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Abstract Background Cell-free DNA (cfDNA) in plasma carries epigenetic signatures specific to tissue or cell of origin. Aberrant methylation patterns in circulating cfDNA have emerged as valuable tools for noninvasive cancer detection, prenatal diagnostics, and organ transplant assessment. Such epigenetic changes also hold significant promise for the diagnosis of neurodegenerative diseases, which often progresses slowly and has a lengthy asymptomatic period. However, genome-wide cfDNA methylation changes in neurodegenerative diseases remain poorly understood. Results We used whole-genome bisulfite sequencing (WGBS) to profile age-dependent and ALS-associated methylation signatures in cfDNA from 30 individuals, including young and middle-aged controls, as well as ALS patients with matched controls. We identified 5,223 age-related differentially methylated loci (DMLs) (FDR

Abstract Metaverse is a digital value interaction network based on blockchain technology, with an important economic system component. While both traditional financial industries and crypto‐native industries have made significant progress by leveraging blockchain, the value stream of each remains limited to separate ecosystems. To bridge this gap between off‐chain and on‐chain economic systems, an on‐chain trading model was proposed using HD key derivation technique for direct uploading onto chains without going through centralized services for IoT data transmission. To improve the current status of NFTs as static assets, a token protocol binding each NFT with a unique account address was proposed. Additionally, oracle technique was leveraged with a decentralized and distributed trust model spanning across on‐chain and off‐chain components which securely pushes data between smart contracts and Web‐APIs. A decentralized trading model was developed based on smart contracts implementing automated market makers according to CFMM algorithm. Parallel transaction computing was executed based on the DAG model to ensure high operational performance and security standards of underlying blockchain. Finally, the on‐chain trading system of real world asset backed digital assets was developed integrating all the above key techniques that correspond to crucial functions of a complete economic system in Metaverse.

Objectives The type of ligamentous tear and the degree of knee laxity have important guiding significance for the diagnosis and management of anterior cruciate ligament (ACL) tears. Instrumental measurement is necessary for ACL tears since physical examination and magnetic resonance imaging (MRI) cannot provide an objective and quantitative assessment of knee laxity. This study aimed to compare the application of a novel knee arthrometer and simultaneous stress radiography in differentiating between complete and partial acute ACL tears, and further assess the correlation between the two measurements. Methods A total of 106 patients with complete acute ACL tears and 52 patients with partial acute ACL tears were included in the study. Preoperative arthrometry and simultaneous stress radiography were performed using the Ligs arthrometer at 90, 120, and 150 N to assess side‐to‐side difference (SSD) in anterior knee laxity. The optimal threshold was determined using the receiver operating characteristic (ROC) curve. The area under the ROC curve (AUC) was used to assess the diagnostic value of the measurement. Pearson's correlation coefficient was used to assess the correlation between the two measurements. Results The optimal differential SSD thresholds in the Ligs arthrometer were 2.7 mm at 90 N, 3.8 mm at 120 N, and 4.6 mm at 150 N. Similarly, the optimal differential SSD thresholds in simultaneous stress radiography were 3.8 mm at 90 N, 5.1 mm at 120 N, and 5.6 mm at 150 N. The AUC analysis revealed that the Ligs arthrometer was fairly informative at 90 N (AUC = 0.851), 120 N (AUC = 0.878), and 150 N (AUC = 0.884), and simultaneous stress radiography was highly informative at 90 N (AUC = 0.910), 120 N (AUC = 0.925), and 150 N (AUC = 0.948). Moreover, the AUC of the combined measurements was 0.914 at 90 N, 0.931 at 120 N, and 0.951 at 150 N. A significantly strong correlation was found between the two measurements at 90 N (r = 0.743, p

This paper reports the control strategy for the core power in an accelerator drive sub-critical (ADS) system. In an ADS system, the intense external neutron source provided by a proton accelerator coupled to a spallation target is used to drive a sub-critical reactor. The proposed control strategy is to control the reactor power by adjusting the proton beam power, where the beam power is adjusted by changing either the duty factor or the intensity of the proton beam. As an example, the reactor power control of the China initiative Accelerator Driven System (CiADS) facility has been studied by adjusting the beam power. Firstly, the beam power is set roughly by assigning a new duty factor, where the duty factor is set by changing the beam macro-pulse length and the pulse repetition rate of the proton beam. Both the pulse length and the repetition rate are assigned by a timing system. Secondly, the power is adjusted precisely by changing the beam intensity. To change continuously the beam intensity, an adjustable aperture is used to block the outer particles of the beam line in the accelerator. In order to evaluate the proposed control strategy, a CiADS core model is built based on the multi-node point reactor dynamics model. Three cases, the start of the facility, the decrease of core power and the increase of core power, have been simulated with the model. The simulation results indicate that the control strategy for the core power by changing either the duty factor or the intensity of the proton beam works very well during the operation of the facility.

Abstract Adenoid hypertrophy can lead to adenoidal mouth breathing, which can result in “adenoid face” and, in severe cases, can even lead to respiratory tract obstruction. The Fujioka ratio method, which calculates the ratio of adenoid (A) to nasopharyngeal (N) space in an adenoidal-cephalogram (A/N), is a well-recognized and effective technique for detecting adenoid hypertrophy. However, this process is time-consuming and relies on personal experience, so a fully automated and standardized method needs to be designed. Most of the current deep learning-based methods for automatic diagnosis of adenoids are CNN-based methods, which are more sensitive to features similar to adenoids in lateral views and can affect the final localization results. In this study, we designed a local attention-based method for automatic diagnosis of adenoids, which takes AdeBlock as the basic module, fuses the spatial and channel information of adenoids through two-branch local attention computation, and combines the downsampling method without losing spatial information. Our method achieved mean squared error (MSE) 0.0023, mean radial error (MRE) 1.91, and SD (standard deviation) 7.64 on the three hospital datasets, outperforming other comparative methods.

ABSTRACT We analyze the impact of the refractive index of optical fibers on the focusing properties of a miniaturized graded‐index (GRIN) fiber probe. The ABCD ray transfer matrix and characteristic parameters are employed to characterize the working distance, focusing spot size, and the depth of field effectively. The three‐dimensional (3‐D) function diagrams and two‐dimensional (2‐D) graphs are used to illustrate the impact of the no‐core fiber (NCF) refractive index and the center refractive index of GRIN fiber on the focusing properties. Numerical analysis results show that when the length of the NCF is 0.36 mm and the GRIN fiber is 0.1 mm, the variation of the refractive index of the NCF between 1.44 and 1.52 leads to the variation of the working distance in the range of 0.02 mm, while the focusing spot size varies in the range of 5 μm. A comparison of 12 probe samples reveals that a 0.02 difference in the center refractive index of GRIN fiber could result in a 0.16 mm variation in working distance and a variation in focusing spot size of over 3 μm. The experimental results indicate that alterations in the length of the fibers have a considerable effect on the focusing properties of the probe. In contrast, the range of variation in focusing properties with fiber refractive index is relatively limited.

To enhance the security and supervision of emergency materials from their source to transport, thus preventing safety incidents, a tripartite evolution model integrating the government, material production enterprises, and logistics entities is proposed. This model, situated within the framework of a government-established blockchain platform, combines evolutionary game theory and prospect theory. It examines the strategy evolution of emergency material’s security subjects amid diverse government reward punishment measures and enterprise risk perceptions. Our findings indicate that employing dynamic reward–punishment measures not only conserves government regulatory resources but also incentivizes enterprises to enhance the quality of emergency materials security. This dynamic approach effectively encourages responsible behavior, averting rebellious tendencies or speculative mindsets in enterprises with deviating risk perceptions regarding emergency materials security.

Salvia miltiorrhiza is a herbaceous plant that possesses significant medicinal value. Land salinization affects the growth of S. miltiorrhiza, resulting in a decline in its quality and yield. Knotted1-like homeobox (KNOX) genes are transcription factors that play important roles in plant growth and abiotic stress. The characteristics and functions of KNOX genes in S. miltiorrhiza remain unclear. Here, we identified ten KNOX genes in S. miltiorrhiza, all of which possess the characteristic four domains: KNOX1, KNOX2, ELK, and HD. These SmKNOXs were divided into two groups together with homologous genes. Cis-acting element analysis indicated all SmKNOXs contained elements associated with phytohormone, light, and stress response. The SmKNOXs show tissue-specific expression among roots, stems, leaves, and flowers. We assessed the response of the SmKNOXs to salt stress using quantitative RT-PCR analysis. Notably, SmKNOX4 expression significantly decreased within 24 h of salt exposure, while SmKNOX1, SmKNOX2, SmKNOX3, SmKNOX8, and SmKNOX9 showed significant increases. The expression of SmKNOX1, SmKNOX2, and SmKNOX3 was significantly positively correlated with that of their target genes, GA20ox1 and S11 MYB. These findings suggest that SmKNOXs and their target genes respond to salt stress, providing a foundation for studies of SmKNOXs and the potential genetic improvement of S. miltiorrhiza.

Oxidative stress, a critical factor affecting the health and productivity of aquatic organisms, arises from the imbalance between reactive oxygen species (ROS) production and antioxidant defenses. In aquaculture, natural antioxidants have gained increasing attention as sustainable feed additives to mitigate oxidative damage, enhance immune responses, and improve overall growth performance. This review provides a comprehensive synthesis of the antioxidative mechanisms of key natural antioxidants, including carotenoids, polysaccharides, vitamins, polyphenols, and flavonoids. By neutralizing ROS and modulating cellular signaling pathways such as Nrf2/ARE, these compounds offer significant protective effects against oxidative damage in aquatic species. The manuscript consolidates recent advancements in antioxidant research, highlighting their practical applications in feed formulation and their role in promoting sustainability in aquaculture. This review aims to provide an integrative framework for understanding natural antioxidants’ potential, guiding future research and practical implementation in aquaculture systems.

Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color is also closely related to melanin, so understanding the mechanisms and proteins that produce melanin is very important. There are many proteins involved in the process of melanin expression, For example, proteins involved in melanin formation such as p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) and pax3 (paired box gene 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 (tyrosinase-related protein-2), and can be regulated by changing their content to control the production rate of melanin. Others, such as OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) and Mlph (Melanophilin), have been found to control the transfer rate of melanosomes from melanocytes to keratinocytes, and regulate the amount of human epidermal melanin to control the depth of human skin color. In addition to the above proteins, there are other protein families also involved in the process of melanin expression, such as BLOC, Rab and Rho. This article reviews the origin of melanocytes, the related proteins affecting melanin and the basic causes of related gene mutations. In addition, we also summarized the active ingredients of 5 popular whitening cosmetics and their mechanisms of action.

Abstract Chinese classical gardens, an essential part of World Cultural Heritage, are well exemplified by Xishu Garden as a notable branch of this tradition. This research focuses on the San Su Shrine—a quintessential example of Xishu Garden—and explores the application of digital technologies in the commemorative research and quantitative preservation of these gardens. By integrating terrestrial laser scanning and terrestrial digital photogrammetry, we acquired quantitative data and constructed digital models to innovate upon the methodological approach to garden conservation. The innovation of this study is its analysis of Xishu Garden’s commemorative spaces through both temporal and spatial dimensions. 1) Temporally, this study examines the evolution and stratification of the garden's commemorative elements across various historical periods. 2) Spatially, it explores the interconnectedness of commemorative elements within the garden's buildings, rockery stones, water landscape and plant landscape. This dual-faceted approach yields novel insights and methods for assessing the universal value of the commemorative aspects of Xishu Garden. Moreover, it promotes the application of digital technology in the study and preservation of Xishu and other Chinese classical gardens.

Objective To investigate the prognostic value of reactive oxygen species metabolic derivatives(D-ROM) in elderly patients with heart failure before and after cardiopulmonary exercise testing. Methods A prospective study was conducted on 300 elderly patients with acute heart failure admitted to Xinjiang Uygur Autonomous Region People's Hospital from July 2020 to September 2021.The patients were followed up for 1 year and divided into a poor prognosis group(45 cases) and a good prognosis group(255 cases) according to their prognosis.The clinical laboratory data of the patients were collected,and cardiopulmonary exercise tests were performed after the patients were stable to detect the serum D-ROM,superoxide dismutase(SOD),and malondialdehyde(MDA) levels before and after the test;left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),left atrial diameter(LAD),inferior vena cava diameter(IVCD),and interventricular septum thickness(IVST) were measured by echocardiography.Multivariate logistic regression model was used to analyze the related factors affecting the prognosis of patients,and restricte. Results The poor prognosis group was older than the good prognosis group,the proportion of atrial fibrillation was higher than the good prognosis group,LVEDD,IVCD,IVST were longer than the good prognosis group,LVEF was lower than the good prognosis group,D-ROM and D-ROM after exercise were higher than the good prognosis group,the differences were statistically significant(P0.05).Multivariate logistic regression model analysis showed that LVEF,without atrial fibrillation were the independent protective factor for poor prognosis in elderly patients with heart failure(P

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

Background Although both psychological resilience and social support are widely believed to be effective in alleviating post-traumatic psychiatric symptoms in individuals with traumatic events, there has been a lack of comparative analysis of their intervention effects on different post-traumatic psychiatric symptoms. Furthermore, previous studies have mostly failed to control for potential confounding effects caused by different traumatic events. Aims We used the novel network analysis approach to examine the differential moderating effects of psychological resilience and social support on post-traumatic psychiatric symptoms, controlling for the confounding effects of traumatic events. Method We recruited 264 front-line rescuers who experienced the same traumatic event. Quantified edge weights and bridge expected influence (BEI) were applied to compare the alleviating effects of psychological resilience and social support. Results Our study revealed distinct correlations in a sample of front-line rescuers: social support negatively correlates more with psychosomatic symptoms, notably fatigue in depressive networks and sleep disturbance in post-traumatic stress disorder (PTSD) networks, whereas psychological resilience shows fewer such correlations. Quantitative analysis using BEI indicated that psychological resilience more effectively suppresses depressive and anxiety symptom networks, whereas social support more significantly inhibits PTSD symptom networks. Conclusions The current study represents the first attempt to examine the differential effects of psychological resilience and social support on post-traumatic outcomes in real-world emergency rescuers, controlling for the confounding effect of traumatic events. Our results can act as the theoretical reference for future precise and efficient post-trauma psychological interventions.

Iron overload occurs due to excessive iron intake compared to the body’s demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Abstract Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.

Objective: Some studies have proved that polyethylene glycol loxenatide (PEG-Loxe) has significant effects on controlling blood glucose and body weight in patients with type 2 diabetes mellitus (T2DM), but there is still some controversy over the improvement of blood lipid profiles (BLP) and blood pressure (BP), and more evidences are needed to verify such effects. Therefore, this study was conducted to provide a comprehensive evaluation of the efficacy of PEG-Loxe in improving blood glucose (BG), BLP, BP, body mass index (BMI), and body weight (BW) in patients with T2DM for clinical reference.Methods: Randomized controlled trials (RCT) in which PEG-Loxe was applied to treat T2DM were retrieved by searching PubMed, Cochrane Library, Embase, Medline, Scopus, Web of Science, China National Knowledge Infrastructure, China Scientific Journal, Wanfang Data, and SinoMed databases. Outcome measures included BG, BLP, BP, BMI, and BW. RevMan 5.3 software was used to perform data analysis.Results: Eighteen trials were identified involving 2,166 patients. In experimental group 1,260 patients received PEG-Loxe alone or with other hypoglycemic agents, while in control group 906 patients received placebo or other hypoglycemic agents. In the overall analysis, PEG-Loxe significantly reduced the levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2-h PBG), BMI, and BW compared with control group. However, it had no obvious effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP).Conclusion: PEG-Loxe has better hypoglycemic effects compared with placebo in patients with T2DM, but could not significantly improved TG, LDL-C, HDL-C, SBP, and DBP. And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients.Systematic Review Registration:www.inplasy.com, identifier INPLASY202350106

Water diversion is a common strategy to enhance water quality in eutrophic lakes by increasing available water resources and accelerating nutrient circulation. Its effectiveness depends on changes in the source water and lake conditions. However, the challenge of optimizing water diversion remains because it is difficult to simultaneously improve lake water quality and minimize the amount of diverted water. Here, we propose a new approach called dynamic water diversion optimization (DWDO), which combines a comprehensive water quality model with a deep reinforcement learning algorithm. We applied DWDO to a region of Lake Dianchi, the largest eutrophic freshwater lake in China and validated it. Our results demonstrate that DWDO significantly reduced total nitrogen and total phosphorus concentrations in the lake by 7% and 6%, respectively, compared to previous operations. Additionally, annual water diversion decreased by an impressive 75%. Through interpretable machine learning, we identified the impact of meteorological indicators and the water quality of both the source water and the lake on optimal water diversion. We found that a single input variable could either increase or decrease water diversion, depending on its specific value, while multiple factors collectively influenced real-time adjustment of water diversion. Moreover, using well-designed hyperparameters, DWDO proved robust under different uncertainties in model parameters. The training time of the model is theoretically shorter than traditional simulation-optimization algorithms, highlighting its potential to support more effective decision-making in water quality management.

Abstract Background Dioscorea opposita Thunb, as a dual-purpose edible plant with excellent nutritional and medical value, accumulates abundant bioactive compounds, including polysaccharides. Polysaccharides from D. opposita have been widely recognized and studied due to various biological activities, such as anti-inflammatory and anti-cancer, which are influenced by their complex structures. In recent years, numerous studies have investigated the structures and activities of D. opposita polysaccharides, and the relationships between them. However, the detailed structures remain different because the structures are susceptible to various species, producing areas, growth conditions (weather, soil, temperature, moisture, etc.), and extraction and separation methods. In this study, the structures of purified polysaccharides from D. opposita were determined and the biological activities were preliminarily investigated including anti-inflammatory and anti-tumor activities. Results The crude polysaccharides DOP1 and DOP2 were isolated and purified via DEAE-52 and Sephadex G-100 to obtain two purified polysaccharides fractions (DOP1-1 and DOP2-1), with the molecular weights of 15.63 kDa and 32.32 kDa, respectively. The structures of DOP1-1 and DOP2-1 were analyzed by HPLC, FT-IR, methylation, and 1D (1H, 13C) and 2D (HSQC, COSY, TOCSY, and ROESY) NMR spectra. The results indicated the presence of → 2)-β-Manp-(1 → 4)-α-Glcp-(1 → 2)-β-Manp-(1 → , → 1)-β-Manp-(2 → 1)-α-GalpA-(4 →, and → 2)-β-Manp-(1 → 2)-β-Manp-(1 → in DOP1-1, and the ratio was 2:11:5. The bone structure of DOP2-1 was predicted as → 1)-β-d-Galp-(4 → , along with two main branching structures composed of arabinose of different degrees of polymerization. Preliminary anti-inflammatory and anti-tumor activities were investigated. DOP1-1 and DOP2-1 demonstrated inhibitory effects on macrophages cells (RAW264.7). DOP2-1 exhibited anti-tumor effects against hepatocellular carcinoma (SNU-739 and HepG2). Conclusions The structures and bioactivities of DOP1-1 and DOP2-1 were analyzed to provide a basis for the establishment of structure/function relationships. The polysaccharides derived from Dioscorea opposita could be potentially employed in functional food, health care, and pharmaceutical industries. Graphical Abstract

Accurately annotating cell types is a fundamental step in single-cell omics data analysis. Here, the authors develop a computational method called Cellcano based on a two-round supervised learning algorithm to identify cell types for scATAC-seq data and perform benchmarking to demonstrate its accuracy, robustness and computational efficiency.

Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague–Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of “course simulation” type of oligospermia animal model.

Tuna cooking liquid has unpleasant aroma. In our previous studies, Cyberlindnera fabianii JGM9-1 and Lactobacillus plantarum RP26 demonstrated the ability to degrade this unpleasant aroma. However, the mechanism of microbial deodorization remains unclear. In this study, tuna cooking liquid was fermented using JGM9-1 alone, RP26 alone, and a combination of both strains. Changes in volatile aromatic compounds during fermentation were analyzed using HS-SPME-GC/MS. The unpleasant aroma of tuna cooking liquid were nine characteristic aromatic compounds associated with fishy, stinky, and greasy aromas. Furthermore, we found that the fermentation of microbes removed these unpleasant aromatic compounds and replaced them with pleasant aromatic compounds that contributed to fruity, grassy, and floral aromas. Finally, we screened 21 strong pairwise correlations between the production and consumption of characteristic volatile aromatic compounds by RP26 and JGM9-1, through HCA, VIP, OAV and Spearman’s pairwise correlation analysis. These results help to clarify the metabolic mechanisms of microbial deodorization in tuna cooking liquid.

Abstract N‐Glycosylation, a main post‐translational modification of Immunoglobulin G (IgG), plays a significant role in modulating the immune functions of IgG. However, the precise function elucidation of IgG N‐glycosylation remains impeded due to the obstacles in obtaining comprehensive and well‐defined N‐glycans. Here, an easy‐to‐implement divergent approach is described to synthesize a 64‐membered IgG N‐glycan library covering all possible biantennary and bisected N‐glycans by reprogramming biosynthetic assembly lines based on the inherent branch selectivity and substrate specificity of enzymes. The unique binding specificities of 64 N‐glycans with different proteins are deciphered by glycan microarray technology. This unprecedented collection of synthetic IgG N‐glycans can serve as standards for N‐glycan structure identification in complex biological samples and the microarray data enrich N‐glycan glycomics to facilitate biomedical applications.

This paper proposed a novel distributed memetic evolutionary model, where four modules distributed exploration, intensified exploitation, knowledge transfer, and evolutionary restart are coevolved to maximize their strengths and achieve superior global optimality. Distributed exploration evolves three independent populations by heterogenous operators. Intensified exploitation evolves an external elite archive in parallel with exploration to balance global and local searches. Knowledge transfer is based on a point-ring communication topology to share successful experiences among distinct search agents. Evolutionary restart adopts an adaptive perturbation strategy to control search diversity reasonably. Quantum computation is a newly emerging technique, which has powerful computing power and parallelized ability. Therefore, this paper further fuses quantum mechanisms into the proposed evolutionary model to build a new evolutionary algorithm, referred to as quantum-inspired distributed memetic algorithm (QDMA). In QDMA, individuals are represented by the quantum characteristics and evolved by the quantum-inspired evolutionary optimizers in the quantum hyperspace. The QDMA integrates the superiorities of distributed, memetic, and quantum evolution. Computational experiments are carried out to evaluate the superior performance of QDMA. The results demonstrate the effectiveness of special designs and show that QDMA has greater superiority compared to the compared state-of-the-art algorithms based on Wilcoxon’s rank-sum test. The superiority is attributed not only to good cooperative coevolution of distributed memetic evolutionary model, but also to superior designs of each special component.

Background: The elevated Cyclin B1 expression contributes to various tumorigenesis and poor prognosis. Cyclin B1 expression could be regulated by ubiquitination and deubiquitination. However, the mechanism of how Cyclin B1 is deubiquitinated and its roles in human glioma remain unclear. Methods: Co-immunoprecipitation and other assays were performed to detect the interacting of Cyclin B1 and USP39. A series of in vitro and in vivo experiments were performed to investigate the effect of USP39 on the tumorigenicity of tumor cells. Results: USP39 interacts with Cyclin B1 and stabilizes its expression by deubiquitinating Cyclin B1. Notably, USP39 cleaves the K29-linked polyubiquitin chain on Cyclin B1 at Lys242. Additionally, overexpression of Cyclin B1 rescues the arrested cell cycle at G2/M transition and the suppressed proliferation of glioma cells caused by USP39 knockdown in vitro. Furthermore, USP39 promotes the growth of glioma xenograft in subcutaneous and in situ of nude mice. Finally, in human tumor specimens, the expression levels of USP39 and Cyclin B1 are positively relevant. Conclusion: Our data support the evidence that USP39 acts a novel deubiquitinating enzyme of Cyclin B1 and promoted tumor cell proliferation at least in part through Cyclin B1 stabilization, represents a promising therapeutic strategy for tumor patients.

Genome-wide profiling of chromatin accessibility by DNase-seq or ATAC-seq has been widely used to identify regulatory DNA elements and transcription factor binding sites. Here the authors develop a computational model, SELMA, to estimate and correct enzymatic cleavage biases in chromatin accessibility profiling data.

To further improve the performance of reversible data hiding in encrypted image, an algorithm for lossless compression of the prediction error bit-plane using joint encoding was proposed, which could make full use of image redundancy and reserve more embedding room.Firstly, the image owner calculated the prediction error of the image and divided the prediction error bit-plane into non-overlapping blocks of the same size.Then, the prediction error bit-plane was rearranged according to blocks and the rearranged bitstream was compressed by run-length encoding and Huffman encoding to reserve room.The data hider embedded information in the reserved room of the encrypted image.At the receiving end, the legitimate receiver extracted information and recovered images losslessly and separately.Experimental results show that the proposed algorithm makes full use of the bit-plane distribution characteristics and achieves higher embedding performance.The average embedding rates in BOSSbase and BOWS-2 datasets reach 3.763 bpp and 3.642 bpp, which are at least 0.081 bpp and 0.058 bpp higher than the state-of-the-art algorithms.

Abstract Background Postoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations. Methods This was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively. Results The complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01–0.27; P

This paper proposes a new topology optimization formulation for obtaining shape memory alloy actuators which are designed with prescribed two-way transforming shapes. The actuation behaviors of shape memory alloy structures are governed by austenite-martensite phase transformations effected by thermal-mechanical loading processes; therefore, to realize the precise geometric shape variations of shape memory alloy actuators, traditional methods involve iteration processes including heuristic structural design, numerical predictions and experimental validation. Although advanced structural optimization methods such as topology optimization have been used to design three-dimensional (3D) shape memory alloy actuators, the maximization/minimization of quantities such as structural compliance or inaccurate stroke distances has usually been selected as the optimization objective to obtain feasible solutions. To bridge the gap between precise shape-morphing requirements and efficient shape memory alloy actuator designs, this paper formulates optimization criteria with quantitatively desired geometric shapes, and investigates the automatic designs of two-way prescribed shape morphing shape memory alloy structures based on the proposed topology optimization method. The super element method and adjoint method are used to derive the analytical sensitivities of the objective functions with respect to the design variables. Numerical examples demonstrate that the proposed method can obtain 3D actuator designs that have the desired two-way transforming shapes.

This paper reports the control method for the core power of the China initiative Accelerator Driven System (CiADS) facility. In the CiADS facility, an intense external neutron source provided by a proton accelerator coupled to a spallation target is used to drive a sub-critical reactor. Without any control rod inside the sub-critical reactor, the core power is controlled by adjusting the proton beam intensity. In order to continuously change the beam intensity, an adjustable aperture is considered to be used at the Low Energy Beam Transport (LEBT) line of the accelerator. The aperture size is adjusted based on the Proportional Integral Derivative (PID) controllers, by comparing either the setting beam intensity or the setting core power with the measured value. To evaluate the proposed control method, a CiADS core model is built based on the point reactor kinetics model with six delayed neutron groups. The simulations based on the CiADS core model have indicated that the core power can be controlled stably by adjusting the aperture size. The response time in the adjustment of the core power depends mainly on the adjustment time of the beam intensity.

Abstract During the lifetime of females, mammary epithelial cells undergo cyclical expansion and proliferation depending on the cyclical activation of mammary gland stem/progenitor cells (MaSCs) in response to the change of hormone level. The structural shrink of mammary duct tree and the functional loss of mammary gland occur along with inactivation of MaSCs in old females, even leading to breast cancer occasionally. However, the gene expression signature in MaSCs across the lifespan remains unclear. Herein, we tested the tissue regeneration ability of CD24+CD49fhigh MaSCs over six time points from neonatal (4-day-old) to aged mice (360-day-old). Further RNA-seq analyses identified four clusters of gene signatures based on the gene expression patterns. A subset of stemness-related genes was identified, showing the highest level at day 4 of the neonatal age, and the lowest level at the old age. We also identified an aging-related gene signature showing significant change in the old mice, in which an association between aging process and stemness loss was indicated. The aging-related gene signature showed regulation of cancer signaling pathways, as well as aging-related diseases including Huntington disease, Parkinson disease, and Alzheimer disease. Moreover, 425, 1056, 418, and 1107 gene variants were identified at D20, D40, D90, and D180, respectively, which were mostly reported to associated with tumorigenesis and metastasis in cancer. In summary, the current study is the first to demonstrate the gene expression shift in MaSCs from neonatal to aging, which leads to stemness loss, aging, aging-related diseases, and even breast cancer in old mice.

BackgroundFirefighters, as first responders with a high risk of occupational exposure to traumatic events and heavy working stress, have a high prevalence of PTSD symptoms and depressive symptoms. But no previous studies analyzed the relationships and hierarchies of PTSD and depressive symptoms among firefighters. Network analysis is a novel and effective method for investigating the complex interactions of mental disorders at the symptom level and providing a new understanding of psychopathology. The current study was designed to characterize the PTSD and depressive symptoms network structure in the Chinese firefighters.MethodThe Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the Self-Rating Depression Scale (SDS) were applied to assess PTSD and depressive symptoms, respectively. The network structure of PTSD and depressive symptoms was characterized using “expected influence (EI)” and “bridge EI” as centrality indices. The Walktrap algorithm was conducted to identify communities in the PTSD and depressive symptoms network. Finally, Network accuracy and stability were examined using the Bootstrapped test and the case-dropping procedure.ResultsA total of 1,768 firefighters were enrolled in our research. Network analysis revealed that the relationship between PTSD symptoms, “Flashback” and “Avoidance,” was the strongest. “Life emptiness” was the most central symptom with the highest EI in the PTSD and depression network model. Followed by “Fatigue” and “Interest loss.” Bridge symptoms connecting PTSD and depressive symptoms in our study were “Numb,” “High alertness,” “Sad mood,” and “Compunction and blame,” successively. The data-driven community detection suggested the differences in PTSD symptoms in the clustering process. The reliability of the network was approved by both stability and accuracy tests.ConclusionTo the best of our knowledge, the current study first demonstrated the network structure of PTSD and depressive symptoms among Chinese firefighters, identifying the central and bridge symptoms. Targeting interventions to the symptoms mentioned above may effectively treat firefighters suffering from PTSD and depressive symptoms.

IntroductionThe rapid growth in the population of older adults has put tremendous pressure on medical and social services in countries including China. Community care services are a feasible solution for promoting healthy aging in developing countries. This study investigated the association between community care services and the health of older adults in China.MethodUsing nationally representative survey data from China, consisting of four waves conducted in 2005, 2008, 2011, and 2014, a balanced panel dataset was constructed using a sample of 4,700 older adults (33.1% aged 80 years or older, 51.0% residing in rural areas, and 48.8% women). We employed linear regression models with time-fixed effects and instrumental variable approaches to estimate the effect of community care services on the health of older adults, as well as the differences in these effects across subgroups.ResultsThe results showed that community care services lead to a significant improvement in both the objective and subjective health and wellbeing of older adults. Among the various service offerings, spiritual recreation services led to a significant increase in both objective and subjective health scores, while medical care services significantly improved wellbeing. This suggests a varied effect of subdivided service types. Further evidence suggests that spiritual recreation services have a significant health-enhancing effect on multiple groups of older adults, and the effect of medical care services is more effective for those living in rural areas, women, and those who are older than 80 years (all p < 0.05).DiscussionFew studies have examined the impact of community care services on the health of older adults in developing countries. The findings present important implications for improving the health status of older adults and provide suggestions for establishing a socialized aged care system in China.

Abstract In the ship design, there are strict vibration‐proof requirements for precision instruments. Therefore, a ship repulsive magnetic levitation damping device is designed to achieve vibration reduction. And one self‐tuning predictive control method is proposed to achieve the stable levitation of this device. Firstly, a predictive control (MPC) method with state constraints and input constraints is adopted to realise the stable suspension of the floater. The MPC can solve the problem of position imbalance of the magnetic levitation system under the external complex disturbances. Secondly, a self‐tuning MPC method based on recursive least square is proposed to solve the problem caused by the fixed parameters of the traditional predictive controller. At the beginning of each control cycle, the recursive least‐squares (RLS) method is used to estimate the parameters of the system. Thus, the optimal control model could be obtained for the current situation. Then, this model is applied to the predictive controller to solve the problem of parameter fixation in the traditional predictive control. Finally, the simulation results show that it can improve the accuracy, dynamic response and anti‐interference performance obviously.

Glioma cells are characterized by high migration and invasion ability; however, the molecular mechanism behind both processes still remains to be investigated. Several studies have demonstrated that ubiquitin‐specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression was significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with short hairpin RNA (shRNA) against USP39 revealed that disintegrin and metalloproteinase domain‐containing protein 9 (ADAM9), a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Furthermore, USP39 induced ADAM9 messenger RNA (mRNA) maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data show that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered potential target for treating patients with glioma.

Abstract Excess mental stress may harm health, and even accelerate cancer initiation and progression. One fourth of breast cancer patients suffer mental stress including anxiety, sadness, or depression, which negatively affect prognosis and survival. However, the regulatory mechanism is yet to be determined. Herein, we applied unpredictable stress stimuli to the breast tumor-bearing mice to establish a xenograft model of breast cancer suffering mental stress, followed by behavioral tests, tumor growth tracking, immune analysis, miRNA screening, and tumor cell proliferation analysis as well. As a result, increased stress hormone levels in serum, decreased percentage of T and NK cells in both blood and tumor samples and accelerated tumor growth in vivo were observed in the mice exposed to mental stress. Promoted cell proliferation was observed in both primary tumor cells derived from the stressed mice and 4T1 breast cancer cells treated with stress hormone corticosterone. In addition, a subset of miRNAs including miR-326, 346, 493, 595, 615, and 665 were identified through a miRNA screening with downregulation in tumors of the stressed mice. CCND1 was identified as a common target gene of miR-346 and miR-493, the top two most significantly downregulated miRNAs by stress exposure. The stress-miRNA-CCND1 signaling regulation of the tumor cell proliferation was further validated in 4T1 cells treated with corticosterone in vitro. GO terms and KEGG pathways analyses on the target genes of miR-346 and miR-493 revealed their involvement in the regulation of human cancer and neuron system, indicating the importance of non-coding genome in mediating the mental stress-induced cancer regulation. In conclusion, this study not only explored immune and nonimmune mechanisms through which mental stress exposure contributes to tumor growth in breast cancer, but also suggested a new therapeutic strategy for cancer patients suffering mental stress.

Abstract Background Cell type identification is one of the most important questions in single-cell RNA sequencing (scRNA-seq) data analysis. With the accumulation of public scRNA-seq data, supervised cell type identification methods have gained increasing popularity due to better accuracy, robustness, and computational performance. Despite all the advantages, the performance of the supervised methods relies heavily on several key factors: feature selection, prediction method, and, most importantly, choice of the reference dataset. Results In this work, we perform extensive real data analyses to systematically evaluate these strategies in supervised cell identification. We first benchmark nine classifiers along with six feature selection strategies and investigate the impact of reference data size and number of cell types in cell type prediction. Next, we focus on how discrepancies between reference and target datasets and how data preprocessing such as imputation and batch effect correction affect prediction performance. We also investigate the strategies of pooling and purifying reference data. Conclusions Based on our analysis results, we provide guidelines for using supervised cell typing methods. We suggest combining all individuals from available datasets to construct the reference dataset and use multi-layer perceptron (MLP) as the classifier, along with F-test as the feature selection method. All the code used for our analysis is available on GitHub ( https://github.com/marvinquiet/RefConstruction_supervisedCelltyping ).

Abstract Background Septic shock comprises a heterogeneous population, and individualized resuscitation strategy is of vital importance. The study aimed to identify subclasses of septic shock with non-supervised learning algorithms, so as to tailor resuscitation strategy for each class. Methods Patients with septic shock in 25 tertiary care teaching hospitals in China from January 2016 to December 2017 were enrolled in the study. Clinical and laboratory variables were collected on days 0, 1, 2, 3 and 7 after ICU admission. Subclasses of septic shock were identified by both finite mixture modeling and K-means clustering. Individualized fluid volume and norepinephrine dose were estimated using dynamic treatment regime (DTR) model to optimize the final mortality outcome. DTR models were validated in the eICU Collaborative Research Database (eICU-CRD) dataset. Results A total of 1437 patients with a mortality rate of 29% were included for analysis. The finite mixture modeling and K-means clustering robustly identified five classes of septic shock. Class 1 (baseline class) accounted for the majority of patients over all days; class 2 (critical class) had the highest severity of illness; class 3 (renal dysfunction) was characterized by renal dysfunction; class 4 (respiratory failure class) was characterized by respiratory failure; and class 5 (mild class) was characterized by the lowest mortality rate (21%). The optimal fluid infusion followed the resuscitation/de-resuscitation phases with initial large volume infusion and late restricted volume infusion. While class 1 transitioned to de-resuscitation phase on day 3, class 3 transitioned on day 1. Classes 1 and 3 might benefit from early use of norepinephrine, and class 2 can benefit from delayed use of norepinephrine while waiting for adequate fluid infusion. Conclusions Septic shock comprises a heterogeneous population that can be robustly classified into five phenotypes. These classes can be easily identified with routine clinical variables and can help to tailor resuscitation strategy in the context of precise medicine.

Using data from 30 provincial-level in China during 2005–2019, this paper investigates the impact of foreign direct investment (FDI) quality characteristics on carbon emission intensity. Based on the Copeland-Taylor model, the mechanism of the impact of FDI quality characteristics on carbon emission intensity is also investigated. The key findings demonstrate that FDI quality traits considerably lower regional carbon intensity, and the result is still robust after considering the spatial correlation and using IV-2sls in consideration of endogeneity. The FDI quality characteristics mainly reduce carbon emission intensity through green technology improvement, industrial structure, and factor endowment structure optimization. Moreover, further evidence shows that there are heterogeneous effects with regard to regional and FDI quality characteristics. From the standpoint of FDI quality characteristics, this study adds to the literature on FDI and environmental pollution. Policy recommendations for China are also discussed in this paper, which can serve as a guide for other emerging nations.

China recently commenced the Sponge City initiative for the effective management of urban stormwater runoff. Numerous studies have been carried out to evaluate the cost-effectiveness of low impact development (LID) practices in Sponge City planning and implementation. However, most of the studies were at the site- or subcatchment scale, and few were conducted at the watershed scale, given the dramatically increased routing complexity and number of decision variables. This study demonstrates the cost-effective Sponge City planning process for a 25.90 km2 high-plateau watershed in southwest China. The Stormwater Management Model was coupled with the System for Urban Stormwater Treatment and Analysis Integrated (SUSTAIN) model to perform both continuous simulations and watershed-level optimization analyses, using the reduction of 85% annual runoff volume as the optimization target. Based on over 11,000 optimization runs, a near-optimal aggregated LID scenario was identified for each subcatchment. The aggregated LID size was first converted into a generic LID storage volume for individual subcatchments, and the storage volume was then disaggregated into site-level LID layouts regarding specific site conditions. The disaggregated LID layout yielded an annual average runoff volume reduction of 87.61% and close to 85% reduction for the annual average total suspended solids, total nitrogen, and total phosphorus loads. The systematic approach outlined in this study could be used for watershed-level Sponge City planning and implementation analyses in other cities.

Plant microbiota are of great importance for host nutrition and health. As a C4 plant species with a high carbon fixation capacity, sugarcane also associates with beneficial microbes, though mechanisms underlying sugarcane root-associated community development remain unclear. Here, we identify microbes that are specifically enriched around sugarcane roots and report results of functional testing of potentially beneficial microbes propagating with sugarcane plants. First, we analyzed recruitment of microbes through analysis of 16S rDNA enrichment in greenhouse cultured sugarcane seedlings growing in field soil. Then, plant-associated microbes were isolated and assayed for beneficial activity, first in greenhouse experiments, followed by field trials for selected microbial strains. The promising beneficial microbe SRB-109, which quickly colonized both roots and shoots of sugarcane plants, significantly promoted sugarcane growth in field trials, nitrogen and potassium acquisition increasing by 35.68 and 28.35%, respectively. Taken together, this report demonstrates successful identification and utilization of beneficial plant-associated microbes in sugarcane production. Further development might facilitate incorporation of such growth-promoting microbial applications in large-scale sugarcane production, which may not only increase yields but also reduce fertilizer costs and runoff.

An amendment to this paper has been published and can be accessed via the original article.

It remains a challenge to prepare flame-retardant composites via the addition of a low content of flame retardant. In this work, a novel DOPO-functionalized reduced graphene oxide hybrid (DOPO-M-rGO) flame-retardant system was synthesized for epoxy resin (EP). The phosphorus-nitrogen-reduced graphene oxide ternary synergistic effect provided DOPO-M-rGO with high flame-resistance efficiency in EP; thus, the EP-based composite exhibited superior fire-resistant performance at extremely low DOPO-M-rGO loading. The limiting oxygen index (LOI) of the EP-based composite was increased from 25% to 32% with only 1.5 wt% DOPO-M-rGO addition, and the peak heat release rate (pHRR), total heat release (THR), and total smoke production (TSP) were significantly decreased by 55%, 30%, and 20%, respectively. In addition, as a halogen-free flame-retardant system, DOPO-M-rGO presents great application potential as an eco-friendly additive for the flame-resistance improvement of thermosetting polymer materials.

Illegal use of salbutamol (SAL), a β-adrenergic leanness-enhancing agent, has posed potential threat to human health in China. The excretion and depletion of SAL in pigs and goats were investigated, and the concentration correlations between edible tissues and living samples were analyzed to find out a suitable living sample for pre-slaughter monitoring of SAL in pigs and goats. After a single oral dosage of 1.2 mg/kg SAL, approximately 70% of the dose was excreted by pigs and goats from their excreta. When pigs and goats were supplied feed containing SAL (20 mg/kg) for 14 consecutive days, high concentrations of SAL were observed in the liver and kidneys, and the longest persistence was observed in hair. Unlike pigs, SAL was presented primarily as conjugated SAL in goats. Excellent concentration correlations of SAL were observed between urine and edible tissues both in pigs and goats, and in addition, good correlations also were found between hair and edible tissues in pigs and between feces and edible tissues in goats. Hence, urine and hair could accurately predict SAL concentrations in edible tissues of pigs, whereas feces and urine were satisfactory for predicting SAL concentrations in edible tissues of goats. These data make it possible for pre-slaughter monitoring of SAL residues in the edible tissues of pigs and goats.

Acute myeloid leukemia (AML) is the most common subtype of hematological malignancy in humans, and its incidence increases with age. The treatment of AML still faces challenges. Therefore, there is an urgent need to develop more effective targeted therapies. The receptor tyrosine kinase C-KIT confers critical proliferative signals to AML. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an endogenous inhibitor of protein phosphatase 2A (PP2A), which promotes the growth and transformation of various solid tumors. These actions make CIP2A a promising target for tumor treatment. Here, we reported the effects and underlying mechanisms of a natural compound, cucurbitacin B (CuB), on AML. We reported that CuB suppressed growth and induced apoptosis in AML cells. The inhibition of growth and activation of apoptosis were mediated through CuB-induced downregulation of the CIP2A/PP2A/C-KIT signal pathway. Furthermore, CuB inactivated the JAK2 and STAT3 molecules downstream of C-KIT via the downregulation of CIP2A. These results advance our understanding of CuB-induced growth inhibition and apoptosis and support further investigation of CuB as a CIP2A inhibitor for AML therapies. Keywords: Cucurbitacin B, Acute myeloid leukemia, CIP2A, C-KIT, PP2A

Doxorubicin (Dox) is a widely utilized chemotherapeutic; however, it carries side effects, including drug-induced immune thrombocytopenia (DITP) and increased risk of venous thromboembolism (VTE). Currently, the mechanisms for Dox-associated DITP and VTE are poorly understood, and an effective inhibitor to relieve these complications remains to be developed. In this study, we found that Dox significantly induced platelet activation and enhanced platelet phagocytosis by macrophages and accelerated platelet clearance. Importantly, we determined that salvianolic acid C (SAC), a water-soluble compound derived from Danshen root traditionally used to treat cardiovascular diseases, inhibited Dox-induced platelet activation more effectively than current standard-of-care anti-platelet drugs aspirin and ticagrelor. Mechanism studies with tyrosine kinase inhibitors indicate contributions of phospholipase C, spleen tyrosine kinase, and protein kinase C signaling pathways in Dox-induced platelet activation. We further demonstrated that Dox enhanced platelet-cancer cell interaction, which was ameliorated by SAC. Taken together, these findings suggest SAC may be a promising therapy to reduce the risk of Dox-induced DITP, VTE, and the repercussions of amplified platelet-cancer interaction in the tumor microenvironment.

Nuclear factor Y (NF-Y) is a ubiquitous transcription factor in eukaryotes, which is composed of three subunits (NF-YA, NF-YB, and NF-YC). NF-Y has been identified as a key regulator of multiple pathways in plants. Although the NF-Y gene family has been identified in many plants, it has not been reported in potato (Solanum tuberosum). In the present study, a total of 41 NF-Y proteins in potato (StNF-Ys) were identified, including 10 StNF-YA, 22 StNF-YB, and nine StNF-YC subunits, and their distribution on chromosomes, gene structure, and conserved motif was analyzed. A synteny analysis indicated that 14 and 38 pairs of StNF-Y genes were orthologous to Arabidopsis and tomato (Solanum lycopersicum), respectively, and these gene pairs evolved under strong purifying selection. In addition, we analyzed the expression profiles of NF-Y genes in different tissues of double haploid (DM) potato, as well as under abiotic stresses and hormone treatments by RNA-seq downloaded from the Potato Genome Sequencing Consortium (PGSC) database. Furthermore, we performed RNA-seq on white, red, and purple tuber skin and flesh of three potato cultivars at the tuber maturation stage to identify genes that might be involved in anthocyanin biosynthesis. These results provide valuable information for improved understanding of StNF-Y gene family and further functional analysis of StNF-Y genes in fruit development, abiotic stress tolerance, and anthocyanin biosynthesis in potato.