Inflammation Causes Exacerbation of COVID-19: How about Skin Inflammation?

COVID-19 is a recently emerged viral infection worldwide. SARS-CoV-2, the causative virus, is believed to have emerged from bat coronaviruses, probably through host conversion. The bat coronavirus which has the highest gene homology to SARS-CoV-2 specifically infects deep forest bats in China whose habitat extends through the Middle East to Southern Europe. Host conversion might have occurred due to the deforestation by humans exposing wild bats to the environment they had never encountered before. SARS-CoV-2 infects cells through two mechanisms: through its receptor ACE2 with the help of enzyme TMPRSS and through membrane fusion with the help of elastases in the inflammatory condition. Obesity, hypertension, diabetes mellitus, and pulmonary diseases cause poor prognosis of COVID-19. Aging is another factor promoting poor prognosis. These diseases and aging cause low-level and persistent inflammation in humans, which can promote poor prognosis of COVID-19. Psoriasis and atopic dermatitis are the major inflammatory skin diseases. These inflammatory skin conditions, however, do not seem to cause poor prognosis for COVID-19 based on the epidemiological data accumulated so far. These mechanisms need to be elucidated.     

Indentation creep of the wrought AZ31 magnesium alloy

Creep behavior of a wrought Mg–3Al–1Zn (AZ31) alloy was investigated by long-term Vickers indentation testing under constant loads of 5 and 10 N and at temperatures in the range 423–523 K. Based on the steady-state power-law creep relationship, the stress exponents were determined. The creep behavior can be divided into two stress regimes with different stress exponents and activation energy values. The low-stress regime activation energy of 96.2 kJ mol⁻¹, which can be interpreted as that for the activation energy for Al diffusion in Mg, and stress exponents of about 3.0–3.4 suggest that the operative creep mechanism is dislocation viscous glide governed by the diffusion of aluminum atoms in magnesium. This behavior is in contrast to the high-stress regime, in which the average values of n = 6 and Q = 132.4 kJ mol⁻¹ imply that dislocation climb-controlled creep is the dominant deformation mechanism. Stress exponents and activation energies obtained by different analysis methods of the indentation tests are in good agreement with each other and with those of the conventional tensile creep tests on AZ31 magnesium alloy reported in the literature. The localized indentation creep tests are, thus, considered capable of acquiring reliable information on the creep behavior of wrought magnesium alloys.     

Inflammatory Molecules Associated with Ultraviolet Radiation-Mediated Skin Aging

Skin is the largest and most complex organ in the human body comprised of multiple layers with different types of cells. Different kinds of environmental stressors, for example, ultraviolet radiation (UVR), temperature, air pollutants, smoking, and diet, accelerate skin aging by stimulating inflammatory molecules. Skin aging caused by UVR is characterized by loss of elasticity, fine lines, wrinkles, reduced epidermal and dermal components, increased epidermal permeability, delayed wound healing, and approximately 90% of skin aging. These external factors can cause aging through reactive oxygen species (ROS)-mediated inflammation, as well as aged skin is a source of circulatory inflammatory molecules which accelerate skin aging and cause aging-related diseases. This review article focuses on the inflammatory pathways associated with UVR-mediated skin aging.     

A coupled finite element genetic algorithm for optimum design of stiffened liquid-filled steel conical tanks

In the current study an optimum design technique of stiffened liquid-filled steel conical tanks subjected to global and local buckling constraints is developed using a numerical tool that couples a non-linear finite element model developed in-house and a genetic algorithm optimization technique. This numerical tool is an extended version of an earlier one, adapted for the optimum design of unstiffened conical tanks. The design variables considered in the current study are the shell thicknesses, the geometry of the steel vessel as well as the dimensions and number of stiffeners. The developed numerical tool is capable of selecting the set of design variables that leads to optimum safe design. The analysis is conducted twice; first, case of stiffeners free at their bottom edge, which represents the case of retrofitting an existing tank. In the second case the stiffeners are assumed to be anchored to the bottom slab of the tank, which represents the situation of a newly designed tank. Finally, the optimum design of the stiffened tanks is compared to the optimum design of unstiffened tanks computed in a previous study.     

A coupled finite element genetic algorithm technique for optimum design of steel conical tanks

Steel conical tanks having an upper cylindrical section and supported by a reinforced concrete shaft are widely used for water containment in elevated tanks. During the past few decades, a number of conical tanks have failed as a result of buckling of the steel vessel due to inadequate selection of the shell thickness. In the current study a powerful numerical tool that couples a non-linear finite element model and a genetic algorithm optimization technique is developed specifically for the analysis and design of steel conical tanks. The developed numerical tool is capable of selecting the set of design variables which satisfies the structure safety requirements while achieving a minimum structure weight and consequently minimum cost.     

A sequential quadratically constrained quadratic programming technique for a multi-objective optimization problem

In this article a line search algorithm is proposed for solving constrained multi-objective optimization problems. At every iteration of the proposed method, a subproblem is formulated using quadratic approximation of all functions. A feasible descent direction is obtained as a solution of this subproblem. This scheme takes care some ideas of the sequential quadratically constrained quadratic programming technique for single objective optimization problems. A non-differentiable penalty function is used to restrict constraint violations at every iterating point. Convergence of the scheme is justified under the Slater constraint qualification along with some reasonable assumptions. The proposed algorithm is verified and compared with existing methods with a set of test problems. It is observed that this algorithm provides better results in most of the test problems.     

Immunotherapy for the Treatment of Squamous Cell Carcinoma: Potential Benefits and Challenges

Melanoma and nonmelanoma skin cancers (NMSCs) are recognized as among the most common neoplasms, mostly in white people, with an increasing incidence rate. Among the NMSCs, squamous cell carcinoma (SCC) is the most prevalent malignancy known to affect people with a fair complexion who are exposed to extreme ultraviolet radiation (UVR), have a hereditary predisposition, or are immunosuppressed. There are several extrinsic and intrinsic determinants that contribute to the pathophysiology of the SCC. The therapeutic modalities depend on the SCC stages, from actinic keratosis to late-stage multiple metastases. Standard treatments include surgical excision, radiotherapy, and chemotherapy. As SCC represents a favorable tumor microenvironment with high tumor mutational burden, infiltration of immune cells, and expression of immune checkpoints, the SCC tumors are highly responsive to immunotherapies. Until now, there are three checkpoint inhibitors, cemiplimab, pembrolizumab, and nivolumab, that are approved for the treatment of advanced, recurrent, or metastatic SCC patients in the United States. Immunotherapy possesses significant therapeutic benefits for patients with metastatic or locally advanced tumors not eligible for surgery or radiotherapy to avoid the potential toxicity caused by the chemotherapies. Despite the high tolerability and efficiency, the existence of some challenges has been revealed such as, resistance to immunotherapy, less availability of the biomarkers, and difficulty in appropriate patient selection. This review aims to accumulate evidence regarding the genetic alterations related to SCC, the factors that contribute to the potential benefits of immunotherapy, and the challenges to follow this treatment regime.     

Evaluation of antibacterial properties of triorganotin carboxylates containing functionalised ester groups in tests against some pathogenic bacteria

Bacterial screening employing the agar diffusion test on triphenyltin carboxylates containing various functional residues in the ester moiety revealed appreciable differences in their activities relative to triphenyltin acetate. Among these, [3-(Diethylphosphono)propionato] triphenyltin (1) and [N-cyclohexylcarbamoyl) glycinato] triphenyltin displayed activities comparable to tri-n-butyltin cinnamate (2) towards both Gram-positive and Gram-negative bacteria; the latter compound was the most active among the eleven triorganotin compounds tested, which included cyclopentyldiphenyltin hydroxide (3) and its methacrylate derivative. Applying the more quantitative plate count and optical density tests on compounds 1-3, it was shown that their inhibitory activity ranked in the order 2 > 3 >1. Significantly, 3 caused around 90% inhibition of both Eschechia coli (-) and Pseudomonas aeruginosa (-) when incubated for 24 h at 37+/-1 at the 10.0 mug/ mL concentration level. Compound 2 was less effective against P.aeruginosa than against E.coli. While the Gram-positive bacteria were all readily inhibited, Bacillus subtilis (+) appeared to the most susceptible among them towards the test compounds.