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Abstract Developing a facile and feasible strategy to fabricate thermally activated delayed fluorescence materials exhibiting full-color tunability remains an appealing yet challenging task. In this work, a general supramolecular strategy for fabricating thermally activated delayed fluorescence materials is proposed. Consequently, a series of host–guest cocrystals are prepared by electron-donating calix[3]acridan and various electron-withdrawing guests. Owing to the through-space charge transfer mediated by multiple noncovalent interactions, these cocrystals all display efficient thermally activated delayed fluorescence. Especially, by delicately modulating the electron-withdrawing ability of the guest molecules, the emission colors of these cocrystals can be continuously tuned from blue (440 nm) to red (610 nm). Meanwhile, high photoluminescence quantum yields of up to 87% is achieved. This research not only provides an alternative and general strategy for the fabrication of thermally activated delayed fluorescence materials, but also establishes a reliable supramolecular protocol toward the design of advanced luminescent materials.

Abstract Blocking immune checkpoint CD47/SIRPα is a useful strategy to engineer macrophages for cancer immunotherapy. However, the roles of CD47-related noncoding RNA in regulating macrophage phagocytosis for lung cancer therapy remain unclear. This study aims to investigate the effects of long noncoding RNA (lncRNA) on the phagocytosis of macrophage via CD47 and the proliferation of non-small cell lung cancer (NSCLC) via TIPRL. Our results demonstrate that lncRNA KCTD21-AS1 increases in NSCLC tissues and is associated with poor survival of patients. KCTD21-AS1 and its m6A modification by Mettl14 promote NSCLC cell proliferation. miR-519d-5p gain suppresses the proliferation and metastasis of NSCLC cells by regulating CD47 and TIPRL. Through ceRNA with miR-519d-5p, KCTD21-AS1 regulates the expression of CD47 and TIPRL, which further regulates macrophage phagocytosis and cancer cell autophagy. Low miR-519d-5p in patients with NSCLC corresponds with poor survival. High TIPRL or CD47 levels in patients with NSCLC corresponds with poor survival. In conclusion, we demonstrate that KCTD21-AS1 and its m6A modification promote NSCLC cell proliferation, whereas miR-519d-5p inhibits this process by regulating CD47 and TIPRL expression, which further affects macrophage phagocytosis and cell autophagy. This study provides a strategy through miR-519-5p gain or KCTD21-AS1 depletion for NSCLC therapy by regulating CD47 and TIPRL.

Abstract Mitochondrial diseases (MDs) were a large group multisystem disorders, attributable in part to the dual genomic control. The advent of massively sequencing has improved diagnostic rates and speed, and was increasingly being used as a first-line diagnostic test. Paediatric patients (aged

Robust millimeter-sized spherical particles with controlled compositions and microstructures hold promises of important practical applications. Here the authors develop a liquid marble method to facilely fabricate robust millimeter-sized supraparticles with controlled microstructures through the bottom-up assembly of silica nanoparticles.

The long-time behavior of highly elastic fibers in a shear flow is investigated experimentally and numerically. Characteristic attractors of the dynamics are found. It is shown that for a small ratio of bending to hydrodynamic forces, most fibers form a spinning elongated double helix, performing an effective Jeffery orbit very close to the vorticity direction. Recognition of these oriented shapes, and how they form in time, may prove useful in the future for understanding the time history of complex microstructures in fluid flows and considering processing steps for their synthesis.

Abstract Background The distant metastasis is the primary cause of cancer morbidity and mortality for bladder cancer (BLCA) paitents. All the recommended therapy for it largely depends on how far the cancer has invaded. It has been confirmed that epithelial to mesenchymal transition (EMT) is the leading reason for the BLCA metastasis which makes BLCA difficult to cure. The aim of the present study is to identify the BLCA-related genes that can be used as the new prognostic biomarker and treatment target, and to investigate the functional mechanisms of TEAD4 in EMT dysregulation. Methods The "limma" R package was used to identify the differentially expressed genes (DEGs) between the normal and the tumor samples from TCGA BLCA and GTEx databases. Kaplan–Meier and UniCox analysis were used to filter DEGs with prognostic value in BLCA. Step muti-Cox analysis was used to construct a prognostic risk score model based on clinical phenotype characters. Gene set enrichment analysis (GSEA) was performed to explore the possible molecular mechanisms affecting the prognosis in BLCA. Unsupervised hierarchical clustering analysis was performed to evaluate the effects of EMT process on the prognosis. Single-sample GSEA (ssGSEA) was used to calculate the correlation betweeen the expression of DEGs and EMT enrichment scores. TEAD4 expression and its association with pathological grading and survival were appraised in samples from TCGA dataset and BLCA tissue microarray. Colony formation assays and CCK8 assays were performed to study the changes in BLCA cell proliferation when the TEAD4 levels was down- or up-regulated in BLCA cells. Transwell and wound healing assays were utilized to analyze the impact of TEAD4 on the invasion and metastasis of the BLCA cells. Western Blot was carried out to detect the changes of EMT-related markers and the active molecules involved in PI3K/AKT signaling in BLCA cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted on the genes related to TEAD4 expression. 740Y-P (activator of PI3K/AKT pathway) and LY294002 (inhibitor of PI3K/AKT pathway) were applied to evaluate the contribution of PI3K/AKT signaling pathway in the EMT of BLCA cells. To examine the in vivo effect of TEAD4 on tumor metastasis, we designed a metastatic nude-mouse model by tail vein injection of TEAD4-knockdown BLCA cells. And PET/CT imaging was used to assess the extent of lung metastases. Results A total of 1592 DEGs were recognized, among which 4 DEGs have been identified as independent prognostic factors for BLCA, such as FASN, IGFL2, PLOD1 and TEAD4. TCGA BLCA samples were divided into significantly different low- and high-risk groups according to the median risk score; GSEA analysis showed that HALLMARK EMT pathway was the top enriched gene signature when compared high-risk and low-risk groups, which was also verified by unsupervised cluster analysis. EMT signature-derived ssGSEA scores demonstrated that TEAD4 had the most positive correlation with EMT process. In addition, TEAD4 expression was upregulated in TCGA BLCA samples and correlated with pT stage, tumor stage and tumor grade. Functional studies showed that TEAD4 knockdown via lentiviral TEAD4 shRNA inhibited cell migration and invasion in vitro and in vivo, with the reduced expression of EMT related markers in BLCA cell lines; the migration and invasion of TEAD4 knockdown cells could be restored by ectopic expression of TEAD4. Meanwhile, KEGG enrichment analysis of genes related to TEAD4 expression showed that enrichment was significantly related to PI3K/AKT pathway. The pathway inhibitor LY294002 blocked the TEAD4-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas the agonist 740Y-P rescued the decreased migration, invasion and EMT induced by TEAD4 knockdown. Conclusions TEAD4 is closely correlated with poor prognosis in BLCA and mediates its metastasis through regulating EMT via PI3K/AKT pathway, proving that TEAD4 is not only an effective biomarker for predicting the prognosis but also a great potential target for treatment of metastatic BLCA.

There is often obvious particle breakage for silica sand under high-stress, which will lead to the bearing capacity reduction and excessive settlement of the foundation. This paper focuses on the particle breakage characteristics of marine silica sand from the East China Sea under high-stress conditions. A series of conventional triaxial tests for silica sand, including consolidated drained (CD) and consolidated undrained (CU) shear tests, were conducted under the confining pressures in the range of 2–8 MPa to investigate the breakage rule during the shearing process. The developments of particle breakage index Br with axial strain ε1 and volumetric strain εv present hyperbolic and linear trends, respectively. A hyperbolic model was adopted to describe the relationship of Br and ε1 and the corresponding model parameters were obtained. The particle breakage index also has a good correlation with the input work per unit volume under various average stresses, regardless of the stress history. Furthermore, the relationship between the fractal dimension and the particle breakage was studied based on the particle size distribution curve. It is concluded that the fractal dimension increases in an up–convex hyperbolic trend with the increase of particle breakage index. The dividing radius for whether the silica sand particles exhibit the fractal features is determined as approximately 0.4 mm. This is anticipated to provide reference and supplementary test data for analyzing sand constitutive models/environments regarding particle crushing.

Controlling localization of multiple metal nanoparticles on a single support is at the cutting edge of designing innovatory cascade catalysts. Here, the authors report a multicompartmentalized mesoporous organosilica to spatially position different metal nanoparticles in intimate proximity for efficient sequential hydrogenation reactions.

Background: Buyang Huanwu decoction (BHD) is a traditional Chinese medicine herbal formula used for treating hypertension, particularly in the later stages of hypertension when it is associated with intracerebral hemorrhage. This study aims to investigate the treatment mechanism of BHD to provide a basis for its clinical application in hypertension treatment. Methods: Network pharmacology analysis and cell culture experiments were performed to explore the potential proteins and mechanisms of action of BHD against hypertension. Bioactive compounds related to BHD were screened, and relevant targets associated with hypertension and BHD were retrieved. Molecular docking technology was used to identify the effective signaling pathway based on the Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction network cores. Lastly, the effects and mechanisms of BHD on salt-sensitive hypertensive endothelial cells were investigated. Results: Ninety-three potential therapeutic targets for BHD and salt-sensitive hypertension were found to be closely associated with the PI3K/Akt/eNOS signaling pathway and oxidative stress. Cell experiments further indicated the pivotal role of endothelial cells in hypertension, and validation analysis showed that BHD significantly preserved cell morphology, suppressed oxidative stress reactions, activated the PI3K/Akt/eNOS signaling pathways, preserved normal endothelial cell function, and reduced cell apoptosis. Conclusion: BHD effectively activates the PI3K/Akt/VEGF signaling pathway, attenuates oxidative stress-induced injury in endothelial cells exposed to high salt levels, and mitigates apoptosis, supporting the use of traditional Chinese medicine BHD in the treatment of salt-sensitive hypertension. [ABSTRACT FROM AUTHOR]

Background: Current guidelines recommend bismuth‐containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth‐containing quadruple therapy for first‐line treatment of H. pylori infection. Methods: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment‐naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth‐containing quadruple therapies: esomeprazole 20 mg twice‐daily; bismuth 220 mg twice‐daily; amoxicillin 1000 mg twice‐daily; and tetracycline 500 mg three times daily (TET‐T) versus 500 mg four times daily (TET‐F). At least 6 weeks post‐treatment, a 13C‐urea breath test was performed to evaluate H. pylori eradication. Results: In total, 406 patients were randomly assigned to the two treatment groups. Intention‐to‐treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%–95.44%) versus 90.15% (183/203; 95% CI 86.05%–94.25%) (p = 0.0005) and per‐protocol eradication rates were 95.34% (184/193; 95% CI 92.36%–98.31%) versus 95.72% (179/187; 95% CI 92.82%–98.62%) (p = 0.0002) for the TET‐T and TET‐F group, respectively. TET‐T‐treated patients had a lower incidence of adverse effects than TET‐F‐treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. Conclusion: As a first‐line therapy for H. pylori infection, the eradication rate of the TET‐T therapy was noninferior to that of the TET‐F therapy while significantly reducing the incidence of adverse reactions. Trial Registration: ClinicalTrials.gov identifier: NCT05431075 [ABSTRACT FROM AUTHOR]

BackgroundThis study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively).MethodsWe comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs.ResultsTwo ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses.ConclusionThis work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.

The three application scenarios of 5G make forward higher requirements for network delay,bandwidth,connection and security,which drive 5G to sink the core capabilities of network,computing,storage and application to the edge of the network.The 5G base station which is closer to the terminal/user and has complete resources such as base station power,operation and maintenance will be the best choice for 5G edge computing deployment.Based on the multi-point 5G base station site resource and the architecture of edge computing deployment,the feasibility of multi-operator 5G edge computing shared deployment was studied,three feasible co-building and sharing schemes,such as base station infrastructure sharing,IaaS facility sharing and PaaS platform sharing were proposed.By coordinating the development needs of 5G edge computing and realizing the co-construction and sharing of edge computing,the construction cost and operation cost of edge computing can be greatly reduced,and the rapid scale development of edge computing can be realized,to build an intensive and efficient,economic and applicable,intelligent green,safe and reliable edge computing system.

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

Major power projects are normally critical nodes of the national power producing and transmission networks. However, the management of major power projects faces a variety of difficulties such as large scale, technical complexity, high quality standard, and frequent coordination. To improve the scientificity and effectiveness of the construction management of major power projects, a comprehensive framework of major power projects is established, which can be further decomposed into 8 subsystems and 28 indicators through system thinking. Then, by combining the G1 method with the cloud model, a new way of management performance evaluation of power projects is provided. Finally, taking the Kunliulong DC demonstration project as a case, the total performance evaluation result using the cloud model is between “excellent” and “great,” and more inclined to “excellent,” the performance of Schedule Control is close to the “outstanding” level, while the performance of Project Breakdown Structure is reaching the “good” level. The result shows that the established management evaluation system of major power engineering is relatively comprehensive, which can provide a reference for the realization of multiobjective and full-cycle overall management. Meanwhile, the exposed weak links in management, such as structural decomposition and environmental protection, should be highly valued and strictly controlled.

In this study, we aimed to identify an immune-related signature for predicting prognosis in cutaneous melanoma (CM). Sample data from The Cancer Genome Atlas (TCGA; n = 460) were used to develop a prognostic signature with 23 immune-related gene pairs (23 IRGPs) for CM. Patients were divided into high- and low-risk groups using the TCGA and validation datasets GSE65904 (n = 214), GSE59455 (n = 141), and GSE22153 (n = 79). The ability of the 23-IRGP signature to predict CM was precise, with the stratified high-risk groups showing a poor prognosis, and it had a significant predictive power when used for immune microenvironment and biological analyses. We subsequently established a novel promising prognostic model in CM to determine the association between the immune microenvironment and CM patient results. This approach may be used to discover signatures in other diseases while avoiding the technical biases associated with other platforms.

Background: The purpose of our study was to develop a prognostic risk model based on differential genomic instability-associated (DGIA) long non-coding RNAs (lncRNAs) of left-sided and right-sided colon cancers (LCCs and RCCs); therefore, the prognostic key lncRNAs could be identified.Methods: We adopted two independent gene datasets, corresponding somatic mutation and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Identification of differential DGIA lncRNAs from LCCs and RCCs was conducted with the appliance of “Limma” analysis. Then, we screened out key lncRNAs based on univariate and multivariate Cox proportional hazard regression analysis. Meanwhile, DGIA lncRNAs related prognostic model (DRPM) was established. We employed the DRPM in the model group and internal verification group from TCGA for the purpose of risk grouping and accuracy verification of DRPM. We also verified the accuracy of key lncRNAs with GEO data. Finally, the differences of immune infiltration, functional pathways, and therapeutic sensitivities were analyzed within different risk groups.Results: A total of 123 DGIA lncRNAs were screened out by differential expression analysis. We obtained six DGIA lncRNAs by the construction of DRPM, including AC004009.1, AP003555.2, BOLA3-AS1, NKILA, LINC00543, and UCA1. After the risk grouping by these DGIA lncRNAs, we found the prognosis of the high-risk group (HRG) was significantly worse than that in the low-risk group (LRG) (all p < 0.05). In all TCGA samples and model group, the expression of CD8+ T cells in HRG was lower than that in LRG (all p < 0.05). The functional analysis indicated that there was significant upregulation with regard to pathways related to both genetic instability and immunity in LRG, including cytosolic DNA sensing pathway, response to double-strand RNA, RIG-Ⅰ like receptor signaling pathway, and Toll-like receptor signaling pathway. Finally, we analyzed the difference and significance of key DGIA lncRNAs and risk groups in multiple therapeutic sensitivities.Conclusion: Through the analysis of the DGIA lncRNAs between LCCs and RCCs, we identified six key DGIA lncRNAs. They can not only predict the prognostic risk of patients but also serve as biomarkers for evaluating the differences of genetic instability, immune infiltration, and therapeutic sensitivity.

Phased array ultrasonic testing, an effective ultrasonic testing (UT) technology, has been widely used in steel inspection because of its high accuracy, sensitivity, and efficiency. However, as its application in as-cast magnesium alloys has just begun, more research is needed. Considering the important role of the gain compensation in quantifying defects in magnesium alloys by ultrasonic phased array technology, the effects of microstructure, the position, size, and overlap of defects, and boundary distance (distance from the defect position to the side surface of the test casting) on gain compensation of as-cast AZ80 and AZ31 magnesium alloys were studied. Results show the gain compensation increases with the increase of grain size. There is a strict linear positive correlation between gain compensation and defect depth, but such relationship no longer exists due to the defects overlap, orientation and boundary distance. In addition, there is a strict linear negative correlation between the gain compensation and defect size.

Abstract Metabolic reprogramming is a central hallmark of cancer. Therefore, targeting metabolism may provide an effective strategy for identifying promising drug targets for cancer treatment. In prostate cancer, cells undergo metabolic transformation from zinc‐accumulating, citrate‐producing cells to citrate‐oxidizing malignant cells with lower zinc levels and higher mitochondrial aconitase (ACO2) activity. ACO2 is a Krebs cycle enzyme that converts citrate to isocitrate and is sensitive to reactive oxygen species (ROS)‐mediated damage. In this study, we found that the expression of ACO2 is positively correlated with the malignancy of prostate cancer. Both zinc and p53 can lead to an increase in ROS. ACO2 can be a target for remodeling metabolism by sensing changes in the ROS levels of prostate cancer. Our results indicate that targeting ACO2 through zinc and p53 can change prostate cancer metabolism, and thus provides a potential new therapeutic strategy for prostate cancer.

Gaeumannomyces graminis var. tritici is a soil borne pathogenic fungus associated with wheat roots. The accurate quantification of gene expression during the process of infection might be helpful to understand the pathogenic molecular mechanism. However, this method requires suitable reference genes for transcript normalization. In this study, nine candidate reference genes were chosen, and the specificity of the primers were investigated by melting curves of PCR products. The expression stability of these nine candidates was determined with three programs-geNorm, Norm Finder, and Best Keeper. TUBβ was identified as the most stable reference gene. Furthermore, the exopolygalacturonase gene (ExoPG) was selected to verify the reliability of TUBβ expression. The expression profile of ExoPG assessed using TUBβ agreed with the results of digital gene expression analysis by RNA-Seq. This study is the first systematic exploration of the optimal reference genes in the infection process of Gaeumannomyces graminis var. tritici.

In the last few decades, the incidences of obesity and related metabolic disorders worldwide have increased dramatically. Major pathophysiology of obesity is termed “lipotoxicity” in modern western medicine (MWM) or “dampness-heat” in traditional Chinese medicine (TCM). “Dampness-heat” is a very common and critically important syndrome to guild clinical treatment in TCM. However, the pathogenesis of obesity in TCM is not fully clarified, especially by MWM theories compared to TCM. In this review, the mechanism underlying the action of TCM in the treatment of obesity and related metabolic disorders was thoroughly discussed, and prevention and treatment strategies were proposed accordingly. Hypoxia and inflammation caused by lipotoxicity exist in obesity and are key pathophysiological characteristics of “dampness-heat” syndrome in TCM. “Dampness-heat” is prevalent in chronic low-grade systemic inflammation, prone to insulin resistance (IR), and causes variant metabolic disorders. In particular, the MWM theories of hypoxia and inflammation were applied to explain the “dampness-heat” syndrome of TCM, and we summarized and proposed the pathological path of obesity: lipotoxicity, hypoxia or chronic low-grade inflammation, IR, and metabolic disorders. This provides significant enrichment to the scientific connotation of TCM theories and promotes the modernization of TCM.

Abstract Purpose: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. Methods: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. Results: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. Conclusions: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.

Gegen Qilian Decoction (GGQLD) is a well-established classic Chinese medicine prescription in treating nonalcoholic steatohepatitis (NASH). However, the molecular mechanism of GGQLD action on NASH is still not clear. This study aimed to assess the anti-NASH effect of GGQLD, and to explore its molecular mechanisms in vivo and in vitro. In HFD-fed rats, GGQLD decreased significantly serum triglyceride (TG), cholesterol (CHO), total bile acid (TBA), low-density lipoprotein (LDL), free fatty acid (FFA) and lipopolysaccharide (LPS) levels, increased levels of differentially expressed proteins (DEPs) Ahcy, Gpx1, Mat1a, GNMT, and reduced the expression of ALDOB. In RAW264.7 macrophages, GGQLD reduced the expression levels of inflammatory factors TNF-α and IL-6 mRNA, and diminished NASH by increasing differentially expressed genes (DEGs) CBS, Mat1a, Hnf4α and Pparα to reduce oxidative stress or lipid metabolism. The results of DEGs verification also showed that GGQLD up-regulated expressions of Hnf4α, Pparα and Cbs genes. In HepG2 cells, GGQLD decreased IL-6 levels and intracellular TG content, and inhibited FFA-induced expression of toll-like receptor 4 (TLR4). In summary, GGQLD abates NASH associated liver injuries via anti-oxidative stress and anti-inflammatory response involved inhibition of TLR4 signal pathways. These findings provide new insights into the anti-NASH therapy by GGQLD.

Three-dimensional dynamics of flexible fibers in shear flow are studied numerically, with a qualitative comparison to experiments. Initially, the fibers are straight, with different orientations with respect to the flow. By changing the rotation speed of a shear rheometer, we change the ratio A of bending to shear forces. We observe fibers in the flow-vorticity plane, which gives insight into the motion out of the shear plane. The numerical simulations of moderately flexible fibers show that they rotate along effective Jeffery orbits, and therefore the fiber orientation rapidly becomes very close to the flow-vorticity plane, on average close to the flow direction, and the fiber remains in an almost straight configuration for a long time. This ‘ordering’ of fibers is temporary since they alternately bend and straighten while tumbling. We observe numerically and experimentally that if the fibers are initially in the compressional region of the shear flow, they can undergo compressional buckling, with a pronounced deformation of shape along their whole length during a short time, which is in contrast to the typical local bending that originates over a long time from the fiber ends. We identify differences between local and compressional bending and discuss their competition, which depends on the initial orientation of the fiber and the bending stiffness ratio A . There are two main finding. First, the compressional buckling is limited to a certain small range of the initial orientations, excluding those from the flow-vorticity plane. Second, since fibers straighten in the flow-vorticity plane while tumbling, the compressional buckling is transient—it does not appear for times longer than 1/4 of the Jeffery period. For larger times, bending of fibers is always driven by their ends.

Background/Aims: Osteogenesis of periodontal ligament cells (PDLCS) is essential for alveolar bone repair. Varieties of factors have been found involved in the regulation of PDLCs osteoblast differentiation. Aim of this study was to identify microRNA as a regulator of the os-teogenic differentiation of PDLCs. Methods: The CD markers were analyzed by flow cytometry analysis. Osteoblast differentiation of PDLCs was induced by treatment with dexamethasone, β-glycerol phosphate and α-ascorbic acid. The expression of osteoblastic phenotype was evaluated after the induction by simultaneous monitoring of alkaline phosphatase activity, the expression of genes involved in osteoblastic differentiation by RT-qPCR and Western Blot, and mineralization at the same time. MicroRNA and NKIRAS2 expression was determined by RT-qPCR. Luciferase reporter assays were performed to test whether miR-125b is capable of interacting with the 3’UTR sequence of NKIRAS2. The possible signaling pathway was determined by Western Blot. Results: In this study, we found that the expression of miR-125b was down regulated during the process of ostoblast differentiation of PDLCs. When the expression of miR-125b was up regulated, the osteogenic differentiation of PDLCs was inhibited. During this process, the over-expressed miR-125b led to the activation of NF-κB. NF-κB inhibitor interacting RAS-like 2 (NKIRAS2) is one of target gene of miR-125b, and it is a regulator of NF-κB signaling that plays various roles in osteoblastic differentiation. We demonstrate thatmiR-125b is involved in osteogenic differentiation of PDLCs. Conclusion: Our data support the hypothesis that that miR-125b attenuates PDLCs osteoblastic differentiation by targeting NKIRAS2 and enhancing NF-κB signaling.

The ability to form density layering in a fluid in a simple and repeatable way is of relevance to a number of industrial and environmental processes. Here Xue et al. show formation of layers by simple injection of a hot liquid into a warm one at a predetermined critical pouring velocity.

Epigallocatechin gallate (EGCG) is associated with various health benefits. In this review, we searched current work about the effects of EGCG and its wound dressings on skin for wound healing. Hydrogels, nanoparticles, micro/nanofiber networks and microneedles are the major types of EGCG-containing wound dressings. The beneficial effects of EGCG and its wound dressings at different stages of skin wound healing (hemostasis, inflammation, proliferation and tissue remodeling) were summarized based on the underlying mechanisms of antioxidant, anti-inflammatory, antimicrobial, angiogenesis and antifibrotic properties. This review expatiates on the rationale of using EGCG to promote skin wound healing and prevent scar formation, which provides a future clinical application direction of EGCG.

In the field of ultrafast magnetism, i.e., subpicosecond or femtosecond time scales, the dynamics of magnetization can be described by the inertial Landau–Lifhitz–Gilbert equation. In terms of this equation, the intrinsic characteristics are investigated in detail for the theoretical limit of the magnetization reversal field. We can find that there is a critical value for the inertia parameter τ c, which is affected by the damping and anisotropy parameter of the system. When the inertial parameter factor τ < τ c, the limit value of the magnetization reversal field under the ultrafast magnetic mechanism is smaller than that of the fast magnetic mechanism. When τ > τ c, the limit value of the magnetization reversal field will be larger than the limit value under the fast magnetic mechanism. Moreover, it is important to point out that the limit value of the magnetization reversal field under the ultrafast magnetic mechanism decreases with the increasing inertial factor, as τ < τ c/2, which increases with inertial factor τ as τ > τ c/2. Finally, with the joint action of damping and anisotropy, compared with fast magnetism, we find that the limit value of the magnetization reversal field has rich variation characteristics, i.e., there is not only a linear and proportional relationship, but also an inverse relationship, which is very significant for the study of ultrafast magnetism. [ABSTRACT FROM AUTHOR]

Abstract A mathematical model of Dengue virus transmission between mosquitoes and humans, incorporating a control strategy of imperfect vaccination and vector maturation delay, is proposed in this paper. By using some analytical skills, we obtain the threshold conditions for the global attractiveness of two disease-free equilibria and prove the existence of a positive equilibrium for this model. Further, we investigate the sensitivity analysis of threshold conditions. Additionally, using the Pontryagin maximum principle, we obtain the optimal control strategy for the disease. Finally, numerical simulations are delivered to verify the correctness of the theoretical results, the feasibility of a vaccination control strategy, and the influences of the controlling parameters on the control and elimination of this disease. Theoretical results and numerical simulations show that the vaccination rate and effectiveness of vaccines are two key factors for the control of Dengue spread, and the manufacture of the Dengue vaccine is also architecturally significant.

Blood supply shortages, especially the shortage of rare blood types, threaten the current medical system. Research on stem cells has shed light on in vitro blood cell manufacturing. The in vitro production of universal red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has become the focus of transfusion medicine. To obtain O‐type Rh D‐negative blood, we developed O‐type Rh D‐negative human (h)iPSCs using homology‐directed repair (HDR)‐based CRISPR/Cas9. HuAiPSCs derived from human umbilical arterial endothelial cells and showing haematopoietic differentiation preferences were selected for gene modification. Guide RNAs (gRNAs) were selected, and a donor template flanked by gRNA‐directed homologous arms was set to introduce a premature stop code to RHD exon 2. CRISPR/Cas9 gene editing has resulted in the successful generation of an RHD knockout cell line. The HuAiPSC‐A1‐RHD−/− cell line was differentiated into haematopoietic stem/progenitor cells and subsequently into erythrocytes in the oxygen concentration‐optimized differentiation scheme. HuAiPSC‐A1‐RHD−/− derived erythrocytes remained positive for the RBC markers CD71 and CD235a. These erythrocytes did not express D antigen and did not agglutinate in the presence of anti‐Rh D reagents. In conclusion, taking the priority of haematopoietic preference hiPSCs, the HDR‐based CRISPR/Cas9 system and optimizing the erythroid‐lineage differentiation protocol, we first generated O‐type Rh D‐negative universal erythrocytes from RHD knockout HuAiPSCs. Its production is highly efficient and shows great potential for clinical applications. [ABSTRACT FROM AUTHOR]

Addition of particles to a viscoelastic suspension dramatically alters the properties of the mixture, particularly when it is sheared or otherwise processed. Shear-induced stretching of the polymers results in elastic stress that causes a substantial increase in measured viscosity with increasing shear, and an attractive interaction between particles, leading to their chaining. At even higher shear rates, the flow becomes unstable, even in the absence of particles. This instability makes it very difficult to determine the properties of a particle suspension. Here, we use a fully immersed parallel plate geometry to measure the high-shear-rate behavior of a suspension of particles in a viscoelastic fluid. We find an unexpected separation of the particles within the suspension resulting in the formation of a layer of particles in the center of the cell. Remarkably, monodisperse particles form a crystalline layer which dramatically alters the shear instability. By combining measurements of the velocity field and torque fluctuations, we show that this solid layer disrupts the flow instability and introduces a single-frequency component to the torque fluctuations that reflects a dominant velocity pattern in the flow. These results highlight the interplay between particles and a suspending viscoelastic fluid at very high shear rates. [ABSTRACT FROM AUTHOR]

Methylmercury is the most toxic form among mercury compounds in the aquatic ecosystem, and poses health risks to organisms through the food chain.The effective control of methylation processes of mercury is an active research field in environmental chemistry and toxicology.Selenium(Se) has a significant suppression effect on the methylation processes of mercury(Hg).Therefore, it will be beneficial to the prevention and control of mercury contamination to clarify the speciation characteristic of mercury and the interaction mechanisms between mercury and selenium in the aquatic ecosystem.Mercury toxicity is closely associated with the levels of selenium in organisms, the interaction between Hg and Se are mainly embodied in the formation of insoluble compounds to contribute mercury demethylation or methylmercury directly ruled out by inhibition of biological a selenium related enzyme, which inhibits the toxic effect of mercury.In this paper, the speciation and distribution characteristics of mercury and selenium in the aquatic ecosystem and their interaction mechanisms were reviewed.Meanwhile, the reasonable addition of selenium compounds into water will be an effective way to inhibit the methylation processes of mercury in organisms.The development direction for the studies of interaction mechanisms between mercury and selenium and its physical effects in organisms were also reviewed.

Abstract Due to its high theoretical energy density (2600 Wh kg−1), low cost, and environmental benignity, the lithium–sulfur (Li‐S) battery is attracting strong interest among the various electrochemical energy storage systems. However, its practical application is seriously hampered by the so‐called shuttle effect of the highly soluble polysulfides. Herein, a novel design of multifunctional sandwich‐structured polymer electrolyte (polymer/cellulose nonwoven/nanocarbon) for high‐performance Li‐S batteries is demonstrated. It is verified that Li‐S battery with this sandwich‐structured polymer electrolyte delivers excellent cycling stability (only 0.039% capacity decay cycle−1 on average exceeding 1500 cycles at 0.5 C) and rate capability (with a reversible capacity of 594 mA h g−1 at 4 C). These electrochemical performances are attributed to the synergistic effect of each layer in this unique sandwich‐structured polymer electrolyte including steady lithium stripping/plating, strong polysulfide absorption ability, and increased redox reaction sites. More importantly, even with high sulfur loading of 4.9 mg cm−2, Li‐S battery with this sandwich‐structured polymer electrolyte can deliver high initial areal capacity of 5.1 mA h cm−2. This demonstrated strategy here may open up a new era of designing hierarchical structured polymer electrolytes for high‐performance Li‐S batteries.

Kernel adaptive filtering (KAF) is an effective nonlinear learning algorithm, which has been widely used in time series prediction. The traditional KAF is based on the stochastic gradient descent (SGD) method, which has slow convergence speed and low filtering accuracy. Hence, a kernel conjugate gradient (KCG) algorithm has been proposed with low computational complexity, while achieving comparable performance to some KAF algorithms, e.g., the kernel recursive least squares (KRLS). However, the robust learning performance is unsatisfactory, when using KCG. Meanwhile, correntropy as a local similarity measure defined in kernel space, can address large outliers in robust signal processing. On the basis of correntropy, the mixture correntropy is developed, which uses the mixture of two Gaussian functions as a kernel function to further improve the learning performance. Accordingly, this article proposes a novel KCG algorithm, named the kernel mixture correntropy conjugate gradient (KMCCG), with the help of the mixture correntropy criterion (MCC). The proposed algorithm has less computational complexity and can achieve better performance in non-Gaussian noise environments. To further control the growing radial basis function (RBF) network in this algorithm, we also use a simple sparsification criterion based on the angle between elements in the reproducing kernel Hilbert space (RKHS). The prediction simulation results on a synthetic chaotic time series and a real benchmark dataset show that the proposed algorithm can achieve better computational performance. In addition, the proposed algorithm is also successfully applied to the practical tasks of malware prediction in the field of malware analysis. The results demonstrate that our proposed algorithm not only has a short training time, but also can achieve high prediction accuracy.

As the main driving force of LTE is data service, which cannot provide voice service. As for WCDMA operators, the CSFB needs to be deployed, before the VoLTE is prepared. The deployment issues of CSFB and impacts on the network were analyzed in detail. In the end, recommendations of CSFB deployment were given.

Nowadays, botnet is still a kind of severe threat on the Internet. It wastes lots of time for traditional passive monitoring approaches to collect enough evidence, to detect and react. Only after real malicious activities occur can we find the existence of botnet. An active probing approach was proposed based on botnet controller's communication pro-tocol fingerprint. Botnet samples including client and server were analyzed and the command and control protocol of the botnet were collected. The communication protocol fingerprint was also extracted from controller's response message and the host on the Internet was scanned with the communication protocol fingerprint. Active Spear active probing system was designed and implemented based on the approach. The system employs distributed architecture and IP used in the scanning is dynamic. The system supports to scan many botnets owning different types of protocols as their command and control protocols. The functional verification in the testing environment proves the effectiveness of the approach and the evaluation to scanning efficiency in the real network environment shows the ability that the system can finish task of scanning a large scale of IP section in an acceptable time.