaluate the expression levels of SOCS6 among GIST patients. The impacts of SOCS6 expression on overall survival (OS) and recurrence-free survival (RFS) of GIST patients were assessed by Cox proportional hazard regression model analysis and Kaplan-Meier curve analysis. Results It was demonstrated that the expression level of SOCS6 was significantly associated with tumor size (P=0.001). Then according to Kaplan-Meier curve analysis, low expression of SOCS6 was significantly correlated with worse OS and RFS of GIST patients. Ultimately, it was revealed by Cox proportional regression model analysis that low expression of SOCS6 was an independent predictive factor for OS and RFS. Conclusions Low expression of SOCS6 was an independent prognostic factor for GIST, suggesting its potential as a novel biomarker predicting survival of GIST patients.

Alzheimer disease (AD) is a progressive neurodegenerative disease resulting from the accumulation of extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles. There are currently no objective diagnostic measures for AD. The aim of this study was to identify potential diagnostic markers for AD and evaluate the role of immune cell infiltration in disease pathogenesis. AD expression profiling data for human hippocampus tissue (GSE48350 and GSE5281) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software and the Human Protein Atlas database was used to screen AD-related DEGs. We performed functional enrichment analysis and established a protein–protein interaction (PPI) network to identify disease-related hub DEGs. The fraction of infiltrating immune cells in samples was determined with the Microenvironment Cell Populations-counter method. The random forest algorithm was used to develop a prediction model and receiver operating characteristic (ROC) curve analysis was performed to validate the diagnostic utility of the candidate AD markers. The correlation between expression of the diagnostic markers and immune cell infiltration was also analyzed. A total of 107 AD-related DEGs were screened in this study, including 28 that were upregulated and 79 that were downregulated. The DEGs were enriched in the Gene Ontology terms GABAergic synapse, Morphine addiction, Nicotine addiction, Phagosome, and Synaptic vesicle cycle. We identified 10 disease-related hub genes and 20 candidate diagnostic genes. Synaptophysin (SYP) and regulator of G protein signaling 4 (RGS4) (area under the ROC curve = 0.909) were verified as potential diagnostic markers for AD in the GSE28146 validation dataset. Natural killer cells, B lineage cells, monocytic lineage cells, endothelial cells, and fibroblasts were found to be involved in AD; additionally, the expression levels of both SYP and RGS4 were negatively correlated with the infiltration of these immune cell types. These results suggest that SYP and RGS4 are potential diagnostic markers for AD and that immune cell infiltration plays an important role in AD development and progression.

Fatty Acid Desaturase-1 (FADS1) or delta 5 desaturase (D5D) is a rate-limiting enzyme involved in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs), i.e., arachidonic acid (ARA) and eicosapentaenoic (EPA). These LC-PUFAs and their metabolites play essential and broad roles in cancer cell proliferation, metastasis, and tumor microenvironment. However, the role of FADS1 in cancers remains incompletely understood. Utilizing The Cancer Genome Atlas (TCGA) database, we explored the role of FADS1 across different cancer types using multiple bioinformatics and statistical tools. Moreover, we studied the impact of a FADS1 inhibitor (D5D-IN-326) on proliferation of multiple cancer cell lines. We identified that FADS1 gene is a predictor for cancer survival in multiple cancer types. Compared to normal tissue, the mRNA expression of FADS1 is significantly increased in primary tumors while even higher in metastatic and recurrent tumors. Mechanistically, pathway analysis demonstrated that FADS1 is associated with cholesterol biosynthesis and cell cycle control genes. Interestingly, FADS1 expression is higher when TP53 is mutated. Tumors with increased FADS1 expression also demonstrated an increased signatures of fibroblasts and macrophages infiltration among most cancer types. Our in vitro assays showed that D5D-IN-326 significantly inhibited cell proliferation of kidney, colon, breast, and lung cancer cell lines in a dose-dependent manner. Lastly, single nucleotide polymorphisms (SNPs) which are well-established expression quantitative trait loci (eQTLs) for FADS1 in normal human tissues are also significantly correlated with FADS1 expression in tumors of multiple tissue types, potentially serving as a marker to stratify cancer patients with high/low FADS1 expression in their tumor tissue. Our study suggests that FADS1 plays multiple roles in cancer biology and is potentially a novel target for precision cancer treatment.

The fatty acid desaturase 1 (FADS1), also known as delta‐5 desaturase (D5D), is one of the rate‐limiting enzymes involved in the desaturation and elongation cascade of polyunsaturated fatty acids (PUFAs) to generate long‐chain PUFAs (LC‐PUFAs). Reduced function of D5D and decreased hepatic FADS1 expression, as well as low levels of LC‐PUFAs, were associated with nonalcoholic fatty liver disease. However, the causal role of D5D in hepatic lipid homeostasis remains unclear. In this study, we hypothesized that down‐regulation of FADS1 increases susceptibility to hepatic lipid accumulation. We used in vitro and in vivo models to test this hypothesis and to delineate the molecular mechanisms mediating the effect of reduced FADS1 function. Our study demonstrated that FADS1 knockdown significantly reduced cellular levels of LC‐PUFAs and increased lipid accumulation and lipid droplet formation in HepG2 cells. The lipid accumulation was associated with significant alterations in multiple pathways involved in lipid homeostasis, especially fatty acid oxidation. These effects were demonstrated to be mediated by the reduced function of the peroxisome proliferator–activated receptor alpha (PPARα)–fibroblast growth factor 21 (FGF21) axis, which can be reversed by treatment with docosahexaenoic acid, PPARα agonist, or FGF21. In vivo, FADS1‐knockout mice fed with high‐fat diet developed increased hepatic steatosis as compared with their wild‐type littermates. Molecular analyses of the mouse liver tissue largely corroborated the observations in vitro, especially along with reduced protein expression of PPARα and FGF21. Conclusion: Collectively, these results suggest that dysregulation in FADS1 alters liver lipid homeostasis in the liver by down‐regulating the PPARα‐FGF21 signaling axis.

Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.

Abstract Background Studies have demonstrated that long noncoding RNAs (lncRNAs) have essential impacts on the development of atherosclerosis (AS). This study aimed to identify the role and functional mechanism of lncRNA CASC2 in the development and migration of vascular smooth muscle cells (VSMCs). Method The serum of 40 pairs of AS patients and healthy volunteers were collected and the expression of CASC2 was evaluated. qRT-PCR and western blotting were carried out to examine the expression levels of at mRNA and protein level, repectively. Cell proliferation assay, colony formation assay, transwell migration assay, dual-luciferase reporter assay, and wound healing assay were conducted to evaluate cell proliferation, colony formation, migration, transcription, targeting, and self-restoration. Results The expression levels of CASC2 were decreased, while the expression levels of miR-532-3p were elevated in AS patient samples and VSMCs. Overexpression of CASC2 inhibited the proliferation and migration of VSMCs and enhanced cell apoptosis. CASC2 inhibited the expression of miR-532-3p, and inversely upregulated the expression of PAPD5, which was a target of miR-532-3p. In addition, knockdown of miR-532-3p-mimic and PAPD5 could attenuate the impact of overexpression of CASC2 on proliferation, migration, and apoptosis in ox-LDL-VSMCs. Conclusion CASC2 suppressed cell reproduction and promoted cell apoptosis by regulating the miR-532-3p/PAPD5 axis in ox-LDL-mediated VSMCs. This might be important for AS therapeutics.

Abstract Background Chemotherapy is a widely used treatment for cancer. However, the development of acquired multidrug resistance (MDR) is a serious issue. Emerging evidence has shown that the extracellular vesicles (EVs) mediate MDR, but the underlying mechanism remains unclear, especially the effects of chemotherapeutic agents on this process. Methods Extracellular vesicles isolation was performed by differential centrifugation. The recipient cells that acquired ATP-binding cassette sub-family B member 1 (ABCB1) proteins were sorted out from co-cultures according to a stringent multi-parameter gating strategy by fluorescence-activated cell sorting (FACS). The transfer rate of ABCB1 was measured by flow cytometry. The xenograft tumor models in mice were established to evaluate the transfer of ABCB1 in vivo. Gene expression was detected by real-time PCR and Western blotting. Results Herein, we show that a transient exposure to chemotherapeutic agents can strikingly increase Rab8B-mediated release of extracellular vesicles (EVs) containing ABCB1 from drug-resistant cells, and accelerate these EVs to circulate back onto plasma membrane of sensitive tumor cells via the down-regulation of Rab5. Therefore, intercellular ABCB1 transfer is significantly enhanced; sensitive recipient cells acquire a rapid but unsustainable resistance to evade the cytotoxicity of chemotherapeutic agents. More fascinatingly, in the xenograft tumor models, chemotherapeutical drugs also locally or distantly increase the transfer of ABCB1 molecules. Furthermore, some Non-small-cell lung carcinoma (NSCLC) patients who are undergoing primary chemotherapy have a rapid increase of ABCB1 protein in their monocytes, and this is obviously associated with poor chemotherapeutic efficacy. Conclusions Chemotherapeutic agents stimulate the secretion and recycling of ABCB1-enriched EVs through the dysregulation of Rab8B and Rab5, leading to a significant increase of ABCB1 intercellular transfer, thus assisting sensitive cancer cells to develop an urgent resistant phenotype. Our findings provide a new molecular mechanism of how chemotherapeutic drugs assist sensitive cancer cells in acquiring an urgent resistance.

Depression is one very common mental health disorder which can cause morbidity and mortality if not addressed. Recent studies have provided strong evidence that depression may be accompanied by immune activation, secondary inflammatory reaction, and hyperactivity of the Hypothalamic Pituitary Adrenal (HPA) axis. It is well-known that it takes at least 2 weeks for conventional antidepressants, especially SSRIs (Selective serotonin reuptake inhibitors) to produce effects. To better understand the mechanism of antidepressant effects on depression and subsequently further elucidate the pathogenesis of depression, we selected phytestrogen daidzein (DD) to observe its effects on the depression-like and anxiety-like behavior in two different rodent models of depression which were induced by learned helplessness and chronic mild stress (CMS) and then simultaneous evaluation of the depression-like behavior, the activity of HPA axis, and circulatory cytokines. Our results showed that daidzein attenuated depression-like behaviors through alleviating HPA axis hyperactivity, decreasing the levels of stress-related hormones, and partly rectifying some inflammatory cytokines imbalance in both the rodent models of depression.

Although metasurfaces have received enormous attention and are widely applied in various fields, the realization of multiple functions using a single metasurface is still rarely reported to date. In this work, we propose a novel dual-functional metasurface that can be applied as a mid-infrared narrowband thermal light source in optical gas sensing and a long-wave infrared broadband absorber in photodetection. By actively tailoring the structure and constituent materials of the metasurface, the device yields an absorptivity of over 90% from 8 µm to 14 µm, while it exhibits an emissivity of 97.4% at the center wavelength of 3.56 μm with a full width at half-maximum of 0.41 µm. Notably, the metasurface is insensitive to the incident angle under both TM- and TE-polarized light. The proposed dual-functional metasurface possesses many advantages, including a simple structure, thin thickness, angle and polarization insensitivity, and compatibility with optical devices, which are expected to simplify the existing imaging systems and improve the performance of photodetection equipment.

Abstract Background Mediator complex subunit 12 (MED12) is an essential hub for transcriptional regulation, in which mutations and overexpression were reported to be associated with several kinds of malignancies. Nevertheless, the role of MED12 in non-small cell lung cancer (NSCLC) remains to be elucidated. Methods MED12 mutation was detected by Next-generation sequencing. The expression of MED12 in 179 human NSCLC tissue samples and 73 corresponding adjacent normal lung tissue samples was measured by immunohistochemistry (IHC). CRISPR-Cas9 was used to knock out MED12 in PC9 and SPC-A1 cells. MED12 rescued stable cell lines were generated by lentivirus infection. We traced cell division process by live cell imaging. The molecular mechanism of aborted cytokinesis resulted by MED12 knockout was investigated by RNA-seq. Effects of MED12 deletion on the proliferation of NSCLC cells were determined by MTT assay and Colony-formation assay in vitro and xenograft tumor model in nude mouse. Cell senescence was measured by SA-β-gal staining. Results In our study, no MED12 exon mutation was detected in NSCLC samples, whereas we found that MED12 was overexpressed in human NSCLC tissues, which positively correlated with the tumor volume and adversely affected patient survival. Furthermore, knockout MED12 in NSCLC cell lines resulted in cytokinesis failure, displayed a multinuclear phenotype, and disposed to senescence, and become non-viable. Lack of MED12 decreased the proliferative potential of NSCLC cells and limited the tumor growth in vivo. Mechanism investigations revealed that MED12 knockout activated LIMK2, caused aberrant actin cytoskeleton remodeling, and disrupted the abscission of intercellular bridge, which led to the cytokinesis failure. Reconstitution of exogenous MED12 restored actin dynamics, normal cytokinesis and cell proliferation capacity in MED12 knockout cells. Conclusions These results revealed a novel role of MED12 as an important regulator for maintaining accurate cytokinesis and survival in NSCLC cells, which may offer a therapeutic strategy to control tumor growth for NSCLC patients especially those highly expressed MED12.

The treatment of chronic myeloid leukemia (CML) with BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, has yielded clinical success. However, the direct targeting of BCR-ABL does not eradicate CML cells expressing mutant BCR-ABL, especially the T315I mutation in BCR-ABL. Moreover, increasing mutations were identified in BCR-ABL domain, resulting in TKIs resistance recently. It is necessary to find BCR-ABL-independent target for treating CML patients with various mutations, including T315I mutation in BCR-ABL. The dichotomous behavior of CREB binding protein (CBP) and E1A protein (p300), recruited by β-catenin associated with self-renewal and differentiation, have been identified in hematopoietic stem cells, respectively. In this study, CBP was aberrantly expressed in CML cells on the basis of Oncomine dataset. The β-catenin bound with much more CBP than p300 in CML cells. Down-regulation of CBP inhibited cell proliferation capacity and increased the binding of β-catenin to p300, thus promoting cell differentiation and p53-dependent cell senescence in CML cells with either wild type or T315I mutant BCR-ABL in vitro and in vivo models. These demonstrate CBP blockage can be developed for the treatment of CML independent of BCR-ABL mutation status including T315I.

Background and AimNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Previous observational studies suggested that cannabis use may be associated with a lower risk for NAFLD but the causal relationship remains unclear. We aim in this study to examine the causal effect of cannabis consumption on the risk of NAFLD using a Mendelian randomization analysis. Clarifying this causal effect is important for cannabis-based drug discovery for NAFLD.MethodsWe used data from the largest-to-date GWAS meta-analysis on lifetime use of cannabis (yes or no) consisting of three cohorts [International Cannabis Consortium (ICC), 23andMe, and the UK Biobank] of European ancestry (total N = 184,765). We also used other GWAS data on cannabis use dependence and cannabis use disorder (CUD). The NAFLD GWAS data were generated from the UK Biobank population (1,122 cases and 399,900 controls). The inverse variance weighted (IVW) method was used to assess the causal impact of cannabis lifetime use on the risk of NAFLD. We also performed a sensitivity analysis using weighted median estimator and MR-Egger.ResultsThere was no statistically significant causal effect between either the lifetime cannabis use, cannabis use dependence or CUD and the risk for NAFLD (p > 0.05 for all tests). No significant pleotropic effect was observed based on both MR-PRESSO global test (p = 0.99) and the modified Q’ statistics. However, the study may be underpowered.ConclusionOur results demonstrated no evidence that cannabis consumption has a causal effect of protection against the development of NAFLD.

Background/Aims: Multidrug resistance (MDR) induced by the ABC transporter subfamily B member 1 (ABCB1) and subfamilyG member 2 (ABCG2) limits successful cancer chemotherapy and no commercially available MDR modulator is used in the clinic. In the current study, we aimed to investigate the effects of PCI29732 on the enhancement of chemotherapeutic agents. Methods: Cell cytotoxicity and reversal effect were measured with MTT assay. Additionally, flow cytometry was employed to detect the accumulation and efflux of the drugs. We investigated the interaction of PCI29732 and the substrate binding sites of ABCG2 was investigated via the photo-labeling of ABCG2 with the [125I] iodoarylazidoprazosin. The vanadate-sensitive ATPase activity of ABCG2 was measured to identify whether the drug affected the ATPase activity. RT-PCR and Western blot were utilized to analyze mRNA and protein expression respectively. Results: Here, we found that PCI29732 significantly enhanced the efficacy of substrate chemotherapeutic agents in ABCG2-overexpressing cells and also in xenografts harboring the H460/MX20 cell that overexpress ABCG2, but not in their parental sensitive cells and ABCB1-overexpressing cells. Mechanistically, the intracellular accumulations of doxorubicin and Rhodamine 123 were increased in ABCG2-overexpressing S1-MI-80 cells with the presence of PCI29732. PCI29732 stimulated the ATPase activity of ABCG2 at low concentrations. However at the high concentrations, PCI29732 inhibited the ATPase activity, and competed with [125I]-iodoarylazidoprazosin for photo-affinity labeling of ABCG2. PCI29732 did neither alter the mRNA or protein expression levels of ABCG2 nor the phosphorylation levels of AKT and ERK1/2. Conclusion: Our study demonstrates that PCI29732 inhibits the function of ABCG2 by competitively binding to the ATP-binding site of ABCG2 and enhances the anti-tumor efficacy of substrate chemotherapeutic agents, This findings encourages the development of combinational chemotherapy for the treatment of ABCG2- overexpressing cancer patients.

Abstract It has long been an aspirational goal to create artificial evaporators that allow omnidirectional energy absorptance, adequate water supply, and fast vapor transportation, replicating the feat of plant transpiration, to solve the global water crisis. This work reveals that magnolia fruits, as a kind of tree‐like living organism, can be outstanding 3D tree‐like evaporators through a simple carbonization process. The arterial pumping, branched diffusion, and confined evaporation are achieved by the “trunk,” “branches,” and “leaves,” respectively, of the mini tree. The mini tree possesses omnidirectional high light absorptance with minimized heat loss and gains energy from the environment. Water confined in the fruit possesses reduced vaporization enthalpy and transports quickly following the Murray's law. A record‐high vapor generation rate of 1.22 kg m−2 h−1 in dark and 3.15 kg m−2 h−1 under 1 sun illumination is achieved under the assistance of the gully‐like furry surface. The “absorption of nutrients” enables the fruit to recover valuable heavy metals as well as to produce clean water from wastewater efficiently. These findings not only reveal the hidden talent of magnolia fruits as cheap materials for vapor generation but also inspire future development of high‐performance, full‐time, and all‐weather vapor generation and water treatment devices.

Abstract Background ATP-binding cassette subfamily G member 2 (ABCG2), a member of the ABC transporter superfamily proteins, mediates multidrug resistance (MDR) by transporting substrate anticancer drugs out of cancer cells and decreasing their intracellular accumulation. MDR is a major hurdle to successful chemotherapy. A logical approach to overcome MDR is to inhibit the transporter. However, no safe and effective MDR inhibitor has been approved in the clinic. Methods The MTT assay was used to evaluate cell cytotoxicity and MDR reversal effect. Drug efflux and intracellular drug accumulation were measured by flow cytometry. The H460/MX20 cell xenograft model was established to evaluate the enhancement of anticancer efficacy of topotecan by dacomitinib in vivo. To ascertain the interaction of dacomitinib with the substrate binding sites of ABCG2, the competition of dacomitinib for photolabeling of ABCG2 with [125I]- iodoarylazidoprazosin (IAAP) was performed. Vanadate-sensitive ATPase activity of ABCG2 was measured in the presence of a range of different concentrations of dacomitinib to evaluate the effect of dacomitinib on ATP hydrolysis as the energy source of the transporter. A flow cytometry-based assay and western blotting were employed to study whether dacomitininb could inhibit the expression level of ABCG2. The mRNA expression levels of ABCG2 were analyzed by real-time quantitative RT-PCR. The protein expression level of AKT, ERK and their phosphorylations were detected by Western blotting. Results Here, we found that dacomitinib, an irreversible pan-ErbB tyrosine kinase inhibitor (TKI) in phase III clinical trial, could enhance the efficacy of conventional chemotherapeutic agents specifically in ABCG2-overexpressing MDR cancer cells but not in the parental sensitive cells. Dacomitinib was found to significantly increase the accumulation of ABCG2 probe substrates [doxorubicin (DOX),Rhodamine 123 (Rho 123) and Hoechst 33342] by inhibiting the transporter efflux function. Moreover, dacomitinib stimulated ABCG2 ATPase activity and competed with [125I]-IAAP photolabeling of ABCG2 in a concentration-dependent manner. However, dacomitinib did not alter ABCG2 expression at protein and mRNA levels or inhibit ErbB downstream signaling of AKT and ERK. Importantly, dacomitinib significantly enhanced the efficacy of topotecan in ABCG2-overexpressing H460/MX20 cell xenografts in nude mice without incurring additional toxicity. Conclusions These results suggest that dacomitinib reverses ABCG2-mediated MDR by inhibiting ABCG2 efflux function and increasing intracellular accumulation of anticancer agents. Our findings advocate further clinical investigation of combinations of dacomitinib and conventional chemotherapy in cancer patients with ABCG2-overexpressing MDR tumors.

Background/Aims: Previous studies have suggested that autophagy is activated in distinct cerebrovascular diseases, including stroke. However, the underlying regulatory mechanism of autophagy under stroke remained elusive. Accumulating evidence indicates that dysfunctions of microRNAs (miRNAs) are involved in the pathological process of stroke. Therefore, this study was taken to identify the effect of microRNA-9a-5p (miR-9a-5p) on autophagy in rats following stroke. Methods: The rat model of focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) surgery; The neurological outcomes were defined by neurological evaluation and infarct volume; The western blotting and immunofluorescence assays were used to detected the protein levels of microtubule-associated protein 1 light chain 3 (LC3) and autophagy related 5 (ATG5); The mRNA level of miR-9a-5p, LC3 and ATG5 were quantified by real-time RT-PCR; The luciferase activities of ATG5 and miR-9a-5p was detected by luciferase assay. Results: We showed here that the level of miR-9a-5p was decreased in the ischemic region of rats after MCAO. Overexpression of miR-9a-5p by miR-9a-5p agomir reduced infarct volume and alleviated neurological deficit. Moreover, we found that autophagy was activated by miR-9a-5p inhibition and inactivated by miR-9a-5p overexpression both in the MCAO rat and in SY-5Y cell lines, and unchanged by miR-masks as indicated by LC3 expression. Furthermore, the protein level of ATG5 was decreased by miR-9a-5p overexpression, but increased by miR-9a-5p inhibition and unchanged by miR-masks transfection. In addition, the luciferase assay data showed that miR-9a-5p suppressed the luciferase activity of 3’UTR of ATG5, whereas the repressive effect was relieved by mutation of binding sites. Conclusion: Our study demonstrated that miR-9a-5p may play a critical role in regulating the process of autophagy through targeting ATG5 expression, and overexpression of miR-9a-5p may be a potential approach in alleviating ischemia injury induced by MCAO.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Purpose: To investigate the impact of tissue derived biological particles on enzyme-mediated weakened corneas. Methods: Rabbit corneas were treated with enzymes to create an ex vivo ectatic model that simulated representative characteristics of keratoconus (KC). Porcine cornea, cartilage, and lymph node tissues were processed to remove most cellular components and cryomilled into microparticles. The KC corneas were cultured in medium containing the tissue-derived biological particles (TDP) overnight. The mechanical, thermal, ultrastructural changes, and gene expressions of corneal stromal cells were characterized to evaluate the effects of the TDP treatment. Results: The enzyme treatment significantly reduced corneal mechanics and thermal stability, and also disrupted the extracellular matrix ultrastructure. After culturing with TDP medium, the Young’s modulus of the modeled KC corneas increased by ~50%, comparable to normal cornea controls. Similarly, the thermal denaturation temperature of the corneas was restored. These findings also corresponded to a significant increase in collagen fibril density after TDP treatment. Furthermore, corneas cultured in TDP medium significantly downregulated expression of the pro-inflammatory gene Tnfα, and restored the expression of the key keratocyte markers Aldh, keratocan, and biglycan. Conclusions: Tissue-derived biological particles reinforce mechanical and thermal properties of corneal tissue in an ex vivo model of KC. Through this study, we demonstrate and characterize the previously unexplored impact of tissue-derived biological scaffolds on corneal biomechanics, thermal stability, and gene expression, presenting a potential new therapy for ocular disease.

Abscisic acid (ABA) has been known participate in a wider range of adaptive responses to diverse environmental abiotic stresses such as drought, osmosis, and low temperatures. ABA signaling is initiated by its receptors PYR/PYL/RCARs, a type of soluble proteins with a conserved START domain which can bind ABA and trigger the downstream pathway. Previously, we discovered that poplar (Populus trichocarpa) genome encodes 14 PYR/PYL/RCAR orthologs (PtPYRLs), and two of them, PtPYRL1 and PtPYRL5 have been functionally characterized to positively regulate drought tolerance. However, the physiological function of these ABA receptors in poplar remains uncharacterized. Here, we generated transgenic poplar plants overexpressing PtPYRL1 and PtPYRL5 and found that they exhibited more vigorous growth and produced greater biomass when exposed to drought stress. The improved drought tolerance was positively correlated with the key physiological responses dictated by the ABA signaling pathway, including increase in stomatal closure and decrease in leaf water loss. Further analyses revealed that overexpression lines showed improved capacity in scavenging reactive oxygen species and enhanced the activation of antioxidant enzymes under drought stress. Moreover, overexpression of PtPYRL1 or PtPYRL5 significantly increased the poplar resistance to osmotic and cold stresses. In summary, our results suggest that constitutive expression of PtPYRL1 and PtPYRL5 significantly enhances the resistance to drought, osmotic and cold stresses by positively regulating ABA signaling in poplar.

In this article, we modeled image target tracking into reinforcement learning framework, and we proposed a two-step reinforcement learning algorithm for target tracking. In this algorithm, we set multiple tracker agent to track the pixel of target, the intention of reinforcement learning is to achieve tracking strategy of every tracker agent, we divided each learning step of tracker into two parts, one is to learn the division strategy, another is to learn the action strategy, every tracker agent shares the experiences they have learned. Simulation experimental results illustrate the feasibility and effectiveness of the algorithm.

Multiple-phase fluids’ simulation and 3D visualization comprise an important cooperative visualization subject between fluid dynamics and computer animation. Interactions between different fluids have been widely studied in both physics and computer graphics. To further the study in both areas, cooperative research has been carried out; hence, a more authentic fluid simulation method is required. The key to a better multiphase fluid simulation result is surface extraction. Previous works usually have problems in extracting surfaces with unnatural fluctuations or detail missing. Gaps between different phases also hinder the reality of simulation. In this paper, we propose a unified surface extraction approach integrated with a modified density model for the particle-based multiphase fluid simulation. We refine the original asymmetric smoothing kernel used in the color field and address a binary tree scheme for surface extraction. Besides, we employ a multiphase fluid framework with modified density to eliminate density deviation between different fluids. With the methods mentioned above, our approach can effectively reconstruct the fluid surface for particle-based multiphase fluid simulation. It can also resolve the issue of overlaps and gaps between different fluids, which has widely existed in former methods for a long time. The experiments carried out in this paper show that our approach is able to have an ideal fluid surface condition and have good interaction effects.

Background and objective Hsp90 is a major molecular chaperone, which overexpression is involved in oncogenesis, development and drug resistance in many human cancers. The aim of this study is to investigate the relationship between the GGA-induced overexpression of Hsp90 and chemoresistance to Cisplatin in SPCA-1 and H446 cell line. Methods The protein expressions of Hsp90 induced by GGA at different concentrations were analyzed by Immunofluorescence and Western blotting. Cells survival to Cisplatin was determined using the MTT assays. The effect of Hsp90 expression on the drug resistance to Cisplatin in two Cell Lines was analyzed. Results Compared with the respective control cells, Hsp90 expressions in both experimental cell lines were up-regulated obviously, exhibiting a dose-dependent manner to GGA. MTT assays revealed that the IC50s of cisplatin also showed a substantial elevation for the experimental cells of SPCA-1 and H446, and this elevation was also associated with GGA concerntration. Conclusion GGA is effective for the induction of Hsp90 in the SPCA-1 and H446 cell line. Up-regulated Hsp90 is associated with the chemoresistance to Cisplatin in SPCA-1and H446 cells.