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Abstract Cell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.

Abstract Biochar can improve soil health and fix CO2 by altering soil microenvironment, thus impacting the global carbon cycle and the change of soil ecological environment. Recent studies show that cotton byproduct-derived biochar is a potential effective amendment for soil improvement so that it could play an important role in agricultural and environmental conservation. In this work, research topics on cotton byproduct-derived biochar in soil in last decade and so are systematically reviewed for better understanding of the progresses of cotton byproduct-derived biochar in (i) the morphologic and physicochemical characterization, (ii) latest research hotspots and trends, (iii) the roles in soil reclamation, and (iv) relevant carbon sequestration mechanisms. Finally, the future research directions regarding cotton byproduct-derived biochar mingled to soil environment are discussed. Insight derived from this work would provide scientific basis for promoting more applications of cotton byproduct-derived biochar in soil ecological restoration and carbon fixation. Graphical Abstract

Abstract Sintering of active metal species often happens during catalytic reactions, which requires redispersion in a reactive atmosphere at elevated temperatures to recover the activity. Herein, we report a simple method to redisperse sintered Cu catalysts via O2-H2O treatment at room temperature. In-situ spectroscopic characterizations reveal that H2O induces the formation of hydroxylated Cu species in humid O2, pushing surface diffusion of Cu atoms at room temperature. Further, surface OH groups formed on most hydroxylable support surfaces such as γ-Al2O3, SiO2, and CeO2 in the humid atmosphere help to pull the mobile Cu species and enhance Cu redispersion. Both pushing and pulling effects of gaseous H2O promote the structural transformation of Cu aggregates into highly dispersed Cu species at room temperature, which exhibit enhanced activity in reverse water gas shift and preferential oxidation of carbon monoxide reactions. These findings highlight the important role of H2O in the dynamic structure evolution of supported metal nanocatalysts and lay the foundation for the regeneration of sintered catalysts under mild conditions.

Abstract The human microbiome, comprising microorganisms residing within and on the human body, plays a crucial role in various physiological processes and has been linked to numerous diseases. To analyze microbiome data, it is essential to account for inherent heterogeneity and variability across samples. Normalization methods have been proposed to mitigate these variations and enhance comparability. However, the performance of these methods in predicting binary phenotypes remains understudied. This study systematically evaluates different normalization methods in microbiome data analysis and their impact on disease prediction. Our findings highlight the strengths and limitations of scaling, compositional data analysis, transformation, and batch correction methods. Scaling methods like TMM show consistent performance, while compositional data analysis methods exhibit mixed results. Transformation methods, such as Blom and NPN, demonstrate promise in capturing complex associations. Batch correction methods, including BMC and Limma, consistently outperform other approaches. However, the influence of normalization methods is constrained by population effects, disease effects, and batch effects. These results provide insights for selecting appropriate normalization approaches in microbiome research, improving predictive models, and advancing personalized medicine. Future research should explore larger and more diverse datasets and develop tailored normalization strategies for microbiome data analysis.

ABSTRACT: Ultrasound-induced egg white fluidic gels (UEFG) were prepared through ultrasonic pretreatment followed by subsequent heating. The optimal preparation parameters for UEFG were: ultrasonic power density between 0.2 to 0.8 W/mL, ultrasonic treatment time surpassing 150 s, heating temperature within 70 to 76°C, and heating time under 16 min. The prepared UEFG is a milky white solution with a viscosity lower than that of fresh egg white, and displayed a particle size distribution primarily between 100 and 1,200 nm. Stability assessments conducted over 28 d at 4°C revealed that UEFG remained stable at pH 6-10, with exceptional stability from pH 8 to 10, while it is less stable in highly acidic (pH 2-4) or basic environments (pH 12). The UEFG also showed commendable stability in the presence of salt and sucrose solutions. We report a simple and novel method for preparing UEFG with good flowability after heating treatment. The UEFG has broad applications in the food industry, such as precooked egg white powder, high protein beverages, composite dairy products, etc.

Hemochromatosis, also known as siderosis, is a disease caused by excessive iron deposition in human organs and tissues, resulting from iron metabolism disorders. It is clinically characterized by skin pigmentation (bronze color), liver cirrhosis, diabetes, weakness, and fatigue. Additional symptoms may include arthritis, hypothyroidism, heart failure, and sexual hypofunction. Clinical manifestations can vary from person to person, with a few patients showing no clinical manifestations, which makes the diagnosis difficult for clinicians. In this case report, we described hereditary hemochromatosis related to a mutation in the HAMP gene in Fuyang City, China, as a reference for clinicians. Hereditary hemochromatosis is rarely reported in China. Clinicians in China have relatively insufficient knowledge of this disease, which leads to frequent misdiagnosis. In this case report, we describe hereditary hemochromatosis related to HAMP gene mutation in Fuyang City, China, for the clinician’s reference.

Genotype-to-phenotype mapping is an essential problem in the current genomic era. While qualitative case-control predictions have received significant attention, less emphasis has been placed on predicting quantitative phenotypes. This emerging field holds great promise in revealing intricate connections between microbial communities and host health. However, the presence of heterogeneity in microbiome datasets poses a substantial challenge to the accuracy of predictions and undermines the reproducibility of models. To tackle this challenge, we investigated 22 normalization methods that aimed at removing heterogeneity across multiple datasets, conducted a comprehensive review of them, and evaluated their effectiveness in predicting quantitative phenotypes in three simulation scenarios and 31 real datasets. The results indicate that none of these methods demonstrate significant superiority in predicting quantitative phenotypes or attain a noteworthy reduction in Root Mean Squared Error (RMSE) of the predictions. Given the frequent occurrence of batch effects and the satisfactory performance of batch correction methods in predicting datasets affected by these effects, we strongly recommend utilizing batch correction methods as the initial step in predicting quantitative phenotypes. In summary, the performance of normalization methods in predicting metagenomic data remains a dynamic and ongoing research area. Our study contributes to this field by undertaking a comprehensive evaluation of diverse methods and offering valuable insights into their effectiveness in predicting quantitative phenotypes.

Abstract Dietary exposure to heavy metals and metalloids [metal(loid)s] deserves increased attention; however, there is a lack of a comprehensive understanding of the risks of dietary exposure from multi-type food intake and multi-metal(loid) exposure using a bioaccessibility-corrected method. Here, we determined the concentration and bioaccessibility of six toxic metal(loid)s in six major food groups in an industrial city with intensive smelting activity. By incorporating children’s dietary patterns, the probability distribution of health risks from dietary metal(loid)s exposure was assessed. Marked differences were observed in the dietary exposure characteristics within metal(loid)s and major food groups. Cereal and vegetables were the major food groups local children intake. Cereals, meat, beans, and aquatic products had the highest concentrations of Cu and Cd, Pb and Cr, Ni, and As, respectively. Generally, meat, eggs, and aquatic products exhibited higher bioaccessibility than cereals, beans, and vegetables. The bioaccessibility of metal(loid)s decreased in the following order: Pb > Cr > Cu > Ni > As > Cd. For non-carcinogenic risks, the average hazard index was 7.3, with 99.6% exceeding acceptable levels. Arsenic was the dominant risk element and aquatic product was the main risk source. The aggregated carcinogenic risk was 3.4 × 10–3, with Cr the major risk contributor and cereals and meat the dominant food sources. The findings demonstrated that (1) the metal(loid) dietary exposure risk of children from areas with intensive smelting activities should be taken seriously, and (2) it is necessary to identify the specific food category and metal(loid) based on a comprehensive analysis of the metal(loid) concentration and bioaccessibility, and dietary habits of the population to effectively reduce risk.

Abstract As the cornerstone of enterprises, employees have played a pivotal role in navigating the challenges posed by the COVID-19 pandemic and ensuring the survival and growth of businesses. The global wave of unemployment triggered by the pandemic has given rise to innovative work engagements, including remote work and employee sharing. This shift prompts employees to reconsider their relationship with the organization, the extent of their collaboration, and their commitment to sustaining the enterprise’s viability and development. Amidst the diverse performance level of employees, the question arises: will they redouble their efforts to showcase their value or succumb to a state of inertia? Additionally, the outbreak of the COVID-19 epidemic has brought about adverse impacts, making enterprises think about how to inhibit employees’ social loafing, stimulate their enthusiasm, and to rely on collective strength to overcome the crisis. During the pandemic, uncertainty of the work environment was elevated, and the factors influecing employees’ social loafing, perception of organizational justice, and organizational commitment became more significant. Based on the social exchange theory, this paper conducts research on how employees’ perception of organizational justice level weakens their social loafing and incorporates organizational commitment into the research framework in order to explore new presentations of relationships between these variables in the context of the epidemic. Through the data analysis of 276 questionnaires, the study found that: (1) the organizational justice has a negative impact on the social loafing of employees; (2) the organizational commitment plays a complete mediating role between the organizational justice and employees’ social loafing.

In this paper, we studied a double-phase eigenvalue problem with large variable exponents. Let $ \lambda^{1}_{(p_{n}(\cdot), \, q_{n}(\cdot))} $ be the first eigenvalues and $ u_{n} $ be the first eigenfunctions, normalized by $ \|u_{n}\|_{\mathcal{H}_{n}} = 1 $. Under some assumptions on the variable exponents $ p_{n}(\cdot) $ and $ q_{n}(\cdot) $, we showed that $ \lambda^{1}_{(p_{n}(\cdot), \, q_{n}(\cdot))} $ converges to $ \Lambda_{\infty} $, $ u_{n} $ converges to $ u_{\infty} $ uniformly in the space $ C^{\alpha}(\Omega)\, (0 < \alpha < 1) $ and $ u_{\infty} $ is a nontrivial viscosity solution to a Dirichlet $ \infty $-Laplacian problem. Even in the case where the variable exponents reduce to the constant exponents, our work is the first one dealing with a double-phase eigenvalue problem with large exponents.

ABSTRACT: To elucidate the regulatory mechanisms that impact variability in albumen quality of laying hens from the peak of lay to the late production phase. A 60-wk study was conducted on a cohort of 20,000 Hy-Line Brown laying hens from 20 to 80 wk old. Before commencement at 20 wk, the 10-wk-old hens were acclimatized for 10 wk. This study examined changes in albumen quality, serum, and liver antioxidant capacity, magnum morphology, and expression of albumen-protein-related genes in the magnum. To reduce sampling error, we collected eggs (n = 90) from pre-determined cages at every sampling point (5-wk intervals), and 8 hens were selected at 10-wk intervals for blood and tissue collection. Our findings revealed that age significantly affected most evaluated parameters. Albumen gel properties, including hardness, gumminess, and chewiness, increased significantly with age (P < 0.05). With the increasing of hens' age from 20 to 80 wk, the albumen proportion of eggs was decreased, but eggshell proportion, yolk proportion, thick albumen proportion, thick to thin ratio, thick albumen solid content, albumen height, Haugh units (HU), and yolk color were increased and then decreased (P < 0.05). Compared to hens aged 20 to 60 wk, the hens (70–80 wk) had significantly reduced total antioxidant capacity (TAC) and glutathione levels (GSH) in the liver and lower serum TAC and superoxide dismutase levels (SOD) (P < 0.05). The magnum mucosal folds were highest in 40 to 60 wk-old hens, and the luminal diameter increased with age (P < 0.05). In the magnum, the mRNA expression levels for OVA, CPE, and NUP205 increased significantly between 30 and 40 wk, while FBN1 expression was higher between 30 and 50 wk (P < 0.05). At 70 to 80 wk, the expression of BRCA2 was significantly downregulated (P < 0.05). Albumen height, thick albumen proportion with protein secretion-related genes, enhanced antioxidant function, and luminal diameter correlated positively. However, the thick-to-thin albumen ratio negatively correlated with BRCA2, downregulated in aged laying hens. We used principal component and cluster analysis to deduce albumen quality changes during 3 phases: 25 to 35, 40 to 55, and 60 to 80 wk. The decline in albumen quality in aging hens is linked with decreased antioxidant capacity, magnum health, and downregulation of key genes involved in protein synthesis and secretion. These findings emphasize critical albumen quality changes in laying hens and suggest molecular pathways underlying age-related albumen quality alterations.

ABSTRACT: Chicken egg chalaza (CLZ) is a natural colloidal structure in eggs that exists as an egg yolk stabilizer and is similar in composition to egg white. In this study, the proteome, phosphoproteome, and N-glycoproteome of CLZ were characterized in depth. We hydrolyzed the CLZ proteins and enriched the phosphopeptides and glycopeptides. We identified 45 phosphoproteins and 80 N-glycoproteins, containing 59 phosphosites and 203 N-glycosylation sites, respectively. Typically, the ovalbumin in CLZ was both phosphorylated and N-glycosylated, with 4 phosphosites and 4 N-glycosylation sites. Moreover, we identified 2 N-glycosylated subunits of ovomucin, mucin-5B and mucin-6, with 32 and nine N- glycosylation sites, respectively. Analysis of the phosphorylation and N-glycosylation status of CLZ proteins could provide novel insights into the structural and functional characteristics of CLZ.

The objective of this study was to investigate the function of the aquaporin 4 gene (LvAQP4), which had previously been characterized in Pacific white shrimp, Litopenaeus vannamei. To achieve this, double-stranded RNA (dsRNA) targeting LvAQP4 was synthesized and injected into shrimp, resulting in a significant reduction in the expression of LvAQP4. Subsequent to the evaluation of the impact of LvAQP4 transcriptional silencing on shrimp under salinity challenges, we observed that the downregulation of LvAQP4 expression in the gills resulted in the downregulation of aquaglyceroporin (LvAQP3) and unorthodox aquaporin (LvAQP11) genes, as well as ion transporter genes, such as LvNKAα, LvNKAβ, LvCAc, and LvVHA-a. Notably, the inhibition of LvAQP4 had a significant impact on the expression patterns of these osmoregulatory genes, particularly during periods of high salinity stress. Furthermore, there was a notable increase in the mortality rate of shrimp under high-salinity stress. Moreover, the suppression of LvAQP4 through RNA interference led to a significant delay in the molting rate of shrimp. Furthermore, it resulted in an increase in the expression of LvMIH and a significant reduction in key genes involved in the ecdysone signaling pathway, including LvEcR, LvRXR, and LvE75. These findings suggest that LvAQP4 may play a regulatory role in the molting process of shrimp by modulating MIH and the ecdysone signaling pathway. Moreover, this study lays the groundwork for future investigations into the functions of aquaporins in shrimp osmoregulation and growth, contributing to an enhanced understanding of these essential regulatory mechanisms.

BackgroundBreast cancer persists as a major public health issue on a global scale. Lymphangiogenesis is an indispensable element in the promotion of breast cancer metastasis. Inhibiting the metastasis of breast cancer can be accomplished through targeting lymphangiogenesis. The purpose of this study was to examine research trends, major topics, and development directions of lymphangiogenesis in breast cancer through a bibliometric analysis, which may serve as a reference for future research and clinical practice.MethodsEnglish publications with article type article or review about lymphangiogenesis in breast cancer from inception to September 30, 2023, retrieved from the Web of Science Core Collection Database (WOSCC), and VOSviewer, CiteSpace, and Microsoft Excel were applied for bibliometric study.ResultsIn this paper, a total of 369 articles and reviews were included. The 369 papers were written by 2120 authors from 553 organizations across 42 countries, published in 199 journals, and cited 12458 references from 1801 journals up to September 30, 2023. Moreover, the annual publications had a rising trajectory between 2004 to 2014 but declined from 2015. The US was the leading nation in publications and citations. Meanwhile, academics Mousumi Majumder and Peeyush Lala had the highest cumulative number of publications. Based on the number of publications/citations, Cancer Research was the most influential journal. The most cited paper was “Lymphangiogenesis: Molecular Mechanisms and Future Promise” by Tuomas Tammela, published in the Journal of Cell. Additionally, keywords frequency analysis demonstrated that “lymphangiogenesis,” “breast cancer,” “VEGF-C,” “angiogenesis,” and “metastasis” were the most frequent keywords, and the newly emergent topics could be represented by “tumor microenvironment,” “metastasis,” “stem-cell,” “triple-negative breast cancer,” and “blood vessels.”ConclusionsCurrently, there is a strong research basis for lymphangiogenesis in breast cancer. The core research team was primarily situated in the US. Investigating the mechanism of lymphangiogenesis in breast cancer will always remain a highly discussed topic. In particular, it was essential to emphasize the relationship between lymphangiogenesis and tumor microenvironment, stem cells, triple-negative breast cancer, and metastasis, which could be the frontiers.

Abstract Objectives This study aims to evaluate the efficacy of multi-model incorporated by radiomics, deep learning, and transcriptomics features for predicting pathological grade and survival in patients with clear cell renal cell carcinoma (ccRCC). Methods In this study, data were collected from 177 ccRCC patients, including radiomics features, deep learning (DL) features, and RNA sequencing data. Diagnostic models were then created using these data through least absolute shrinkage and selection operator (LASSO) analysis. Additionally, a multi-model was developed by combining radiomics, DL, and transcriptomics features. The prognostic performance of the multi-model was evaluated based on progression-free survival (PFS) and overall survival (OS) outcomes, assessed using Harrell’s concordance index (C-index). Furthermore, we conducted an analysis to investigate the relationship between the multi-model and immune cell infiltration. Results The multi-model demonstrated favorable performance in discriminating pathological grade, with area under the ROC curve (AUC) values of 0.946 (95% CI: 0.912–0.980) and 0.864 (95% CI: 0.734–0.994) in the training and testing cohorts, respectively. Additionally, it exhibited statistically significant prognostic performance for predicting PFS and OS. Furthermore, the high-grade group displayed a higher abundance of immune cells compared to the low-grade group. Conclusions The multi-model incorporated radiomics, DL, and transcriptomics features demonstrated promising performance in predicting pathological grade and prognosis in patients with ccRCC. Critical relevance statement We developed a multi-model to predict the grade and survival in clear cell renal cell carcinoma and explored the molecular biological significance of the multi-model of different histological grades. Key points 1. The multi-model achieved an AUC of 0.864 for assessing pathological grade. 2. The multi-model exhibited an association with survival in ccRCC patients. 3. The high-grade group demonstrated a greater abundance of immune cells. Graphical Abstract

By exploiting the local randomness in close-call labor elections, the authors find a negative impact of labor unionization at a firm on its real earnings management (REM). The finding suggests a managerial pressure effect of increased labor power. In a local regression discontinuity (RD) analysis, firms that narrowly pass the 50% threshold show a significant decrease in REM, relative to their peers that narrowly fail. This effect is stronger for firms headquartered in right-to-work states and when managers have less pressure to manage earnings. Evidence from a global parametric RD analysis and a multivariate OLS test using industry-level unionization measures confirms the external validity of results in local RD analysis. Overall, the research sheds new light on the economic consequence of labor unionization on employers' accounting decisions.

Purpose: To investigate perioperative risk factors that affect the recovery of postoperative gastrointestinal function in patients undergoing gynecological surgery and to establish a preoperative risk prediction scoring system. Methods: In this retrospective cohort study, characteristics and perioperative factors of patients who underwent elective gynecological surgery at Union Hospital from January 2021 to March 2022 were extracted from electronic medical records. Patients were grouped according to the Intake, Feeling nauseated, Emesis, physical Exam, and Duration of symptoms (I-FEED) scoring system to compare collected data. Results: In total, clinical data from 208 gynecological patients were extracted. The incidence of poor postoperative gastrointestinal recovery was 7.21 %. The number of previous abdominal surgeries (0.73 ± 0.06 vs 1.20 ± 0.24, p = 0.044), the incidence of malignant disease (20.2 % vs 53.3 %, p = 0.003), postoperative maximum WBC count (9.15 vs 12.44, p = 0.005) and postoperative minimum potassium (3.97 ± 0.36 vs 3.76 ± 0.37, p = 0.036) were not only associated with poor postoperative gastrointestinal recovery, but also malignant disease (p = 0.000), postoperative maximum WBC count (p = 0.027) and postoperative minimum potassium (p = 0.024) were significantly associated with the severity of postoperative gastrointestinal function. An increased number of previous abdominal surgeries and malignant primary disease could increase the risk of an I-FEED score >2 as independent risk factors. Conclusion: Patients with poor postoperative GI function had poorer postoperative recovery outcomes. A preoperative score prediction system was established, in which patients with ≥2 points had a 19.4 % risk of poor postoperative gastrointestinal recovery. Higher-quality prospective studies should be performed to achieve more precise risk stratification and to construct a more accurate prediction system.

Objectives The objective of this study was to explore the correlation between the distribution of traditional Chinese medicine (TCM) syndromes and molecular types of breast cancer in the perichemotherapy period.

ABSTRACT: Egg yolk (EY) can be divided into yolk granules (EYG) and yolk plasma (EYP) after water dilution and centrifugation. EYP had a significantly higher lipid content and is predominantly in the form of low-density lipoprotein (LDL) while EYG has a higher protein content. In order to explore the nutritional differences between EY, EYP and EYG, quantitative metabolomic analysis was carried out by ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The results showed that a total of 588 small molecule metabolites were identified, mainly glycerol phospholipids (51.59–66.46%), coenzymes, and vitamins (1.21–1.84%). A quantitative comparison showed that amino acids and their metabolites were the most representative metabolites of differential abundance in the contrast of EY and EYG, EYP and EYG. Carbohydrates and their metabolites were the representative metabolites of differential abundance between EY and EYP. The study provided important information for understanding the metabolic composition of EY, EYG, and EYP, as well as providing a reference for utilizing the whole egg.

ABSTRACT: The process of egg yolk formation involves the transport and uptake of a large number of small molecule metabolites. A qualitative and relative quantitative analysis of metabolites in the 3 formation periods of egg yolk was performed by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical workflow. A total of 398 metabolites were identified, of which “amino acids and their metabolites”, “lipid”, and “organic acids and their derivatives” were the dominant egg yolk metabolite categories with the most metabolite species. The findings suggested that a number of amino acids, organic acids, nucleotides and their metabolites were deposited during follicular development to provide material support for later embryonic development. At the same time, some vitamins and carbohydrates were consumed during follicular development to support the normal development process. In addition, the small hierarchical follicle (SF) period may be a critical period for the regulation of the transport and deposition of some active ingredients. These results contribute to a comprehensive understanding of the nutrient deposition pattern and nutritional properties of egg yolk.

This chapter presents a systematic study of the inhibition effect of chlorine dioxide treatment alone and in combination with ultrasound treatment of Salmonella and the physiological metabolic processes within the treated cells. The low-power ultrasound (0.03 W/mL) significantly enhanced the effectiveness (110.00 %) of low concentrations of chlorine dioxide (0.25 mg/L) in inhibiting Salmonella, which, in turn, would significantly reduce the potential environmental impact. In addition, further studies found that low-power ultrasound may enhance the structural and functional damage of chlorine dioxide on Salmonella cell membranes (significant increase in permeability of the outer and inner cell membranes) and disrupt intracellular substance metabolism (small molecule and nucleotide metabolism) and energy metabolism (significant reduction in ATP content and ATPase activity) balance to improve the bacterial inhibitory effect of chlorine dioxide. The results of the study will provide a theoretical basis and methodological guidance for the implementation of “cleaner production” in the food industry.

Ensuring source location privacy is crucial for the security of underwater acoustic sensor networks amid the growing use of marine environmental monitoring. However, the traditional source location privacy scheme overlooks multi-attacker cooperation strategies and also has the problem of high communication overhead. This paper addresses the aforementioned limitations by proposing an underwater source location privacy protection scheme based on game theory under the scenario of multiple cooperating attackers (SLP-MACGT). First, a transformation method of a virtual coordinate system is proposed to conceal the real position of nodes to a certain extent. Second, through using the relay node selection strategy, the diversity of transmission paths is increased, passive attacks by adversaries are resisted, and the privacy of source nodes is protected. Additionally, a secure data transmission technique utilizing fountain codes is employed to resist active attacks by adversaries, ensuring data integrity and enhancing data transmission stability. Finally, Nash equilibrium could be achieved after the multi-round evolutionary game theory of source node and multiple attackers adopting their respective strategies. Simulation experiments and performance evaluation verify the effectiveness and reliability of SLP-MACGT regarding aspects of the packet forwarding success rate, security time, delay and energy consumption: the packet delivery rate average increases by 30%, security time is extended by at least 85%, and the delay is reduced by at least 90% compared with SSLP, PP-LSPP, and MRGSLP.

Underwater acoustic sensor networks (UASNs) are vital for applications like marine environmental monitoring, disaster prediction, and national defense security. Due to the prolonged exposure of underwater sensor nodes in unattended and potentially hostile environments, the application of UASNs is confronted with numerous security threats. Trust models are an important means to detect anomalous nodes in UASNs and ensure security. However, when confronted with intricate underwater surroundings, the assessment of trust is prone to disruption, and current trust models lack a flexible mechanism for updating trust. Consequently, this study introduces a dynamic evaluation trust model (DRFTM) for underwater acoustic sensor networks that integrate deep reinforcement learning and the random forest algorithm. First, the DRFTM comprehensively considers indicators including communication, data, energy, and environment to provide reliable trust evidence for the next evaluation; second, under the conditions of node mobility and dynamic updating of network topology, we propose a predictive model for assessing the trust status of sensor nodes based on random forest training; last, the utilization of deep reinforcement learning is instrumental in determining the most effective trust update strategy, leading to improved detection accuracy of the trust model. The simulation results demonstrate the effectiveness of the DRFTM in detecting malicious nodes, reducing false positives, and accurately assessing trust, achieving a remarkable 99% accuracy in identifying malicious nodes.

This study aims to comprehensively investigate the effects of hot-air dehydration on the quality of blue honeysuckle berries (Lonicera caerulea L.). The results demonstrated that drying with hot air at 40–65 °C for 7–72 h resulted in blue honeysuckle berries with a moisture content of 0.21–1.10 g H2O/g dry weight. Generally, low to medium temperatures (40–55 °C) showed a better effect on the quality than high temperatures (60–65 °C). Specifically, drying at 40 °C exclusively resulted in better retention of cuticular wax, the best sensory appearance, and the highest total phenolic content. Drying at 45 °C and 50 °C resulted in the highest antioxidant capacity and the optimal sensory flavor. Drying at 55 °C led to the highest soluble solid/acid ratio, ascorbic acid concentration, total flavonoid, and total anthocyanin. The work introduces an innovative raw berry product and provides a comprehensive practical and theoretical framework for convective dehydration of blue honeysuckle berries.

Abstract Halide double perovskites have recently emerged as an environmentally green candidate toward electronic and optoelectronic applications owing to their non-toxicity and versatile physical merits, whereas study on high-temperature antiferroelectric (AFE) with excellent anti-breakdown property remains a huge blank in this booming family. Herein, we present the first high-temperature AFE of the lead-free halide double perovskites, (CHMA)2CsAgBiBr7 (1, where CHMA+ is cyclohexylmethylammonium), by incorporating a flexible organic spacer cation. The typical double P-E hysteresis loops and J-E curves reveal its concrete high-temperature AFE behaviors, giving large polarizations of ~4.2 μC/cm2 and a high Curie temperature of 378 K. Such merits are on the highest level of molecular AFE materials. Particularly, the dynamic motional ordering of CHMA+ cation contributes to the formation of antipolar alignment and high electric breakdown field strength up to ~205 kV/cm with fatigue endurance over 104 cycles, almost outperforming the vast majority of molecule counterparts. This is the first demonstration of high-temperature AFE properties in the halide double perovskites, which will promote the exploration of new “green” candidates for anti-breakdown energy storage capacitor.

Abstract Introduction Stage IB (deep myometrial invasion) high‐grade endometrioid adenocarcinoma (EA), regardless of LVSI status, is classified into high‐intermediate risk groups, requiring surgical lymph node staging. Intraoperative frozen section (IFS) is commonly used, but its adequacy and reliability vary between reports. Hence, we determined the utility of IFS in identification of high‐risk factors, including deep myometrial invasion and high‐grade. Method We retrospectively analyzed 9,985 cases operated with hysterectomy and diagnosed with FIGO stage I/II EA in postoperative paraffin section (PS) results at 30 Chinese hospitals from 2000 to 2019. We determined diagnostic performance of IFS and investigated whether the addition of IFS to preoperative biopsy and imaging could improve identification of high‐risk factors. Results IFS and postoperative PS presented the highest concordance in assessing deep myometrial invasion (Kappa: 0.834), followed by intraoperative gross examination (IGE Kappa: 0.643), MRI (Kappa: 0.395), and CT (Kappa: 0.207). IFS and postoperative PS presented the highest concordance for high‐grade EA (Kappa: 0.585) compared to diagnostic curettage (D&C 0.226) and hysteroscope (Hys 0.180). Sensitivity and specificity for detecting deep myometrial invasion were 86.21 and 97.20% for IFS versus 51.72 and 88.81% for MRI, 68.97 and 94.41% for IGE. These figures for detecting high‐grade EA were 58.21 and 96.50% for IFS versus 16.42 and 98.83% for D&C, 13.43 and 98.64% for Hys. Parallel strategies, including MRI‐IFS (Kappa: 0.626), D&C‐IFS (Kappa: 0.595), and Hys‐IFS (Kappa: 0.578) improved the diagnostic efficiencies of individual preoperative examinations. Based on the high sensitivity of IFS, parallel strategies improved the sensitivities of preoperative examinations to 89.66% (MRI), 64.18% (D&C), 62.69% (Hys), respectively, and these differences were statistically significant (p = 0.000). Conclusion IFS presented reasonable agreement rates predicting postoperative PS results, including deep myometrial invasion and high‐grade. IFS helps identify high‐intermediate risk patients in preoperative biopsy and MRI and guides intraoperative lymphadenectomy decisions in EA.

In 2022, China faced unusually high temperatures, leading to a lack of hydropower in the southwest and increased power demand in the east. This incongruity exerted substantial strain on the power system. To tackle this, a structured method called orderly power utilization (OPU) is suggested as an effective approach to manage short-term power shortages and prevent recurring blackouts. However, typical OPU strategies tend to overlook the principles of fairness, openness, and justice (OEJ), potentially causing problems for various users, especially major industries. Herein, we introduce a comprehensive OPU framework. According to the demand difference in OPU plans in different periods, the optimization cycle is divided into several intervals to achieve computational enhancement. Furthermore, in the interest of judiciously managing the manifold OPU resources characterized by heterogeneous parameters, we introduce an aggregated operational model underpinned by the formalism of zonotopic sets. Numerical simulation results indicate the great potential of the proposed method to solve power shortage problems while upholding the imperatives of OEJ.

ObjectiveTo investigate the adult iodine nutrition and the prevalence of thyroid diseases in Qinghai Province, and analyze the correlation between iodine and thyroid diseases, so as to provide a basis for adjusting the salt iodization plan in Qinghai Province.MethodsUsing cluster and stratified sampling method to select 2628 permanent residents over 18 years old in Qinghai Province for questionnaire survey, physical examination, thyroid color ultrasound, and laboratory index detection.Results1. The coverage of iodized salt in adults is 99.71%. 2. The detection rates of thyroid disorders in adults were as follows: Clinical hyperthyroidism was 1.20%, subclinical hyperthyroidism was 0.20%, clinical hypothyroidism was 1.00%, subclinical hypothyroidism was 29.20%, and the goiter was 2.10%. The percentages positivity of TPO Ab, TG Ab, goiter was 9.80%, 9.20%, 2.10%, respectively. Among them single thyroid nodule was 6.40%, multi-nodule thyroid gland was 1.80%. 3. The percentages of mild iodine deficiency, moderate iodine deficiency, Severe iodine deficiency, adequate iodine intake (AI), more than adequate iodine intake (MAI)and excessive iodine intake (EI)were 8.41%, 2.17%, 0.26%, 33.22%, 28.35%, and 27.59%, respectively. The percentages of mild, moderate and severe iodine deficiency in urban populations (7.13%, 0.87%, 0.0%) were significantly lower than those in rural populations (9.81%, 3.59%, 0.56%) (P < 0.05), and the rates of adequate, more than adequate iodine intake in urban populations (36.03%, 30.93%) were significantly higher than that in rural populations (30.14%, 25.52%). The rate of excess iodine intake was higher in rural areas (30.38%) than in urban areas (25.04%). 4. The positive rates of subclinical hypothyroidism, goiter, TPO Ab and TG Ab in female adults (35.28%, 3.39%, 13.54%, 13.94%) were higher than those in male adults (23.58%, 0.96%, 6.266%, 4.79%). The detection rate of single thyroid nodules was higher in urban (8.01%) than rural populations (4.70%), while the detection rate of hypothyroidism, subclinical hypothyroidism, and goiter (0.58%, 25.84%, 1.38%) was lower than that in rural populations (1.52%, 32.96%, 2.96%) (P0.05). The positive rate of hypothyroidism in the iodine deficiency group is higher than in other iodine nutrition groups.ConclusionThe nutritional status of iodine in Qinghai Province is iodine excess. Subclinical hypothyroidism was detected at a high rate. Subclinical hypothyroidism, goiter, TPO Ab, and TG Ab were more common in female than in male. The proportion of mild, moderate, and severe iodine deficiency was higher in urban areas than in rural areas. The detection rate of thyroid nodules was higher in urban than in rural areas, and that of hypothyroidism, subclinical hypothyroidism, and goiter was lower than that in rural populations. The detection rate of clinical hypothyroidism was statistically significant in different iodine nutritional states (P< 0.05).

Summary: Secondary infection in patients with sepsis triggers a new wave of inflammatory response, which aggravates organ injury and increases mortality. Trained immunity boosts a potent and nonspecific response to the secondary challenge and has been considered beneficial for the host. Here, using a murine model of polymicrobial infection, we find that the primary infection reprograms granulocytes to boost enhanced inflammatory responses to the secondary infection, including the excessive production of inflammatory cytokines, respiratory burst, and augmented phagocytosis capacity. However, these reprogramed granulocytes exhibit “non-classic” characteristics of innate immune memory. Two mechanisms are independently involved in the innate immune memory of granulocytes: a metabolic shift in favor of glycolysis and fatty acid synthesis and chromatin remodeling leading to the transcriptional inactivity of genes encoding inhibitors of TLR4-initiated signaling pathways. Counteracting the deleterious effects of stressed granulocytes on anti-infection immunity might provide a strategy to fight secondary infections during sepsis.

Electrospray ionization (ESI) mass spectrometry is invaluable for studying complex biological systems, and although lipid nanodiscs are a powerful tool for the study of membrane proteins, a lack of clear understanding of the ESI mechanism presents a challenge for spectral interpretation and assignments. Here, the authors study the release behavior of lipid nanodiscs from charged nano-droplets in the ESI process using microsecond atomistic molecular dynamics simulations.

Abstract The purpose of this study was to investigate the association between time restricted feeding (TRF) and different areas of cognitive function in the elderly in Chinese communities. This study consisted of 1353 community-dwelling Chinese older adults aged 60 years and older in Chongming area, Shanghai (563 males; the mean age, 73.38 ± 6.16 years). Mild cognitive impairment (MCI) and six different cognitive domains was assessed by the Chinese-version of Mini Mental State Examination (MMSE). Recording the eating time of each meal through oral inquiry to calculate the time window between the first meal and the last meal of the average day. Participants with an eating time window duration of more than 10 h were then identified, as well as those with eating time restricted to less than 10 h (TRF). Our study found that TRF may be associated with a higher incidence rate of cognitive impairment. TRF only limited the eating time window and did not change the frequency of participants' dietary intake. We used a linear regression model to study the association of TRF with cognitive function. After adjusting for confounding variables, the results showed that TRF was related to MMSE score (P

Abstract The increasing use of distributed generation (DG) in power systems can result in frequent online voltage problems. In scenarios in which substantial DG prediction errors occur because of high DG accommodation levels, traditional technical solutions cannot meet the online voltage regulation requirements. Hence, new resources for online voltage regulation are needed. Here, flexible network reconfiguration is proposed to coordinate with the existing resources for severe online voltage deviations. For online topology‐based voltage regulation (OTVR), the authors develop a deep reinforcement learning (DRL) algorithm based on the following specially designed modelling to enhance the computational performance. The mechanism of action incorporates the concepts of local research, branch exchange, and action separation, and it effectively simplifies the action dimension and action space. In addition, for the graph data in OTVR, a graph convolution network (GCN) is applied to obtain better feature extraction. Case studies performed on IEEE 14‐bus, 33‐bus, 141‐bus systems and a practical system verify that our proposed algorithm can obtain close to optimal solutions in 2 s which can meet the needs of online voltage regulation. Moreover, we verify that the developed OTVR effectively increases DG penetration and decreases the need for investment in additional regulating devices.

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of ‘Hosui’ and ‘Wonwhang’ pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.

There are an estimated 800,000 small reservoirs globally with a range of uses. Given the collective importance of these reservoirs to water resource management and wider society, it is essential that we can monitor and understand the hydrological dynamics of ungauged reservoirs, particularly in a changing climate. However, unlike large reservoirs, continuous and systematic hydrological observations of small reservoirs are often unavailable. In response, this study has developed a retrieval framework for water levels of small reservoirs using a deep learning algorithm and remotely sensed satellite data. Demonstrated at four reservoirs in California, satellite imagery from both Sentinel-1 and Sentinel-2 along with corresponding water level field measurements was collected. Post-processed images were fed into a water level inversion convolutional neural network model for water level inversion, while different combinations of these satellite images, sampling approaches for training/testing data, and attention modules were used to train the model and evaluated for accuracy. The results show that random sampling of training data coupled with Sentinel-2 satellite imagery was generally the most accurate initially. Performance is improved by incorporating a channel attention mechanism, with the average R2 increasing by 8.6% and the average RMSE and MAE decreasing by 15.5% and 36.4%, respectively. The proposed framework was further validated on three additional reservoirs in different regions. In conclusion, the retrieval framework proposed in this study provides a stable and accurate methodology for water level estimation of small reservoirs and can be a powerful tool for small reservoir monitoring over large spatial scales.

Amylase is an indispensable hydrolase in insect growth and development. Its varied enzymatic parameters cause insects to have strong stress resistance. Amylase gene replication is a very common phenomenon in insects, and different copies of amylase genes enable changes in its location and function. In addition, the classification, structure, and interaction between insect amylase inhibitors and amylases have also invoked the attention of researchers. Some plant-derived amylase inhibitors have inhibitory activities against insect amylases and even mammalian amylases. In recent years, an increasing number of studies have clarified the effects of pesticides on the amylase activity of target and non-target pests, which provides a theoretical basis for exploring safe and efficient pesticides, while the exact lethal mechanisms and safety in field applications remain unclear. Here, we summarize the most recent advances in insect amylase studies, including its sequence and characteristics and the regulation of amylase inhibitors (α-AIs). Importantly, the application of amylases as the nanocide trigger, RNAi, or other kinds of pesticide targets will be discussed. A comprehensive foundation will be provided for applying insect amylases to the development of new-generation insect management tools and improving the specificity, stability, and safety of pesticides.

In this study, a stable aqueous solution of paprika oleoresin (PO, the natural colorant extracted from the fruit peel of Capsicum annuum L) was constructed. The solubility of PO in an alkline aqueous solution (pH 10.95–11.10) increased rapidly. However, the aqueous solution of PO (pH 12.00) was unstable, obvious stratification was observed, and the color retention rate was only 52.99% after 28 days of storage. Chicken egg yolk low-density lipoprotein (LDL) was added combined with ultrasonic treatment to improve the stability of LDL-PO solution. The method could decrease the turbidity by 17.5 %, reduce the average particle size of the LDL-PO solution (13.9%), and enhance the interaction and combination of LDL and PO. The prepared PO aqueous solution was used in yogurt, egg white gel, fish balls and soymilk, and it could significantly improve the color of products and provided potential health benefits.

Abstract Background Skeletal muscle‐secreted myokines widely participate in lipids metabolism through autocrine, paracrine and endocrine actions. The myokines represented by FGF21 and Irisin can promote the browning of adipocytes and serve as promising targets for treating obesity. Although recombinant myokines replacement therapy and AAV (adeno‐associated virus)‐based myokines overexpression have shown a definite effect in ameliorating obesity, novel myokine activation strategies with higher efficacy and safety are still in pressing need. This study aimed to evaluate the therapeutic potential of a novel CRISPR‐based myokines activation strategy in obesity treatments. Methods In this study, we used lentivirus and a single AAV vector containing dCas9‐VP64 with a single‐guide RNA to selectively activate Fgf21 and Fndc5 expression in skeletal muscles both in vitro and in vivo. The activation efficacy of the CRISPRa system was determined by qRT‐PCR, Western blotting and ELISA. The treatment effect of CRISPR‐based myokines activation was tested in 3T3‐L1‐derived adipocytes and diet‐induced obese (DIO) mice (male C57BL/6 mice, induced at 6‐week‐old for 10 weeks). Results The virus upregulates myokines expression in both mRNA and protein levels of muscle cells in vitro and in vivo. Myokines secreted by muscle cells promoted browning of 3T3‐L1‐derived adipocytes. In vivo activation of myokines by AAVs can reduce body weight and fat mass, increase the adipocytes browning and improve glucose tolerance and insulin sensitivity in DIO mice. Conclusions Our study provides a novel CRISPR‐based myokines activation strategy that can ameliorate obesity by promoting adipocytes browning.

ABSTRACT: Chicken egg yolk granule is a natural micro–nano aggregate in egg yolk, and its assembly structure varies under different processing conditions. In this study, the effects of NaCl concentration, pH, temperature, and ultrasonic treatment on the properties and microstructure of yolk granule were determined. The results showed that ionic strength (above 0.15 mol/L), alkaline environment (pH 9.5 and 12.0), and ultrasonic treatment induced the depolymerization of egg yolk granule; while freezing-thawing, heat treatment (65°C, 80°C, and 100°C), and mild acidic pH (pH 4.5) induced the aggregation of yolk granule. Scanning electron microscopy observation showed the assembly structure of yolk granule varied with different treatment conditions and confirmed the aggregation-depolymerization of yolk granule under different conditions. Correlation analysis showed that turbidity and average particle size are the 2 most critical indicators that can reflect the aggregation structure of yolk granule in solution. The results are important for understanding the changing mechanism of yolk granule during processing, and provide important information for the applications of yolk granule.

Resumo Objetivo Desenvolver uma modalidade de educação em saúde baseado na teoria do comportamento planejado (TCP) e explorar sua influência no estilo de vida pós-operatório de pacientes com câncer cervical. Métodos Um total de 122 pacientes diagnosticados de janeiro de 2019 a junho de 2020 foram divididos nos grupos Controle e Educação (n = 61) usando uma tabela de números aleatórios. O grupo Controle recebeu educação em saúde tradicional após a cirurgia, enquanto o grupo Educação recebeu educação em saúde baseada em TCP após a cirurgia e seus dados gerais, adesão à medicação, adesão à dieta, tempo de alta, incidência de complicações, estilo de vida, qualidade de vida (QV) e estado mental antes e depois da cirurgia foram comparados. Resultados Não foram encontradas diferenças significativas nos dados gerais, pontuação de estilo de vida pré-operatório, pontuação de qualidade de vida e pontuação de estado mental entre os dois grupos (P>0,05). No grupo Educação, as pontuações de adesão à medicação e adesão à dieta foram significativamente maiores do que no grupo Controle, enquanto o tempo de alta e a incidência total de complicações foram mais precoces e menores do que no grupo Controle (P

The purpose is to compare the development of innovative thinking in two groups of students who learn the intangible cultural heritage of the ancient ethnic group and master oil painting techniques in two formats: distantly and visiting the Miao settlement in the deep southeast of Guizhou. In addition to the traditional learning of oil painting techniques, the students learnt folklore and the cultural heritage of ethnic minorities as a part of the art curriculum. For practice, the control group (96 students) visited the villages of Miao in Guizhou, and the experimental group (96 students) gained experience and knowledge about the Miao ethnic minority distantly, through videos and e-discussions. At the end of the training, the students presented their final oil paintings on the life of the Miao. They have been assessed by teachers and art critics to identify innovative thinking among students as a driving force of creativity. The control group showed higher results on parameters such as Integrity (454 points) and Flexibility (287 points). The high-end result of the control group proved that innovative thinking is best developed by immersing students in the real world of the Miao and allowing them to experiment and feel their works.

Abstract Participants in the supply and demand sides of electricity markets can potentially exercise their market power for their benefits. Hence, market power mitigation is an essential component of market management that physically and economically benefits operators by ensuring fairness in deregulated electricity markets. However, the mechanisms of mitigating market power in electricity markets pose several challenges in terms of market structure monitoring, market power evaluation, and market power mitigation. Therefore, this study provides a comprehensive analysis of market power mitigation mechanisms in electricity markets. First, a review of market structure monitoring and market power evaluation methods is provided to assess participants’ potential and degree of use/abuse of market power. Then, a detailed review of optimal bidding strategies in the supply and demand sides of electricity markets is provided. Accordingly, a systematic classification of market power mitigation is described. Finally, market power mitigation challenges and potential future research directions are discussed.

Abstract Objective Congenital chylothorax (CC) is an uncommon congenital disease. The objective of this study was to analyze the clinical features, treatment, and outcome of infants with CC in a Chinese tertiary medical center. Methods CC was defined as a non-traumatic pleural effusion with ≥ 80% lymphocytes detected before birth or within 28 days after birth. Clinical data were collected in CC infants discharged from June 2017 to March 2021. Results A total of 24 CC infants were discharged during the study period, accounting for 67% of congenital pleural effusions. The median gestational age at birth was 36+4 weeks (range 29+5–41 weeks) and the birth weight was 3025 g (range 1850–4250 g). Twenty-one infants were diagnosed antenatally. The median gestational age at the time of diagnosis was 30+3 weeks (range 24–36+6 weeks). Nine infants presented with hydrops fetalis; 18 were bilateral. Prenatal interventions were performed in 13 fetuses. Nine infants (38%) had birth asphyxia. Compared with the infants without hydrops fetalis, the infants with CC and hydrops fetalis had lower Apgar scores at 1 and 5 min (P

The linker histone H1 binds to the nucleosome core particle at the site where DNA enters and exits, and facilitates folding of the nucleosomes into a higher-order chromatin structure in eukaryotes. Additionally, some variant H1s promote specialized chromatin functions in cellular processes. Germline-specific H1 variants have been reported in some model species with diverse roles in chromatin structure changes during gametogenesis. In insects, the current understanding of germline-specific H1 variants comes mainly from the studies in Drosophila melanogaster, and the information on this set of genes in other non-model insects remains largely unknown. Here, we identify two H1 variants (PpH1V1 and PpH1V2) that are specifically predominantly expressed in the testis of the parasitoid wasp Pteromalus puparum. Evolutionary analyses suggest that these H1 variant genes evolve rapidly, and are generally maintained as a single copy in Hymenoptera. Disruption of PpH1V1 function in the late larval stage male by RNA interference experiments has no phenotype on spermatogenesis in the pupal testis, but results in abnormal chromatin structure and low sperm fertility in the adult seminal vesicle. In addition, PpH1V2 knockdown has no detectable effect on spermatogenesis or male fertility. Collectively, our discovery indicates distinct functions of male germline-enriched H1 variants between parasitoid wasp Pteromalus and Drosophila, providing new insights into the role of insect H1 variants in gametogenesis. This study also highlights the functional complexity of germline-specific H1s in animals.

Summary: Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, the rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations.

To improve the flammability of foamed polyurethane/wood-flour composites (FWPC), ammonium polyphosphate (APP) was used as a flame retardant to modified FWPC. The effects of different flame treatment processes on flame performance, smoke suppression, thermal property, and surface micrographs of flame retardant FWPC were investigated. The results showed that FWPC with the addition or impregnation process both improved the combustion behaviors. Compared with the addition process, FWPC-impregnation (FWPC–I) had a lower total heat release (THR), lower peak heat release rate (PHRR), prolonged time to ignition (TTI), more residues, and better combustion safety. FWPC-I had the highest residual carbon rate reaching 39.98%. A flame-retardant layer containing the P–O group was formed in the residual carbon of FWPC-I. Although APP had negative effects on the physical properties of FWPC, it was an effective flame-retardant ability for foamed polyurethane/wood-flour composites.

Background Mismatch repair deficiency (dMMR) is a well-recognized biomarker for response to immune checkpoint blockade (ICB). Strategies to convert MMR-proficient (pMMR) to dMMR phenotype with the goal of sensitizing tumors to ICB are highly sought. The combination of bromodomain containing 4 (BRD4) inhibition and ICB provides a promising antitumor effect. However, the mechanisms underlying remain unknown. Here, we identify that BRD4 inhibition induces a persistent dMMR phenotype in cancers.Methods We confirmed the correlation between BRD4 and mismatch repair (MMR) by the bioinformatic analysis on The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium data, and the statistical analysis on immunohistochemistry (IHC) scores of ovarian cancer specimens. The MMR genes (MLH1,MSH2,MSH6,PMS2) were measured by quantitative reverse transcription PCR, western blot, and IHC. The MMR status was confirmed by whole exome sequencing, RNA sequencing, MMR assay and hypoxanthine-guanine phosphoribosyl transferase gene mutation assay. The BRD4i AZD5153 resistant models were induced both in vitro and in vivo. The transcriptional effects of BRD4 on MMR genes were investigated by chromatin immunoprecipitation among cell lines and data from the Cistrome Data Browser. The therapeutic response to ICB was testified in vivo. The tumor immune microenvironment markers, such as CD4, CD8, TIM-3, FOXP3, were measured by flow cytometry.Results We identified the positive correlation between BRD4 and MMR genes in transcriptional and translational aspects. Also, the inhibition of BRD4 transcriptionally reduced MMR genes expression, resulting in dMMR status and elevated mutation loads. Furthermore, prolonged exposure to AZD5153 promoted a persistent dMMR signature both in vitro and in vivo, enhancing tumor immunogenicity, and increased sensitivity to α-programmed death ligand-1 therapy despite the acquired drug resistance.Conclusions We demonstrated that BRD4 inhibition suppressed expression of genes critical to MMR, dampened MMR, and increased dMMR mutation signatures both in vitro and in vivo, sensitizing pMMR tumors to ICB. Importantly, even in BRD4 inhibitors (BRD4i)-resistant tumor models, the effects of BRD4i on MMR function were maintained rendering tumors sensitive to ICB. Together, these data identified a strategy to induce dMMR in pMMR tumors and further, indicated that BRD4i sensitive and resistant tumors could benefit from immunotherapy.

Benign breast nodules, thyroid nodules, and myoma of the uterus are similar in etiology and pathogenesis. These three diseases are classified according to accumulation patterns in traditional Chinese medicine theory and can be treated with the same prescription. Yang stagnation is the basic pathogenesis of benign accumulation patterns in young and middle-aged women. Its treatment principle should be “unblocking yang,” and its treating methods should include diffusing yang, warming yang, dissolving phlegm, and dissipating stasis, which can unblock yang qi and dissolve stasis. Meanwhile, heart-nourishing and mind-calming ingredients should be included in the prescriptions to improve the clinical manifestations.

Abstract Dysbiosis of human gut microbiota has been reported in association with ulcerative colitis (UC) in both children and adults using either 16S rRNA gene or shotgun sequencing data. However, these studies used either 16S rRNA or metagenomic shotgun sequencing but not both. We sequenced feces samples from 19 pediatric UC and 23 healthy children ages between 7 to 21 years using both 16S rRNA and metagenomic shotgun sequencing. The samples were analyzed using three different types of data: 16S rRNA genus level abundance, microbial species and pathway abundance profiles. We demonstrated that (a) the alpha diversity of pediatric UC cases is lower than that of healthy controls; (b) the beta diversity within children with UC is more variable than within the healthy children; (c) several microbial families including Akkermansiaceae, Clostridiaceae, Eggerthellaceae, Lachnospiraceae, and Oscillospiraceae, contain species that are depleted in pediatric UC compared to controls; (d) a few associated species unique to pediatric UC, but not adult UC, were also identified, e.g. some species in the Christensenellaceae family were found to be depleted and some species in the Enterobacteriaceae family were found to be enriched in pediatric UC; and (e) both 16S rRNA and shotgun sequencing data can predict pediatric UC status with area under the receiver operating characteristic curve (AUROC) of close to 0.90 based on cross validation. We showed that 16S rRNA data yielded similar results as shotgun data in terms of alpha diversity, beta diversity, and prediction accuracy. Our study demonstrated that pediatric UC subjects harbor a dysbiotic and less diverse gut microbial population with distinct differences from healthy children. We also showed that 16S rRNA data yielded accurate disease prediction results in comparison to shotgun data, which can be more expensive and laborious. These conclusions were confirmed in an independent data set of 7 pediatric UC cases and 8 controls.

Plant photosynthetic capacity directly determines crop yield. Light quality regulates photosynthetic capacity. This review discusses plant responses to far-red light from the phenotypic to the molecular level, focusing specifically on the improvement of photosynthetic capacity by adjustment of photosynthetic electron transport and the path of light energy. Far-red light can also regulate leaf angle and increase plant height and leaf area, via expression of associated genes, to capture more light energy. Thus, far-red light regulates plant morphology and photosynthetic capacity. Identifying the mechanism of this regulation may lead to increased crop yields.

Abstract Background Breast cancer is the most common cancer in women worldwide. More than 70% of breast cancers are estrogen receptor (ER) alpha positive. Compared with ER alpha-negative breast cancer, which is more aggressive and has a shorter survival time, ER alpha-positive breast cancer could benefit from endocrine therapy. Selective estrogen receptor modulators, such as tamoxifen, are widely used in endocrine therapy. Approximately half of ER alpha-positive breast cancer patients will eventually develop endocrine resistance, making it a major clinical challenge in therapy. Thus, decoding the throughput of estrogen signaling, including the control of ER alpha expression and stability, is critical for the improvement of breast cancer therapeutics. Methods TRIM3 and ER alpha protein expression levels were measured by western blotting, while the mRNA levels of ER alpha target genes were measured by RT–PCR. A CCK-8 assay was used to measure cell viability. RNA sequencing data were analyzed by Ingenuity Pathway Analysis. Identification of ER alpha signaling activity was accomplished with luciferase assays, RT–PCR and western blotting. Protein stability assays and ubiquitin assays were used to detect ER alpha protein degradation. Ubiquitin-based immunoprecipitation assays were used to detect the specific ubiquitination modification on the ER alpha protein. Results In our current study, we found that TRIM3, an E3 ligase, can promote ER alpha signaling activity and breast cancer progression. TRIM3 depletion inhibits breast cancer cell proliferation and migration, while unbiased RNA sequencing data indicated that TRIM3 is required for the activity of estrogen signaling on the -genome-wide scale. The immunoprecipitation assays indicated that TRIM3 associates with ER alpha and promotes its stability, possibly by inducing K63-linked polyubiquitination of ER alpha. In conclusion, our data implicate a nongenomic mechanism by which TRIM3 stabilizes the ER alpha protein to control ER alpha target gene expression linked to breast cancer progression. Conclusion Our study provides a novel posttranslational mechanism in estrogen signaling. Modulation of TRIM3 expression or function could be an interesting approach for breast cancer treatment. Graphical abstract Video abstract