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Abstract Objectives This study aimed at exploring how using different kinds of sheaths will affect the very first ablation procedure of apprentices. Methods 15 patients with paroxysmal atrial fibrillation were randomized to used fixed-curve, conventional steerable or visualized steerable sheath, and received complete isolation of pulmonary veins. All ablations were the very first procedure performed by 15 ablation apprentices. The use of fluoroscopy and catheter stability during the PVI were analyzed. Results Procedure duration was much longer in the fixed-curve group (116.8 ± 27 vs. 62.2 ± 17 vs. 60.4 ± 17, p

Abstract Background The causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence. Methods Mendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease. Results In the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations. Conclusions This study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.

Abstract Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

Abstract We demonstrate an adaptation of deep learning for label-free imaging of the micro-scale lymphatic vessels and aqueous veins in the eye using optical coherence tomography (OCT). The proposed deep learning-based OCT lymphangiography (DL-OCTL) method was trained, validated and tested, using OCT scans (23 volumetric scans comprising 19,736 B-scans) from 11 fresh ex vivo porcine eyes with the corresponding vessel labels generated by a conventional OCT lymphangiography (OCTL) method based on thresholding with attenuation compensation. Compared to conventional OCTL, the DL-OCTL method demonstrates comparable results for imaging lymphatics and aqueous veins in the eye, with an Intersection over Union value of 0.79 ± 0.071 (mean ± standard deviation). In addition, DL-OCTL mitigates the imaging artifacts in conventional OCTL where the OCT signal modelling was corrupted by the tissue heterogeneity, provides ~ 10 times faster processing based on a rough comparison and does not require OCT-related knowledge for correct implementation as in conventional OCTL. With these favorable features, DL-OCTL promises to improve the practicality of OCTL for label-free imaging of lymphatics and aqueous veins for preclinical and clinical imaging applications.

Abstract It is vital to investigate the complex mechanisms underlying tumors to better understand cancer and develop effective treatments. Metabolic abnormalities and clinical phenotypes can serve as essential biomarkers for diagnosing this challenging disease. Additionally, genetic alterations provide profound insights into the fundamental aspects of cancer. This study introduces Cancer-Alterome, a literature-mined dataset that focuses on the regulatory events of an organism’s biological processes or clinical phenotypes caused by genetic alterations. By proposing and leveraging a text-mining pipeline, we identify 16,681 thousand of regulatory events records encompassing 21K genes, 157K genetic alterations and 154K downstream bio-concepts, extracted from 4,354K pan-cancer literature. The resulting dataset empowers a multifaceted investigation of cancer pathology, enabling the meticulous tracking of relevant literature support. Its potential applications extend to evidence-based medicine and precision medicine, yielding valuable insights for further advancements in cancer research.

Colorectal cancer (CRC) stands as a prevalent malignancy globally. A pivotal event in CRC pathogenesis involves the loss-of-function mutation in the APC gene, leading to the formation of benign polyps. Despite the well-established role of APC, the contribution of CUL4B to CRC initiation in the pre-tumorous stage remains poorly understood. In this investigation, we generated a murine model by crossing ApcMin/+ mice with Cul4bΔIEC mice to achieve specific deletion of Cul4b in the gut epithelium against an ApcMin/+ background. By employing histological methods, RNA-sequencing (RNA-seq), and flow cytometry, we assessed alterations and characterized the immune microenvironment. Our results unveiled that CUL4B deficiency in gut epithelium expedited ApcMin/+ adenoma formation. Notably, CUL4B in adenomas restrained the accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs). In vivo inhibition of MDSCs significantly delayed the growth of CUL4B deleted ApcMin/+ adenomas. Furthermore, the addition of MDSCs to in vitro cultured ApcMin/+; Cul4bΔIEC adenoma organoids mitigated their alterations. Mechanistically, CUL4B directly interacted with the promoter of Csf3, the gene encoding granulocyte-colony stimulating factor (G-CSF) by coordinating with PRC2. Inhibiting CUL4B epigenetically activated the expression of G-CSF, promoting the recruitment of MDSCs. These findings offer novel insights into the tumor suppressor-like roles of CUL4B in regulating ApcMin/+ adenomas, suggesting a potential therapeutic strategy for CRC initiation and progression in the context of activated Wnt signaling.

There are two sets of thermal reservoirs with different rock types in the Gucheng geothermal field of Hebei Province, namely the Ordovician fractured carbonate thermal reservoir and the Neogene Guantao sandstone thermal reservoir, each developed using independent well networks. The energy demand per unit area in the region is high, and the existing geothermal development methods cannot meet the regional energy demand. For this type of block, combined with the development characteristics of different types of thermal reservoirs, numerical simulation methods were used to study the geothermal development trends of Ordovician fractured carbonate reservoirs and Neogene Guantao Formation sandstone reservoirs. When simulating sandstone thermal storage, priority should be given to demonstrating the optimal recharge flow rate, while in simulating carbonate thermal storage, the focus should be on considering the influence of fracture development direction on development trends. Through numerical simulation of thermal storage development and combined with well network design, the optimal well spacing, production reinjection flow rate, and reinjection temperature for two sets of thermal reservoirs developed using the same well network were determined. It is predicted that the average heat flow in the study can increase by 47.8 %. This study presents reasonable development technical countermeasures to maximize the heating capacity of the geothermal development zone and provides an effective reference for the efficient development of similar geothermal resources in the Bohai Bay Basin.

Protocatechuic acid (PCA) and protocatechuic aldehyde (PAL) are important phenolic compounds in plants. We here investigated their possible beneficial effect against fungal infection and the underlying mechanism. The model animal of Caenorhabditis elegans was used as host, and Candida albicans was used as fungal pathogen. The nematodes were first infected with C. albicans, and the PCA and PAL treatment were then performed. Post-treatment with 10–100 μM PCA and PAL suppressed toxicity of C. albicans infection in reducing lifespan. Accompanied with this beneficial effect, treatment with 10–100 μM PCA and PAL inhibited C. albicans accumulation in intestinal lumen. In addition, treatment with 10–100 μM PCA and PAL suppressed the increase in expressions of antimicrobial genes caused by C. albicans infection. The beneficial effect of PCA and PAL against C. albicans infection depended on p38 MAPK and insulin signals. Moreover, although treatment with 10–100 μM PCA and PAL could not exhibit noticeable antifungal activity, PCA and PAL treatment obviously suppressed biofilm formation, inhibited hyphal growth, and reduced expressions of virulence genes (ALS3, CaVps34, Vma7, Vac1, and/or HWP1) related to biofilm formation and hyphal growth in C. albicans. Therefore, our data demonstrated the potential of PCA and PAL post-treatment against fungal infection and fungal virulence.

Cartilage damage and synovial inflammation are vital pathological changes in osteoarthritis (OA). Biqi Capsule, a traditional Chinese medicine formula used for the clinical treatment of arthritis in China, yields advantages in attenuating OA progression. The drawback here is that the bioactive components and pharmacological mechanisms by which Biqi Capsule exerts its anti-inflammatory and chondroprotective effects have yet to be fully clarified. For in vivo studies, a papain-induced OA rat model was established to explore the pharmacological effects and potential mechanisms of Biqi Capsule against OA. Biqi Capsule alleviated articular cartilage degeneration and chondrocyte damage in OA rats and inhibited the phosphorylation of NF-κB and the expression of pro-inflammatory cytokines in synovial tissue. Network pharmacology analysis suggested that the primary biological processes regulated by Biqi Capsule are inflammation and oxidative stress, and the critical pathway regulated is the PI3K/AKT signaling pathway. The result of this analysis was later verified on SW1353 cells. The in vitro studies demonstrated that Glycyrrhizic Acid and Liquiritin in Biqi Capsule attenuated H2O2-stimulated SW1353 chondrocyte damage via activation of PI3K/AKT/mTOR pathway. Moreover, Biqi Capsule alleviated inflammatory responses in LPS-stimulated RAW264.7 macrophages via the NF-κB/IL-6 pathway. These observations were suggested to have been facilitated by Brucine, Liquiritin, Salvianolic Acid B, Glycyrrhizic Acid, Cryptotanshinone, and Tanshinone ⅡA. Put together, this study partially clarifies the pharmacological mechanisms and the bioactive components of Biqi capsules against OA and suggests that it is a promising therapeutic option for the treatment of OA. Chemical compounds studied in this article. Strychnine (Pubchem CID:441071); Brucine (Pubchem CID:442021); Liquiritin (Pubchem CID:503737); Salvianolic Acid B (Pubchem CID:6451084); Glycyrrhizic Acid (Pubchem CID:14982); Cryptotanshinone (Pubchem CID:160254); Tanshinone ⅡA (Pubchem CID:164676).

Abstract Background In this study, we evaluated the predictive utility of neutrophil percentage-to-albumin ratio (NPAR) for all-cause mortality in patients with chronic heart failure (CHF). Methods Patients diagnosed as CHF enrolled in this retrospective cohort study were from Beijing Chaoyang Hospital, capital medical university. Admission NPAR was calculated as neutrophil percentage divided by serum albumin. The endpoints of this study were defined as 90-day, 1-year and 2-year all-cause mortality. Multivariable Cox proportional hazard regression model was performed to confirm the association between NPAR and all-cause mortality. Receiver operating characteristics (ROC) curves were used to evaluate the ability for NPAR to predict all-cause mortality. Results The 90-day (P = 0.009), 1-year (P

Abstract The heavy metal, cadmium (Cd), causing growth retardation and yield reduction on rice and impacting the fitness of organisms inhabiting on rice through bottom-up effects, has become a great challenge to rice production. However, the effect of Cd-exposure on the development of an economically important and destructive rice pest, Chilo suppressalis remains unexplored. By exposing the larvae of C. suppressalis to different Cd-exposed artificial diets (0, 0.2, 1.0, 2.5, 5.0, and 10.0 mg/kg), we found that Cd exposure did not affect the larval duration or pupation rate of C. suppressalis, but caused negative effects on pupal weight at high Cd levels (5.0 and 10.0 mg/kg) and on adult deformity rate from 2.5 and 5.0 mg/kg treatments. Although Cd significantly increased the female pupae ratio, C. suppressalis did not oviposit when Cd treatment was more than 2.5 mg/kg. Meanwhile, Cd transferred to pupae, females, exuviae of pupa and eggs of C. suppressalis from Cd treated larvae, and exhibited a dose-dependent response on Cd accumulation. Our results indicated that Cd had a negative effect on rice stem borer and can be transferred to eggs of C. suppressalis, but more work is needed to further assess the bottom-up effect on third tropic levels in Cd-polluted fields.

Abstract When analyzing data from in situ RNA detection technologies, cell segmentation is an essential step in identifying cell boundaries, assigning RNA reads to cells, and studying the gene expression and morphological features of cells. We developed a deep-learning-based method, GeneSegNet, that integrates both gene expression and imaging information to perform cell segmentation. GeneSegNet also employs a recursive training strategy to deal with noisy training labels. We show that GeneSegNet significantly improves cell segmentation performances over existing methods that either ignore gene expression information or underutilize imaging information.

(1) Background: In-stent Restenosis (ISR) is a major factor influencing the prognosis and revascularization of target lesions. The plaque composition is unclear; therefore, it is critical to investigate ISR composition to identify clinical intervention markers. (2) Methods: This study was conducted on 36 patients with drug-eluting stent restenosis. The patients were classified into a Low Neutrophil–Lymphocyte Ratio (L-NLR) and High Neutrophil–Lymphocyte Ratio (H-NLR) according to the median NLR level of 36 patients. Discrepancies in the current information such as baseline data, biochemical examination, cardiac ultrasound data, etc., were examined to identify the underlying risk factors, and a multifactorial linear regression analysis of plaque properties was conducted. (3) Results: NLR = 2.64 was utilized to classify 18 patients into the L-NLR group and 18 patients into the H-NLR group. There were statistically significant differences in age, a pre-percutaneous coronary intervention (PCI) SYNTAX II score, a C-reactive protein (CRP), interleukin (IL)-6, plaque loading, a fibro-lipid tissue area, calcified nubs, and virtual histology-thin fibrous cap atherosclerotic (VH-TCFA). The significant impacts of variations in age, neutrophil–lymphocyte ratio (NLR) levels, and IL-6 levels on the plaque stress and percentage of the fibro-lipid tissue in virtual histology-intravascular ultrasound (VH-IVUS) were identified through multifactorial linear regression. (4) Conclusions: The high NLR group demonstrated increased myocardial injury severity, consistent with higher SYNTAX II scores, a higher plaque burden, and higher proportions of vulnerable components. NLR proved to be a risk factor for both the plaque load and the proportion of the fibro-lipid tissue in ISR.

Transgenerational nanoplastic toxicity could be detected in Caenorhabditis elegans after exposure at the parental generation (P0-G); however, the underlying mechanisms remain largely unclear. We aimed to examine the role of germline nuclear hormone receptors (NHRs) in controlling the transgenerational toxicity of polystyrene nanoparticles (PS-NPs) based on gene expression screening and functional analysis. Among germline NHR genes, daf-12, nhr-14, and nhr-47 expressions were increased and nhr-12 expression was decreased by PS-NPs (1 and 10 μg/L). Transgenerational alterations in expressions of these four NHR genes were also induced by PS-NPs (1 and 10 μg/L). RNAi of daf-12, nhr-14, and nhr-47 caused resistance, whereas RNAi of nhr-12 conferred susceptibility to transgenerational PS-NP toxicity. After PS-NP exposure, expressions of ins-3, daf-28, and ins-39 encoding insulin ligands, efn-3 encoding Ephrin ligand, and lin-44 encoding Wnt ligand, as well as expressions of their receptor genes (daf-2, vab-1, and/or mig-1), were dysregulated by the RNAi of daf-12, nhr-14, nhr-47, and nhr-12. Therefore, alteration in certain germline NHRs could mediate the induction of transgenerational nanoplastic toxicity by affecting secreted ligands and their receptors in the offspring of exposed organisms.

Abstract Cancer relapse and metastasis are major obstacles for effective treatment. One important mechanism to eliminate cancer cells is to induce apoptosis. Activation of executioner caspases is the key step in apoptosis and was considered “a point of no return”. However, in recent years, accumulating evidence has demonstrated that cells can survive executioner caspase activation in response to apoptotic stimuli through a process named anastasis. Here we show that breast cancer cells that have survived through anastasis (anastatic cells) after exposure to chemotherapeutic drugs acquire enhanced proliferation and migration. Mechanistically, cadherin 12 (CDH12) is persistently upregulated in anastatic cells and promotes breast cancer malignancy via activation of ERK and CREB. Moreover, we demonstrate that executioner caspase activation induced by chemotherapeutic drugs results in loss of DNA methylation and repressive histone modifications in the CDH12 promoter region, leading to increased CDH12 expression. Our work unveils the mechanism underlying anastasis-induced enhancement in breast cancer malignancy, offering new therapeutic targets for preventing post-chemotherapy cancer relapse and metastasis.

Abstract Chemotherapy is a common strategy to treat cancer. However, acquired resistance and metastasis are the major obstacles to successful treatment. Anastasis is a process by which cells survive executioner caspase activation when facing apoptotic stress. Here we demonstrate that colorectal cancer cells can undergo anastasis after transient exposure to chemotherapeutic drugs. Using a lineage tracing system to label and isolate cells that have experienced executioner caspase activation in response to drug treatment, we show that anastasis grants colorectal cancer cells enhanced migration, metastasis, and chemoresistance. Mechanistically, treatment with chemotherapeutic drugs induces upregulated expression of cIAP2 and activation of NFκB, which are required for cells to survive executioner caspase activation. The elevated cIAP2/NFκB signaling persists in anastatic cancer cells to promote migration and chemoresistance. Our study unveils that cIAP2/NFκB-dependent anastasis promotes acquired resistance and metastasis after chemotherapy.

Abstract Background Previous studies have shown that insomnia affects human prefrontal function and that there are specific patterns of brain activation to counteract sleep and improve cognition. However, the effects of insomnia on the prefrontal cortex of MDD (major depressive disorder) patients and the patterns of activation to counteract sleep in MDD patients remain unclear. The aim of this study is to examine this using fNIRS (functional near-infrared spectroscopy). Methods Eighty depressed patients and 44 healthy controls were recruited for this study. fNIRS was used to assess changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex of all participants during the VFT (verbal fluency test) and to record the number of words created to assess cognitive ability. The Pittsburgh Sleep Quality Index was used to assess sleep quality, and the Hamilton Rating Scale for Depression (24-item) and Hamilton Rating Scale for Anxiety (14-item) were used to assess the severity of depression and anxiety. Results When comparing patients, the healthy control group had significantly higher [oxy-Hb] values in the bilateral prefrontal cortex during VFT than the MDD group. In the MDD group, the [oxy-Hb] values in all brain regions except the right DLPFC were significantly higher in the group with insomnia than in the group without insomnia, but their VFT performance was significantly lower than in the group without insomnia and the healthy group. PSQI scores were positively correlated with [oxy-Hb] values in some left-brain regions, whereas HAMD and HAMA scores were not correlated with [oxy-Hb] values. Conclusion The PFC was significantly less active during VFT in those with MDD than in healthy controls. All brain regions, except the right DLPFC, were significantly more active in MDD patients with insomnia than in those without insomnia, suggesting that sleep quality needs to be an important indicator in fNIRS screening. In addition, there was a positive correlation between the severity of insomnia in the left VLPFC and the level of activation, suggesting a role for the left brain region in the neurophysiology of overcoming sleepiness in MDD patients. these findings may provide new ideas for the treatment of MDD patients in the future. Trial registration Our experiment was registered in the China Clinical Trial Registry (registration number ChiCTR2200065622) on November 10.( The first patient was recruited in 10/11/2022.)

Summary: The medicinal effect of a drug acts through a series of genes, and the pathological mechanism of a disease is also related to genes with certain biological functions. However, the complex information between drug or disease and a series of genes is neglected by traditional message passing methods. In this study, we proposed a new framework using two different strategies for gene-drug/disease and drug-disease networks, respectively. We employ long short-term memory (LSTM) network to extract the flow of message from series of genes (gene path) to drug/disease. Incorporating the resulting information of gene paths into drug-disease network, we utilize graph convolutional network (GCN) to predict drug-disease associations. Experimental results showed that our method GeneDR (gene-based drug repurposing) makes better use of the information in gene paths, and performs better in predicting drug-disease associations.

This paper proposes a golden sine grey wolf optimizer (GSGWO) that can be adapted to the obstacle-crossing function to solve the path planning problem of obstacle-crossable robot. GSGWO has been improved from the gray wolf optimizer (GWO), which provide slow convergence speed and easy to fall into local optimum, especially without obstacle-crossing function. Firstly, aiming at the defects of GWO, the chaotic map is introduced to enrich the initial population and improve the convergence factor curve. Then, the convergence strategy of the golden sine optimizer is introduced to improve the shortcomings of GWO, such as insufficient convergence speed in the later stage and the ease with which it falls into the local optimum. Finally, by adjusting the working environment model, path generation method and fitness function, the path-planning problem of the obstacle-crossing robot is adapted. In order to verify the feasibility of the algorithm, four standard test functions and three different scale environment models are selected for simulation experiments. The results show that in the performance test of the algorithm, the GSGWO has higher convergence speed and accuracy than the GWO under different test functions. In the path-planning experiment, the length, number and size of inflection points and stability of the path planned by the GSGWO are better than those of the GWO. The feasibility of the GSGWO is verified.

This study investigates the deposition of CrAlYN nanomultilayer films with different yttrium (Y) contents on M2 tool steel and single-crystal Si wafer using unbalanced magnetron-sputtering ion-plating technology. Transmission and scanning electron microscopic and scanning morphologies, x-ray diffraction pattern, energy dispersive spectra, nanoindentation, high-temperature oxidation, and high-temperature tribological analyses show that CrAlYN nanomultilayer films have a face-centered cubic (fcc) crystal structure with a modulation period of CrN/YN+AlN/CrN/AlN. CrAlYN films exhibit optimal mechanical performance when Y content is 1.13at%. However, a substantial drop occurs when Y content increases to 2.67at%. As Y content increases, the high-temperature oxidation resistance, friction, and wear of CrAlYN films first increase and then decrease. Notably, films with the Y content of 1.13at% have optimal resistance to high-temperature oxidation, friction, and wear.

This study presents a novel method that combines a computational fluid-structure interaction model with an interpretable deep-learning model to explore the fundamental mechanisms of seal whisker sensing. By establishing connections between crucial signal patterns, flow characteristics, and attributes of upstream obstacles, the method has the potential to enhance our understanding of the intricate sensing mechanisms. The effectiveness of the method is demonstrated through its accurate prediction of the location and orientation of a circular plate placed in front of seal whisker arrays. The model also generates temporal and spatial importance values of the signals, enabling the identification of significant temporal-spatial signal patterns crucial for the network’s predictions. These signal patterns are further correlated with flow structures, allowing for the identification of important flow features relevant for accurate prediction. The study provides insights into seal whiskers’ perception of complex underwater environments, inspiring advancements in underwater sensing technologies.

The quantitative prediction of more process parameter variables for fewer layer geometry variables is challenging in wire-laser DED. This study’s novelty is combining machine learning models with a non-dominated sorting genetic algorithm-II (NSGA-II) to predict process parameters for desired layer geometries accurately. Thirty single-layer deposition experiments are conducted to obtain response data of layer geometries to process parameters. Two support vector regression (SVR) models are trained by these data to predict the layer height and width, respectively, and the mean absolute percentage errors (MAPEs) of these models are 4.16% and 1.76%. A reverse system, consisting of both SVR models and the NSGA-II algorithm, is designed to search the optimal process parameters for the desired layer geometries. The maximum MAPE between the actual layer geometry deposited by the predicted process parameters and the desired layer geometry is less than 5.5%, providing solid confirmation of this methodology’s reliability.

Paeoniflorin is one of the important components in Paeoniaceae plants. In this study, we used Caenorhabditis elegans as a model host and Pseudomonas aeruginosa as a bacterial pathogen to investigate the possible role of paeoniflorin treatment against P. aeruginosa infection in the host and the underlying mechanisms. Posttreatment with 1.25–10 mg/L paeoniflorin could significantly increase the lifespan of P. aeruginosa infected nematodes. After the infection, the P. aeruginosa colony-forming unit (CFU) and P. aeruginosa accumulation in intestinal lumen were also obviously reduced by 1.25–10 mg/L paeoniflorin treatment. The beneficial effects of paeoniflorin treatment in increasing lifespan in P. aeruginosa infected nematodes and in reducing P. aeruginosa accumulation in intestinal lumen could be inhibited by RNAi of pmk-1, egl-1, and bar-1. In addition, paeoniflorin treatment suppressed the inhibition in expressions of pmk-1, egl-1, and bar-1 caused by P. aeruginosa infection in nematodes, suggesting that paeoniflorin could increase lifespan of P. aeruginosa infected nematode by activating PMK-1, EGL-1, and BAR-1. Moreover, although treatment with 1.25–10 mg/L paeoniflorin did not show obvious anti-P. aeruginosa activity, the P. aeruginosa biofilm formation and expressions of related virulence genes (pelA, pelB, phzA, lasB, lasR, rhlA, and rhlC) were significantly inhibited by paeoniflorin treatment. Treatment with 1.25–10 mg/L paeoniflorin could further decrease the levels of related virulence factors of pyocyanin, elastase, and rhamnolipid. In addition, 2.5–10 mg/L paeoniflorin treatment could inhibit the swimming, swarming, and twitching motility of P. aeruginosa, and treatment with 2.5–10 mg/L paeoniflorin reduced the cyclic-di-GMP (c-di-GMP) level. Therefore, paeoniflorin treatment has the potential to extend lifespan of P. aeruginosa infected hosts by reducing bacterial accumulation in intestinal lumen and inhibiting bacterial biofilm formation.

Network slicing is a key technology for 5G networks, which divides the traditional physical network into multiple independent logical networks to meet the diverse requirements of end-users. This paper focuses on the resource allocation problem in the scenario where public and non-public network slices coexist. There are two kinds of resources to be allocated: one is the resource blocks (RBs) allocated to the users in the radio access network, and the other is the server resources in the core network. We first formulate the above resource allocation problem as a nonlinear integer programming problem by maximizing the operator profit as the objective function. Then, a combination of deep reinforcement learning (DRL) and machine learning (ML) algorithms are used to solve this problem. DRL, more specifically, independent proximal policy optimization (IPPO), is employed to provide the RB allocation scheme that makes the objective function as large as possible. ML, more specifically, random forest (RF), assists DRL agents in receiving fast reward feedback by determining whether the allocation scheme is feasible. The simulation results show that the IPPO-RF algorithm has good performance, i.e., not only are all the constraints satisfied, but the requirements of the non-public network slices are ensured.

Purpose: Fermented camel milk from Xinjiang is rich in probiotics and has immunomodulatory effects as an important source of bioactive peptides. However, it is not clear whether it is the probiotic or the bioactive peptide that acts. The present study aimed to extract and identify bioactive peptides from fermented camel milk in Xinjiang and investigate their immunomodulatory effects and mechanisms based on network pharmacology and molecular docking.Methods: Four probiotic bacteria were used to ferment the fresh camel milk and the bioactive peptides were extracted and isolated by ultrafiltration and column chromatography. Network pharmacology predicts targets and pathways of action. GeneCards and OMIM-GENE-MAP database were used in order to search disease target genes and screen common target genes. Then we used STRING web to construct a protein-protein interaction (PPI) interaction network of the common target protein. The key targets were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis through the David database. The "drug (bioactive peptide)-disease-targets-pathway" network was established and molecular docking was used for prediction.Results: Two fractions were obtained by UV spectrophotometer; whey acidic protein, α-lactalbumin, and peptidoglycan recognition protein 1 were the main protein-like components of Xinjiang fermented camel milk-derived bioactive peptides. The repeat sequence of peptidoglycan recognition protein 1 was selected and then seven bioactive peptides were obtained. Bioactive peptides had 222 gene targets, anti-inflammatory diseases had 2598 gene targets, and immune regulation had 866 gene targets, the intersection of which was 66 in common gene targets. Gene ontology and KEGG analysis reveals that bioactive peptides mainly play a vital role in the signaling pathways of lipid and atherosclerosis, pathways in cancer. The molecular docking results showed that the seven bioactive peptides bound well to the top four scoring proteins.Conclusion: The immunomodulatory and anti-inflammatory effects and mechanisms of Xinjiang fermented camel milk-derived bioactive peptides were initially investigated by network pharmacology and molecular docking, providing a scientific basis for future studies.

Salt stress is one of the major environmental stresses that imposes constraints to plant growth and production. Abscisic acid (ABA) has been well-proven to function as a central integrator in plant under salt stress, and trehalose (Tre) has emerged as an excellent osmolyte to induce salt tolerance. However, the interacting mechanism between ABA and Tre in rice seedlings under salt stress is still obscure. Here, we found that the application of exogenous Tre significantly promoted the salt tolerance of rice seedlings by enhancing the activities of antioxidant enzymes. In addition, the expression of OsNCED3 was significantly induced by salt stress. The overexpression of the OsNCED3 gene enhanced the salt tolerance, while the knockout of OsNCED3 reduced the salt tolerance of the rice seedlings. Metabolite analysis revealed that the Tre content was increased in the OsNCED3-overexpressing seedlings and reduced in the nced3 mutant. The application of both ABA and Tre improved the salt tolerance of the nced3 mutant when compared with the WT seedling. OsTPP3 was found to be induced by both the ABA and salt treatments. Consistent with the OsNCED3 gene, the overexpression of OsTPP3 enhanced salt tolerance while the knockout of OsTPP3 reduced the salt tolerance of the rice seedlings. In addition, the Tre content was also higher in the OsTPP3-overexpressing seedling and lower in the tpp3 mutant seedling than the WT plant. The application of exogenous Tre also enhanced the salt tolerance of the tpp3 mutant plant. Overall, our results demonstrate that salt-increased ABA activated the expression of OsTPP3, which resulted in elevated Tre content and thus an improvement in the salt tolerance of rice seedlings.

Recently, biomaterials for cartilage regeneration has been intensively investigated. However, the development of scaffolds that capture regenerated cartilage with biomechanical and structural recovery has rarely been reported. To address this challenge, platelet-rich plasma (PRP)-based cartilage constructs with a well-orchestrated symphony of cellular, biochemical and biomechanical elements were prepared by simultaneously employing chondrogenic progenitor cells (CPCs) as a cell source, optimizing platelet concentration, and adding an enzyme-ion activator. It was shown that this triple-optimized PRP + CPC construct possessed increased biomechanical properties and suitable biochemical signals. The following in vitro study demonstrated that the triple-optimized PRP + CPC constructs generated cartilage-like tissue with higher expression levels of chondrogenic-specific markers, more deposition of cartilage-specific extracellular matrix (ECM), and greater biomechanical values than those of the other constructs. Twelve weeks after the construct was implanted in a cartilage defect in vivo, histological analysis, qPCR, and biomechanical tests collectively showed that the triple-optimized constructs yielded a more chondrocyte-like cell phenotype with a higher synthesis of Col-II and aggrecan. More importantly, the triple-optimized constructs facilitated cartilage regeneration with better biomechanical recovery than that of the other constructs. These results demonstrate the efficacy of the triple-optimization strategy and highlight the simplicity and potency of this PRP + CPC construct for cartilage regeneration.

Hydroxyapatite (HA) coatings have been widely used for improving the bone-implant interface (BII) bonding of the artificial joint prostheses. However, the incidence of prosthetic revisions due to aseptic loosening remains high. Porous materials, including three-dimensional (3D) printing, can reduce the elastic modulus and improve osseointegration at the BII. In our previous study, we identified a porous material with a sintered bionic trabecular structure with in vitro and in vivo bio-safety as well as in vivo mechanical safety. This study aimed to compare the difference in osseointegration ability of the different porous materials and HA-coated titanium alloy in the BII. We fabricated sintered bionic trabecular porous titanium acetabular cups, 3D-printed porous titanium acetabular cups, and HA-coated titanium alloy acetabular cups for producing a hip prosthesis suitable for beagle dogs. Subsequently, the imaging and histomorphological analysis of the three materials under mechanical loading in animals was performed (at months 1, 3, and 6). The results suggested that both sintered bionic porous titanium alloy and 3D-printed titanium alloy exhibited superior performances in promoting osseointegration at the BII than the HA-coated titanium alloy. In particular, the sintered bionic porous titanium alloy exhibited a favorable bone ingrowth performance at an early stage (month 1). A comparison of the two porous titanium alloys suggested that the sintered bionic porous titanium alloys exhibit superior bone in growth properties and osseointegration ability. Overall, our findings provide an experimental basis for the clinical application of sintered bionic trabecular porous titanium alloys.

In the clinical intensive care units (ICU), the traditional Chinese medicine (TCM) formulation of Xuebijing has been frequently used for treating sepsis. Nevertheless, the underlying pharmacological mechanisms of Xuebijing remain largely unclear. Caenorhabditis elegans is an important experimental host for bacterial infections. Using C. elegans as an animal model, we here examined the potential of Xuebijing treatment against bacterial infection and the underlying mechanisms. Xuebijing treatment could inhibit the reduction tendency of lifespan caused by Pseudomonas aeruginosa infection. For the cellular mechanisms of this antibacterial infection property, we found that Xuebijing treatment rescued C. elegans lifespan to be against P. aeruginosa infection by inhibiting Pseudomonas colonization in the intestinal lumen. Meanwhile, the increase in the expression of antimicrobial genes induced by Pseudomonas infection was also suppressed by Xuebijing treatment. Moreover, the beneficial effect of Xuebijing against Pseudomonas infection depended on insulin, p38 MAPK, Wnt, DBL-1/TGF-β, ELT-2, and programmed cell death (PCD)-related signals. Although Xuebijing did not show obvious antibacterial activity, Xuebijing (100%) treatment could inhibit the Pseudomonas biofilm formation and decrease the expression of virulence genes (lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS) and quorum sensing (QS)-related genes (lasI, lasR, rhlI, rhlR, pqsA, and pqsR). Our results support the potential role of Xuebijing treatment against bacterial infection in hosts.

The heat dissipation characteristics of the lithium-ion battery pack will have an effect on the overall performance of electric vehicles. To investigate the effects of the structural cooling system parameters on the heat dissipation properties, the electrochemical thermal coupling model of the lithium-ion power battery has been established, and the discharge experiment of the single battery has been designed. The voltage and temperature curves with time are similar to those obtained from the numerical model at various discharge rates, and the experimental results are relatively accurate. Based on this model, the height, angle, and number of different air inlets and outlets are designed, and the heat dissipation characteristics of different structural parameters are analyzed. The results show that the maximum temperature decreases by 3.9 K when the angle increases from 0° to 6°, the average temperature decreases by 2 K and the maximum temperature difference decreases by 2.9 K when the height increases from 12 mm to 16 mm, and the more the number of air inlets and outlets there are, the better the heat dissipation effect is. Therefore, the air vent of the battery cooling system has an important impact on the heat dissipation characteristics of the battery, which should be fully considered in the design.

Abstract Background Radial extracorporeal shockwave (r-ESW), an innovative and noninvasive technique, is gaining increasing attention in regenerative medicine due to its mechanobiological effects. Subchondral bone stem/progenitor cells (SCB-SPCs), originating from the pivotal zone of the osteochondral unit, have been shown to have multipotency and self-renewal properties. However, thus far, little information is available regarding the influences of r-ESW on the biological properties of SCB-SPCs and their therapeutic effects in tissue regeneration. Methods SCB-SPCs were isolated from human knee plateau osteochondral specimens and treated with gradient doses of r-ESW in a suspension stimulation system. The optimized parameters for SCB-SPC self-renewal were screened out by colony-forming unit fibroblast assay (CFU-F). Then, the effects of r-ESW on the proliferation, apoptosis, and multipotency of SCB-SPCs were evaluated. Moreover, the repair efficiency of radial shockwave-preconditioned SCB-SPCs was evaluated in vivo via an osteochondral defect model. Potential mechanisms were explored by western blotting, confocal laser scanning, and high-throughput sequencing. Results The CFU-F data indicate that r-ESW could augment the self-renewal of SCB-SPCs in a dose-dependent manner. The CCK-8 and flow cytometry results showed that the optimized shockwave markedly promoted SCB-SPC proliferation but had no significant influence on cell apoptosis. Radial shockwave exerted no significant influence on osteogenic capacity but strongly suppressed adipogenic ability in the current study. For chondrogenic potentiality, the treated SCB-SPCs were mildly enhanced, while the change was not significant. Importantly, the macroscopic scores and further histological analysis strongly demonstrated that the in vivo therapeutic effects of SCB-SPCs were markedly improved post r-ESW treatment. Further analysis showed that the cartilage-related markers collagen II and proteoglycan were expressed at higher levels compared to their counterpart group. Mechanistic studies suggested that r-ESW treatment strongly increased the expression of YAP and promoted YAP nuclear translocation in SCB-SPCs. More importantly, self-renewal was partially blocked by the YAP-specific inhibitor verteporfin. Moreover, the high-throughput sequencing data indicated that other self-renewal-associated pathways may also be involved in this process. Conclusion We found that r-ESW is capable of promoting the self-renewal of SCB-SPCs in vitro by targeting YAP activity and strengthening its repair efficiency in vivo, indicating promising application prospects.

Abstract Background MiRNA-155 and miRNA-145 have been demonstrated to function as a key regulator in the development of the cardiovascular system. Recent experimental and clinical studies have indicated the cardioprotective role of sildenafil during ischemia/reperfusion (I/R) injury. This study was designed to investigate if administration of sildenafil will attenuate post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions. Methods Thirty-two male pigs (weighing 30 ± 2 kg) were randomly divided into 4 groups, sildenafil group (n = 8), sildenafil +NG-nitro-l-arginine methyl ester (L-NAME) (20 mg/kg L) group (n = 8), saline (SA group, n = 8); and sham operation group (sham group, n = 8). Eight minutes of untreated VF was followed by defibrillation in anesthetized, closed-chest pigs. Hemodynamic status and blood samples were obtained at 0 min, 0.5, 1, 2, 4 and 6 h after return of spontaneous circulation (ROSC), and the hearts were removed and analyzed under electron microscopy, quantitative real-time polymerase chain reaction and ultra structural analysis were performed to evaluate myocardial injury. Results Compared with the sildenafil + L-NAME and saline groups, the sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, and attenuated myocardial injury; In this study, CA pigs showed evidently increased levels of miR-155-5p and miR-145-5p, while the sildenafil treatment decreased the levels of miR-155-5p and miR-145-5p in CA pigs. In addition, the levels of eNOS was decreased in CA pigs, validating sildenafil attenuating post-resuscitation myocardial dysfunction by regulating miRNA-155 and miR-145 expressions. Conclusions Sildenafil group had better outcomes in terms of hemodynamic and oxygen metabolism parameters as well as 24-h survival rate, inhibited the increases in the miR-155-5p and miR-145-5p levels and attenuated myocardial injury in a porcine model of CA and resuscitation.

In the realm of power grids environmental protection, low-frequency harmonic noise radiated from transformers has always been the focus of attention for decades. The existing noise control technologies, such as traditional noise barriers, sound insulation enclosures, and damping panels, not only occupying a large space but also causing difficulties in heat dissipation and daily maintenance of transformers. Therefore, explorations on the theory and design of low-noise power transformers become particularly necessary. In this paper, we started from the concept of acoustic radiation efficiency and discussed the radiation efficiency of a typical distribution transformer with radiators. It is found that the overall radiation efficiency is reduced below 230 Hz (low-frequency band) due to radiator barriers compared with that of the flat transformer tank. Furthermore, the phase effect of vibration distribution was also studied with a validated BEM code, inspired by the “acoustic short circuit” phenomenon. It is verified that the acoustic short circuit phenomenon truly exists for a typical transformer enclosure and affects its sound radiation. These supporting results might lead to a promising noise reduction technology from the perspective of radiation control of transformer tanks, i.e., acoustic metamaterials for noise source phase control.

A risk assessment for storm surge disasters can provide scientific support for coastal management as well as marine disaster prevention and mitigation. By taking the Wenchang City of Hainan Province as a pilot area, a risk assessment approach for typhoon-induced storm surge disasters is introduced in detail in this article. First, a numerical simulation system for storm surge inundation is developed, which is applied for the simulation and calculation of the probable maximum storm surge in Wenchang, and the obtained inundation areas and depths are used to assess the storm surge hazard. Then, the data of land use and disaster-bearing bodies are used to classify and assess the vulnerability of Wenchang. Finally, by taking the community as unit, the risk assessment for typhoon-induced storm surge affecting Wenchang is performed by combining the assessment results of both hazard and vulnerability, thereby obtaining a level map of risk distribution. The results show that there are risks of typhoon-induced storm surge in most of the coastal areas of Wenchang, especially for its northeast and east coastal areas, where the risks reach Levels I–II. This approach can be conveniently applied to risk assessments of storm surge in other coastal areas. Note that this approach focuses on the current risk of typhoon-induced storm surge in coastal areas, and further studies will be conducted on the assessment methods for the potential risk.

Leaf–device interaction can effectively be modeled with a finite element model when proper finite element model parameters are applied. In order to investigate the contact mechanism of picking up sugarcane leaf during the operation of a sugarcane leaf cutting and returning machine, a geometric solid model of sugarcane leaf picking was established. A finite element numerical model to analyze the large deformation problem of flexible bodies was developed in LS-DYNA to simulate the picking process of the returning machine. A dynamic simulation of the sugarcane leaf-picking process was carried out to obtain the change of stress field and the motion posture of the sugarcane leaf and the elastic teeth. The picking process of the picking mechanism, the change in posture of the sugarcane leaves, the change in stress on the sugarcane leaf, the change in the bending angle of the sugarcane leaf and the change in stress on the elastic teeth were analyzed in detail. The results showed that the picking process can be divided into four stages: picking, lifting, pushing and retrieving. The posture changes of sugarcane leaf are “C”, logarithmic curve, wavy shape and “V”, in turn. During the picking process, the sugarcane blade showed some breakage, the sugarcane vein remained intact, and the elastic teeth did not fail. During the whole picking cycle, the maximum Von Mises stress of the blade, vein and elastic teeth were 22.8 MPa, 17.5 MPa and 900 MPa, respectively. An evaluation criterion of bending angle was creatively put forward to measure the bending deformation of leaves. The trend in the sugarcane leaf bending angle shows that it is largely variable, gradually decreasing, fluctuating and increasing with interval fluctuations. The working process of the picking mechanism was observed through a quick camera experiment. Comparing the experiment with the simulation, the changing trend of the simulation data and experimental data was generally similar. The experimental and simulation values of the average sugarcane leaf bending angle were 27° and 19°, respectively. The relative error of the average bending angle was 29.6%. It was concluded that the developed finite element model is substantial and could be applied to optimize and improve the picking mechanism. In addition, some references were provided for the contact mechanism between the picking mechanism and the sugarcane leaf.

Therapeutic targeting of advanced or metastatic non-small-cell lung cancer (NSCLC) represents a major goal of clinical treatment. Polo-like kinase 1 (PLK1) is an essential mitotic kinase in cell cycle progression and is associated with oncogenesis in a large spectrum of cancer types, including NSCLC. Volasertib (BI 6727) is a potent, selective, PLK1 inhibitor that is currently under phase 2 clinical trials with modest antitumor activity against solid tumors. As the combination of volasertib with pemetrexed does not improve efficacy for NSCLC treatment, it is crucial to identify compounds that could enhance efficacy with volasertib. Immunomodulatory drugs (IMiDs) bind to E3 ligase CRBN and repurposes it to ubiquitinate other proteins as neo-substrates, representing an effective treatment for hematologic malignancies. In this study, by screening IMiDs, we found that a novel CRBN modulator, CC-885, can synergistically inhibit NSCLC with volasertib both in vitro and in vivo. This synergistic effect overcomes volasertib resistance caused by PLK1 mutations and is compromised in CRBN-or p97-depleted cells. Mechanistically, CC-885 selectively promotes CRBN- and p97-dependent PLK1 ubiquitination and degradation, thereby enhancing the sensitivity of NSCLC to volasertib. In conclusion, our findings reveal that PLK1 is a neo-substrate of CUL4-CRBN induced by CC-885 and represent a combinational approach for treating NSCLC.

Radiofrequency (RF) catheter ablation has emerged as an effective alternative for the treatment of atrial fibrillation (AF), but ablation lesions will result in swelling and hematoma of local surrounding tissue, triggering inflammatory cell infiltration and increased release of inflammatory cytokines. Some studies have shown that the inflammatory response may be related to the early occurrence of AF. The most direct way to inhibit perioperative inflammation is to use anti-inflammatory drugs such as glucocorticoids. Here, we prepared polylactic-co-glycolic acid (PLGA) nanoparticles loaded with budesonide (BUD) and delivered them through irrigation of saline during the onset of ablation. Local high temperature promoted local rupture of PLGA nanoparticles, releasing BUD, and produced a timely and effective local myocardial anti-inflammatory effect, resulting in the reduction of acute hematoma and inflammatory cell infiltration and the enhancement of ablation effect. Nanoparticles would also infiltrate into the local myocardium and gradually release BUD ingredients to produce a continuous anti-inflammatory effect in the next few days. This resulted in a decrease in the level of inflammatory cytokine IL-6 and an increase of anti-inflammatory cytokine IL-10. This study explored an extraordinary drug delivery strategy to reduce ablation-related inflammation, which may prevent early recurrence of AF.

Background: Understanding the levels of health literacy among different groups is essential for better public health interventions targeting specific subgroups of the population. Additionally, this article explores the prevalence and influencing factors of the health literacy levels of different age groups during the COVID-19 epidemic.Methods: Multistage stratified cluster random sampling and the Probability Proportion to Size (PPS) method were used to select permanent residents aged 15–69 in Chongqing (54,706) for the questionnaire survey. The survey period is from July 2019 and July 2020. Single-factor analysis and logistic regression models were used to study the relationship between demographics, socioeconomic factors, other independent covariates, and health literacy.Results: The health literacy levels of residents declined with age, and there were significant differences in health literacy levels between age groups (χ2 = 3332.884, P < 0.05). As far as the factors affecting health literacy level are concerned, high education and high income are the protective factors for health literacy level for residents of all ages. For adolescents (OR = 1.383, 95% CI: 1.217–1.571), young adults (OR = 1.232, 95% CI = 1.117–1.358), and middle-aged people (OR = 1.096, 95% CI = 1.017–1.182), residence in rural areas was a protective factor. In terms of the dimensions of health literacy, in particular, elderly health literacy in 2020 in Scientific Health Concepts, Safety and First Aid, Basic Medical Care decreased significantly compared with 2019.Conclusions: For adolescents, young adults, middle-aged people, to solve the problem of urban and rural health quality gap, we should not only use the geographical division, but also consider the social population and socio-economic differences. For the elderly, the following four dimensions of health literacy need to be paid more attention than those of other age: Basic Knowledge and Concepts, Scientific Health Concepts, Safety and First Aid, and Basic Medical Care. A lack of knowledge on the prevention and treatment of chronic diseases is the main reason for the recent decline in health literacy. And the health literacy among residents in major public health emergencies is needed.

This study examined the effect of sleep disturbance on gut microbiota (GM), atrial substrate, and atrial fibrillation (AF) inducibility. C57BL/6 mice were subjected to six weeks of sleep deprivation (SD) using the method of modified multiple-platform. Transesophageal burst pacing was performed to evaluate AF inducibility. Feces, plasma, and an atrium were collected and analyzed by 16s rRNA sequencing, liquid chromatography–mass spectrometry (LC-MS)-based metabolome, histological studies, and transcriptome. Higher AF inducibility (2/30 of control vs. 15/30 of SD, p = 0.001) and longer AF duration (p < 0.001), concomitant with aggravated fibrosis, collagen, and lipid accumulation, were seen in the SD mice compared to control mice. Meanwhile, elevated alpha diversity, higher abundance of Flavonifractor, Ruminococcus, and Alloprevotella, as well as imbalanced functional pathways, were observed in the gut of SD mice. Moreover, the global patterns for the plasma metabolome were altered, e.g., the decreased butanoate metabolism intermediates in SD mice. In addition, disrupted metabolic homeostasis in the SD atrium, such as fatty acid metabolism, was analyzed by the transcriptome. These results demonstrated that the crosstalk between GM and atrial metabolism might be a promising target for SD-mediated AF susceptibility.

Hot and humid air with a high marine aerosol content, which is known as 3-high air and is ubiquitous in tropical coastal areas and islands, deteriorates living environments and severely damages human health. A novel type of heat-driven air-conditioning system integrated with marine aerosol removal (AC-MAR) is proposed in this study to treat 3-high air. An integrated prototype with an air treatment capacity of 3000 m3/h is designed and constructed. Function and performance tests on the integrated prototype are performed using auxiliary subsystems, including a marine atmospheric environment simulation subsystem, a heating and cooling water subsystem, and a measurement and control subsystem. The test results show that the integrated prototype has a fresh air treatment capacity of 3000 m3/h, where the fresh air state is 80% RH@30 °C. Air processing using the integrated prototype produces a supply air state of 55% RH@18 °C and decreases the aerosol content by over 94.7%. The system coefficient of performance (COP) is 0.4. Test results show that the proposed method/prototype is especially suitable for tropical islands with prominent energy supply shortages and problems associated with 3-high air.

The length of a spliced pile is 2 m assembled from an original spiral pile using a connector. The whole pile is the structure of the upper straight pipe and the lower spiral. The pile–soil model is established with FEM-SPH by LS-DYNA to simulate and analyze the characteristics of the spliced piles. When the helical pile is subjected to a horizontal load, the pile rotates around the point of rotation, and the contact force position of the soil in the model is as expected. During the process of pile driving, the soil forms an inverted cone stress-area, and the maximum particle stress area near the pile tip and the ground surface is 400 Kpa, which is highly concentrated. When loaded laterally, the area of the interaction stress of the soil particles is divided into three regions: the stress effect region; the transition region; and the critical region. Then, 7° is defined as the ultimate horizontal bearing-capacity of the spliced pile, and the numerical simulation of the horizontal bearing-capacity fundamentally matches the test results. The simulation model realizes the transition from the pile installation to the lateral loading, predicts the ultimate horizontal bearing-capacity, and analyzes the stress distribution of the soil particles and the time-development of the soil displacement.

The installation of screw piles can cause damage to the soil, which is a dynamic and large deformation problem. In this paper, a FEM-SPH numerical model for the analysis of this large deformation problem was developed in LS-DYNA to simulate the installation process of screw piles. In addition, field installation tests of screw piles were carried out. By comparing the FEM-SPH simulation results with the experimental results and traditional FEM simulation results, it was found that the FEM-SPH coupling method has higher efficiency and accuracy in dealing with the large deformation problems caused by the installation of screw piles. Then, numerical simulations of screw piles with various parameters were conducted to analyze the differences in the installation process. The results show that the spiral pitch and pile diameter have a significant effect on the installation torque, soil stress and soil pressure during the installation process. During the installation process, the interaction between the screw pile and the soil is transferable. The installation of the screw pile will lead to the movement of soil particles in the radial and axial directions, resulting in heave damage to the shallow soil and cylindrical shear damage to the middle and deep soil. The influence range on the soil by the heave failure mechanism (HFM) and the cylindrical shear failure mechanism (CSFM) caused by the installation of screw piles is affected by pile parameters. The change in pile diameter will act on both HFM and CSFM, whereas the variation in spiral pitch will only have an influence on CSFM.

Fibers are applied in construction work to improve the strength and avoid brittle failure of soil. In this paper, we analyze the impact mechanism of fiber type and length on the immobilization of microorganisms from macroscopic and microscopic perspectives with fibers of 0.2% volume fraction added to microbial-induced calcite precipitation (MICP)-treated sand. Results show the following: (1) The unconfined compressive strength (UCS) of MICP-treated sand first increases and then decreases with increasing fiber length because short fiber reinforcement can promote the precipitation of calcium carbonate, and the network formed between the fibers limits the movement of sand particles and enhances the strength of the microbial solidified sand. However, the agglomeration caused by overlong fibers leads to uneven distribution of calcium carbonate and a reduction in strength. The optimal fiber length of polypropylene, glass, and polyvinyl alcohol fiber is 9 mm, and that of basalt fiber is 12 mm. (2) The UCS of the different fiber types, from small to large, is basalt fiber < polypropylene fiber < glass fiber < polyvinyl alcohol fiber because the quality of the fiber monofilament differs. More fibers result in more a evident effect of interlacing and bending on sand and higher strength in consolidated sand.

Solution multiplicity of natural ventilation in buildings is of much importance for personnel safety and ventilation design. In this paper, a new mathematical model of buoyancy pressure ventilation for two vertically connected open cavities is presented. Compared with the previous published papers studying two vertically connected open cavities with equal heights and hot source E2 0 in the upper room. By solving and analyzing the equilibrium points and characteristic roots of the differential equations, we analyze the stability of two systems with upward flow pattern and downward pattern and obtain the criteria to determine the stability and existence of solutions for two scenarios. According to these criteria, the multiple steady states of buoyancy ventilation in two vertically connected open cavities with unequal heights and variable strength of hot sources can be obtained. These criteria can be used to design buoyancy ventilation or natural exhaust ventilation systems in two vertically connected open cavities. Compared with two stable states of buoyancy ventilation existing in two vertically connected open cavities with equal heights in the previously published papers, we find that more stable states and unstable states of buoyancy ventilation exist in two vertically connected open cavities with unequal heights in our paper. Finally, bifurcation diagrams and the phase portraits for the two scenarios are given.

The solution multiplicity of natural ventilation in buildings is very important to personnel safety and ventilation design. In this paper, a four-zone model of buoyancy ventilation in typical underground building is proposed. The underground structure is divided to four zones, a differential equation is established in each zone, and therefore, there are four differential equations in the underground structure. By solving and analyzing the equilibrium points and characteristic roots of the differential equations, we analyze the stability of three scenarios and obtain the criterions to determine the stability and existence of solutions for two scenarios. According to these criterions, the multiple steady states of buoyancy ventilation in any four-zone underground buildings for different stack height ratios and the strength ratios of the heat sources can be obtained. These criteria can be used to design buoyancy ventilation or natural exhaust ventilation systems in underground buildings. Compared with the two-zone model in (Liu et al. 2020), the results of the proposed four-zone model are more consistent with CFD results in (Liu et al. 2018). In addition, the results of proposed four-zone model are more specific and more detailed in the unstable equilibrium point interval. We find that the unstable equilibrium point interval is divided into two different subintervals corresponding to the saddle point of index 2 and the saddle focal equilibrium point of index 2, respectively. Finally, the phase portraits and vector field diagrams for the two scenarios are given.

A novel hydrophobic and cationic cyclodextrin-based acrylamide flocculant (AM-β-CD-DMDAAC) was prepared by chemical oxidative polymerization to adsorb water-soluble dyes in dye wastewater. Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscope and thermogravimetric (TG) measurements results demonstrated that the AM-β-CD-DMDAAC was successfully synthesized. The effects of pH, contact time, initial dye concentration, temperature and adsorbent dose on dye removal efficiency for AM-β-CD-DMDAAC flocculants were investigated. The kinetic data were found to follow the pseudo-second-order kinetic model. The equilibrium adsorption data were fitted to the Langmuir isotherm model, with the maximum adsorption capacity of 147.1 mg g−1. The adsorbent retained about 60% of the adsorption efficiency after three adsorption/desorption cycles, which implied a promising application as the dye adsorbent.

The development and plasticity of central auditory system can be influenced by the change of peripheral neuronal activity. However, the molecular mechanism participating in the process remains elusive. Brain-derived neurotrophic factor (BDNF) binding with its functional receptor tropomyosin receptor kinase B (TrkB) has multiple effects on neurons. Here we used a rat model of auditory deprivation by bilateral cochlear ablation, to investigate the changes in expression of BDNF and TrkB in the auditory cortex after auditory deprivation that occurred during the critical period for the development of central auditory system. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry methods were adopted to detect the mRNA and protein expression levels of BDNF and TrkB in the auditory cortex at 2, 4, 6 and 8 weeks after surgery, respectively. The change in the expression of BDNF and TrkB mRNAs and proteins followed similar trend. In the bilateral cochlear ablation groups, the BDNF-TrkB expression level initially decreased at 2 weeks but increased at 4 weeks followed by the reduction at 6 and 8 weeks after cochlear removal, as compared to the age-matched sham control groups. In conclusion, the BDNF-TrkB signaling is involved in the plasticity of auditory cortex in an activity-dependent manner.

Prediction of the relations among drug and other molecular or social entities is the main knowledge discovery pattern for the purpose of drug-related knowledge discovery. Computational approaches have combined the information from different resources and levels for drug-related knowledge discovery, which provides a sophisticated comprehension of the relationship among drugs, targets, diseases, and targeted genes, at the molecular level, or relationships among drugs, usage, side effect, safety, and user preference, at a social level. In this research, previous work from the BioNLP community and matrix or tensor decomposition was reviewed, compared, and concluded, and eventually, the BioNLP open-shared task was introduced as a promising case study representing this area.

China has been suffering from water shortage for a long time. Weather modification and rainfall enhancement via cloud seeding has been proved to be effective to alleviate the problem. Current cloud seeding methods mostly rely on solid carbon dioxide and chemicals such as silver iodide and hygroscopic salts, which may have negative impacts on the environment and are expensive to operate. Lab experiments have proved the efficiency of ion-based cloud seeding compared with traditional methods. Moreover, it is also more environmentally friendly and more economical to operate at a large scale. Thus, it is necessary to carry out a field experiment to further investigate the characteristics and feasibility of the method. This paper provides the design and implementation of the ion-based cloud seeding and rain enhancement trial currently running in Northwest China. It introduces the basic principle of the trial and the devices developed for it, as well as the installation of the bases and the evaluation method design for the trial.