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Aiming at the problems existing in current electric energy replacement, such as the random energy fluctuation of the power grid, the energy storage of the power grid and the consumption of new energy, electromagnetic coupling heating technology and methods based on power frequency high power is proposed. According to the theory of electromagnetic induction heating, Maxwell’s equations are used to establish a three-dimensional electromagnetic field simulation model, determining the size of the core and the windings, and completing the structural design of the heater. Based on the simulation model of electromagnetic coupling heater, the back electromotive force of the primary winding, the induced current of the secondary winding, the B–H curve field diagram of the core, and the J-field diagram of the secondary winding are analyzed to explore heating efficiency of the heater and verify the correctness of electromagnetic coupling heating mechanism. The relationship between the coupling gap, the number of heat dissipation rings, and the air gap and heating efficiency of the heater was further explored, and the model structure of the heater was optimized according to the variation rules so that heating efficiency of the heater reached more than 99%. The electromagnetic coupling heater achieves high efficiency, cleanliness and low carbon, and power frequency high power, which is of great significance to the renewal of electric heater in the future.

In this paper, MoS2 nanosheets were prepared and deposited on BiOBr microflowers to fabricate MoS2/BiOBr heterojuncitons through deposition-hydrothermal strategy. The SEM and TEM images evidenced that few-layer MoS2 were grafted on BiOBr surface to yield 3D sheet-packed MoS2/BiOBr heterostructures. The obtained MoS2/BiOBr samples exhibited tremendous enhanced catalytic activity in comparison with pure BiOBr and the degradation rate reached 92.96% and 90.31% for tetracycline and levofloxacin degradation, respectively. The remarkably enhanced performance could be attributed to the synergistic effect of strong visible-light harvesting ability and the formation of heterojunction between MoS2 and BiOBr. The reactive species capturing experiments evidenced that photo-generated holes and ⋅OH radicals played the dominant roles in the whole photocatalytic decomposition process. A plausible mechanism for the enhanced photocatalytic capability was also proposed.

MicroRNAs (miRNAs) have been recognized as possible biomarkers for Alzheimer's disease (AD). MiR-142-5p has been reported to be abnormally expressed in brain tissues. However, the role of miR-142-5p in AD pathogenesis keeps unclear. This study aimed to investigate the effect of miR-142-5p on the learning and memory of AD rats via regulation of protein tyrosine phosphatase nonreceptor type 1 (PTPN1)-mediated protein kinase B (Akt) pathway.The AD model was established by injection of AβOverexpressed miR-142-5p, down-regulated PTPN1 and inactivated Akt pathway were exhibited in AD. MiR-142-5p targeted PTPN1 to mediate Akt pathway. Reduced miR-142-5p and elevated PTPN1 improved the behavior of AD rats. MiR-142-5p targeted PTPN1 to effectively inhibit Aβ formation and abnormal phosphorylation of p-tau protein, suppress the inflammation in the brain tissues of AD rat, and improve the survival rate of brain tissue cells. MiR-142-5p regulated PTPN1 to activate the Akt pathway, further inhibiting the apoptosis of brain neurons in AD rats.Down-regulating miR-142-5p targets PTPN1 to activate Akt pathway, thus improving the learning and memory of AD rats and playing an anti-AD role.

Computational studies of molecular organic photocatalysts for water splitting, highlighting beneficial factors: a slow exciton recombination and a short charge transfer distance between the photocatalyst and the metal cocatalyst.

By integrating machine learning with automation and robots, accelerated discovery of photocatalysts in the future could be envisioned.

Combination chemotherapy is recognized as a vital medical treatment for cancer, but it has not achieved clinical ideal effects of combination therapy. Herein, we designed a supramolecular combination chemotherapy strategy based on cucurbit[8]uril (CB[8]), which can be facilely assembled into dual platinum drugs. Interestingly, employing the CB[8] carrier led to a greater than 10-fold intracellular Pt content compared to that of dual drugs at 4 h, and the CB[8] complex (CLE) can enhance the infiltration of platinum drugs in colorectal tumor cells tremendously. The platinum drugs can be released from CLE through consuming more tumor biomarker spermidine. Through analyzing the nanomechanical property of the colorectal tumor cellular surface by bioscope AFM, it was revealed that CLE modified the property by decreasing the adhesion and increasing the stiffness. This study provided a facile and sensitive strategy for improving combination chemotherapy by supramolecular materials.

We consider a rental service with a fixed number of rental units distributed across multiple locations. The units are accessed by customers without prior reservation and on an on-demand basis. Customers can decide on how long to keep a unit and where to return it. Because of the randomness in demand and in returns, there is a need to periodically reposition inventory away from some locations and into others. In deciding on how much inventory to reposition and where, the system manager balances potential lost sales with repositioning costs. Although the problem is increasingly common in applications involving on-demand rental services, not much is known about the nature of the optimal policy for systems with a general network structure or about effective approaches to solving the problem. In this paper, first, we show that the optimal policy in each period can be described in terms of a well-specified region over the state space. Within this region, it is optimal not to reposition any inventory, whereas, outside the region, it is optimal to reposition but only such that the system moves to a new state that is on the boundary of the no-repositioning region. We also provide a simple check for when a state is in the no-repositioning region. Second, we leverage the features of the optimal policy, along with properties of the optimal cost function, to propose a provably convergent approximate dynamic programming algorithm to tackle problems with a large number of dimensions. This paper was accepted by David Simchi-Levi, optimization. Funding: The research of S. Benjaafar is in part funded by the US National Science Foundation (NS) [Grant SCC-1831140]. The research of X. Li is in part funded by the SingaporeMinistry of Education [Grant R-266-000-128-133]. This work used the Extreme Science and Engineering Discovery Environment [NSF Grant ACI-1548562], the Bridges-2 system [NSF Grant ACI-1445606], and resources from the University of Pittsburgh Center for Research Computing. Supplemental Material: Data and the electronic companion are available at https://doi.org/10.1287/mnsc.2021.4286 .

ObjectiveHaematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.DesignTPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 onTCF21DNA hypermethylation. Pericyte-conditionalTcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling.ResultsThirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21highTPCs, termed ‘matrix–pericytes’, was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM).Tcf21depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21highTPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impairTCF21DNA hypermethylation in TCF21highTPCs.ConclusionThis study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.

This research aimed to explore the antidepressant components from Dendrobium officinale flowers (DOF) aqueous extract and their mechanism. Multiple depressive models were successfully used to show that alcohol-soluble polysaccharide-enriched fractions separated from DOF aqueous extract exhibited significant antidepressant effects. Subsequently, a novel alcohol-soluble polysaccharide named ASP was isolated, and its molecular mass was 3.10 × 10

Both a conventional flow distributer and an improved one with a flow buffer were applied respectively during the high pressure die casting (HPDC) process, and samples of AZ91D magnesium alloy with different microstructure mainly consisting of α-Mg grains, β-phase and porosities were obtained. According to the grain orientation analysis, the predominant deformation behavior in α-Mg grains was dislocation slip, supplemented by deformation twinning. Dislocation slip was more difficult to occur in the samples with the improved flow distributer on account of the fact that the size of α-Mg grains in the microstructure was finer and more uniform. During the in situ tensile deformation test, cracks were observed to initiate from gas-shrinkage pore and island-shrinkage, and two main crack propagation mechanisms, porosity growth and coalescence were found accordingly. When the crack was in contact with the β-phase, it would pass through and fracture the network β-phase, whereas bypass the island β-phase by detaching it from the surrounding α-Mg grains. Mechanical property tests showed that the samples with relatively more homogeneous microstructure would perform higher mechanical properties, which was the combined effect of matrix α-Mg grains, β-phase, and porosities.

Lupus nephritis (LN) develops in more than a third of all systemic lupus erythematosus (SLE) patients and is the strongest predictor of morbidity and mortality. Increased circulating levels of type I interferon (IFN I) and anti-double stranded DNA (anti-dsDNA) and anti-RNA binding protein (anti-RNP) antibodies lead to increased glomerular injury via leukocyte activation and glomerular infiltration. Uncontrolled Toll-like receptor (TLR) signaling in leukocytes results in increased production of IFN I and anti-dsDNA antibodies. ITGAM gene codes for integrin CD11b, the α-chain of integrin heterodimer CD11b/CD18, that is highly expressed in leukocytes and modulates TLR-dependent pro-inflammatory signaling. Three nonsynonymous SNPs in the ITGAM gene strongly correlate with increased risk for SLE and LN and with IFN I levels. Here we review the literature on the role of CD11b on leukocytes in LN. We also incorporate conclusions from several recent studies that show that these ITGAM SNPs result in a CD11b protein that is less able to suppress TLR-dependent pro-inflammatory pathways in leukocytes, that activation of CD11b via novel small molecule agonists suppresses TLR-dependent pathways, including reductions in circulating levels of IFN I and anti-dsDNA antibodies, and that CD11b activation reduces LN in model systems. Recent data strongly suggests that integrin CD11b is an exciting new therapeutic target in SLE and LN and that allosteric activation of CD11b is a novel therapeutic paradigm for effectively treating such autoimmune diseases.

The newly discovered glymphatic system acts as pseudolymphatic vessels subserving brain waste clearance and is functionally dependent on astrocytic aquaporin-4 channels. The glymphatic system primarily functions during sleep as an interchange between cerebrospinal fluid and interstitial fluid, with cerebrospinal fluid flowing into the parenchyma via the perivascular spaces and then exchanging with interstitial fluid. The discovery of meningeal lymphatics helps refine the conceptual framework of glymphatic pathway, as certain waste products collected alongside perivascular spaces ultimately drain into the cervical lymph nodes via meningeal lymphatics, whose function regulates the functioning of the glymphatic system. The glymphatic and meningeal lymphatic systems are critical for the homeostasis of central nervous system, and their malfunctions complicate cerebral dysfunction and diseases. The present review will shed light on the structure, regulation, functions, and interrelationships of the glymphatic system and meningeal lymphatics. We will also expound on their impairments and corresponding targeted intervention in neurodegenerative diseases, traumatic brain injury, stroke, and infectious/autoimmune diseases, offering valuable references for future research.

Objective To analyze the influencing factors of revascularization in patients with coronary heart disease after PCI, and to construct a Nomo diagram model of revascularization in patients with coronary heart disease after PCI and conduct internal verification. Methods Patients with coronary heart disease who underwent PCI in the National Key Specialty Cardiology Department of a tertiary and first-class hospital in Zhenjiang City from January 2015 to November 2015 were retrospectively collected as the research subjects. Multivariate Logistic regression was used to analyze the influencing factors of repeat revascularization after PCI in patients with coronary heart disease, and a nomogram model was established to predict the risk of repeat revascularization after PCI in patients with coronary heart disease. The predictive performance of the model was internally validated using ROC curves. Results Multivariate analysis showed that poor daily life behaviors [OR=4.208, 95%CI(1.828, 9.686)], high risk of coronary heart disease specific index [OR=3.308, 95%CI(1.157, 9.453)], high fat Hyperemia [OR=7.262, 95%CI(3.236, 16.296)], multivessel disease [OR=2.691, 95%CI(1.061, 6.822); OR=6.068, 95%CI(2.467, 14.925)] was coronary heart disease The independent risk factors of revascularization in patients (PConclusion The main influencing factors of poor daily living behavior, high risk of coronary heart disease-specific index, hyperlipidemia and multivessel disease, the nomogram model established based on the above factors has good predictive performance.

PurposeThis paper aims to identify the impact of the new ambient air quality standards (AAQS) on firm innovation.Design/methodology/approachTaking listed companies from 2009 to 2014 as the research object, the authors focus on the quasinatural experiment of the pilot policy of the new AAQS and apply the time-varying difference-in-differences (DID) method to conduct the empirical test.FindingsThe authors find that the new AAQS has a negative effect on firm innovation, and this negative impact may be caused by the increased environmental expenditures following the implementation of the new AAQS. Furthermore, the authors find that firm profitability and state ownership weaken this negative effect, but the effect of the degree of industrial pollution is statistically insignificant.Originality/valueThe study is an initial effort to explore the causal effect of the new AAQS on firm innovation. This study enriches the literature on the impact of environmental regulations on firm innovation and provides some reference value for the formulation of environmental regulation policies in developing countries.

The weak gravitational lensing is a powerful tool in modern cosmology. To accurately measure the weak lensing signal, one has to control the systematic bias to a small level. One of the most difficult problems is how to correct the smearing effect of the Point Spread Function (PSF) on the shape of the galaxies. The chromaticity of PSF for a broad-band observation can lead to new subtle effects. Since the PSF is wavelength dependent and the spectrum energy distribution between stars and galaxies is different, the effective PSF measured from the star images will be different from that smears the galaxies. Such a bias is called colour bias. We estimate it in the optical bands of the Chinese Space Station Survey Telescope from simulated PSFs, and show the dependence on the colour and redshift of the galaxies. Moreover, due to the spatial variation of spectra over the galaxy image, there exists another higher-order bias, colour gradient bias. Our results show that both colour bias and colour gradient bias are generally below 0.1 percent in CSST. Only for small-size galaxies, one needs to be careful about the colour gradient bias in the weak lensing analysis using CSST data.

BackgroundRecent studies have suggested that long non-coding RNAs (lncRNAs) may play crucial role in low-grade glioma; however, the underlying mechanisms linking them to epigenetic methylation remain unclear.MethodsWe downloaded expression level data for regulators associated with N1 methyladenosine (m1A), 5-methyladenine (m5C), and N6 methyladenosine (m6A) (M1A/M5C/M6A) methylation from the Cancer Genome Atlas-low-grade glioma (TCGA-LGG) database. We identified the expression patterns of lncRNAs, and selected methylation-related lncRNAs using Pearson correlation coefficient>0.4. Non-negative matrix dimensionality reduction was then used to determine the expression patterns of the methylation-associated lncRNAs. We constructed a weighted gene co-expression network analysis (WGCNA) network to explore the co-expression networks between the two expression patterns. Functional enrichment of the co-expression network was performed to identify biological differences between the expression patterns of different lncRNAs. We also constructed prognostic networks based on the methylation presence in lncRNAs in low-grade gliomas.ResultsWe identified 44 regulators by literature review. Using a correlation coefficient greater than 0.4, we identified 2330 lncRNAs, among which 108 lncRNAs with independent prognostic values were further screened using univariate Cox regression at P< 0.05. Functional enrichment of the co-expression networks revealed that regulation of trans-synaptic signaling, modulation of chemical synaptic transmission, calmodulin binding, and SNARE binding were mostly enriched in the blue module. The calcium and CA2 signaling pathways were associated with different methylation-related long non-coding chains. Using the Least Absolute Shrinkage Selector Operator (LASSO) regression analysis, we analyzed a prognostic model containing four lncRNAs. The model’s risk score was 1.12 *AC012063 + 0.74 * AC022382 + 0.32 * AL049712 + 0.16 * GSEC. Gene set variation analysis (GSVA) revealed significant differences in mismatch repair, cell cycle, WNT signaling pathway, NOTCH signaling pathway, Complement and Cascades, and cancer pathways at different GSEC expression levels. Thus, these results suggest that GSEC may be involved in the proliferation and invasion of low-grade glioma, making it a prognostic risk factor for low-grade glioma.ConclusionOur analysis identified methylation-related lncRNAs in low-grade gliomas, providing a foundation for further research on lncRNA methylation. We found that GSEC could serve as a candidate methylation marker and a prognostic risk factor for overall survival in low-grade glioma patients. These findings shed light on the underlying mechanisms of low-grade glioma development and may facilitate the development of new treatment strategies.

The ketocarotenoid fucoxanthin and its derivatives can absorb blue–green light enriched in marine environments. Fucoxanthin is widely adopted by phytoplankton species as a main light-harvesting pigment, in contrast to land plants that primarily employ chlorophylls. Despite its supreme abundance in the oceans, the last steps of fucoxanthin biosynthesis have remained elusive. Here, we identified the carotenoid isomerase-like protein CRTISO5 as the diatom fucoxanthin synthase that is related to the carotenoid cis–trans isomerase CRTISO from land plants but harbors unexpected enzymatic activity. A crtiso5 knockout mutant in the model diatom Phaeodactylum tricornutum completely lacked fucoxanthin and accumulated the acetylenic carotenoid phaneroxanthin. Recombinant CRTISO5 converted phaneroxanthin into fucoxanthin in vitro by hydrating its carbon–carbon triple bond, instead of functioning as an isomerase. Molecular docking and mutational analyses revealed residues essential for this activity. Furthermore, a photophysiological characterization of the crtiso5 mutant revealed a major structural and functional role of fucoxanthin in photosynthetic pigment–protein complexes of diatoms. As CRTISO5 hydrates an internal alkyne physiologically, the enzyme has unique potential for biocatalytic applications. The discovery of CRTISO5 illustrates how neofunctionalization leads to major diversification events in evolution of photosynthetic mechanisms and the prominent brown coloration of most marine photosynthetic eukaryotes.

Figure S1, related to Figure 3. Effect of Spi-B on EMT. (A) Phase-contrast micrographs of HBECs expressing vector or Spi-B. Scale bars are 100μm; (B) western blot showed expression of Spi-B, E-cadherin, Vimentin and Actin; (C) Quantitative RT-PCR assay for Spi-B, Snail1, Snail2, Twist1 and ZEB1. Figure S2, related to Figure 3. (A) Phase-contrast micrographs of H526 cells expressing control or Spi-B shRNAs. Scale bars are 50μm; (B) BrdU in corporation assay of A549 expressing vector or Spi-B; (C) vector or Spi-B-expressing A549 cells were plated on fibronectin-coated plates. After 15 min, attached cells were counted. Scale bars represent 200 mm. Bar graph below shows number of adherent cells. Mean {plus minus} SD of three duplications is shown. Figure S3, related to Figure 5. Expression of claudin-2 in tumor-adjacent tissues. (A) IHC showed expression of claudin-2 in bronchial epithelial cells; (B) IHC showed expression of claudin-2 in alveolar epithelial cells (arrows). Scale bars are 50μm. Figure S4, related to Figure 6. Other Spi-B downregulated tight junction proteins, Claudin-14 and Crumbs3, are not able to rescue Spi-B induced cellular behavior. (A) A549 cells were transduced with Spi-B or Spi-B and Claudin-14 or Spi-B and Crumbs3 as indicated. Representative images of the clones in soft agar were shown in left panels. The bar chart shows the percentage of mass (blue), and loose colonies (red). Error bars indicate means {plus minus} SD for a representative experiment performed in triplicate. Scale bars represent 100 μm. (B) A549 cells were transduced with Spi-B or Spi-B and Claudin-14 or Spi-B and Crumbs3 as indicated. Phase contrast of acini were shown in left panel and quantified in right panel. The bar chart shows the percentage of mass (blue) and grape-like (red). Error bars indicate means {plus minus} SD for a representative experiment performed in triplicate. Scale bars represent 25 μm. (C) A549 cells were transduced with Spi-B or Spi-B and Claudin-14 or Spi-B and Crumbs3 as indicated and subjected to an invasion assay. Error bars indicate means{plus minus} SD for a representative experiment performed in triplicate. Scale bars represent 100 μm. Figure S5. (A) A549 cells were transduced with Spi-B or Spi-B and shRNA of MMP9 as indicated and subjected to an invasion assay. (B) A549 cells were transduced with Spi-B or Spi-B and MMP9 inhibitor (TIMP1) as indicated and subjected to an invasion assay. Error bars indicate means{plus minus} SD for a representative experiment performed in triplicate. Scale bars represent 100 μm.

Supplementary Figure 1 to Supplementary Figure 8 Supplementary Figure 1 | Association of immune score with TILs (A) and cytolytic activity (B). Supplementary Figure 2 | Prognostic evaluation of immune cells in ovarian cancer datasets. (A) Forest plot visualizing hazard ratios (HRs) of infiltrating CD8+ T cells in all cohort datasets. The red diamond shows the fixed-effects meta-analysis summary of HRs over the 16 datasets (HR = 0.92[0.87-0.97]; p = 0.003). HR is determined by univariate Cox proportional hazards regression analysis. (B) Same as (A) but for Plasmacytoid dendritic cells (HR = 1.07[1.01-1.13], p = 0.02). Supplementary Figure 3 | The association of immune score with somatic mutations in TCGA dataset. (A) A volcano plot representation between immune score and gene mutations showing the magnitude and significance of immune score-gene associations. The x-axis measures the average difference of the immune score in patients with somatic mutations of a gene minus the immune score in patients with the wild type gene. The y-axis indicates the statistical significance of immune score between mutated tumors and wild type tumors by Wilcoxon Rank Sum test. Only genes with non-silient mutations in at least five different tumor samples are analyzed. All the associations in the figure are with a FDR > 0.5. (B) The correlation between mutation burden and immune score across tumor samples (Pearson's r = 0.08, p = 0.19). (C) The correlation between neo-antigen burden and immune score across tumor samples (Pearson's r = 0.05, p = 0.43). Supplementary Figure 4 | Genomic assocaitions with immune score in TCGA melanoma cohort. (A) Oncoplot of the copy number status of IFN-γ pathway genes. Copy number loss or gain was determined by GISTIC 2.0 and defined as score < 0 or >0 respectively. Green bar and grey bar indicate the samples with or without copy number loss of IFN-γ pathway genes, respectively. (B) Association between immune score and copy number status of IFN-γ pathway genes. Samples are divided into groups with or without copy number loss of IFN-γ pathway genes, as shown by the green and grey bar in A. (C) Association between immune score and the expression of IRF-1 in melanoma. (D) Association between immune score and the expression of IRF-1 in TCGA ovarian cancer dataset (related to Figure 2D). Significance is determined by Wilcoxon Rank Sum test. Supplementary Figure 5 | Correlation matrix between immune score and the expression of chemokines and antigen-presenting genes in the 16 cohort datasets of ovarian cancer. Color of units represents the Pearson correlation coefficient between immune score and gene expression. Correlation for genes not included in the data platform is shown as NA (black). Supplementary Figure 6 | GSEA reveals the assocation of response to chemotherapy and infiltrating activated CD4+ T cells in TCGA dataset. Supplementary Figure 7 | Prognostic evaluation of immune score for BRCA mutated samples. (A) Kaplan-Meier survival curves of TCGA ovarian cancer patients, divided by BRCA1/2 mutation status and immune score. (B) Kaplan-Meier survival curves of BRCA1/2 wild type patients and patients with BRCA1/2 mutations and diploid copy number status inTCGA ovarian cancer dataset. Supplementary Figure 8 | Immune score is predictive of response to immunotherapy. (A) Immune score for the cohort received anti-CTLA-4 immunotherapy. (B) Kaplan-Meier survival curves of patients with high vs. low immune score in the cohort received anti-CTLA-4 immunotherapy. (C) Receiver operating characteristics (ROC) for immune score and CTLA4 expression in predicting the responders of immunotherapy.

Supplementary Table 1 and Supplementary Table 2