Synthesis of biodegradable Mg-Zn alloy by mechanical alloying: Statistical prediction of elastic modulus and mass loss using fractional factorial design

Biodegradable Mg-Zn alloy was synthesized using mechanical alloying where a statistical model was developed using fractional factorial design to predict elastic modulus and mass loss of the bulk alloy. The effects of mechanical alloying parameters (i.e., milling time, milling speed, ball-to-powder mass ratio and Zn content) and their interactions were investigated involving 4 numerical factors with 2 replicates, thus 16 runs of two-level fractional factorial design. Results of analysis of variance (ANOVA), regression analysis and R² test indicated good accuracy of the model. The statistical model determined that the elastic modulus of biodegradable Mg-Zn alloy was between 40.18 and 47.88 GPa, which was improved and resembled that of natural bone (30–57 GPa). Corrosion resistance (mass loss of pure Mg, 33.74 mg) was enhanced with addition of 3%–10% Zn (between 9.32 and 15.38 mg). The most significant independent variable was Zn content, and only the interaction of milling time and ball-to-powder mass ratio was significant as P-value was less than 0.05. Interestingly, mechanical properties (represented by elastic modulus) and corrosion resistance (represented by mass loss) of biodegradable Mg-Zn alloy can be statistically predicted according to the developed models.     

Thermal cleavage of the fmoc protection group

The Fmoc protection group is among the most commonly used protection groups for the amino function. A fast method for the thermal deavage of this protection group under base-free conditions without the need for dibenzofulvene scavengers is presented. The advantages of this method include straightforward testability by means of a simple high-temperature NMR experiment, usually high yields, and good selectivity towards the BOC protection group and t-butyl ethers.     

Mesenchymal Stem Cell Treatment Perspectives in Peripheral Nerve Regeneration: Systematic Review

Traumatic peripheral nerve lesions affect hundreds of thousands of patients every year; their consequences are life-altering and often devastating and cause alterations in movement and sensitivity. Spontaneous peripheral nerve recovery is often inadequate. In this context, nowadays, cell therapy represents one of the most innovative approaches in the field of nerve repair therapies. The purpose of this systematic review is to discuss the features of different types of mesenchymal stem cells (MSCs) relevant for peripheral nerve regeneration after nerve injury. The published literature was reviewed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A combination of the keywords “nerve regeneration”, “stem cells”, “peripheral nerve injury”, “rat”, and “human” were used. Additionally, a “MeSH” research was performed in PubMed using the terms “stem cells” and “nerve regeneration”. The characteristics of the most widely used MSCs, their paracrine potential, targeted stimulation, and differentiation potentials into Schwann-like and neuronal-like cells are described in this paper. Considering their ability to support and stimulate axonal growth, their remarkable paracrine activity, their presumed differentiation potential, their extremely low immunogenicity, and their high survival rate after transplantation, ADSCs appear to be the most suitable and promising MSCs for the recovery of peripheral nerve lesion. Clinical considerations are finally reported.     

The Triazole Ring as a Privileged Scaffold for Putative Antifungals: Synthesis and Evaluation of a Series of New Analogues

The significant antifungal activity of a series of novel 1,2,4-triazole derivatives against different strains of Candida albicans, Candida krusei and Aspergillus fumigatus, compared to the commercial fungicides ketoconazole and itraconazole, is reported. Systemic mycosis and invasive fungal infections, whether from immunodeficiency or hospital-acquired infection, have been on an upward trend for several years. The 1,2,4-triazole ring substituted with other aromatic and heteroaromatic systems plays an important role in the field of antifungal drug discovery and development. Thus, an extensive series of 29 triazoles, substituted in different positions with a variety of aromatic rings, has been designed, synthesized, and evaluated for their fungicidal activity. Almost all the agents tested in vitro showed high activity against all examined fungal strains. It is noteworthy that, in the case of A. fumigatus, all the examined compounds achieved equal or higher antifungal activity than ketoconazole, but less activity than itraconazole. Among all the derivatives studied, the dichlorourea analogue and bromo-substituted triazole stand out as the most promising compounds. Quantitative structure-activity relationship (QSAR) models were built for a systematic structure-activity relationship (SAR) profile to explain and potentially explore the potency characteristics of 1,2,4-triazole analogues.     

Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes

The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of the tumor microenvironment (TME) collaborate to mechanically condition the extracellular matrix (ECM) making it inhospitable to immune cells. TME is composed of several cell lines besides cancer cells, including tumor-associated macrophages, cancer-associated fibroblasts, CD4⁺ and CD8⁺ lymphocytes, and innate immunity cells. These populations interface with each other to prepare a conservative response, capable of evading the defense mechanisms implemented by the host’s immune system. The presence or absence, in particular, of cytotoxic CD8⁺ cells in the vicinity of the main tumor mass, is able to predict, respectively, the success or failure of drug therapy. Among various mechanisms of immunescaping, in this study, we characterized the modulation of the phenotypic profile of CD4⁺ and CD8⁺ cells in resting and activated states, in response to the mechanical pressure exerted by a three-dimensional in vitro system, able to recapitulate the rheological and stiffness properties of the tumor ECM.     

TG68, a Novel Thyroid Hormone Receptor-β Agonist for the Treatment of NAFLD

Activation of thyroid hormone receptor β (THRβ) has shown beneficial effects on metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of TG68, a novel THRβ agonist, on fatty liver accumulation and liver injury in mice fed a high-fat diet (HFD). C57BL/6 mice fed HFD for 17 or 18 weeks, a time when all mice developed massive steatohepatitis, were then given TG68 at a dose of 9.35 or 2.8 mg/kg for 2 or 3 weeks, respectively. As a reference compound, the same treatment was adopted using equimolar doses of MGL-3196, a selective THRβ agonist currently in clinical phase III. The results showed that treatment with TG68 led to a reduction in liver weight, hepatic steatosis, serum transaminases, and circulating triglycerides. qRT-PCR analyses demonstrated activation of THRβ, as confirmed by increased mRNA levels of Deiodinase-1 and Malic enzyme-1, and changes in lipid metabolism, as revealed by increased expression of Acyl-CoA Oxidase-1 and Carnitine palmitoyltransferase-1. The present results showed that this novel THRβ agonist exerts an anti-steatogenic effect coupled with amelioration of liver injury in the absence of extra-hepatic side effects, suggesting that TG68 may represent a useful tool for the treatment of NAFLD.     

Cationic and radical polymerization of N-vinyl-2-phenylpyrrole: Synthesis of electroconducting,paramagnetic and fluorescent oligomers

Cationic polymerization of N-vinyl-2-phenylpyrrole (catalysts: Me₃SiCl, CF₃COOH, BF₃·OEt₂, HCl, WCl₆, FeCl₃, complex LiBF₄–dimethoxyethane, catalysts concentration 1–2 wt%, 20–70 °C, 24–48 h) affords oligomers (molecular weight 1400–1700) of a unexpected structure with alternating 2-phenylpyrrole and ethylydene units, the yields reaching 63%. The oligomers structure has been supported by isolation and identification of the corresponding dimer, N-vinyl-2-phenyl-5-[N-(2-phenyl-1H-pyrrol-1-yl)ethyl]-1H-pyrrole. Radical polymerization of the same monomer (AIBN, 1.5–4 wt%, 60–80 °C, 40–60 h or UV irradiation or both) gives oligomers (molecular weight 2100–3000) of normal structure having polyethene backbone with pendant 2-phenylpyrrole groups in up to 40% yields. The oligomers of both types are semiconductors (1.3 × 10^?6–3.6 × 10^?6 S/cm) after doping with I₂, paramagnetic (4.2 × 10¹⁷–8.7 × 10¹⁷ g^?1) and fluorescent in a near UV region (λ 355–363 nm, acetonitrile).     

Use of the SAW Sensor Electronic Nose for Detecting the Adulteration of Virgin Coconut Oil with RBD Palm Kernel Olein

An electronic nose (zNose™) was applied to the detection of adulteration of virgin coconut oil. The system, which is based on a surface acoustic wave sensor was used to generate a pattern of volatile compounds present in the samples. Virgin coconut oil was mixed with refined, bleached and deodorized palm kernel olein at a level of adulteration from 1 to 20% (wt/wt). Adulterant peaks were identified from the chromatogram profile and fitted to a curve using linear regression. The best relationship (R ² = 0.91) was obtained between the peak tentatively identified as methyl dodecanoate and the percentage of palm kernel olein added. Pearson’s correlation coefficients (r) of 0.92 and 0.89 were obtained between adulterant peak methyl dodecanoate and of the iodine and peroxide values, respectively. Principal component analysis (PCA) was used to differentiate between pure and adulterated samples. The PCA provided good differentiation of samples with 74% of the variation accounted for by PC 1 and 17% accounted for by PC 2. Pure samples formed a separate cluster from all of the adulterated samples.     

A three-dimensional carbon-coated LiFePO4 electrode for high-power applications

The fabrication process of a new, three-dimensional carbon-coated LiFePO₄ electrode by sol–gel synthesis in situ on interconnected conducting fibers of carbon paper is described. This three-dimensional structure ensures overall electrode conductivity, facilitates lithium diffusion in and out of LiFePO₄ particles and, hence, enables good cycling stability at 1C-rate and maximum pulse-power values that exceed those of planar LiFePO₄ electrodes at high electrode loading.     

alpha,alpha-Cyclopentaneglycine dipeptides capped with biaryls as tachykinin NK(2) receptor antagonists

The NK(2) receptor belongs to the family of tachykinin neurotransmitters. It has been reported to be involved in several pathological conditions, and selective antagonists are potentially useful drugs for the treatment of asthma, irritable bowel syndrome, cystitis, and depression. Starting from in-house capped dipeptide libraries, we were able to identify a number of molecules with sub-nanomolar binding affinity for the hNK(2) receptor. All were characterized by a rigid core structure with a strong constraint induced by an alpha,alpha-cyclopentaneglycine fragment. Herein we report the further elaboration of three initial basic structures. The planar benzothiophene group was substituted with a series of biphenyl and heterobiphenyl moieties that are well tolerated in terms of receptor affinity. The new compounds also maintained good antagonist potency in an in vitro functional assay, and a number of them showed significant in vivo activity after intravenous administration in our guinea pig model.