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Summary: The human skin maintains a comfortable and healthy somatosensory state by sensing different aspects of the thermal environment, including temperature value, heat source, energy level, and duration. However, state-of-the-art thermosensors only measure basic temperature values, not the full range of the thermosensation function of human skin. Here, we propose a heat source recognition (hsr) sensor of poly(butyl acrylate)-lithium bis(n-fluoroalkylsulfonyl)imide (PBA-Li:nFSI; n = 1, 3, 5), which enables response to temperature, pressure, and proximity stimulus signals based on the relaxation behavior of the ionic gel and distinguished between different types of heat sources (i.e., radiation, convection, and conduction). The hsr sensor was integrated into a prosthetic limb covered by an e-skin with isothermal regulation, and experiments with a robot showed that it could achieve human-like thermosensation function, recognizing multidimensional information about thermal environments, such as temperature value, comfort level, and heat source signal. This work deeply mimics the human body’s thermosensation function and provides a reliable solution for the development of bionic e-skin for intelligent robots and prosthetics.

Abstract During the Corona Virus Disease 2019 (COVID-19) pandemic, both high levels of post-traumatic stress and positive personal changes, a phenomenon known as post-traumatic growth (PTG), were experienced by some people. What remains unknown are the constructs and facilitators of PTG during the COVID-19 pandemic. Therefore, this study uses a grounded theory methodology to elucidate the behavioral and cognitional dimensions of PTG in Chinese college students. Twenty-four individual semi-structured interviews were conducted with Chinese college students who had positive experiences during the epidemic. Transcripts were analyzed using initial and focused coding to identify themes that explained the PTG model. The coding results revealed that the Chinese college students’ PTG consisted of four core themes: reflections on the country and society, self-awareness changes, increased social behavior, and lifestyle modifications. Additionally, participants described external factors such as information input and patriotism, which were identified as influencing their PTG during the pandemic. Findings from this study extend prior theory and research by conceptualizing a novel theoretical model for PTG among college students during the pandemic and provide important implications for research and practice.

The relationship between commercial vehicle travel patterns and urban functional areas reveals potential connections between urban form and human geographic flows, which provides critical information for optimizing urban transportation systems. Benefiting from the large-scale trajectory datasets, it would be possible to investigate deeper research by modeling the implied urban travel patterns. This study designs a framework to reveal the collective movement patterns of commercial vehicle trajectories inside the urban environment, focusing on their spatiotemporal variations within functional areas. Stopping behaviors of trajectories were identified to construct spatiotemporal origin-destination (OD) matrices, representing time-varying human geographic flows. The singular value decomposition (SVD) method was employed to quantify spatio-temporal OD matrice to obtain time and space travel features. Travel patterns’ dynamics and spatial interactions within functional areas were then analyzed. The experimental results obtained with real-life datasets from Changsha, China, uncovered three typical travel patterns depicting commercial vehicle activities in urban environment shifts from work-related locations on weekdays to leisure destinations on weekends, with central areas experiencing more short and medium-range trips. The findings provide scientific references for optimizing spatio-temporal travel patterns and functional distribution to meet the demands of urban development and traffic management strategies.

Abstract Background Satellite repeats are one of the most rapidly evolving components in eukaryotic genomes and play vital roles in genome regulation, genome evolution, and speciation. As a consequence, the composition, abundance and chromosome distribution of satellite repeats often exhibit variability across various species, genome, and even individual chromosomes. However, we know little about the satellite repeat evolution in allopolyploid genomes. Results In this study, we investigated the satellite repeat signature in five okra (Abelmoschus esculentus) accessions using genomic and cytogenetic methods. In each of the five accessions, we identified eight satellite repeats, which exhibited a significant level of intraspecific conservation. Through fluorescence in situ hybridization (FISH) experiments, we observed that the satellite repeats generated multiple signals and exhibited variations in copy number across chromosomes. Intriguingly, we found that five satellite repeats were interspersed with centromeric retrotransposons, signifying their involvement in centromeric satellite repeat identity. We confirmed subgenome-biased amplification patterns of these satellite repeats through existing genome assemblies or dual-color FISH, indicating their distinct dynamic evolution in the allotetraploid okra subgenome. Moreover, we observed the presence of multiple chromosomes harboring the 35 S rDNA loci, alongside another chromosomal pair carrying the 5 S rDNA loci in okra using FISH assay. Remarkably, the intensity of 35 S rDNA hybridization signals varied among chromosomes, with the signals predominantly localized within regions of relatively weak DAPI staining, associated with GC-rich heterochromatin regions. Finally, we observed a similar localization pattern between 35 S rDNA and three satellite repeats with high GC content and confirmed their origin in the intergenic spacer region of the 35 S rDNA. Conclusions Our findings uncover a unique satellite repeat signature in the allotetraploid okra, contributing to our understanding of the composition, abundance, and chromosomal distribution of satellite repeats in allopolyploid genomes, further enriching our understanding of their evolutionary dynamics in complex allopolyploid genomes.

Abstract Objective The purpose of this study was to investigate the feasibility of visualizing and quantifying the normal pattern of vortex formation in the left ventricle (LV) and right ventricle (RV) of the fetal heart during diastole using vector flow mapping (VFM). Methods A total of 36 healthy fetuses in the second trimester (mean gestational age: 23 weeks, 2 days; range: 22–24 weeks) were enrolled in the study. Color Doppler signals were recorded in the four-chamber view to observe the phase of the diastolic vortices in the LV and RV. The vortex area and circulation were measured, and parameters such as intraventricular pressure difference (IVPD), intraventricular pressure gradient (IVPG), and average energy loss (EL_AVG) were evaluated at different diastolic phases, including isovolumic relaxation (D1), early diastole (D2), and late diastole (D3). Results Healthy second-trimester fetal vortex formations were observed in both the LV and RV at the end of diastole, with the vortices rotating in a clockwise direction towards the outflow tract. There were no significant differences in vortex area and circulation between the two ventricles (p > 0.05). However, significant differences were found in IVPD, IVPG, and EL_AVG among the diastolic phases (D1, D2, and D3) (p 0.05). Conclusion VFM is a valuable technique for analyzing the formation of vortices in the left and right ventricles during fetal diastole. The application of VFM technology has the potential to enhance the assessment of fetal cardiac parameters.

Abstract With the annual increases in the morbidity and mortality rates of tumors, the use of biomarkers for early diagnosis and real-time monitoring of tumor cells is of great importance. Biomarkers used for tumor cell detection in body fluids include circulating tumor cells, nucleic acids, protein markers, and extracellular vesicles. Among them, circulating tumor cells, circulating tumor DNA, and exosomes have high potential for the prediction, diagnosis, and prognosis of tumor diseases due to the large amount of valuable information on tumor characteristics and evolution; in addition, in situ monitoring of telomerase and miRNA in living cells has been the topic of extensive research to understand tumor development in real time. Various techniques, such as enzyme-linked immunosorbent assays, immunoblotting, and mass spectrometry, have been widely used for the detection of these markers. Among them, the detection of tumor cell markers in body fluids based on electrochemical biosensors and fluorescence signal analysis is highly preferred because of its high sensitivity, rapid detection and portable operation. Herein, we summarize recent research progress in the detection of tumor cell biomarkers in body fluids using electrochemical and fluorescence biosensors, outline the current research status of in situ fluorescence monitoring and the analysis of tumor markers in living cells, and discuss the technical challenges for their practical clinical application to provide a reference for the development of new tumor marker detection methods.

Summary: Understanding the emergence of human notochordal cells (NC) is essential for the development of regenerative approaches. We present a comprehensive investigation into the specification and generation of bona fide NC using a straightforward pluripotent stem cell (PSC)-based system benchmarked with human fetal notochord. By integrating in vitro and in vivo transcriptomic data at single-cell resolution, we establish an extended molecular signature and overcome the limitations associated with studying human notochordal lineage at early developmental stages. We show that TGF-β inhibition enhances the yield and homogeneity of notochordal lineage commitment in vitro. Furthermore, this study characterizes regulators of cell-fate decision and matrisome enriched in the notochordal niche. Importantly, we identify specific cell-surface markers opening avenues for differentiation refinement, NC purification, and functional studies. Altogether, this study provides a human notochord transcriptomic reference that will serve as a resource for notochord identification in human systems, diseased-tissues modeling, and facilitating future biomedical research.

Abstract Differential composition analysis — the identification of cell types that have statistically significant changes in abundance between multiple experimental conditions — is one of the most common tasks in single cell omic data analysis. However, it remains challenging to perform differential composition analysis in the presence of flexible experimental designs and uncertainty in cell type assignment. Here, we introduce a statistical model and an open source R package, DCATS, for differential composition analysis based on a beta-binomial regression framework that addresses these challenges. Our empirical evaluation shows that DCATS consistently maintains high sensitivity and specificity compared to state-of-the-art methods.

Abstract Background Cancer stemness has been proven to affect tumorigenesis, metastasis, and drug resistance in various cancers, including lung squamous cell carcinoma (LUSC). We intended to develop a clinically applicable stemness subtype classifier that could assist physicians in predicting patient prognosis and treatment response. Methods This study collected RNA-seq data from TCGA and GEO databases to calculate transcriptional stemness indices (mRNAsi) using the one-class logistic regression machine learning algorithm. Unsupervised consensus clustering was conducted to identify a stemness-based classification. Immune infiltration analysis (ESTIMATE and ssGSEA algorithms) methods were used to investigate the immune infiltration status of different subtypes. Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotype Score (IPS) were used to evaluate the immunotherapy response. The pRRophetic algorithm was used to estimate the efficiency of chemotherapeutic and targeted agents. Two machine learning algorithms (LASSO and RF) and multivariate logistic regression analysis were performed to construct a novel stemness-related classifier. Results We observed that patients in the high-mRNAsi group had a better prognosis than those in the low-mRNAsi group. Next, we identified 190 stemness-related differentially expressed genes (DEGs) that could categorize LUSC patients into two stemness subtypes. Patients in the stemness subtype B group with higher mRNAsi scores exhibited better overall survival (OS) than those in the stemness subtype A group. Immunotherapy prediction demonstrated that stemness subtype A has a better response to immune checkpoint inhibitors (ICIs). Furthermore, the drug response prediction indicated that stemness subtype A had a better response to chemotherapy but was more resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Finally, we constructed a nine-gene-based classifier to predict patients’ stemness subtype and validated it in independent GEO validation sets. The expression levels of these genes were also validated in clinical tumor specimens. Conclusion The stemness-related classifier could serve as a potential prognostic and treatment predictor and assist physicians in selecting effective treatment strategies for patients with LUSC in clinical practice.

Abstract Gastric cancer (GC) is one of the major causes of cancer deaths with 5-year survival ratio of 20%. RNU12 is one of long noncoding RNAs (lncRNAs) regulating the tumor progression. However, how RNU12 affecting GC is not clear. qRT-PCR was utilized for determining the RNU12 expression in cell lines, 113 cases of paired gastric cancer (GC) and their adjacent normal gastric tissues. The biofunction alterations of RNU12 were assessed by its overexpression or knockdown in GC cells. MTT and cloning assay were assayed for the cell proliferation, the flow cytometry for the detection of cell cycle and the wound healing assay (WHA) and transwell invasion assay (TIA) for examining the migration and invasion of cells. The expressions of a set of genes related proliferation and migration were investigated with the Western Blotting (WB). RNA immunoprecipitation (RIP), biotinylated RNA pull-down and dual luciferase reporter tests were used to detect the interactions of RNU12 with miR-575/BLID. The in vivo proliferation and migration ability of RNU12 infected cells were determined in zebrafish system. This study revealed that RNU12 inhibited proliferation, invasion and metastasis by sponging of miR-575 and regulating the downstream BLID and modulated EMT of GC cells. The RNU12/miR-575/BLID axis is likely to be the prognosis biomarkers and drug targets of GC.

Stress granules (SGs) are membraneless ribonucleoprotein (RNP)-based cellular foci formed in response to stress, facilitating cell survival by protecting against damage. Mammalian spermatogenesis should be maintained below body temperature for proper development, indicating its vulnerability to heat stress (HS). In this study, biotin tracer permeability assays showed that the inhibition of heat-induced SG assembly in the testis by 4–8 mg/kg cycloheximide significantly increased the percentage of seminiferous tubules with a damaged blood–testis barrier (BTB). Western blot results additionally revealed that the suppression of heat-induced SG assembly in Sertoli cell line, TM4 cells, by RNA inference of G3bp1/2 aggravated the decline in the BTB-related proteins ZO-1, β-Catenin and Claudin-11, indicating that SGs could protect the BTB against damage caused by HS. The protein components that associate with SGs in Sertoli cells were isolated by sequential centrifugation and immunoprecipitation, and were identified by liquid chromatography with tandem mass spectrometry. Gene Ontology and KEGG pathway enrichment analysis revealed that their corresponding genes were mainly involved in pathways related to proteasomes, nucleotide excision repair, mismatch repair, and DNA replication. Furthermore, a new SG component, the ubiquitin associated protein 2 (UBAP2), was found to translocate to SGs upon HS in TM4 cells by immunofluorescence. Moreover, SG assembly was significantly diminished after UBAP2 knockdown by RNA inference during HS, suggesting the important role of UBAP2 in SG assembly. In addition, UBAP2 knockdown reduced the expression of ZO-1, β-Catenin and Claudin-11, which implied its potential role in the function of the BTB. Overall, our study demonstrated the role of SGs in maintaining BTB functions during HS and identified a new component implicated in SG formation in Sertoli cells. These findings not only offer novel insights into the biological functions of SGs and the molecular mechanism of low fertility in males in summer, but also potentially provide an experimental basis for male fertility therapies.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12872-023-03524-0.

H9N2 avian influenza poses a significant public health risk, necessitating effective vaccines for mass immunization. Oral inactivated vaccines offer advantages like the ease of administration, but their efficacy often requires enhancement through mucosal adjuvants. In a previous study, we established a novel complex of polysaccharide from Atractylodes macrocephala Koidz binding with zinc oxide nanoparticles (AMP-ZnONPs) and preliminarily demonstrated its immune-enhancing function. This work aimed to evaluate the efficacy of AMP-ZnONPs as adjuvants in an oral H9N2-inactivated vaccine and the vaccine’s impact on intestinal mucosal immunity. In this study, mice were orally vaccinated on days 0 and 14 after adapting to the environment. AMP-ZnONPs significantly improved HI titers, the levels of specific IgG, IgG1 and IgG2a in serum and sIgA in intestinal lavage fluid; increased the number of B-1 and B-2 cells and dendritic cell populations; and enhanced the mRNA expression of intestinal homing factors and immune-related cytokines. Interestingly, AMP-ZnONPs were more likely to affect B-1 cells than B-2 cells. AMP-ZnONPs showed mucosal immune enhancement that was comparable to positive control (cholera toxin, CT), but not to the side effect of weight loss caused by CT. Compared to the whole-inactivated H9N2 virus (WIV) group, the WIV + AMP-ZnONP and WIV + CT groups exhibited opposite shifts in gut microbial abundance. AMP-ZnONPs serve as an effective and safe mucosal adjuvant for oral WIV, improving cellular, humoral and mucosal immunity and microbiota in the gastrointestinal tract, avoiding the related undesired effects of CT.

Summary: Hepatocyte pyroptosis has been shown to be involved in liver damage progression. Previously, we found that growth arrest-specific 5 (GAS5) is a regulator of hepatic stellate cell (HSC) activation. However, whether GAS5 plays a role in hepatocyte pyroptosis remains unclear. In this study, reduced GAS5 was shown in CCl4-treated mice and restoration of GAS5-inhibited liver fibrosis in vivo. Hepatocyte pyroptosis participated in the effects of GAS5-inhibited liver fibrosis, associated with reduced caspase-1, NLRP3, and IL-1β (hepatocyte pyroptosis markers). Notably, AHR expression, a suppressor of NLRP3, was enhanced by GAS5. Silencing AHR inhibited GAS5-mediated hepatocyte pyroptosis. GAS5 and AHR were targets of microRNA-684 (miR-684). In addition, the effects of GAS5 on hepatocyte pyroptosis could be inhibited by miR-684. Interestingly, GAS5-mediated hepatocyte pyroptosis contributed to HSC inactivation. In conclusion, we demonstrate that GAS5 inhibits hepatocyte pyroptosis and HSC activation, at least in part, via regulation of miR-684 and AHR.

Long non-coding RNAs (lncRNAs) have emerged as curial regulators of diverse biological processes in plants. Jasmine (Jasminum sambac) is a world-renowned ornamental plant for its attractive and exceptional flower fragrance. However, to date, no systematic screening of lncRNAs and their regulatory roles in the production of the floral fragrance of jasmine flowers has been reported. In this study, we identified a total of 31,079 novel lncRNAs based on an analysis of strand-specific RNA-Seq data from J. sambac flowers at different stages. The lncRNAs identified in jasmine flowers exhibited distinct characteristics compared with protein-coding genes (PCGs), including lower expression levels, shorter transcript lengths, and fewer exons. Certain jasmine lncRNAs possess detectable sequence conservation with other species. Expression analysis identified 2752 differentially expressed lncRNAs (DE_lncRNAs) and 8002 DE_PCGs in flowers at the full-blooming stage. DE_lncRNAs could potentially cis- and trans-regulate PCGs, among which DE_lincRNAs and their targets showed significant opposite expression patterns. The flowers at the full-blooming stage are specifically enriched with abundant phenylpropanoids and terpenoids potentially contributed by DE_lncRNA cis-regulated PCGs. Notably, we found that many cis-regulated DE_lncRNAs may be involved in terpenoid and phenylpropanoid/benzenoid biosynthesis pathways, which potentially contribute to the production of jasmine floral scents. Our study reports numerous jasmine lncRNAs and identifies floral-scent-biosynthesis-related lncRNAs, which highlights their potential functions in regulating the floral scent formation of jasmine and lays the foundations for future molecular breeding.

WRKY transcription factors are one of the largest families of transcription regulators that play essential roles in regulating the synthesis of secondary metabolites in plants. Jasmine (Jasminum sambac), renowned for its aromatic nature and fragrant blossoms, possesses a significant abundance of volatile terpene compounds. However, the role of the WRKY family in terpene synthesis in jasmine remains undetermined. In this study, 72 WRKY family genes of J. sambac were identified with their conserved WRKY domains and were categorized into three main groups based on their structural and phylogenetic characteristics. The extensive segmental duplications contributed to the expansion of the WRKY gene family. Expression profiles derived from the transcriptome data and qRT-PCR analysis showed that the majority of JsWRKY genes were significantly upregulated in fully bloomed flowers compared to buds. Furthermore, multiple correlation analyses revealed that the expression patterns of JsWRKYs (JsWRKY27/33/45/51/55/57) were correlated with both distinct terpene compounds (monoterpenes and sesquiterpenes). Notably, the majority of jasmine terpene synthase (JsTPS) genes related to terpene synthesis and containing W-box elements exhibited a significant correlation with JsWRKYs, particularly with JsWRKY51, displaying a strong positive correlation. A subcellular localization analysis showed that JsWRKY51 was localized in the nucleus. Moreover, transgenic tobacco leaves and jasmine calli experiments demonstrated that overexpression of JsWRKY51 was a key factor in enhancing the accumulation of β-ocimene, which is an important aromatic terpene component. Collectively, our findings suggest the roles of JsWRKY51 and other JsWRKYs in regulating the synthesis of aromatic compounds in J. sambac, providing a foundation for the potential utilization of JsWRKYs to facilitate the breeding of fragrant plant varieties with an improved aroma.

Abstract Long-term use of antipsychotics is a common cause of myocardial injury and even sudden cardiac deaths that often lead to drug withdrawn or discontinuation. Mechanisms underlying antipsychotics cardiotoxicity remain largely unknown. Herein we performed RNA sequencing and found that NLRP3 inflammasome-mediated pyroptosis contributed predominantly to multiple antipsychotics cardiotoxicity. Pyroptosis-based small-molecule compound screen identified cannabinoid receptor 1 (CB1R) as an upstream regulator of the NLRP3 inflammasome. Mechanistically, antipsychotics competitively bond to the CB1R and led to CB1R translocation to the cytoplasm, where CB1R directly interacted with NLRP3 inflammasome via amino acid residues 177–209, rendering stabilization of the inflammasome. Knockout of Cb1r significantly alleviated antipsychotic-induced cardiomyocyte pyroptosis and cardiotoxicity. Multi-organ-based investigation revealed no additional toxicity of newer CB1R antagonists. In authentic human cases, the expression of CB1R and NLRP3 inflammasome positively correlated with antipsychotics-induced cardiotoxicity. These results suggest that CB1R is a potent regulator of the NLRP3 inflammsome-mediated pyroptosis and small-molecule inhibitors targeting the CB1R/NLRP3 signaling represent attractive approaches to rescue cardiac side effects of antipsychotics.

The influence of nonrelaxation on the Payne effect of carbon black-filled rubber is studied. The prestrain is introduced in the Kraus model in the form of exponential growth. Combined with studies of temperature correlations, an explicit model for predicting the Payne effect at different prestrains and temperatures is developed. Dynamic mechanical analyses are performed to determine model parameters and validate the proposed model. To further verify the proposed model, the heat buildup of rubber columns under dynamic tensile load is tested and simulated. The comparison between simulated and measured data shows that the simulation considering nonrelaxation is more accurate than without considering. With the increase of prestrain, the accuracy of considering nonrelaxation becomes more obvious.

As the world enters the second year of the pandemic, many posts are marketed to promote products under the guise of spreading knowledge to fulfill the users’ requirement for health knowledge. Current research, however, has primarily focused on methods to improve health literacy rather than the impact of this new form. To remedy this deficiency, this research use Cognition–Affect–Conation Pattern (CAC) to investigate digital media users and to determine attitudes towards this new form and influential. Data was collected in December 2021 from 314 users in Guangzhou, China, via a Likert-type scale developed by the researchers. Regression analyzes were also performed. Research has shown that consumer attitudes in health knowledge marketing fall within the standard learning hierarchy, with consumer self-cognition and information quality cognitions showing a positive relationship with their affect and conation. At the same time, affect did play a mediating role in this model. The results of our study provide constructive solutions for companies to optimize the communication environment of health spread in society. The findings not only provide researchers with a new perspective to study the impact of interactive digital media communication on health knowledge, but also help identify users’ information needs and formulate effective strategies to increase consumers’ understanding and application of health knowledge and products. Providing health knowledge content and leveraging digital media to develop well-established communication channels is important to foster relationships with customers.

Abstract Red blood cells (RBCs) have recently emerged as promosing candidates for cancer treatment in terms of relieving tumor hypoxia and inducing oxidative damage against cancer cells, but they are still far from satisfactory due to their limited oxygen transport and reactive oxygen species generation rate in tumor tissue. Herein, artificial RBCs (designated FTP@RBCM) with radical storm production ability were developed for oncotherapy through multidimensional reactivity pathways of Fe-protoporphyrin-based hybrid metal–organic frameworks (FTPs, as the core), including photodynamic/chemodynamic-like, catalase-like and glutathione peroxidase-like activities. Meanwhile, owing to the advantages of long circulation abilities of RBCs provided by their cell membranes (RBCMs), FTP with a surface coated with RBCMs (FTP@RBCM) could enormously accumulate at tumor site to achieve remarkably enhanced therapeutic efficiency. Intriguingly, this ROS-mediated dynamic therapy was demonstrated to induce acute local inflammation and high immunogenic cancer death, which evoked a systemic antitumor immune response when combined with the newly identified T cell immunoglobulin and mucin-containing molecule 3 (Tim-3) checkpoint blockade, leading to not only effective elimination of primary tumors but also an abscopal effect of growth suppression of distant tumors. Therefore, such RBC-mimic nanocatalysts with multidimensional catalytic capacities might provide a promising new insight into synergistic cancer treatment.

With the rapid development of information technology, researchers have paid attention to the pump-driven two-phase cooling loop technology for data centers, which imposes requirements on the efficiency and size of the pump. A fluid self-lubricating centrifugal pump with R134a refrigerant was developed to reach a higher rotation speed and oil-free system, resulting in a more diminutive size. Due to the high rotation speed and refrigerant pressure approaching saturated vapor pressure, the internal flow characteristics and cavitating characteristics are critical and complex. This paper focuses on the prototype’s head and cavitation performance based on experimental and numerical data. The experiments indicated that the head coefficient of the pump under design conditions is 0.9881, and the pump’s critical cavitation number and breakdown number are 0.551 and 0.412, respectively. The numerical results can predict the head and cavitation with deviations less than 2.6%. To study changing patterns in flow characteristics under the different operating conditions in the refrigerant centrifugal pump, the numerical model based on a modified Sauer-Schnerr cavitation model was built to analyze the distributions of pressure, temperature, relative velocity, and bubble volume across every hydraulic component and different degrees of cavitation, and proposed the influence of the thermal effect on refrigerant cavitating. The cavitating flow characteristics were obtained with the aim of providing guidance for the hydraulic design of a refrigerant centrifugal pump.

Abstract Background Photodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy. Results The designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo. Conclusion BCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms. Graphic abstract

ObjectiveChildhood trauma is a strong predictor of major depressive disorder (MDD). Women are more likely to develop MDD than men. However, the neural basis of female MDD patients with childhood trauma remains unclear. We aimed to identify the specific brain regions that are associated with female MDD patients with childhood trauma.MethodsWe recruited 16 female MDD patients with childhood trauma, 16 female MDD patients without childhood trauma, and 20 age- and education level-matched healthy controls. All participants underwent resting-state functional magnetic resonance imaging (MRI). Regional brain activity was evaluated as the amplitude of low-frequency fluctuation (ALFF). Furthermore, functional connectivity (FC) analyses were performed on areas with altered ALFF to explore alterations in FC patterns.ResultsThere was increased ALFF in the left middle frontal gyrus (MFG) and the right postcentral gyrus (PoCG) in MDD with childhood trauma compared with MDD without childhood trauma. The areas with significant ALFF discrepancies were selected as seeds for the FC analyses. There was increased FC between the left MFG and the bilateral putamen gyrus. Moreover, ALFF values were correlated with childhood trauma severity.ConclusionOur findings revealed abnormal intrinsic brain activity and FC patterns in female MDD patients with childhood trauma, which provides new possibilities for exploring the pathophysiology of this disorder in women.

Cadmium (Cd) pollution has detrimental effects on the ecological environment and human health. Currently, phytoremediation is considered an environmentally friendly way to remediate Cd pollution. The application of transgenic plants to remediate soil pollution is a new technology that has emerged in recent years. In this study, PyWRKY75 was isolated and cloned from Populus yunnanensis, and the functionality of PyWRKY75 in woody plants (poplar) under Cd stress was verified. The increase in plant height of the OE-41 line (overexpression poplar) was 33.2% higher than that of the wild type (WT). Moreover, PyWRKY75 significantly promoted the absorption and accumulation of Cd in poplar, which increased by 51.32% in the OE-41 line when compared with the WT. The chlorophyll content of transgenic poplar leaves was higher than that of the WT, which reflected a protective mechanism of PyWRKY75. Other antioxidants, such as POD, SOD, CAT, APX, AsA, GSH and PCs, also made the transgenic poplars more tolerant to Cd, and they behaved differently in roots, stems and leaves. In general, PyWRKY75 played a potential role in regulating plant tolerance to Cd stress. This study provides a scientific basis and a new type of modified poplar for Cd pollution remediation.

Sarcomas are rare, heterogeneous mesenchymal neoplasms with various subtypes, each exhibiting unique genetic characteristics. Although studies have been conducted to improve the treatment for sarcomas, the specific development from normal somatic cells to sarcoma cells is still unclear and needs further research. The diagnosis of sarcomas depends heavily on the pathological examination, which is yet a difficult work and requires expert analysis. Advanced treatment like precise medicine optimizes the efficacy of treatment and the prognosis of sarcoma patients, yet, in sarcomas, more studies should be done to put such methods in clinical practice. The revolution of advanced technology has pushed the multi-omics approach to the front, and more could be learnt in sarcomas with such methods. Multi-omics combines the character of each omics techniques, analyzes the mechanism of tumor cells from different levels, which makes up for the shortage of single-omics, and gives us an integrated picture of bioactivities inside tumor cells. Multi-omics research of sarcomas has reached appreciable progress in recent years, leading to a better understanding of the mutation, proliferation, and metastasis of sarcomas. With the help of multi-omics approach, novel biomarkers were found, with promising effects in improving the process of diagnosis, prognosis anticipation, and treatment decision. By analyzing large amounts of biological features, subtype clustering could be done in a better precision, which may be useful in the clinical procedure. In this review, we summarized recent discoveries using multi-omics approach in sarcomas, discussed their merits and challenges, and concluded with future perspectives of the sarcoma research.

Abstract Background Although obesity can be clinically defined by body mass index (BMI), waist circumference, percent body fat, or visceral fat area, it is unclear which specific measure is best associated with mobility disability in oldest-old adults. Methods Among 589 Chinese participants aged 85 years and older in a population-based cohort in Singapore, we measured waist circumference, computed BMI, estimated appendicular skeletal muscle mass, percent body fat, and visceral fat area using bioelectrical impedance analysis, and evaluated mobility disability using the Loco-Check questionnaire. We computed areas under the receiver operating characteristic curves (AUCROC) to compare how well these measures discriminated between those with and without mobility disability. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between obesity defined by these measures and mobility disability. Results Compared to BMI, which had an AUCROC (95% CI) of 0.68 (0.64–0.72) for the discrimination of mobility disability, only visceral fat area had a significantly higher discriminative performance [AUCROC (95% CI) of 0.71 (0.67–0.75) (Padjusted = 0.002)]. The optimal cut-offs of visceral fat area for the discrimination of mobility disability were ≥ 104 cm2 in men and ≥ 137 cm2 in women. In fully adjusted models, only obesity defined by visceral fat area was significantly associated with mobility disability [OR (95% CI) of 2.04 (1.10–3.77)]; obesity defined by the other measures were not associated with mobility disability after adjusting for visceral fat. Conclusion In oldest-old adults, visceral fat area was the best discriminator for obesity associated with mobility disability.

Childhood trauma is a non-specific risk factor for major depressive disorder (MDD). resting-state functional magnetic resonance imaging (R-fMRI) studies have demonstrated changes in regional brain activity in patients with MDD who experienced childhood trauma. However, previous studies have mainly focused on static characteristics of regional brain activity. This study aimed to determine the specific brain regions associated with MDD with childhood trauma by performing temporal dynamic analysis of R-fMRI data in three groups of patients: patients with childhood trauma-associated MDD (n = 48), patients without childhood trauma-associated MDD (n = 30), and healthy controls (n = 103). Dynamics and concordance of R-fMRI indices were calculated and analyzed. In patients with childhood trauma-associated MDD, a lower dynamic amplitude of low-frequency fluctuations was found in the left lingual gyrus, whereas a lower dynamic degree of centrality was observed in the right lingual gyrus and right calcarine cortex. Patients with childhood trauma-associated MDD showed a lower voxel-wise concordance in the left middle temporal and bilateral calcarine cortices. Moreover, group differences (depressed or not) significantly moderated the relationship between voxel-wise concordance in the right calcarine cortex and childhood trauma history. Overall, patients with childhood trauma-associated MDD demonstrated aberrant variability and concordance in intrinsic brain activity. These aberrances may be an underlying neurobiological mechanism that explains MDD from the perspective of temporal dynamics.

China is getting old before it gets rich. Among women of childbearing age, there seems to be little interest in having multiple children, and parenting stress may be one of the reasons. There are differences in the parenting stress felt by mothers with one child and those with two, but there is no questionnaire specifically aimed at the parenting stress felt by mothers of multiples in China. The purpose of the present study is to develop and verify a questionnaire specifically aimed at measuring the stress of two-child mothers in the Chinese context. We chose mothers as participants who were younger than 50 years old and their second child were younger than 18 years old as participants. The initial questionnaire was created after analyzing the results of 83 participants’ open questionnaires and 16 participants’ qualitative interviews. Item analysis and exploratory factor analysis were conducted with 279 participants. The final questionnaire was created after conducting reliability and validity tests on the responses of 263 participants to 23 items on the questionnaire covering four factors: characteristics of mother, environmental factor, characteristics of child, and relationship between the two siblings. The results of confirmatory factor analysis indicated that the four-factor model fit well (χ2/df = 2.00, CFI = 0.91, TLI = 0.90, SRMR = 0.06, RMSEA = 0.06). McDonald’s omega coefficients and split-half reliability coefficients both ranged from 0.50 to 0.95. The questionnaire scores were significantly positively correlated with parental burnout, the regret of having a second child and parenting stress, and were significantly negatively correlated with the intention of having a third child and support for the three-child policy. Overall, the present study confirmed the reliability and validity of the parenting stress questionnaire for two-child mothers, which can be used to measure the parenting stress experienced by mothers of multiples in China.

BackgroundAcute coronary syndrome (ACS) consists of a range of acute myocardial ischemia-related manifestations. The adverse events of ACS are usually associated with ventricular dysfunction (VD), which could finally develop to heart failure. Currently, there is no satisfactory indicator that could specifically predict the development of ACS and its prognosis. Valosin-containing protein (VCP) has recently been proposed to protect against cardiac diseases. Hence, we aimed to assess whether VCP in serum can serve as a valuable biomarker for predicting ACS and its complication.MethodsHuman serum samples from 291 participants were collected and classified into four groups based on their clinical diagnosis, namely healthy control (n = 64), ACS (n = 40), chronic coronary syndrome (CCS, n = 99), and nonischemic heart disease (non-IHD, n = 88). Clinical characteristics of these participants were recorded and their serum VCP levels were detected by enzyme-linked immunosorbent assay (ELISA). Association of serum VCP with the development of ACS and its complication VD was statistically studied. Subsequently, GWAS and eQTL analyses were performed to explore the association between VCP polymorphism and monocyte count. A stability test was also performed to investigate whether VCP is a stable biomarker.ResultsSerum VCP levels were significantly higher in the ACS group compared with the rest groups. Besides, the VCP levels of patients with ACS with VD were significantly lower compared to those without VD. Multivariate logistic regression analysis revealed that VCP was associated with both the risk of ACS (P = 0.042, OR = 1.222) and the risk of developing VD in patients with ACS (P = 0.035, OR = 0.513) independently. The GWAS analysis also identified an association between VCP polymorphism (rs684562) and monocyte count, whereas the influence of rs684562 on VCP mRNA expression level was further verified by eQTL analysis. Moreover, a high stability of serum VCP content was observed under different preservation circumstances.ConclusionValosin-containing protein could act as a stable biomarker in predicting the development of ACS and its complication VD.

Major depressive disorder (MDD) with childhood maltreatment is a heterogeneous clinical phenotype of depression with prominent features of brain disconnectivity in areas linked to maltreatment-related emotion processing (e.g., the amygdala). However, static and dynamic alterations of functional connectivity in amygdala subregions have not been investigated in MDD with childhood maltreatment. Here, we explored whether amygdala subregions (i.e., medial amygdala [MeA] and lateral amygdala [LA]) exhibited static functional connectivity (sFC) and dynamic functional connectivity (dFC) disruption, and whether these disruptions were related to childhood maltreatment. We compared sFC and dFC patterns in MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). The bilateral MeA and LA were selected as the seeds in the FC analysis. The results revealed a functional connectivity disruption pattern in maltreated MDD patients, characterized by sFC and dFC abnormalities involving the MeA, LA, and theory of mind-related brain areas including the middle occipital area, middle frontal gyrus, superior medial frontal gyrus, angular gyrus, supplementary motor areas, middle temporal gyrus, middle cingulate gyrus, and calcarine gyrus. Significant correlations were detected between impaired dFC patterns and childhood maltreatment. Furthermore, the dFC disruption pattern served as a moderator in the relationship between sexual abuse and depression severity. Our findings revealed neurobiological features of childhood maltreatment, providing new evidence regarding vulnerability to psychiatric disorders.

The Chinese government has adopted many policies to save energy and electricity in the chemical industry by improving technology and reforming its electricity market. The improved electricity efficiency and the electricity reform may indirectly reduce expected energy and electricity savings by decreasing the effective electricity price and the marginal cost of electricity services. To analyze the above issues, this paper employs the Morishima Elasticity of Substitution of the electricity cost share equation which is estimated by the DOLS method. The results show that: 1) There exists a rebound effect in the Chinese chemical industry, but it is quite large because the electricity price is being controlled by the government; 2) the reform of the electricity market reduces the rebound effect to 73.85%, as electricity price begins to reflect cost information to some extent; 3) there is still a lot of space for the reform to improve, and the rebound effect could be reduced further once the electricity price is adjusted to transfer the market information more correctly. In order to succeed in saving electricity and decreasing the rebound effect in the chemical industry, the policy implications are provided from perspectives of the improved energy efficiency and electricity pricing mechanism.

BackgroundTo explore the impact of body composition before neoadjuvant chemoradiotherapy (pre-NCRT) and after neoadjuvant chemoradiotherapy (post-NCRT) on complications, survival, and tumor response in patients with locally advanced rectal cancer (LARC).MethodsPatients with LARC who underwent radical surgery after NCRT between Ja 22nuary 2012 and March 2019 were studied. Body composition parameters, including skeletal muscle area (SMA), muscle density (MD), visceral fat area (VFA), total abdominal fat area (TAFA), and subcutaneous fat area (SFA), was identified at the third lumbar vertebra level on computed tomography (CT). The patients were divided into two groups based on the sex-specific quartile values of SMA, MD, VFA, TAFA, SFA, and body composition change. Patient characteristics, short- and long-term postoperative complications, survival, and tumor response were analyzed.ResultsA total of 122 eligible patients were enrolled. Body composition parameters, except MD, were strongly correlated with BMI (p < 0.001). Pre-NCRT low MD (p = 0.04) and TAFA loss (p = 0.02) were significantly correlated with short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for both disease-free survival (DFS) (HR 2.611, 95% CI 1.129–6.040, p = 0.025) and cancer-specific survival (CSS) (HR 3.124, 95% CI 1.030–9.472, p = 0.044) in the Cox regression multivariate analysis. Multivariate logistic regression analysis identified post-NCRT SFA (OR 3.425, 95% CI 1.392–8.427, p = 0.007) and SFA loss (OR 3.358, 95% CI 1.214–9.289, p = 0.02) as independent risk factors for tumor regression grade (TRG) and downstaging, respectively.ConclusionPre-NCRT low MD and TAFA loss were related to a high incidence of short- and long-term ileus, respectively. Pre-NCRT low SMA was a significant prognostic factor for CSS and DFS. Post-NCRT SFA and SFA loss were independent risk factors for TRG and downstaging, respectively.

The human gut microbiota develops soon after birth and can acquire inter-individual variation upon exposure to intrinsic and environmental cues. However, inter-individual variation has not been comprehensively assessed in a multi-ethnic study. We studied a longitudinal birth cohort of 106 infants of three Asian ethnicities (Chinese, Malay, and Indian) that resided in the same geographical location (Singapore). Specific and temporal influences of ethnicity, mode of delivery, breastfeeding status, gestational age, birthweight, gender, and maternal education on the development of the gut microbiota in the first 2 years of life were studied. Mode of delivery, breastfeeding status, and ethnicity were identified as the main factors influencing the compositional development of the gut microbiota. Effects of delivery mode and breastfeeding status lasted until 6M and 3M, respectively, with the primary impact on the diversity and temporal colonization of the genera Bacteroides and Bifidobacterium. The effect of ethnicity was apparent at 3M post-birth, even before the introduction of weaning (complementary) foods, and remained significant after adjusting for delivery mode and breastfeeding status. Ethnic influences remained significant until 12M in the Indian and Chinese infants. The microbiota of Indian infants was characterized by higher abundances of Bifidobacterium and Lactobacillus, while Chinese infants had higher abundances of Bacteroides and Akkermansia. These findings provide a detailed insight into the specific and temporal influences of early life factors and ethnicity in the development of the human gut microbiota. Trial Registration: Clinicaltrials.gov registration no. NCT01174875.

Abstract Background The outcomes for those with type 2 diabetes mellitus (T2DM) in Singapore are poor. In this TRIal to slow the Progression Of Diabetes (TRIPOD), we will evaluate the effectiveness and cost-effectiveness of a comprehensive diabetes management package (DMP), with or without a financial incentives program, M-POWER Rewards, in efforts to improve HbA1c levels for individuals with T2DM. Methods/design TRIPOD is a randomized, open-label, controlled, multi-center, superiority trial with three parallel arms: (1) usual care only, (2) usual care with DMP, and (3) usual care with DMP plus M-POWER Rewards. A total of 339 adults with sub-optimally controlled T2DM (self-reported HbA1c 7.5–11.0%) will be block randomized according to a 1:1:1 allocation ratio to the three arms. The primary outcome is mean change in HbA1c level at Month 12 from baseline. Secondary outcomes include mean change in HbA1c level at Months 6, 18, and 24; mean changes at Months 6, 12, 18, and 24 in weight, blood pressure, and self-reported physical activity, weight monitoring, blood glucose monitoring, medication adherence, diabetes self-management, sleep quality, work productivity and daily activity impairment, and health utility index; and proportion of participants initiating insulin treatment by Months 6, 12, 18, and 24. Incremental cost-effectiveness ratios will be computed based on costs per improvement in HbA1c at Month 12 and converted to cost per quality-adjusted life year gained. Discussion The TRIPOD study will present insights about the long-term cost-effectiveness and financial viability of the interventions and the potential for integrating within usual care. Trial registration ClinicalTrials.gov, NCT03800680. Registered on 11 January 2019.

Background: Frail older adults have an increased risk of adverse health outcomes and premature death. They also exhibit altered gait characteristics in comparison with healthy individuals.Methods: In this study, we created a Fried’s frailty phenotype (FFP) labelled casual walking video set of older adults based on the West China Health and Aging Trend study. A series of hyperparameters in machine vision models were evaluated for body key point extraction (AlphaPose), silhouette segmentation (Pose2Seg, DPose2Seg, and Mask R-CNN), gait feature extraction (Gaitset, LGaitset, and DGaitset), and feature classification (AlexNet and VGG16), and were highly optimised during analysis of gait sequences of the current dataset.Results: The area under the curve (AUC) of the receiver operating characteristic (ROC) at the physical frailty state identification task for AlexNet was 0.851 (0.827–0.8747) and 0.901 (0.878–0.920) in macro and micro, respectively, and was 0.855 (0.834–0.877) and 0.905 (0.886–0.925) for VGG16 in macro and micro, respectively. Furthermore, this study presents the machine vision method equipped with better predictive performance globally than age and grip strength, as well as than 4-m-walking-time in healthy and pre-frailty classifying.Conclusion: The gait analysis method in this article is unreported and provides promising original tool for frailty and pre-frailty screening with the characteristics of convenience, objectivity, rapidity, and non-contact. These methods can be extended to any gait-related disease identification processes, as well as in-home health monitoring.

Coronary artery spasm (CAS) plays an important role in the pathogenesis of many ischemic heart entities; however, there are no established diagnostic biomarkers for CAS in clinical and forensic settings. This present study aimed to identify such serum biomarkers by establishing a rabbit CAS provocation model and integrating quantitative serum proteomics, parallel reaction monitoring/mass spectrometry-based targeted proteomics, and partial least-squares discriminant analysis (PLS-DA). Our results suggested that SELENBP1 and VCL were potential candidate biomarkers for CAS. In independent clinical samples, SELENBP1 and VCL were validated to be significantly lower in serum but not blood cells from CAS patients, with the reasons for this possibly due to the decreased secretion from cardiomyocytes. The areas under the curve of the receiver operating characteristics (ROC) analysis were 0.9384 for SELENBP1 and 0.9180 for VCL when diagnosing CAS. The CAS risk decreased by 32.3% and 53.6% for every 10 unit increases in the serum SELENBP1 and VCL, respectively. In forensic samples, serum SELENBP1 alone diagnosed CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, and its combination with VCL yielded a diagnostic specificity of 100.0%, which was superior to the traditional biomarkers of cTnI and CK-MB. Therefore, serum SELENBP1 and VCL could be effective biomarkers for both the clinical and forensic diagnosis of CAS.

Abstract Size‐exclusion chromatography (SEC) is a widely adopted method for the isolation of extracellular vesicles (EVs) from complex samples. SEC can efficiently remove high‐abundant proteins, while often requires multiple fractionation operation using diversified column settings. In this study, we aim to establish a simplified SEC method to acquire high quality EVs. In comparison of all three cross‐linked Sepharose resins with the sample types of FBS and human serum (HS), CL‐6B and CL‐4B showed superior performance in regular SEC to CL‐2B in terms of significantly narrower EV and protein peaks, higher resolutions and EV purity. By increasing their bed volumes to 20 ml, the resolutions of CL‐6B and CL‐4B columns could be significantly improved, while the CL‐6B column had the best performance with higher particle yields and tighter EV peaks. With the CL‐6B 20 ml column, we further established a simplified dichotomic SEC method that only requires two bulk elutions to acquire EVs in the Eluate 1 and proteins in the Eluate 2. We further justified that such CL‐6B columns were reusable for at least 10 consecutive times, and the dichotomic SEC was applicable to EV isolations from HS and FBS‐free supernatants of fluorescently labelled and unlabelled SW620 cells. The proteomics analysis implicated that although the two methods had dissimilar abilities in removing different co‐isolating contaminant proteins from EVs, the dichotomic SEC and ultracentrifugation could isolate EVs from human plasma with comparable purity. This dichotomic SEC has its intriguing potential to be used for EV preparation toward clinical testing and/or basic research.

High-speed centrifugal pumps with low specific speed have the characteristics of a small flowrate, a high head, and being compact and light weight, making them promising candidates for applications in the thermal management of aerospace and electronic devices. The energy loss in the low specific speed pump is critical and complex due to the large impeller diameter, the narrow and long flow channel, and the small outlet width. In this paper, an analysis method based on an energy loss model and computational fluid dynamics simulations (ELM/CFD) is proposed to analyze the performance of the low specific speed pump with a fully sealed structure. Experiments were carried out under variable water flowrates. The results show that the empirical correlation method failed to accurately predict the performance of high-speed centrifugal pumps, because the bearing clearance leakage and motor channel leakage are ignored. Moreover, the volume loss and hydraulic loss are calculated based on the empirical parameters of commonly used pumps that are different from the high-speed pump with the low specific speed in the complex flow channel structure. The ELM/CFD method calculates various loss power based on the simulation results and can predict the head and efficiency with deviations less than 2% and 5%, respectively. ELM/CFD can accurately analyze the optimization direction of the pump. The hydraulic loss and the volume loss of the impeller are the dominant factors that restrict the pump efficiency under the lower flowrates, while the hydraulic loss of subsequent flow channels becomes important under the larger flowrates.

Abstract Background Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) in mediating the effects of PTB on future health outcomes. Thus, epigenome-wide association studies (EWAS), where DNAm sites are examined for associations with PTB, can help shed light on the biological mechanisms linking the two. Results In an Asian cohort of 1019 infants (68 preterm, 951 full term), we examined and compared the associations between PTB and genome-wide DNAm profiles using both cord tissue (n = 1019) and cord blood (n = 332) samples on Infinium HumanMethylation450 arrays. PTB was significantly associated (P

Coronary artery spasm (CAS) is a transient reversible subtotal or complete occlusion induced by coronary hypercontraction and the critical cause of myocardial ischaemia with non-obstructive coronary arteries. During the past decades, our knowledge of the risk factors and pathophysiological mechanisms of CAS have been increasingly progressed, and various diagnostic approaches, including imaging technologies and novel biomarkers, have been proposed to serve well to diagnose CAS clinically. This review aims to summarize these research progresses on the risk factors of CAS and introduce current knowledge about the mechanisms accounting for CAS, including endothelial dysfunction, vascular smooth muscle cell hyperreactivity, and adventitial and perivascular adipose tissue inflammation. We also gathered the recently evolved diagnostic approaches and analyzed their advantages/disadvantages, in purpose of enhancing the diagnostic yield on the basis of ensuring accuracy.

A high-speed centrifugal pump with a fully sealed structure has the advantages of a small size, no external leakage, and being pollution-free. The inner leakage passage of a pump with a fully sealed structure includes the tip clearance and the hub clearance. The hub clearance, the lubrication passage of the bearing, and the clearance between the stator and the rotor of the built-in motor constitute the internal flow channel. As a consequence of hub leakage, the complexity of the flow field increases and performance of the pump is affected. However, hub leakage also lubricates the bearing and cools the motor by flowing through the internal flow channel. To obtain the actual flow field distribution and external characteristics of the pump, a coupling calculation based on a conventional CFX simulation and MATLAB was carried out. The results show that hub leakage promotes an increase in tip leakage and changes the distribution of the main flow field. Moreover, hub leakage also significantly affects the efficiency of the pump. Compared with hub leakage, the internal flow has a greater impact on the performance of the pump. The numerical simulation results of the internal flow model are similar to the experimental results, with the maximum absolute error of the head at 0.3 m and the maximum absolute error of the efficiency at 1.7%, indicating that the internal flow model is effective at predicting the performance of the high-speed centrifugal pump with a fully sealed structure.

Summary: Immune cold tumor characterized by low immunogenicity, insufficient and exhausted tumor-infiltrating lymphocytes, and immunosuppressive microenvironment is the main bottleneck responsible for low patient response rate of immune checkpoint blockade. Here, we developed biosynthetic functional vesicles (BFVs) to convert immune cold into hot through overcoming hypoxia, inducing immunogenic cell death, and immune checkpoint inhibition. The BFVs present PD1 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the surface, whereas load catalase into their inner core. The TRAIL can specifically induce immunogenic death of cancer cells to initiate immune response, which is further synergistically strengthened by blocking PD1/PDL1 checkpoint signal through ectogenic PD1 proteins on BFVs. The catalase can produce O2 to overcome tumor hypoxia, in turn to increase infiltration of effector T cells while deplete immunosuppressive cells in tumor. The BFVs elicit robust and systematic antitumor immunity, as demonstrated by significant regression of tumor growth, prevention of abscopal tumors, and excellent inhibition of lung metastasis.

With controllable size, biocompatibility, porosity, injectability, responsivity, diffusion time, reaction, separation, permeation, and release of molecular species, hydrogel microparticles achieve multiple advantages over bulk hydrogels for specific biomedical procedures. Moreover, so far studies mostly concentrate on local responses of hydrogels to chemical and/or external stimuli, which significantly limit the scope of their applications. Tetherless micromotors are autonomous microdevices capable of converting local chemical energy or the energy of external fields into motive forces for self-propelled or externally powered/controlled motion. If hydrogels can be integrated with micromotors, their applicability can be significantly extended and can lead to fully controllable responsive chemomechanical biomicromachines. However, to achieve these challenging goals, biocompatibility, biodegradability, and motive mechanisms of hydrogel micromotors need to be simultaneously integrated. This review summarizes recent achievements in the field of micromotors and hydrogels and proposes next steps required for the development of hydrogel micromotors, which become increasingly important for in vivo and in vitro bioapplications.

Accounting for cellular heterogeneity is essential in neonatal epigenome-wide association studies (EWAS) performed on heterogeneous tissues, such as umbilical cord tissue (CT) or cord blood (CB). Using a reference-panel-based statistical approach, the cell type composition of heterogeneous tissues can be estimated by comparison of whole tissue DNA methylation profiles with cell type-specific DNA methylation signatures. Currently, there is no adequate DNA methylation reference panel for CT, and existing CB panels have been generated on lower coverage Infinium HumanMethylation450 arrays. In this study, we generate a reference panel for CT and improve available CB panels by using the higher coverage Infinium MethylationEPIC arrays. We performed DNA methylation profiling of 9 cell types isolated from CT and CB samples from 14 neonates. In addition to these cell types, we profiled DNA methylation of unfractionated CT and CB. Cell type composition of these unfractionated tissue samples, as estimated by our reference panels, was in agreement with that obtained by flow cytometry. Expectedly, DNA methylation profiles from CT and CB were distinct, reflecting their mesenchymal and hematopoietic stem cell origins. Variable CpGs from both unfractionated CT and its isolated cell types were more likely to be located in open seas and intronic regions than those in CB. Cell type specific CpGs in CT were enriched in intercellular matrix pathways, while those from CB were enriched in immune-related pathways. This study provides an open source reference panel for estimation and adjustment of cellular heterogeneity in CT and CB, and broadens the scope of tissue utilization assessed in future neonatal EWAS studies.

Abstract Background To date, genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants among a variety of traits/diseases, shedding light on the genetic architecture of complex disease. The polygenicity of complex diseases is a widely accepted phenomenon through which a vast number of risk variants, each with a modest individual effect, collectively contribute to the heritability of complex diseases. This imposes a major challenge on fully characterizing the genetic bases of complex diseases. An immediate implication of polygenicity is that a much larger sample size is required to detect individual risk variants with weak/moderate effects. Meanwhile, accumulating evidence suggests that different complex diseases can share genetic risk variants, a phenomenon known as pleiotropy. Results In this study, we propose a statistical framework for Leveraging Pleiotropic effects in large-scale GWAS data (LPG). LPG utilizes a variational Bayesian expectation-maximization (VBEM) algorithm, making it computationally efficient and scalable for genome-wide-scale analysis. To demonstrate the advantages of LPG over existing methods that do not leverage pleiotropy, we conducted extensive simulation studies and applied LPG to analyze two pairs of disorders (Crohn’s disease and Type 1 diabetes, as well as rheumatoid arthritis and Type 1 diabetes). The results indicate that by levelaging pleiotropy, LPG can improve the power of prioritization of risk variants and the accuracy of risk prediction. Conclusions Our methodology provides a novel and efficient tool to detect pleiotropy among GWAS data for multiple traits/diseases collected from different studies. The software is available at https://github.com/Shufeyangyi2015310117/LPG.

Abstract The S-doped Sb2O3 nanocrystals were successfully synthesized using SbCl3 and thioacetamide (TAA) as precursors via a facile one-step hydrothermal method. The effects of pH of the precursor reaction solution on the product composition and property were determined. The results indicated that the doping amount of S could be tuned by adjusting the pH of the precursor solution. Furthermore, the S entered into the interstitial site of Sb2O3 crystals as S2−, which broadened the absorption wavelength range of the Sb2O3 nanocrystal. The S-doped Sb2O3 exhibited an excellent visible-light-driven photocatalytic activity in the decomposition of methyl orange and 4-phenylazophenol. Last, a possible photocatalytic mechanism of the S-doped Sb2O3 under visible light irradiation was proposed.

Abstract Background Epigenomes are tissue specific and thus the choice of surrogate tissue can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) and in their extrapolation to target tissue. To develop a better understanding of the link between tissue specificity and neonatal EWAS, and the contributions of genotype and prenatal factors, we compared genome-wide DNA methylation of cord tissue and cord blood, two of the most accessible surrogate tissues at birth. Methods In 295 neonates, DNA methylation was profiled using Infinium HumanMethylation450 beadchip arrays. Sites of inter-individual variability in DNA methylation were mapped and compared across the two surrogate tissues at birth, i.e., cord tissue and cord blood. To ascertain the similarity to target tissues, DNA methylation profiles of surrogate tissues were compared to 25 primary tissues/cell types mapped under the Epigenome Roadmap project. Tissue-specific influences of genotype on the variable CpGs were also analyzed. Finally, to interrogate the impact of the in utero environment, EWAS on 45 prenatal factors were performed and compared across the surrogate tissues. Results Neonatal EWAS results were tissue specific. In comparison to cord blood, cord tissue showed higher inter-individual variability in the epigenome, with a lower proportion of CpGs influenced by genotype. Both neonatal tissues were good surrogates for target tissues of mesodermal origin. They also showed distinct phenotypic associations, with effect sizes of the overlapping CpGs being in the same order of magnitude. Conclusions The inter-relationship between genetics, prenatal factors and epigenetics is tissue specific, and requires careful consideration in designing and interpreting future neonatal EWAS. Trial registration This birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

Experimental studies show a substantial contribution of early life environment to obesity risk through epigenetic processes. We examined inter-individual DNA methylation differences in human birth tissues associated with child's adiposity. We identified a novel association between the level of CpG methylation at birth within the promoter of the long non-coding RNA ANRIL (encoded at CDKN2A) and childhood adiposity at age 6-years. An association between ANRIL methylation and adiposity was also observed in three additional populations; in birth tissues from ethnically diverse neonates, in peripheral blood from adolescents, and in adipose tissue from adults. Additionally, CpG methylation was associated with ANRIL expression in vivo, and CpG mutagenesis in vitro inhibited ANRIL promoter activity. Furthermore, CpG methylation enhanced binding to an Estrogen Response Element within the ANRIL promoter. Our findings demonstrate that perinatal methylation at loci relevant to gene function may be a robust marker of later adiposity, providing substantial support for epigenetic processes in mediating long-term consequences of early life environment on human health.