Paeonol inhibits melanoma growth by targeting PD1 through upregulation of miR-139-5p.

The abnormal immune response mediated by malignant melanoma is related to PD1. Paeonol has pharmacological antitumor activity. Previous studies have indicated that paeonol induces tumor cell apoptosis, but its underlying mechanism in tumor immunity remains unknown. In this study, malignant melanoma was established in normal and thymectomized mice to determine the important role of the thymus in the antitumor effects of paeonol. Paeonol-treated thymocytes were cocultured with melanoma cell spheres to further evaluate the regulatory role of thymocytes in tumor immune dysfunction. Studies have shown that PD1 may be targeted by miR-139-5p. Our results revealed that tumor-induced thymic atrophy was significantly accompanied by high PD1 expression and low miR-139-5p expression. Interestingly, paeonol significantly reversed thymic atrophy and largely protected thymocytes against low PD1 expression and high miR-139-5p expression. Dual-luciferase assays indicated that miR-139-5p interacted with the 3' untranslated region (3'-UTR) of PD1. These results showed that paeonol alleviates PD1-mediated antitumor immunity by reducing miR-139-5p expression and demonstrated a novel mechanism for melanoma immunotherapy.

Early Results of the Newly-Designed Flowdynamics Dense Mesh Stent for Residual Dissection After Proximal Repair of Stanford Type A or Type B Aortic Dissection: A Preliminary Single-Center Report From a Multicenter, Prospective, and Randomized Study.

BACKGROUND: Negative remodeling of the distal aorta due to residual dissection significantly impacts the long-term outcomes of dissection patients after proximal repair of acute aortic dissection. Branched/fenestrated aortic stents are technically demanding, and studies of the first generation of multilayer flow modulators for tackling this clinical scenario are few and limited. The single-center results from a multicenter, prospective, and randomized controlled study aimed to verify the safety and effectiveness of a newly-designed flowdynamics dense mesh stent for treating residual dissection after proximal repair. METHODS: Patients with nonchronic residual dissection involving visceral branches were prospectively enrolled in 3 centers (ChiCTR1900023638). Eligible patients were randomly assigned to the flowdynamics dense mesh stent (FDMS) group and control group. Follow-up visits were arranged at 1, 3, 6, and 12 months after recruitment. The primary endpoints were all-cause and aortic-related mortality. The secondary endpoints included visceral branch occlusion, reintervention, and severe adverse events. Morphological changes were analyzed to exhibit the therapeutic effect. Our center participated in the multicenter prospective randomized controlled trial, and the preliminary single-center experience was reported. RESULTS: Thirty-six patients were enrolled in our center, and the baseline characteristics of the 2 groups were comparable. Thirty-four patients completed the 12 month follow-up. Freedom from all-cause and aortic-related death were 94.4% and 100%. All visceral branches remained patent in the FDMS group. Increased area of the true lumen (1.03±0.38 vs 0.48±0.63 cm2 at the plane below renal arteries, p=0.006; 1.27±0.80 vs 0.32±0.50 cm2 at the plane 5 cm below renal arteries, p<0.001) and decreased area of the false lumen at the plane below renal arteries (-1.03±0.84 vs -0.15±1.21 cm2, p=0.023) were observed in the FDMS group compared with those parameters in the control group. The FDMS group showed a significant increase in true lumen volume (p<0.001) and a significant decrease in false lumen volume (p=0.018). CONCLUSIONS: This newly-designed FDMS for endovascular repair of residual dissection after the proximal repair is safe and effective at 12 months. CLINICAL IMPACT: One-year results of the randomized controlled clinical trial indicated the short-term safety and promising effect of FDMS on treating non-chronic residual dissection after proximal repair. At the 12th-month follow-up, the true lumen expanded, the false lumen shrunk and all visceral arteries kept patent. As far as I'm concerned, this is the first randomized controlled study concerning utilizing multilayer flow mesh stent treating aortic dissection. Despite a preliminary single-center report, our results are supposed to provide high-quality evidence to guide clinical practice and fill the gap in the application of FDMS.

Iridium-catalysed thioether-directed regioselective cycloaddition of internal alkynes with azides.

We report herein a cationic iridium-catalysed thioether-directed alkyne-azide cycloaddition reaction. Diverse 2-alkynyl phenyl sulfides can undergo cycloaddition with different azides in a regioselective fashion. The reaction features high efficiency, a short reaction time, and a broad substrate scope, providing modular access to complex S-containing triazoles.

Z-Selective access to α-trifluoromethyl arylenes through Pd-catalysed fluoroarylation of 1,1-difluoroallenes.

The synthesis of stereo-defined α-trifluoromethyl arylenes is of great importance in medical chemistry, organic chemistry, and materials science. However, despite the recent advances, the Z-selective formation of α-trifluoromethyl arylenes has remained underdeveloped. Here, we describe a facile approach towards Z-α-trifluoromethyl arylenes through Pd-catalysed stereoselective fluoroarylation of 1,1-difluoroallenes in the presence of a bulky monophosphine ligand.

Atomic Magnetometer Achieves Visual Salience Analysis in Drosophila.

An atomic magnetometer (AM) was used to non-invasively detect the tiny magnetic field generated by the brain of a single Drosophila. Combined with a visual stimulus system, the AM was used to study the relationship between visual salience and oscillatory activity of the Drosophila brain by analyzing changes in the magnetic field. Oscillatory activity of Drosophila in the 1-20 Hz frequency band was measured with a sensitivity of 20 fT/Hz. The field in the 20-30 Hz band under periodic light stimulation was used to explore the correlation between short-term memory and visual salience. Our method opens a new path to a more flexible method for the investigation of brain activity in Drosophila and other small insects.

An Integrated Single-Beam Three-Axis High-Sensitivity Magnetometer.

Three-axis atomic magnetometers have great advantages for interpreting information conveyed by magnetic fields. Here, we demonstrate a compact construction of a three-axis vector atomic magnetometer. The magnetometer is operated with a single laser beam and with a specially designed triangular 87Rb vapor cell (side length is 5 mm). The ability of three-axis measurement is realized by reflecting the light beam in the cell chamber under high pressure, so that the atoms before and after reflection are polarized along two different directions. It achieves a sensitivity of 40 fT/Hz in x-axis, 20 fT/Hz in y-axis, and 30 fT/Hz in z-axis under spin-exchange relaxation-free regime. The crosstalk effect between different axes is proven to be little in this configuration. The sensor configuration here is expected to form further values, especially for vector biomagnetism measurement, clinical diagnosis, and field source reconstruction.

Ni-catalysed deamidative fluorination of amides with electrophilic fluorinating reagents.

We describe here a Ni-catalysed deamidative fluorination of diverse amides with electrophilic fluorinating reagents. Different types of amides including aromatic amides and olefinic amides were well compatible, affording the corresponding acyl fluorides in good to excellent yields.

Direct N-alkylation of sulfur-containing amines.

An efficient ruthenium-catalyzed method has been developed for the direct N-alkylation of sulfur-containing amines with alcohols, for the first time, by a step-economical and environmentally friendly hydrogen borrowing strategy. The present methodology features base-free conditions and broad substrate scope, with water being the only by-product. Moreover, this protocol has been applied to the synthesis of the pharmaceutical drug Quetiapine.

Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases.

Schwann cells (SCs) are a highly plastic cell type capable of undergoing phenotypic changes following injury or disease. SCs are able to upregulate genes associated with nerve regeneration and ultimately achieve functional recovery. During the regeneration process, the extracellular matrix (ECM) and cell morphology play a cooperative, critical role in regulating SCs, and therefore highly impact nerve regeneration outcomes. However, the roles of the ECM and mechanotransduction relating to SC phenotype are largely unknown. Here, we describe the role that matrix stiffness and cell morphology play in SC phenotype specification via known mechanotransducers YAP/TAZ and RhoA. Using engineered microenvironments to precisely control ECM stiffness, cell shape, and cell spreading, we show that ECM stiffness and SC spreading downregulated SC regenerative associated proteins by the activation of RhoA and YAP/TAZ. Additionally, cell elongation promoted a distinct SC regenerative capacity by the upregulation of Rac1/MKK7/JNK, both necessary for the ECM and morphology changes found during nerve regeneration. These results confirm the role of ECM signaling in peripheral nerve regeneration as well as provide insight to the design of future biomaterials and cellular therapies for peripheral nerve regeneration.

Diffusion Modelling on the Microstructure Evolution in MCrAlY-Superalloy System.

Elemental diffusion drives the microstructure development in the MCrAlY-superalloy systems at high temperature. In this paper, two diffusion models were built to simulate the diffusion behavior of elements in the coating or in the coating-substrate system. Firstly, a core-shell model was set up to investigate the thermodynamic and kinetic behavior of the localized microstructure. The results of the simulation successfully explained the mechanism of the formation of α(core)-γ'(shell) structure at lower temperature (750 °C) and γ(core)-ß(shell) structure at higher temperature (1100 °C). Secondly, a coating-substrate planner model was used to simulate the interdiffusion of elements between the MCrAlY coating and the superalloy substrate. The simulation results in the Ni22Cr10AlY-superalloy system semiquantitatively agreed with the experimental observation. Furthermore, by applying the planner diffusion model, the effect of the MCrAlY coatings on the formation of TCP phases in the substrate was studied, and a GOODMAN map for designing TCP-limited MCrAlY coatings can be provided.

Regio- and Enantioselective Friedel-Crafts Benzhydrylation of Indoles in Carbocyclic Ring with ortho-Quinomethanes: Access to Chiral Diarylindolylmethanes.

The functionalization of indoles in the carbocyclic ring has been achieved via organocatalytic enantioselective Friedel-Crafts benzhydrylation of hydroxyindoles with in situ generated ortho-quinomethanes in oil-water biphases, allowing an efficient access to varied diarylindolylmethanes with a wide substrate scope. The high yields, excellent stereoselectivities, mild conditions, low catalyst loading, and easy scalability also demonstrated the interest of this novel methodology.

Nitrate promoted mild and versatile Pd-catalysed C(sp2)-H oxidation with carboxylic acids.

A nitrate-promoted Pd-catalysed mild cross-dehydrogenative C(sp2)-H bond oxidation of oximes or azobenzenes with diverse carboxylic acids has been developed. In contrast to the previous catalytic systems, this protocol features mild conditions (close to room temperature for most cases) and a broad substrate scope (up to 64 examples), thus constituting a versatile method to directly prepare diverse O-aryl esters. Moreover, the superiority of the nitrate additive in this mild transformation was further determined by experimental and computational evidence.

Effects of Hetiao Jianpi Decoction on Intestinal Injury and Repair in Rats with Antibiotic-Associated Diarrhea.

BACKGROUND Through observing the changes of indexes of the intestinal mucosal barrier and intestinal flora in rats, we explored the mechanism by which Hetiao Jianpi Decoction (HTJPD) treats antibiotic-associated diarrhea (AAD) by repairing intestinal mucosal injury and regulating intestinal flora. MATERIAL AND METHODS Samples of colon tissues were collected for HE staining. Enzyme-linked immunosorbent assay (ELISA) was used to assess levels of diamine oxidase (DAO) and D-lactic acid in rat plasma and the expression of secretory immunoglobulin A (SIgA) in colon tissue. We assessed the abundance of intestinal contents by high-throughput sequencing of the 16S rRNA gene. RESULTS Compared with the Model group, the muscle layer and intestinal mucosal edema were improved, and the continuity was restored; the levels of DAO and D-lactic acid in plasma decreased, and the SIgA level were increased in the HTJPD group. The structure of the intestinal flora changed, as indicated by increased levels of certain beneficial bacteria (Verrucomicrobia, Actinobacteria, CF231, and Akkermansia), decreased levels of pathogenic bacteria (Spirochaetes and Treponema), and increased species diversity. CONCLUSIONS By improving the permeability and immune function of the intestinal mucosa, Hetiao Jianpi decoction prevented the occurrence of AAD by repairing the intestinal mucosal damage and regulating the structure and diversity of intestinal flora.

Preparation of Large-Size, Superparamagnetic, and Highly Magnetic Fe3O4@PDA Core⁻Shell Submicrosphere-Supported Nano-Palladium Catalyst and Its Application to Aldehyde Preparation through Oxidative Dehydrogenation of Benzyl Alcohols.

Large-size, superparamagnetic, and highly magnetic Fe3O4@PDA core-shell submicrosphere-supported nano-palladium catalysts were prepared in this study. Dopamine was encapsulated on the surface of Fe3O4 particles via self-polymerization and then protonated to positively charge the microspheres. PdCl42- was dispersed on the surface of the microspheres by positive and negative charge attraction and then reduced to nano-palladium. With air as oxidant, the catalyst can successfully catalyze the dehydrogenation of benzyl alcohols to produce the corresponding aldehydes at 120 °C.

Multiscale Dynamic Growth and Energy Transport of Droplets during Condensation.

Condensation is an important physical process and has direct relevance for a range of engineering applications, including heat transfer, antifrosting, and self-cleaning. Understanding the mechanism of droplet growth during condensation is an important aspect, but past works have not typically considered the dynamics of the multiscale process. In this paper, we developed a dynamic growth model, which considers the continuous and multiscale nature of the droplet growth process from several nanometers to hundreds of microns. This model couples the transient phase change heat transfer and two-phase flow both inside and outside the droplet. Accordingly, the energy transport is distinct from the classical pure conduction model. We show that convection near the liquid-vapor interface and inside the droplets plays an increasingly important role as droplets grow and finally dominates the energy transport process. Driven by strong convection, the droplets mix well and the discrete layers of temperature observed in the pure conduction model disappear at the microscale. This model that considers convection can lead to over 4 times higher predicted overall heat transfer than that obtained with the pure conduction model. The interfacial mass flow through the liquid-vapor interface is the dominant factor responsible for the strong convection. We studied the critical radius where convection starts to have a significant influence on droplet growth under different subcooling temperatures and contact angles. Droplets have smaller critical radii under larger subcooling temperatures or larger contact angles, ranging from 0.5 to 20 µm. This work identifies the modes of energy transport in condensation at different scales, which not only enhances our fundamental understanding of individual droplet growth but provides design guidelines for various dropwise and jumping-droplet condensation research.

[Differential Reflectance Spectroscopy for In-Situ Monitoring of Organic Thin Films Growth in Vacuum Environment].

For realizing the real-time monitoring of organic thin film preparation process in vacuum environment, the present paper proposes a high precision measurement approach based on differential reflectance spectroscopy (DRS). An optical system was constructed with off the shelf optical components, such as off-axis parabolic mirror, optical flat and optical fiber. A differential algorithm was employed to analyze the spectral signals. Based on the homebuilt setup, instability induced by variation of temperature was investigated. It was concluded that with the good control of temperature and air flow, the measurement repeatability of this system is better than 2 per thousand for a long-term period. Furthermore, an initial stage of organic thin film growth of pentacene molecules on the surface of Au was studied. As compared with the data of film thickness gauge and atomic force microscope, DR spectra accurately recorded the fine optical evolution with sub-monolayer resolution, which is related to the growth of the thin film. As a result, the DR optical system exhibits characteristics of broad spectrum (range from 300 to 820 nm), high stability (repeatability better than 2X 10(-3)), and high precision (sub-monolayer resolution) after efforts were done to decrease the influences on the spectral quality produced by misalignments of the optical components, the defects of the optics, and the disturbances of the environmental conditions. It is indicated that the proposed DR method is suitable for real-time online monitoring of thin film growth with high precision.

Copper-catalyzed oxidative cyclization of 1,5-enynes with concomitant C-C bond cleavage: an unexpected access to 3-formyl-1-indenone derivatives.

A Cu(0)/Selectfluor system-mediated oxidative cyclization of 1,5-enynes with concomitant C-C bond cleavage to access 3-formyl-1-indenone derivatives is described. Preliminary mechanistic investigations disclosed that the C-C bond cleavage involved a novel water-participated oxygen-insertion ß-carbon elimination through double oxycuprations.

Mild and versatile nitrate-promoted C-H bond fluorination.

A novel and facile C-H bond fluorination proceeds under remarkably mild conditions (close to room temperature in most cases). Both aromatic and olefinic C(sp(2))-H bonds with a wide range of electronic properties are selectively fluorinated in the presence of a catalytic amount of simple, cheap, and nontoxic nitrate as the promoter. A Pd(II)/Pd(IV) catalytic cycle that is initiated by an in situ generated cationic [Pd(NO3)](+) species was proposed based on preliminary mechanistic studies.

Vector magnetocardiography using compact optically-pumped magnetometers.

Optically pumped magnetometers can provide functionality for bio-magnetic field detection and mapping. This has attracted widespread attention from researchers in the biomedical science field. Magnetocardiography has been proven to be an effective method for examining heart disease. Notably, vector magnetocardiography obtains more spatial information than the conventional method by only taking a component that is perpendicular to the chest surface. In this work, a spin-exchange-relaxation-free (SERF) magnetometer with a compact size of 14 mm × 25 mm × 90 mm was developed. The device has a high sensitivity of 25 fT/ Hz. Meanwhile, in the multichannel working mode, synchronous sensor manipulation and data acquisition can be achieved through our control software without additional data acquisition boards. Since a typical SERF magnetometer only responds to dual-axis magnetic fields, two sensors are orthogonally arranged to form a vector detection channel. Our system consists of seven channels and allows 7 × 9 vector MCG mapping by scanning. High-quality heart vector signals are measured, and P peak, QRS peak, and T peak can be distinguished clearly. To better demonstrate the vectorial information, a vector scatter plot form is also provided. Through a basic bio-electric current model, it demonstrates that triaxial MCG measurements capture a richer spatial current information than traditional uniaxial MCG, offering substantial diagnostic potential for heart diseases and shedding more light on the inversion of cardiac issues.

Multifold bond cleavage and formation between MeOH and quinoxalines (or benzothiazoles): synthesis of carbaldehyde dimethyl acetals.

A K(2)S(2)O(8)-mediated direct cross-coupling of quinoxalines (or benzothiazoles) with methanol leading to 2-quinoxalinyl (or 2-benzothiazolyl) carbaldehyde dimethyl acetals has been achieved. 2-Quinoxalinyl carbaldehyde dimethyl acetals were readily converted into 2-quinoxalinyl carbaldehydes in good to excellent yields under acidic conditions. Preliminary mechanistic studies suggest that the reaction proceeds via multifold bond cleavage and formation between methanol and N-heterocycles involving a dioxygen-participated radical process. This method allows for the synthesis of a variety of 2-quinoxalinyl (or 2-benzothiazolyl) carbaldehyde dimethyl acetals directly via cross-coupling of simple N-heterocyclic C-H bond and methanol under aldehyde-, acid-, and transition-metal-free conditions.