Anomalous wrinkle propagation in polycrystalline graphene with tilt grain boundaries.

Understanding the propagation of dynamic wrinkles in polycrystalline graphene with grain boundaries (GBs) is critical to the practical application of graphene-based nanodevices. Although wrinkle propagation behavior in pristine graphene (PG) and some defect-containing graphene samples have been investigated, there are no studies on the dynamic behavior of graphene with tilt GBs. Here, nine tilt GBs are constructed in graphene, and molecular dynamics (MD) simulations are performed to investigate anomalous wrinkle propagation. The MD simulation results show that a larger misorientation angle α first enhances the shielding effect of tilt GBs on wrinkle propagation before it weakens. The maximum Δz root mean square (RMS) shows that a greater misorientation angle α first increases the maximum RMS of the GB region (RGB) before it then decreases, while the maximum RMS of R80 exhibits the opposite trend. Moreover, approximately 96% of the C60 kinetic energy is converted into kinetic and potential energies in graphene, and the potential energy in graphene presents two evolution modes. Phase diagrams are plotted to study the effect of the distance d1 and rotation angle ß on the wrinkle propagation and sensitivity of the maximum RMS value to d1. It is expected that our results can provide a fundamental understanding of defect engineering and guidelines to design protectors, energy absorbers, and defect detectors in nanodevices.

circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promotes hypoxic pulmonary arterial smooth muscle cell proliferation in COPD.

Hypoxia plays a crucial role in pulmonary vascular remodelling at the early stage of chronic obstructive pulmonary disease (COPD). Circle RNA (circRNA) has been identified to play a critical role in multiple diseases. However, the role of circRNAs in pulmonary vascular remodelling in COPD remains unclear. In this study, we aim to investigate the role of circRNAs in pulmonary arterial smooth muscle cell proliferation and pulmonary vascular remodelling in COPD. COPD patients show lower partial pressure of arterial oxygen and pulmonary arterial remodeling as compared with controls. circRNA microarray and real-time PCR analyses show significantly higher level of circ-BPTF and lower miR-486-5p level in the pulmonary arteries of COPD patients as compared with controls. Hypoxia suppresses miR-486-5p expression but promotes expressions of circ-BPTF and cell migration inducing protein (CEMIP) in human pulmonary arterial smooth muscle cells (PASMCs) in vitro. Loss- and gain-of-function experiments show that circ-BPTF promotes PASMC proliferation in vitro. Moreover, luciferase reporter assay results indicate that circ-BPTF regulates PASMC proliferation by acting as an miR-486-5p sponge. CEMIP is identified as a candidate target gene of miR-486-5p by luciferase reporter assay. Overall, our study shows that circ-BPTF serves as a miR-486-5p sponge to regulate CEMIP and promote hypoxic PASMC proliferation in pulmonary vascular remodelling in COPD.

A theoretical study of wrinkle propagation in graphene with flower-like grain boundaries.

This study investigated dynamic surface wrinkle propagation across a series of flower-like rotational grain boundaries (GBs) in graphene using theoretical solutions and atomistic simulations. It was found that there was significantly less out-of-plane displacement of dynamic wrinkles when curvature of rotational GBs was reduced, which can be explained by a defect shielding effect of flower-like GBs. Potential energy evolved via different modes for pristine graphene and graphene with various GBs. With external excitation, the distinctly different patterns of wrinkle propagation in graphene with various GBs demonstrated how dynamic wrinkling can reveal defects. These results can provide a theoretical basis for guiding the design and implementation of graphene-based nano-mechanical devices such as protectors and detectors.

Resveratrol prevented experimental pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway.

OBJECTIVE: Resveratrol has shown benefit for pulmonary hypertension improvement. Our previous reports showed NR4A3/cyclin D1 pathway promoted pulmonary arterial smooth muscle cells (PASMCs) proliferation. This study tried to explore the mechanism underlying this process, focusing on the role of resveratrol in regulation of miRNA and NR4A3. METHODS: Rats were injected with monocrotaline (MCT) to establish pulmonary hypertension (PH) models. Resveratrol was used to prevent pulmonary vascular remodeling. Primary rat PASMCs were cultured in vitro and stimulated by platelet-derived growth factor (PDGF) with or without resveratrol. Cells proliferation and expression of miR-638 as well as NR4A3 were evaluated. RESULTS: MCT resulted in significant pulmonary vascular remodeling and down-regulation of miR-638, which could be suppressed by resveratrol. Moreover, PDGF-induced PASMC proliferation and miR-638 down-regulation were both significantly prevented by resveratrol treatment in vitro. MiR-638 mimics markedly inhibited PASMC proliferation and percentage of PCNA-positive cells in vitro. But anti-miR-638 could markedly promote cells proliferation and percentage of PCNA-positive cells. The luciferase reporter assay showed that NR4A3 was a direct target of miR-638. The loss-of-function and gain-of-function experiments indicated that NR4A3 promoted proliferation via cyclin D1 pathway. CONCLUSION: Our data indicated that resveratrol prevented MCT-induced pulmonary vascular remodeling via miR-638 regulating NR4A3/cyclin D1 pathway.

Cavitation in inhomogeneous soft solids.

A tiny spherical cavity expands in a homogenous neo-Hookean solid when subjected to an externally applied hydrostatic tension. If the applied tension reaches 2.5 times the shear modulus of the solid, the cavity expands unboundedly. Such a phenomenon is usually referred to as cavitation in soft solids. In previous studies, the soft solid is often assumed to have homogeneous mechanical properties. In this article, we study cavity expansion in inhomogeneous soft solids through analytical formulation and finite element simulations. We find that cavitation in an inhomogeneous soft solid can be greatly different from that in a homogenous one. In particular, we show that the relationship between the applied hydrostatic tension and the cavity size can be either monotonic or non-monotonic, depending on the geometry and material properties of the soft solid. We hope the results obtained in this article will be helpful in understanding the cavitation phenomenon in complex soft materials.

Cavitation to fracture transition in a soft solid.

When a soft solid such as rubber, gel and soft tissue is subject to hydrostatic tension, a small cavity inside the solid expands. For a neo-Hookean solid, when the hydrostatic tension approaches a critical value: 2.5 times its shear modulus, the initially small cavity can expand unboundedly. Such a phenomenon is usually referred to as cavitation instability in soft solids. Several recent experiments have shown that fractures may occur in the material when the hydrostatic tension is far below the critical value. In this article, we study a spherical cavity with a ring crack on its wall and inside a neo-Hookean elastomer subject to hydrostatic tension. We compute the energy release rate associated with the extension of the ring crack, for both pressure-control and (cavity) volume-control loading modes. We find that for the pressure-control mode, the energy release rate increases with the increase of the crack size as well as the magnitude of pressure; for the (cavity) volume-control mode, with a fixed cavity volume, the energy release rate increases with the increase of the crack size when the crack is short; the energy release rate maximizes for an intermediate crack size, and decreases with the increase of crack size when the crack is long. The results obtained in this article may be helpful for understanding cavitation-to-fracture transition in soft solids subject to different loading conditions.

Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.

AIMS: As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation. MATERIALS AND METHODS: Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels. RESULTS: Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly. CONCLUSION: So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.

Nanoscale crosslinking in thermoset polymers: a molecular dynamics study.

In this paper, the nanoscale crosslinking process of thermoset polymer is studied using all-atom molecular dynamics. Based on the crosslinking simulations, the elastic properties of typical E51/593 thermoset polymer are predicted and verified by tensile experiments within a 10% error. The proposed method reveals a reliable understanding of the nanoscale crosslinking reactions occurring in thermoset polymers. Changes in system energy and overall density distribution, as well as the quantification of bond formation, yield a better insight into thermoset crosslinking that would be difficult to obtain through experimentation. The results give us confidence in realizing the virtual design of thermosets leading to tunable properties.

[Diagnostic value of computed tomography-guided percutaneous needle biopsy versus radial probe endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions].

OBJECTIVE: To evaluate the value of computed tomography-guided percutaneous needle biopsy (CT-PNB) and radial probe endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in the diagnosis of peripheral pulmonary lesions(PPLs). METHODS: The clinical data of 213 patients who were diagnosed as to have PPLs in the First Affiliated Hospital of Soochow University between December 1, 2012 and October 1, 2014 were studied retrospectively. The patients were divided into CT-PNB group and EBUS-TBLB group, according to biopsy methods. The diagnostic yield, complications and influencing factors of both groups were evaluated. RESULTS: The diagnostic yield (87.2%, 102/117) and complication rate (18.8%, 22/117) of the CT-PNB group were higher than those of the EBUS-TBLB group(61.5%, 59/96 and 18.8%, 22/117, respectively), the differences being statistically significant (χ(2)=18.906, P=0.000 and χ(2)=10.542, P=0.001, respectively). Analysis of the influencing factors showed that there were statistically significant correlations between pneumothorax and the lesion diameter(χ(2)=5.785, P=0.016) and location(χ(2)=7.559, P=0.006) in the CT-PNB group. The diagnostic yield was correlated with lesion diameter(χ(2)=7.995, P=0.004) and location(χ(2)=4.608, P=0.027) in the EBUS-TBLB group. There was no complicated pneumothorax if the lesions were attached to the chest wall in the CT-PNB group. CONCLUSIONS: The diagnostic yield of CT-PNB in PPLs was better than that of EBUS-TBLB. Although CT-PNB had a higher complication rates, most complications were mild.

The interaction of a cobalt porphyrin with cancer-associated nitrosamines.

A cobalt porphyrin (CY-B) was presented, and its interaction with tobacco-specific nitrosamines (TSNAs) was investigated by UV-Vis spectroscopy and high-resolution mass spectrometry. The results revealed that the stoichiometry of the host-guest interaction was 1:2 and that the binding constant between CY-B and TSNAs was within the range of 0.78×10(8)-7.83×10(8)M(-2). The coordination strength between CY-B and TSNAs decreased in the sequence of NNN>NAB>NAT>NNK based on the binding constant. The interaction mechanism of CY-B with TSNAs involved a coordination interaction, and the π-π interaction between the porphyrin macrocycle and the aromatic frame of the TSNAs pyridines may also have been a driving force. The measured thermodynamic properties demonstrated that the reaction of CY-B with TSNAs was spontaneous and that the driving force for the interaction was a change in enthalpy. The reaction was exothermic, and an increasing temperature inhibited the interaction. The IR spectrum of the complex revealed that the NNO group of TSNAs and the metal cobalt of CY-B formed the six-coordinate complex.

Thermal conductivity of wrinkled graphene ring with defects.

Graphene rings have great prospects in the fields of biological modulators, electrochemical biosensors, and resonators, but are prone to wrinkling which can affect their physical properties. This work establishes a theoretical model predicting the torsional wrinkling behavior of defective monolayer graphene rings, which provides direct understanding and reliable accuracy of the wrinkle levels. Then the thermal conductivity of wrinkled graphene rings is studied considering different wrinkle levels, defect concentrations and radii. It is found that with increased radius, defect concentration and torsional angle, the ratio of wrinkle amplitude to wavelength increases gradually. Vacancy defects and radii have more significant influences on the thermal conductivity than torsional wrinkles. The main influence mechanism of wrinkles and defects on thermal conductivity is revealed by phonon density of state. This work provides theoretical guidance for thermal manipulation based on the wrinkle-tuning approach.

Study on the rationality of small diameter metallic airway stent in treatment of tracheal stenosis in injured rabbits.

BACKGROUND: To observe the occurrence of related complications after self-expandable metallic (SEM) airway stents implantation with different diameters at different time points, and to provide theoretical basis for the optimal chioce of existing airway stents in clinical practice. METHODS: Healthy New Zealand white rabbits were used to establish benign tracheal stenosis models after chest CT examination. Forty-fivemodel rabbits with more than 50% of airway stenosis were divided into two groups. Small-diameter SEM stents (The ratio of stent diameter to airway diameter is nearly 1.0) were implanted in Group A in 21 rabbits, and large-diameter tracheal stents (The ratio of stent diameter to airway diameter is more than 1.2) were implanted in Group B in 24 rabbits. Stent-related complications were observed after stent implantation in 2nd,4th,8th, and 12th week by bronchoscopygross anatomy, pathological and the expressions of IL-1RA, IL-8 and MMP9 in involved tracheal. RESULTS: The incidence rate of tracheomalacia of stent was significantly higher in group B (24/24 100%) than that in group A (1 /21,4.8%) (P < 0.05). The incidence rate of scar contracture at both ends of stent was significantly higher than in group B (11 / 24,45.8%) that in group A (2 /21, 9.5%) (P < 0.05). The pathological results of both A and B showed that the columnar epithelium of bronchial mucosa began to damage and detach, inflammatory cells infiltrated after 2nd and 4th week of stenting, The epithelium was repaired, the lamina propria glands almost disappeared, collagen fiber proliferation was obvious, and scars were formed after 8th and 12th week of stenting. ELISA results revealed that the expressions of IL-1RA, IL-8, and MMP9 were increased in the stent group than in model rabbit with benign tracheal stenosis. IL-1RA and MMP9 increased at different periods in group B, but the expression of IL-1RA and MMP9 showed a tread of increasing in the early stage and then decreasing in group A. CONCLUSION: Metal stents can cause different degrees of stent-related complications in rabbits with benign tracheal stenosis. The incidence of stent-induced tracheomalacia and scar contracture were higher in Group B than that in Group A. IL-1RA, IL-8 and MMP9 may be involved in the development of complications after stentimplantation and peak value of group B movered backward. ing.

Suppression of cyclin D1 by plasmid-based short hairpin RNA ameliorated experimental pulmonary vascular remodeling.

Our previous study has demonstrated that a plasmid-based short hairpin RNA (shRNA) against cyclin D1 could attenuate the pulmonary artery smooth muscle cell (PASMC) proliferation and pulmonary vascular remodeling in smoking rats. In this report, we examined the efficiency of this shRNA plasmid in monocrotaline-induced pulmonary vascular remodeling. A single injection of monocrotaline induced pulmonary vascular remodeling and cyclin D1 over-expression in pulmonary vascular smooth muscle. The shRNA successfully suppressed the up-regulation of cyclin D1 in pulmonary vessels of monocrotaline-treated rats. Moreover, this shRNA decreased the percentage of muscularized vessels and the wall thickness of pulmonary vessels. So, we concluded that plasmid-based shRNA against cyclin D1 ameliorated pulmonary vascular remodeling in monocrotaline-treated rats. Cyclin D1 might be a potential target for the therapy of pulmonary vascular remodeling and pulmonary hypertension.

The physics of wrinkling in graphene membranes under local tension.

The wrinkling characteristics of a rectangular graphene membrane under local tension are studied in this paper based on the continuum theory. The characteristics of the primary bifurcation and secondary wrinkling are studied to discover the physics of graphene wrinkling. The wrinkling geometry is predicted by a continuum theory model. The results reveal that the first wrinkle is formed at the primary bifurcation point. The non-uniform stretch-induced compressed effects, that originate from both the loaded portion and the clamped edges, buckle the graphene to form the first wrinkle. Secondary wrinkling is generated on the boundary of the wrinkled regions and the slack regions near the loaded portion in the post-wrinkling stage is the intrinsic nature of the wrinkling rupture and evolution of graphene. In addition, the length of the loaded portion and the aspect ratio of graphene have great effects on the wrinkling characteristics. These results are tremendously useful in understanding the intrinsic nature of the structural instability of graphene.

Circulating microRNAs as potential biomarkers for smoking-related interstitial fibrosis.

Numerous efforts have been made to indentify reliable and predictive biomarkers to detect the early signs of smoking-induced lung disease. Using 6-month cigarette smoking in mice, we have established smoking-related interstitial fibrosis (SRIF). Microarray analyses and cytokine/chemokine biomarker measurements were made to select circulating microRNAs (miRNAs) biomarkers. We have demonstrated that specific miRNAs species (miR-125b-5p, miR-128, miR-30e, and miR-20b) were significantly changed, both in the lung tissue and in plasma, and exhibited mainstream (MS) exposure duration-dependent pathological changes in the lung. These findings suggested a potential use of specific circulating miRNAs as sensitive and informative biomarkers for smoking-induced lung disease.

A retrospective cohort study of sintilimab and pembrolizumab as first-line treatments for advanced non-small cell lung cancer.

Background: Pembrolizumab and sintilimab have both been approved by the China National Medical Products Administration (NMPA) for the first-line treatment of advanced non-small cell lung cancer (NSCLC). These two drugs have several differences in biological characteristics and population in clinical trials. The current retrospective study was conducted to compare the efficacy and safety of sintilimab and pembrolizumab as first-line treatments in patients with advanced NSCLC. Methods: Consecutive patients with advanced NSCLC who received sintilimab or pembrolizumab as first-line therapy, with or without chemotherapy, from November 2018 to October 2021 in the First Affiliated Hospital of Soochow University and Dushu Lake Hospital Affiliated to Soochow University were retrospectively reviewed. Clinical data and treatment response were collected and survival was followed up. Kaplan-Meier method was used to estimate survival curves. The patients were divided into the sintilimab group and the pembrolizumab group according to the PD-1 inhibitors they received during treatment. The primary objective was to compare objective response rate (ORR) and progression-free survival (PFS) between the two groups. The secondary objectives were to compare disease control rate (DCR) and analyze adverse events (AEs) of the two groups. Results: A total of 124 patients were enrolled, including 68 patients (54.8%) in the sintilimab group and 56 patients (45.2%) in the pembrolizumab group. The baseline characteristics of the patients were comparable between the two groups. The ORR was 50% in the sintilimab group and 46.4% in the pembrolizumab group (P=0.69). The DCR was 89.7% and 89.3% in the sintilimab group and the pembrolizumab group, respectively (P=0.94). The median PFS time was 9.9 months in patients treated with sintilimab compared to 10.8 months in patients on pembrolizumab treatment [hazard ratio (HR) =0.960; 95% confidence interval (CI): 0.574-1.606; P=0.875]. The median OS time was not reached in either group of patients. The incidence of grade 3-4 treatment-related adverse events (TRAEs) was 25% (17/68) in the sintilimab group and 21.4% (12/56) in the pembrolizumab group. Conclusions: Sintilimab has similar efficacy to pembrolizumab as a first-line treatment option for patients with advanced NSCLC in clinical practice, with manageable AEs.

A Novel Strategy to Enhance the Performance of CO2 Adsorption Separation: Grafting Hyper-cross-linked Polyimide onto Composites of UiO-66-NH2 and GO.

Graphene oxide (GO) is widely used to improve the pore structure, dispersion capacity, adsorption selectivity, resistance to acids and bases, and thermal stability of metal-organic frameworks (MOFs). However, it remains a daunting challenge to enhance selectivity simply by modifying the pore surface polarity and producing a suitable pore structure for CO2 molecules through a combination of GO with MOFs. Herein, we demonstrate a novel porous hyper-cross-linked polyimide-UiO-graphene composite adsorbent for CO2 capture via in situ chemical knitting and condensation reactions. Specifically, a network of polyimides rich in carbonyl and nitrogen atoms with amino terminations was synthesized via the reaction of 4,4'-oxydiphthalic anhydride (ODPA) and 2,4,6-trimethyl-1,3-phenylenediamine (DAM). The product plays a crucial role in the separation of CO2 from N2. As expected, the resulting composite (PI-UiO/GO-1) exhibited a 3-fold higher CO2 capacity (8.24 vs 2.8 mmol·g-1 at 298 K and 30 bar), 4.2 times higher CO2/N2 selectivity (64.71 vs 15.43), and significantly improved acid-base resistance stability compared with those values of pristine UiO-66-NH2. Furthermore, breakthrough experiments verified that the porous composites can effectively separate CO2 from simulated fuel gas (CO2/N2 = 15/85 vol %) with great potential in industrial applications. More importantly, this strategy can be extended to prepare other MOF-based composites. This clearly advances the development of MOF-polymer materials for gas capture.