A soft-chemistry approach to the synthesis of amorphous calcium ortho/pyrophosphate biomaterials of tunable composition.

The development of amorphous phosphate-based materials is of major interest in the field of biomaterials science, and especially for bone substitution applications. In this context, we herein report the synthesis of gel-derived hydrated amorphous calcium/sodium ortho/pyrophosphate materials at ambient temperature and in water. For the first time, such materials have been obtained in a large range of tunable orthophosphate/pyrophosphate molar ratios.

Study of the interactions of a novel monoclonal antibody, mAb059c, with the hPD-1 receptor.

Programmed cell death 1 (PD-1) monoclonal antibodies have been approved by regulatory agencies for the treatment of various types of cancer, and the mechanism involves the restoration of T cell functions. We report herein the X-ray crystal structure of a fully human monoclonal antibody mAb059c fragment antigen-binding (Fab) in complex with the PD-1 extracellular domain (ECD) at a resolution of 1.70 Å.

One-pot synthesis of N-confused porphyrin-dipyrrin conjugates and their optical properties.

A conjugated N-confused porphyrin-dipyrrin system NCP-IN-X (X = H, Br, Cl, OMe, COOEt) has been reported via N-Confused tetraphenylporphyrin (NCTPP) as a π-enlarged pyrrole and substituted trimethylindole subunits in 75-82% yields by one pot. All the NCP-INs show red-shifted absorption and emission in the NIR range compared with NCTPP in a series nonpolar and polar solvents. Interesting, relative higher emission in DMF can be observed.

Intraspinal Paragonimiasis in Children: MRI Findings and Suggestions for Pathogenesis.

Background And Purpose: Intraspinal paragonimiasis is a rare entity for which imaging findings have seldom been described. The present study investigated the MR imaging features of spinal paragonimiasis, thus providing diagnostic imaging evidence and exploring the possible pathogenesis of intraspinal paragonimiasis.

Materials And Methods: The clinical and imaging findings of spinal paragonimiasis in 6 children were analyzed retrospectively.

Immunomodulatory Effects of Fruiting Body Extract and Solid-State-Cultivated Mycelia of .

is a rare and valuable medicinal mushroom indigenous to Taiwan. It has traditionally been used to promote good health. This study aimed to explore the immunomodulatory effects of "Leader Deluxe capsule" (LDAC).

Mechanistic and Kinetic Investigations on the Ozonolysis of Biomass Burning Products: Guaiacol, Syringol and Creosol.

The lignin pyrolysis products generated by biomass combustion make an essential contribution to the formation of secondary organic aerosols (SOAs). The ozone-initiated oxidation of guaiacol, syringol and creosol, major constituents of biomass burning, were investigated theoretically by using the density functional theory (DFT) method at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. Six primary addition reaction pathways and further decomposition routes with corresponding thermodynamic values were proposed.

In Situ Transformation of Prussian-Blue Analogue-Derived Bimetallic Carbide Nanocubes by Water Oxidation: Applications for Energy Storage and Conversion.

Using bimetallic Prussian blue analogue (PBA) as a precursor is effective for preparing electrocatalysts for the oxygen evolution reaction (OER); however, the role of these PBA-derived catalysts in the OER is still ambiguous. Herein, by simply controlling synthesis temperature, a bimetallic PBA-derived O,N-codoped Ni-Fe carbide, can be well tuned to optimize structure and OER performance. Importantly, by a series of ex situ and in situ investigations, real active species of NiFeO H are in situ formed on the surface during the OER, which reveals a "pre-catalyst" role of O,N-codoped Ni-Fe carbides.

Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.

Background: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

Methods: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death.

A non-covalent inhibitor XMU-MP-3 overrides ibrutinib-resistant Btk mutation in B-cell malignancies.

Background And Purpose: Bruton's tyrosine kinase (BTK) plays a key role in B-cell receptor signalling by regulating cell proliferation and survival in various B-cell malignancies. Covalent low-MW BTK kinase inhibitors have shown impressive clinical efficacy in B-cell malignancies. However, the mutant Btk poses a major challenge in the management of B-cell malignancies by disrupting the formation of the covalent bond between BTK and irreversible inhibitors, such as ibrutinib.

Interplay of Collective Electrostatic Effects and Level Alignment Dictates the Tunneling Rates across Halogenated Aromatic Monolayer Junctions.

Predictions about the electrical conductance across molecular junctions based on self-assembled monolayers (SAMs) are often made from the SAM precursor properties. Collective electrostatic effects, however, in a densely packed SAM can override these predictions. We studied, experimentally and theoretically, molecular tunneling junctions based on thiolate SAMs with an aromatic biphenyl backbone and variable, highly polarizable halogen termini X (S-(CH)X; X = H, F, Cl, Br, or I).

High-Nuclearity Chiral 3 d-4 f Heterometallic Clusters LnCu and LnCu.

Based on the anion template and chiral ligand inducting role, two series of high-nuclearity 3 d-4 f heterometallic clusters with formulas [NO@LnCu(μ-OH)(μ-OH)(OAc)( R/ S-L)(HO)](NO)· x(HO) (Ln = Dy, x = 30 for 1a( R-L) and 1b( S-L); Ln = Tb, x = 40 for 2a( R-L) and 2b( S-L)) and (EtNH)[LnCu(μ-OH)(μ-Cl)Cl( R/ S-L)]Cl· x(HO) (Ln = Dy, x = 28 for 3a( R-L) and 3b( S-L); Ln = Tb, x = 33 for 4a ( R-L) and 4b( S-L); HL = ( R/ S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid), have been synthesized and characterized. Structural analysis reveals that the metal skeleton of compounds 1 and 2 display a LnCu octahedral inner core encapsulated by six outer Cu units. In the LnCu octahedron, 6 Ln ions located at the six vertices and 12 inner Cu ions located at the 12 edges of octahedron, and one NO locates in the center of the octahedron.

Silencing of Long Noncoding RNA Nespas Aggravates Microglial Cell Death and Neuroinflammation in Ischemic Stroke.

Background and Purpose- Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and a major cause of long-term disability. Recently, long noncoding RNAs have been revealed, which are tightly associated with several human diseases. However, the functions of long noncoding RNAs in ischemic stroke still remain largely unknown.

Rhodium-Catalyzed C═N Bond Formation through a Rebound Hydrolysis Mechanism and Application in β-Lactam Synthesis.

A rhodium-catalyzed reaction of N-hydroxyanilines with diazo compounds to produce α-imino esters was developed. Distinct from the commonly accepted 1,2-H transfer for normal X-H insertion reactions, density functional theory calculations indicate that this transformation proceeds via a novel rebound hydrolysis mechanism. Furthermore, a three-component reaction was explored to synthesize highly functionalized β-lactams in good yields and diastereoselectivities.

Hybrid channel induced forming-free performance in nanocrystalline-Si:H/a-SiNx:H resistive switching memory.

The unique forming-free feature of Si-based resistive switching memory plays a key role in the industrialization of next generation memory in the nanoscale. Here we report on a new forming-free nanocrystalline-Si:H (nc-Si:H)/SiN:H resistive switching memory that can be obtained by deposition of hydrogen diluted nc-Si on hydrogen plasma treated a-SiN:H layer. It is found that nc-Si dots with areal density of 5.

A tightly-bonded and flexible mesoporous zeolite-cotton hybrid hemostat.

Achieving rapid definitive hemostasis is essential to ensure survival of patients with massive bleeding in pre-hospital care. It is however challenging to develop hemostatic agents or dressings that simultaneously deliver a fast, long-lasting and safe treatment of hemorrhage. Here, we integrate meso-/micro-porosity, blood coagulation and stability into a flexible zeolite-cotton hybrid hemostat.

Impact of Platelet Endothelial Aggregation Receptor-1 Genotypes on Platelet Reactivity and Early Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention and Treated With Aspirin and Clopidogrel.

Background: The genetic determinants of response to clopidogrel and aspirin are incompletely characterized. Recently, PEAR1 (platelet endothelial aggregation receptor-1) rs12041331 polymorphism has been shown to influence the platelet reactivity, but its impact on cardiovascular outcomes remains unclear in patients treated with antiplatelet agents.

Methods And Results: In this prospective cohort study, 2439 Chinese patients with acute coronary syndrome or stable coronary artery disease undergoing coronary stent implantation and receiving clopidogrel and aspirin were consecutively recruited.

Synthesis, crystal structures and insulin-like activity of three new oxidovanadium(V) complexes with aroylhydrazone ligand.

Three new oxidovanadium(V) complexes were designed, synthesized and characterized by C, H, N elemental analysis, single crystal X-ray diffraction，UV/Vis and IR spectra. Complex 1: [VOLX] (HL = (E)-N'-(2-hydroxybenzylidene)-3-methbenzohydrazide, HX = ethylmaltol = 2-ethyl-3-hydroxy-4-pyrone), Complex 2: [VOL(CHO)(CHOH)], (HL = CHNO = (E)-N'-(2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide, CHOH = methanol), Complex 3: [VOLX] (HL = (E)-N'-(3-ethoxy-2-hydroxybenzylidene)-3,5-dimethoxybenzohydrazide). The insulin-like activity of the three complexes was tested.

Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma.

Relapsed and refractory (R/R) multiple myeloma (MM) patients have very poor prognosis. Chimeric antigen receptor modified T (CAR T) cells is an emerging approach in treating hematopoietic malignancies. Here we conducted the clinical trial of a biepitope-targeting CAR T against B cell maturation antigen (BCMA) (LCAR-B38M) in 17 R/R MM cases.

Cardiomyocyte PKA Ablation Enhances Basal Contractility While Eliminates Cardiac β-Adrenergic Response Without Adverse Effects on the Heart.

Rationale: PKA (Protein Kinase A) is a major mediator of β-AR (β-adrenergic) regulation of cardiac function, but other mediators have also been suggested. Reduced PKA basal activity and activation are linked to cardiac diseases. However, how complete loss of PKA activity impacts on cardiac physiology and if it causes cardiac dysfunction have never been determined.

One-step deconvolution for multi-angle TIRF microscopy with enhanced resolution.

Total internal reflection fluorescence microscopy (TIRF microscopy) uses a rapid decay of evanescent waves to excite fluorophores within several hundred nanometers () beneath the plasma membrane, which can effectively suppress excitation of fluorescence signals in the deep layers. From image stacks obtained with a plurality of different incident angles, a three-dimensional spatial structure of the observed sample can be reconstructed by a Multi-Angle-TIRF (MA-TIRF) algorithm that provides an axial resolution of ~50 . Taking into account the point spread function (PSF) of the TIRF microscopes, we further increase its lateral resolution by introducing a fast deconvolution algorithm into the reconstruction of MA-TIRF data (DMA-TIRF), which is approached in just one step of minimizing the reconstruction function.

DKK3 (Dikkopf-3) Transdifferentiates Fibroblasts Into Functional Endothelial Cells-Brief Report.

Objective- To determine the role of a cytokine-like protein DKK3 (dikkopf-3) in directly transdifferentiating fibroblasts into endothelial cells (ECs) and the underlying mechanisms. Approach and Results- DKK3 overexpression in human fibroblasts under defined conditions for 4 days led to a notable change in cell morphology and progenitor gene expression. It was revealed that these cells went through mesenchymal-to-epithelial transition and subsequently expressed KDR (kinase insert domain receptor) at high levels.

MRI of Iron Oxide Nanoparticles and Myeloperoxidase Activity Links Inflammation to Brain Edema in Experimental Cerebral Malaria.

Purpose To investigate the association of inflammation and brain edema in a cerebral malaria (CM) mouse model with a combination of bis-5-hydroxy-tryptamide-diethylenetriaminepentaacetate gadolinium, referred to as MPO-Gd, and cross-linked iron oxide nanoparticle (CLIO-NP) imaging. Materials and Methods Female wild-type (n = 23) and myeloperoxidase (MPO) knock-out (n = 5) mice were infected with the Plasmodium berghei ANKA strain from May 2016 to July 2018. Seven healthy mice served as control animals.

Theoretical and conceptual DFT study of pnicogen- and halogen-bonded complexes of PHX---BrCl.

The pnicogen and halogen bonding interactions in the PHX---BrCl(X = H, F, OH, OCH and CH) complexes have been studied at the MP2/aug-cc-pVTZ level. Analysis of interaction energies shows that the pnicogen-bonded structures are less stable than the corresponding halogen-bonded structures. The pnicogen and halogen bonds were also studied by conceptual DFT reactivity indices.

Glucose-Sensitive Myokine/Cardiokine MG53 Regulates Systemic Insulin Response and Metabolic Homeostasis.

Background: Mitsugumin 53 (MG53 or TRIM72), a striated muscle-specific E3 ligase, promotes ubiquitin-dependent degradation of the insulin receptor and insulin receptor substrate-1 and subsequently induces insulin resistance, resulting in metabolic syndrome and type 2 diabetes mellitus (T2DM). However, it is unknown how MG53 from muscle regulates systemic insulin response and energy metabolism. Increasing evidence demonstrates that muscle secretes proteins as myokines or cardiokines that regulate systemic metabolic processes.