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Abstract Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients’ samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.

This meta-analysis aims to systematically evaluate if different physical activities (PA) improve the social communication impairments (SCI) seen in children with autism spectrum disorder (ASD). For this meta-analysis, five databases (Web of Science, PubMed and Cochrane Library database in English, and CNKI and Wanfang Data Knowledge Service Platform in Chinese) were searched from database inception to September 11, 2024. The eligibility criteria included (1) study population comprised children with ASD, with no gender restriction; (2) experimental group consisted of a PA intervention; (3) control group consisted of nonPA interventions or routine activities; (4) outcomes were assessed using validated SCI scales (e.g., social cognition, social motivation, and/or social awareness); and (5) study design involved a randomized parallel group design. The quality of the evidence for each study was assessed using the Cochrane Risk of Bias tool. From a pool of 2714 potentially relevant articles, 17 were eligible for inclusion in this review. The results of overall response of PA intervention to SCI illustrated a Medium degree of statistical heterogeneity between studies (I2 = 53.3 %, p

Abstract This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30–15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: − 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: − 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: − 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

Abstract. Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m6A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m6A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m6A.

In recent years, landscape pattern optimization has been regarded as a cutting-edge science in various fields, and basin hydrology is no exception. Its effect on basin water purification has also been focused on. Based on the analysis of land use types and landscape patterns in the Danjiangkou Reservoir Basin, and combined with the determination of water quality indicators in the Danjiangkou Reservoir Basin, the relationship between the spatial pattern of Landscape Morphology and water quality was studied; It is found that among the basic characteristic indicators of many basins, the main influencing factors of water quality with high Variable importance for the projection (VIP>1) are IJI (Interspersion and Juxtaposition Index), COHE (Patch Cohesion Index), AI (Aggregation Index), PD (Patch Density), ED (Edge Density); Using PLSR (Partial Least Squares Regression) analysis, the main influencing factors of water quality were discussed. It was found that there was a significant negative regression relationship (Rc

Abstract. Background:. The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. Methods:. We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. Results:. We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. Conclusions:. REDH is accessible at http://www.redhdatabase.com/. This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

AbstractContext Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS.Objective This study determines whether baicalin could affect the progression of PCOS.Materials and methods To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 μM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 μM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect.Conclusions Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

An event camera is a neuromimetic sensor inspired by the human retinal imaging principle, which has the advantages of high dynamic range, high temporal resolution, and low power consumption. Due to the interference of hardware and software and other factors, the event stream output from the event camera usually contains a large amount of noise, and traditional denoising algorithms cannot be applied to the event stream. To better deal with different kinds of noise and enhance the robustness of the denoising algorithm, based on the spatio-temporal distribution characteristics of effective events and noise, an event stream noise reduction and visualization algorithm is proposed. The event stream enters fine filtering after filtering the BA noise based on spatio-temporal density. The fine filtering performs time sequence analysis on the event pixels and the neighboring pixels to filter out hot noise. The proposed visualization algorithm adaptively overlaps the events of the previous frame according to the event density difference to obtain clear and coherent event frames. We conducted denoising and visualization experiments on real scenes and public datasets, respectively, and the experiments show that our algorithm is effective in filtering noise and obtaining clear and coherent event frames under different event stream densities and noise backgrounds.

IntroductionIn cognitive behavioral experiments, we often asked participants to make judgments within a deadline. However, the most common instruction of “do the task quickly and accurately” does not highlight the importance of the balance between being fast and accurate.MethodsOur research aimed to explore how instructions about speed or accuracy affect perceptual process, focus on event-related potentials (ERPs) and event-related oscillations (EROs) of two brain responses for visual stimuli, known as P1 and N1. Additionally, we compared the conventional analysis approach with principal component analysis (PCA) based methods to analyze P1 and N1 ERP amplitude and ERO power.ResultsThe results showed that individuals instructed to respond quickly had lower P1 amplitude and alpha ERO than those who prioritized accuracy, using the PCA-based approach. However, these two groups had no differences between groups in the N1 theta band using both methods. The traditional time-frequency analysis method could not detect any ERP or ERO distinctions between groups due to limitations in detecting specific components in time or frequency domains. That means PCA is effective in separating these components.DiscussionOur findings indicate that the instructions given regarding speed and accuracy impact perceptual process of subjects during cognitive behavioral experiments. We suggest that future researchers should choose their instructions carefully, considering the purpose of study.

Heterostructure engineering for sulfur hosts is an effective way to achieve interfacial synergistic effects on suppressing the "shuttle effect" of polysulfides and thus improve electrochemical performance of lithium–sulfur (Li–S) batteries. Rational selection and design of different components into heterostructures is vital to enhance the synergistic effect. Herein, MoS2/MoP Mott–Schottky heterostructure nanoparticles decorated on reduced graphene oxide (MoS2/MoP@rGO) are fabricated and used as sulfur host firstly. Theoretical calculation and experiment results reveal that the in-situ introduction of MoP could tune the electronic structure, activate the basal plane of MoS2, and achieve the interfacial synergistic effects between adsorption (MoS2) and fast conversion (MoP). Such synergistic effects enable MoS2/MoP@rGO to not only remarkably facilitate Li2S deposition during the discharging process but also significantly accelerate the Li2S dissolution during the charging process, demonstrating bidirectional promotion behaviors. Thus, the designed cathode delivers initial capacity of 919.5 mA∙h∙g−1 with capacity of 502.3 mA∙h∙g−1 remaining after 700 cycles at 0.5 C. Even under higher sulfur loading of 4.31 mg∙cm−2 and lower electrolyte to sulfur (E/S) ratio of 8.21 μL∙mg−1, the MoS2/MoP@rGO@S cathode could still achieve good capacity and cycle stability. This work provides a novel and efficient structural design strategy of sulfur hosts for high-performance Li–S energy storage systems.

Systemic lupus erythematosus (SLE) is a debilitating autoimmune disorder characterized by unknown pathogenesis and heterogeneous clinical manifestations. The current existing serum biomarkers for SLE have limited sensitivity or specificity, making early and precise diagnosis difficult. Here, we identified two N-glycans on serum immunoglobulin G (IgG) as excellent diagnostic biomarkers for SLE based on in-depth glycomic analyses of 389 SLE patients and 304 healthy controls. These two N-glycan biomarkers are specific for diagnosing SLE, as no significant changes in these biomarkers were observed in other systemic autoimmune diseases that are easily confused with SLE, such as rheumatoid arthritis, primary Sjögren’s syndrome, or systemic sclerosis. Notably, the two N-glycan biomarkers proved to be autoantibody-independent and all-stage patient suitable. The two N-glycan biomarkers are demonstrated to be located on the Fc region based on fragment-specific glycan analysis and glycopeptide analysis, suggesting their close correlation with disease activity. Enzyme analyses revealed dysregulation of a series of glycotransferases in SLE, which might be responsible for the observed glycan alteration. Our findings provide insights into efficient population screening based on serum IgG glycosylation and potential new pathogenic factors of SLE.

Summary: Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2’s activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.

This study aims to examine and compare clinical, radiological, and pathological data between colorectal cancer (CRC) patients with and without schistosomiasis and uncover distinctive CRC characteristics when accompanied by schistosomiasis. This retrospective study is based on data collected from 341 patients diagnosed with CRC post-surgery and pathology. Of these patients, 101 (Group A) were diagnosed with colorectal cancer co-occurring with schistosomiasis (CRC-S), while 240 patients (Group B) were diagnosed with colorectal cancer without concurrent schistosomiasis (CRC-NS). Both groups were compared and analyzed based on their clinical data, imaging-based TNM staging, lymph node metastasis, nerve invasion, vascular cancer thrombus, and histopathological differentiation. A Chi-squared test revealed a significant difference in gender distribution between the patients with CRC-S (Group A) and CRC-NS (Group B), with a p -value of 0.043 and χ2 = 4.115. Specifically, a higher incidence rate was observed among males in Group A. There was a difference in the overall distribution of TNM staging between the two groups (p = 0.034, χ2 = 6.764). After pairwise comparison, a statistically significant difference was observed in the T3 stage (p 0.05). Among the 101 patients with CRC-S, 87 (86%) showed linear calcification on CT imaging. Patients with CRC-S are mainly male, with tumor staging mostly in the middle stage, high tumor differentiation, and low malignancy. CT imaging can help identify the presence of lumps and linear calcification indicative of schistosome deposits. MRI can early clarify TNM staging and determine the presence of lymph node metastasis and nerve and vascular invasion.

Abstract Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome‐wide study of miRNA‐derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene‐originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc‐301b from miR‐301b and miR‐130b, functions as an “RNA decoy” to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc‐301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation‐associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large‐scale and single‐cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA‐derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.

The application of intracranial electroencephalogram (iEEG) to predict seizures remains challenging. Although channel selection has been utilized in seizure prediction and detection studies, most of them focus on the combination with conventional machine learning methods. Thus, channel selection combined with deep learning methods can be further analyzed in the field of seizure prediction. Given this, in this work, a novel iEEG-based deep learning method of One-Dimensional Convolutional Neural Networks (1D-CNN) combined with channel increment strategy was proposed for the effective seizure prediction. First, we used 4-sec sliding windows without overlap to segment iEEG signals. Then, 4-sec iEEG segments with an increasing number of channels (channel increment strategy, from one channel to all channels) were sequentially fed into the constructed 1D-CNN model. Next, the patient-specific model was trained for classification. Finally, according to the classification results in different channel cases, the channel case with the best classification rate was selected for each patient. Our method was tested on the Freiburg iEEG database, and the system performances were evaluated at two levels (segment- and event-based levels). Two model training strategies (Strategy-1 and Strategy-2) based on the K-fold cross validation (K-CV) were discussed in our work. (1) For the Strategy-1, a basic K-CV, a sensitivity of 90.18%, specificity of 94.81%, and accuracy of 94.42% were achieved at the segment-based level. At the event-based level, an event-based sensitivity of 100%, and false prediction rate (FPR) of 0.12/h were attained. (2) For the Strategy-2, the difference from the Strategy-1 is that a trained model selection step is added during model training. We obtained a sensitivity, specificity, and accuracy of 86.23%, 96.00% and 95.13% respectively at the segment-based level. At the event-based level, we achieved an event-based sensitivity of 98.65% with 0.08/h FPR. Our method also showed a better performance in seizure prediction compared to many previous studies and the random predictor using the same database. This may have reference value for the future clinical application of seizure prediction.

To solve the problem of inaccurate object segmentation caused by unbalanced samples for in-vehicle point cloud, an improved semantic segmentation network RangeNet++ based on asymmetric loss function (AsL-RangeNet++) is proposed, which uses asymmetric loss (AsL) function and Adam optimizer to calculate and adjust object weights, achieve optimal point cloud segmentation. AsL-RangeNet++ can solve the problem of unbalance between positive and negative samples and label error in multi-label classification by calculating the weights of positive and negative samples respectively and more accurately segments the point cloud of small targets. A large number of experiments on the widely used SemanticKITTI dataset show that the proposed method has higher segmentation accuracy and better adaptability than the current mainstream methods.

The study explores the characteristics of morning extreme precipitation (MEP) during the pre-summer in inland Guangdong. Based on the principal modes, MEP events can be classified into four groups. The first group of MEP (G1) is a typical southeastward-propagating rainfall system originating from the northwestern mountains. This is caused by the strongest accelerated southwesterly winds at night, which bring abundant moist and warm air from the South China Sea (SCS) along with the shear line and the highest convective available potential energy (CAPE). The second group of MEP (G2) is warm-sector heavy rainfall with large-scale warming and higher CAPE. This local rainfall system originates in the south of Nanling mountains at night and reaches its mature stage in the morning. The rainfall system of the third group (G3) originates in central Guangxi and propagates to the southern inland region. The southeasterly winds in Guangxi intensify at night due to the anomalous cyclonic circulation. However, in the morning, the easterly winds shift to the westerlies, favoring eastward propagation. After SCS monsoon onset, cold air intrudes southward, colliding with moist warm air from the SCS, leading to heavy frontal precipitation in the inland region, classified as the fourth group MEP (G4).

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

Abstract Background To assess the root angle characteristics of maxillary incisors, and to analyze the relationship between the root angle and other implant-related anatomical indices to use the sagittal root angle as an index for immediate implant evaluation and design. Methods A random sample consisting of 400 cone-beam computed tomography (CBCT) images and 65 maxillary plaster models were selected for the present study. CBCT and stereolithography (STL) scan images were imported as DICOM files into coDiagnostiX software for matching the hard and soft tissue. The angle between the long axis of the anterior tooth and the corresponding alveolar bone and implant-related hard and soft tissue indices were measured in the sagittal section. Descriptive statistics, frequency analysis, multi-level comparisons, and correlation analyses were performed. Results The average sagittal root angles were 15° at the central incisor and 19° at the lateral incisor. The root angle in males was significantly larger than that in females, and increased with age. The largest angle, 22.35°, was found in the lateral incisors of the oldest (> 50 years old) male group. The root angle was found to correlate with coronal buccal bone thickness, coronal palatal bone thickness, apical buccal bone thickness, palatal bone thickness, and the below apex bone thickness. Conclusions The sagittal root angle could reflect the distribution of other implant-related anatomical indices, which may provide additional reference for the evaluation of immediate implant placement.

Abstract Background Cellular RNA-binding proteins (RBPs) have multiple roles in post-transcriptional control, and some are shown to bind DNA. However, the global localization and the general chromatin-binding ability of RBPs are not well-characterized and remain undefined in hematopoietic cells. Results We first provide a full view of RBPs’ distribution pattern in the nucleus and screen for chromatin-enriched RBPs (Che-RBPs) in different human cells. Subsequently, by generating ChIP-seq, CLIP-seq, and RNA-seq datasets and conducting combined analysis, the transcriptional regulatory potentials of certain hematopoietic Che-RBPs are predicted. From this analysis, quaking (QKI5) emerges as a potential transcriptional activator during monocytic differentiation. QKI5 is over-represented in gene promoter regions, independent of RNA or transcription factors. Furthermore, DNA-bound QKI5 activates the transcription of several critical monocytic differentiation-associated genes, including CXCL2, IL16, and PTPN6. Finally, we show that the differentiation-promoting activity of QKI5 is largely dependent on CXCL2, irrespective of its RNA-binding capacity. Conclusions Our study indicates that Che-RBPs are versatile factors that orchestrate gene expression in different cellular contexts, and identifies QKI5, a classic RBP regulating RNA processing, as a novel transcriptional activator during monocytic differentiation.

Abstract Background Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in hepatocellular carcinoma (HCC). However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in anti-HCC relapse are rarely understood. Methods HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, long non-coding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA) by RNA sequence, and significant differential expression (DE) of these types of RNAs were selected for further analysis. A ceRNA regulatory network was constructed to explore the potential mechanisms of IFN-α intervention on anti-HCC relapse. Finally, the potential prognostic associated genes among these DE RNAs were identified. Results Totally, 556 mRNAs, 120 circRNAs, 87 lncRNAs, and 96 miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A, IGFBP4 and MARCH3, as the prognostic associated genes for HCC. Furthermore, MARCH3 expression correlated with infiltrating levels of tumor infiltrating immune cells (TICCs) in HCC. MARCH3 expression also showed strong correlations with the gene markers of diverse immune cells in HCC. Conclusion Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.

The olfactory system is an important component of insect behavior and is vital for survival and reproduction. However, the genomic characterization and molecular basis of the olfactory response of Megalurothrips usitatus remain relatively unknown. RNA sequencing-built developmental transcriptomes of nymphs, pupae, and adult M. usitatus were examined in order to establish the sequence-based background of M. usitatus olfactory responses. A total of 56,669 unigenes were annotated using GO, NR, Pfam, eggNOG, SwissProt, and KEGG. The number of differentially expressed genes between pupae and nymphs, males and nymphs, and females and nymphs were 10,498, 9,235, and 10,964, respectively. One odorant-binding protein (MusiOBP1) and one chemosensory protein (MusiCSP1) were selected from the transcriptome, and their full-length sequences were obtained using RACE PCR. The relative expression of MusiOBP1 was the highest in primordial females, whereas the relative expression of MusiCSP1 was the highest in primordial pupae. The strongest binding ability to the odor-binding protein MusiOBP1 was observed for β-citronellol. 3-Hydroxy-2-methyl-4-pyrone showed the strongest binding affinity to MusiCSP1. Our analysis suggests that MusiOBP1 and MusiCSP1 may play significant roles in mediating M. usitatus host recognition. This research will improve our knowledge of odorant-binding proteins and chemosensory proteins, which will in turn improve our understanding of insect olfactory systems.

Bi12O15Cl6/g-C3N4 binary type Ⅱ heterojunction photocatalyst was prepared by wet impregnation method. The crystal structure, morphology, and optical absorption of the samples were characterized by XRD, SEM, and UV-vis diffuse reflectance spectroscopy. With tetracycline as the target pollutant, the effects of doping ratio, dosage, and initial solution concentration on the photocatalytic degradation of Bi12O15Cl6/g-C3N4 were investigated under visible light. The results show that the removal rate of tetracycline is 96.43% in visible light irradiation for 150 min when the doping ratio is 50%, the dosage is 1.6 g/L, and the initial concentration of the solution is 10 mg/L. Finally, through the free radical capture experiment, it was proved that the free radicals playing the main role in the process of photocatalysis are h+ and ·O2-.

Remarkably, nanomaterials can interact with the cells of immune system and either enhance or inhibit its function in many ways. Unfortunately, such valuable information has been overlooked in studies of polysaccharide immune activity. This study isolated a nano-polysaccharide from vinegar-baked Radix Bupleuri by membrane separation system, DEAE-52 and Sephadex-G200. The physicochemical characterization and immunoregulatory activity were studied through DLS, Congo red, Scanning Electron Microscope, UV–Vis, HPGPC, FT-IR, Methylation, NMR, MTT, neutral red and enzyme linked immunosorbent assay. Results showed that VBCP2.5 was an acidic polysaccharide with a molecular weight of 674 kDa. Its monosaccharides composed of mannose, rhamnose, galacturonic acid, glucose, galactose and arabinose at a molar ratio of 1.72: 9.59: 57.63: 5.37: 6.71: 18.99. VBCP2.5 possessed micelle forming ability at 52.574 µg/mL and flexible chain conformation, as well as with a small size distribution ∼ 84.99 nm and positive charge in stimulated blood fluid and different from that in deionized water. The microtopography was characterized by irregular lamellar, dendritic, cylindrical or spherical aggregates, with folds and cracks on the surface. Structure analyses showed that VBCP2.5 characterized by high proportion of 1,4 linked-α-D-GalpA and a small fraction of RG-I, some other glycosidic linkages included 1,5 linked-α-L-Araf, 1,3,5 linked-α-L-Araf, 1,3,4 linked-Galp, 1,4,6 linked-Manp, t-α-L-Araf, t-β-D-Glcp and t-α-D-Galp were also comprised. VBCP2.5 exhibited immunomodulatory potential which included the promotion of phagocytosis, the release of NO and the secretion of TNF-α and IL-6 of RAW264.7 cells. The possible activation of macrophages by VBCP2.5 may be mediated through endocytosis pathway. Small size, positive charge, shape and flexible conformation may accelerate this process. The information gathered here could lead to new platform for comprehensive understand included primary structure, properties of nanoscale, and correlation with immunoregulation of polysaccharides.

Abstract Background Babesia is a protozoan parasite that infects red blood cells in some vertebrates. Some species of Babesia can induce zoonoses and cause considerable harm. As the largest immune organ in mammals, the spleen plays an important role in defending against Babesia infection. When infected with Babesia, the spleen is seriously injured but still actively initiates immunomodulatory responses. Methods To explore the molecular mechanisms underlying the immune regulation and self-repair of the spleen in response to infection, this study used data-independent acquisition (DIA) quantitative proteomics to analyse changes in expression levels of global proteins and in phosphorylation modification in spleen tissue after Babesia microti infection in mice. Results After mice were infected with B. microti, their spleens were seriously damaged. Using bioinformatics methods to analyse dynamic changes in a large number of proteins, we found that the spleen still initiated immune responses to combat the infection, with immune-related proteins playing an important role, including cathepsin D (CTSD), interferon-induced protein 44 (IFI44), interleukin-2 enhancer-binding factor 2 (ILF2), interleukin enhancer-binding factor 3 (ILF3) and signal transducer and activator of transcription 5A (STAT5A). In addition, some proteins related to iron metabolism were also involved in the repair of the spleen after B. microti infection, including serotransferrin, lactoferrin, transferrin receptor protein 1 (TfR1) and glutamate-cysteine ligase (GCL). At the same time, the expression and phosphorylation of proteins related to the growth and development of the spleen also changed, including protein kinase C-δ (PKC-δ), mitogen-activated protein kinase (MAPK) 3/1, growth factor receptor-bound protein 2 (Grb2) and P21-activated kinase 2 (PAK2). Conclusions Immune-related proteins, iron metabolism-related proteins and growth and development-related proteins play an important role in the regulation of spleen injury and maintenance of homeostasis. This study provides an important basis for the diagnosis and treatment of babesiosis.

As a treasure left over from Chinese traditional culture, martial arts have a long history and lasts for a long time. With the country’s promotion and support of martial arts culture, martial arts have also attracted more and more people’s attention. In order to carry forward the martial arts culture, the combination of martial arts and sports has formed a set of martial arts sports suitable for today’s students, such as martial arts aerobics. It is used as a class exercise for students, and basically, every student in the school has learned it and practiced it often. However, with the development of the times, it is difficult for today’s students to arouse students’ enthusiasm for martial arts sports for traditional martial arts sports. Artificial intelligence technology and virtual reality, as products of today’s digital age, attract the attention and use of students with their unique features. This also means that the reform of martial arts sports based on artificial intelligence and virtual reality technology is imperative in order to make more students regain their enthusiasm for martial arts sports. However, the specific impact of artificial intelligence and virtual reality on the physical and mental development of students in martial arts sports is a problem to be confirmed by research. Through in-depth research on artificial intelligence and virtual reality technology, this paper shows that artificial intelligence and virtual reality martial arts sports can increase the lung capacity of boys by about 14% and girls by 16%; the effect on physical fitness can increase the lower body strength of boys by 3% and the flexibility of girls by 30%; as for the impact on mental health, it can be concluded that the emotional and cognitive dimensions of boys and girls have increased by about 19% compared with the previous values.

Abstract Background Ticks are notorious blood-feeding arthropods that can spread a variety of deadly diseases. The salivary gland is an important organ for ticks to feed on blood, and this organ begins to develop rapidly when ixodid ticks suck blood. When these ticks reach a critical weight, the salivary glands stop developing and begin to degenerate. The expression levels of a large number of proteins during the development and degeneration of salivary glands change, which regulate the biological functions of the salivary glands. Furthermore, to the best of our knowledge, there are only a few reports on the role of molecular motor and TCA cycle-related proteins in the salivary glands of ticks. Results We used iTRAQ quantitative proteomics to study the dynamic changes in salivary gland proteins in female Haemaphysalis longicornis at four feeding stages: unfed, partially fed, semi-engorged and engorged. Using bioinformatics methods to analyze the dynamic changes of a large number of proteins, we found that molecular motor and TCA cycle-related proteins play an important role in the physiological changes of the salivary glands. The results of RNAi experiments showed that when dynein, kinesin, isocitrate dehydrogenase and citrate synthase were knocked down independently, the weight of the engorged female ticks decreased by 63.5%, 54.9%, 42.6% and 48.6%, respectively, and oviposition amounts decreased by 83.1%, 76.0%, 50.8%, and 55.9%, respectively, and the size of type III acini of females salivary glands decreased by 35.6%, 33.3%, 28.9%, and 20.0%, respectively. Conclusions The results showed that the expression of different types of proteins change in different characteristics in salivary glands during the unfed to engorged process of female ticks. Corresponding expression changes of these proteins at different developmental stages of female ticks are very important to ensure the orderly development of the organ. By analyzing these changes, some proteins, such as molecular motor and TCA cycle-related proteins, were screened and RNAi carried out. When these mRNAs were knocked down, the female ticks cannot develop normally. The research results provide a new protein target for the control of ticks and tick-borne diseases.

PurposeThis study aimed to develop and verify a multi-phase (MP) computed tomography (CT)-based radiomics nomogram to differentiate pancreatic serous cystic neoplasms (SCNs) from mucinous cystic neoplasms (MCNs), and to compare the diagnostic efficacy of radiomics models for different phases of CT scans.Materials and MethodsA total of 170 patients who underwent surgical resection between January 2011 and December 2018, with pathologically confirmed pancreatic cystic neoplasms (SCN=115, MCN=55) were included in this single-center retrospective study. Radiomics features were extracted from plain scan (PS), arterial phase (AP), and venous phase (VP) CT scans. Algorithms were performed to identify the optimal features to build a radiomics signature (Radscore) for each phase. All features from these three phases were analyzed to develop the MP-Radscore. A combined model comprised the MP-Radscore and imaging features from which a nomogram was developed. The accuracy of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration tests, and decision curve analysis.ResultsFor each scan phase, 1218 features were extracted, and the optimal ones were selected to construct the PS-Radscore (11 features), AP-Radscore (11 features), and VP-Radscore (12 features). The MP-Radscore (14 features) achieved better performance based on ROC curve analysis than any single phase did [area under the curve (AUC), training cohort: MP-Radscore 0.89, PS-Radscore 0.78, AP-Radscore 0.83, VP-Radscore 0.85; validation cohort: MP-Radscore 0.88, PS-Radscore 0.77, AP-Radscore 0.83, VP-Radscore 0.84]. The combination nomogram performance was excellent, surpassing those of all other nomograms in both the training cohort (AUC, 0.91) and validation cohort (AUC, 0.90). The nomogram also performed well in the calibration and decision curve analyses.ConclusionsRadiomics for arterial and venous single-phase models outperformed the plain scan model. The combination nomogram that incorporated the MP-Radscore, tumor location, and cystic number had the best discriminatory performance and showed excellent accuracy for differentiating SCN from MCN.

PurposeTo construct a novel radiogenomics biomarker based on hypoxic-gene subset for the accurate prognostic prediction of clear cell renal cell carcinoma (ccRCC).Materials and MethodsInitially, we screened for the desired hypoxic-gene subset by analysis using the GSEA database. Through univariate and multivariate cox regression hazard ratio analysis, survival-related hypoxia genes were identified, and a genomics signature was constructed in the TCGA database. Building on this, a hypoxia-gene related radiogenomics biomarker (prediction of hypoxia-genes signature by contrast-enhanced CT radiomics) was constructed in the TCIA-KIRC database by extracting features in the venous phase of contrast-enhanced CT images, selecting features using the mRMR and LASSO algorithms, and building logistic regression models. Finally, we validated the prognostic capability of the new biomarker for patients with ccRCC in an independent validation cohort at Huashan Hospital of Fudan University, Shanghai, China.ResultsThe hypoxia-related genomics signature consisting of five genes (IFT57, PABPN1, RNF10, RNF19B and UBE2T) was shown to be significantly associated with survival for patients with ccRCC in the TCGA database, delineated by grouping of the signature expression as either low- or high-risk. In the TCIA database, we constructed a radiogenomics biomarker consisting of 13 radiomics features that were optimal predictors of hypoxia-gene signature expression levels (low- or high-risk) in patients at each institution, that demonstrated AUC values of 0.91 and 0.91 in the training and validation groups, respectively. In the independent validation cohort at Huashan Hospital, our radiogenomics biomarker was significantly associated with prognosis in patients with ccRCC (p=0.0059).ConclusionsThe novel prognostic radiogenomics biomarker that was constructed achieved excellent correlation with prognosis in both the cohort of TCGA/TCIA-KIRC database and the independent validation cohort of Huashan hospital patients with ccRCC. It is anticipated that this work may assist in clinical preferential treatment decisions and promote the process of precision theranostics in the future.

Abstract Timely detection of liver fibrosis by X‐ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X‐ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X‐ray attenuation characteristics of the scanned matter. Herein, an X‐ray energy‐dependent attenuation strategy originated from bismuth (Bi)‐based nanoprobes (BiF3@PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3@PDA@HA can exhibit characteristic attenuation depending on different levels of X‐ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3@PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3@PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy‐dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging‐based disease diagnosis.

Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.

Functional miRNAs derived from the 5p or 3p arm of some miRNA duplexes have opposite roles in cancer progression. Here, the authors show that oncogenic miR-574-5p has greater preference in aggressive gastric cancer as compared with miR-574-3p and this arm preference is partly dependent on complementary targets mediated miRNA decay.

Summary: Growth hormone (GH) binds to its receptor (growth hormone receptor [GHR]) to exert its pleiotropic effects on growth and metabolism. Disrupted GH/GHR actions not only fail growth but also are involved in many metabolic disorders, as shown in murine models with global or tissue-specific Ghr deficiency and clinical observations. Here we constructed an adipose-specific Ghr knockout mouse model Ad-GHRKO and studied the metabolic adaptability of the mice when stressed by high-fat diet (HFD) or cold. We found that disruption of adipose Ghr accelerated dietary obesity but protected the liver from ectopic adiposity through free fatty acid trapping. The heat-producing brown adipose tissue burning and white adipose tissue browning induced by cold were slowed in the absence of adipose Ghr but were recovered after prolonged cold acclimation. We conclude that at the expense of excessive subcutaneous fat accumulation and lower emergent cold tolerance, down-tuning adipose GHR signaling emulates a healthy obesity situation which has metabolic advantages against HFD. : Physiology; Cellular Physiology; Endocrinology; Diabetology Subject Areas: Physiology, Cellular Physiology, Endocrinology, Diabetology

The walnut green husk has antibacterial, anti-oxidant, anti-inflammatory and other biological activities, but its lipid-lowering activity has not been reported. This study investigated the effects of walnut green husk extract (WGH) on lipid levels and gut bacteria flora in obese rats induced by high-fat diet. The results showed that WGH significantly reduced body weight gain, reversed liver TC, TG, LDL-C, HDL-C, MDA, ALT, AST and serum TC, TG, LDL-C, MDA, leptin levels, insulin resistance and glucose tolerance in high fat diet-induced obesity rats. Meanwhile, fat accumulation, hepatic steatosis and adipose tissue hypertrophy of HFD were reduced by WGH. 16S rRNA sequencing demonstrated that WGH dramaticlly reversed the disorders of gut bacteria flora HFD-induced, reduced the relative abundance of Fusobacteria, Firmicutes and enhanced the relative abundance of Bacteroidetes at the phylum level, reduced the relative abundance of and Peptostreptococcaceae at the family level, furthermore, reduced the relative abundance of Romboutsia, Lachnoclostridium and increased the relative abundance of Bacteroides at the genus level. In conclusion, these beneficial effects of WGH on reducing obesity and lipid disorders could be associated with the modulation of the gut bacteria.

For hundreds of years, Atractylodes chinensis (DC.) Koidz. (AK) has been widely used as a treatment for spleen and stomach diseases in China. The AK polysaccharides (AKPs) have been thought to be the important bioactive components. In this stud, the impacts of different extraction methods were analyzed. The differences between AKPs extracted by hot water extraction (HWE), AKPs extracted by ultrasonic extraction (UAE), and AKPs extracted by enzyme extraction (EAE) were compared in terms of yield, total carbohydrate content, molecular weight distribution, monosaccharide composition, and synergistic activity of the AKPs with apatinib were determined. The results indicated that the yield of the polysaccharide obtained from HWE was higher than that of UAE and EAE. However, activity assays indicated that UAE-AKPs and HWE-AKPs enhanced apoptosis of human gastric cancer cells (SGC-7901) treated with apatinib and UAE-AKPs showed the strongest synergistic activities. This is also in agreement with the fact that UAE-AKPs have a smaller molecular weight, β-configuration, and higher galactose content. These findings suggested that UAE is an efficient and environmentally friendly method for producing new polysaccharides from Atractylodes chinensis (DC.) Koidz. for the development of natural synergist and for the treatment of gastric cancer.

Platycodon grandiflorum is an edible and medicinal plant, and polysaccharides are one of its important components. To further improve the utilization rate of P. grandiflorum, we investigated the effects of four different extraction methods, including hot water, ultrasonic-assisted, acid-assisted, and alkali-assisted extractions, on the polysaccharides, which were named PG-H, PG-U, PG-C, and PG-A. The findings indicated that the extraction method had a significant impact on the yield, characteristics, and immunoregulatory activity. We observed that the yields decreased in the following order: PG-H, PG-U, PG-C, and PG-A. Galacturonic acid, glucose, galactose, and arabinose were the most prevalent monosaccharides in the four PGs. However, their proportions varied. In addition, the difference between the content of glucose and galacturonic acid was more significant. PG-U had the highest glucose content, whereas PG-C had the lowest. Galacturonic acid content was highest in PG-A, while the lowest in PG-U. The molecular weight decreased in the order of PG-U, PG-H, PG-C, and PG-A; the particle size was in the order of PG-U, PG-A, PG-H, and PG-C. Moreover, the extraction method had a great impact on immunoregulatory activity. The ability to stimulate the immune function of macrophages was as follows: PG-A > PG-C > PG-U > PG-H. The results indicated that PGs, with lower molecular weights and higher GalA content, exhibited better immune-stimulating activity. And more important the AAE method was a good way to extract polysaccharides from Platycodon grandiflorum for use as a functional product and immunological adjuvant.

(1) Background: To better carry out air pollution control and to assist in accurate investigations of air pollution, in this study, we fully explore the spatial distribution characteristics of air pollution complaint results and provide guidance for air pollution control by combining regional air monitoring data. (2) Methods: By selecting the air pollution complaint information in Beijing from 2019 to 2020, in this study, we extract the names and addresses of complaint points, as well as the complaint times and types by adopting the BERT (bidirectional encoder representations from transformers) + CRF (conditional random field) model deep learning method. Moreover, through further filtering and processing of the complaint points’ address information, we achieve address matching and spatial positioning of the complaint points, and realize the regional spatial representation of air pollution complaints in Beijing in the form of a heat map. (3) Results: The experimental results are compared and analyzed with the ranking data of total suspended particulate (TSP) concentration of townships (streets) in Beijing during the same period, indicating that the key areas of air pollution complaints have a high correlation with the key polluted township (street) areas. The distribution of complaints and the types of complaints in each township (street) differ according to the population density in each township (street), the level of education, and economic activity. (4) Conclusions: The results of this study show that the public, as the intuitive perceiver of air pollution, is sensitive to the air pollution situation at a smaller spatial scale; furthermore, complaints can provide guidance and reference for the direction of air pollution control and law enforcement investigations when coupled with geographical features and economic status.

Shikimic acid (SA) is a key intermediate in the aromatic amino-acid biosynthetic pathway, as well as an important precursor for synthesizing many valuable antiviral drugs. The asymmetric reduction of 3-dehydroshikimic acid (DHS) to SA is catalyzed by shikimate dehydrogenase (AroE) using NADPH as the cofactor; however, the intracellular NADPH supply limits the biosynthetic capability of SA. Glucose dehydrogenase (GDH) is an efficient enzyme which is typically used for NAD(P)H regeneration in biocatalytic processes. In this study, a series of NADPH self-sufficient whole-cell biocatalysts were constructed, and the biocatalyst co-expressing Bmgdh–aroE showed the highest conversion rate for the reduction of DHS to SA. Then, the preparation of whole-cell biocatalysts by fed-batch fermentation without supplementing antibiotics was developed on the basis of the growth-coupled l-serine auxotroph. After optimizing the whole-cell biocatalytic conditions, a titer of 81.6 g/L SA was obtained from the supernatant of fermentative broth in 98.4% yield (mol/mol) from DHS with a productivity of 40.8 g/L/h, and cofactor NADP+ or NADPH was not exogenously supplemented during the whole biocatalytic process. The efficient relay-race synthesis of SA from glucose by coupling microbial fermentation with a biocatalytic process was finally achieved. This work provides an effective strategy for the biosynthesis of fine chemicals that are difficult to obtain through de novo biosynthesis from renewable feedstocks, as well as for biocatalytic studies that strictly rely on NAD(P)H regeneration.

Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the lung in mice and investigated the metabolic alternations by analyzing the metabolome and the transcriptome, which were confirmed in breast cancer cells, mouse models, and patients' tissues. The effects and the mechanisms of nucleotide de novo synthesis in cancer metastasis were further evaluated in vitro and in vivo. In our study, we report an increased nucleotide de novo synthesis as a key metabolic hallmark in metastatic breast cancer cells and revealed that enforced nucleotide de novo synthesis was enough to drive the metastasis of breast cancer cells. An increased key metabolite of de novo synthesis, guanosine-5'-triphosphate (GTP), is able to generate more cyclic guanosine monophosphate (cGMP) to activate cGMP-dependent protein kinases PKG and downstream MAPK pathway, resulting in the increased tumor cell stemness and metastasis. Blocking de novo synthesis by silencing phosphoribosylpyrophosphate synthetase 2 (PRPS2) can effectively decrease the stemness of breast cancer cells and reduce the lung metastasis. More interestingly, in breast cancer patients, the level of plasma uric acid (UA), a downstream metabolite of purine, is tightly correlated with patient's survival. Our study uncovered that increased de novo synthesis is a metabolic hallmark of metastatic breast cancer cells and its metabolites can regulate the signaling pathway to promote the stemness and metastasis of breast cancer.

Summary: Xenopus laevis tolerate dehydration when their environments evaporate during summer months. Protein phosphorylation has previously shown to regulate important adaptations in X. laevis, including the transition to anaerobic metabolism. We therefore performed phosphoproteomic analysis of X. laevis to further elucidate the cellular and metabolic responses to dehydration. Phosphoproteins were enriched in cellular functions and pathways related to glycolysis/gluconeogenesis, the TCA cycle, and protein metabolism, among others. The prominence of phosphoproteins related to glucose metabolism led us to discover that the hypoxia-inducible PFKFB3 enzyme was highly phosphorylated and likely activated during dehydration, a feature of many cancers. Expression of the four transcript variants of the pfkfb3 gene was found all to be upregulated during dehydration, potentially due to the enrichment of hypoxia responsive elements in the pfkfb3 promoter. These results further support the role of anaerobic glycolysis during dehydration in X. laevis and elucidate a potential mechanism for its increased rate.

PurposeTo construct and verify a CT-based multidimensional nomogram for the evaluation of lymph node (LN) status in pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsWe retrospectively assessed data from 172 patients with clinicopathologically confirmed PDAC surgically resected between February 2014 and November 2016. Patients were assigned to either a training cohort (n = 121) or a validation cohort (n = 51). We acquired radiomics features from the preoperative venous phase (VP) CT images. The maximum relevance–minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) methods were used to select the optimal features. We used multivariable logistic regression to construct a combined radiomics model for visualization in the form of a nomogram. Performance of the nomogram was evaluated by the receiver operating characteristic (ROC) curve approach, calibration testing, and analysis of clinical usefulness.ResultsA Rad score consisting of 10 LN status-related radiomics features was found to be significantly associated with the actual LN status (P < 0.01). A nomogram that consisted of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status performed well in terms of predictive power in the training cohort (area under the curve, 0.92), and this was confirmed in the validation cohort (area under the curve, 0.95). The nomogram also performed well in the calibration test and decision curve analysis, demonstrating its potential clinical value.ConclusionA multidimensional radiomics nomogram consisting of Rad scores, CT-reported parenchymal atrophy, and CT-reported LN status may contribute to the non-invasive evaluation of LN status in PDAC patients.

Pressed degreased walnut meal (WM) was prepared from walnut kernel by cold-press deoil. It was rich in polyphenols with high activities of lowering lipids, antioxidation, anti-inflammation, and others, but the hypoglycemic activity has scarcely been reported. The purpose of this research was to investigate the preventive effect of the extracts of WM (WMP) on T2DM rats and the regulation of WMP on intestinal flora. Some results showed that WMP significantly held FBG, FINS and GSP, OGTT, the serum and hepatic TG, TC, HDL-C, LDL-C, AST, ALT, LPS, TNF-α, IL-6, and the hepatic MDA, CAT, SOD, as well as, prevented the pathological damage of the liver and the pancreas. The results of 16SrDNA sequencing demonstrated that WMP impeded the changes of intestinal flora in feces, mainly including Firmicutes, Bacteroidetes, and Proteobacteria. These indicated that WMP had promising effects on T2DM, which could be associated with the modulation of gut bacteria.

RNA-binding proteins (RBPs) regulate RNA activity and are implicated in haematopoietic malignancies, but their role in myeloid cell specification is unclear. Here, the authors show a role for the RBP KSRP in promoting granulocyte fate over monocyte fate through the biogenesis of miR-129 and a decrease in RUNX1.

The repetitive application of pesticides at high doses against Spodoptera litura Fabricius has resulted in development of pesticide resistance and harmful effects to the natural environmental. Hence, finding alternate pest control strategies, such as entomopathogenic fungi or their application in combination with other natural chemicals, is of great importance to solve the abovementioned problems. This study presents the toxic effects of Beauveria brongniartii and matrine (individual or in combination with each other) against tobacco cutworm (S. litura). Different matrine treatments caused a dose dependent increase in S. litura mortality at different time intervals. The biological parameters of B. brongniartii (germination rate and average daily mycelia growth) were not inhibited by different matrine treatments. Different conidial concentrations of B. brongniartii caused significantly different mortalities of 2nd instar S. litura larvae at different time intervals. Different combined treatments of B. brongniartii and matrine showed a significant synergistic effect against S. litura under laboratory and semi-field conditions. The current findings showed a strong synergistic action for combined application of B. brongniartii and matrine against S. litura. Our results will provide baseline information on combined application of entomopathogenic fungi and natural chemicals in integrated pest management programs against S. litura.

An increasing number of studies have found that athletes have a higher level of aggression than non-athletes. Anger is an important factor in the generation of aggressive behavior, and anger has been found to relate to both approach behavior and avoidance behavior. The present pilot study compared the aggression level of athletes and non-athletes using the Buss-Perry Aggression Questionnaire, and examined the responses of participants to anger-related stimuli using the manikin task, a paradigm that measures approach-avoidance behavior. In total, 15 athletes and 15 non-athletes finished the questionnaire and the manikin task, which included two conditions. In the anger approach condition, participants were asked to approach anger-associated words and to avoid neutral words. The instructions for the anger avoidance condition were the opposite (i.e., move away from the anger-associated words and toward the neutral words). Brain activity was recorded during the manikin task. Results showed that, compared with non-athletes, athletes had significantly higher physical aggression on the questionnaire. The athlete group showed significantly shorter reaction times in anger approach condition than anger avoidance condition. Theta oscillation activity induced during the anger approach condition was significantly lower than that during the anger avoidance condition in the athlete group. No significant correlation was found in present pilot study. These findings may suggest that when anger-related stimuli are present, athletes are more likely to approach, indicating stronger behavioral approach motivation that may result in aggressive behavior.

To certain degree, multi-objective optimization problems obey the law of symmetry, for instance, the minimum of one objective function corresponds to the maximum of another objective. To provide effective support for the multi-objective operation of the aerospace product shell production line, this paper studies multi-objective aerospace shell production scheduling problems. Firstly, a multi-objective optimization model for the production scheduling of aerospace product shell production lines is established. In the presented model, the maximum completion time and the cost of production line construction are optimized simultaneously. Secondly, to tackle the characteristics of discreteness, non-convexity and strong NP difficulty of the multi-objective problem, a knowledge-driven multi-objective evolutionary algorithm is designed to solve the problem. In the proposed approach, structural features of the scheduling plan are extracted during the optimization process and used to guide the subsequent optimization process. Finally, a set of test instances is generated to illustrate the addressed problem and test the proposed approach. The experimental results show that the knowledge-driven multi-objective evolutionary algorithm designed in this paper has better performance than the two classic multi-objective optimization methods.

The n-type doping of Ge is a self-limiting process due to the formation of vacancy-donor complexes (D _n V with n ⩽ 4) that deactivate the donors. This work unambiguously demonstrates that the dissolution of the dominating P _4 V clusters in heavily phosphorus-doped Ge epilayers can be achieved by millisecond-flash lamp annealing at about 1050 K. The P _4 V cluster dissolution increases the carrier concentration by more than three-fold together with a suppression of phosphorus diffusion. Electrochemical capacitance–voltage measurements in conjunction with secondary ion mass spectrometry, positron annihilation lifetime spectroscopy and theoretical calculations enabled us to address and understand a fundamental problem that has hindered so far the full integration of Ge with complementary-metal-oxide-semiconductor technology.

Yifei Tongluo (YFTL) is a traditional Chinese medicine (TCM) formulation which has been shown clinical efficacy in treatment of patients with multidrug-resistant tuberculosis in China. However, the underlying mechanisms of the effects of YFTL are lacking. This study investigated the effects of YFTL on immune regulation with a mouse lung infection model with Bacille Calmette-Guérin (BCG). We found that compared with untreated mice, the lung mycobacterial load in YFTL-treated mice was significantly reduced, accompanied by alleviated pulmonary inflammation with reduction of pro-inflammatory cytokines and increase of prostaglandin E2 (PGE2). Flow cytometry analyses showed that Th1 cells were significantly higher in the lungs of YFTL-treated mice at early infection time. The results suggest that YFTL-treatment down-regulates pulmonary inflammation, which facilitates a rapid infiltration of Th1 cells into the lungs. Moreover, the Th1 cells in the lungs were resolved faster at later time concomitant with increased the regulatory T cells (Tregs). The reduction of mycobacterial burden associated with improved tissue pathology, faster Th1 cell trafficking, and accelerated resolution of Th1 cells in the lungs of YFTL-treated mice indicates that YFTL improves mycobacterial clearance by maintaining lung homeostasis and dynamically regulating T cells in the lung parenchyma, and suggests that YFTL can be used as host-directed therapies that target immune responses to mycobacterial infection.