Search

Abstract Objective Free fatty acids (FFA) can increase the expression of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in local tissues and organs. However, the mechanism underlying the effect of FFA on 11β-HSD1 expression remains unclear. Methods A total of 24 male Syrian golden hamsters (SPF grade) were selected and randomly divided into a control group (Con, n = 8) fed a normal diet, and a high-fat diet group (n = 16) fed for 12 weeks. After successfully establishing the hyperlipidemia hamster model, the high-fat group was further divided into a high-fat group (HF) and a fenofibrate intervention group (Feno). Following an oral fat tolerance test (OFTT), blood lipids and FFA levels were measured. The expression levels of endoplasmic reticulum stress (ERS) marker GRP78, downstream key molecule CHOP, C/EBPα, and 11β-HSD1 were analyzed using Western blot and RT-PCR. Results After OFTT, FFA levels in all three groups initially decreased and then increased, with the highest levels observed in the HF group (Ps 0.05). Hepatic FFA, 11β-HSD1, and corticosterone levels were highest in the HF group (Ps 0.05). Hepatic 11β-HSD1 and corticosterone levels were positively correlated with FFA levels (Ps

Abstract Glomerular endothelial cells (GECs) are pivotal in developing glomerular sclerosis disorders. The advancement of focal segmental glomerulosclerosis (FSGS) is intimately tied to disruptions in lipid metabolism. Sphingosine-1-phosphate (S1P), a molecule transported by high-density lipoproteins (HDL), exhibits protective effects on vascular endothelial cells by upregulating phosphorylated endothelial nitric oxide synthase (p-eNOS) and enhancing nitric oxide (NO) production. Nevertheless, the abundance of S1P within HDL in individuals with FSGS and minimal change disease (MCD) is yet to be elucidated, and its defensive role in GECs necessitates empirical confirmation. A total of 14 FSGS patients, 16 MCD patients, and 16 healthy controls (NC) were included in the study, with FSGS and MCD confirmed by renal biopsy. After blood sample collection, HDL was isolated and categorized into intact HDL, phospholipid-depleted HDL(apo-HDL), phospholipid-remained HDL(phoHDL), and recombinant HDL (rHDL). Various HDL samples, comprising intact, apo-HDL, pho-HDL and rHDL, were co-cultivated with human renal glomerular endothelial cells (HRGECs). Western blotting was utilized to quantify p-eNOS levels and assess PI3K-AKT pathway activation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyzed S1P concentrations, while real-time quantitative PCR evaluated the expression of enzymes involved in S1P metabolism. Fluorescence labeling methods measured NO levels, and an immunofluorescence colocalization assay investigated Sphingosine-1-phosphate receptor 1 (S1PR1) expression in GECs across distinct kidney tissue groups. The HDL from FSGS patients demonstrated a significantly enhanced ability to promote p-eNOS expression and NO release in HRGECs compared to MCD patients and healthy controls. Additionally, the synthesis activity of S1P in renal tissues of FSGS patients was markedly higher than that observed in MCD patients and healthy controls, suggesting that S1P may play a crucial protective role in the progression of FSGS. Immunofluorescence staining showed that compared with MCD and NC, the expression of S1PR1 in GECs of FSGS patients was significantly decreased. Recombinant HDL with added S1P promoted the increase of p-eNOS in HRGECs. Knockdown of S1PR1 using siRNA reduced the expression of p-eNOS and NO release. The mechanism underlying the regulation of p-eNOS expression by rHDL was associated with the PI3K-AKT signaling pathway. The enhanced presence of S1P on HDL could serve as a diagnostic marker to differentiate FSGS from MCD. Incorporating S1P into HDL enhances glomerular endothelial cell function, suggesting that the S1P/S1PR pathway might offer a promising therapeutic avenue for FSGS.

Abstract The rapid development of high-throughput sequencing techniques provides an unprecedented opportunity to generate biological insights into microbiome-related diseases. However, the relationships among microbes, metabolites and human microenvironment are extremely complex, making data analysis challenging. Here, we present NMFGOT, which is a versatile toolkit for the integrative analysis of microbiome and metabolome data from the same samples. NMFGOT is an unsupervised learning framework based on nonnegative matrix factorization with graph regularized optimal transport, where it utilizes the optimal transport plan to measure the probability distance between microbiome samples, which better dealt with the nonlinear high-order interactions among microbial taxa and metabolites. Moreover, it also includes a spatial regularization term to preserve the spatial consistency of samples in the embedding space across different data modalities. We implemented NMFGOT in several multi-omics microbiome datasets from multiple cohorts. The experimental results showed that NMFGOT consistently performed well compared with several recently published multi-omics integrating methods. Moreover, NMFGOT also facilitates downstream biological analysis, including pathway enrichment analysis and disease-specific metabolite-microbe association analysis. Using NMFGOT, we identified the significantly and stable metabolite-microbe associations in GC and ESRD diseases, which improves our understanding for the mechanisms of human complex diseases.

Abstract Background Fibroblast activation protein (FAP) has gained attention as a promising molecular target with potential utility for cancer diagnosis and therapy. [68Ga]Ga-labeled FAP-targeting peptides have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To meet the applicable demand for peptide-based FAP tracers with high patient throughput, we herein report the radiosynthesis, preclinical evaluation, and the first-in-human imaging of a novel [18F]F-labeled FAP-targeting peptide. Results [18F]AlF-FAP-NUR was automatedly prepared within 45 min with a non-decay corrected radiochemical yield of 18.73 ± 4.25% (n = 3). Compared to [68Ga]Ga-FAP-2286, the [18F]F-labeled peptide demonstrated more rapid, higher levels of cellular uptake and internalization, and lower levels of cellular efflux in HT1080-FAP cells. Micro-PET imaging and biodistribution studies conducted on xenograft mice models revealed a similar distribution pattern between the two tracers. However, [18F]AlF-FAP-NUR demonstrated significantly higher tumor-specific uptake resulting in improved Tumor-Background Ratios (TBRs). In the patients, a significant accumulation of [18F]AlF-FAP-NUR was found in the primary tumor. High uptake of the tracer within the bladder indicated that its major route of excretion was through urine. Conclusions Based on the physical imaging properties and longer half-life of [18F]F, [18F]AlF-FAP-NUR exhibited promising characteristics such as enhanced tumor-specific accumulation and elevated TBRs, which made it a viable candidate for further clinical investigation. Trial registration www.Chictr.org.cn , ChiCTR2300076976 Retrospectively registered 25 October 2023. at, URL: https://www.chictr.org.cn/showproj.html?proj=206753 .

Objective: To assess the diagnostic ability of peripapillary vessel density (pVD) in primary open-angle glaucoma suspect (GS) patients. Methods: Sixteen primary open-angle GS patients (22 eyes) and 20 normal controls (22 eyes) were included. In the GS group, OCTA measurements of pVD (superior, inferior, nasal, temporal, and global), OCT measurements of retinal nerve fiber layer (RNFL) thickness, disc area, rim area and ganglion cell complex (GCC) thickness were examined. In the control group, pVD measurements were performed. The vessel density between the two groups was compared. The correlation between OCTA and OCT parameters was evaluated. The receiver operating characteristic curve (ROC) was used to evaluate the diagnostic efficacy of OCTA measurements. Results: The global (P < 0.001), nasal (P = 0.003), and inferior (P = 0.002) quadrant pVD in GS group was considerably lower than the control group. The global pVD was positively correlated with the inferior RNFL thickness (r = 0.492, P = 0.023) and rim area (r = 0.483, P = 0.027). The inferior pVD was positively correlated with the inferior RNFL thickness (r = 0.648, P = 0.001), the nasal RNFL thickness (r = 0.441, P = 0.045), the rim area (r = 0.439, P = 0.046) and the GCC thickness (r = 0.472, P = 0.048). The global pVD had the best diagnostic value (AUC=0.825, sensitivity 86.36 %, specificity 72.73 %, cutoff value 45 %), followed by the inferior (AUC=0.749) and nasal (AUC=0.748) quadrant pVD. Conclusion: In primary open-angle GS patients, the global and inferior quadrant pVD was lower than that of normal people, and it was positively correlated with the inferior RNFL thickness and rim area. The diagnostic value of pVD for discriminating GS from normal people was excellent with high sensitivity and specificity.

Abstract Background Advances of spatial transcriptomics technologies enabled simultaneously profiling gene expression and spatial locations of cells from the same tissue. Computational tools and approaches for integration of transcriptomics data and spatial context information are urgently needed to comprehensively explore the underlying structure patterns. In this manuscript, we propose HyperGCN for the integrative analysis of gene expression and spatial information profiled from the same tissue. HyperGCN enables data visualization and clustering, and facilitates downstream analysis, including domain segmentation, the characterization of marker genes for the specific domain structure and GO enrichment analysis. Results Extensive experiments are implemented on four real datasets from different tissues (including human dorsolateral prefrontal cortex, human positive breast tumors, mouse brain, mouse olfactory bulb tissue and Zabrafish melanoma) and technologies (including 10X visium, osmFISH, seqFISH+, 10X Xenium and Stereo-seq) with different spatial resolutions. The results show that HyperGCN achieves superior clustering performance and produces good domain segmentation effects while identifies biologically meaningful spatial expression patterns. This study provides a flexible framework to analyze spatial transcriptomics data with high geometric complexity. Conclusions HyperGCN is an unsupervised method based on hypergraph induced graph convolutional network, where it assumes that there existed disjoint tissues with high geometric complexity, and models the semantic relationship of cells through hypergraph, which better tackles the high-order interactions of cells and levels of noise in spatial transcriptomics data.

Abstract Flowering plants rely on the polarized growth of pollen tubes to deliver sperm cells (SCs) to the embryo sac for double fertilization. In pollen, the vegetative nucleus (VN) and two SCs form the male germ unit (MGU). However, the mechanism underlying directional transportation of MGU is not well understood. In this study, we provide the first full picture of the dynamic interplay among microtubules, actin filaments, and MGU during pollen germination and tube growth. Depolymerization of microtubules and inhibition of kinesin activity result in an increased velocity and magnified amplitude of VN’s forward and backward movement. Pharmacological washout experiments further suggest that microtubules participate in coordinating the directional movement of MGU. In contrast, suppression of the actomyosin system leads to a reduced velocity of VN mobility but without a moving pattern change. Moreover, detailed observation shows that the direction and velocity of VN’s movement are in close correlations with those of the actomyosin-driven cytoplasmic streaming surrounding VN. Therefore, we propose that while actomyosin-based cytoplasmic streaming influences on the oscillational movement of MGU, microtubules and kinesins avoid MGU drifting with the cytoplasmic streaming and act as the major regulator for fine-tuning the proper positioning and directional migration of MGU in pollen.

Abstract The molecular categorization of colon cancer patients remains elusive. Gene set enrichment analysis (GSEA), which investigates the dysregulated genes among tumor and normal samples, has revealed the pivotal role of epithelial-to-mesenchymal transition (EMT) in colon cancer pathogenesis. In this study, we employed multi-clustering method for grouping data, resulting in the identification of two clusters characterized by varying prognostic outcomes. These two subgroups not only displayed disparities in overall survival (OS) but also manifested variations in clinical variables, genetic mutation, and gene expression profiles. Using the nearest template prediction (NTP) method, we were able to replicate the molecular classification effectively within the original dataset and validated it across multiple independent datasets, underscoring its robust repeatability. Furthermore, we constructed two prognostic signatures tailored to each of these subgroups. Our molecular classification, centered on EMT, hold promise in offering fresh insights into the therapy strategies and prognosis assessment for colon cancer.

Characterized by frequent earthquakes and a dense population, Yunnan Province, China, faces significant seismic hazards and is a hot place for earthquake forecasting research. In a previous study, we evaluated the performance of the b value for 5-year seismic forecasting during 2000–2019 and made a forward prediction of M ≥ 5.0 earthquakes in 2020–2024. In this study, with the forecast period having passed, we first revisit the results and assess the forward prediction performance. Then, the background seismicity rate, which may also offer valuable long-term forecasting information, is incorporated into earthquake prediction for Yunnan Province. To assess the effectiveness of the prediction, the Molchan Error Diagram (MED), Probability Gain (PG), and Probability Difference (PD) are employed. Using a 25-year catalog, the spatial b value and background seismicity rate across five temporal windows are calculated, and 86 M ≥ 5.0 earthquakes as prediction samples are examined. The predictive performance of the background seismicity rate and b value is comprehensively tested and shown to be useful for 5-year forecasting in Yunnan. The performance of the b value exhibits a positive correlation with the predicted earthquake magnitude. The synergistic effect of combining these two predictors is also revealed. Finally, using the threshold corresponding to the maximum PD, we integrate the forecast information of background seismicity rates and the b value. A forward prediction is derived for the period from January 2025 to December 2029. This study can be helpful for disaster preparedness and risk management in Yunnan Province, China.

The two primary types of non-puerperal mastitis (NPM) are granulomatous lobular mastitis (GLM) and plasma cell mastitis (PCM). Existing research indicates that immune inflammatory response is considered to be the core of the pathogenesis of GLM and PCM, and both innate and adaptive immune responses play an important role in the pathophysiology of PCM and GLM. However, the regulatory balance between various immune cells in these diseases is still unclear. Consequently, we present a comprehensive summary of the immune-related variables and recent advances in GLM and PCM.

BackgroundChina exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China’s pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks.MethodsRetrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny.ResultsVarious diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation.ConclusionThis investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19’s disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Background Pneumoconiosis mostly combines pulmonary and cardiovascular diseases, among which pulmonary heart disease (PHD) is of major concern due to its significant impact on the survival of pneumoconiosis patients. White cell count (WCC), red cell distribution width (RDW) and platelet parameters are thought to affect inflammatory responses and may be predictors of various cardiovascular diseases. However, very few studies have focused on PHD.Objectives To examine the relationship between baseline complete blood count parameters (WCC, RDW, platelet parameters) and the risk of incident PHD in pneumoconiosis patients.Design A retrospective cohort study.Setting This was a single-centre, retrospective cohort study that used data from an Occupational Disease Hospital, Chengdu, Sichuan.Participants A total of 946 pneumoconiosis patients from January 2012 to November 2021 were included in the study. Female patients and patients who had PHD, coronary heart disease, hypertensive heart disease, cardiomyopathy, heart failure, oncological disease, multiple organ dysfunction, AIDS at baseline and follow-up time of less than 6 months were also excluded.Outcome measures We identified PHD according to the patient’s discharge diagnosis. We constructed Cox proportional hazard regression models to assess the HR of incident PHD in pneumoconiosis, as well as 95% CIs.Results In the multiple Cox proportional hazard regression analysis, platelet count (PLT) and plateletcrit (PCT) above the median at baseline were associated with an increased risk of PHD in pneumoconiosis with adjusted HR of 1.52 (95% CI 1.09 to 2.12) and 1.42 (95% CI 1.02 to 1.99), respectively.Conclusion Higher baseline PLT and PCT are associated with a higher risk of PHD in pneumoconiosis.

BackgroundBreast cancer is the most prevalent cancer globally and is associated with significant mortality. Recent research has provided crucial insights into the role of gut microbiota in the onset and progression of breast cancer, confirming its impact on the disease’s management. Despite numerous studies exploring this relationship, there is a lack of comprehensive bibliometric analyses to outline the field’s current state and emerging trends. This study aims to fill that gap by analyzing key research directions and identifying emerging hotspots.MethodPublications from 2013 to 2023 were retrieved from the Web of Science Core Collection database. The VOSviewer, R language and SCImago Graphica software were utilized to analyze and visualize the volume of publications, countries/regions, institutions, authors, and keywords in this field.ResultsA total of 515 publications were included in this study. The journal Cancers was identified as the most prolific, contributing 21 papers. The United States and China were the leading contributors to this field. The University of Alabama at Birmingham was the most productive institution. Peter Bai published the most papers, while James J. Goedert was the most cited author. Analysis of highly cited literature and keyword clustering confirmed a close relationship between gut microbiota and breast cancer. Keywords such as “metabolomics” and “probiotics” have been prominently highlighted in the keyword analysis, indicating future research hotspots in exploring the interaction between metabolites in the breast cancer microenvironment and gut microbiota. Additionally, these keywords suggest significant interest in the therapeutic potential of probiotics for breast cancer treatment.ConclusionResearch on the relationship between gut microbiota and breast cancer is expanding. Attention should be focused on understanding the mechanisms of their interaction, particularly the metabolite-microbiota-breast cancer crosstalk. These insights have the potential to advance prevention, diagnosis, and treatment strategies for breast cancer. This bibliometric study provides a comprehensive assessment of the current state and future trends of research in this field, offering valuable perspectives for future studies on gut microbiota and breast cancer.

This meta-analysis assessed the impact of three induction methods on athletes’ jump and sprint performances. Experimental research on the acute effects of exercise intervention on the Post-Activation Performance Enhancement (PAPE) of jumping and sprinting performances in athletes was searched using the Web of Science, PubMed, and Embase databases. The meta-analysis results show that, when employing resistance exercises as Conditioning Activities (CAs) for enhancing jumping performance, there are statistically significant differences in favor of utilizing resistance exercises as CAs (Hedges’s g = 0.2, 0.2, and 0.23; 95%Cl: (0.05, 0.34), (0.02, 0.39), and (0.05, 0.41); p < 0.05). In contrast, no significant differences were detected when plyometric exercises or mixed exercises were compared pre-intervention (p > 0.05). In terms of sprint performance, when employing resistance exercises as CAs, the effect sizes were −0.11, −0.44, and −0.32, respectively. Their corresponding 95%Cls were (−0.22, 0.00), (−0.63, 0.25), and (−0.50, −0.13), with all p-values < 0.05, indicating statistically significant differences favoring the utilization of resistance exercises as CAs. However, no significant differences were noted when comparing plyometric or mixed exercises to pre-intervention (p > 0.05). In conclusion, compared with plyometric exercises and mixed exercises, resistance exercises had a more significant effect on athletes’ jumping and sprinting performances.

IntroductionMetabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT).Patients and methodsIn total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed.ResultsSerum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403).ConclusionDyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

Carbamate is a key structural motif in the development of fungicidal compounds, which is still promising and robust in the discovery of green pesticides. Herein, we report the synthesis and evaluation of the fungicidal activity of 35 carbamate derivatives, among which 19 compounds were synthesized in our previous report. These derivatives were synthesized from aromatic amides in a single step, which was a green oxidation process for Hofmann rearrangement using oxone, KCl and NaOH. Their chemical structures were characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry. Their antifungal activity was tested against seven plant fungal pathogens. Many of the compounds exhibited good antifungal activity in vitro (inhibitory rate > 60% at 50 μg/mL). Compound 1ag exhibited excellent broad-spectrum antifungal activities with inhibition rates close to or higher than 70% at 50 μg/mL. Notably, compound 1af demonstrated the most potent inhibition against F. graminearum, with an EC50 value of 12.50 μg/mL, while compound 1z was the most promising candidate fungicide against F. oxysporum (EC50 = 16.65 μg/mL). The structure–activity relationships are also discussed in this paper. These results suggest that the N-aryl carbamate derivatives secured by our green protocol warrant further investigation as potential lead compounds for novel antifungal agents.

Halobenzoquinones (HBQs) were recently discovered as an emerging class of drinking water disinfection byproducts with carcinogenic concern. However, the molecular mechanism underlying HBQs-induced DNA damage is not clear. In this study, we integrated in vitro genotoxicity, computational toxicology, and the quantitative toxicogenomic analysis of HBQs on DNA damage/repair pathways in human bladder epithelial cells SV-HUC-1. The results showed that HBQs could induce cytotoxicity with the descending order as 2,6-DIBQ > 2,6-DCBQ ≈ 2,6-DBBQ. Also, HBQs can increase DNA damage in SV-HUC-1 cells and thus generate genotoxicity. However, there is no significant difference in genotoxicity among the three HBQs. The results of molecular docking and molecular dynamics simulation further confirmed that HBQs had high binding fractions and stability to DNA. Toxicogenomic analysis indicated that HBQs interfered with DNA repair pathways, mainly affecting base excision repair, nucleotide excision repair and homologous recombination repair. These results have provided new insights into the underlying molecular mechanisms of HBQs-induced DNA damage, and contributed to the understanding of the relationship between exposure to DBPs and risks of developing bladder cancer.

The concrete-faced rockfill dam (CFRD) has been widely constructed worldwide, and the reliability of the concrete panels, the most important containment structure, is critical to the safety of the CFRDs and downstream communities. Several practical projects show that concrete slab cracking usually occurs during the water storage period, which can be attributed to the rapid increase of hydrostatic pressure and uneven settlement of the dam body. In this paper, a time-dependent reliability analysis method considering the fuzziness of the failure criterion is presented to assess the slab cracking risk of the Houziyan CFRD during the water storage period. Based on the observed deformation, the material parameters are calibrated to ensure the fidelity of the numerical simulation. Based on the Drucker–Prager yield criterion and tensile strength criterion, the response surface method is utilized to construct the performance functions at different moments, and then the time-dependent reliability analysis considering the fuzzy failure criteria is implemented for the concrete slab. The case study of the Houziyan CFRD shows that, during the initial period of water storage, the reliability index of the concrete slab decreases with the rise of the water level. With a stable water level, the probability of cracking of the concrete slab slowly decreases as the deformation of the dam body and slab tend to be coordinated. Especially, considering the fuzziness of the failure criteria, the reliability index decreased by about 2%, indicating that the proposed evaluation method is biased toward safety. The method proposed in this paper can reflect the evolution law of concrete slab reliability with the operating environment and provides a new approach to evaluate the performance of the concrete slab during the water storage period.

Highlights The super-elastic and robust MXene aerogels are created herein by assembling the 1D fibrous MXenes with sufficiently large aspect ratios and superior flexibility. The underlying regulatory mechanism and a complete diagram for the pore structure evolution of MXene aerogels are revealed for the first time, which are particularly instructive for future structure-specific designs. Fibrous MXene aerogels exhibit 8.3% plastic deformation at the 1000th compressions and achieve high evaporation rate (1.48 kg m−2 h−1) and light to thermal conversion efficiency (92.08%) on oil-contaminated seawater.

IntroductionThe increase in incidence of multidrug-resistant bacteria and the inadequacy of new antimicrobial drugs have led to a widespread outbreak of bacterial antimicrobial resistance. To discover new antibiotics, biodiversity, and novelty of culturable actinobacteria dwelled in soil of the Western Qinghai-Tibet Plateau were investigated. By integrating antibacterial assay with omics tools, Amycolatopsis sp. A133, a rare actinobacterial strain and its secondary metabolites were further studied.MethodCulture-dependent method was used to obtain actinobacterial strains from two soil samples collected from Ali region in Qinghai-Tibet Plateau. The cultural extractions of representative strains were assayed against “ESKAPE” pathogens by paper-disk diffusion method and the double fluorescent protein reporter “pDualrep2” system. An Amycolatopsis strain coded as A133 was prioritized and its secondary metabolites were further analyzed and annotated by omics tools including antiSMASH and GNPS (Global Natural Social Molecular Networking). The predicted rifamycin analogs produced by Amycolatopsis sp. A133 were isolated and identified by chromatographic separation, such as Sephadex LH-20 and HPLC, and spectral analysis, such as NMR and UPLC-HRESI-MS/MS, respectively.ResultsA total of 406 actinobacteria strains affiliated to 36 genera in 17 families of 9 orders were isolated. Out of 152 representative strains, 63 isolates exhibited antagonistic activity against at least one of the tested pathogens. Among them, 7 positive strains were identified by the “pDualrep2” system as either an inhibitor of protein translation or DNA biosynthesis. The cultural broth of Amycolatopsis sp. A133 exhibited a broader antimicrobial activity and can induce expression of TurboRFP. The secondary metabolites produced by strain A133 was annotated as rifamycins and zampanolides by antiSMASH and GNPS analysis. Five members of rifamycins, including rifamycin W, protorifamycin I, rifamycin W-M1, proansamycin B, and rifamycin S, were purified and identified. Rifamycin W-M1, was found as a new member of the naturally occurring rifamycin group of antibiotics.DiscussionAssisted by omics tools, the successful and highly efficient discovery of rifamycins, a group of clinically used antibiotics from actinobacteria in Ali area encouraged us to devote more energy to explore new antibiotics from the soils on the Western Tibetan Plateau.

Abstract Aims/Introduction Insulin sensitivity and β‐cell function are affected by lipid metabolism disorders, even before the onset of type 2 diabetes. People are in the postprandial state most of the time. Therefore, identifying postprandial hyperlipemia is important. This study aimed to assess patients with abnormalities in lipid metabolism, but with normal glucose tolerance, using oral fat tolerance testing (OFTT) to identify defects in insulin sensitivity and β‐cell function. Materials and Methods We included 248 volunteers with normal glucose tolerance who underwent OFTT. They were divided into three groups in accordance with their fasting and 4‐h postprandial triglyceride (TG) concentrations. Their lipid concentrations during OFTT were compared. The disposition index (DI) was applied to estimate β‐cell function, and the Matsuda insulin sensitivity index (ISIM) was used to assess insulin sensitivity. We used multiple linear regression analysis to estimate the relationships of fasting and postprandial TG concentrations with β‐cell function and insulin sensitivity . Results The changes in TG concentrations during OFTT were more marked than those in low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol or total cholesterol concentrations. As lipid metabolism deteriorated, the ISIM and the DI gradually decreased. Multiple linear regression analysis showed that fasting and 4‐h postprandial TG concentrations affected LnISIM and LnDI. Conclusions In individuals with normal glucose tolerance, β‐cell function and insulin sensitivity gradually decrease with a deterioration in the lipid profile. Not only fasting TG, but also postprandial TG concentrations are independent risk factors for impaired β‐cell function and insulin resistance.

Breast cancer is currently the most common malignancy and has a high mortality rate. Ginsenosides, the primary bioactive constituents of ginseng, have been shown to be highly effective against breast cancer both in vitro and in vivo. This study aims to comprehensively understand the mechanisms underlying the antineoplastic effects of ginsenosides on breast cancer. Through meticulous bibliometric analysis and an exhaustive review of pertinent research, we explore and summarize the mechanism of action of ginsenosides in treating breast cancer, including inducing apoptosis, autophagy, inhibiting epithelial-mesenchymal transition and metastasis, and regulating miRNA and lncRNA. This scholarly endeavor not only provides novel prospects for the application of ginsenosides in the treatment of breast cancer but also suggests future research directions for researchers.

Abstract Background and objective Epimedii has long been used as a traditional medicine in Asia for the treatment of various common diseases, including Alzheimer's disease, cancer, erectile dysfunction, and stroke. Studies have reported the ameliorative effects of Icariside II (ICS II), a major metabolite of Epimedii, on acute ischemic stroke (AIS) in animal models. Based on network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we conducted a systematic review to evaluate the effects and neuroprotective mechanisms of ICS II on AIS. Methods First, we have searched 6 databases using studies with ICS II treatment on AIS animal models to explore the efficacy of ICS II on AIS in preclinical studies. The literature retrieval time ended on March 8, 2022 (Systematic Review Registration ID: CRD42022306291). There were no restrictions on the language of the search strategy. Systematic review follows the Patient, Intervention, Comparison and Outcome (PICO) methodology and framework. SYCLE's RoB tool was used to evaluate the the risk of bias. In network pharmacology, AIS-related genes were identified and the target-pathway network was constructed. Then, these targets were used in the enrichments of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology (GO). Molecular docking and MD simulation were finally employed between ICS II and the potential target genes. Results Twelve publications were included describing outcomes of 1993 animals. The literature details, animal strains, induction models, doses administered, duration of administration, and outcome measures were extracted from the 12 included studies. ICS II has a good protective effect against AIS. Most of the studies in this systematic review had the appropriate methodological quality, but some did not clearly state the controlling for bias of potential study. Network pharmacology identified 246 targets with SRC, CTNNB1, HSP90AA1, MAPK1, and RELA as the core target proteins. Besides, 215 potential pathways of ICS II were identified, such as PI3K-Akt, MAPK, and cGMP-PKG signaling pathway. GO enrichment analysis showed that ICS II was significantly enriched in subsequent regulation such as MAPK cascade. Molecular docking and MD simulations showed that ICS II can closely bind with important targets. Conclusions ICS II is a promising drug in the treatment of AIS. However, this systematic review reveals key knowledge gaps (i.e., the protective role of ICS II in women) that ICS II must address before it can be used for the treatment of human AIS. Our study shows that ICS II plays a protective role in AIS through multi-target and multi-pathway characteristics, providing ideas for the development of drugs for the treatment of AIS.

BackgroundThe European Medicines Agency (EMA) interacts with many different stakeholders involved in the development of drugs, including academic researchers. In recent years, EMA has collaborated more closely with academia, inter alia by taking part in external research projects such as those set up under the Horizon 2020 program in general and the Innovative Medicines Initiative in particular. The aim of this study was to evaluate the perceived added value of EMA’s involvement in these projects, both from the perspective of the Agency’s participating Scientific Officers and of the coordinators of the consortia that undertook them.MethodsSemi-structured interviews were conducted with the coordinators of 21 ongoing or recently finalized projects in which EMA has participated, as well as with the Agency experts contributing to them.ResultsIn total, 40 individuals were interviewed, of whom 23 were project coordinators and 17 were EMA staff members. While most of the projects were reported to suffer from delays due to the SARS-CoV-2 pandemic, the consortia adapted to the circumstances and their members still expected to deliver on their objectives. EMA’s input into the projects ranged from providing guidance by reviewing documents and attending meetings to creating project materials and disseminating them. The frequency of communication between EMA and the consortia varied widely. The projects generated a diverse set of outputs, which encompassed new or improved medicinal products, methodological standards, research infrastructures, and educational tools. All of the coordinators expressed that EMA’s contributions to their projects had increased the scientific relevance of their consortium’s work, and the EMA experts found that the knowledge and the deliverables produced by the projects were valuable, taking into consideration the time they had invested into them. In addition, interviewees highlighted some actions which could be taken to increase the regulatory significance of the project outcomes.ConclusionEMA’s engagement in external research projects benefits the consortia conducting them and supports the Agency’s mission to foster scientific excellence and advance regulatory science.

BackgroundPrevious studies focused more on the short-term risk of cardiovascular (CV) death due to traumatic psychological stress after a cancer diagnosis and the acute cardiotoxicity of anticancer treatments than on the long-term risk of CV death.MethodsTime trends in the proportions of CV death (PCV), cancer death (PCA), and other causes in deaths from all causes were used to show preliminary relationships among the three causes of death in 4,806,064 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER) program. Competing mortality risk curves were used to investigate when the cumulative CV mortality rate (CMRCV) began to outweigh the cumulative cancer mortality rate (CMRCA) for patients with cancer who survived for more than 10 years. Multivariable competing risk models were further used to investigate the potential factors associated with CV death.ResultsFor patients with cancer at all sites, the PCV increased from 22.8% in the 5th year after diagnosis to 31.0% in the 10th year and 35.7% in the 20th year, while the PCA decreased from 57.7% in the 5th year after diagnosis to 41.2 and 29.9% in the 10th year and 20th year, respectively. The PCV outweighed the PCA (34.6% vs. 34.1%) since the 15th year for patients with cancer at all sites, as early as the 9th year for patients with colorectal cancer (37.5% vs. 33.2%) and as late as the 22nd year for patients with breast cancer (33.5% vs. 30.6%). The CMRCV outweighed the CMRCA since the 25th year from diagnosis. Multivariate competing risk models showed that an increased risk of CV death was independently associated with older age at diagnosis [hazard ratio and 95% confidence intervals [HR (95%CI)] of 43.39 (21.33, 88.28) for ≥ 80 vs. ≤ 30 years] and local metastasis [1.07 (1.04, 1.10)] and a decreased risk among women [0.82 (0.76, 0.88)], surgery [0.90 (0.87, 0.94)], and chemotherapy [0.85 (0.81, 0.90)] among patients with cancer who survived for more than 10 years. Further analyses of patients with cancer who survived for more than 20 years and sensitivity analyses by cancer at all sites showed similar results.ConclusionCV death gradually outweighs cancer death as survival time increases for most patients with cancer. Both the cardio-oncologist and cardio-oncology care should be involved to reduce CV deaths in long-term cancer survivors.

Background Traffic-related air pollution (TRAP) is hypothesised to play a role in the development of allergic rhinitis (AR). Prenatal and early-life exposure to traffic-related air pollution is considered critical for later respiratory health. However, we could not find any articles systematically reviewing the risk of prenatal and early-life exposure to traffic-related air pollution for allergic rhinitis in children. Methods A systematic literature search of PubMed, Web of Science and Medline was conducted to identify studies focused on the association between prenatal and early-life exposure to TRAP and AR in children. Other inclusion criteria were: 1) original articles; 2) based upon prospective or retrospective studies or case-control studies; and 3) publications were restricted to English. Literature quality assessment was processed using the Newcastle-Ottawa Scale (NOS) evaluation scale. This systematic literature review has been registered on the prospero (crd.york.ac.uk/prospero) with the following registry number: CRD42022361179. Results Only eight studies met the inclusion criteria. The exposure assessment indicators included PM2.5, PM2.5 absorbance, PM10, NOx, CO, and black carbon. On the whole, exposure to TRAP during pregnancy and the first year of life were positively associated with the development of AR in children. Conclusions This systematic review presents supportive evidence about prenatal and early-life exposure to TRAP and the risk of AR in children.

Purpose. The aim of this study was to analyze choroidal vascular density alteration in high myopia with or without choroidal neovascularization by using optical coherence tomography angiography (OCTA). Methods. This was a cross-sectional, observational study that included 60 high-myopia eyes. All the participants had comprehensive ophthalmic assessments with visual acuity, intraocular pressure, slit lamp-assisted biomicroscopy, color fundus photography, axial length, optometry, and OCTA. Age, sex, and comorbidities were collected from their medical charts. Univariate and multiple analyses were made to compare the age, spherical equivalent, choroidal vascular density, gender, and choroidal thickness between normal and patients with choroidal neovascularization. Results. 60 eyes with high myopia were included in our study, including 30 eyes with choroidal neovascularization and 30 eyes without choroidal neovascularization or other fundus pathology. The mean age of high myopic patients was older in the choroidal neovascularization group than in the normal group (48.43 ± 19.06 years vs. 28.83 ± 9.92 years, p

BackgroundImbalance of oral salivary microbiota has been linked to the pathogenesis of a variety of systemic diseases, and oral bacterial species have been shown to be useful biomarkers for systemic diseases.This study aimed to characterize the alterations of oral microbiota in patients with esophageal squamous cell carcinoma (ESCC) and to evaluate the diagnostic performance of oral microbial biomarkers for ESCC.MethodsThe relative abundance of flora in saliva samples was analyzed by 16S rDNA sequencing, and differences in the species present in samples from ESCC patients and healthy controls (HCs) were identified by analyzing species diversity and performing LEfSe analysis. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of the characteristic bacteria individually and in combination.ResultsDifferences in bacterial diversity indexes were observed for the saliva of ESCC patients versus HCs (P0.05). LEfSe analysis showed that Leptotrichia, Porphyromonas (Pg), Streptococcus, Rothia, Lactobacillus and Peptostreptococcus were more abundant in ESCC patient saliva than in HC saliva, whereas Haemophilus, Alloprevotella (All), Prevotella_7, Prevotella (Pre), Prevotella_6, Pasteurellaceae and Pasteurellales were significantly less abundant in ESCC patient saliva (P

On the basis of the three-component synthetic methodology developed by us, a total of twenty-six pyrazole compounds bearing aryl OCF3 were designed and synthesized. Their chemical structures were characterized by 1H and 13C nuclear magnetic resonance and high-resolution mass spectrometry. These compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi by the mycelium growth rate method. Most of the compounds showed some activity against each of the fungi at 100 μg/mL. Compounds 1t and 1v exhibited higher activity against all the tested fungi, and 1v displayed the highest activity against F. graminearum with an EC50 value of 0.0530 μM, which was comparable with commercial pyraclostrobin. Structure–activity relationship analysis showed that, with respect to the R1 substituent, the straight chain or cycloalkyl ring moiety was a key structural moiety for the activity, and the R2 substituent on the pyrazole ring could have significant effects on the activity. Simple and readily available pyrazoles with potent antifungal activity were obtained, which are ready for further elaboration to serve as a pharmacophore in new potential antifungal agents.

BackgroundChinese medicine (CM) syndrome differentiation is one of the fundamental principles that guide the practice of Chinese herbal medicine (CHM). CHM has been widely used among breast cancer patients. Contemporary literature varies in syndrome diagnosis, and there is a need to standardize syndrome differentiation according to the different stages of breast cancer treatment. This multicenter clinical study aims to identify the CM syndromes and the clinical signs and symptoms in women with early breast cancer.MethodsParticipants who met the inclusion and exclusion criteria were interviewed during the five treatment stages: preoperative, postoperative, chemotherapy, radiation therapy, and endocrine therapy. Patient demographic data and CM syndrome (as recorded by the treating CM clinicians in medical records) were gathered. Signs and symptoms were analyzed using descriptive statistics to derive the standardized CM syndromes using hierarchical cluster analysis.ResultsThe analysis included 964 interviews with 620 participants enrolled between April 29, 2020 and May 30, 2021 from eight participating hospitals in China. The two most frequent syndromes recorded in medical records were dual deficiency of qi and blood, and dual deficiency of qi and yin during all but the preoperative stage. The symptoms of lassitude, lack of strength, and insomnia were common in all but the preoperative stage. Cluster analysis identified two clusters in the preoperative stage that most closely resembled the syndrome diagnoses of liver stagnation with congealing phlegm, and dual deficiency of the liver and kidney. Two clusters—dual deficiency of qi and blood, and dual deficiency of qi and yin—were common to multiple treatment stages. The syndrome cluster of spleen and stomach disharmony existed in both the postoperative and chemotherapy stages. Cluster analysis of the radiation therapy stage identified the unique syndrome of yin deficiency with fire toxin, while the endocrine therapy included the syndromes of liver depression and kidney deficiency.ConclusionsThis multicenter clinical study showed consistency between results from cluster analysis and the most common syndromes recorded in the medical records. Findings from this clinical study will be further validated in a Delphi study to standardize CM syndromes for various stages of breast cancer treatment.Clinical Trial Registrationwww.chictr.org.cn/index.aspx, identifier ChiCTR2000032497.

Inflammatory pain is the most common type of pain encountered in clinical practice; however, the currently available treatments are limited by insufficient efficacy and side effects. Therefore, new methods to relieve inflammatory pain targeting new mechanisms are urgently needed. Preclinical investigations have shown that CR (calorie restriction) exerts analgesic effects in neuropathic and cancer pain; however, the effect of CR on chronic inflammatory pain remains unknown. During calorie restriction, autophagy, a lysosome-dependent degradation process, can be activated to support cell survival. In the present study, we investigated the analgesic effects of CR on complete Freund’s adjuvant (CFA)-induced inflammatory pain. The accumulation of LC3-II and p62 showed impaired autophagic flux in the ipsilateral spinal cord of mice with CFA-induced inflammatory pain. CR alleviated mechanical allodynia and thermal hyperalgesia and reduced paw edema and pro-inflammatory factors following CFA administration. CR exerted an analgesic effect by restoring autophagic flux in the spinal cord. Regarding the mechanisms underlying the analgesic effects of CR, β-hydroxybutyric acid (BHB) was studied. CR increased BHB levels in the ipsilateral spinal cord. Furthermore, exogenous BHB administration exerted an analgesic effect by restoring autophagic flux in the spinal cords of CFA-induced inflammatory pain mice. Taken together, these results illustrated that CR relieved inflammatory pain by restoring autophagic flux in the spinal cord, while BHB controlled the benefits of CR, suggesting that CR or BHB might be a promising treatment for inflammatory pain.

One important question in earthquake prediction is whether a moderate or large earthquake will be followed by an even bigger one. Through temporal b-value evolution analysis, the traffic light system can be used to estimate if an earthquake is a foreshock. However, the traffic light system does not take into account the uncertainty of b-values when they constitute a criterion. In this study, we propose an optimization of the traffic light system with the Akaike Information Criterion (AIC) and bootstrap. The traffic light signals are controlled by the significance level of the difference in b-value between the sample and the background rather than an arbitrary constant. We applied the optimized traffic light system to the 2021 Yangbi earthquake sequence, which could be explicitly recognized as foreshock–mainshock–aftershock using the temporal and spatial variations in b-values. In addition, we used a new statistical parameter related to the distance between earthquakes to track earthquake nucleation features. We also confirmed that the optimized traffic light system works on a high-resolution catalog that includes small-magnitude earthquakes. The comprehensive consideration of b-value, significance probability, and seismic clustering might improve the reliability of earthquake risk judgment.

Newly mined bauxitic claystone resources have received attention due to the rapidly growing demand for lithium. However, existing methods for extracting lithium from bauxitic claystone are still difficult and costly. This study proposed a novel aluminum hydroxide precipitation method to improve the extraction rate of Li by cleverly utilizing Al from bauxitic claystone. First, the ball-milled and calcined bauxitic claystone samples were leached by sulfuric acid to obtain a leaching solution with a high concentration of Al3+. Then, a NaOH solution was added to form amorphous aluminum hydroxide to adsorb Li+. The precipitation rate of Li+ reached 97.2% under the suitable precipitation conditions. Lastly, the precipitate was calcined and leached with deionized water to extract lithium. Li+ reached a water-leaching rate of 86.13%. According to the X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR) results, the prepared precipitate was mainly amorphous aluminum hydroxide and part was composed of a gibbsite phase. The elution experiment showed that the amorphous aluminum hydroxide had good adsorption selectivity for Li+. In addition, Al2O3 could be recovered from the solid phase after water-leaching, which can significantly reduce the cost.

The fungus Parastagonospora nodorum uses proteinaceous necrotrophic effectors (NEs) to induce tissue necrosis on wheat leaves during infection, leading to the symptoms of septoria nodorum blotch (SNB). The NEs Tox1 and Tox3 induce necrosis on wheat possessing the dominant susceptibility genes Snn1 and Snn3B1/Snn3D1, respectively. We previously observed that Tox1 is epistatic to the expression of Tox3 and a quantitative trait locus (QTL) on chromosome 2A that contributes to SNB resistance/susceptibility. The expression of Tox1 is significantly higher in the Australian strain SN15 compared to the American strain SN4. Inspection of the Tox1 promoter region revealed a 401 bp promoter genetic element in SN4 positioned 267 bp upstream of the start codon that is absent in SN15, called PE401. Analysis of the world-wide P. nodorum population revealed that a high proportion of Northern Hemisphere isolates possess PE401 whereas the opposite was observed in representative P. nodorum isolates from Australia and South Africa. The presence of PE401 removed the epistatic effect of Tox1 on the contribution of the SNB 2A QTL but not Tox3. PE401 was introduced into the Tox1 promoter regulatory region in SN15 to test for direct regulatory roles. Tox1 expression was markedly reduced in the presence of PE401. This suggests a repressor molecule(s) binds PE401 and inhibits Tox1 transcription. Infection assays also demonstrated that P. nodorum which lacks PE401 is more pathogenic on Snn1 wheat varieties than P. nodorum carrying PE401. An infection competition assay between P. nodorum isogenic strains with and without PE401 indicated that the higher Tox1-expressing strain rescued the reduced virulence of the lower Tox1-expressing strain on Snn1 wheat. Our study demonstrated that Tox1 exhibits both 'selfish' and 'altruistic' characteristics. This offers an insight into a complex NE-NE interaction that is occurring within the P. nodorum population. The importance of PE401 in breeding for SNB resistance in wheat is discussed.

In order to focus on the application of green environmental protection lightweight thermal insulation materials, an in-depth study is carried out on the basis of joint architectural design. The application of green environmental protection materials in the construction industry was successfully analyzed through methods such as layout design method, optimization design method, and scientific optimization of material selection. In the process of urbanization development in our country, the number of urban population has increased sharply, and the demand for buildings has also increased. Therefore, it is necessary to rapidly promote green building design while the construction industry is developing rapidly and complete the upgrading and transformation of the building in terms of form design. We pay attention to the needs of buildings in terms of shading and lighting, and improve the conditions of building shading and lighting through green building technology. As a result, on the basis of maintaining the residual heat of the building, the diffuse radiation of the ultraviolet rays of the sun is realized, which effectively improves the utilization efficiency of natural energy and reduces the consumption of internal energy. Architectural design under the concept of green building design not only can it meet the current functional requirements of people for architecture but also imperceptibly promote the stable development of our country’s construction industry. After the research on the application of green environmental protection materials, the integration and application of green building design concepts in architectural design is of great significance not only to meet people's health and ecological needs of buildings but also to promote social stability and sustainable development.

This study examines the feature of reasoning talk used by 37 Chinese families at the dinner table across three generations with the background of co-parenting and in consideration of different communicative contexts. Drawing upon Hasan’s semantic framework, reasons were mainly coded as logical or social types. We categorize the communicative context of reasoning talk into contextualized (meal-related) and decontextualized topics. When the proportion of social reasoning was found slightly higher than that of logical reasoning, the families’ reasoning talk account for only 3.85% of the total language. Specifically, the count of mothers’ total reasoning talk was significantly above other family members, while there were no significant differences among the other participants. The effect of the communicative contexts on family members’ social reasoning was found. The reasoning talk grounded on local rules (family-made rules) and coercive power occurred significantly more frequently in contextualized than decontextualized context. A higher rate of local-rule grounded reasoning talk of all family members appeared in contextualized than decontextualized context, and this gap was particularly obvious among mothers. These findings reveal the significant role of mothers in family communications and confirm the pedagogical values of decontextualized communicative context for promoting children’s learning opportunities at the dinner table.

Abstract Lightweight and compressible aerogels have been widely considered as promising materials for electromagnetic interference (EMI) shielding. Herein, a lightweight cellulose nanofibril/reduced graphene oxide carbon aerogel fabricated by unidirectional freeze‐drying and pyrolysis processes is reported. The results show that the aerogels with unidirectionally aligned pores possess better compression resilience and EMI shielding performance in the radial direction. The unidirectional aerogel with low density (≈0.0058 g cm−3) exhibits a high EMI shielding effectiveness (SE) of ≈33 dB at 8.2–12.4 GHz and a specific EMI SE of 5759 dB cm3 g−1. Therefore, the fabricated aerogel demonstrates a promising potential in the field of next‐generation EMI shielding materials.

Background: Human cytomegalovirus (HCMV) is a common pathogen that causes many diseases in young children. HCMV glycoprotein H (gH) genotypes may be associated with the type and severity of some diseases. In this study, systematic surveillance was conducted on the prevalence of HCMV infections and HCMV gH genotypes in children. Methods: Urine samples were collected from children admitted to the inpatient wards and outpatient departments between January 2015 and December 2016 in the Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China), and these were tested by real-time PCR for HCMV DNA detection and HCMV gH genotyping. Results: During the study period, a total of 32,542 urine samples were collected and analyzed using real-time PCR to confirm HCMV infection, and 5286 (16.2%) cases were positive for HCMV DNA. From our results, children aged less than one year were the most susceptible population to HCMV. Based on the data obtained from gH probes combined with real-time PCR assay, 964 HCMV-positive samples were genotyped for gH. Among them, 584 (60.6%) were positive for gH1 subtype, 307 (31.8%) for gH2 subtype, and 73 (7.6%) for both gH1 and gH2 subtypes. The gH2 rate of 42.9% indicated HCMV infection was the highest subtype in the group aged ≤28 days while gH1 rate of 77% was the highest in the group aged >3 years. The highest gH2 rate (36.4%) and lowest gH1 rate (50.0%) were detected in children with HCMV viremia, whereas the highest gH1 rates (65.0%) and lowest gH2 rates (28.8%) were found in children with HCMV hepatitis. Conclusion: The findings of our study show that children less than 1-year-old are the major population among HCMV-infected children. gH1 is the predominant genotype of HCMV in China, which occurs more frequently than gH2 genotype in the case of HCMV hepatitis. However, the opposite tendency is observed in HCMV viremia, where the gH2 genotype is predominant. Key Words: children, glycoprotein H, human cytomegalovirus

Existing researches on cascading failures of interdependent networks are mainly based on the percolation theory and do not consider the influence of dynamic load propagation and dependency groups. In this paper, we develop a novel interdependent system model to capture this phenomenon, also known as the hybrid cascading failure model. A degree-based targeted attack strategy on the cascading failure process of interdependent networks is studied. Combining dependency groups, interdependent relations, and traffic loads, small fraction of initial failed nodes may lead to the complete fragmentation of interdependent networks. The influence of two different dependency groups distributions on the robustness of interdependent networks under three coupling preferences is studied respectively. We provide a thorough analysis of the dynamics of cascading failures in interdependent networks initiated with a targeted attack. The system robustness is quantified as the surviving fraction of nodes in the giant connected component at the end of cascading failures. Our results highlight the need to consider loads, group effects and coupling preferences when designing the robust interdependent networks. And it is necessary to take steps in the early stage to reduce the losses caused by the large-scale cascading failures of infrastructure networks.

Trajectory planning is an important subject in the field of unmanned aerial vehicles (UAVs). However, existing methods do not solve some problems well, such as slow convergence speed and low searching efficiency of related algorithms and collisions between UAVs and the obstacles. Therefore, a method is proposed to solve a trajectory planning problem for multi-UAV in a static environment, which includes three main phases: the initial trajectory generation, the trajectory correction, and the smooth trajectory planning. First, the improved algorithm called MACO which introduces the metropolis criterion into the node screening mechanism of the ant colony optimization (ACO) algorithm is presented to generate the initial trajectory that can effectively avoid falling into the local optimal solution and stagnation. Then, considering size constraint of UAVs, this paper gives three trajectory correction schemes to solve the collision avoidance problem and further to optimize the initial trajectory. Last, the discontinuity originated from the sharp turn which occurred in the trajectory planning is solved by the inscribed circle (IC) smooth method, and the produced trajectory has shown better performance in reducing fuel consumption and improving the trajectory safety. Experimental results demonstrate that the proposed method has the high feasibility and effectiveness from aspects of the optimal solution, the collision avoidance, and the smooth trajectory in the trajectory planning problem for UAVs.

The incidence of hypertension and diabetes is increasing, it is reported that adipocytokines might be involved in the pathogenesis of diabetes and hypertension. We aimed to investigate the features of adipocytokines, included of Leptin, Irisin, LGR4, and Sfrp5 in type 2 diabetes mellitus (T2DM) patients with hypertension, simultaneously analyzed the connection of the alteration of adipocytokines with blood pressure and glucose. 424 patients with T2DM and 90 healthy subjects were included in the study. The patients with T2DM were divided into 4 groups based on the blood pressure. The levels of adipocytokines (Leptin, Irisin, LGR4, and Sfrp5) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly higher levels of Leptin and lower levels of Irisin, LGR4 and Sfrp5 were seen in patients with diabetes compared with non-diabetes (P

Distribution of Paleogene lacustrine high-quality source rocks in the Bozhong sag in Bohai Bay Basin is analyzed through data of geochemistry, geology and well logging, and its differences under the control of climate and tectonics is also well discussed. Distribution characteristics of the high-quality source rocks developed in the saline environment controlled by the climate are quite different from that developed in the rapid subsidence environment controlled by tectonics. The high-quality source rocks in Member 1 of Shahejie Formation developed in the saline environment account for 81.9% of total subsag area, and are distributed widely and extensively. The high-quality source rocks in Member 3 of Shahejie Formation and Member 3 of Dongying Formation is developed in the tectonic subsidence environment, and horizontally, the subsag subsidence rates has a positive correlation with the area proportion of the high-quality source rocks in the sag; vertically, the reduction-oxidation interface of the lake controls the enrichment of high-quality source rocks. Controlled by the saline environment and rapid subsidence environment, the high-quality source rocks in the Bozhong sag and adjacent areas have three types of development condition: the saline water, the tectonic subsidence, and joint control of the saline water and the tectonic subsidence. The humid climate and low subsidence rate are not favorable for development of high-quality source rocks. Keywords: Lacustrine high-quality source rocks, Saline environment, Rapid subsidence, Reduction-oxidation interface, Bozhong sag, Bohai Bay Basin

Abstract Background To investigate the prevalence and risk factors of premature thelarche (PT) in girls and gynecomastia (GM) in boys in Southern China. Methods We conducted a cross-sectional study of preschool children across 9 cities in Zhejiang province. A total of 6273 children in the age-group of 2–7 years were recruited from January 2014 to March 2015. Relevant information was collected from mothers through face-to-face interviews. Logistic regression models were used to examine the correlates of PT and GM. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Results The prevalence of PT among girls was 4.8% and that of GM among boys was 0.8%. One hundred girls were diagnosed with PT before the age of 2 years; 69 (69.0%) of these girls experienced spontaneous resolution of PT. Twenty-four boys were diagnosed with GM before the age of 2 years; 10 (41.7%) of these experienced spontaneous resolution of GM. Children borne of mothers with early onset of menarche and those belonging to high-income families were at a higher risk of premature breast development. Greater consumption of eggs was associated with premature breast development in early childhood. Conclusions Socioeconomic status of family, early onset of menarche in mother, and consumption of eggs were strongly associated with premature breast development in early childhood.

With the development of technology and the increase of equipment usage intensity, the original support mode of circuit repair, with an ideal model and single objective, is no longer applicable. Therefore, we focus on improving the support mode of circuit repair in this article. First, in this article, we propose three rest strategies, and consider the scheduling optimization of flexible rest for repair teams, for the first time. We build a more scientific and comprehensive mathematical model for the task scheduling of circuit repair. Specifically, this model aims to maximize benefits and minimize risks during scheduling up to a certain moment, taking into account constraints, such as geographic information, resources, etc. Second, in this article, we design three hybrid algorithms, namely, NSGAII-2Opt-DE(N2D), SPEA2-2Opt-DE(S2D) and MOEA/D-2Opt-DE(M2D). Third, in this article, we design a comprehensive evaluation indicator, area. It mainly contributes to evaluation of the convergence speed of the multi-objective optimization algorithms. Finally, extensive computational experiments were conducted to verify the scientificity of the rest strategies, model, algorithms and evaluation indicator proposed in this article. The experimental results showed that our proposed N2D, S2D and M2D outperformed the existing algorithms, in terms of solution quality and convergence speed.

Metabolites are closely related to human disease. The interaction between metabolites and drugs has drawn increasing attention in the field of pharmacomicrobiomics. However, only a small portion of the drug-metabolite interactions were experimentally observed due to the fact that experimental validation is labor-intensive, costly, and time-consuming. Although a few computational approaches have been proposed to predict latent associations for various bipartite networks, such as miRNA-disease, drug-target interaction networks, and so on, to our best knowledge the associations between drugs and metabolites have not been reported on a large scale. In this study, we propose a novel algorithm, namely inductive logistic matrix factorization (ILMF) to predict the latent associations between drugs and metabolites. Specifically, the proposed ILMF integrates drug–drug interaction, metabolite–metabolite interaction, and drug-metabolite interaction into this framework, to model the probability that a drug would interact with a metabolite. Moreover, we exploit inductive matrix completion to guide the learning of projection matrices U and V that depend on the low-dimensional feature representation matrices of drugs and metabolites: Fm and Fd. These two matrices can be obtained by fusing multiple data sources. Thus, FdU and FmV can be viewed as drug-specific and metabolite-specific latent representations, different from classical LMF. Furthermore, we utilize the Vicus spectral matrix that reveals the refined local geometrical structure inherent in the original data to encode the relationships between drugs and metabolites. Extensive experiments are conducted on a manually curated “DrugMetaboliteAtlas” dataset. The experimental results show that ILMF can achieve competitive performance compared with other state-of-the-art approaches, which demonstrates its effectiveness in predicting potential drug-metabolite associations.

A network is an efficient tool to organize complicated data. The Laplacian graph has attracted more and more attention for its good properties and has been applied to many tasks including clustering, feature selection, and so on. Recently, studies have indicated that though the Laplacian graph can capture the global information of data, it lacks the power to capture fine-grained structure inherent in network. In contrast, a Vicus matrix can make full use of local topological information from the data. Given this consideration, in this paper we simultaneously introduce Laplacian and Vicus graphs into a symmetric non-negative matrix factorization framework (LVSNMF) to seek and exploit the global and local structure patterns that inherent in the original data. Extensive experiments are conducted on three real datasets (cancer, cell populations, and microbiome data). The experimental results show the proposed LVSNMF algorithm significantly outperforms other competing algorithms, suggesting its potential in biological data analysis.

Cancer survivorship has traditionally received little prioritisation and attention. For a long time, the treatment of cancer has been the main focus of healthcare providers’ efforts. It is time to increase the amount of attention given to patients’ long‐term well‐being and their ability to return to a productive and good life. This article describes the current state of knowledge and identifies research areas in need of development to enable interventions for improved survivorship for all cancer patients in Europe. The article is summed up with 11 points in need of further focus.

BackgroundXihuang Pill (XHP) is mainly used to treat “Ru Yan (breast cancer)”. Evidence-based medical evidence and showed that XHP improves the efficacy of chemotherapy and reduced chemotherapy-induced toxicity in breast cancer patients. However, the mechanism of XHP against breast cancer is not clear.MethodsThe effect of XHP extract on cell half-inhibitory concentration (IC50) and cell viability of MD-MB-231 cells was detected by CCK-8 method. The cell inhibition rate of MDA-MB-453 cells were detected by MTT method. Apoptosis was detected by flow cytometry, cell transfer ability was detected by Transwell method, and cell proliferation ability was detected by colony formation assay. The expression of Notch1, β-catenin and c-myc mRNA in MDA-MB-453 cells were detected by real-time fluorescence quantitative PCR. Then, chemical informatics and transcriptomics methodology was utilized to predict the potential compounds and targets of XHP, and collect triple negative breast cancer (TNBC) genes and the data of Olibanum and β-boswellic acid intervention MD-MB-231 cells (from GSE102891). The cytoscape software was utilized to undergo network construction and network analysis. Finally, the data from the network analysis was imported into the DAVID database for enrichment analysis of signaling pathways and biological processes.ResultsThe IC50 was 15.08 g/L (for MD-MB-231 cells). After interfering with MD-MB-231 cells with 15.08 g/L XHP extract for 72 h, compared with the control group, the cell viability, migration and proliferation was significantly decreased, while early apoptosis and late apoptosis were significantly increased (P < 0.01). After interfering with MDA-MB-453 cells with 6 g/L XHP extract for 72 h, compared with the control group, the cell inhibition and apoptosis rate increased, while the expression of Notch1, β-catenin and c-myc mRNA decreased. (P < 0.05). The chemical informatics and transcriptomics analysis showed that four networks were constructed and analyzed: (1) potential compounds-potential targets network of XHP; (2) XHP-TNBC PPI network; (3) DEGs PPI network of Olibanum-treated MD-MB 231 cells; (4) DEGs PPI network of β-boswellic acid -treated MD-MB 231 cells. Several anti-TNBC biological processes, signaling pathways, targets and so on were obtained.ConclusionXHP may exert anti-TNBC effects through regulating biological processes, signaling pathways, targets found in this study.

Dynamic cluster network localization requires taking the following factors into consideration: 1) the localization time of network nodes; 2) the communication load among all cluster nodes, and; 3) the presence of the abnormal distance measurement data. However, most of the existing network localization algorithms only focus on localization accuracy. To solve the localization problem of the dynamic cluster network nodes, an improved combined trilateral localization algorithm is proposed. This proposed algorithm not only inherits the advantages of trilateration but also addresses the error propagation and accumulation problem with the strategies of anchor nodes selection in combined trilateral localization. Furthermore, by filtering the candidate positions, this algorithm can deal with some abnormal distance measurement data existing in the localization process. Finally, the extensive simulation of the algorithm is performed considering the actual unmanned aerial vehicle (UAV) cluster network, and the experimental results demonstrate the proposed algorithm can achieve high localization accuracy and have robustness as well as good adaptability to the dynamic network.