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Well-resolved direct numerical simulations of turbulent open channel flows (OCFs) are performed for friction Reynolds numbers up to $Re_\tau =2000$ . Various turbulent statistics are documented and compared with the closed channel flows (CCFs). As expected, the mean velocity profiles of the OCFs match well with the CCFs in the near-wall region but diverge notably in the outer region. Interestingly, a logarithmic layer with Kárman constant $\kappa =0.363$ occurs for OCF at $Re_\tau =2000$ , distinctly different from CCF. Except for a very thin layer near the free surface, most of the velocity and vorticity variances match between OCFs and CCFs. The one-dimensional energy spectra reveal that the very-large-scale motions (VLSMs) with streamwise wavelength $\lambda _x>3 h$ or spanwise wavelength $\lambda _z>0.5 h$ contribute the most to turbulence intensity and Reynolds shear stress in the overlap and outer layers (where h is the water depth). Furthermore, the VLSMs in OCFs are stronger than those in CCFs, resulting in a slightly higher streamwise velocity variance in the former. Due to the footprint effect, these structures also have significant contributions to the mean wall shear stress, and the difference between OCF and CCF enlarges with increasing $Re_\tau$ . In summary, the free surface in OCFs plays an essential role in various flow phenomena, including the formation of stronger VLSMs and turbulent kinetic energy redistribution.

Purpose Intestinal polyps and metabolic syndrome (MetS) are closely related to the occurrence and development of colorectal cancer (CRC). This study aimed to provide a potential target for the mechanism analysis between the occurrence of intestinal polyps with metabolic abnormalities and the development of CRC. Methods In this study, we used clinical samples of patients with intestinal polyps with MetS (the control group was patients with common intestinal polyps), screened relevant pathways and genes by transcriptome sequencing and public database association analysis, and verified the targets by immunohistochemistry (IHC). Results Compared with the control group, 75 up-regulated and 61 down-regulated differential expressed genes (DEGs) were found in MetS patients with polyps. KEGG enrichment showed that these DEGs were mainly involved in cell cycle and mitotic pathways. By association with the public databases CTD and TCGA, 44 CRC-related hub genes were further screened, among which 8 genes showed the same difference trend in the RNA-Seq and GEPIA-COAD databases. Protein interaction analysis showed that PCP4, OLFM1, FN1, TGF-β3 were all related to MAPK signaling pathway. Tumor correlation analysis showed that FN1, PCP4 and TGF-β3 were higher risk genes but OLFM1 was lower risk gene. Immunohistochemical results showed that only OLFM1 was decreased in MetS patients with intestinal polyps. Conclusion In intestinal polyps with MetS, the expression of OLFM1 was reduced and may affect mitosis. Under the influence of MetS and the decrease of OLFM1, exosomes and NF-κB pathway may be involved in this process.

The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Lung adenocarcinoma (LUAD) remains a major reason of cancer-associated mortality globally, and there exists a lack of indicators for survival in LUAD patients. Therefore, it is clinically required to obtain a novel prognostically indicator for guiding clinical management. In this study, we established a circadian rhythm (CR) related signature by a combinative investigation of multiple datasets. The newly-established signature showed an acceptable ability to predict survival and could serve as an independent indicator for prognosis. Moreover, the newly-established signature was critically associated with tumor malignancy, including proliferation, invasion, EMT and metastasis. The newly-established signature was predictive of response to immune checkpoint blockade. Collectively, we established a CR-related gene signature that could forecast survival, tumor malignancy and therapeutic response; our findings could help guiding clinical management.

Purpose Long-leg-radiography (LLR) is commonly used for the measurement of lower limb alignment. However, limb rotations during radiography may interfere with the alignment measurement. This study examines the effect of limb rotation on the accuracy of measurements based on the mechanical and anatomical axes of the femur and tibia, with variations in knee flexion and coronal deformity. Methods Forty-five lower limbs of 30 patients were scanned with CT. Virtual LLRs simulating five rotational positions (neutral, ± 10$$^{\circ }$$ ∘ , and ± 20$$^{\circ }$$ ∘ internal rotation) were generated from the CT images. Changes in the hip–knee–ankle angle (HKA) and the femorotibial angle (FTA) were measured on each image with respect to neutral values. These changes were related to knee flexion and coronal deformity under both weight- and non-weight-bearing conditions. Results The measurement errors of the HKA and FTA derived from limb rotation were up to 4.84 ± 0.66$$^{\circ }$$ ∘ and 7.35 ± 0.88$$^{\circ }$$ ∘ , respectively, and were correlated with knee flexion (p < 0.001) and severe coronal deformity (p < 0.001). Compared with the non-weight-bearing position, the coronal deformity measured in the weight-bearing condition was 2.62$$^{\circ }$$ ∘ greater, the correlation coefficients between the coronal deformity and the deviation ranges of HKA and FTA were also greater. Conclusions Flexion and severe coronal deformity have a significant influence on the measurement error of lower limb alignment. Errors can be amplified in the weight-bearing condition compared with the non-weight-bearing condition. When using HKA and FTA to represent the mechanical axis and the anatomical axis on LLR, limb rotation impacts the anatomic axis more than the mechanical axis in patients with severe deformities. Considering LLR as the gold standard image modality, attention should be paid to the measurement of knee alignment. Especially for the possible errors derived from weight-bearing long-leg radiographs of patients with severe knee deformities.

Recently, intelligent cephalometric landmark detection systems that employ deep convolutional neural networks (DCNNs) have been widely developed. In this paper, we concentrate on two challenging difficulties of DCNNs based cephalometric landmark detection. First, previous DCNN methods usually decreased the resolution of high-resolution cephalometric images. Hence, the trained DCNNs missed the detailed local features of original images. Moreover, the detected landmarks’ locations were recovered using a fixed ratio, so location error was increased after recovery. Second, the performance of cephalometric landmark detection is dependent on DCNNs’ translational invariance because the target landmarks’ locations are influenced by any shift of the cephalometric images. However, modern DCNNs have limited translational invariance, and previous DCNN methods did not take translational invariance into consideration. In this paper, we developed the widely used two-stage framework to resolve the above two challenges. In the first stage, we train a global detection network, which receives the whole images as input, to generate candidate landmarks. In the second stage, we split the input image into patches and train a local refine network, which receives image patches as input, to refine the landmarks’ locations. The proposed local refine network can produce accurate landmarks’ locations because it entirely focuses on the detailed local features of high-resolution cephalometric images. The global detection network and local refine network are structured with translational invariance as their primary consideration. The proposed method achieved robust performance on a private dataset and the public Automatic Cephalometric X-ray Landmark Detection Challenge 2015 dataset.

Background The Mediator complex is an evolutionarily conserved multi-subunit protein complex that plays major roles in transcriptional activation and is essential for cell growth, proliferation, and differentiation. Recent studies revealed that some Mediator subunits formed nuclear condensates that may facilitate enhancer-promoter interactions and gene activation. The assembly, regulation, and functions of these nuclear condensates remain to be further understood. Results We found that Med15, a subunit in the tail module of the Mediator complex, formed nuclear condensates through a novel mechanism. Nuclear foci of Med15 were detected by both immunostaining of endogenous proteins and live cell imaging. Like Med1 foci and many other biomolecular condensates, Med15 foci were sensitive to 1, 6-Hexanediol and showed rapid recovery during fluorescence recovery after photobleaching. Interestingly, overexpressing DYRK3, a dual-specificity kinase that controls the phase transition of membraneless organelles, appeared to disrupt Med1 foci and Med15 foci. We identified two regions that are required to form Med15 nuclear condensates: the glutamine-rich intrinsically disordered region (IDR) and a short downstream hydrophobic motif. The optodroplet assay revealed that both the IDR and the C-terminal region of Med15 contributed to intracellular phase separation. Conclusions We identified that the Mediator complex subunit Med15 formed nuclear condensates and characterized their features in living cells. Our work suggests that Med15 plays a role in the assembly of transcription coactivator condensates in the nucleus and identifies Med15 regions that contribute to phase separation.

For investigating the compression strength characteristics of the soil reinforced with wheat straws and its deformation and failure mode, unconfined compression strength (UCS) tests were carried out by changing the content and length of wheat straws. The mesostructure changes in the reinforced and unreinforced soil specimens during loading were compared and analyzed by using the computed tomography (CT) scanning. The results showed that the relationship curves between the axial stress and the strain of both soil specimens were the stress-softening type. The addition of wheat straws could effectively control the radial deformation of the soil specimens and improve their UCS. With an increase in the axial strain, the ability of the reinforcement to resist deformation was gradually increased to weaken the tendency of forming cracks through a plane. With the optimum content and length of wheat straws, UCS of the soil specimens reached the maximum value which was about 2.1 times that of the unreinforced soil samples. The CT scanning results also showed that the reinforcement with wheat straws could restrict soil deformation and crack growth. These results can provide references for the application of soil reinforcement with wheat straws in the geotechnical engineering field such as slope protection and ecological slope protection.

Background Norovirus (NoV) is the main cause of non-bacterial acute gastroenteritis (AGE) outbreaks worldwide. From September 2015 through August 2018, 203 NoV outbreaks involving 2500 cases were reported to the Shenzhen Center for Disease Control and Prevention. Methods Faecal specimens for 203 outbreaks were collected and epidemiological data were obtained through the AGE outbreak surveillance system in Shenzhen. Genotypes were determined by sequencing analysis. To gain a better understanding of the evolutionary characteristics of NoV in Shenzhen, molecular evolution and mutations were evaluated based on time-scale evolutionary phylogeny and amino acid mutations. Results A total of nine districts reported NoV outbreaks and the reported NoV outbreaks peaked from November to March. Among the 203 NoV outbreaks, 150 were sequenced successfully. Most of these outbreaks were associated with the NoV GII.2[P16] strain (45.3%, 92/203) and occurred in school settings (91.6%, 186/203). The evolutionary rates of the RdRp region and the VP1 sequence were 2.1 × 10–3 (95% HPD interval, 1.7 × 10–3–2.5 × 10–3) substitutions/site/year and 2.7 × 10–3 (95% HPD interval, 2.4 × 10–3–3.1 × 10–3) substitutions/site/year, respectively. The common ancestors of the GII.2[P16] strain from Shenzhen and GII.4 Sydney 2012[P16] diverged from 2011 to 2012. The common ancestors of the GII.2[P16] strain from Shenzhen and previous GII.2[P16] (2010–2012) diverged from 2003 to 2004. The results of amino acid mutations showed 6 amino acid substitutions (*77E, R750K, P845Q, H1310Y, K1546Q, T1549A) were found only in GII.4 Sydney 2012[P16] and the GII.2[P16] recombinant strain. Conclusions This study illustrates the molecular epidemiological patterns in Shenzhen, China, from September 2015 to August 2018 and provides evidence that the epidemic trend of GII.2[P16] recombinant strain had weakened and the non-structural proteins of the recombinant strain might have played a more significant role than VP1.

Background Primary omental tumors are uncommon, and omental fibromas account for 2% of these tumors. Due to the low incidence of omental fibromas and the limited relevant literature, it is challenging for clinicians to make an accurate diagnosis of this condition, especially before surgery. Case summary A 30-year-old man was admitted to the hospital because of a left epididymal mass with vague discomfort for more than 1 mo. A physical examination was performed, and the findings showed that the epididymal mass may have entered the abdominal cavity. Pelvic computed tomography was performed in our hospital and revealed a left inguinal hernia with a mass in the hernial contents, and no masses were found in the left epididymis. A traditional inguinal hernia incision was made. Intraoperative hernia contents were found to be of the greater omentum, and a 2.5 cm-diameter mass was found at the distal end of the greater omentum. The scrotum and epididymis did not exhibit other masses. Then, the mass of the greater omentum was excised. Intraoperative frozen pathological examination suggested a spindle cell tumor. The postoperative pathological examination suggested that the mass was an omental angiofibroma. Postoperatively, the patient recovered well and was discharged. Outpatient re-examinations were performed at 1 mo and half a year after the operation and showed no obvious abnormalities. Conclusion Due to the low morbidity rate associated with and latent nature of omental tumors, these tumors are difficult to diagnose preoperatively; thorough medical history taking, detailed physical examinations, and necessary imaging auxiliary examinations can help clinicians diagnose and treat these cases.

Postnatal colonization and development of the gut microbiota is linked to health and growth. A comprehensive understanding of the postnatal compositional changes and development of the microbial community is helpful to understand the gut health and improve the survival rate of South China tiger cubs (Panthera tigris amoyensis). Fecal samples from three tiger cubs were collected on the day of birth in 2018 (June 17–21 [G0], July 18 [G1], July 31 [G2], and August 7 [G3]). The 16S rRNA genes of the fecal microflora were sequenced. Results showed that 38 phyla, 58 classes, 134 orders, 272 families, and 636 genera of bacteria from 3,059 operational taxonomic units were identified from 12 fecal samples. The diversity and abundance of species of group G0 were significantly higher (p < 0.05 or 0.01) than those of groups G2 and G3. The predominant phylum was Proteobacteria in groups G0 and G1 (38.85% and 48%, respectively) and Firmicutes in groups G2 and G3 (71.42% and 75.29%, respectively). At the phylum level, the abundance of Deinococcus-Thermus was significantly decreased in groups G1, G2, and G3 as compared to group G0 (p < 0.05), while that of Firmicutes was significantly increased in groups G2 and G3 (p < 0.05). At the genus level, the abundance of Faecalibacterium, Ralstonia, and unidentified Rickettsiales was significantly decreased in groups G1, G2, and G3 as compared with group G0 (p < 0.05), while that of Pseudomonas was significantly decreased in groups G2 and G3 (p < 0.05). The composition and structure of fecal microbiota of South China tiger cubs changed after birth.

The mechanical microenvironment affects the morphology and mechanical properties of cells, and it also plays an important role in cell functions. Pluripotent stem cells (PSCs) grow as multicellular colonies, and the coupling effects of cell–cell and cell-extracellular matrix interactions are complex but necessary for the formations and functions of tissues. This paper uses the finite element method to establish a three-dimensional calculation model of a pair of deformed PSCs in contact with each other and considers the growth and depolymerization of actin filaments. Then the effects of substrate stiffness on the morphology of cells and nuclei and the rearrangement of cytoskeleton are demonstrated. As the substrate becomes softer, the nuclei become loose and round, and the actin filaments will be assembled at a lower level, which could promote the formation of compacted cell colony while having a positive effect on maintaining pluripotency and inducing reprogramming efficiency. In addition, stronger activation of cytoskeleton contractility will compress the cytoplasm and nuclei. The cell mechanics model proposed in this paper provides a strategy for studying the cell morphology and cytoskeleton response of the two-cell system under different biophysical stimuli, and also lays the foundation for the further research on more mechanical factors of cell pluripotency.

In this study, we investigated a means to improve the robustness of deep network training on visual recognition tasks without sacrificing accuracy. The contribution of this work can reduce the dependence on model decay to gain a strong defense against malicious attacks, especially from adversarial samples. There are two major challenges in this study. First, the model defense capability should be strong and improved over the training stage. The other is that the degrading of the model performance must be minimized to ensure visual recognition performance. To tackle these challenges, we propose active dropblock (ActDB) by incorporating active learning into a dropblock. Dropblock effectively perturbs the feature maps, thus enhancing the invulnerability of gradient-based adversarial attacks. In addition, it selects an optimal perturbation solution to minimize the objective loss function, thereby reducing the model degradation. The proposed organic integration successfully solved the model robustness and accuracy simultaneously. We validated our approach using extensive experiments on various datasets. The results showed significant gains compared to state-of-the-art methods.

Pancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors. 4.1R has been reported to suppress the anti-tumor activity of T cell responses. In this study, we investigated the anti-tumor activity of 4.1R deletion in natural killer group 2D (NKG2D)-CAR T cells against PC. The CAR T cells were obtained by transfecting T cells with lentiviral vector carrying NKG2D-CAR, NC-NKG2D-CAR, or KD2-NKG2D-CAR. In vitro, NKG2D-CAR T cells showed higher cytotoxicity than Mock T cells. However, compared to NKG2D-CAR T cells, furtherly higher cytotoxicity against PC cells in a dose-dependent manner was found in KD2-NKG2D-CAR T cells. In addition, the proliferation rate and cytotoxic activity of KD2-NKG2D-CAR T cells were significantly higher than those of NKG2D-CAR T cells. Besides, the inhibitory receptors PD-1 and TIM-3 were expressed in lower level on KD2-NKG2D-CAR T cells. In vivo, KD2-NKG2D-CAR T cells suppressed tumor growth more effectively in a xenograft model compared to NKG2D-CAR T cells. Mechanistically, 4.1R regulated CAR T cell function via activating ERK signaling pathway. Therefore, the study provides a new idea to enhance the anti-tumor efficiency of CAR T therapy.

The application of heterogeneous catalysts in dimethyl carbonate (DMC) synthesis from methanol is hindered by low activation efficiency of methanol to methoxy intermediates (CH3O*), which are the key intermediates for DMC generation. Herein, a catalyst of alkali metal K anchored on the CuO/ZnO oxide is rationally designed for offering Lewis acid-base pairs as dual active centers to improve the activation efficiency of methanol. Characterizations of CO2-TPD，XPS and DRIFTS revealed that the addition of Lewis base K observably boosted the dissociation of methanol and combined with Lewis acid CuO/ZnO oxide to stably adsorb the formed CH3O*, thus synergistically promoted the transesterification. Finally, the CuO/ZnO-9%K2O catalyst exhibited the optimal catalytic activity, achieving a high yield of 74.4% with an excellent selectivity of 98.9% for DMC at a low temperature of 90 °C. The strategy of constructing Lewis acid-base pairs provides a reference for the design of heterogeneous catalysts.

In practical applications, multi-view data depicting objectives from assorted perspectives can facilitate the accuracy increase of learning algorithms. However, given multi-view data, there is limited work for learning discriminative node relationships and graph information simultaneously via graph convolutional network that has drawn the attention from considerable researchers in recent years. Most of existing methods only consider the weighted sum of adjacency matrices, yet a joint neural network of both feature and graph fusion is still under-explored. To cope with these issues, this paper proposes a joint deep learning framework called Learnable Graph Convolutional Network and Feature Fusion (LGCN-FF), consisting of two stages: feature fusion network and learnable graph convolutional network. The former aims to learn an underlying feature representation from heterogeneous views, while the latter explores a more discriminative graph fusion via learnable weights and a parametric activation function dubbed Differentiable Shrinkage Activation (DSA) function. The proposed LGCN-FF is validated to be superior to various state-of-the-art methods in multi-view semi-supervised classification.

Background With the application of immune checkpoint inhibitors (ICIs) in cancer treatment, more and more attention has been paid to checkpoint inhibitor-related pneumonitis (CIP), which requires a better understanding of its clinical characteristics and therapeutic effects. Methods The clinical and imaging data of 704 patients with non-small cell lung cancer (NSCLC) who received immunotherapy were analyzed retrospectively; the clinical characteristics of CIP were summarized, and the therapeutic regimens and effects of the patients were summarized. Results 36 CIP patients were included in the research. The most common clinical symptoms were cough, shortness of breath and fever. The CT manifestations were summarized as follows: Organizing pneumonia (OP) in 14 cases (38.9%), nonspecific interstitial pneumonia (NSIP) in 14 cases (38.9%), hypersensitiviy pneumonitis(HP) in 2 cases (6.3%), diffuse alveolar damage in 1 case (3.1%) and atypical imaging manifestations in 5 cases (13.9%). 35 cases received glucocorticoid therapy, 6 patients were treated with gamma globulin and 1 patient was treated with tocilizumab. There were no deaths in CIP G1-2 patients and 7 deaths occured in CIP G3-4 patients. 4 patients were treated again with ICIs. Conclusion We found that glucocorticoid 1–2 mg/kg was effective for most patients with moderate to severe CIP, and a few patients with hormone insensitivity needed early immunosuppressive therapy. A few patients can be rechallenged with ICIs, but CIP recurrence needs to be closely monitored.

Hydrolysis plays an imperative role in the abiotic transformation process of antibiotics in aqueous solutions. However, little information is available on the hydrolysis process of spectinomycin (an aminocyclitol antibiotic). This study systematically investigated the spectinomycin hydrolysis kinetics and mechanisms under different pH via experiments and density functional theory (DFT) computation. Hydrolysis was first conducted in a pure water system under pH of 4.0-9.0 and temperature of 25 °C, 50 °C and 70 °C, respectively. Results showed that hydrolysis was highly dependent on pH and temperature. When pH 6.0, spectinomycin hydrolysis was accelerated by the catalysis of OH

Background Wheat root-associated microbes play an indispensable role in helping plants obtain phosphorus (P) from soil. However, it is not clear how the effects of soil P on microorganisms vary with growth stage and variety. Therefore, revealing the interactive effects of soil P content, growth stage and variety on wheat root-associated microorganisms, which is important for further improving the P absorption strategy of plants. Methods Three wheat varieties were selected for pot experiment under three levels of soil P content, and sampling at seedling, flowering and mature stage, respectively. Using 16S rRNA gene profiling, we investigated the relative contribution of compartment niche, growth stage, variety and soil P content and their interaction effects on wheat root-associated prokaryotic communities. Results Wheat root-associated prokaryotic community assembly was mainly shaped by compartment niches. For each compartment niche, growth stage had higher contribution to the variations of prokaryotic communities than soil P content and wheat variety. The effects of P content on the prokaryotic communities varied by growth stage and variety. Meanwhile, the effects of wheat variety were also influenced by growth stage and soil P content. It is worth mentioning that low P content exacerbated the variation of prokaryotic communities among varieties. Conclusions This study revealed the interaction of host selection and soil P content on root-associated prokaryotic communities. The effects of soil P on wheat root-associated prokaryotic communities are dependent on P content, growth stage and variety. Our study provides a fundamental understanding on the relationship between soil P content and microorganisms.

Background Symptomatic intracranial artery stenosis (ICAS) is a significant worldwide economic and great threat to public health. Currently, little is known about the accurate status of the efficient and tolerable dose of dual antiplatelet therapy (DAPT) as the mainstay treatment for ICAS. The aim of this study is to evaluate the efficacy and safety of aspirin plus clopidogrel in small doses for the treatment of symptomatic ICAS in the elderly. Methods This research included 142 older adults with symptomatic ICAS who were enrolled between April 2013 and April 2018. They were split into two groups: 73 patients in the lower dose group who received 75 mg of aspirin daily and 50 mg of clopidogrel daily, and 69 patients in the usual group who received 100 mg of aspirin daily and 75 mg of clopidogrel daily. Results Ages of 142 patients ranged from 60 to 81, with a mean of 70.9 ± 6.4. 58 participants were with IS and 84 were with TIA. A total of 132 patients were followed up. The low-dose group had a lower recurrence risk of ischemic stroke (IS) or transient ischaemic attack (TIA) than the conventional group at 1-year and 2-year follow-up, as well as a reduced frequency of adverse events and gastrointestinal injury (P P > 0.05). Conclusion The efficacy and safety of low-dose aspirin combined with clopidogrel were significantly better than those of ordinary dose within 24 months in elderly patients with symptomatic ICAS. However, the small size of this study limits the validity of the results.

Nano-boron, as a potential high-energy additive due to its high calorific value, is widely studied in propellants, explosives, and thermites. However, the unexpected agglomeration of surface oxidation hinders its further application, especially in the casting of energetic materials. The fluorine-modified nano-boron nB@F2603 and nB@F2603@CL-20 preagglomerated microspheres were prepared by electrospray to improve the ignition and combustion reactions and the rheological properties of boron-containing casting systems. Sphericity microspheres could be obtained by controlling the voltage and propulsion rate. The morphology and elemental distribution of the microspheres were characterized by the scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffractometer (XRD). Results showed that the particle size of the microspheres ranged from 4 to 14 µm. Boron, fluorine and nitrogen were uniformly distributed on the surface of the microspheres. XRD results showed that CL-20 in nB@F2603@CL-20 microspheres was β-crystal. The thermal reaction properties were studied by differential scanning calorimetry, thermogravimetry and mass spectrometry (TG-DSC-MS), oxygen bomb calorimeter, laser ignition, and volume combustion cell test. Results showed that F2603 could significantly promote the ignition and combustion of nano-boron, causing higher energy release and pressurization rates, and lower ignition temperature. Adding CL-20 to the microspheres could also greatly promote the reaction rates and energy release. The hydrophobicity and corrosion resistance of the structures were also studied, and results showed that the preagglomerated microspheres had good stabilities. Therefore, fluorine-containing nB@F2603 and nB@F2603@CL-20 microspheres might be used in composite energetic materials, replacing nano-boron.

Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.

In our previous work, we isolated a novel bisphenol named capillarisenol C (Cap C) from Artemisia capillaris. Preliminary studies indicated potential anti-hepatocellular carcinoma (HCC) activity. However, its mechanism remains unclear. In this study, we aimed to investigate the function and molecular mechanism of the anti-HCC activity of Cap C. First, We evaluated the inhibitory effect of Cap C on the viability of HepG2 and Huh7 cells using CCK8 assays. The results showed that Cap C sharply reduced the viability of HepG2 and Huh7 cells in a time- and concentration-dependent manner, however, lenvatinib (clinical drugs for the treatment of HCC) had no obvious growth inhibitory effect on HepG2 and Huh7 cells at the corresponding concentration. By calculation, the half maximal inhibitory concentrations (IC50) of Cap C were 8.58 and 4.96 µM for for HepG2 and Huh7 cells at 48 h. Then, we investigated its autophagic effects on liver cancer cells using immunofluorescence staining and CRISPR/Cas9 assays. To study the mechanism of Cap C, we used quantitative PCR and western blotting. We found that Cap C effectively inhibited the proliferation of HepG2 cells and increased MAP1LC3-II expression. Moreover, Cap C–induced cell death was attenuated by autophagy-related gene ATG7 knockdown. Mechanistic studies showed that Cap C significantly promoted the expression of endoplasmic reticulum (ER) stress–related proteins. Our results suggest that Cap C may lead to autophagic HCC cell death by inducing ER stress.

Background: Racial differences in metabolomic profiles may reflect underlying differences in social determinants of health by self-reported race and may be related to racial disparities in coronary heart disease (CHD) among women in the United States. However, the magnitude of differences in metabolomic profiles between Black and White women in the United States has not been well-described. It also remains unknown whether such differences are related to differences in CHD risk. Methods: Plasma metabolomic profiles were analyzed using liquid chromatography-tandem mass spectrometry in the WHI-OS (Women’s Health Initiative-Observational Study; 138 Black and 696 White women), WHI-HT trials (WHI-Hormone Therapy; 156 Black and 1138 White women), MESA (Multi-Ethnic Study of Atherosclerosis; 114 Black and 219 White women), JHS (Jackson Heart Study; 1465 Black women with 107 incident CHD cases), and NHS (Nurses’ Health Study; 2506 White women with 136 incident CHD cases). First, linear regression models were used to estimate associations between self-reported race and 472 metabolites in WHI-OS (discovery); findings were replicated in WHI-HT and validated in MESA. Second, we used elastic net regression to construct a racial difference metabolomic pattern (RDMP) representing differences in the metabolomic patterns between Black and White women in the WHI-OS; the RDMP was validated in the WHI-HT and MESA. Third, using conditional logistic regressions in the WHI (717 CHD cases and 719 matched controls), we examined associations of metabolites with large differences in levels by race and the RDMP with risk of CHD, and the results were replicated in Black women from the JHS and White women from the NHS. Results: Of the 472 tested metabolites, levels of 259 (54.9%) metabolites, mostly lipid metabolites and amino acids, significantly differed between Black and White women in both WHI-OS and WHI-HT after adjusting for baseline characteristics, socioeconomic status, lifestyle factors, baseline health conditions, and medication use (false discovery rate P trend =0.02), independent of self-reported race and known CHD risk factors. In race-stratified analyses, the RDMP-CHD associations were more pronounced in White women. Similar patterns were observed in Black women from the JHS and White women from the NHS. Conclusions: Metabolomic profiles significantly and substantially differ between Black and White women and may be associated with CHD risk and racial disparities in US women.

Isoginkgetin (ISO), a natural biflavonoid, exhibited cytotoxic activity against several types of cancer cells. However, its effects on hepatocellular carcinoma (HCC) cells and mechanism remain unclear. Here, we revealed that ISO effectively inhibited HCC cell proliferation and migration in vitro. LC3-II expression and autophagosomes were increased under ISO treatment. In addition, ISO-induced cell death was attenuated by treatment with chloroquine or knockdown of autophagy-related genes (

To improve the condensed-phase reaction rate of ε-CL-20, polydopamine (PDA)–nickel complex-coated multiwalled carbon nanotubes (CNTs) have been prepared and used as combustion catalysts. The PDA–Ni complex has been prepared and in situ coprecipitated with ε-CL-20 by an antisolvent crystallization process in its dimethyl sulfoxide (DMSO) solution. It has been shown that crystalline CL-20 composites included with PDA–Ni complexes are polygon-shaped with a smooth surface and an average diameter of 10–15 μm, whereas it is 140 μm for raw ε-CL-20 crystals. The catalytic reactivity of the complex on thermolysis of CL-20 has been investigated using the differential scanning calorimetry (DSC) and thermogravimetry (TG)-coupled Fourier transform infrared (FT-IR) spectroscopy technique. It has been found that CNT@PDA–Ni complexes have catalytic effects on the decomposition of ε-CL-20 by decreasing/shifting of the exothermic peak from Tp = 240.1 to 238.7 °C. The FT-IR spectra of CL-20 decomposition products under the effect of the catalyst predominantly show peaks at 1274, 1644 and 1596, 1912, 2265, and 1956–1800 cm–1, indicating the presence of fragments with N2O, NO2, NO, HNCO, and NO/CO, respectively. The change in the ε-CL-20 decomposition mechanism should be attributed to the catalytic action of CNT, decreasing the formation of NO2. Also, under the effect of the carbon-based catalyst, the HNCO formation was detected at another temperature in comparison with raw CL-20, with peak absorption at 224.1 vs 232.3 °C and the evolution was completed at 250.8 vs 246.2 °C, respectively.