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Abstract The RON receptor tyrosine kinase is critical in the pathogenesis of various cancer types, however, its role in bladder cancer invasive growth is still largely unknown. Here, we found that over 90% of bladder cancer samples exhibit elevated levels of RON expression, with significantly higher expression levels observed in invasive bladder cancer compared to non-invasive bladder cancer. In vitro, RON activation resulted in increased bladder cancer cell migration and invasiveness. Results from mRNA sequencing and transcriptome analysis further demonstrated that MMP12, a downstream molecule of RON, is functionally involved in regulating RON-mediated bladder cancer cell migration and invasiveness. The underlying mechanism appeared to be the RON-mediated inhibition of HIF-2α ubiquitination, which is channeled through the activation of the JNK signaling pathway. Consequently, the activated JNK pathway increased MMP12 expression, ultimately driving bladder cancer cell migration and invasion. As evident in bioinformatics and dual-luciferase reporter assays, the RON mRNA at its 3′-untranslated regions specifically interacted with hsa-miR-659-3p. The binding of hsa-miR-659-3p downregulated the RON gene expression, attenuating the receptor-mediated tumorigenic activities of bladder cancer cells in vitro and in vivo. In conclusion, aberrant RON expression in bladder cancer cells and MMP12 and HIF-2α activities form a functional axis that causes increased bladder cancer cell migration and invasion. The fact that hsa-miR-659-3p downregulates RON expression indicates its critical role in attenuating RON-mediated tumorigenic effect on bladder cancer cells. These findings highlight the importance of RON targeting as a therapeutic means for potential bladder cancer therapy.

Abstract Previous hospitality research typically focuses on consumers’ positive attitudes and intentions toward addressing an existing research gap in the literature on consumer attitude and behaviour in green hotel marketing. Those studies have frequently neglected to investigate the effects of negative attitudes and perspectives. This study aims to explore the relationships between seven indicators of perceived risk, familiarity, novelty, trust, attitude, subjective norm, perceived behavioural control, and intention to visit green hotels. A total of 606 questionnaires were collected and analysed using structural equation modelling. Results showed that perceived risk negatively influences trust, subjective norm, and perceived behavioural control. Familiarity positively influences perceived risk but negatively influences attitude. Novelty negatively influences perceived risk and attitude, while trust positively influences attitude and intention. Subjective norm positively influences attitude, perceived behavioural control, and intention, and attitude influences intention. This study provides an alternative negative factor perspective on green hotel visitation using a theoretically driven approach.

Abstract Accumulating evidences are challenging the paradigm that methane in surface water primarily stems from the anaerobic transformation of organic matters. Yet, the contribution of oxygenic photosynthetic bacteria, a dominant species in surface water, to methane production remains unclear. Here we show methanogenesis triggered by the interaction between oxygenic photosynthetic bacteria and anaerobic methanogenic archaea. By introducing cyanobacterium Synechocystis PCC6803 and methanogenic archaea Methanosarcina barkeri with the redox cycling of iron, CH4 production was induced in coculture biofilms through both syntrophic methanogenesis (under anoxic conditions in darkness) and abiotic methanogenesis (under oxic conditions in illumination) during the periodic dark-light cycles. We have further demonstrated CH4 production by other model oxygenic photosynthetic bacteria from various phyla, in conjunction with different anaerobic methanogenic archaea exhibiting diverse energy conservation modes, as well as various common Fe-species. These findings have revealed an unexpected link between oxygenic photosynthesis and methanogenesis and would advance our understanding of photosynthetic bacteria’s ecological role in the global CH4 cycle. Such light-driven methanogenesis may be widely present in nature.

Androgen deprivation therapy (ADT) has long been the only treatment for metastatic hormone-sensitive prostate cancer (mHSPC). In recent years, with the use of docetaxel chemotherapy and the emergence of various novel hormone therapy drugs, such as Abiraterone, Enzalutamide, Apalutamide, Darolutamide, and Rezvilutamide, the treatment strategies for mHSPC have been greatly changed. Furthermore, local treatment has been added to the treatment of low tumor burden mHSPC and triple therapy has been regarded as an important treatment choice for high tumor burden mHSPC. The survival rate of mHSPC patients has increased significantly and the quality of life also improved with these new treatment strategies. This article reviews the latest advances and controversies in the current treatment of mHSPC. Ongoing clinical trials are introduced and further directions are also discussed in this mini-review.

Abstract It has been previously shown that devices based on microbial biofilms can generate hydrovoltaic energy from water evaporation. However, the potential of hydrovoltaic energy as an energy source for microbial growth has remained unexplored. Here, we show that the electroautotrophic bacterium Rhodopseudomonas palustris can directly utilize evaporation-induced hydrovoltaic electrons for growth within biofilms through extracellular electron uptake, with a strong reliance on carbon fixation coupled with nitrate reduction. We obtained similar results with two other electroautotrophic bacterial species. Although the energy conversion efficiency for microbial growth based on hydrovoltaic energy is low compared to other processes such as photosynthesis, we hypothesize that hydrovoltaic energy may potentially contribute to microbial survival and growth in energy-limited environments, given the ubiquity of microbial biofilms and water evaporation conditions.

Purpose: To quantify interocular differences in the retinal microvasculature between disparate eyes and explore associations between the retinal microvasculature and visual field abnormalities within the same asymmetric thyroid-associated ophthalmopathy (TAO) patients. Methods: Within the same asymmetric TAO eye, the eye with a severer visual field abnormality (based on the mean deviation [MD]) was considered a severe eye, and the fellow eye was considered mild. The densities of radial peripapillary capillary (RPC) and superficial retinal capillary plexuses (SRCP) were determined using optical coherence tomography angiography. Interocular differences in RPC and SRCP densities were analyzed. A generalized estimating equation (GEE) was used to form a predictive model for visual field abnormalities. Pearson's correlation was used to show the correlation between MD and the densities of RPC and SRCP. Results: In 57 asymmetric TAO patients, the global RPC density in severe eyes was lower than that in mild eyes (P < 0.001), but there was no significant difference in SRCP density between the two groups (P = 0.114). In a multivariate GEE model with MD as the outcome, MD was associated only with global RPC density (coefficient β=0.327, P < 0.001). The global RPC density was correlated with MD (r = 0.360, P = 0.003) in severe eyes, but not in mild eyes (r = 0.179, P = 0.092). No significant correlation was observed between global SRCP density and MD in either group (Both P > 0.05). Conclusions: RPC density decreased significantly and correlated with visual field abnormalities in severe eyes of TAO patients. Alterations in RPC density may contribute to visual field abnormalities in TAO eyes.

Fujian Province, China was chosen as the study area for estimating the marginal agricultural abatement costs within the province based on data for 2010-2020. The study employed these estimations as a pivotal factor affecting the efficiency of carbon emissions reduction, constructed an index model to gauge the potential of agricultural carbon emissions reduction, and delved into the urban agricultural carbon emissions reduction potential from the perspectives of economic development rights (equity) and carbon emissions reduction difficulty (efficiency). Our findings indicated a marked regional disparity in the marginal abatement costs of agriculture across Fujian Province, with the highest recorded at EUR 1.3771 × 108 per 104 tonnes and the lowest at EUR 0.6526 × 108 per 104 tonnes, albeit demonstrating general upward inter-annual trends. Furthermore, the assessment of agricultural carbon emissions reduction potential, grounded in the principles of equity and efficiency, revealed four distinct developmental tiers. Resource allocation pathways for carbon emissions reduction were subsequently delineated, informed by the stratification of high- and low-carbon emissions reduction potential indices alongside typological characteristics. The outcomes of this study offer strategic guidance to the government of Fujian Province in crafting suitable carbon emissions reduction strategies and in devising targeted action plans aimed at achieving the twin goals of 'carbon peaking' and 'carbon neutrality'.

The conventional passivity-based controller design of LCL-type grid-connected inverters can ensure the stability of the inverter-grid system, but cannot guarantee sufficient stability margin. Harmonic resonance caused by insufficient phase margin at the intersection of inverter output admittance and grid admittance can degrade power quality. To address this issue, this article proposes an admittance shaping method based on capacitor voltage feedforward and control delay reduction to passivate the output admittance up to the Nyquist frequency with satisfactory passivity margin for both inverter-side and grid-side current-controlled LCL-type grid-connected inverters. It is found that the controller parameter design problem for making the inverter comply with the passivity margin criterion can be formulated as a bilevel optimization problem. A nested black widow optimization algorithm is developed to solve this bilevel optimization problem, which can automatically design a passive output admittance with desired passivity margin for both inverter-side and grid-side current control by optimizing the gain of current regulator and capacitor voltage feedforward and the control delay of the corresponding paths, so that the system has sufficient phase margin regardless of inductive grid conditions. Experimental results verify the effectiveness of the proposed method.

The consumption value seems to be insufficient to explain consumers' domestic electric vehicle purchase behaviour, especially in a highly competitive global environment. This study aims to investigate how consumer ethnocentrism and perceived interactivity influence consumption value and pro-environmental value, subsequently affecting attitude and intention. A total of 353 valid questionnaires were collected through convenience sampling in Xuzhou, China, and the partial least square (PLS) path modelling approach was performed to test the hypotheses. The results show that consumer ethnocentrism and perceived interactivity positively influence function value, emotional value, and social value; perceived interactivity also positively influences altruistic value, biospheric value, and collectivistic value. Function value, social value, and collectivistic value positively influence attitude; however, emotional value, altruistic value and biospheric value did not find a correlation with attitude. Furthermore, attitude positively influences intention to adopt domestic electric vehicles. Finally, the theoretical and practical implications, as well as limitations were discussed accordingly.

Inverter-side current (ISC) control has been widely used in LCL-type grid-connected inverters due to its cost-effectiveness. However, the ISC-controlled inverters suffer from instability and injected grid current distortion under weak grid conditions, such as grid impedance variations and background harmonics. To solve these problems, this article presents an admittance shaping scheme based on capacitor voltage feedforward (CVF) for ISC-controlled LCL-type grid-connected inverters. A delay compensated proportional CVF method is used to shape the inverter output admittance to be passive almost up to the Nyquist frequency. Then, another high-pass filter-based CVF method is employed to shape the grid harmonic admittance to greatly reduce the admittance magnitude at the harmonic frequencies. Thanks to the proposed admittance shaping scheme, the ISC-controlled inverter system can operate stably regardless of the grid impedance and has excellent grid-current harmonic suppression capability. The effectiveness of the proposed admittance shaping scheme is verified by detailed simulation and experimental results.

A novel design for hierarchical-porous acoustic metamaterials (HPAM) is proposed to enhance the functionality of Helmholtz-type resonators and porous materials, achieving continuous and efficient broadband sound absorption. This method can potentially eliminate absorption valley and improve the coupling strength through a synergistic energy dissipation mechanism and hybrid impedance matching behavior. Excellent sound-absorbing capability of the elaborately crafted HPAM was demonstrated analytically, numerically, and experimentally. Specifically, the results revealed an impressive average absorption coefficient of 0.77, with 73 % of the α points exceeding 0.8 across the entire test frequency range. Furthermore, the sound absorption of HPAM can be further optimized to attain ultra-broadband properties by modifying the hierarchical configuration and composite design of the porous materials. The physical mechanism is revealed through the integration of the hierarchical scaling effect and the energy-trapped mode. Numerical simulations revealed the emergence of three distinct absorption peaks at frequencies of 0.76, 1.4, and 3.6 kHz, respectively, and the effective absorption spectrum exceeded 3.4 kHz. Overall, the proposed design highlights the role of hierarchical structures and porous materials in synthesizing superior sound-absorbing properties that fully elucidate the relationship between structure and performance, and provide an avenue for potential noise-control applications.

Energy management strategy (EMS), as a core technology in fuel cell vehicles (FCVs), profoundly influences the lifespan of fuel cells and the economy of the vehicle. Aiming at the problem of the EMS of FCVs based on a global optimization algorithm not being applicable in real-time, a rule extraction-based EMS is proposed for fuel cell commercial vehicles. Based on the results of the dynamic programming (DP) algorithm in the CLTC-C cycle, the deep learning approach is employed to extract output power rules for fuel cell, leading to the establishment of a rule library. Using this library, a real-time applicable rule-based EMS is designed. The simulated driving platform is built in a CARLA, SUMO, and MATLAB/Simulink joint simulation environment. Simulation results indicate that the proposed strategy yields savings ranging from 3.64% to 8.96% in total costs when compared to the state machine-based strategy.

Abstract Objectives Gut microbiota is relevant to the pathogenesis of mental disorders including depression. This study aimed to investigate the influence of fluoxetine (FLX) on the gut microbiota in rats with Chronic Unpredictable Mild Stresses (CUMS)-induced depression. Results We confirmed that the 28-day CUMS-induced depression rat model. Chronic FLX administration weakly improved depressive-like behaviors in rats. Illumina 16S rRNA gene sequencing on rat feces showed CUMS increased the relative abundance of Firmicutes (60.31% vs. 48.09% in Control, p

Abstract A critical challenge of existing cancer vaccines is to orchestrate the demands of antigen‐enriched furnishment and optimal antigen‐presentation functionality within antigen‐presenting cells (APCs). Here, a complementary immunotherapeutic strategy is developed using dendritic cell (DC)‐tumor hybrid cell‐derived chimeric exosomes loaded with stimulator of interferon genes (STING) agonists (DT‐Exo‐STING) for maximized tumor‐specific T‐cell immunity. These chimeric carriers are furnished with broad‐spectrum antigen complexes to elicit a robust T‐cell‐mediated inflammatory program through direct self‐presentation and indirect DC‐to‐T immunostimulatory pathway. This chimeric exosome‐assisted delivery strategy possesses the merits versus off‐the‐shelf cyclic dinucleotide (CDN) delivery techniques in both the brilliant tissue‐homing capacity, even across the intractable blood–brain barrier (BBB), and the desired cytosolic entry for enhanced STING‐activating signaling. The improved antigen‐presentation performance with this nanovaccine‐driven STING activation further enhances tumor‐specific T‐cell immunoresponse. Thus, DT‐Exo‐STING reverses immunosuppressive glioblastoma microenvironments to pro‐inflammatory, tumoricidal states, leading to an almost obliteration of intracranial primary lesions. Significantly, an upscaling option that harnesses autologous tumor tissues for personalized DT‐Exo‐STING vaccines increases sensitivity to immune checkpoint blockade (ICB) therapy and exerts systemic immune memory against post‐operative glioma recrudesce. These findings represent an emerging method for glioblastoma immunotherapy, warranting further exploratory development in the clinical realm.

Abstract Aims Caused by multiple risk factors, heavy burden of major depressive disorder (MDD) poses serious challenges to public health worldwide over the past 30 years. Yet the burden and attributable risk factors of MDD were not systematically known. We aimed to reveal the long-term spatio-temporal trends in the burden and attributable risk factors of MDD at global, regional and national levels during 1990–2019. Methods We obtained MDD and attributable risk factors data from Global Burden of Disease Study 2019. We used joinpoint regression model to assess the temporal trend in MDD burden, and age–period–cohort model to measure the effects of age, period and birth cohort on MDD incidence rate. We utilized population attributable fractions (PAFs) to estimate the specific proportions of MDD burden attributed to given risk factors. Results During 1990–2019, the global number of MDD incident cases, prevalent cases and disability-adjusted life years (DALYs) increased by 59.10%, 59.57% and 58.57%, respectively. Whereas the global age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR) and age-standardized DALYs rate (ASDR) of MDD decreased during 1990–2019. The ASIR, ASPR and ASDR in women were 1.62, 1.62 and 1.60 times as that in men in 2019, respectively. The highest age-specific incidence, prevalence and DALYs rate occurred at the age of 60–64 in women, and at the age of 75–84 in men, but the maximum increasing trends in these age-specific rates occurred at the age of 5–9. Population living during 2000–2004 had higher risk of MDD. MDD burden varied by socio-demographic index (SDI), regions and nations. In 2019, low-SDI region, Central sub-Saharan Africa and Uganda had the highest ASIR, ASPR and ASDR. The global PAFs of intimate partner violence (IPV), childhood sexual abuse (CSA) and bullying victimization (BV) were 8.43%, 5.46% and 4.86% in 2019, respectively. Conclusions Over the past 30 years, the global ASIR, ASPR and ASDR of MDD had decreased trends, while the burden of MDD was still serious, and multiple disparities in MDD burden remarkably existed. Women, elderly and populations living during 2000–2004 and in low-SDI regions, had more severe burden of MDD. Children were more susceptible to MDD. Up to 18.75% of global MDD burden would be eliminated through early preventing against IPV, CSA and BV. Tailored strategies-and-measures in different regions and demographic groups based on findings in this studywould be urgently needed to eliminate the impacts of modifiable risk factors on MDD, and then mitigate the burden of MDD.

Abstract Congenital heart disease (CHD) is the most common type of birth defect and the main noninfectious cause of death during the neonatal stage. The non-POU domain containing, octamer-binding gene, NONO, performs a variety of roles involved in DNA repair, RNA synthesis, transcriptional and post-transcriptional regulation. Currently, hemizygous loss-of-function mutation of NONO have been described as the genetic origin of CHD. However, essential effects of NONO during cardiac development have not been fully elucidated. In this study, we aim to understand role of Nono in cardiomyocytes during development by utilizing the CRISPR/Cas9 gene editing system to deplete Nono in the rat cardiomyocytes H9c2. Functional comparison of H9c2 control and knockout cells showed that Nono deficiency suppressed cell proliferation and adhesion. Furthermore, Nono depletion significantly affected the mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis, resulting in H9c2 overall metabolic deficits. Mechanistically we demonstrated that the Nono knockout impeded the cardiomyocyte function by attenuating phosphatidyl inositol 3 kinase-serine/threonine kinase (Pi3k/Akt) signaling via the assay for transposase-accessible chromatin using sequencing in combination with RNA sequencing. From these results we propose a novel molecular mechanism of Nono to influence cardiomyocytes differentiation and proliferation during the development of embryonic heart. We conclude that NONO may represent an emerging possible biomarkers and targets for the diagnosis and treatment of human cardiac development defects.

Background: 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) is a polyphenol ellagic compound with a variety of pharmacological effects and has an inhibitory effect on lots of cancers. Objective: To explore the antitumor effects and mechanism of 1,2,3,4,6-Penta-O-galloyl-β-D-glucose on human hepatocellular carcinoma HepG2 cells. Design: A network pharmacology method was first used to predict the possible inhibition of hepatocellular carcinoma growth by 1,2,3,4,6-Penta-O-galloyl-β-D-glucose (β-PGG) through the p53 signaling pathway. Next, the Cell Counting Kit (CCK-8) assay was performed to evaluate changes in the survival rate of human hepatocellular carcinoma HepG2 cells treated with different concentrations of the drug; flow cytometry was used to detect changes in cell cycle, apoptosis, mitochondrial membrane potential (MMP) and intracellular Ca2+ concentration; real-time fluorescence quantification and immunoblotting showed that the expression of P53 genes and proteins associated with the p53 signaling pathway was significantly increased by β-PGG treatment. Reasult: It was found that β-PGG significantly inhibited survival of HepG2 cells, promoted apoptosis, decreased MMP and intracellular Ca2+ concentration, upregulated P53 gene and protein expression, increased CASP3 expression, and induced apoptosis in HepG2 cells. Conclusion: This study has shown that network pharmacology can accurately predict the target of β-PGG’s anti-hepatocellular carcinoma action. Moreover, it was evident that β-PGG can induce apoptosis in HepG2 cells by activating the p53 signaling pathway to achieve its anti-hepatocellular carcinoma effect in vitro.

Abstract Background To assess the accuracy of contrast sensitivity function (CSF) in detecting dysthyroid optic neuropathy (DON) at an early stage in thyroid-associated ophthalmopathy (TAO) patients and to examine potential factors that may be linked to early visual impairments in these individuals. Methods A total of 81 TAO patients (50 non-DON and 31 DON), and 24 control subjects participated in the study. CSF was measured with the quick CSF (qCSF) method. Optical coherence tomography angiography (OCTA) images of the ganglion cell complex layer (GCCL), superficial and deep retinal capillary plexuses (SRCP and DRCP) in a 3 mm diameter area around the macula were evaluated. Results Compared with the controls, the area under the log contrast sensitivity function (AULCSF) and SRCP density were significantly reduced in non-DON and DON patients (all P

In order to improve the efficiency of gearshift controller parameter optimization and obtain a good gearshift controller control effect, this article proposes an optimization method for electric vehicle transmission gearshift controller, and selects dual clutch transmission as the research object that establishes an 11-degree-of-freedom gearshift dynamics model and a feedforward-feedback gearshift control model. The feedforward control is chosen from the target trajectory given by the Legendre pseudo-spectral approach, and the feedback controller is a Gaussian kernel radial basis function neural network controller. The feedback controller performs parameter optimization by the Probabilistic Inference for Learning Control (PILCO) reinforcement learning algorithm to obtain a control strategy that matches the actual gearshift conditions. By comparing how well the main/secondary moving disk can follow the target trajectory during various optimization iterations, it is verified that the algorithm requires only a few experiments to complete the optimization, and the optimized Radial Basis Function Neural Network (RBFNN) control has a better control effect by comparing the results of different iterations. Applying the learned controller to various slope and load circumstances yields data that demonstrate that all can have an obvious optimization effect with good robustness. Additionally, the reinforcement learning technique suggested in this research can be used for various gearshift controller parameter optimization to assist engineers and technicians in increasing the effectiveness of their Research and Development.

While the combination of synthetic and biological systems offers an appealing strategy for solar-to-fuel conversion, such hybrid systems typically suffer from low selectivity. Here, authors integrate a bimetallic alloy with a CdS-containing methanogen for selective CO2 reduction to methane.

While auxin has been implicated in the development of tomato fruit with pointed tips, the mechanism are largely unknown. Here, the authors report variation of a C2H2-type zinc finger transcription factor affects transcription of FUL2, which consequently regulates auxin transport and distribution to determine tomato fruit shape.

AIM: To study the clinical features, microbial spectrum, associated factors and prognosis of endogenous endophthalmitis (EE) in a group of Chinese patients. METHODS: The medical records from 32 eyes of 29 patients diagnosed with EE in Peking Union Medical College Hospital from January 2009 to October 2019 were reviewed. RESULTS: The initial visual acuity (VA) of 30 eyes in this study was worse than 20/400. Twenty-three eyes were diagnosed with fungal endophthalmitis and nine with bacterial endophthalmitis. The most common fungal and bacterial isolates were Candida and Klebsiella pneumoniae, respectively. Several rare fungi and bacteria species were also isolated from our patients, including Cryptococcus, Paecilomyces, Brucella, and Bacillus licheniformis. The leading risk factor for EE was diabetes. The most common extraocular infection locus was genitourinary tract. Vitrectomy was performed on twenty-nine eyes. Eight eyes achieved final VA of 20/400 or better. EE caused by Candida had a better prognosis. CONCLUSION: The visual outcome of EE is based on pathogens and prompt intervention. Early vitrectomy and antimicrobial treatment are beneficial for EE.

Abstract Background CONSTANS (CO) and CONSTANS-LIKE (COL) transcription factors have been known to regulate a series of cellular processes including the transition from the vegetative growth to flower development in plants. However, their role in regulating fruit yield in tomato is poorly understood. Result In this study, the tomato ortholog of Arabidopsis CONSTANS, SlCOL1, was shown to play key roles in the control of flower development and fruit yield. Suppression of SlCOL1 expression in tomato was found to lead to promotion of flower and fruit development, resulting in increased tomato fruit yield. On the contrary, overexpression of SlCOL1 disturbed flower and fruit development, and significantly reduced tomato fruit yield. Genetic and biochemical evidence indicated that SlCOL1 controls inflorescence development by directly binding to the promoter region of tomato inflorescence-associated gene SINGLE-FLOWER TRUSS (SFT) and negatively regulating its expression. Additionally, we found that SlCOL1 can also negatively regulate fruit size in tomato. Conclusions Tomato SlCOL1 binds to the promoter of the SFT gene, down-regulates its expression, and plays a key role in reducing the fruit size.

Recommended travel itinerary planning is an important issue in travel platforms or travel systems. Most research focuses on minimizing the time spent traveling between attractions or the cost of attractions. This study makes four contributions to recommended travel itinerary planning in travel platforms or travel systems. The first contribution is to consider recommended travel itinerary planning which can account for attractions, restaurants, and hotels at the same time. Due to the fact that restaurants and hotels can be repeated on the recommended itinerary, the second contribution is to propose an improved ant colony system (ACS) with repeatedly used nodes for the optimization of travel itinerary planning. In the third contribution, the proposed improved ACS allows repeated use of certain nodes without falling into a pattern of infinitely hovering within a certain interval or over certain nodes, through the interactive operation of a Watch List and a Tabu List. In the fourth contribution, the user satisfaction calculation for restaurants and hotels is also added to the travel itinerary planning in order to fully meet the needs of tourists. The experimental results verify the efficiency of the proposed improved ACS.

Abstract Background Previous studies reported that emodin extracted from Rheum palmatum L. exerts antiproliferation and antimetastatic effects in a variety of human cancer types. However, the role of emodin in hepatocellular carcinoma (HCC) remain unknown. Methods EdU and colony formation assays were performed to evaluate the effects of emodin on proliferation. The mobility capacities of HCC treated with emodin were evaluated using wound healing assay. Transwell invasion and migration assays were performed to evaluate anti-migratory and anti-invasive effects of emodin on HCC. Annexin V-FITC/PI was performed to analyze the apoptosis. PI stain was performed to analyze cell cycle. RNA sequencing technology was used to identify the differentially expressed genes (DEGs) induced by emodin in HCC. The impact of emodin on autophagic flux in HepG2 cells was examined by mCherry-GFP-LC3 analysis. Western blot was used to assess the protein expressions of epithelial-mesenchymal transition (EMT), autophagy, PI3K/AKT/mTOR and Wnt/β-catenin signaling pathway. Results We found that emodin inhibited the growth of HepG2 cells in a dose- and time-dependent manner. In addition, emodin inhibited cell proliferation, induced S and G2/M phases arrest, and promoted apoptosis in HepG2 cells. The migration and invasion of HepG2 cells were also suppressed by emodin. Enrichment analysis revealed that DEGs involved in cell adhesion, cancer metastasis and cell cycle arrest. Moreover, western bolt results show that emodin-induced autophagy promotes Snail and β-catenin degradation. We also found that blocking autophagic flux after emodin treatment caused EMT reversal. Furthermore, the PI3K agonist Y-P 740 significantly reversed the phosphorylation levels of GSK3β and mTOR. These results indicated that emodin induced autophagy and inhibited the EMT in part through suppression of the PI3K/AKT/mTOR and Wnt/β-catenin pathways. Conclusion Our study indicated that emodin inhibited cell metastasis in HCC via the crosstalk between autophagy and EMT.

Objective To explore and analyze on the factors that influence the returning of plateletpheresis donors. Methods A total of 1 302 plateletpheresis donors, selected from 2014 to 2020 in the blood center, were followed up for 1 year, and their re-donations were recorded. The data of factors were analyzed through Univariate analysis and Logistic regression on statistical software. Results From 2014 to 2020, there were 1 302 donors participated first-time plateletpheresis donation, including 1070 males and 232 females, aged 18-55 years old, with an average age (28.69±12.90) of years old. As to the education level, 539 cases were junior high school education level and below, 435 cases senior school or technical secondary school education level, and 328 cases junior college education level and above. Within the 1 302 first-time platelet donors, 16 developed adverse reactions to blood donation. 455 donors donated one dose, and 847 cases donated two doses. 506 were public or permanent employed, and 796 were unemployed. 1 267 were ethnic Hans and 35 were ethnic minorities. 21.81%(284/1 302) returned to donate within one year. Univariate and multivariate Logistic regression analysis showed that gender, age, educational level, whether suffered adverse reactions during the first-time donation, doses of donation, ethnicity and occupations all affected the returning of plateletpheresis donors. Conclusion Plateletpheresis donors with younger age, lower education level, unemployed status, ethnic minorities, no adverse reactions occurring during the first-time donation, and donation history of two doses are more likely to return to donate.

The transform domain provides a useful tool in the field of confidential data hiding and protection. In order to protect and transmit patients’ information and competence, this study develops an amplitude quantization system in a transform domain by hiding patients’ information in an electrocardiogram (ECG). In this system, we first consider a non-linear model with a hiding state switch to enhance the quality of the hidden ECG signals. Next, we utilize particle swarm optimization (PSO) to solve the non-linear model so as to have a good signal-to-noise ratio (SNR), root mean square error (RMSE), and relative root mean square error (rRMSE). Accordingly, the distortion of the shape in each ECG signal is tiny, while the hidden information can fulfill the needs of physiological diagnostics. The extraction of hidden information is reversely similar to a hiding procedure without primary ECG signals. Preliminary outcomes confirm the effectiveness of our proposed method, especially an Amplitude Similarity of almost 1, an Interval RMSE of almost 0, and SNRs all above 30.

ObjectiveThe application of advanced Cognitive Diagnosis Models (CDMs) in the Patient Reported Outcome (PRO) is limited due to its complex statistics. This study was designed to measure resilience using CDMs and its prediction of 6-month Quality of Life (QoL) in breast cancer.MethodsA total of 492 patients were longitudinally enrolled from Be Resilient to Breast Cancer (BRBC) and administered with 10-item Resilience Scale Specific to Cancer (RS-SC-10) and Functional Assessment of Cancer Therapy-Breast (FACT-B). Generalized Deterministic Input, Noisy “And” Gate (G-DINA) was performed to measure cognitive diagnostic probabilities (CDPs) of resilience. Integrated Discrimination Improvement (IDI) and Net Reclassification Improvement (NRI) were utilized to estimate the incremental prediction value of cognitive diagnostic probabilities over total score.ResultsCDPs of resilience improved prediction of 6-month QoL above conventional total score. AUC increased from 82.6–88.8% to 95.2–96.5% in four cohorts (all P < 0.001). The NRI ranged from 15.13 to 54.01% and IDI ranged from 24.69 to 47.55% (all P < 0.001).ConclusionCDPs of resilience contribute to a more accurate prediction of 6-month QoL above conventional total score. CDMs could help optimize Patient Reported Outcomes (PROs) measurement in breast cancer.

Abstract Objective Resilience instruments specific to family caregivers (FCs) in cancer are limited. This study was designed to validate the 10-item Resilience Scale Specific to Cancer (RS-SC-10) in FCs using multidimensional item response theory (MIRT) analysis. Methods 382 FCs were enrolled from Be Resilient to Cancer Program (BRCP) and administered with RS-SC-10 and 36-item Short Form Health Survey (SF-36). MIRT was performed to evaluate item parameters while Generalized Additive Model (GAM) and Latent Profile Analysis (LPA) were performed to test the non-linear relationship between resilience (RS-SC-10) and Quality of Life (QoL, SF-36). Results RS-SC-10 retained 10 items with high multidimensional discrimination, monotonous thresholds and its original two-factor structure (Generic and Shift-Persist). Four latent resilience subgroups were identified and a non-linear dose–response pattern between resilience and QoL was confirmed (per-SD increase OR = 1.62, 95% CI 1.16–2.13, p = 0.0019). Conclusion RS-SC-10 is a brief and suitable resilience instrument for FCs in cancer. The resilience screening of patients and FCs can be performed simultaneously in clinical practice.

PurposeTo quantify the retinal vessel density in thyroid-associated ophthalmology (TAO) patients with visual field (VF) defect and examine its associations with mechanical and system vascular risk factors for underlying pathogenesis of VF defect in TAO.MethodsThe cohort was composed of 62 TAO eyes (39 with VF defect and 23 without VF defect). The pulse pressure (PP), intraocular pressure (IOP), ophthalmic rectus muscular index (MI), superficial retinal capillary plexus (SRCP), radial peripapillary capillary (RPC) density, and other related parameters were measured. The associations among these factors and VF mean deviation (MD) were analyzed.ResultsIn TAO patients with VF defect, reduced RPC density, higher PP, and larger horizontal and vertical MI were found (all P < 0.03) when compared to TAO patients without VF defect. The RPC density was correlated with VF MD value (r = 0.242, P = 0.029), while SRCP density was not (P = 0.419). In univariable general estimating equation (GEE) analysis with RPC density as the outcome, PP and its fluctuation showed a significant association (both P < 0.04). In the final RPC model with multivariable GEE analysis, only PP (β = -0.082, P = 0.029) showed significance while PP fluctuation (P = 0.080) did not.ConclusionsThe elevated PP was correlated with reduced retinal peripapillary perfusion in TAO resulting in VF defect. These data suggested that the system vascular factor may be important in the pathogenesis of reduced retinal perfusion resulting in visual impairment in TAO.

PurposeWe explored whether thyroid-associated ophthalmopathy (TAO) patients without clinical signs of dysthyroid optic neuropathy (DON) would have a selective deficit mediated by S-cone.MethodsThirty-two TAO patients without clinical signs of DON (non-DON, 42.03 ± 9.59 years old) and 27 healthy controls (41.46 ± 6.72 years old) participated in this prospective, cross-sectional study. All observers were tested psychophysically after passing color screening tests and a comprehensive ocular examination. Isolated L-, M-, and S-cone contrast thresholds were measured at 0.5 cyc/deg using Gabor patches. We calculated the area under the receiver operating characteristic (ROC) curve to quantify the ability of chromatic contrast sensitivity to detect the early visual function changes in non-DON patients.ResultsS-cone contrast sensitivity in non-DON patients was found to be lower than that of healthy controls (P < 0.001), whereas the sensitivities to L- and M-cone Gabor patches were similar between these two groups (P = 0.297, 0.666, respectively). Our analysis of the ROC curve revealed that the sensitivity to S-cone had the highest index to discriminate non-DON patients from healthy controls (AUC = 0.846, P < 0.001). The deficit of S-cone was significantly correlated with muscle index in non-DON patients (R = 0.576, P = 0.001).ConclusionThere is a selective S-cone deficit in the early stage of TAO. S-cone contrast sensitivity could serve as a sensitive measure of visual impairments associated with early DON in patients with TAO.