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Abstract Background Although beta blockers, such as metoprolol, have been widely used in the management of vasovagal syncope (VVS), their efficacy remains debated, with larger studies showing limited benefit. Identifying patient-specific characteristics that predict a positive response to metoprolol could optimize its use. This study aims to investigate the key factors that may determine which VVS patients are suitable candidates for metoprolol treatment. Methods This retrospective study was conducted at a single center. Patients diagnosed with VVS and treated with metoprolol for a minimum of three months were included. A 50% reduction in syncope symptom score (SS) after three months of metoprolol treatment was used to define metoprolol responders, while those who did not achieve this reduction were classified as non-responders. After a three-month follow-up, patients were divided into two groups: responders and non-responders. Baseline data—including age, gender, comorbidities, laboratory tests, and the type of VVS—were analyzed for each patient. Changes in heart rate (HR) and blood pressure during the head-up tilt test (HUTT) were also evaluated between the two groups. Logistic regression analysis was performed to identify potential predictors of metoprolol response, and receiver operating characteristic (ROC) curve analysis was used to assess the value of these predictors in selecting potential responders. Results A total of 168 VVS patients were enrolled between January 2016 and December 2020. Of these, 100 patients responded positively to metoprolol, while 68 did not. No significant differences in baseline characteristics or HUTT results were observed between the two groups (p > 0.05). However, responders exhibited a significantly higher peak HR compared to non-responders during the HUTT (120.13 ± 19.33 vs. 106.60 ± 22.32, p

Abstract Posttranslational modifications (PTMs) of tubulin, termed the “tubulin code”, play important roles in regulating microtubule functions within subcellular compartments for specialized cellular activities. While numerous tubulin PTMs have been identified, a comprehensive understanding of the complete repertoire is still underway. In this study, we report that α-tubulin lactylation is catalyzed by HDAC6 by using lactate to increase microtubule dynamics in neurons. We identify lactylation on lysine 40 of α-tubulin in the soluble tubulin dimers. Notably, lactylated α-tubulin enhances microtubule dynamics and facilitates neurite outgrowth and branching in cultured hippocampal neurons. Moreover, we discover an unexpected function of HDAC6, acting as the primary lactyltransferase to catalyze α-tubulin lactylation. HDAC6-catalyzed lactylation is a reversible process, dependent on lactate concentrations. Intracellular lactate concentration triggers HDAC6 to lactylate α-tubulin, a process dependent on its deacetylase activity. Additionally, the lactyltransferase activity may be conserved in HDAC family proteins. Our study reveals the primary role of HDAC6 in regulating α-tubulin lactylation, establishing a link between cell metabolism and cytoskeleton functions.

Abstract Background In research to improve the quality of transgenic crops, it is often necessary to introduce multiple functionally related genes into recipient plants simultaneously to improve crop genetic traits effectively. Compared with unidirectional promoters, bidirectional promoters simultaneously regulate the expression of multiple genes and improve the efficiency of biotechnology. Therefore, in this study, bidirectional gene pairs were systematically analyzed in Gossypium hirsutum TM-1, and the structure, function and evolutionary relationships of the bidirectional genes were analyzed. The endogenous bidirectional promoters of cotton were mined, and their specific regulatory elements and biological functions were explored to provide useful promoter resources and a theoretical basis for cultivating new cotton germplasms with excellent fiber quality. Results Using an improved search model, a total of 1,383 bidirectional transcript pairs were identified in the Gossypium hirsutum TM-1 genome, and their gene structure and functional annotations were systematically analyzed. Thirty bidirectional intergenic sequences were randomly screened for promoter activity analysis via a transient expression system, and 25 intergenic sequences were found to have bidirectional promoter activity. Comparative analysis of the bidirectional gene profiles of the four cotton subspecies revealed that these subspecies presented abundant bidirectional gene pairs with high homology and that the bidirectional genes in the cotton subspecies were more similar in terms of their molecular functions, cellular components and biological processes. In addition, parallel analysis of bidirectional genes in dicotyledons and monocotyledons revealed that abundant bidirectional gene pairs exist in different species. Although the total number of orthologous bidirectional genes was similar, there was a significant difference in the number of orthologous bidirectional gene pairs between dicotyledons and monocotyledons. This evolutionary analysis of the function and structure of homologous bidirectional gene pairs in different varieties and different subspecies of the same species revealed potential pathways by which these gene pairs originated, which may be necessary for the evolution of a new species. Conclusion In this study, many bidirectional gene pairs in Gossypium hirsutum TM-1 were identified using computer programming, and systematic analysis was conducted to explore their functions and evolutionary relationships. In addition, the promoter activity of the bidirectional intergenic sequences was verified. The combination of computer programming screening, experimental validation and other methods is expected to provide preferred bidirectional promoters for transgenic breeding work via multigene cotransformation methods, and this information is valuable for genetic engineering research and applications.

The escalating prevalence of non-alcoholic fatty liver disease (NAFLD), driven by inadequate dietary habits and metabolic imbalances, underscores the urgent need for effective dietary interventions. This study investigated the potential of 80 % peanut diacylglycerol (DAG) as a functional lipid component in preventing NAFLD and associated intestinal microenvironment based on a high-cholesterol diet (HCD)-induced zebrafish model. We first found that the zebrafish fatty liver model shared multiple similar pathways like lipid-induced atherosclerosis, insulin resistance with NAFLD patient in terms of lipid metabolism. Employing larvae and grown zebrafish, we aimed to elucidate the preventive and alleviating effect of a DAG diet on NAFLD respectively. Results showed that DAG post-intervention significantly decreased hepatic lipid accumulation and diminished intestinal inflammatory in fatty liver zebrafish model. Notably, transcriptomic sequencing illuminated upregulation in genes related to lipid metabolism (e.g., fasn, mogat2, cd36), suggesting that peanut DAG accelerated lipid transportation and fostered a metabolic environment less conducive to NAFLD symptoms. Besides, reduced liver lipid droplets and hepatic inflammatory suggested DAG feeding could also prevent the formation of NAFLD. The study provided compelling evidence supporting the incorporation of DAG into the diet as a strategy for the prevention and management of fatty liver disease, proposing a novel approach to functional food development aimed at combating metabolic diseases.

Abstract Objective The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. Methods We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. Results Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5–25%), normal (25–75%), high (75–95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. Conclusion Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.

In this paper, the microstructure and mechanical properties of SLM-GH3230 superalloy treated by different post treatments (single hot isostatic pressing and heat treatments after hot isostatic pressing) were studied. The micro-morphologies show that the grains along building direction after HIP + HT are mainly columnar grains, which is consistent to that after single HIP. The granular precipitates distribute intergranularly and intragranularly after HIP, but gradually re-dissolve into matrix with the increase of the temperature of the post HT processes. XRD and EDS analyses results indicate that the matrix mainly consists of austenitic γ phase and the granular precipitates are mainly M6C carbides enriched in W element. The average grain size decreases after HT compared to that after HIP, and the crystallographic orientation of grains tends to be more uniform. The Vickers hardness decreases after HIP and HIP + HT processes within a certain degree. According to tensile test results, the sample shows a better combination of strength and plastic performance under HIP+1250 °C/30 min processing, which can also be verified by the characteristic of the fracture morphology with more tearing dimples.

The repair of secondary critical bone defects is an international medical challenge. Bone tissue engineering provides methods and technology for bone repair. The bone regeneration mechanism serves as inspiration for the material and structural design of bone tissue engineering scaffolds. In terms of materials, this review draws inspiration from the biological characteristics of host cells in the osteogenic microenvironment (including osteoblast lineage, vascular cell lineage, inflammatory cells, etc.), reviewing the regulatory mechanisms of bone self-healing and proposing autonomous living materials scaffolds which prepared by in-situ manufacturing. Autonomous living scaffolds regulate cell migration, proliferation and differentiation in real time by releasing living cells steadily for long-term. Regarding structure, we review the functional role of natural bone structures in bone homeostasis, providing insights into the design of bone-inspired scaffolds. Due to the conflict between the mechanical properties and bone regeneration ability, this review proposes assembled scaffolds. They can prolong the half-life of living cells, provide mechanical support and attachment points for new bone growth, and autonomously regulate osteogenic microenvironment. The assembled scaffolds have potential to advance the research progress in bone tissue engineering field and pave the way for novel clinical bone repair treatments.

Single-atom nanozymes (SAzymes) represent a cutting-edge advancement in nanomaterials, merging the high catalytic efficiency of natural enzymes with the benefits of atomic economy. Traditionally, natural enzymes exhibit high specificity and efficiency, but their stability are limited by environmental conditions and production costs. Here we show that SAzymes, with their large specific surface area and high atomic utilization, achieve superior catalytic activity. However, their high dispersibility poses stability challenges. Our review focuses on recent structural and preparative advancements aimed at enhancing the catalytic specificity and stability of SAzymes. Compared to previous nanozymes, SAzymes demonstrate significantly improved performance in biomedical applications, particularly in tumor medicine. This progress positions SAzymes as a promising tool for future cancer treatment strategies, integrating the robustness of inorganic materials with the specificity of biological systems. The development and application of SAzymes could revolutionize the field of biocatalysis, offering a stable, cost-effective alternative to natural enzymes.

Abstract To address the issues of probiotic activity loss during storage and feeding, as well as the limited efficacy of single probiotics, a solution was devised by embedding a mixture of Bacillus coagulans SN‐8 (SN‐8) and Saccharomyces boulardii SN‐6 (SN‐6) in a gel. The initial step involved screening the probiotic microcapsules' preparation method and wall material. Using sodium alginate and β‐cyclodextrin as composite wall material and chitosan as the outer coating material allowed for an embedding rate of 82.11% in composite probiotic microcapsules prepared by the air atomization method. Next, in vitro, simulated digestion experiments were conducted to determine the number of viable bacteria and the release rate of the microcapsules. The results showed that compared to the free strain, the mixed probiotic microcapsules retained a survival rate of 67.5% after 3 h of simulated gastric juice exposure and 70.56% after 42 days of storage at 4°C. This demonstrated higher survival rates and storage stability. The prepared probiotic microcapsules were then administered to dairy cows. 16S rDNA gene sequencing showed that consumption of the microcapsules reduced the number of harmful bacteria, such as Paeniclostridium, in the intestinal tract of dairy cows while accelerating the growth of beneficial bacteria, such as Bifidobacterium. In particular, this resulted in a significant improvement in the lactation performance of the cows, with a 4.5% increase in milk fat content, a 92.5% increase in milk protein content, and a 3.5% increase in milk urea nitrogen content (6.75 mL/dL). In conclusion, probiotic microcapsules can effectively regulate intestinal flora, improving milk production, and quality in dairy cows.

High-frequency (HF) surface wave radar has been widely used for measuring sea surface current, but its accuracy and spatial coverage of sea wave measurement are limited. A wave height mapping method based on HF radar-measured surface currents is proposed in this article. The tidal currents are first estimated and subtracted from the radar-measured surface currents, and then the geostrophic currents are removed. The remaining currents, along with the wind directions, are used as input data to a cascaded long short-term memory network. This network contains two stages. The first stage divides the input data into two groups of high and low sea states, and the second stage performs wave height inversion for each group separately. By combining the inversion results of the two groups, wave height maps are obtained. The algorithm is verified using the experimental data from the southwestern Taiwan Strait. Using the numerical wave height fields as the ground truth, the proposed algorithm has a root-mean-square error of 0.35 m and a correlation coefficient of 0.90.

BackgroundTuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB.MethodsWe conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed.ResultsThe overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination.ConclusionLAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.

In the development of chronic liver disease, the hepatic stellate cell (HSC) plays a pivotal role in increasing intrahepatic vascular resistance (IHVR) and inducing portal hypertension (PH) in cirrhosis. Our research demonstrated that HSC contraction, prompted by angiotensin II (Ang II), significantly contributed to the elevation of type I collagen (COL1A1) expression. This increase was intimately associated with enhanced cell tension and YAP nuclear translocation, mediated through α-smooth muscle actin (α-SMA) expression, microfilaments (MF) polymerization, and stress fibers (SF) assembly. Further investigation revealed that the Rho/ROCK signaling pathway regulated MF polymerization and SF assembly by facilitating the phosphorylation of cofilin and MLC, while Ca2+ chiefly governed SF assembly via MLC. Inhibiting α-SMA-MF-SF assembly changed Ang II-induced cell contraction, YAP nuclear translocation, and COL1A1 expression, findings corroborated in cirrhotic mice models. Overall, our study offers insights into mitigating IHVR and PH through cell mechanics, heralding potential breakthroughs.

To reveal the role of gut microbiota (GM) in the occurrence and development of idiopathic central precocious puberty (ICPP) using 16S rDNA sequencing and bioinformatics analysis. The Danazol-induced ICPP model was successfully constructed in this study. ZBDH and GnRHa treatments could effectively inhibit ICPP in rats, as manifested by the delayed vaginal opening time, reduced weight, decreased uterine organ coefficient, and decreased uterine wall thickness and corpus luteum number, as well as remarkably reduced serum hormone (LH, FSH, and E2) levels. According to 16S rDNA sequencing analysis results, there was no significant difference in the GM community diversity across different groups; however, the composition of the microbial community and the abundance of the dominant microbial community were dramatically different among groups. ZBDH and GnRHa treatments could effectively reduce the abundance of Muribaculateae and Lactobacillus and promote Prevotella abundance. ZBDH and GnRHa were effective in treating Danazol-induced ICPP model rats. The therapeutic effects of ZBDH and GnRHa could be related to the changes in GM in rats.

Abstract The aim of this study was to examine the parenting characteristics of young patients with bipolar disorder (BD) and explore the sex differences. The parental rearing pattern of young patients with BD was measured and compared with the healthy control of young adults. The EMBU scale was used to assess parental rearing patterns. Patients with BD reported significantly higher scores in the punishment and severity index, as well as of the rejection and denial index, but lower scores in the warmth & affectionate index in the paternal rearing pattern, compared with healthy controls. In addition, patients scored higher on the punishment and severity index and rejection and patterns index in maternal rearing patterns. More importantly, we found significant sex differences in maternal rearing patterns (pBonferroni

Bacterial wilt caused by Ralstonia solanacearum is one of the most important diseases in solanaceous plants, including peppers. It generally tends to be more serious under warm−temperature and moist (WM) conditions than at moist room−temperature (RM) conditions. Although immunity mechanisms at room temperature have been intensively studied, the mechanisms underlying WM conditions remain poorly understood. Herein, the pepper cysteine protease CaZingipain2 was expressed and functionally characterized in pepper immunity against R. solanacearum at WM conditions and at room temperature. The results showed that CaZingipain2 localized to the nucleus and was upregulated at the transcript level in pepper plants upon R. solanacearum infection under WM conditions (RSWM). Virus−induced gene silencing of CaZingipain2 significantly increased the susceptibility of pepper plants to RSWM, and was coupled with the downregulation of CaPRP1 and CaMgst3, which are specifically related to pepper immunity against RSWM, according to our previous studies, while its overexpression significantly reduced the susceptibility of N. benethamiana plants to RSWM compared to that of wild−type plants. In addition, our data showed that CaZingipain2 also acts positively in pepper immunity against R. solanacearum infection at room temperature by upregulating the SA− and JA−responsive PR genes, including CaNPR1 and CaDEF1. All these results indicate that CaZingipain2 improves pepper immunity against R. solanacearum under WM conditions and at room temperature by regulating different PR genes.

The aim of this study was to monitor the spectrum of viral pathogens involved in febrile rash illness (FRI) and their epidemiology. A large-scale study was conducted in multiple provinces of China from 2009 to 2021. A total of 14,168 patients of all age groups were enrolled and tested for seven common viruses causing FRI: measles virus (MV), rubella virus (RuV), enterovirus (EV), varicella zoster virus (VZV), human parvovirus B19 (HPV B19), human herpes virus 6 (HHV6), and dengue virus (DENV). Of 14,168 patients with FRI, 9,443 tested positive for a virus, thus yielding a viral positivity rate of 66.65%. Among the seven viruses detected, EV (61.04%), MV (23.32%), RuV (7.74%), and VZV (5.26%) had high detection rates and exhibited different age-specific positivity rates and seasonal prevalence patterns. Early in the Coronavirus Disease 2019 (COVID-19) pandemic, the number of EV, MV, RuV, and VZV cases significantly declined, and the seasonal patterns also changed in 2020, with delay or disappearance of traditional epidemic peaks. EV, MV, RuV, and VZV were found to be the main causal pathogens of FRI among patients in China, and their epidemic levels and seasonal patterns changed during the COVID-19 pandemic, because of large-scale implementation of non-pharmacological interventions.

In the field of wind power prediction, traditional methods typically rely on one-dimensional time-series data for feature extraction and prediction. In this study, we propose an innovative short-term wind power forecasting approach using a “visual” 2D image prediction method that effectively utilizes spatial pattern information in time-series data by combining wind power series and related environmental features into a 2D GASF image. Firstly, the wind power data are decomposed using the ICEEMDAN algorithm optimized by the BWO (Beluga Whale Optimization) algorithm, extracting the submodal IMF (Intrinsic Mode Function) components with different frequencies. Then, modal reconstruction is performed on the basis of the permutation entropy value of the IMF components, selecting meteorological features highly correlated with reconstructed components through Spearman correlation analysis for data splicing and superposition before converting them into GASF images. Finally, the GASF images are input into the UniFormer model for wind power sequence prediction. By leveraging wind power data predictions from a coastal wind farm in East China and Sotavento in Spain, this study demonstrates the significant benefits and potential applications of this methodology for precise wind power forecasting. This research combines the advantages of image feature extraction and time-series prediction to offer novel perspectives and tools for predicting renewable energy sources such as wind power.

In view of various threats of strong electromagnetic environment to ship information equipment under electromagnetic space countermeasures and the requirement of electromagnetic protection, the mechanism of strong electromagnetic environment effect and basic protection principle of ship electronic equipment are prospected. The principle and development of frequency selective surface, energy selective surface and new electromagnetic shielding materials used to reduce the coupling of radiation field to ship electronic system are described; the principle and development of RF front-end protection technology based on gas discharge tube, semiconductor limiter, RF high power limiter technology based PIN diode and electromagnetic pulse protection technology based on plasma for suppressing the strong electromagnetic pulse transmission on the "circuit" are also introduced. This paper analyzes the applicability and advantages of different protection technologies in the design of ship equipment for strong electromagnetic pulse, and forecasts the future development trends of strong electromagnetic environment protection technology for ship equipment, provides support for the design of strong electromagnetic environment protection for ship equipment.

Heat is almost everywhere. Unlike electricity, which can be easily manipulated, the current ability to control heat is still highly limited owing to spontaneous thermal dissipation imposed by the second law of thermodynamics. Optical illumination and pressure have been used to switch endothermic/exothermic responses of materials via phase transitions; however, these strategies are less cost-effective and unscalable. Here, we spectroscopically demonstrate the glassy crystal state of 2-amino-2-methyl-1,3-propanediol (AMP) to realize an affordable, easily manageable approach for thermal energy recycling. The supercooled state of AMP is so sensitive to pressure that even several megapascals can induce crystallization to the ordered crystal, resulting in a substantial temperature increase of 48 K within 20 s. Furthermore, we demonstrate a proof-of-concept device capable of programable heating with an extremely high work-to-heat conversion efficiency of ∼383. Such delicate and efficient tuning of heat may remarkably facilitate rational utilization of waste heat.

Abstract Metastasis is responsible for at least 90% of colon cancer (CC)‐related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further investigation. Herein, through the utilisation of single‐cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1‐ konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1‐KO. Notably, we revealed that lovastatin can block the SULT2B1‐induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

The conductive potential of nano carbon black (NCB) in cement paste is restricted due to its tendency to agglomerate. To address this issue, sodium dodecyl sulfate (SDS) is proposed as a dispersant to enhance the performance of the nano carbon black-filled cement paste. Additionally, the microstructure characteristics of the nano carbon black-filled cement paste with SDS are explored systematically from the perspective of micromorphology, hydration degree and pore structure. UV–Vis spectrophotometry (UV–Vis) proves that SDS can enhance the dispersion of NCB in suspensions. Adding 0.4% SDS to the nano carbon black-filled cement paste can effectively improve the fluidity, accelerate the setting time, decrease the resistivity and increase mechanical strength. Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) reveal that SDS adsorbed on the surface of NCB plays a dispersing role in cement paste. Thermogravimetry (TG) indicates that well-dispersed NCB promotes the hydration of cement clinker, accelerates the formation of calcium silicate hydrates (C–S–H) and increases the content of Ca(OH)2. N2 adsorption-desorption (NAD) verifies that the accumulated hydration products effectively increase the specific surface area and decrease the total pore volume, indicating that SDS has a positive effect on optimizing the pore structure of the nano carbon black-filled cement paste.

The Invar 36 alloy was additively manufactured by laser powder bed fusion (PBF-LB), and systematical observations and experiments for microstructure, defects, metallography, especially high cycle fatigue behaviour and fractography were conducted. Inadequate laser energy density results in hardly overlapping melting traces, generating numerous defects. Accordingly, the fabricated Invar 36 alloy presents an inferior high cycle fatigue life, as it failures from the rapid aggregation of the defects. In contrast, an adequate laser energy density remarkably enlarges the overlapping between adjacent melting traces. The large molten pools with steady boundaries are beneficially to generate favourable microstructures and low porosity. Consequently, the Invar 36 alloy shows superior high cycle fatigue life, completely generated from small crack propagation, long crack propagation and final fracture stages. Above experimental results and analysis primarily link up the PBF-LB process, microstructures (defects) and high cycle fatigue performance for PBF-LB Invar 36 alloy.

Major Depressive Disorder (MDD) - can be evaluated by advanced neurocomputing and traditional machine learning techniques. This study aims to develop an automatic system based on a Brain-Computer Interface (BCI) to classify and score depressive patients by specific frequency bands and electrodes. In this study, two Residual Neural Networks (ResNets) based on electroencephalogram (EEG) monitoring are presented for classifying depression (classifier) and for scoring depressive severity (regression). Significant frequency bands and specific brain regions are selected to improve the performance of the ResNets. The algorithm, which is estimated by 10-fold cross-validation, attained an average accuracy rate ranging from 0.371 to 0.571 and achieved average Root-Mean-Square Error (RMSE) from 7.25 to 8.41. After using the beta frequency band and 16 specific EEG channels, we obtained the best-classifying accuracy at 0.871 and the smallest RMSE at 2.80. It was discovered that signals extracted from the beta band are more distinctive in depression classification, and these selected channels tend to perform better on scoring depressive severity. Our study also uncovered the different brain architectural connections by relying on phase coherence analysis. Increased delta deactivation accompanied by strong beta activation is the main feature of depression when the depression symptom is becoming more severe. We can therefore conclude that the model developed here is acceptable for classifying depression and for scoring depressive severity. Our model can offer physicians a model that consists of topological dependency, quantified semantic depressive symptoms and clinical features by using EEG signals. These selected brain regions and significant beta frequency bands can improve the performance of the BCI system for detecting depression and scoring depressive severity.

It is well known that the epitaxial strain plays a vital role in tuning the magnetic states in transition metal oxide LaCoO3 films. Here, we reported a robust long-range ferromagnetic (FM) ground state in a tensile-strained perovskite LaCoO3 film on a SrTiO3 (STO) substrate, which has a very significant attenuation when the thickness ranges from 10 to 50 nm. It is speculated that such attenuation may be caused by the appearance of the cross-hatched grain boundary, which relaxes the tensile strain around the crosshatch, resulting in the local non-FM phases. Magnetic force microscope observation reveals non-FM patterns correlated with the structural crosshatches in the strain-relaxed film even down to a temperature of 2 K and up to a magnetic field of 7 T, suggesting the phase separation origin of magnetization attenuation. Furthermore, the investigations of the temperature-dependent inverse magnetic susceptibility show a deviation from the Curie–Weiss law above the transition temperature in a 50-nm-thick LaCoO3/STO film but not in the LaCoO3/LaAlO3 film, which is ascribed to the Griffiths phase due to the crosshatch-line grain boundaries. These results demonstrated that the local strain effect due to structural defects is important to affect the ferromagnetism in strain-engineered LaCoO3 films, which may have potential implications for future oxide-based spintronics.

Conventional point prediction methods encounter challenges in accurately capturing the inherent uncertainty associated with photovoltaic power due to its stochastic and volatile nature. To address this challenge, we developed a robust prediction model called QRKDDN (quantile regression and kernel density estimation deep learning network) by leveraging historical meteorological data in conjunction with photovoltaic power data. Our aim is to enhance the accuracy of deterministic predictions, interval predictions, and probabilistic predictions by incorporating quantile regression (QR) and kernel density estimation (KDE) techniques. The proposed method utilizes the Pearson correlation coefficient for selecting relevant meteorological factors, employs a Gaussian Mixture Model (GMM) for clustering similar days, and constructs a deep learning prediction model based on a convolutional neural network (CNN) combined with a bidirectional gated recurrent unit (BiGRU) and attention mechanism. The experimental results obtained using the dataset from the Australian DKASC Research Centre unequivocally demonstrate the exceptional performance of QRKDDN in deterministic, interval, and probabilistic predictions for photovoltaic (PV) power generation. The effectiveness of QRKDDN was further validated through ablation experiments and comparisons with classical machine learning models.

Abstract Aims Available evidence is incomplete and inconsistent in the outcomes of heart failure (HF) patients with preserved ejection fraction (HFpEF), mildly reduced ejection fraction (HFmrEF), and reduced ejection fraction (HFrEF). There are also limited data on the proportions and long‐term prognosis among the three HF phenotypes in China. We aimed to characterize the 5 year prognosis in three HF phenotypes according to EF in a cohort of hospitalized HF patients undergoing coronary angiography in southern China. Methods and results Hospitalized patients with HF were enrolled from the Cardiorenal ImprovemeNt registry (CIN; ClinicalTrials.gov NCT04407936) between January 2007 and December 2014. HF phenotypes were defined as HFpEF (EF ≥ 50%), HFmrEF (EF 41–49%), and HFrEF (EF ≤ 40%). Kaplan–Meier and Cox proportional hazards models were constructed to examine differences in 5 year outcomes in HF patients with different phenotypes. A total of 4880 HF patients [mean age: 61.8 ± 10.3, male: 3156 (64.7%)] were included: 2768 (57%) had HFpEF, 1015 (21%) had HFmrEF, and 1097 (22%) had HFrEF. Patients with HFrEF were older than those with HFpEF (62.5 ± 10.6 vs. 61.3 ± 10.1, P

Abstract Owing to their unique advantages, single‐electrode triboelectric nanogenerators (SETENGs) have gained wide attention and have been applied in myriad areas, especially in the burgeoning flexible/wearable electronics. However, there is still a lack of a clear understanding of SETENGs. For example, previous simulation models generally put the reference electrode perpendicularly below the working part, but in practice, the reference electrode is designed in various scenarios and noticeable differences in outputs often occur when the reference electrode changes. With SETENGs developing towards wearability and portability, its reference electrode is often required to be constructed inside the device. Consequently, to achieve optimum performance, it is essential to understand the reference electrode's influence on the outputs. Here, the influence of the reference electrode on the performance of SETENGs is systematically investigated and the targeted optimization strategies are thoroughly revealed. First, theoretical simulations are conducted to investigate the reference electrode's effect on the performance of SETENGs with different structures and in various working modes. Secondly, the theoretical results are certified through corresponding experiments. Based on the results, the targeted optimization strategies for SETENGs are comprehensively demonstrated. This work provides fundamental guidance for the development of TENGs and the design and fabrication of new electronic devices.

BackgroundObesity is a common and highly convincing risk factor for many cancers, including liver cancer. Sex disparities in the body composition and regulatory mechanisms involved in energy homeostasis may contribute to the difference in the incidence of cancer. However, evidence on the gender-specific association between body composition and liver cancer incidence is limited. We performed this study to investigate the linear and non-linear associations of body composition with liver cancer risk by gender.Materials and methodsThis prospective analysis included 4,75,659 participants free of cancer, based on the UK Biobank. We used Cox proportional hazard models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for potential confounders. Restricted cubic spline was performed to investigate the potential non-linear associations.ResultsDuring a median follow-up, 275 cases (174 male patients and 101 female patients) of liver cancer were identified. Male patients in the highest body fat percentage group are more likely to develop liver cancer (HR = 1.89, 95% CI: 1.17–3.03) compared with those in the lowest group. The one-unit increase of whole-body fat mass, arm fat mass, and trunk fat mass was associated with 1.03-, 1.14-, and 1.05-fold increased risk of liver cancer in male subjects, respectively. U-shaped associations of body composition with liver cancer risk were observed in the female subjects. Both high and low levels of whole-body fat-free mass, particularly in the arm and trunk, were associated with an increased risk of liver cancer.ConclusionThis study found a gender-specific association between body composition and liver cancer risk and provided evidence for individualized weight management for the prevention of liver cancer.

Introduction: Insulin has an effect on neurodegenerative diseases. However, the role and mechanism of insulin in vascular dementia (VD) and its underlying mechanism are unknown. In this study, we aimed to investigate the effects and mechanism of insulin on VD.Methods: Experimental rats were randomly assigned to control (CK), Sham, VD, and insulin (INS) + VD groups. Insulin was administered by intranasal spray. Cognitive function was evaluated using the Morris's water maze. Nissl's staining and immunohistochemical staining were used to assess morphological alterations. Apoptosis was evaluated using TUNEL-staining. Transcriptome and metabolome analyses were performed to identify differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs), respectively.Results: Insulin significantly improved cognitive and memory functions in VD model rats (p < 0.05). Compared with the VD group, the insulin + VD group exhibited significantly reduced the number of Nissl's bodies numbers, apoptosis level, GFAP-positive cell numbers, apoptosis rates, and p-tau and tau levels in the hippocampal CA1 region (p < 0.05). Transcriptomic analysis found 1,257 and 938 DEGs in the VD vs. CK and insulin + VD vs. VD comparisons, respectively. The DEGs were mainly enriched in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse signaling pathways. In addition, metabolomic analysis identified 1 and 14 DEMs between groups in negative and positive modes, respectively. KEGG pathway analysis indicated that DEGs and DEMs were mostly enriched in metabolic pathway.Conclusion: Insulin could effectively improve cognitive function in VD model rats by downregulating tau and p-tau expression, inhibiting astrocyte inflammation and neuron apoptosis, and regulating genes involved in calcium signaling, cAMP signaling, axon guidance, and glutamatergic synapse pathways, as well as metabolites involved in metabolic pathway.

Abstract Background Bone-related proteins (such as sclerostin and osteoprotegerin [OPG]) are involved in the development of atherosclerosis. However, the relationship between bone-related proteins and acute myocardial infarction (AMI) has not been extensively evaluated. The purpose of this study was to assess the association of serum sclerostin and OPG with the presence, severity and prognosis in patients with AMI. Methods This study prospectively enrolled 152 patients attacked by acute chest pain. Serum sclerostin and OPG were detected within the first 24 h after AMI diagnosis by ELISA kits. The AMI predictive efficacy of sclerostin and OPG were analyzed by receiver operating characteristics (ROC) curve. Univariable and multivariable linear regression analyses were performed to determine the association between bone-related proteins and scores indicating the severity of coronary artery occlusion. Moreover, prognostic values were assessed by Kaplan–Meier curves and Cox regression analysis. Results There were 92 patients in AMI group, 60 in non-AMI group. Serum levels of sclerostin and OPG were significantly higher in AMI group than in non-AMI group (all p

Abstract We aimed to explore the association between the number of primary healthcare workers and infectious diarrhea morbidity at community levels and to provide evidence-based implications for optimizing primary healthcare manpower resource allocations. We collected annual infectious diarrhea morbidity and relevant data of 4321 communities in Sichuan Province, China, from 2017 to 2019. Global and local Moran’s I were calculated to detect the spatial clustering of infectious diarrhea morbidity and to identify areas where increased primary healthcare manpower resources should be allocated. The spatial lag fixed effects panel data model was adopted to explore the association between the number of primary healthcare workers per 1000 residents and infectious diarrhea morbidity. Significantly high–high and low–low clusters of infectious diarrhea cases were found to be mainly distributed in underdeveloped and developed areas during the studied period years, respectively. The infectious diarrhea morbidity was found to be statistically negatively associated with the number of primary healthcare workers per 1000 residents with a coefficient of − 0.172, indicating that a 0.172 reduction of infectious diarrhea morbidity (1/10,000) was associated with doubled amounts of primary healthcare workers per 1000 residents. Our findings highlighted the role of primary healthcare in the process of infectious diarrhea prevention and control, and implied that constant efforts should be addressed to facilitate infectious diarrhea prevention and control, especially in the underdeveloped areas.

CRISPR-Cas9 is a common tool for gene editing, and appropriate sgRNAs are the key factor for successful editing. In this study, the effect of sgRNA length and number on editing efficiency was analyzed in rice using CYP81A6 as the target gene. A series of CRISPR-Cas9 plant expression vectors containing single sgRNAs with different lengths (17, 18, 19, 20, 21, 22, 23 nt) or two sgRNAs were constructed and introduced into rice cultivar Zhonghua11 by Agrobacterium-mediated transformation. Analysis of the editing status of 1283 transgenic rice plants showed that 371 were successfully edited with base preference. Single A or T insertions were the most frequent among the six edited types. The editing efficiency of transgenic rice with two sgRNAs was higher than that with a single sgRNA. Editing efficiency and sgRNA length showed a normal distribution with 20 nt sgRNA (25%) being the most efficient. The editing efficiency decreased slightly with decreases of 1–2 bases (19 nt 20%, 18 nt 21%), but decreased significantly with a decrease of 3 bases (17 nt 4.5%). Editing efficiency was significantly reduced by adding 1 to 3 bases (21 nt 16.8%, 22 nt 13%, 23 nt 13%) to the sgRNA. These results provide data for successful gene editing or rice by CRISPR-Cas9.

The coexistence of mcr-1 and blaNDM-5 in the plasmid of Escherichia coli has been widely reported and such strains have been mainly isolated from animal and human feces. However, few reports have focused on the genetic diversity of mcr-1-carrying chromosomes and blaNDM-5-carrying plasmids in E. coli isolates from lesion-bearing animal organs. This study investigated the genetic characteristics of chromosome-mediated mcr-1 and plasmid-mediated blaNDM-5 in E. coli isolated from lesion-bearing animal organs. Nine mcr-1- and blaNDM-5-positive E. coli strains (MNPECs) showed extensive drug resistance (XDR). The predominant clonal complexes (CC) mainly belonged to CC156, CC10, and CC165 from the 56 MNEPCs (including nine strains in this study) retrieved from the literature. These strains were widely distributed in China, and originated from pig fecal samples, human stool/urine samples as well as intestinal contents of chicken. Two transconjugants harboring blaNDM-5 gene were also successfully obtained from two donors (J-8 and N-14) and this transfer increased the MIC for meropenem by 256 times. However, conjugative transfer of mcr-1 gene failed. Both J-8 and N-14 strains contained point mutations associated with quinolone resistance and more than three types of AMR genes, including the mcr-1 gene on the chromosome and the blaNDM-5 gene on the IncX3-type plasmid. The genetic structure of mcr-1 located on the chromosome was an intact Tn6330, and blaNDM-5-carrying IncX3-type plasmid was ISAb125-IS5-blaNDM-5-bleO-trpF-tat-cutA-IS26 gene cassette. Moreover, differences between chromosomes included additional partial sequence of phage integrated into host genome and the different genes associated with O-antigen synthesis.

BackgroundsThe widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection.ObjectiveThis study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time.MethodsWe summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022.ResultsIn this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients.ConclusionThis is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.

Pancreatic ductal adenocarcinoma (PDAC) is one of most lethal cancers and is projected to be the second leading cause of cancer deaths in the United States by 2030. The lack of effective treatment and increased incidence in PDAC encourage a deeper knowledge of PDAC progression. By analyzing a long noncoding RNA (lncRNA) dataset, we found that increased LINC00941 expression led to poor outcomes in PDAC patients. Furthermore, in vitro and in vivo experiments revealed that LINC00941 promoted PDAC cancer cell growth by enhancing aerobic glycolysis. Mechanistically, LINC00941 was found to interact with mammalian STE20-like protein kinase 1 (MST1), which facilitated the protein phosphatase 2A (PP2A)-mediated dephosphorylation of MST1, resulting in Hippo pathway activation and consequently, enhanced glycolysis in PDAC. These results suggest that LINC00941 plays a key role in regulating PDAC tumorigenesis, potentially highlighting novel avenues for PDAC therapy.

Abstract Cotton is an important natural fiber crop and economic crop worldwide. The quality of cotton fiber directly determines the quality of cotton textiles. Identifying cotton fiber development-related genes and exploring their biological functions will not only help to better understand the elongation and development mechanisms of cotton fibers but also provide a theoretical basis for the cultivation of new cotton varieties with excellent fiber quality. In this study, RNA sequencing technology was used to construct transcriptome databases for different nonfiber tissues (root, leaf, anther and stigma) and fiber developmental stages (7 days post-anthesis (DPA), 14 DPA, and 26 DPA) of upland cotton Coker 312. The sizes of the seven transcriptome databases constructed ranged from 4.43 to 5.20 Gb, corresponding to approximately twice the genome size of Gossypium hirsutum (2.5 Gb). Among the obtained clean reads, 83.32% to 88.22% could be compared to the upland cotton TM-1 reference genome. By analyzing the differential gene expression profiles of the transcriptome libraries of fiber and nonfiber tissues, we obtained 1205, 1135 and 937 genes with significantly upregulated expression at 7 DPA, 14 DPA and 26 DPA, respectively, and 124, 179 and 213 genes with significantly downregulated expression. Subsequently, Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analyses were performed, which revealed that these genes were mainly involved in catalytic activity, carbohydrate metabolism, the cell membrane and organelles, signal transduction and other functions and metabolic pathways. Through gene annotation analysis, many transcription factors and genes related to fiber development were screened. Thirty-six genes were randomly selected from the significantly upregulated genes in fiber, and expression profile analysis was performed using qRT-PCR. The results were highly consistent with the gene expression profile analyzed by RNA-seq, and all of the genes were specifically or predominantly expressed in fiber. Therefore, our RNA sequencing-based comparative transcriptome analysis will lay a foundation for future research to provide new genetic resources for the genetic engineering of improved cotton fiber quality and for cultivating new transgenic cotton germplasms for fiber quality improvement.

Crop breeding is an important global strategy to meet sustainable food demand. CRISPR/Cas is a most promising gene-editing technology for rapid and precise generation of novel germplasm and promoting the development of a series of new breeding techniques, which will certainly lead to the transformation of agricultural innovation. In this review, we summarize recent advances of CRISPR/Cas technology in gene function analyses and the generation of new germplasms with increased yield, improved product quality, and enhanced resistance to biotic and abiotic stress. We highlight their applications and breakthroughs in agriculture, including crop de novo domestication, decoupling the gene pleiotropy tradeoff, crop hybrid seed conventional production, hybrid rice asexual reproduction, and double haploid breeding; the continuous development and application of these technologies will undoubtedly usher in a new era for crop breeding. Moreover, the challenges and development of CRISPR/Cas technology in crops are also discussed.

Recurrent pregnancy loss (RPL) affects 1-2% of couples of reproductive age. Immunological analysis of the immune status in RPL patients might contribute to the diagnosis and treatment of RPL. However, the exact immune cell composition in RPL patients is still unclear. Here, we used flow cytometry to investigate the immune cell profiles of peripheral blood and decidual tissue of women who experienced RPL. We divided peripheral immune cells into 14 major subgroups, and the percentages of T, natural killer T (NKT)-like and B cells in peripheral blood were increased in RPL patients. The decidual immune cells were classified into 14 major subpopulations and the percentages of decidual T, NKT-like cells and CD11chi Mφ were increased, while those of CD56hi decidual NK cells and CD11clo Mφ were decreased in RPL patients. The spearmen correlation analysis showed that the proportion of peripheral and decidual immune cells did not show significant correlations with occurrences of previous miscarriages. By using flow cytometry, we depicted the global peripheral and decidual immune landscape in RPL patients. The abnormalities of peripheral and decidual immune cells may be involved in RPL, but the correlations with the number of previous miscarriages need further verification.

At present, with the accelerated development of the global biotechnology industry, novel transgenic technologies represented by gene editing are developing rapidly. A large number of gene-edited products featuring one or a few base indels have been commercialized. These have led to great challenges in the use of traditional nucleic acid detection technology and in safety regulation for genetically modified organisms (GMOs). In this study, we developed a portable clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins 12a-based (CRISPR/Cas12a-based) biosensing platform named Cas12aFVD (fast visual detection) that can be coupled with recombinase polymerase amplification (RPA) for on-site detection of mutants in gene-edited rice in one tube. The detection procedure can be accomplished in 40 min with a visible result, which can be observed by the naked eye under blue light (470–490 nm). By accurate recognition of targets based on Cas12a/CRISPR RNA (crRNA), Cas12aFVD exhibits excellent performance for the detection of two- and three-base deletions, one-base substitution, and one-base insertion mutants with a limit of detection (LOD) of 12 copies/μl showing great potential for mutant detection, especially single-base mutants. The Cas12aFVD biosensing platform is independent of laboratory conditions, making it a promising and pioneering platform for the detection of gene-edited products.

Riemerella anatipestifer (RA) is an important pathogen found in poultry. RA infection can kill ducks and lead to significant economic losses. Seven RA strains with different susceptibility phenotypes were chosen to study the pharmacokinetic/pharmacodynamic (PK/PD) integration of florfenicol (FF) alone and in combination with doxycycline (DOX). The checkerboard assay indicated that synergy [fractional inhibitory concentration index (FICI) ≤ 0.5] was detected in the CVCC3952 strain of RA and that additivity (FICI >0.5 to ≤ 1) was observed in other strains. Static time–kill curves showed that the bactericidal effect of FF against RA was produced at a FF concentration ≥4 MIC, and the antibacterial activity of FF against RA was enhanced from the aspects of efficacy and efficacy in combination with DOX. Dynamic time–kill curves indicated that FF elicited bactericidal activity against the CVCC3857 strain with a reduction ≥4.88 log10CFU/ml when the dose was ≥8 mg/L. However, a bactericidal effect was not achieved at the maximum administered dose of FF monotherapy (20 mg/L) for isolates with a MIC ≥4 μg/ml. The effect of FF against RA was enhanced upon combination with DOX. The combination of FF with DOX reduced the bacterial burden ≥4.53 log10CFU/ml for all strains with a MIC ≥4 μg/ml. Data were fitted to a sigmoidal Emax model. The PK/PD parameters of AUC24h/MIC (the area under the concentration–time curve over 24 h divided by the MIC) and %T >MIC (the cumulative percentage of time over a 24-h period at which the concentration exceeded the MIC) of FF for eliciting a reduction of 3 log10CFU/ml was 40.10 h and 58.71, respectively. For strains with a MIC ≤ 16 μg/ml, the magnitude of the AUC24h/MIC and Cmax/MIC required for a 3 log10CFU/ml of bacterial killing was 34.84 h and 4.74 in the presence of DOX at 0.5 MIC, respectively. These data suggest that combination of FF with DOX enhanced the activity against RA strains with various susceptibilities to FF and DOX.

ObjectiveAdipose tissue is recognized as a crucial regulator of atrial fibrillation (AF). However, the effect of epicardial adipose tissue (EAT) on the pathophysiology of AF might be different from that of other adipose tissues. The purpose of this study was to explore the distribution features of different adipose tissues in AF patients and their relationships with left atrial (LA) remodeling and function.MethodsA total of 205 participants (including 112 AF and 93 non-AF patients) were recruited. Color doppler ultrasound was used to measure the thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue. Cardiac CT scan was performed to measure the mean thickness of EAT surrounding the whole heart (total-EAT) and specific regions, including left atrium (LA-EAT), left ventricle, right ventricle, interventricular groove, and atrioventricular groove. LA anatomical remodeling and function were measured by echocardiography, while electrical remodeling was evaluated by P-wave duration and dispersion using Electrocardiography (obtained after cardioversion or ablation in AF patients). Relationship between the thickness of different adipose tissues and LA remodeling and function was analyzed.ResultsThe thickness of subcutaneous, extraperitoneal, and intra-abdominal adipose tissue was similar between AF and non-AF patients, and had no or only weak association with LA remodeling and dysfunction. However, compared to non-AF participants, total-EAT thickness significantly increased in both paroxysmal and persistent AF patients (non-AF vs. paroxysmal AF vs. persistent AF: 6.31 ± 0.63 mm vs. 6.76 ± 0.79 mm vs. 7.01 ± 1.18 mm, P < 0.001), which was positively correlated with the LA size and P-wave duration and dispersion, and negatively correlated with LA ejection fraction and peak strain rate. More interestingly, EAT thickness in AF patients did not increase uniformly in different regions of the heart. Compared to EAT surrounding the other regions, LA-EAT was found to accumulate more greatly, and had a closer relationship to LA remodeling and dysfunction. Multivariate logistic regression analysis also showed that LA-EAT was significantly correlated with the presence of AF (OR = 4.781; 95% CI 2.589–8.831, P < 0.001).ConclusionRather than other adipose tissues, accumulation and redistribution of EAT, especially surrounding the LA, is associated with LA remodeling and dysfunction in AF patients.

BackgroundCurrent electrocardiogram (ECG) criteria of left ventricular hypertrophy (LVH) have low sensitivity. Deep learning (DL) techniques have been widely used to detect cardiac diseases due to its ability of automatic feature extraction of ECG. However, DL was rarely applied in LVH diagnosis. Our study aimed to construct a DL model for rapid and effective detection of LVH using 12-lead ECG.MethodsWe built a DL model based on convolutional neural network-long short-term memory (CNN-LSTM) to detect LVH using 12-lead ECG. The echocardiogram and ECG of 1,863 patients obtained within 1 week after hospital admission were analyzed. Patients were evenly allocated into 3 sets at 3:1:1 ratio: the training set (n = 1,120), the validation set (n = 371) and the test set 1 (n = 372). In addition, we recruited 453 hospitalized patients into the internal test set 2. Different DL model of each subgroup was developed according to gender and relative wall thickness (RWT).ResultsThe LVH was predicted by the CNN-LSTM model with an area under the curve (AUC) of 0.62 (sensitivity 68%, specificity 57%) in the test set 1, which outperformed Cornell voltage criteria (AUC: 0.57, sensitivity 48%, specificity 72%) and Sokolow-Lyon voltage (AUC: 0.51, sensitivity 14%, specificity 96%). In the internal test set 2, the CNN-LSTM model had a stable performance in predicting LVH with an AUC of 0.59 (sensitivity 65%, specificity 57%). In the subgroup analysis, the CNN-LSTM model predicted LVH by 12-lead ECG with an AUC of 0.66 (sensitivity 72%, specificity 60%) for male patients, which performed better than that for female patients (AUC: 0.59, sensitivity 50%, specificity 71%).ConclusionOur study established a CNN-LSTM model to diagnose LVH by 12-lead ECG with higher sensitivity than current ECG diagnostic criteria. This CNN-LSTM model may be a simple and effective screening tool of LVH.

Objectives In order to improve the performance of traditional absorbing materials, a high-absorptivity broadband absorber is designed. Methods The absorber consists of a resistive film, dielectric substrate and metal ground plate. The element unit of the resistive film is composed of a Jerusalem cross unit and outer square loop. Results The simulated results indicate that the absorption of the designed absorber is more than 90% in the frequency range of 2.9–5.1 GHz, and an absorptivity peak of 99.4% can be achieved. Absorption performance can also be maintained in wide-angle cases and polarization-insensitive cases. Conclusions The absorber proposed in this paper has significance for the design and application of broadband absorbers.

Numerical well testing is used mostly in oil/gas, geothermal, and coalbed methane injection/falloff well-testing interpretations while few published studies have been presented on how to adjust the models and numerical experiments parameters. Meanwhile, there is no simple and highly applicable evaluation standard on the approximation degree between the simulated and field-measured pressure response. In this paper, seven groups of numerical experiments were conducted to obtain the simulated pressure response. The Pearson correlation coefficients and the grey correlation between the simulated and field-measured pressure response were calculated to evaluate the approximation degree. In homogeneous, stress-independent, multi-layered, heterogeneous and integrated models, the simulated pressure response curves all fit to the field data well at the early and late time of the falloff period. However, the highest approximation degree was only found in the integrated model. Finally, the permeability, initial pressure, skin factor and investigation radius of the tested CBM reservoir were determined. The results show that, to obtain a reliable interpretation result, it is best to give an approximation degree evaluation standard on the approximation degree between the simulated and field-measured pressure response, build an integrated numerical model, and input the correct parameters, such as the effective thickness and the testing fluid viscosity. Otherwise, it will also drop into a pitfall of multi-results. The method we used is very relevant to CBM exploration and safe mining in Hedong coalfield.

GRAS is a transcription regulator factor, which plays an important role in plant growth and development. Previous analyses found that several GRAS functions have been identified, such as axillary bud meristem formation, radial root elongation, gibberellin signaling, light signaling, and abiotic stress. The GRAS family has been comprehensively evaluated in several species. However, little finding is on the GRAS transcription factors (TFs) in Chinese white pear. In this study, 99 PbGRAS were systemically characterized and renamed PbGRAS1 to PbGRAS99 according to their chromosomal localizations. Phylogenetic analysis and structural features revealed that could be classified into eight subfamilies (LISCL, Ls, SHR, HAM, SCL, PAT, SCR, and DELLA). Further analysis of introns/exons and conserved motifs revealed that they are diverse and functionally differentiated in number and structure. Synteny analysis among Pyrus bretschenedri, Prunus mume, Prunus avium, Fragaria vesca, and Prunus persica showed that GRAS duplicated regions were more conserved. Dispersed duplication events are the most common mechanism and may play a crucial role in the expansion of the GRAS gene family. In addition, cis-acting elements of the PbGRAS gene were found in promoter regions associated with hormone and environmental stress responses. Notably, the expression pattern detected by qRT-PCR indicated that PbGRAS genes were differentially expressed under gibberellin (GA), abscisic acid (ABA), and auxin (IAA) conditions, which are responsive to abiotic stress. PbGRAS89 and PbGRAS99 were highly expressed at different stages of hormone treatment and may play important role in leaf development. Therefore, we selected PbGRAS89 and PbGRAS99 to clone and construct pCAMBIA1301-PbGRAS89, 99 and transferred them into Arabidopsis thaliana. Finally, we observed and compared the changes of overexpressed plants and wild-type plants during regeneration. This method was used to analyze their roles in leaf regeneration of Chinese white pear. In addition, we also constructed pCAMBIA1305-PbGRAS89, 99, and transferred them into onion cells to determine the subcellular localization. Subcellular localization experiments showed that PbGRAS89 and PbGRAS99 were localized in the nucleus. In summary, the results of this study indicate that PbGRAS89 and PbGRAS99 are mainly responsible for leaf regeneration of Chinese white pear, which plays a positive role in callus formation and provides rich resources for studying GRAS gene functions.

Biological treatment can remove more than 89.8% of total organic carbon (TOC) and 94.4% of fluorescent dissolved organic matter (DOM) in the coking wastewater, thereby affecting the migration, transformation and bioavailability and binding characteristics of heavy metals (HMs). The results of parallel factor analysis (PARAFAC) show that protein-like materials accounted for 97.53% in the coking wastewater DOM, a large number of humic-like substances are produced and accounted for more than 55.40% after biological treatment. A new spectral data processing method, the 1/n-th power transformation after two-dimensional correlated spectroscopy (2D-COS) in combination with synchronous fluorescence spectra (SFS), can identify small features obscured by strong peaks, and reveal more binding sites as well as preserve the sequential order information. The result indicates that the preferential bonding of Cu(II) is at 306 nm (protein-like) for coking wastewater DOM, and at 514 nm (humic-like) for effluent DOM. The C−O group of esters and alcohols can preferentially complexate with Cu(II) in the coking wastewater and effluent DOM. The log KM values of PARAFAC components with Cu(II) are in the range of 3.59–5.06 for coking wastewater DOM, and in the range of 4.80–5.64 for the effluent DOM. Log KM values for protein-like materials with Cu(II) are higher than these for fulvic- and humic-like substances. Humic-like substances can form more stable complexes with Cu(II) in the effluent DOM. Biological treatment increases the chemical stability of DOM-Cu(II) complexes, thereby further reducing the environmental risk of Cu(II).

As the consumption of Chinese medicine resources increases, the waste of traditional Chinese medicine extraction cannot be disposed of reasonably, which has a serious impact on the environment. Dissolved organic matter (DOM), a crucial fraction in herbal extraction residue, can bond to heavy metals (HMs), creating a potential environmental risk. This study investigated the binding property of herbal extraction residue DOM with Cu(II) via two-dimensional Fourier transform infrared (FTIR) and synchronous fluorescence correlation spectroscopy (2D-COS) in conjunction with parallel factor (PARAFAC) modeling. Through PARAFAC analysis, three kinds of protein components and one kind of fulvic acid can be obtained, and protein-like substances are dominant in the residual DOM of Chinese medicine extracts, becoming the main factor of water quality deterioration. A fluorescence quenching experiment shows that protein-like materials provide the primary binding sites with Cu(II). During the detection, the long-wavelength low-intensity signal will be obscured. The 2D-COS obtained by the 1/9th power transformation can enhance the fluorescence signal so as to get even more information about the binding sites and heterogeneity of DOM and heavy metal ion ligands. The N−H of amine in the protein-like materials could prioritize combining with Cu(II). This study urges that continuous and effective attention be paid to the impact of the herbal extraction residue on the geochemical behavior of HMs.

Abstract Background Presently, there is no comprehensive analysis of the transcription regulation network in hematopoiesis. Comparison of networks arising from gene co-expression across species can facilitate an understanding of the conservation of functional gene modules in hematopoiesis. Results We used single-cell RNA sequencing to profile bone marrow from human and mouse, and inferred transcription regulatory networks in each species in order to characterize transcriptional programs governing hematopoietic stem cell differentiation. We designed an algorithm for network reconstruction to conduct comparative transcriptomic analysis of hematopoietic gene co-expression and transcription regulation in human and mouse bone marrow cells. Co-expression network connectivity of hematopoiesis-related genes was found to be well conserved between mouse and human. The co-expression network showed “small-world” and “scale-free” architecture. The gene regulatory network formed a hierarchical structure, and hematopoiesis transcription factors localized to the hierarchy’s middle level. Conclusions Transcriptional regulatory networks are well conserved between human and mouse. The hierarchical organization of transcription factors may provide insights into hematopoietic cell lineage commitment, and to signal processing, cell survival and disease initiation.