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Flood forecasting using traditional physical hydrology models requires consideration of multiple complex physical processes including the spatio-temporal distribution of rainfall, the spatial heterogeneity of watershed sub-surface characteristics, and runoff generation and routing behaviours. Data-driven models offer novel solutions to these challenges, though they are hindered by difficulties in hyperparameter selection and a decline in prediction stability as the lead time extends. This study introduces a hybrid model, the RS-LSTM-Transformer, which combines Random Search (RS), Long Short-Term Memory networks (LSTM), and the Transformer architecture. Applied to the typical Jingle watershed in the middle reaches of the Yellow River, this model utilises rainfall and runoff data from basin sites to simulate flood processes, and its outcomes are compared against those from RS-LSTM, RS-Transformer, RS-BP, and RS-MLP models. It was evaluated against RS-LSTM, RS-Transformer, RS-BP, and RS-MLP models using the Nash–Sutcliffe Efficiency Coefficient (NSE), Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Bias percentage as metrics. At a 1-h lead time during calibration and validation, the RS-LSTM-Transformer model achieved NSE, RMSE, MAE, and Bias values of 0.970, 14.001m3/s, 5.304m3/s, 0.501% and 0.953, 14.124m3/s, 6.365m3/s, 0.523%, respectively. These results demonstrate the model's superior simulation capabilities and robustness, providing more accurate peak flow forecasts as the lead time increases. The study highlights the RS-LSTM-Transformer model's potential in flood forecasting and the advantages of integrating various data-driven approaches for innovative modelling. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR)-based plasma fatty acids are objective biomarkers of many diseases. Herein, we aim to explore the associations of NMR-based plasma fatty acids with the risk of hepatocellular carcinoma (HCC) and chronic liver disease (CLD) mortality in 252,398 UK Biobank participants. Here we show plasma levels of n-3 poly-unsaturated fatty acids (PUFA) and n-6 PUFA are negatively associated with the risk of incident HCC [HRQ4vsQ1: 0.48 (95% CI: 0.33–0.69) and 0.48 (95% CI: 0.28–0.81), respectively] and CLD mortality [HRQ4vsQ1: 0.21 (95% CI: 0.13–0.33) and 0.15 (95% CI: 0.08–0.30), respectively], whereas plasma levels of saturated fatty acids are positively associated with these outcomes [HRQ4vsQ1: 3.55 (95% CI: 2.25–5.61) for HCC and 6.34 (95% CI: 3.68–10.92) for CLD mortality]. Furthermore, fibrosis stage significantly modifies the associations between PUFA and CLD mortality. This study contributes to the limited prospective evidence on the associations between plasma-specific fatty acids and end-stage liver outcomes. Different fatty acids have been associated to liver diseases. Here, the authors show that plasma levels of different circulating fatty acids are either negatively or positively associated with the risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank cohort. [ABSTRACT FROM AUTHOR]

Objective: The treatment of eosinophilic chronic rhinosinusitis with nasal polyps (E-CRSwNP) remains a challenge due to its complex pathogenesis. Inositol polyphosphate-4-phosphatase type IA (INPP4A), a lipid phosphatase, has been implicated in allergic asthma. However, the expression and function of INPP4A in E-CRSwNP remain unclear. This study aims to investigate the role of INPP4A in macrophages in E-CRSwNP. Methods: We assessed the expression of INPP4A in human and mouse nasal mucosal tissues via immunofluorescence staining. THP-1 cells were cultured and exposed to various cytokines to investigate the regulation of INPP4A expression and its functional role. Additionally, we established a murine nasal polyp (NP) model and administrated an INPP4A-overexpressing lentivirus evaluate its impact on NP. Results: The percentage of INPP4A + CD68 + macrophages among total macrophages decreased in the E-CRSwNP group compared to the control and the non-eosinophilic CRSwNP (NE-CRSwNP) groups, exhibiting an inverse correlation with an increased percentage of CD206 + CD68 + M2 macrophages among total macrophages. Overexpression of INPP4A led to a reduced percentage of THP-1 cells polarizing towards the M2 phenotype, accompanied by decreased levels of associated chemotactic factors including CCL18, CCL22, CCL24, and CCL26. We also validated the involvement of the PI3K-AKT pathway in the function of INPP4A in vitro. Furthermore, INPP4A overexpression in the murine NP model resulted in the attenuation of eosinophilic inflammation in the nasal mucosa. Conclusions: INPP4A deficiency promotes macrophage polarization towards the M2 phenotype, leading to the secretion of chemokines that recruit eosinophils and Th2 cells, thereby amplifying eosinophilic inflammation in E-CRSwNP. INPP4A may exert a suppressive role in eosinophilic inflammation and could potentially serve as a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

In this study, ceramic samples of Bi2Sr2Co2Oy + v wt% B2O3 (v = 0.0, 0.1, 0.2, 0.3, 0.4) were synthesized using the solid state reaction method, and the influence of B2O3 additive on their microstructure and thermoelectric properties were investigated. On one hand, the B2O3 additive acted as a sintering aid, enhancing carrier mobility. On the other hand, B2O3 dispersion served as a nano-second-phase, increasing hetero-interfaces and strengthen phonon scattering, thereby effectively suppressing lattice thermal conductivity. By dual optimization of both electric and thermal transport performance, the Bi2Sr2Co2Oy + 0.3 wt% B2O3 sample achieved a high ZT value (thermoelectric figure of merit) of 0.31 at 923 K, which was improved by approximately 33% compared with the pristine Bi2Sr2Co2Oy sample. [ABSTRACT FROM AUTHOR]

Fibrotic kidney injury from hepatocarcinogenesis seriously impacts treatment effect. Astragaloside IV (AS-IV), an extract of Astragalus membranaceus, has several pharmacological activities, which are useful in the treatment of edema and fibrosis. Nrf2/HO-1 is a key antioxidant stress pathway and help treatment of kidney injury. Smad3 phosphorylation is implicated in hepatocarcinogenesis. Our previous study clarified that Smad3 is differentially regulated by different phosphorylated forms of Smad3 on hepatocarcinogenesis. Therefore, we investigated the contribution of AS-IV on the therapy of kidney fibrosis from hepatocarcinogenesis. And the focus was on whether the phosphorylation of Smad3 and the regulation of Nrf2/HO-1 pathway were involved during AS-IV therapy and whether there is an effect of Nrf2 knockout on the phosphorylation of Smad3. We performed TGF-β1 stimulation on HK-2 cells and intervened with AS-IV. Furtherly, we investigated renal injury of AS-IV on Nrf2 knockout mice during hepatocarcinogenesis and its mechanism of action. On the one hand, in vitro results showed that AS-IV reduced the ROS and α-SMA expression of HK-2 by promoting the expression pSmad3C/p21 of and Nrf2/HO-1 and suppressed the expression of pSmad3L/PAI-1. On the other hand, the in vivo results of histopathological features, serological biomarkers, and oxidative damage indicators showed that Nrf2 knockout aggravated renal injury. Besides, Nrf2 deletion decreased the nephroprotective effect of AS-IV by suppressing the pSmad3C/p21 pathway and promoting the pSmad3L/PAI-1 pathway. The experimental results were as we suspected. And we identify for the first time that Nrf2 deficiency increases renal fibrosis from hepatocarcinogenesis and attenuates the therapeutic effects of AS-IV via regulating pSmad3C/3L signal pathway. [ABSTRACT FROM AUTHOR]

Refractive index sensing is of great significance in biological detection. Especially, all-dielectric metasurfaces can greatly improve the sensitivity of biological detection. However, the Q factor and electric field enhancement of most metasurfaces are generally low, resulting in low sensitivity and figure of merit (FOM). Meanwhile, fabrication tolerances may result in inability to achieve high-performance refractive index sensing. Here, we use finite element method (FEM) simulation to design a conical hole structure on an all-dielectric metasurface. The toroidal dipole resonance based on a conical hole structure can achieve a large-area electric field enhancement and a high Q factor, thereby achieving a sensitivity of 540 nm/RIU and FOM of 154.3. Meanwhile, considering the real fabrication tolerance, the proposed structure can still achieve high-sensitivity sensing when the conical hole structure changes the ellipsoidal structure. Therefore, the high sensitivity, high FOM, and robustness of the proposed structure make it highly significant for practical applications. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review was to describe the characteristics of breast cancer cells prone to developing bone metastasis and determine how they are regulated by the bone microenvironment. Recent Findings: The bone is a site of frequent breast cancer metastasis. Bone metastasis accounts for 70% of advanced breast cancer cases and remains incurable. It can lead to skeletal-related events, such as bone fracture and pain, and seriously affect the quality of life of patients. Breast cancer cells escape from the primary lesion and spread to the bone marrow in the early stages. They can then enter the dormant state and restore tumourigenicity after several years to develop overt metastasis. In the last few years, an increasing number of studies have reported on the factors promoting bone metastasis of breast cancer cells, both at the primary and metastatic sites. Summary: Identifying factors associated with bone metastasis aids in the early recognition of bone metastasis tendency. How to target these factors and minimize the side effects on the bone remains to be further explored. [ABSTRACT FROM AUTHOR]

Carbon trading and new energy markets are two key mechanisms for carbon reduction. However, theoretical analysis cannot reveal the complex links between carbon, green, and grey markets. Therefore, this study resorts to the frequency spillover index to explore the overall and directional connectedness of carbon-energy systems in China. The spillover effect indicates the cross-market propagation of information shocks and the potential ripple effects of specific shocks on system-wide changes. Dynamic spillovers suggest that the role of a certain market is not unchanged. In the time domain, both the overall and directional spillovers are closely related with the trading of carbon allowances and tend to show jumps at the beginning and end of the cycle. In the frequency domain, the short-term effects are much stronger than the medium- and long-term effects on all dimensions of the spillover effect. Comparatively, the grey energy is the main information transmitter at the high frequency, whereas it is the green energy playing such a role at medium and low frequencies. Comparing the overall spillovers on carbon markets, the effect of grey energy exceeds that of green energy. Even so, the carbon market plays an important role in the carbon-energy system with extremely significant effects on green and grey energy stocks at certain periods. The results provide profound implications for the management of carbon markets and portfolio optimization. [ABSTRACT FROM AUTHOR]

In this paper, we consider a type of discrete-time fractional-order complex-valued fuzzy neural networks. First, based on symbolic functions and complex-valued theory, two new inequalities are established to study synchronization problems of networks. Secondly, two simple and original control strategies including linear feedback controller and adaptive controller which can better reduce the control cost, are designed to guarantee quasi-projective synchronization and Mittag-Leffler synchronization of the considered networks, then sufficient synchronization criteria with simplified algebraic conditions are established on the basis of our established lemmas and some inequality techniques. Finally, numerical simulations are given to check effectiveness of the proposed results. [ABSTRACT FROM AUTHOR]

This study proposes a novel hybrid LSTM-SWMM model that integrates the advantages of the SWMM model and the LSTM neural network for the first time. The aim is to build an efficient and rapid model that considers the physical mechanism, in order to effectively simulate urban floods. The results indicate a good agreement between the simulated discharge process of the LSTM-SWMM model and the observed discharge process during the training and testing periods, reflecting the actual rainfall runoff process. The R 2 of the LSTM-SWMM model is 0.969, while the R 2 of the LSTM model is 0.954. Additionally, for a forecasting period of 1, the NSE value of the LSTM-SWMM model is 0.967, representing the highest forecasting accuracy. However, for a forecasting period of 6, the NSE value of the LSTM-SWMM model decreases to 0.939, indicating lower accuracy. As the forecasting period increases, the NSE values consistently decrease, leading to a gradual decrease in accuracy. [ABSTRACT FROM AUTHOR]

Ammonia, as the only high-concentration alkaline gas in the atmosphere, plays an extremely important role in the initial nucleation process of aerosols. A rise in the concentration of NH3 after sunrise has been observed in many areas, known as the "morning peak phenomenon", which is likely related to the dew evaporation process because of the considerable amount of NH4+ present in dew. To investigate and compare the flux and rate of NH3 release from dew evaporation in downtown (WH) and suburban areas (SL), the dew amount and chemical makeup were measured and analyzed in Changchun, in northeastern China, from April to October 2021. The differences in the fraction of NH4+ released as NH3 gas and the NH3 emission flux and rate during the process of dew evaporation between SL and WH were identified. The results showed that the daily dew amount in WH (0.038 ± 0.017 mm) was lower than that in SL (0.065 ± 0.032 mm) (P < 0.01), and the pH in SL (6.58 ± 0.18) was approximately 1 pH unit higher than that in WH (5.60 ± 0.25). SO42−, NO3−, Ca2+ and NH4+ were the main ions in WH and SL. The ion concentration in WH was significantly higher than that in SL (P < 0.05), which was influenced by human activities and pollution sources. A total of 24%-48% NH4+ was released as NH3 gas during dew evaporation in WH, which was lower than the conversion fraction of SL dew (44%-57%). The evaporation rate of NH3 was 3.9–20.6 ng/m2·s (9.9 ± 5.7 ng/m2·s) in WH and 3.3–15.9 ng/m2·s (8.6 ± 4.2 ng/m2·s) in SL. The dew evaporation process makes an important contribution to the NH3 morning peak phenomenon, but it is not the only contributor. [ABSTRACT FROM AUTHOR]

It is of engineering interest to explore recovered shale gas composition and its effects on total gas production trend over a long-term extraction period. However, there are previous experimental studies mostly focused on short term development for small scaled cores, which is less convincing to mimic reservoir-scaled shale production process. In addition, the previous production models mostly failed to account for comprehensive gas nonlinear effects. As a result, in this paper, to illustrate the full-life-cycle production decline phenomenon for shale gas reservoir, dynamic physical simulation was performed for more than 3433 days to simulate shale gas transport out of the formations over a relatively long production period. Moreover, a five-region seepage mathematical model was then developed and was subsequently validated by the experimental results and shale well production data. Our findings show that for physical simulation, both the pressure and production declined steadily at an annual rate of less than 5%, and 67% of the total gas in the core was recovered. These test data supported earlier finding that shale gas is of low flow ability and slow pressure decline in the shale matrices. The production model indicated that free gas accounts for the majority of recovered shale gas at the initial stage. Based on a shale gas well example, free gas extraction makes up 90% of produced total gas. The adsorbed gas constitutes a primary gas source during the later stage. Adsorbed gas contributes more than 50% of the gas produced in the seventh year. The 20-year-cumulative adsorbed gas makes up 21% of the EUR for a single shale gas well. The results of this study can provide a reference for optimizing production systems and adjusting development techniques for shale gas wells throughout the combinations of mathematical modeling and experimental approaches. [ABSTRACT FROM AUTHOR]

The use of gaseous and air-captured CO2 for technical biosynthesis is highly desired, but elusive so far due to several obstacles including high energy (ATP, NADPH) demand, low thermodynamic driving force and limited biosynthesis rate. Here, we present an ATP and NAD(P)H-free chemoenzymatic system for amino acid and pyruvate biosynthesis by coupling methanol with CO2. It relies on a re-engineered glycine cleavage system with the NAD(P)H-dependent L protein replaced by biocompatible chemical reduction of protein H with dithiothreitol. The latter provides a higher thermodynamic driving force, determines the reaction direction, and avoids protein polymerization of the rate-limiting enzyme carboxylase. Engineering of H protein to effectively release the lipoamide arm from a protected state further enhanced the system performance, achieving the synthesis of glycine, serine and pyruvate at g/L level from methanol and air-captured CO2. This work opens up the door for biosynthesis of amino acids and derived products from air. The use of gaseous and air-captured CO2 for technical biosynthesis is highly desired but challenging due to high energy demands. Here, the authors present an ATP and NAD(P)H-free chemoenzymatic system for glycine, serine, and pyruvate biosynthesis by coupling methanol with gaseous and air-captured CO2. [ABSTRACT FROM AUTHOR]

The deployment of the sensor nodes (SNs) always plays a decisive role in the system performance of wireless sensor networks (WSNs). In this work, we propose an optimal deployment method for practical heterogeneous WSNs which gives a deep insight into the trade-off between the reliability and deployment cost. Specifically, this work aims to provide the optimal deployment of SNs to maximize the coverage degree and connection degree, and meanwhile minimize the overall deployment cost. In addition, this work fully considers the heterogeneity of SNs (i.e. differentiated sensing range and deployment cost) and three-dimensional (3-D) deployment scenarios. This is a multi-objective optimization problem, non-convex, multimodal and NP-hard. To solve it, we develop a novel swarm-based multi-objective optimization algorithm, known as the competitive multi-objective marine predators algorithm (CMOMPA) whose performance is verified by comprehensive comparative experiments with ten other state-of-the-art multi-objective optimization algorithms. The computational results demonstrate that CMOMPA is superior to others in terms of convergence and accuracy and shows excellent performance on multimodal multi-objective optimization problems. Sufficient simulations are also conducted to evaluate the effectiveness of the CMOMPA based optimal SNs deployment method. The results show that the optimized deployment can balance the trade-off among deployment cost, sensing reliability and network reliability. The source code is available on https://github.com/iNet-WZU/CMOMPA. [ABSTRACT FROM AUTHOR]

Background: Triple-positive breast cancer (TPBC) is a tumor that simultaneously expresses estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2). Luminal A-like TPBC is a special subtype with a favorable prognosis but benefits less from HER2-targeted therapy. However, little is known about how to identify luminal A-like TPBCs. Therefore, our study aims to explore a clinically feasible method to identify luminal A-like TPBCs using immunohistochemical (IHC) markers. Methods: Our cohort enrolled consecutive 190 patients with early-stage TPBCs diagnosed, treated and followed up in our hospital between 2013 and 2019. Patients whose IHC staining displayed ≥ 50% in both ER and PR scores and B-cell lymphoma 2 (BCL2) positivity were classified as cohort A (n = 64), and the rest were enrolled in cohort B (n = 126). Kaplan–Meier plotter and log-rank test were used to compare the survival difference between cohort A and cohort B and the efficacy of trastuzumab therapy in the two cohorts. Results: The disease-free survival (DFS) of patients in cohort A was significantly better than in cohort B (p = 0.031). In cohort A, there was no statistically significant difference in DFS between patients treated with trastuzumab and those without trastuzumab (p = 0.663). While in cohort B, patients treated with trastuzumab had significantly better DFS than those without trastuzumab (p = 0.032). Multivariate survival analysis showed that cohort A was associated with better DFS(95%CI 1.046–11.776, p = 0.042). Conclusion: TPBCs consist of heterogeneous subtypes. Detecting the expression of ER, PR and BCL2 via IHC can help identify luminal A-like TPBCs. This study will enable individualized treatment of TPBCs. [ABSTRACT FROM AUTHOR]

Water vapor condenses on the surface of ground objects at night with atmospheric particles functioning as condensation nuclei, forming dew, which is a temporary sink of water vapor and pollutants (particles, gases, etc.). Dew is transferred from sink to source in the dew evaporation process, thereby releasing pollutants, which may affect the near-surface atmospheric air quality. Based on the pressure-state-response (PSR) model, this paper established an evaluation index system including 13 indexes to analyze and evaluate the environmental effects of dew evaporation from pressure, state, and response aspects. The synthetic weight method (analytic hierarchy process (AHP) and entropy) was used to obtain parameter weights. The comprehensive evaluation index (E) was determined to quantitatively evaluate the environmental effects of dew evaporation events during the plant growth period (May to October) in the Changchun green area in 2021. The results indicated that the dew evaporation intensity was the lowest in May and June and the highest in September due to the relative humidity (RH) effect. The dry evaporation process was the slowest in July and August due to the wind speed, and the evaporation time lasted up to 5 h. The weights of the pressure, state, and response layers were 0.1072–0.1486, 0.2261–0.2863, and 0.5811–0.6262, respectively. HONO, RH, particles with an aerodynamic diameter equal to or smaller than 10 μm (PM10), NH3, and PM2.5 contributed more than 0.50 to environmental effects. Among these factors, HONO contributed the most, namely 0.1393–0.1975. The average E values were 0.5563 ± 0.1128 and 0.5274 ± 0.0992 at an evaporation intensity lower and higher, respectively, than 0.02 mm. Dew evaporation events could negatively affect the near-surface atmospheric environment. [ABSTRACT FROM AUTHOR]

Due to strong stress sensitivity resulted from unconventional tight formationsit is of practical interest to formulate a reasonable pressure drawdown plan to improve gas extraction recovery. The impact of water-shale interactions on the reservoir permeability was previously ignored in the managed pressure drawdown optimization. The controlled-pressure production dynamic analysis was mostly conducted using numerical simulation, lack of rigorous theoretical support. Hence in this paper, a theoretical production prediction model was proposed and verified with HIS RTA 2015by incorporating multiple pressure drawdown mechanisms and various non-linear gas flow process. The on-site production effects dominated by two different pressure drop methods was further compared, indicating that compared to depressurization production, the production reversion can occur in the controlled pressure production process and the EUR of single well can be increased by about 30% under the control of managed pressure drawdown approach. Finally, the pressure drawdown optimization strategy was carried out on the field test from the both production effect and economic benefits, which demonstrated that the best economic solution can generally be obtained in the early stage of production. The research results can be closely linked to the on-site production practice of shale gas wells, providing insights into designing optimized production strategy scheme. [ABSTRACT FROM AUTHOR]

Precise prediction on vacant parking space (VPS) information plays a vital role in intelligent transportation systems for it helps drivers to find the parking space quickly to reduce unnecessary waste of time and excessive environmental pollution. By analyzing the historical zone-wise VPS data, we find that for the number of VPSs, there is not only a solid temporal correlation within each parking lot, but also an obvious spatial correlation among different parking lots. Given this, this paper proposes a hybrid deep learning framework, known as the dConvLSTM-DCN (dual Convolutional Long Short-Term Memory with Dense Convolutional Network), to make short-term (within 30 min) and long-term (over 30 min) predictions on the VPS availability zone-wisely. Specifically, the temporal correlations of different time scales, namely the 5-min and daily-wise temporal correlations of each parking lot, and the spatial correlations among different parking lots can be effectively captured by the two parallel ConvLSTM components, and meanwhile, the dense convolutional network is leveraged to further improve the propagation and reuse of features in the prediction process. Besides, a two-layer linear network is used to extract the meta-info features to promote the prediction accuracy. For long-term predictions, two methods, namely the direct and iterative prediction methods, are developed. The performance of the prediction model is extensively evaluated with practical data collected from nine public parking lots in Santa Monica. The results show that the dConvLSTM-DCN framework can achieve considerably high accuracy in both short-term and long-term predictions. [ABSTRACT FROM AUTHOR]

The large permanent magnet synchronous machine (PMSM) brings great difficulties in manufacture, assembly, and maintenance. A kind of unwinding stator module-combined permanent magnet synchronous machine (SMCPMSM) is proposed. This structure achieves modular manufacture of large PMSM, convenient for machining, repairing, and replacing. By removing part of the coils, the stator is divided into blocks to achieve this decoupling of the windings between modules. The three-phase winding is symmetrical, and each module can operate independently. This paper describes the SMCPMSM structure and the stator block rule. The winding analysis is performed using the slot electromotive force phasor diagram method. The winding distribution coefficient, winding electromotive force, and magnetomotive force are calculated. The electromagnetic performance is simulated and analyzed. An 80 kW prototype is developed, and its experiments are carried out. The experimental results verify the feasibility and rationality of the proposed SMCPMSM. [ABSTRACT FROM AUTHOR]

Learning performance is an important indicator of online learning, is related to the quality of online education and the performance of students. Previous studies have found that learners' learning performance is related to learning motivation and academic emotion, but the role of non-intellectual factors such as academic emotion has received less attention in empirical research. In order to make up for this gap, this study explored the mediating effect of positive academic emotions on college students' online learning motivation and online learning performance, as well as the differences in mediating effects under different learning methods (i.e., online learning and offline learning). The data comes from 1088 college students who participate in online courses and offline courses in China. This study adopts correlation analysis and multiple mediation analysis to analyze the intermediary effect of online and offline students and multi-group comparisons. The results showed that the (1) online learning motivation is positively affecting online learning performance and positive academic emotions, and positive academic emotions are related to online learning performance. There is also a positive correlation between the dimensions of the three; (2) positive academic emotions part of the intermediary role between college students' online learning motivation and online learning performance; (3) the intermediary effect of positive academic emotions in offline learning is significantly greater than that of online learning. This study is not only conducive to understanding academic emotions, learning motives and learning performance, but also provides important enlightenment online learning performance management in promoting open curriculum construction. [ABSTRACT FROM AUTHOR]

Oversampling is a promising preprocessing technique for imbalanced datasets which generates new minority instances to balance the dataset. However, improper generated minority instances, i.e., noise instances, may interfere the learning of the classifier and impact it negatively. Given this, in this paper, we propose a simple and effective oversampling approach known as ASN-SMOTE based on the k-nearest neighbors and the synthetic minority oversampling technology (SMOTE). ASN-SMOTE first filters noise in the minority class by determining whether the nearest neighbor of each minority instance belongs to the minority or majority class. After that, ASN-SMOTE uses the nearest majority instance of each minority instance to effectively perceive the decision boundary, inside which the qualified minority instances are selected adaptively for each minority instance by the proposed adaptive neighbor selection scheme to synthesize new minority instance. To substantiate the effectiveness, ASN-SMOTE has been applied to three different classifiers and comprehensive experiments have been conducted on 24 imbalanced benchmark datasets. ASN-SMOTE is also extensively compared with nine notable oversampling algorithms. The results show that ASN-SMOTE achieves the best results in the majority of datasets. The ASN-SMOTE implementation is available at: https://www.github.com/yixinkai123/ASN-SMOTE/. [ABSTRACT FROM AUTHOR]

Effective dental care can reduce the incidence of oral diseases (dental caries, dentin sensitivity, tooth discoloration, etc.). However, delayed or inappropriate usage of care tools not only fails to eliminate external adverse stimuli, but sometimes even causes dental injury. Inspired by the traditional culture of "lacquer teeth", a sprayable superhydrophobic protectant (ZFP) composed of ZnO, fluorine modified nano-silica (FSNs), and polydimethylsiloxane (PDMS) is constructed similar to automobile wax, for routine dental protection. With its superhydrophobic properties, this protective membrane can effectively resist the adhesion of bacteria, proteins, and food residues to the teeth surface. Meanwhile, ZFP exerts stable superhydrophobic self-cleaning properties under external mechanical stimulation, temperature alternation, and acidic environment. In addition, ZnO in ZFP can significantly restrain the growth of dental caries-related bacteria (Streptococcus mutans), with an enhanced antibacterial capacity when combined with yellow light irradiation. Both in vivo and in vitro experiments demonstrate that ZFP is a safe, convenient, and quadruplex-effective dental protectant, which is expected to serve as a promising toothpaste companion for joint maintenance of dental health. [ABSTRACT FROM AUTHOR]

Metabolic adaptation is an emerging hallmark of cancer, as it provides tumor cells sufficient energy and metabolic intermediates. Although tumor cells are believed to highly rely on Warburg effect to satisfy their energy demand, more studies have pointed out that various types of tumor cells are highly dependent on oxidative phosphorylation to drive the tumorigenesis. Peroxisome proliferator-activated receptor-c coactivator 1α (PGC1α), the crucial member of PGC1 family, is aberrantly expressed in several cancer types, implicating its role in tumor proliferation, migration, invasion, metastasis, and chemoresistance. Numerous studies have reported that PGC1α participates in the regulation of tumor development by altering the transcriptional programs as well as the metabolic phenotypes. Thus, PGC1α-targeted therapy is therapeutically exploitable to target the metabolic vulnerabilities in tumor cells. This review mainly focuses on the current underlying mechanisms for its roles in regulating metabolic adaptation of tumor cells and its upstream regulators; how PGC1α participates in the regulation of the tumor proliferation, migration, invasion, metastasis, therapy resistance; and the feasibility of PGC1α-targeted therapy for cancer treatment. [ABSTRACT FROM AUTHOR]

Purpose: Paclitaxel, belongs to tubulin-binding agents (TBAs), shows a great efficacy against breast cancer via stabilizing microtubules. Drug resistance limits its clinical application. Here we aimed to explore a role of Polarity protein Par3 in improving paclitaxel effectiveness. Methods: Breast cancer specimens from 45 patients were collected to study the relationship between Par3 expression and paclitaxel efficacy. The Kaplan–Meier method was used for survival analysis. Cell viability was measured in breast cancer cells (SK-BR-3 and T-47D) with Par3 over-expression or knockdown. The flow cytometry assays were performed to measure cell apoptosis and cell cycle. BrdU incorporation assay and Hoechst 33,258 staining were performed to measure cell proliferation and cell apoptosis, respectively. Immunofluorescence was used to detect microtubule structures. Results: Par3 expression was associated with good response of paclitaxel in breast cancer patients. Consistently, Par3 over-expression significantly sensitized breast cancer cells to paclitaxel by promoting cell apoptosis and reducing cell proliferation. In Par3 overexpressing cells upon paclitaxel treatment, we observed intensified cell cycle arrests at metaphase. Further exploration showed that Par3 over-expression stabilized microtubules of breast cancer cells in response to paclitaxel and resists to microtubules instability induced by nocodazole, a microtubule-depolymerizing agent. Conclusion: Par3 facilitates polymeric forms of tubulin and stabilizes microtubule structure, which aggravates paclitaxel-induced delay at the metaphase-anaphase transition, leading to proliferation inhibition and apoptosis of breast cancer cells. Par3 has a potential role in sensitizing breast cancer cells to paclitaxel, which may provide a more precise assessment of individual treatment and novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: Thalamic pain, a neuropathic pain syndrome, frequently occurs after stroke. This research aimed to investigate the effect of dexmedetomidine (DEX) on thalamic pain. Methods: The cellular localization of the TLR4 protein was determined by immunostaining. The expression of Iba1, GFAP and protein associated with the TLR4/NF-κB/ERK1/2 pathway was measured by Western blotting. Continuous pain hypersensitivity was evaluated by behavioural tests. The results were analysed by one-way ANOVA, two-way ANOVA and Tukey's post hoc test. Results: The results demonstrated that DEX obviously alleviated thalamic pain induced by haemorrhage on the ipsilateral side and delayed the development of pain hypersensitivity. Furthermore, the expression levels of Iba1, GFAP and proteins associated with the TLR4/NF-κB/ERK1/2 signalling pathway were greatly increased in mice with thalamic pain, but these effects were reversed by DEX. Conclusion: Our findings suggest that DEX alleviates the inflammatory response during thalamic pain through the TLR4/NF-κB/ERK1/2 signalling pathway and might be a potential therapeutic agent for thalamic pain. [ABSTRACT FROM AUTHOR]

RNA N6-methyladenosine (m6A) modifications are essential in plants. Here, we show that transgenic expression of the human RNA demethylase FTO in rice caused a more than threefold increase in grain yield under greenhouse conditions. In field trials, transgenic expression of FTO in rice and potato caused ~50% increases in yield and biomass. We demonstrate that the presence of FTO stimulates root meristem cell proliferation and tiller bud formation and promotes photosynthetic efficiency and drought tolerance but has no effect on mature cell size, shoot meristem cell proliferation, root diameter, plant height or ploidy. FTO mediates substantial m6A demethylation (around 7% of demethylation in poly(A) RNA and around 35% decrease of m6A in non-ribosomal nuclear RNA) in plant RNA, inducing chromatin openness and transcriptional activation. Therefore, modulation of plant RNA m6A methylation is a promising strategy to dramatically improve plant growth and crop yield. Rice and potato plants are more productive after epitranscriptome engineering. [ABSTRACT FROM AUTHOR]

Super-enhancers (SEs) govern macrophage polarization and function. However, the mechanism underlying the signal-dependent latent SEs remodeling in macrophages remains largely undefined. Here we show that the epigenetic reader ZMYND8 forms liquid compartments with NF-κB/p65 to silence latent SEs and restrict macrophage-mediated inflammation. Mechanistically, the fusion of ZMYND8 and p65 liquid condensates is reinforced by signal-induced acetylation of p65. Then acetylated p65 guides the ZMYND8 redistribution onto latent SEs de novo generated in polarized macrophages, and consequently, recruit LSD1 to decommission latent SEs. The liquidity characteristic of ZMYND8 is critical for its regulatory effect since mutations coagulating ZMYND8 into solid compartments disable the translocation of ZMYND8 and its suppressive function. Thereby, ZMYND8 serves as a molecular rheostat to switch off latent SEs and control the magnitude of the immune response. Meanwhile, we propose a phase separation model by which the latent SEs are fine-tuned in a spatiotemporal manner. Macrophages employ epigenetic remodeling, especially the regulation of superenhancers (SEs), to promote classical polarization and function; whether liquid-liquid phase separation (LLPS) is involved is not known. Here, the authors show the epigenetic reader ZMYND8 forms condensates to deactivate latent SEs in a spatiotemporal manner and thereby restrict macrophage-mediated inflammation. [ABSTRACT FROM AUTHOR]

Learning vector autoregressive models from multivariate time series is conventionally approached through least squares or maximum likelihood estimation. These methods typically assume a fully connected model which provides no direct insight to the model structure and may lead to highly noisy estimates of the parameters. Because of these limitations, there has been an increasing interest towards methods that produce sparse estimates through penalized regression. However, such methods are computationally intensive and may become prohibitively time-consuming when the number of variables in the model increases. In this paper we adopt an approximate Bayesian approach to the learning problem by combining fractional marginal likelihood and pseudo-likelihood. We propose a novel method, PLVAR, that is both faster and produces more accurate estimates than the state-of-the-art methods based on penalized regression. We prove the consistency of the PLVAR estimator and demonstrate the attractive performance of the method on both simulated and real-world data. [ABSTRACT FROM AUTHOR]

Purpose: RC48 contains the novel humanized anti-HER2 antibody hertuzumab conjugated to MMAE via a cleavable linker. A phase I study was initiated to evaluate the toxicity, MTD, PK, and antitumor activity of RC48 in patients with HER2-overexpressing locally advanced or metastatic solid carcinomas, particularly gastric cancer. Patients and methods: This was a 2-part phase I study. Successive cohorts of patients received escalating doses of RC48 (0.1 mg/kg, 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, 2.5 mg/kg, and 3.0 mg/kg). Dose expansion proceeded at the dose of 2.0 mg/kg Q2W. The efficacy and safety set included all patients who received at least one dose of RC48. Results: Fifty-seven patients were enrolled, the MTD was unavailable due to termination of 3.0 mg/kg cohort; 2.5 mg/kg Q2W was declared the RP2D. RC48 was well tolerated, the most frequent grade 3 or worse TRAEs included neutropenia (19.3%), leukopenia (17.5%), hypoesthesia (14.0%), and increased conjugated blood bilirubin (8.8%). Four deaths occurred during the whole study, three of which were believed to be related to RC48. Overall, ORR and DCR were 21.0% (12/57) and 49.1% (28/57). Notably, patients who were HER2 IHC2+/FISH- responded similarly to those who were IHC2+/FISH+ and IHC3+, with ORRs of 35.7% (5/14), 20% (2/10), and 13.6% (3/22), respectively. In patients who were pretreated with HER2-targeted drugs, RC48 also showed promising efficacy, with ORR of 15.0% (3/20) and DCR of 45.0% (9/20). Conclusion: RC48 was well tolerated and showed promising antitumor activity in HER2-positive solid tumors, including gastric cancer with HER2 IHC 2+/FISH- status. Clinical trial information: NCT02881190. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common cause of dementia. Increasing evidence shows that mitochondrial DNA (mtDNA) methylation plays an essential role in many diseases related to mitochondrial dysfunction. Since mitochondrial impairment is a key feature of AD, mtDNA methylation may also contribute to AD, but few studies have addressed this issue. Methylation changes of the mitochondrial cytochrome b (CYTB) and cytochrome c oxidase II (COX II) genes in AD have not been reported. We analyzed mtDNA methylation changes of the CYTB and COX II genes in an APP/PS1 transgenic mouse model of AD using pyrosequencing. We examined mtDNA copy numbers and the levels of expression by quantitative real-time PCR. Average methylation levels of different CpG sites were ≤ 4.0%. Methylated mtDNA accounted for only a small part of the total mtDNA. We also observed hypermethylation of mitochondrial CYTB and COX II genes with decreased mtDNA copy numbers and expression in the hippocampi of APP/PS1 transgenic mice. mtDNA methylation may play an important role in AD pathology, which may open a new window for AD therapy. [ABSTRACT FROM AUTHOR]

We examine whether gold is an effective hedge against inflation over different time horizons. Using a stationary test with a flexible Fourier function, we consider all possible structural breaks with unknown forms and find that real gold returns over horizons ranging from 1 month to 15 years are nonlinear stationary processes. Although the real gold return may deviate from the inflation hedge rate because of holding opportunity cost and insufficient demand, over time it reverts to the long-run hedge rate. The results indicate that gold has generally maintained its purchasing power for the past 39 years. Therefore, gold can be a reliable hedge against inflation in both short and long time horizons. It is reasonable for investors to hold a certain amount of gold to hedge against the risk of inflation or to diversify assets, regardless of holding period. [ABSTRACT FROM AUTHOR]

We examined the association between prenatal fish intake and child autism-related traits according to Social Responsiveness Scale (SRS) and cognitive development scores in two US prospective pregnancy cohorts. In adjusted linear regression analyses, higher maternal fish intake in the second half of pregnancy was associated with increased child autism traits (higher raw SRS scores; ß = 5.60, 95%CI 1.76, 12.97). Differences by fish type were suggested; shellfish and large fish species were associated with increases, and salmon with decreases, in child SRS scores. Clear patterns with cognitive scores in the two cohorts were not observed. Future work should further evaluate potential critical windows of prenatal fish intake, and the role of different fish types in association with child autism-related outcomes. [ABSTRACT FROM AUTHOR]

Proteoglycans (PGs) are composed of a core protein and one or more chains of glycosaminoglycans (GAGs). The highly heterogeneous GAG chains play an irreplaceable role in the functions of PGs. However, the lack of an approach to control the exact structure of GAG chains conjugated to PGs tremendously hinders functional studies of PGs. Herein, by using glypican-3 as a model, we establish an aldehyde tag-based approach to assemble PGs with specific GAG chains on the surface of living cells. We show that the engineered glypican-3 can regulate Wnt and Hedgehog signaling like the wild type. Furthermore, we also present a method for studying the interaction of PGs with their target glycoproteins by combining the assembly of PGs carrying specific GAG chains with metabolic glycan labeling, and most importantly, we obtain evidence of GPC3 directly interacting with Frizzled. In conclusion, this study provides a very useful platform for structural and functional studies of PGs with specific GAG chains. Currently, it is not possible to generate proteoglycans displaying glycosaminoglycan chains with specific structures. Here the authors show that by using an aldehyde tag-based methodology it is possible to insert these specific chains onto proteoglycans expressed on the cell surface. [ABSTRACT FROM AUTHOR]

Spin flash drying equipment is widely used in chemical, food and other fields. Drying process consumes large amounts of energy and reduction in operating cost will be extremely beneficial for the industry. Therefore, in order to improve the efficiency of spin flash dryer. A three-dimensional CFD model of the drying process was established by computational fluid dynamics, and the flow field characteristics and heat transfer mechanism of the drying process were obtained. We studied the specific effects of different parameters on the drying process, and verified the results with calcium carbonate as raw material. The experimental results are basically consistent with the simulation results. The velocity, temperature and pressure in the drying chamber near the wall are greater than those in the central region, which generally decrease with height. The speed of the cutter set has a large effect on the tangential and radial velocity, but the influence on the pressure drop is not significant. Meanwhile the temperature and velocity of inlet air have a greater impact on distribution of flow field and material drying, the variable structure improves the stability of the drying process. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate potential therapeutic effects of IFN-γ primed human umbilical cord mesenchymal stem cell (IFN-γ-hUCMSCs) transplantation on experimental autoimmune encephalomyelitis (EAE) in mice. In this study, EAE mouse model was established by MOG35-55 immunization method. Outcomes of the EAE mice in terms of body weight and clinical symptoms were analyzed. Electromyography (EMG) was performed to evaluate nerve conduction. ELISA was applied to quantify inflammatory cytokine levels in serum. Our results showed that IFN-γ could up-regulate protein expression of indoleamine 2, 3-dioxygenease 1 (IDO1), an important molecule released by MSCs to exert their immune suppressive activity (p < 0.01). In this study treatment efficacy for EAE was compared between transplantation of hUCMSCs alone and the IFN-γ-hUCMSCs which were cultured in the presence of IFN-γ for 48 h prior to be harvested for transplantation. Compared with hUCMSCs alone and control (PBS transfusion) group, transplantation of the IFN-γ-hUCMSCs could significantly alleviate the body weight loss and clinical symptoms of EAE mice (p < 0.05). Consistently EMG latency was significantly improved in treatment groups (p < 0.001), and the IFN-γ-hUCMSCs group was even better than the hUCMSCs group (p < 0.05). Moreover, the concentrations of IL-17A and TNF-α in serum of the mice treated by IFN-γ-hUCMSCs were significantly lower than hUCMSCs alone and controls, respectively (p < 0.05). In few of the roles of IL-17A and TNF-α in the pathogenesis of EAE, IFN-γ-hUCMSCs treatment associated-suppression of IL-17A and TNF-α expression may contribute in part to their therapeutic effects on EAE. In sum, our study highlights a great clinical potential of IFN-γ-hUCMSCs for multiple sclerosis (MS) treatment. [ABSTRACT FROM AUTHOR]

A salt-tolerant denitrifying bacterium strain F2 was isolated from seawall muddy water in Dalian City, Liaoning Province, China. Strain F2 was identified by morphological observations, physiological and biochemical characteristics and 16 S rDNA identification. The salt tolerance of strain F2 was verified and the factors affecting the removal ability of strain F2 to nitrous nitrogen (NO2–N) and nitrate nitrogen (NO3–N) in saline conditions were investigated. Strain F2 was identified as Alishewanella sp., named Alishewanella sp. F2. Strain F2 can tolerate NaCl concentrations up to 70 g/L, and its most efficient denitrification capacity was observed at NaCl concentrations of 0−30 g/L. In the medium with NaCl concentrations of 0−30 g/L, strain F2 exhibited high removal efficiencies of NO2–N and NO3–N, with the removal percentages for both NO2–N and NO3–N of approximately 99%. In saline conditions with 30 g/L NaCl, the optimum culture pH, NaNO2 initial concentrations and inoculation sizes of strain F2 were 8−10, 0.4−0.8 g/L and 5−7%, respectively. Strain F2 was highly effective in removing NO2–N and NO3–N in saline conditions, and it has a good application potential in saline wastewater treatment. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the practical potential of using constructed wetlands (CWs) for treating saline wastewater containing various heavy metals. The results demonstrated that CWs growing Canna indica with porous slag as substrate could efficiently remove heavy metals (Cu, Zn, Cd, and Pb) from saline wastewater at an electrical conductivity (EC) of 7 mS/cm, especially under low influent load. Salts with salinity level (characterized as EC) of 30 mS/cm suppressed the removal of some heavy metals, dependent on heavy metal species and their influent concentrations. The presence of salts in CWs can improve the accumulation of Cu, Zn, and Pb in plant tissues as compared to control treatment, irrespective of metal concentrations in solution. The influence of salts on Cd accumulation depended on both salinity levels and Cd concentrations in solution. Although more heavy metals were accumulated in roots than in shoots, the harvesting of aboveground plant materials is still efficient addition for heavy metal removal due to the greater biomass and growth rate of aboveground plant material. Furthermore, replacing all plants instead of preserving roots from harvested plants in CWs over a period of time is essential for heavy metal removal, because the continued accumulation by roots can be inhibited by the increasing accumulated heavy metals from saline wastewater. [ABSTRACT FROM AUTHOR]

Purpose: The bag of visual words (BoVW) model is a powerful tool for feature representation that can integrate various handcrafted features like intensity, texture, and spatial information. In this paper, we propose a novel BoVW-based method that incorporates texture and spatial information for the content-based image retrieval to assist radiologists in clinical diagnosis. Methods: This paper presents a texture-specific BoVW method to represent focal liver lesions (FLLs). Pixels in the region of interest (ROI) are classified into nine texture categories using the rotation-invariant uniform local binary pattern method. The BoVW-based features are calculated for each texture category. In addition, a spatial cone matching (SCM)-based representation strategy is proposed to describe the spatial information of the visual words in the ROI. In a pilot study, eight radiologists with different clinical experience performed diagnoses for 20 cases with and without the top six retrieved results. A total of 132 multiphase computed tomography volumes including five pathological types were collected. Results: The texture-specific BoVW was compared to other BoVW-based methods using the constructed dataset of FLLs. The results show that our proposed model outperforms the other three BoVW methods in discriminating different lesions. The SCM method, which adds spatial information to the orderless BoVW model, impacted the retrieval performance. In the pilot trial, the average diagnosis accuracy of the radiologists was improved from 66 to 80% using the retrieval system. Conclusion: The preliminary results indicate that the texture-specific features and the SCM-based BoVW features can effectively characterize various liver lesions. The retrieval system has the potential to improve the diagnostic accuracy and the confidence of the radiologists. [ABSTRACT FROM AUTHOR]

This paper estimates information stickiness with regard to inflation expectations in the United States and the Eurozone for the 1981/06-2015/12 and 1998/Q4-2015/Q2 periods, respectively, and further investigates whether such information stickiness is state-dependent. Based on a bootstrap sub-sample rolling-window estimation, we find that information stickiness varies over time, which contradicts the strict time dependency implied under sticky-information theory. We provide evidence that information stickiness depends on inflation volatility, which indicates that information stickiness is state-dependent and that it has a time trend. Using a threshold model, we estimate structural changes in the state-dependence and time-trend of information stickiness. The results show that information stickiness has been more dependent on inflation volatility and has had a higher time-trend in both regions following the 2008 financial crisis. [ABSTRACT FROM AUTHOR]

We have demonstrated the improved performance of oxygen evolution reactions (OER) using Au/nickel phosphide (NiP) core/shell nanoparticles (NPs) under basic conditions. NPs with a NiP shell and a Au core, both of which have well-defined crystal structures, have been prepared using solution-based synthetic routes. Compared with pure NiP NPs and Au-NiP oligomer-like NPs, the core/shell crystalline structure with Au shows an improved OER activity. It affords a current density of 10 mA/cm at a small overpotential of 0.34 V, in 1 M KOH aqueous solution at room temperature. This enhanced OER activity may relate to the strong structural and effective electronic coupling between the single-crystal core and the shell. [ABSTRACT FROM AUTHOR]

Lignocellulosic biomass from various types of wood has become a renewable resource for production of biofuels and biobased chemicals. Because xylan is the major component of wood hemicelluloses, highly efficient enzymes to enhance xylan hydrolysis can improve the use of lignocellulosic biomass. In this study, a xylanolytic gene cluster was identified from the crude oil-degrading thermophilic strain Geobacillus thermodenitrificans NG80-2. The enzymes involved in xylan hydrolysis, which include two xylanases (XynA1, XynA2), three β-xylosidases (XynB1, XynB2, XynB3), and one α- l-arabinofuranosidase (AbfA), have many unique features, such as high pH tolerance, high thermostability, and a broad substrate range. The three β-xylosidases were highly resistant to inhibition by product (xylose) accumulation. Moreover, the combination of xylanase, β-xylosidase, and α- l-arabinofuranosidase exhibited the largest synergistic action on xylan degradation (XynA2, XynB1, and AbfA on oat spelt or beechwood xylan; XynA2, XynB3, and AbfA on birchwood xylan). We have demonstrated that the proposed enzymatic cocktail almost completely converts complex xylan to xylose and arabinofuranose and has great potential for use in the conversion of plant biomass into biofuels and biochemicals. [ABSTRACT FROM AUTHOR]

Understanding the mechanism of acetaldehyde dehydrogenase 1 (ALDH1) folding is important because this enzyme is directly involved in several types of cancers and other diseases. We investigated the urea-mediated unfolding of ALDH1 by integrating kinetic inhibition studies with computational molecular dynamics (MD) simulations. Conformational changes in the enzyme structure were also analyzed using intrinsic and 1-anilinonaphthalene-8-sulfonate (ANS)-binding fluorescence measurements. Kinetic studies revealed that the direct binding of urea to ALDH1 induces inactivation of ALDH1 in a manner of mixed-type inhibition. Tertiary structural changes associated with regional hydrophobic exposure of the active site were observed. The urea binding regions on ALDH1 were predicted by docking simulations and were partly shared with active site residues of ALDH1 and with interface residues of the oligomerization domain for tetramer formation. The docking results suggest that urea prevents formation of the ALDH1 normal shape for the tetramer state as well as entrance of the substrate into the active site. Our study provides insight into the structural changes that accompany urea-mediated unfolding of ALDH1 and the catalytic role associated with conformational changes. [ABSTRACT FROM AUTHOR]