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Intensified atmospheric nitrogen (N) deposition, coupled with increased application of N fertilizers in forest plantations, has resulted in N and phosphorus (P) imbalance in the forest soil system. However, it is seldom investigated whether an addition of N counteracts the effects of low P stress on N and P nutrient absorption and utilization efficiencies. Thus, we conducted a greenhouse experiment on three clones of Chinese fir (clones 061, 020 and 2 C) with four levels of N addition (2, 5, 10, and 15 mmol·L− 1 sodium nitrate) under normal P supply (1.0 mmol·L− 1 KH2PO4), moderately P deficiency (0.5 mmol·L− 1 KH2PO4) and severely P deficiency (0.1 mmol·L− 1 KH2PO4) conditions. The results showed that addition of moderate concentration of N (10 mmol·L− 1 N) significantly promoted root elongation, root dry mass accumulation, root surface area and root APase activity of Chinese fir seedlings under P-deficient conditions, with distinct clonal variation. Seedlings of clone 061 showed the most root APase activity in response to addition of moderate concentration of N under P deficient condition while clones 061 and 020 had the longest roots and the largest root dry mass accumulation. Under severe P deficiency, the N and P absorption efficiencies (NAE and PAE) of Chinese fir seedlings increased with increasing N concentration, while the N and P utilization efficiencies (NUE and PUE) decreased. The findings demonstrate that addition of moderate level of N modulates the adaptive responses of Chinese fir to P deficiency and enhances the absorption efficiency of P. The variation among clones suggests that the responses are genetically controlled and there exists great potential for breeding highly phosphorus efficient genotypes under coupled conditions of P deficiency and increased atmospheric nitrogen deposition. [ABSTRACT FROM AUTHOR]

We presents an innovative approach to addressing the mechanical properties limitations of fluororubber (FKM) in the industrial field. A novel functionalized nano-silica spheres (SiO2), grafted with amino groups, were constructed by utilizing chemical grafting. The surface modification of the nanosilica microspheres enables the formation of C=N bonds between the amino-functionalized nanosilica microspheres and FKM promoting high dispersion and strong interfacial bonding of SiO2, resulting in an exceptional mechanical enhancement function for FKM composite. Compared to original FKM, the FKM/SM-A-10 composite demonstrates remarkable improvements in both tensile strength and hardness by 242% and 49%, respectively. Additionally, there is a notable 40% enhancement in thermal conductivity of the FKM/SM-A-10 composite. This straightforward and efficient manufacturing approach for achieving high-performance FKM proves to be a valuable and practical foundation for industrial design. [ABSTRACT FROM AUTHOR]

Background: Emphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica. Case presentation: An 86-year-old man presented with severe back pain of 3 days' duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered. Conclusions: Emphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment. [ABSTRACT FROM AUTHOR]

This paper introduces an enhanced Whale Optimization Algorithm, named the Multi-Swarm Improved Spiral Whale Optimization Algorithm (MISWOA), designed to address the shortcomings of the traditional Whale Optimization Algorithm (WOA) in terms of global search capability and convergence velocity. The MISWOA combines an adaptive nonlinear convergence factor with a variable gain compensation mechanism, adaptive weights, and an advanced spiral convergence strategy, resulting in a significant enhancement in the algorithm's global search capability, convergence velocity, and precision. Moreover, MISWOA incorporates a multi-population mechanism, further bolstering the algorithm's efficiency and robustness. Ultimately, an extensive validation of MISWOA through "simulation + experimentation" approaches has been conducted, demonstrating that MISWOA surpasses other algorithms and the Whale Optimization Algorithm (WOA) and its variants in terms of convergence accuracy and algorithmic efficiency. This validates the effectiveness of the improvement method and the exceptional performance of MISWOA, while also highlighting its substantial potential for application in practical engineering scenarios. This study not only presents an improved optimization algorithm but also constructs a systematic framework for analysis and research, offering novel insights for the comprehension and refinement of swarm intelligence algorithms. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether changes in presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 levels predict mortality in septic patients in the intensive care unit. This study enrolled septic patients between November 2020 and December 2021. Levels of presepsin, procalcitonin, high-sensitivity C-reactive protein, and interleukin 6 were measured on the first (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and third days (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional hazards regression analysis, ΔPSEP (= PSEP_3 – PSEP_0) > 211.49 pg/mL (hazard ratio, 2.70; 95% confidence interval, 1.17–6.22), ΔPCT (= PCT_3 – PCT_0) > –0.13 ng/mL (hazard ratio, 7.31; 95% confidence interval, 2.68–19.80), ΔhsCRP (= hsCRP_3 – hsCRP_0) > −19.29 mg/L (hazard ratio, 6.89; 95% confidence interval, 1.61–29.40), and ΔIL-6 (= IL-6_3 – IL-6_0) > 1.00 pg/mL (hazard ratio, 3.13; 95% confidence interval, 1.35–7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all 4 distinct biomarkers was highest (concordance index, 0.83; 95% confidence interval, 0.76–0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the Acute Physiology and Chronic Health Evaluation II and Sequential (sepsis-related) Organ Failure Assessment scores, the combination of the 4 biomarkers had a larger net benefit. Interestingly, interleukin 6 was predominantly produced by monocytes upon lipopolysaccharide stimulation in peripheral blood mononuclear cells. ΔPSEP, ΔPCT, ΔhsCRP, and ΔIL-6 are reliable biomarkers for predicting mortality in septic patients in the intensive care unit, and their combination has the best performance. [ABSTRACT FROM AUTHOR]

As a kind of well-known moxibustion material across the world, Artemisia argyi Folium (AAF) has a definite curative effect. From 1996 to now, various studies on AAF have been increasing year by year. That is why this paper is conducted because of no comprehensive summary except for an essential oil review recently published in 2023. Using "AAF" and "mugwort" as keywords, the related literature was summarized in four internationally recognized databases: PubMed, Web of Science, ACS, and ScienceDirect, mainly include four aspects such as botany, phytochemistry, pharmacology, and clinical application. Four traditional identification methods and two new ones were reported. A total of 136 compounds were identified, among which 23 new terpenoids and two new flavonoids were discovered. The pharmacological effects of AAF mainly focus on anti-inflammatory, anti-tumor, antioxidant, antibacterial, and other aspects. Clinically, it is mainly used in respiratory, immune, digestive, and nervous systems in addition to gynecology. The current research mainly focuses on the composition and pharmacology of AAF. Future studies should thoroughly establish the quality criteria and pharmacokinetics of AAF. According to the different application fields, the corresponding quality standards should be formulated to ensure the efficacy of drugs in the actual treatment. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose)polymerases (PARPs) have emerged as promising targets for the treatment of diseases, particularly in cancers, due to their significant biological functions involved in DNA damage. As a result, researchers worldwide have made substantial advances in this field. However, studies have revealed that PARPs inhibitors lack selectivity due to the conserved domain, limiting their clinical applications and emphasizing the need for selective inhibitors. In this perspective, we summarize the recent advancements in PARPs inhibitors, with a focus on selective inhibitors among PARP family. We discuss the designed strategy, structure-activity relationships, and crystal structure, while explaining the underlying mechanisms of selectivity, hoping to provide insights for the design of next generation of PARPs selective inhibitors. [ABSTRACT FROM AUTHOR]

T helper cells, particularly T follicular helper (TFH) cells, are essential for the neutralizing antibody production elicited by pathogens or vaccines. However, in immunocompromised individuals, the inefficient support from TFH cells could lead to limited protection after vaccine inoculation. Here we showed that the conjugation of inducible T cell costimulatory (ICOS) onto the nanoparticle, together with immunogen, significantly enhanced the immune response of the vaccines specific for SARS-CoV-2 or human immunodeficiency virus type-1 (HIV-1) in TFH-deficient mice. Further studies indicated that ICOSL on B cells was triggered by ICOS binding, subsequently activated the PKCβ signaling pathway, and enhanced the survival and proliferation of B cells. Our findings revealed that the stimulation of ICOS-ICOSL interaction by adding ICOS on the nanoparticle vaccine significantly substitutes the function of TFH cells to support B cell response, which is significant for the immunocompromised people, such as the elderly or HIV-1-infected individuals. [ABSTRACT FROM AUTHOR]

The Yangtze River Delta (YRD) is an important engine of national economic development and a leading region in international competition. As economic exchanges and resource flows in the YRD region become closer, the inter-regional industrial linkages continue to grow, resulting in the formation of an industrial network structure characterized by a "complex network". The strength of the links between industrial sectors and the value and significance of the existence of industries in the network change over time, thus causing the overall evolution of the industrial network in the YRD region. Based on the input-output tables of the YRD region in 2012 and 2017, this paper uses the prediction index of network structure similarity to construct the prediction model of industrial network link between the YRD regions, and calculates the possibility of future links between industries in the Yangtze River Delta region through comparative analysis and selection of the RWR index of random walk similarity with the best effect, and concludes that: (1) the homogeneity of industries among provinces and cities in the Yangtze River Delta region is relatively high, resulting in homogeneous competition; (2) the overall nature of the industrial layout of the YRD is not prominent, and the depth and intensity of cross-regional industrial cooperation are lacking. On the basis of analysis and research, the countermeasures and suggestions for effectively realizing industrial integration are put forward from the macro level of the government and the meso level of the industry, so as to achieve a more complete industrial network in the YRD region and a more extensive length and width of the cross-regional industrial chain. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis cytolethal distending toxin (GpCDT) can induce cell cycle arrest and apoptosis. Our laboratory's previous work demonstrated that GTPase 4b (Rab4b) is a key host protein implicated in GpCDT-induced cytotoxicity. This study investigated the probable involvement of Rab4b in the process. Our study used CRISPR/Cas9 technology to create a Rab4b-knockout cell line. The results showed greater resistance to GpCDT-induced cell cytotoxicity. In contrast, forced Rab4b overexpression increased GpCDT-induced cytotoxicity. Further immunoprecipitation study reveals that GpCDT may bind with Rab4b. In PK-15 cells, GpCDT is transported to the early endosomes and late endosomes, while after knocking out Rab4b, GpCDT cannot be transported to the early endosome via vesicles. Rab4b appears essential for GpCDT-induced cytotoxicity in PK-15 cells. [ABSTRACT FROM AUTHOR]

Environmental context: Atmospheric particulate NH4+, primarily produced from the reaction of NH3 and acids, is an important component of PM2.5. In this study, nitrogen stable isotope analyses and an atmospheric chemistry model were used to estimate the contribution of major NH3 sources to particulate NH4+ in Tianjin, a megacity in North China Plain (NCP). Our research has implications for investigations of NH3 emission sources and relevant pollution control in Tianjin and NCP. Rationale: The North China Plain (NCP) has been identified as an NH3 emission hotspot. Source apportionment of NH3 is a prerequisite for controlling NH3 or NH4+ pollution. Nitrogen stable isotope (δ 15N) analysis is a promising method for NH3 source apportionment but its accuracy is still in question. Methodology: In this study, daytime and nighttime PM2.5 samples were collected from two sites in Tianjin, NCP, in autumn. Concentrations and δ 15N of particulate NH4+ were then measured. Nitrogen stable isotope analyses and isotope mixing model (MixSIAR), and an atmospheric chemistry model (WRF-CMAQ-ISAM) were used to estimate the sources of NH3 in Tianjin. Results: Results from the MixSIAR and WRF-CMAQ-ISAM models suggested that all the sources including livestock breeding, N-fertiliser application, fossil fuels, NH3 slip (especially from traffic), human waste and biomass burning (mostly from bioapplication) were non-negligible to NH3 and NH4+ in Tianjin. This high complexity is due to significant agricultural and industrial production and residential life in Tianjin and the surrounding regions. Our results indicate all NH3 sources need to be considered if we want to reduce NH4+ pollution in Tianjin in autumn. Environmental context. Atmospheric particulate NH4+, primarily produced from the reaction of NH3 and acids, is an important component of PM2.5. In this study, nitrogen stable isotope analyses and an atmospheric chemistry model were used to estimate the contribution of major NH3 sources to particulate NH4+ in Tianjin, a megacity in North China Plain (NCP). Our research has implications for investigations of NH3 emission sources and relevant pollution control in Tianjin and NCP. Photograph by Libin Wu. This article belongs to the collection Dedication to Roy Harrison. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate associations of wildfire fine particulate matter ≤2.5 mm in diameter (PM2.5) with diabetes across multiple countries and territories. RESEARCH DESIGN AND METHODS: We collected data on 3,612,135 diabetes hospitalizations from 1,008 locations in Australia, Brazil, Canada, Chile, New Zealand, Thailand, and Taiwan during 2000–2019. Daily wildfire-specific PM2.5 levels were estimated through chemical transport models and machine-learning calibration. Quasi-Poisson regression with distributed lag nonlinear models and random-effects meta-analysis were applied to estimate associations between wildfire-specific PM2.5 and diabetes hospitalization. Subgroup analyses were by age, sex, location income level, and country or territory. Diabetes hospitalizations attributable to wildfire-specific PM2.5 and nonwildfire PM2.5 were compared. RESULTS: Each 10 µg/m3 increase in wildfire-specific PM2.5 levels over the current day and previous 3 days was associated with relative risks (95% CI) of 1.017 (1.011–1.022), 1.023 (1.011–1.035), 1.023 (1.015–1.032), 0.962 (0.823–1.032), 1.033 (1.001–1.066), and 1.013 (1.004–1.022) for all-cause, type 1, type 2, malnutrition-related, other specified, and unspecified diabetes hospitalization, respectively. Stronger associations were observed for all-cause, type 1, and type 2 diabetes in Thailand, Australia, and Brazil; unspecified diabetes in New Zealand; and type 2 diabetes in high-income locations. An estimate of 0.67% (0.16–1.18%) and 1.02% (0.20–1.81%) for all-cause and type 2 diabetes hospitalizations were attributable to wildfire-specific PM2.5. Compared with nonwildfire PM2.5, wildfire-specific PM2.5 posed greater risks of all-cause, type 1, and type 2 diabetes and were responsible for 38.7% of PM2.5-related diabetes hospitalizations. CONCLUSIONS: We show the relatively underappreciated links between diabetes and wildfire air pollution, which can lead to a nonnegligible proportion of PM2.5-related diabetes hospitalizations. Precision prevention and mitigation should be developed for those in advantaged communities and in Thailand, Australia, and Brazil. [ABSTRACT FROM AUTHOR]

Recent advancements in high-throughput sequencing technologies have significantly enhanced our ability to unravel the intricacies of gene regulatory processes. A critical challenge in this endeavor is the identification of variant effects, a key factor in comprehending the mechanisms underlying gene regulation. Non-coding variants, constituting over 90% of all variants, have garnered increasing attention in recent years. The exploration of gene variant impacts and regulatory mechanisms has spurred the development of various deep learning approaches, providing new insights into the global regulatory landscape through the analysis of extensive genetic data. Here, we provide a comprehensive overview of the development of the non-coding variants models based on bulk and single-cell sequencing data and their model-based interpretation and downstream tasks. This review delineates the popular sequencing technologies for epigenetic profiling and deep learning approaches for discerning the effects of non-coding variants. Additionally, we summarize the limitations of current approaches in variant effect prediction research and outline opportunities for improvement. We anticipate that our study will offer a practical and useful guide for the bioinformatic community to further advance the unraveling of genetic variant effects. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study is to prepare Maillard reaction products (MRPs) with low Browning intensity for microencapsulation of Lactococcus lactis and to improve its processing stability and anti‐digestive ability. In this study, whey protein isolate (WPI) was combined with xylose oligosaccharides (XOS) and feruloyl oligosaccharides (FOs) at 90 °C for 90 min to prepare two Maillard reaction products (MRPs), which were applied to the construction of L. lactis microcapsules. The results showed that WPI‐FOs had a lower Browning intensity and slightly lower intermediate content than WPI‐XOS. Both MRPs showed strong inhibitory effects on the pathogens and probiotics effect on L. lactis. In addition, L. lactis coated with MRPs showed significantly enhanced resistance to heat and mechanical stress. Therefore, this study demonstrated that the Maillard conjugation of WPI with oligosaccharides has the potential to be the encapsulant for probiotic microcapsules. [ABSTRACT FROM AUTHOR]

As a new paradigm of distributed computing, mobile edge computing (MEC) has gained increasing attention due to its ability to expand the capabilities of centralized cloud computing. In MEC environments, a software application typically consists of multiple micro‐services, which can be composed together in a flexible manner to achieve various user requests. However, the composition of micro‐services in MEC is still a challenging research issue arising from three aspects. Firstly, composite micro‐services constructed by ignoring the processing capabilities of different micro‐services may cause waste of edge resources. Secondly, edge servers' limitations in terms of computational power can easily cause service occupancy between composite micro‐services, severely affecting the user experience. Thirdly, in dynamic and unstable mobile environments, different edge users have different sensitivities to request latency, which increases the complexity of micro‐service composition. In order to improve edge resource utilization and user experience on micro‐service invocations, in this paper, we comprehensively consider the above three factors, and we first model the micro‐services composition problem in MEC as a constrained multi‐objective optimization problem. Then, a micro‐service composition optimization method M3C combining graph search and branch‐and‐bound strategy is proposed to find a composition solution set with low energy consumption and high success rate for multiple edge users. Finally, we perform a series of experiments on two widely used datasets. Experimental results show that our proposed approach significantly outperforms the four competing baseline approaches, and that it is sufficiently efficient for practical deployment. [ABSTRACT FROM AUTHOR]

Most of net energy captured by the increase in greenhouse gasses are subsequently absorbed by the oceans, with the majority being taken up by the subpolar North Atlantic and the Southern Ocean, in the form of ocean heat uptake (OHU). In this study, we examine the temporal evolution of OHU from the Coupled Model Intercomparison Project Phase 5&6 (CMIP 5&6) data, with a focus on the time period that would follow reaching CO2 concentration maximum. Our results show that the Southern Ocean and global mean OHU would show a negative trend following abrupt CO2 quadrupling. In contrast, the OHU in the subpolar North Atlantic would still rise and then remain at a high level for a century or longer. The SSP experiments show the same phenomenon when CO2 concentration starts decreasing. This opposite trend of OHU between the Southern Ocean and subpolar North Atlantic is mainly driven by the surface latent heat flux. Further analysis and a freshwater perturbation experiment using a coupled ocean–atmosphere model suggest that the prolonged period of strong OHU over the North Atlantic in the post-CO2 concentration maximum era would be the result of an overshoot of the Atlantic Meridional Overturning Circulation (AMOC) in response to the increase of CO2 concentration. [ABSTRACT FROM AUTHOR]

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The goal of bundle recommendation is to offer users a set of items that match their preferences. Current methods mainly categorize user preferences into bundle and item levels, and then use graph neural networks to obtain representations of users and bundles at both levels. However, real-world interaction data often contains irrelevant and uninformative noise connections, leading to inaccurate representations of user interests and bundle content. In this paper, we introduce a Multi-view Denoising Contrastive Learning approach for Bundle Recommendation (MDCLBR), aiming to reduce the negative effects of noisy data on users' and bundles' representations. We use the original view, which includes bundle and item levels, to guide data augmentation for creating augmented views. Then, we apply the multi-view contrastive learning paradigm to enhance collaboration within the original view, the augmented views, and between them. This leads to more accurate representations of users and bundles, reducing the impact of noisy data. Our method outperforms previous approaches in extensive experiments on three real-world public datasets. [ABSTRACT FROM AUTHOR]

Recent years have witnessed renewed interest in aqueous zinc-ion batteries, but challenges persist due to the rapid capacity decay and irreversible cycling of zinc anodes, primarily stemming from uncontrolled dendritic growth. To overcome this issue, in this work, sucralose is utilized as a functional electrolyte additive to enhance the stability and electrochemical performance of the zinc metal anode. According to the experimental characterization and theoretical calculations, sucralose molecules tend to be adsorbed on the Zn metal surface due to the presence of hydroxyl and chlorine groups, which regulated the solvation structure of Zn2+ near the interface of the electrode and electrolyte to inhibit dendrite formation and facilitate uniform Zn metal plating. Utilizing sucralose as an electrolyte additive, a significantly improved cycling lifespan of 1800 cycles under 5 mA cm−2/1 mA h cm−2 and a coulombic efficiency as high as 99.9% are retained in Zn–Cu asymmetric cells. Moreover, the assembled Zn-ion full cells with the sucralose additive in the electrolyte exhibit a high-capacity retention of 73.5% after 1000 cycles, which was almost increased by 300% in comparison with the cells using the pure ZnSO4 electrolyte. Furthermore, the assembled punch full cells can maintain a capacity of 166.3 mA h g−1 and stable cyclability with a capacity retention of 82.5% after 100 cycles at 5 A g−1. Our innovative approach provides insights into using functional electrolyte additives to regulate the solvation structure of Zn2+ ions near the electrode/electrolyte interface as a promising electrolyte design strategy for enhancing the performance and sustainability of aqueous zinc-ion batteries. [ABSTRACT FROM AUTHOR]

The stator of a flat wire motor is the core component of new energy vehicles. However, detecting quality defects in the coating process in real-time is a challenge. Moreover, the number of defects is large, and the pixels of a single defect are very few, which make it difficult to distinguish the defect features and make accurate detection more difficult. To solve this problem, this article proposes the YOLOv8s-DFJA network. The network is based on YOLOv8s, which uses DSFI-HEAD to replace the original detection head, realizing task alignment. It enhances joint features between the classification task and localization task and improves the ability of network detection. The LEFG module replaces the C2f module in the backbone of the YOLOv8s network that reduces the redundant parameters brought by the traditional BottleNeck structure. It also enhances the feature extraction and gradient flow ability to achieve the lightweight of the network. For this research, we produced our own dataset of stator coating quality regarding flat wire motors. Data augmentation technology (Gaussian noise, adjusting brightness, etc.) enriches the dataset, to a certain extent, which improves the robustness and generalization ability of YOLOv8s-DFJA. The experimental results show that in the performance of YOLOv8s-DFJA compared with YOLOv8s, the mAP@.5 index increased by 6.4%, the precision index increased by 1.1%, the recall index increased by 8.1%, the FPS index increased by 9.8FPS/s, and the parameters decreased by 3 Mb. Therefore, YOLOv8s-DFJA can be better realize the fast and accurate detection of the stator coating quality of flat wire motors. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC), an aggressive malignancy with virtually 100% disease‐specific mortality, has long posed a formidable challenge in oncology due to its resistance to conventional treatments and the severe side effects associated with current regimens such as doxorubicin chemotherapy. Consequently, there was urgent need to identify novel candidate compounds that could provide innovative therapeutic strategies for ATC. Ophiopogonin D′ (OPD'), a triterpenoid saponin extracted, yet its roles in ATC has not been reported. Our data demonstrated that OPD' potently inhibited proliferation and metastasis of ATC cells, promoting cell cycle arrest and apoptosis. Remarkably, OPD' impeded growth and metastasis of ATC in vitro and in vivo, displaying an encouraging safety profile. Regulator of G‐protein signalling 4 (RGS4) expression was significantly up‐regulated in ATC compared to normal tissues, and this upregulation was suppressed by OPD' treatment. Mechanistically, we elucidated that the transcription factor JUN bound to the RGS4 promoter, driving its transactivation. However, OPD' interacted with JUN, attenuating its transcriptional activity and thereby disrupting RGS4 overexpression. In summary, our research revealed that OPD' bound with JUN, which in turn resulted in the suppression of transcriptional activation of RGS4, thereby eliciting cell cycle arrest and apoptosis in ATC cells. These findings could offer promise in the development of high‐quality candidate compounds for treatment in ATC. [ABSTRACT FROM AUTHOR]

Fluororubber (FKM) has an important application in the industrial field. However, the coloring problem of FKM has been affecting the performance of its mechanical properties. Herein, a novel silicon dioxide (SiO2) colored with acid orange 7 (AO7) was prepared by sol–gel method to ameliorate the mechanical properties and coloring property of FKM. Acid orange silica sol was prepared by adding AO7 to sodium silicate solution, and then colored SiO2-AO7 was prepared by freeze drying. The effects of SiO2-AO7 modified FKM on mechanical properties, thermal conductivity and coloring were systematically studied. The results show that SiO2-AO7 has the advantage of enhancing the mechanical properties of FKM without affecting its color appearance. Relative to the unmodified FKM, the tensile strength and modulus at 300% elongation saw enhancements of 47.2% and 21.8% respectively. The SiO2-AO7 offers exceptional coloration and mechanical reinforcement, showing strong suitability for industrial application. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on bleomycin-induced IPF rats. Methods: The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis. Key findings: Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-β1 in the pulmonary tissue. Secondly, Masson's trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies. Conclusions: Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent. [ABSTRACT FROM AUTHOR]

This paper addresses the challenge of detecting unknown or unforeseen obstacles in railway track transportation, proposing an innovative detection strategy that integrates an incremental clustering algorithm with lightweight segmentation techniques. In the detection phase, the paper innovatively employs the incremental clustering algorithm as a core method, combined with dilation and erosion theories, to expand the boundaries of point cloud clusters, merging adjacent point cloud elements into unified clusters. This method effectively identifies and connects spatially adjacent point cloud clusters while efficiently eliminating noise from target object point clouds, thereby achieving more precise recognition of unknown obstacles on the track. Furthermore, the effective integration of this algorithm with lightweight shared convolutional semantic segmentation algorithms enables accurate localization of obstacles. Experimental results using two combined public datasets demonstrate that the obstacle detection average recall rate of the proposed method reaches 90.3%, significantly enhancing system reliability. These findings indicate that the proposed detection strategy effectively improves the accuracy and real-time performance of obstacle recognition, thereby presenting important practical application value for ensuring the safe operation of railway tracks. [ABSTRACT FROM AUTHOR]

Under the background of the worsening global food and water crisis, efficient agricultural practices have become increasingly important. This study investigated the impact of different irrigation and cultivation modes on rice growth parameters, gas exchange, rice yield components, and water footprints in Jiangsu, China. Four treatments were employed in a randomized complete block design with three replications: (i) transplanted rice with frequent shallow irrigation (T-FSI), (ii) transplanted rice with rain-catching and controlled irrigation (T-RCCI), (iii) direct-seeded rice with frequent shallow irrigation (D-FSI), (iv) and direct-seeded rice with rain-catching and controlled irrigation (D-RCCI). The results revealed that the D-RCCI treatment significantly improved growth and physiological parameters. The D-FSI treatment drastically increased rice yield whereas T-RCCI increased the stem bending resistance and reduced lodging risk. The water footprint analysis showed significant water savings by optimized management practices. Compared to T-FSI, the T-RCCI, D-FSI, and D-RCCI treatments reduced the blue-green water footprint by 33%, 25%, and 25%, respectively. Additionally, water production efficiency increased by 13%, 106%, and 154% for T-RCCI, D-FSI, and D-RCCI respectively. The water footprint per unit yield of T-RCCI, D-FSI, and D-RCCI treatments was significantly reduced by 12%, 5,3%, and 63% compared to T-FSI. Overall, D-RCCI is the optimal strategy for rice cultivation in Jiangsu province and similar climatic areas due to its positive impact on yield, water savings, and environmental benefits. [ABSTRACT FROM AUTHOR]

Hyperparameters optimization (HPO) is vital for machine learning models. Besides model accuracy, other tuning intentions such as model training time and energy consumption are also worthy of attention from data analytic service providers. Therefore, it is essential to take both model hyperparameters and system parameters into consideration to execute cross-layer multi-objective hyperparameter auto-tuning. Toward this challenging target, we propose HyperTuner in this paper which leverages a well-designed ADUMBO algorithm to find the Pareto-optimal configuration set. Compared with vanilla Bayesian optimization-based methods, ADUMBO selects the most promising configuration from the generated Pareto candidate set during each iteration via maximizing a novel adaptive uncertainty metric. We evaluate HyperTuner on our local distributed TensorFlow cluster, and experimental results show that it is always able to find a better Pareto configuration front superior in both convergence and diversity compared with the other four baseline algorithms. Besides, experiments with different training datasets, different optimization objectives, and different machine learning platforms verify that HyperTuner can well adapt to various data analytic service scenarios. [ABSTRACT FROM AUTHOR]

Glaesserella parasuis is usually a benign swine commensal in the upper respiratory tract, but virulent strains can cause systemic infection characterized by pneumonia, meningitis, and fibrinous polyserositis. The intensive pulmonary inflammatory response following G. parasuis infection is the main cause of lung injury and death in pigs. Vaccination has failed to control the disease due to the lack of extended cross-protection. Accumulating evidence indicates that the heme-binding protein A (HbpA) is a potential virulence determinant and a promising antigen candidate for the development of a broader range of vaccines. However, it is not yet known whether HbpA contributes to G. parasuis virulence or has any potential immune protective effects against G. parasuis. Here, we show that HbpA can induce the transcription and secretion of proinflammatory cytokines (IL-6, TNF-α, and MCP-1) in porcine alveolar macrophages (PAM, 3D4/31). The HbpA protein is recognized by Toll-like receptors 2 and 4 on 3D4/21 macrophages, resulting in the activation of MAP kinase and NF-κB signalling cascades and the transcription and secretion of proinflammatory cytokines. HbpA contributes to virulence and bacterial pulmonary colonization in C57BL/6 mice and plays a role in adhesion to host cells and evasion of the bactericidal effect of pulmonary macrophages. In addition, mice immunized with HbpA were partially protected against challenge by G. parasuis SC1401. The results suggest that HbpA plays an important role in the pathogenesis of disease caused by G. parasuis and lay a foundation for the development of a subunit or chimeric anti-G. parasuis vaccine. [ABSTRACT FROM AUTHOR]

A hydrophobic self-assembled monolayer designated as Me-4PACz was used as a hole-selective interlayer in PM6:Y6 organic photovoltaic devices. A comparative analysis was conducted on the performance of solar cells incorporating Me-4PACz, 2PACz, and the conventional hole material MoO3. The device in which Me-4PACz was utilized exhibited higher transmittance and lower resistivity than the solar cell using MoO3. Furthermore, the solar cell based on Me-4PACz demonstrated enhanced charge transport capability and optimized contact relative to those employing 2PACz. The device incorporating Me-4PACz achieved superior long-term stability and the highest power conversion efficiency of 17.06%, outperforming the devices utilizing 2PACz (15.67%) and MoO3 (14.09%) as hole transport materials. These results indicate the potential of hydrophobic Me-4PACz as a promising candidate for hole transport in organic solar cells. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that long noncoding RNAs (lncRNAs) play important regulatory roles in biological processes and are dysregulated in numerous tumors. The lncRNA GRASLND functions as an oncogene in many cancers, but its role in skin cutaneous melanoma (SKCM) requires further investigation. Methods: SiRNA transfection, wound − healing and transwell assays were performed to evaluate the effect of GRASLND on cellular function. Results: The present study demonstrated that GRASLND expression is increased in SKCM tissues and cell lines. The high expression of GRASLND was correlated with poor prognosis and immunotherapy outcomes. Knockdown of GRASLND significantly inhibited cell migration and invasion. In addition, we found that miR-218-5p directly binds to its binding site on GRASLND, and GRASLND and miR-218-5p demonstrate mutual inhibition. Furthermore, the miR-218-5p inhibitor partially eliminated the knockdown of GRASLND and inhibited its expression. We also demonstrated that GRASLND acts as a miR-218-5p sponge that positively regulates STAM2 expression in SKCM cells. Conclusion: In summary, these data suggest that GRASLND functions by regulating miR-218-5p/STAM2 expression, suggesting an important role for the lncRNA‒miRNA–mRNA functional network and a new potential therapeutic target for SKCM. [ABSTRACT FROM AUTHOR]

Since the 1950s, observations and climate models show an amplification of sea surface temperature (SST) seasonal cycle in response to global warming over most of the global oceans except for the Southern Ocean (SO), however the cause remains poorly understood. In this study, we analyzed observations, ocean reanalysis, and a set of historical and abruptly quadrupled CO2 simulations from the Coupled Model Intercomparison Project Phase 6 archive and found that the weakened SST seasonal cycle over the SO could be mainly attributed to the intensification of summertime westerly winds. Under the historical warming, the intensification of summertime westerly winds over the SO effectively deepens ocean mixed layer and damps surface warming, but this effect is considerably weaker in winter, thus weakening the SST seasonal cycle. This wind‐driven mechanism is further supported by our targeted coupled model experiments with the wind intensification effects being removed. Plain Language Summary: The Southern Ocean (SO) sea surface temperature (SST) has experienced a decreased seasonal cycle since the 1950s, in contrast with the overall amplified seasonal cycle in the rest of global oceans. Here we investigated observations and climate model simulations and found that the decrease of SST seasonal cycle was associated with less warming in summer than in winter during the historical period. The suppressed warming in summer is accompanied by a deepened ocean mixed layer due to the intensification of surface westerlies. An enhanced mixed layer depth means the incoming heat flux will be trapped in a deeper mixed layer in summer, causing a cooler summer SST, which then leads to a weaker SST annual cycle. When the wind intensification effect is removed in our model simulations, the decreased SST seasonal cycle in the SO disappears. Key Points: Observations and climate models show a weakening sea surface temperature (SST) seasonal cycle induced by the delayed warming of summer SST over Southern Ocean (SO)The summer mixed layer depth and wind stress show increasing trends during the same period over the SOThe summer wind‐induced mixed layer deepening suppresses SO surface warming and thus weakening the SST seasonal cycle [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis and care of children and adolescents with neurodevelopmental disorders presents a public health crisis in China. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent conditions. Many Chinese children and adolescents with ADHD are underdiagnosed and undertreated. This study aimed to evaluate the awareness and attitude parents have about ADHD, and investigated potential factors influencing ADHD medical visit status among school-aged children in Shanghai. Methods: A random cluster sampling method was used, and four primary schools in Shanghai were selected. One class was randomly selected from each grade, including students and their parents. Parents completed the Swanson, Nolan, and Pelham Version IV Questionnaire (SNAP-IV) parent form and questionnaire concerning ADHD awareness, knowledge, attitude and status of ADHD medical visit. Descriptive analysis was conducted on the overall results and logistic regression analysis was performed to explore the influencing factors of ADHD medical visit. Results: We received 617 valid questionnaires. There were 313 boys (50.7%) and 304 girls (49.2%), with a median age of 8 years old (p25 = 7, p75 = 9). 42.4% parents believed they had some knowledge about ADHD, and 73.5% of them thought ADHD was a neurologically based disorder or neurological condition by nature. Parental ADHD information came from the following sources: Internet/TV (n = 458, 74.2%), families/friends (n = 267, 43.2%), print publication (n = 208, 33.7%), psychiatrists/pediatricians (n = 192, 31.1%), schools/teachers (n = 186, 30.1%) and other ADHD patients (n = 48, 7.7%). When children had ADHD-like behaviors, most parents (61.5%) educated children to behave themselves, 59.1% parents tried to get help from psychiatrists/pediatricians, 55.5% of them would ask psychologist for help. In terms of the ADHD prevalence, the SNAP-IV positive screen rate was 4.3% (n = 27). Only 33.3% (9/27) of parents went to the hospital for consultation and treatment. Multivariate logistic regression model showed that parental knowledge about ADHD (OR = 13.67, 95%CI: 1.72, 144.39, P = 0.01) was significantly correlated with the medical visit. Parents with sufficient knowledge of ADHD tend to visit hospital for help when they thought their children had ADHD related symptoms. Conclusions: The majority of parents accepted ADHD as a neurodevelopmental disorder by nature, but some parents still had certain misunderstandings about ADHD. The main source of information for parents to obtain information about ADHD was through the TV/Internet. Parents' perceptions and knowledge were key to whether children received appropriate treatment for their ADHD. However, medical visits to address ADHD among school-aged children were still lower than expected. Government and healthcare institutes should work to improve ADHD public awareness and to help patients and their families gain access to mental health resources. [ABSTRACT FROM AUTHOR]

Extremely large magnetoresistance (XMR) is highly applicable in spintronic devices such as magnetic sensors, magnetic memory, and hard drives. Typically, XMR is found in Weyl semimetals characterized by perfect electron–hole symmetry or exceptionally high electric conductivity and mobility. Our study explores this phenomenon in a recently developed graphene moiré system, which demonstrates XMR owing to its topological structure and high-quality crystal formation. We investigate the electronic properties of three-dimensional intertwined twisted graphene spirals (TGS), manipulating the screw dislocation axis to achieve a rotation angle of 7.3°. Notably, at 14 T and 2 K, the magnetoresistance of these structures reaches 1.7 × 107%, accompanied by a metal–insulator transition as the temperature increases. This transition becomes noticeable when the magnetic field exceeds a minimal threshold of approximately 0.1 T. These observations suggest the possible existence of complex, correlated states within the partially filled three-dimensional Landau levels of the 3D TGS system. Our findings open up possibilities for achieving XMR by engineering the topological structure of 2D layered moiré systems. Twisted graphene spirals are emerging material structures that may host topological phenomena. Here, the authors demonstrate extremely large magnetoresistance and a metal-insulator transition in twisted graphene spirals. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15%‐30% of children and 10% of adults globally, with its incidence being influenced by genetic, environmental, and various other factors. While the immune plays a crucial role in the development, the composition of gut microbiota and serum metabolites also contribute to its pathogenesis. Subject: Study the characteristics of gut microbiota and serum metabolites in patients with atopic dermatitis Method: In this study, we collected stool and serum samples from 28 AD patients and 23 healthy individuals (NC) for metagenomic sequencing of gut microbiota and non‐targeted metabolomic sequencing of serum. Result: Our results revealed a lower diversity of gut microbiota in the AD group compared to the NC group. The predominant Phylum in AD patients were Bacteroidetes, Pseudomonas, and Verrucomicrobia, with the most dominant bacterial genus being Faecalibacterium. At the species level, Prevotella copri and Faecalibacterium prausnitzii were found to be the most abundant bacteria. Significant differences in serum metabolite profiles were observed between NC and AD patients, with noticeable variations in metabolite expression levels. The majority of metabolites in the serum of AD patients exhibited low expression, while a few showed high expression levels. Notably, metabolites such as Cholesterol glucuronide, Styrene, Lutein, Betaine, Phosphorylcholine, Taurine, and Creatinine displayed the most pronounced alterations. Conclusion: These findings contribute to a further understanding of the complexities underlying this disease. [ABSTRACT FROM AUTHOR]

To adapt to the increasing proportion of new energy power generation capacity, coal power must transition from its traditional role as the primary power source to serving as a fundamental backup and system regulation energy source. The circulating fluidized bed technology is known for its wide range of load regulation capabilities; however, emissions of pollutants during load regulation can exhibit significant variability. This study utilized Aspen Plus software to develop a circulating fluidized bed combustion model based on a gas-solid fluid dynamics model, an equivalent coal pyrolysis model, and a multi-phase macroscopic combustion reaction dynamics model of pyrolysis products. This model was used to predict both the temperature distribution within the furnace chamber and the distribution of pollutant concentrations. Predictions of pollutant emissions from 100 % load to 30 % load of the circulating fluidized bed were explored under the original combustion condition and 5 % proportion of recirculated flue gas. Under the primary combustion condition, the emission concentration of NOx showed a decreasing and then increasing trend with decreasing load, while the concentration of nitrous oxide, in contrast to NOx, showed an increasing and then decreasing trend. The effect of recirculated flue gas on pollutant emissions was not significant at reduced loads. This study aims to provide technical support and theoretical guidance for the management of pollutant emissions from the deep peak regulation of actual circulating fluidized beds. [ABSTRACT FROM AUTHOR]

With the development of Internet technology, many manufacturers encroach into the retail market by selling products directly to consumers, which is called manufacturer encroachment. In practice, the manufacturer may encroach in normal sales period, markdown period, or both periods in a two‐period supply chain. It is a challenging task for the firm manager to provide appropriate quality level under different channel structures. This research originally studies manufacturer encroachment with endogenous quality investment decision in a two‐period supply chain considering that consumers' valuation of products depreciates over time. Using a game‐theoretic framework, this work explores four channel strategies of the manufacturer and discusses equilibrium decisions and profits. The analysis generates several insights. First, the manufacturer should promote quality investment if encroachment occurs when the direct selling is efficient. Second, regardless of which period and scenario, encroachment may increase wholesale price when the direct selling cost is smaller than a threshold. Third, results show the effect of encroachment time on price could be classified into quality investment effect, wholesale price effect, and channel‐adding effect. The quality investment effect increases retail price, while the channel‐adding effect and wholesale price effect decrease retail price. Finally, results reveal that encroachment is always the best choice for the manufacturer and it does not always harm the retailer's profits. Overall, our results and managerial insights can help the manufacturer to formulate channel strategies, wholesale price, and selling quantity decisions while help the retailer to make order quantity decision. [ABSTRACT FROM AUTHOR]

Pulsed lasers alter the optical properties of semiconductors and affect the photoelectric function of the photodetectors significantly, resulting in transient changes known as bleaching. Bleaching has a profound impact on the control and interference of photodetector applications. Experiments using pump–probe techniques have made significant contributions to understanding ultrafast carrier dynamics. However, there are few theoretical studies to the best of our knowledge. Here, carrier dynamic models for semiconductors and photodetectors are established, respectively, employing the rectified carrier drift-diffusion model. The pulsed laser bleaching effect on seven types of semiconductors and photodetectors from visible to long-wave infrared is demonstrated. Additionally, a continuous bleaching method is provided, and the finite-difference time-domain (FDTD) method is used to solve carrier dynamic theory models. Laser parameters for continuous bleaching of semiconductors and photodetectors are calculated. The proposed bleaching model and achieved laser parameters for continuous bleaching are essential for several applications using semiconductor devices, such as infrared detection, biological imaging, and sensing. [ABSTRACT FROM AUTHOR]

Prostate cancer has high heritability. Healthy lifestyle has been associated with lower lethal prostate cancer risk among men at increased genetic susceptibility, but the role of healthy dietary patterns remains unknown. We prospectively followed 10,269 genotyped men in the Health Professionals Follow‐up Study (1993–2019). Genetic risk was quantified using an established polygenic risk score (PRS). Five dietary patterns were investigated: healthy eating index, Mediterranean, diabetes risk‐reducing, hyperinsulinemic and inflammatory diet. Overall and lethal prostate cancer rates (metastatic disease/prostate cancer‐specific death) were analyzed using multivariable Cox proportional hazards models. During 26 years of follow‐up, 2133 overall and 253 lethal prostate cancer events were documented. In the highest PRS quartile, higher adherence to a diabetes risk‐reducing diet was associated with lower rates of overall (top vs. bottom quintile HR [95% CI], 0.74 [0.58–0.94]) and lethal prostate cancer (0.43 [0.21–0.88]). A low insulinemic diet was associated with similar lower rates (overall, 0.76 [0.60–0.95]; lethal, 0.46 [0.23–0.94]). Other dietary patterns showed weaker, but similar associations. In the highest PRS quartile, men with healthy lifestyles based on body weight, physical activity, and low insulinemic diet had a substantially lower rate (0.26 [0.13–0.49]) of lethal prostate cancer compared with men with unhealthy lifestyles, translating to a lifetime risk of 3.4% (95% CI, 2.3%–5.0%) among those with healthy lifestyles and 9.5% (5.3%–16.7%) among those with unhealthy lifestyles. Our findings indicate that lifestyle modifications lowering insulin resistance and chronic hyperinsulinemia could be relevant in preventing aggressive prostate cancer among men genetically predisposed to prostate cancer. [ABSTRACT FROM AUTHOR]

Pruning deep neural networks is crucial for enabling their deployment on resource-constrained edge devices, where the vast number of parameters and computational requirements pose significant challenges. However, many of these methods consider only the importance of a single filter to the network and neglect the correlation between filters. To solve this problem, we propose a novel filter pruning method, called Filter Pruning via Attention and Rank Enhancement for Deep Convolutional Neural Networks Acceleration (FPAR), based on the attention mechanism and rank of feature maps. Moreover, the inspiration for it comes from a discovery: for a network with attention modules, irrespective of the batch of input images, the mean of channel-wise weights of the attention module is almost constant. Thus, we can use a few batches of input data to obtain this indicator to guide pruning. A large number of experiments have proved that our method outperforms the most advanced methods with similar accuracy. For example, using VGG-16, our method removes 62.8% of floating-point operations (FLOPs) even with a 0.24% of the accuracy increase on CIFAR-10. With ResNet-110, our FPAR method can reduce FLOPs by 61.7% by removing 62.7% of the parameters, with slight improvement of 0.05% in the top 1 accuracy on CIFAR-10. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common skin disease, the pathogenesis of which has not been fully elucidated. The gut microbiota is the largest micro-ecosystem in the human body that affects the immune system and skin barrier function. Recent studies have shown that in addition to the environmental factors, skin barrier, genetic factors and immune response, gut microbiota disturbance may also cause AD. This review described the correlation of AD with gut microbiota and existing research status of AD treatment via targeting gut microbiota. [ABSTRACT FROM AUTHOR]

A pure nickel film and a carbon/nickel (C/Ni) composite film were produced using radio frequency magnetron sputtering. The structure of the films was regulated by adjusting the sputtering power and the time allocation of sputtering nickel and graphite targets. Furthermore, a scanning electron microscope, an x-ray diffractometer, and a Raman spectrometer were employed for sample characterization. The results demonstrated that the thickness of the pure nickel film and C/Ni composite film with a total deposition time of 60 s was between 44.96 and 65.31 nm. The nickel film exhibited preferential growth along the crystal plane (111), and the structure of carbon materials was in the second stage of the three-stage model known as "amorphization trajectory of graphite." The prepared films' electromagnetic interference shielding effectiveness (EMI SE) in the X-band was investigated using a vector network analyzer. It was observed that the C/Ni composite film with a thickness of 44.96 nm demonstrated a superior EMI SE with a maximum value reaching 21 dB. The EMI SE of the C/Ni composite film can reach the same performance and even exceed that of the pure nickel film obtained at the power of 200 W for 60 s in certain frequency segments. In conclusion, the pure nickel film can be replaced by C/Ni composite film prospectively due to their excellent EMI SE along with advantages such as reduced thickness, lighter weight, and lower cost. [ABSTRACT FROM AUTHOR]

In modern cancer therapy, blockage of more than one target is a standard approach, and there are already many dual‐target drugs that can achieve multiple inhibition through a single molecule. Herein, we designed and synthesized a series of novel derivatives with signal transducer and activator of transcription 3 (STAT3) and histone deacetylase (HDAC) inhibitory activity through strategy of combining pharmacophore based on the STAT3 inhibitor E28 and HDAC inhibitor MS‐275. Among them, compound 24 (IC50 = 8.22 ± 0.27 μM) showed better anti‐tumor activity than the clinical Class I HDAC inhibitor MS‐275 (IC50 = 14.65 ± 0.24 μM) in MCF‐7 breast cancer cells. Furthermore, the dual inhibition to HDAC and STAT3 of compound 24 was validated by western blot analysis. The study provides new tool compounds for further exploration of STAT3–HDAC pathway inhibitor achieved with a single molecule. [ABSTRACT FROM AUTHOR]

Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy‐saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide‐induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC. [ABSTRACT FROM AUTHOR]

Oxysulfides BiCuSO, with a natural superlattice structure, have extremely low thermal conductivity and high Seebeck coefficient. However, the thermoelectric performance of BiCuSO is restricted by its high electrical resistivity resulting from its low carrier concentration and Hall mobility. In this study, BiCuSO was rapidly prepared by one-step high pressure technique. The Pb doping at the Bi site of BiCuSO increases the carrier concentration and decreases the resistivity significantly, which results in an enhanced power factor of ~ 1.0 μWcm−1K−2 at room temperature for Bi0.97Pb0.03CuSO. Meanwhile, substituting Se for S in BiCuSO not only improves the Hall mobility but also decreases the phonon thermal conductivity. Benefiting from the high power factor and low thermal conductivity induced by Pb doping and Se alloying, an enhanced ZT of ~ 0.17 at 673 K is obtained for the sample of Bi0.97Pb0.03CuS0.55Se0.45O. [ABSTRACT FROM AUTHOR]

Background: Use of multivitamin supplements has been associated with lower incidence of colorectal cancer (CRC). However, its influence on CRC survival remains unknown. Methods: Among 2424 patients with stage I–III CRC who provided detailed information about multivitamin supplements in the Nurses' Health Study and Health Professionals Follow‐up Study, the authors calculated multivariable hazard ratios (HRs) of multivitamin supplements for all‐cause and CRC‐specific mortality according to post‐diagnostic use and dose of multivitamin supplements. Results: During a median follow‐up of 11 years, the authors documented 1512 deaths, among which 343 were of CRC. Compared to non‐users, post‐diagnostic users of multivitamin supplements at a dose of 3–5 tablets/week had lower CRC‐specific mortality (HR, 0.55; 95% confidence interval [CI], 0.36–0.83, p =.005), and post‐diagnostic users at doses of 3–5 and 6–9 tablets/week had lower all‐cause mortality (HR, 0.81; 95% CI, 0.67–0.99, p =.04; HR, 0.79; 95% CI, 0.70–0.88), p <.001). The dose–response analysis showed a curvilinear relationship for both CRC‐specific (pnonlinearity <.001) and all‐cause mortality (pnonlinearity =.004), with the maximum risk reduction observed at 3–5 tablets/week and no further reduction at higher doses. Compared to non‐users in both pre‐ and post‐diagnosis periods, new post‐diagnostic users at dose of <10 tablets/week had a lower all‐cause mortality (HR, 0.81; 95% CI, 0.71–0.94, p =.005), whereas new users at a dose of ≥10 tablets/week (HR, 1.58; 95% CI, 1.07–2.33) and discontinued users (HR, 1.35; 95% CI, 1.14–1.59) had a higher risk of mortality. Conclusions: Use of multivitamin supplements at a moderate dose after a diagnosis of nonmetastatic CRC is associated with lower CRC‐specific and overall mortality, whereas a high dose (≥10 tablets/week) use is associated with higher CRC‐specific mortality. In this prospective study of 2424 patients with stage I–III colorectal cancer (CRC), the authors observed a curvilinear relationship in the use of multivitamin supplements: compared to non‐users, users at a dose of 3–9 tablets/week had a lower risk of CRC‐specific and all‐cause mortality, whereas users at a dose higher than 10 tablets/week had a higher CRC‐specific mortality. [ABSTRACT FROM AUTHOR]