Nonionic Water-Soluble Oligo(ethylene glycol)-Modified Polypeptides with a ß-Sheet Conformation.

The secondary structures of polypeptides, such as an α-helix and a ß-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a ß-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EGmK-NCA, where m = 1-3) and the corresponding polymers EGmKn are synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of EGmKn is delicately regulated by both m and n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, EG2Kn adopts a ß-sheet conformation with good water solubility at an appropriate DP and forms physically cross-linked hydrogels at a concentration as low as 1 wt %. The secondary structures of EG1Kn can be tuned by DP, exhibiting either a ß-sheet or an α-helix, whereas EG3Kn appears to a adopt pure and stable α-helix with no dependence on DP. Compared to previous works reporting EG-modified lysine-derived polypeptides bearing exclusively an α-helix conformation, this work highlights the important and unexpected role of the urethane connecting unit and provides useful case studies for understanding the secondary structure of polypeptides.

Agrin Yes-associated Protein Promotes the Proliferation of Epicardial Cells.

ABSTRACT: Embryonic epicardial cells make an important contribution to cardiac development. However, their proliferation mechanism is still unclear. Epicardial cells from E12.5 fetal hearts were used in our study. Agrin was used to treat these cells. The expression of Aurora B, Ki67, and pH3 was measured by quantitative reverse transcription-polymerase chain reaction and immunofluorescence. The proportion of cells in G1/S/G2 phase was determined by flow cytometry. The results showed that agrin significantly increased the expression of ki67, pH3, and Aurora B in epicardial cells. Flow cytometry results showed that agrin significantly increased the proportion of epicardial cells in S phase. However, blocking yes-associated protein significantly downregulated the levels of ki67, pH3, and Aurora B and the proportion of epicardial cells in S phase. Thus, our results suggest that agrin may promote the proliferation of epicardial cells by regulating the yes-associated protein activity. This may be useful in exploring heart development mechanisms and preventing congenital heart disease.

Autophagy is involved in the differentiation of epicardial progenitor cells into vascular smooth muscle cells in mice.

Most coronary smooth muscle cells(CoSMCs) are differentiated from epicardial progenitor cells(EPCs), but the specific mechanism is not fully investigated. Previous studies have shown that autophagy plays an important role for smooth muscle cells(SMCs) differentiation, yet whether autophagy is involved in the differentiation of EPCs into CoSMCs remains unclear. In the present study, We first isolated and cultured EPCs and continuously cultured them for 72 h. Then the autophagy induction and inhibition experiment was established by using the autophagy inducer Rapamycin(RAPA) and the inhibitor 3-Methyladenine(3-MA). And further animal experiments were conducted to observe the effects of autophagy on the development of coronary arteries. Our data showed that autophagy occurred in the differentiation of EPCs into SMCs. Over activation of autophagy may lead to early transient differentiation of EPCs, enhanced migration ability and weakened systolic function, but overall, CoSMC development is still inhibited. However, inhibition of autophagy may delay the differentiation of EPCs, thus reducing the number of coronary arteries. Together, all these processes indicate that autophagy may regulate the differentiation of EPCs into CoSMCs by affecting the time point of differentiation, and appropriate autophagy intensity is required during the development of CoSMCs.

Versatile Types of Polysaccharide-Based Drug Delivery Systems: From Strategic Design to Cancer Therapy.

Chemotherapy is still the most direct and effective means of cancer therapy nowadays. The proposal of drug delivery systems (DDSs) has effectively improved many shortcomings of traditional chemotherapy drugs. The technical support of DDSs lies in their excellent material properties. Polysaccharides include a series of natural polymers, such as chitosan, hyaluronic acid, and alginic acid. These polysaccharides have good biocompatibility and degradability, and they are easily chemical modified. Therefore, polysaccharides are ideal candidate materials to construct DDSs, and their clinical application prospects have been favored by researchers. On the basis of versatile types of polysaccharides, this review elaborates their applications from strategic design to cancer therapy. The construction and modification methods of polysaccharide-based DDSs are specifically explained, and the latest research progress of polysaccharide-based DDSs in cancer therapy are also summarized. The purpose of this review is to provide a reference for the design and preparation of polysaccharide-based DDSs with excellent performance.

Epicardial fat tissue in patients with diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Epicardial fat tissue (EFT) is the visceral fat distributed along the coronary arteries between the pericardium and the myocardium. Increases in EFT are closely related to the occurrence of diabetes mellitus (DM) and cardiovascular disease. To further understand the link between EFT and DM, we conducted a meta-analysis of the relevant literature. METHODS: We systematically searched electronic databases for studies on EFT performed in DM patients and published up to 30 September 2018. We included data on EFT in a DM patient group and a non-DM control group. We then assessed the effect of DM on EFT by meta-analysis and trial sequential analysis (TSA). All statistical analyses were performed using Stata 12.0 and TSA software. RESULTS: A total of 13 studies (n = 1102 patients) were included in the final analysis. Compared with the control group, DM patients had significantly higher EFT (SMD: 1.23; 95% CI 0.98, 1.48; P = 0.000; TSA-adjusted 95% CI 0.91, 2.13; P < 0.0001). The TSA indicated that the available samples were sufficient and confirmed that firm evidence was reached. According to the regression analysis and subgroup analyses, DM typing, EFT ultrasound measurements, total cholesterol (TC) and triglyceride (TG) levels were confounding factors that significantly affected our results. CONCLUSIONS: Our meta-analysis suggests that the amount of EFT is significantly higher in DM patients than in non-DM patients.

Implication for DNA methylation involved in the host transfer of diamondback moth, Plutella xylostella (L.).

DNA methylation exerts extensive impacts on gene expression of various living organisms exposed to environmental variation. However, little is known whether DNA methylation is involved in the host transfer of diamondback moth, Plutella xylostella (L.), a worldwide destructive pest of crucifers. In this study, we found that P. xylostella genome exhibited a relatively low level of DNA methylation on the basis of the CpG O/E prediction and experimental validation. A significant positive linear correlation was observed between the stage-specific expressions of PxDNMT1 and DNA methylation levels (5mC content). Particularly, high levels of DNA methylation and gene expression of PxDNMT1 were observed in eggs and mature females of P. xylostella. After host transfer of P. xylostella from Raphanus sativus to Arabidopsis thaliana, we identified some potential genomic loci that might have changed methylation levels. Using the method of fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP), we also found the corresponding genes primarily involved in neural system and signaling. The expressions of six candidate genes were verified by qRT-PCR. One of the genes, Px009600, might be regulated by a DNA methylation-mediated mechanism in response to host transfer. Our study provides evidence for a functional system of DNA methylation in P. xylostella and its possible role in adaptation during host transfer. Further studies should examine methylation as responsive factors to different host plants and environmental cues in insect pests.

Sphingosine 1-phosphate induces epicardial progenitor cell differentiation into smooth muscle-like cells.

Epicardial progenitor cells (EpiCs) which are derived from the proepicardium have the potential to differentiate into coronary vascular smooth muscle cells during development. Whether sphingosine 1-phosphate (S1P), a highly hydrophobic zwitterionic lysophospholipid in signal transduction, induces the differentiation of EpiCs is unknown. In the present study, we demonstrated that S1P significantly induced the expression of smooth muscle cell specific markers α-smooth muscle actin and myosin heavy chain 11 in the EpiCs. And the smooth muscle cells differentiated from the EpiCs stimulated by S1P were further evaluated by gel contraction assay. To further confirm the major subtype of sphingosine 1-phosphate receptors (S1PRs) involved in the differentiation of EpiCs, we used the agonists and antagonists of different S1PRs. The results showed that the S1P1/S1P3 antagonist VPC23019 and the S1P2 antagonist JTE013 significantly attenuated EpiCs differentiation, while the S1P1 agonist SEW2871 and antagonist W146 did not affect EpiCs differentiation. These results collectively suggested that S1P, principally through its receptor S1P3, increases EpiCs differentiation into VSMCs and thus indicated the importance of S1P signaling in the embryonic coronary vasculature, while S1P2 plays a secondary role.

Insulin-like growth factor 1 receptor signaling regulates embryonic epicardial cell proliferation through focal adhesion kinase pathway.

Embryonic epicardial cells (EPCs) can facilitate cardiomyocyte growth through secreting several essential growth factors, and participate in cardiac development through auto-differentiating into many cardiac cell lineages. Proper proliferation of EPCs is the precondition of these functions, so it is quite necessary to explore the mechanisms involving in EPC proliferation. In this study, we aimed to explore whether insulin-like growth factor 1 receptor (IGF1R) signaling participated in regulating the proliferation of EPCs. Our results showed that the expressions of IGF1R and its ligands IGF1 and IGF2 can be clearly spotted on the epicardium layer from E11.5d to E17.5d. Inhibition of IGF1R signaling using picropodophyllin or NVP-AEW541 significantly decreased the proliferation activity and blocked the cell cycle progression of epicardial cells in vitro. On the contrary, activating IGF1R with recombinant IGF1 and IGF2 promoted epicardial cell proliferation and cell cycle. We also found that decreased expression and phosphorylation of FAK in IGF1R inhibitor-treated cells and use of FAK inhibitor Y15 could significantly inhibit the IGFs-induced EPC proliferation. In conclusion, our results suggest that IGF1R signaling plays an important role in regulating EPC proliferation, and this effect may be mediated by FAK pathway.

Triiodothyronine promotes the proliferation of epicardial progenitor cells through the MAPK/ERK pathway.

Thyroid hormone has important functions in the development and physiological function of the heart. The aim of this study was to determine whether 3,5,3'-Triiodothyronine (T3) can promote the proliferation of epicardial progenitor cells (EPCs) and to investigate the potential underlying mechanism. Our results showed that T3 significantly promoted the proliferation of EPCs in a concentration- and time-dependent manner. The thyroid hormone nuclear receptor inhibitor bisphenol A (100 µmol/L) did not affect T3's ability to induce proliferation. Further studies showed that the mRNA expression levels of mitogen-activated protein kinase 1 (MAPK1), MAPK3, and Ki67 in EPCs in the T3 group (10 nmol/L) increased 2.9-, 3-, and 4.1-fold, respectively, compared with those in the control group (P < 0.05). In addition, the mRNA expression of the cell cycle protein cyclin D1 in the T3 group increased approximately 2-fold compared with the control group (P < 0.05), and there were more EPCs in the S phase of the cell cycle (20.6% vs. 12.0%, P < 0.05). The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway inhibitor U0126 (10 µmol/L) significantly inhibited the ability of T3 to promote the proliferation of EPCs and to alter cell cycle progression. This study suggested that T3 significantly promotes the proliferation of EPCs, and this effect may be achieved through activation of the MAPK/ERK signaling pathway.

Biological characteristics of embryonic epicardial cells in vitro correlate with embryonic day.

The epicardial cell (EpiC) culture system plays an important role in investigating the specific mechanisms and signaling molecules that are involved in the development of EpiCs. From this early formation until adulthood, EpiCs undergo dynamic changes in the expression of embryonic genes that correlate with changes in the embryonic EpiC properties. The differences of embryonic EpiC properties may affect the related results of experiments in which EpiC culture system is used; however, these differences have not been explored. Therefore, in this study we examined the differences in the biological characteristics of EpiCs on different embryonic days in vitro EpiCs were isolated from embryonic ventricle explants on embryonic day (E) 11.5, E13.5, and E15.5. The differences in the migration, proliferation and differentiation were studied in EpiCs of different embryonic day by scratch assay, cell cycle analysis and platelet derived growth factor-bb (PDGF-BB) treatment. The results showed that EpiCs were successfully cultured from E11.5, E13.5, and E15.5 embryonic ventricle explants. The time windows of E11.5, E13.5, and E15.5 EpiC isolation out of the explants were different. The migration abilities of E11.5, E13.5, and E15.5 EpiCs decreased during embryonic development. Smooth muscle cell differentiation potential of early stage EpiCs was better than that of the later stage EpiCs. Although the proliferation ability of E11.5 EpiCs was significantly weaker than those of E13.5 and E15.5 EpiCs, the proliferation abilities of E13.5 and E15.5 EpiCs did not differ. These results suggest that the biological characteristics of EpiCs correlate with the timing of embryonic development, and different embryonic stage of ventricle should be properly chosen for culturing EpiCs depending on the purposes of the specific experiments.

Angiotensin â ¡ induces the differentiation of mouse epicardial progenitor cells into vascular smooth muscle-like cells.

Epicardial progenitor cells (EpiCs) have a crucial role in cardiac development and vasculature formation. Here we detected the expression of Angiotensin II (Ang II) receptors AT1 and AT2 on EpiCs and demonstrated that AngII could increase the expression of smooth muscle specific markers, including α-smooth muscle actin (α-SMA) and myosin heavy chain 11 (Myh11) in EpiCs. Moreover, the expression of α-SMA and Myh11 induced by Ang II was blocked by pretreatment of EpiCs with the AT1 receptor antagonist losartan, but not the AT2 receptor antagonist PD123319. We further showed that the AngII-induced cells showed significant contractile responses to carbachol. These results implied that AngII could effectively induce EpiCs to differentiate into vascular smooth muscle-like cells through the AT1 receptor.

Acoustic properties of multiple cavity resonance liner for absorbing higher-order duct modes.

This paper describes analytical and experimental studies conducted to investigate the acoustic properties of axially non-uniform multiple cavity resonance liner for absorbing higher-order duct modes. A three-dimensional analytical model is proposed based upon transfer element method. The model is assessed by making a comparison with results of a liner performance experiment concerning higher-order modes propagation, and the agreement is good. According to the present results, it is found that the performance of multiple cavity resonance liner is related to the incident sound waves. Moreover, an analysis of the corresponding response of liner perforated panel-cavity system is performed, in which the features of resonance frequency and dissipation of the system under grazing or oblique incidence condition are revealed. The conclusions can be extended to typical non-locally reacting liners with single large back-cavity, and it would be beneficial for future non-locally reacting liner design to some extent.

Aeroacoustic model of a modulation fan with pitching blades as a sound generator.

This paper is to develop an aeroacoustic model for a type of modulation fan termed as rotary subwoofer that is capable of radiating low-frequency sound at high sound pressure levels. The rotary subwoofer is modeled as a baffled monopole whose source strength is specified by the fluctuating mass flow rate produced by the pitching blades that rotate at constant speed. An immersed boundary method is established to simulate the detailed unsteady flow around the blades and also to estimate the source strength for the prediction of the far-field sound pressure level (SPL). The numerical simulation shows that the rotary subwoofer can output oscillating air flow that is in phase with the pitching motion of the blades. It is found that flow separation is more likely to occur on the pitching blades at higher modulation frequency, resulting in the reduction of the radiated SPL. Increasing the maximum blade excursion is one of the most effective means to enhance the sound radiation, but this effect can also be compromised by the flow separation. As the modulation frequency increases, correspondingly increasing the rotational speed or using larger blade solidity is beneficial to suppressing the flow separation and thus improving the acoustic performance of the rotary subwoofer.

Exploration of port environmental efficiency measurement and influential factors in the Yangtze River Delta Pilot Free Trade Zone.

This study focuses on the environmental efficiency of ports in China's Yangtze River Delta Pilot Free Trade Zone (YRD PFTZ), a critical factor in advancing the high-quality development of ports and facilitating Chinese-style modernization. Current research on port efficiency primarily focuses on the geographical level, with relatively few studies examining the economic regional framework. We selected the YRD PFTZ port for our study to address this gap. Covering 2013 to 2021, we employed the Super-SBM with undesirable outputs and utilized the GML index method. We conducted a spatiotemporal analysis to assess dynamic and static aspects and used the Tobit model to thoroughly investigate the factors influencing the GML Index of these ports. The study showed that: (1) the overall environmental efficiency of these ports was relatively high with a fluctuating trend of initial increase, followed by a decrease, and then an upturn. (2) From a dynamic perspective, the average Green Total Factor Productivity (GTFP) Index is 1.549, denoting an exceptional level primarily driven by technological efficiency. The technical efficiency change index is the main factor improving GTFP in Shanghai, Jiangsu, and Anhui provinces. (3) The port cargo volume and total import and export volume significantly impact the environmental efficiency.

An NIR-responsive hydrogel loaded with polydeoxyribonucleotide nano-vectors for enhanced chronic wound healing.

Chronic diabetic wounds are difficult to treat due to imbalanced inflammatory responses, high blood glucose levels, and bacterial infections. Novel therapeutic approaches based on nucleic acid analogues have been proposed, with unique advantages in improving angiogenesis, increasing collagen synthesis, and exerting anti-inflammatory effects. However, the inherent electronegativity of nucleic acids makes them less susceptible to cellular uptake. In this paper, a kind of near infrared (NIR)-responsive nanocomposite hydrogel loaded with nucleic acid vectors was proposed for promoting wound healing. The redox system composed of molybdenum disulphide nanosheets (MoS2 NSs) initiated the copolymerization of quaternized chitosan containing double bonds and N-isopropylacrylamide (NIPAAm) to form the matrix. In addition, MoS2 NSs with photothermal conversion performance endow the nanocomposite hydrogel to have NIR-response property and act as physical crosslinking points in the matrix. Polydeoxyribonucleotides (PDRN), which have the effect of promoting wound healing, were made into nucleic acid vectors, and loaded into the NIR-responsive hydrogel. MoS2 NSs can convert NIR irradiation into heat, causing phase transitions of temperature-sensitive segments that trigger volume contraction of the hydrogel to extrude the nucleic acid vector. Promoting angiogenesis, slowing inflammation, and guiding tissue regeneration were demonstrated in the diabetic wound model treated with the NIR-responsive nanocomposite hydrogel.

Spatio-temporal changes and root-cause identification for embodied carbon emissions based on production and consumption in China's Yangtze River Economic Belt.

The Yangtze River Economic Belt (YEB) is at the centre of China's economy and development. Its regional carbon emissions account for about 36.9% of the country's total carbon emissions, and thus, there is an urgent need to sustain the development of a low-carbon economy. However, the complex patterns of embodied carbon flows arising from multi-scale trade in such a megaregion are often ignored in carbon environmental governance. This study incorporates a megaregion into an environmentally extended multi-regional input-output (EEMRIO) framework and identifies the drivers of production and consumption-based carbon emissions using four measures through structural decomposition analysis (SDA). The results show that (1) the YEB strengthens inter-provincial trade links while reducing international trade links; (2) there is obvious carbon transfer in multi-scale trade in the YEB, with a corresponding transfer of responsibility for carbon reduction occurring; and (3) consumption volume and carbon intensity are the main drivers and inhibitors of the increasing carbon emissions, respectively, and the optimisation of production structure and consumption structure are effective ways to control production-based carbon emissions (PBEs) and consumption-based carbon emissions (CBEs), respectively. This study extends the research scale of "national-provincial-city" to a megaregion. Studies based on multiple trade scales would provide additional insights to understand the carbon reduction responsibilities of megaregions and help achieve coordinated regional carbon reductions.

Spatial-temporal differentiation of coupling coordination degree for green finance and green innovation efficiency: a case study in China.

Continued investment in finance and innovation is beneficial to economic development, and the joining of green system can accelerate the process of economic recovery from environmental distress. To better enhance the relationship of green finance and green innovation, it is vital to demonstrate the synergy between the two thoroughly. Thirty provinces in China are selected to examine the coupling coordination relationship between the two, specifically testing the spatial aggregation and evolutionary differences in the coupling coordination by adopting the coupling coordination degree (CCD) model, spatial autocorrelation, and kernel density estimation. Conclusions of the paper show that green finance is calculated by the EW-TOPSIS method, and the overall score of provinces is low. Using super-SBM model to evaluate green innovation, the uneven distribution of efficiency is obvious, although it is gradually increasing. The CCD in most provinces is in low-level or basic coordination, with significant regional heterogeneity. The global Moran's index becomes gradually evident with time. The local Moran scatter diagram presents a downward trend from east to west, but with more L-L aggregation provinces emerging in 2020. The center of the national kernel density curve gradually shifts to the right, indicating that the national overall synergy level is improving. Deepening the understanding of the empirical results facilitates the formulation of reasonable policies that fit the four major regions.

A chitosan derivative-crosslinked hydrogel with controllable release of polydeoxyribonucleotides for wound treatment.

Nucleic acid-based agents have advantages in therapeutic efficacy and biological safety. However, due to its facile degradability, it lacks an effective route of administration in wound treatment. Designing smart hydrogels for the spatiotemporally controllable delivery of nucleic acids is of great significance for clinical applications. Here, a near-infrared (NIR)-responsive nanocomposite hydrogel was prepared using methyl methacrylate (GMA)-modified chitosan as the macromolecular cross-linker, N-isopropylacrylamide (NIPAAm) as the backbone, and molybdenum disulfide nanosheets (MoS2 NSs) as the nanocomponents. The polydeoxyribonucleotide (PDRN), a nucleic acid-based agent that promotes tissue regeneration, was loaded and delivered. The photothermal conversion capability of MoS2 NSs enables customized care of PDRNs and antibacterial enhancement. In a full-thickness skin defect model, high-quality wound healing effects were demonstrated under the action of nanocomposite hydrogels. The proposed nanocomposite hydrogel provides a new reference for local delivery of nucleic acid-based agents.

Glucose Oxidase of a Crucifer-Specialized Insect: A Potential Role in Suppressing Plant Defense via Modulating Antagonistic Plant Hormones.

Glucose oxidase (GOX) is a representative compound found in most insect saliva that can suppress plant-defensive responses. However, little is known about the origin and role of GOX in the crucifer-specialized pest Plutella xylostella. In this study, we showed obvious regurgitation from the larval gut of P. xylostella and identified abundant peptides highly similar to known GOX. Three PxGOX genes were verified with PxGOX2 preferentially expressed in the gut. The heterologously expressed PxGOX2 confirmed its function to be a GOX, and it was detected in plant wounds together with the gut regurgitant. Further experiments revealed that PxGOX2 functioned as an effector and may suppress defensive responses in plant through the production of H2O2, which modulates levels of antagonistic salicylic acid and jasmonic acid. However, excessive H2O2 in the host plant may be neutralized by peroxidase, thus forming defensive feedback. Our findings provided new insights into understanding the GOX-mediated insect-plant interactions.

Discrete vortex model of a Helmholtz resonator subjected to high-intensity sound and grazing flow.

In this paper, a theoretical model is developed to study the acoustical response of a Helmholtz resonator as a duct-branched acoustic absorber subjected to both high-intensity sound and grazing flow. The present model is comprised of a discrete vortex model in combination with a one-dimensional duct sound propagation model. The present work is to study the overall effect of incident sound interacting with grazing flow but putting emphasis on the nonlinear or intermediate regime where the sound intensity has a marked or non-negligible influence on the acoustic behavior of the Helmholtz resonator. The numerical results reveal that the flow field around the orifice is dominated by the evolution of the vortex sheet and the flow pattern is influenced by the ratio of the orifice flow velocity to the grazing flow velocity. When the incident sound pressure is high or the resonance occurs, the resonator shows nonlinearity, i.e., the acoustic impedance and absorption coefficient vary not only with duct flow Mach number buy also with incident frequency and incident sound pressure level.