Non-Local Vectorial Internal Variables and Generalized Guyer-Krumhansl Evolution Equations for the Heat Flux.

In this paper, we ask ourselves how non-local effects affect the description of thermodynamic systems with internal variables. Usually, one assumes that the internal variables are local, but that their evolution equations are non-local, i.e.

Non-Equilibrium Thermodynamics of Heat Transport in Superlattices, Graded Systems, and Thermal Metamaterials with Defects.

In this review, we discuss a nonequilibrium thermodynamic theory for heat transport in superlattices, graded systems, and thermal metamaterials with defects. The aim is to provide researchers in nonequilibrium thermodynamics as well as material scientists with a framework to consider in a systematic way several nonequilibrium questions about current developments, which are fostering new aims in heat transport, and the techniques for achieving them, for instance, defect engineering, dislocation engineering, stress engineering, phonon engineering, and nanoengineering. We also suggest some new applications in the particular case of mobile defects.

Tunable Heat-Flux Rectification in Graded Nanowires in Non-Linear Guyer-Krumhansl Regime.

We study heat rectification in composition-graded nanowires, with nonlocal and nonlinear effects taken into account in a generalized Guyer-Krumhansl equation. Using a thermal conductivity dependent on composition and temperature, the heat equation is solved. Introducing a non-vanishing heat supply (as for instance, a lateral radiative heat supply), we explore the conditions under which either nonlocal or nonlinear effects or both contribute to heat rectification and how they may be controlled by means of the external radiative flux.

Prostatic metaplasia and pilar differentiation in gender-affirming mastectomy specimens.

With the increasing practice of gender-affirming mastectomy as a therapeutic procedure in the setting of gender dysphoria, there has come a profusion of literature on the pathologic findings within these specimens. Findings reported in over 1500 patients have not included either prostatic metaplasia or pilar metaplasia of breast epithelium. We encountered both of these findings in the course of routine surgical pathology practice and therefore aimed to analyze these index cases together with a retrospective cohort to determine the prevalence, anatomic distribution, pathologic features, and associated clinical findings of prostatic metaplasia and pilar metaplasia in the setting of gender-affirming mastectomy.

Impact of a Modified HistoGel Method for Processing Endocervical Curettage Specimens on Diagnostic Yield.

Objectives: Endocervical curettage (ECC) specimens may be limited by scant tissue. We evaluated whether a cellular concentration processing method could improve their diagnostic quality.

Methods: Between October 2018 and June 2019, ECC specimens were assigned chronologically to one of two groups: nonconcentrated ECC (NECC) or concentrated ECC (CECC).

Relationships between rational extended thermodynamics and extended irreversible thermodynamics.

We consider a few conceptual questions on extended thermodynamics, with the aim to contribute to a higher contact between rational extended thermodynamics and extended irreversible thermodynamics. Both theories take a number of fluxes as independent variables, but they differ in the formalism being used to deal with the exploitation of the second principle (rational thermodynamics in the first one and classical irreversible thermodynamics in the second one). Rational extended thermodynamics is more restricted in the range of systems to be analysed, but it is able to obtain a wider number of restrictions and deeper specifications from the second law.

The bioelements, the elementome, and the biogeochemical niche.

Every living creature on Earth is made of atoms of the various bioelements that are harnessed in the construction of molecules, tissues, organisms, and communities, as we know them. Organisms need these bioelements in specific quantities and proportions to survive and grow. Distinct species have different functions and life strategies, and have therefore developed distinct structures and adopted a certain combination of metabolic and physiological processes.

The influence of non-modifiable and modifiable factors on cardiac biomarkers after marathon running.

Background: This study investigated the influence of modifiable (training) and non-modifiable factors (age and gender) on cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP) levels post-marathon.

Methods: Thirteen female and nine male recreational runners participated in the 2015 Hartford Marathon. A venous blood draw was taken from each subject at 24 hours pre-race, immediately post-race and 24 hours post-race.

Bazedoxifene exhibits growth suppressive activity by targeting interleukin-6/glycoprotein 130/signal transducer and activator of transcription 3 signaling in hepatocellular carcinoma.

The interleukin (IL)-6/glycoprotein (GP)130/signal transducer and activator of transcription (STAT)3 pathway is emerging as a target for the treatment of hepatocellular carcinoma. IL-6 binds to IL-6R, forming a binary complex, which further combines with GP130 to transduce extracellular signaling by activating STAT3. Therefore, blocking the interaction between IL-6 and GP130 may inhibit the IL-6/GP130/STAT3 signaling pathway and its biological effects.

Ursolic acid prevents angiotensin II-induced abdominal aortic aneurysm in apolipoprotein E-knockout mice.

Background And Aims: Abdominal aortic aneurysms (AAA) is a chronic inflammatory disease in which signal transducer and activator of transcription 3 (STAT3), and disintegrin and metalloproteinase 17 (ADAM17) play important roles. However, it remains unclear whether ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, can have an impact on STAT3 and ADAM17 and hence influence the formation of AAA. The objective of this study was to characterize the potential effect of UA on the pathogenesis of AAA and on STAT3 and ADAM17.

Growth-suppressive activity of raloxifene on liver cancer cells by targeting IL-6/GP130 signaling.

Background: Interleukin-6 (IL-6) is a multifunctional cytokine, which is involved in the regulation of differentiation and growth of certain types of tumor cells. Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) induced by IL-6 is frequently detected in liver cancer and has emerged as a viable molecular target for liver cancer treatment. However, few inhibitors targeting up-streams of STAT3 are available for the therapy of liver cancer.

Hamiltonian and Godunov structures of the Grad hierarchy.

The time evolution governed by the Boltzmann kinetic equation is compatible with mechanics and thermodynamics. The former compatibility is mathematically expressed in the Hamiltonian and Godunov structures, the latter in the structure of gradient dynamics guaranteeing the growth of entropy and consequently the approach to equilibrium. We carry all three structures to the Grad reformulation of the Boltzmann equation (to the Grad hierarchy).

STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells.

Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+).

A novel small molecule STAT3 inhibitor, LY5, inhibits cell viability, colony formation, and migration of colon and liver cancer cells.

Signal Transducer and Activator of Transcription 3 (STAT3) is persistently activated in human liver and colon cancer cells and is required for cancer cell viability, survival and migration. Therefore, inhibition of STAT3 signaling may be a viable therapeutic approach for these two cancers. We recently designed a non-peptide small molecule STAT3 inhibitor, LY5, using in silico site-directed Fragment-based drug design (FBDD).

A novel small molecular STAT3 inhibitor, LY5, inhibits cell viability, cell migration, and angiogenesis in medulloblastoma cells.

Signal transducers and activators of transcription 3 (STAT3) signaling is persistently activated and could contribute to tumorigenesis of medulloblastoma. Numerous studies have demonstrated that inhibition of the persistent STAT3 signaling pathway results in decreased proliferation and increased apoptosis in human cancer cells, indicating that STAT3 is a viable molecular target for cancer therapy. In this study, we investigated a novel non-peptide, cell-permeable small molecule, named LY5, to target STAT3 in medulloblastoma cells.

Drug design targeting protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning: discovery of raloxifene and bazedoxifene as novel inhibitors of IL-6/GP130 interface.

The IL-6/GP130/STAT3 pathway is critical for the progression of multiple types of cancers. We report here the discovery of raloxifene and bazedoxifene as novel inhibitors of IL-6/GP130 protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning approaches. Multiple drug scaffolds were simultaneously docked into hot spots of GP130 D1 domain by MLSD to compete with the key interacting residues of IL-6, followed by tethering to generate virtual hit compounds.

Mesoscopic hydrothermodynamics of complex-structured materials.

Some experimental results in the study of disordered systems, polymeric fluids, solutions of micelles and surfactants, ionic-glass conductors, and others show a hydrodynamic behavior labeled "anomalous" with properties described by some kind of fractional power laws in place of the standard ones. This is a consequence of the fractal-like structure that is present in these systems of which we do not have a detailed description, thus impairing the application of the conventional ensemble formalism of statistical mechanics. In order to obtain a physical picture of the phenomenon for making predictions which may help with technological and industrial decisions, one may resort to different styles (so-called nonconventional) in statistical mechanics.

Ursolic acid inhibits the growth of colon cancer-initiating cells by targeting STAT3.

Background: We have previously reported Signal Transducer and Activator of Transcription 3 (STAT3) to be constitutively activated in aldehyde dehydrogenase (ALDH)(+)/cluster of differentiation-133 (CD133)(+) colon cancer-initiating cells. In the present study we tested the efficacy of inhibiting STAT3 signaling in human colon cancer-initiating cells by ursolic acid (UA), which exists widely in fruits and herbs.

Results: Our data demonstrated that UA inhibited STAT3 phosphorylation, and induced caspase-3 cleavage of ALDH(+)/CD133(+) colon cancer-initiating cells.

XZH-5 inhibits STAT3 phosphorylation and enhances the cytotoxicity of chemotherapeutic drugs in human breast and pancreatic cancer cells.

Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in breast and pancreatic cancer. Inhibiting constitutive STAT3 signaling represents a promising molecular target for therapeutic approach. Using structure-based design, we developed a non-peptide cell-permeable, small molecule, termed as XZH-5, which targeted STAT3 phosphorylation.

Fragment-based drug design and drug repositioning using multiple ligand simultaneous docking (MLSD): identifying celecoxib and template compounds as novel inhibitors of signal transducer and activator of transcription 3 (STAT3).

We describe a novel method of drug discovery using MLSD and drug repositioning, with cancer target STAT3 being used as a test case. Multiple drug scaffolds were simultaneously docked into hot spots of STAT3 by MLSD, followed by tethering to generate virtual template compounds. Similarity search of virtual hits on drug database identified celecoxib as a novel inhibitor of STAT3.

Diffuse-interface model for rapid phase transformations in nonequilibrium systems.

A thermodynamic approach to rapid phase transformations within a diffuse interface in a binary system is developed. Assuming an extended set of independent thermodynamic variables formed by the union of the classic set of slow variables and the space of fast variables, we introduce finiteness of the heat and solute diffusive propagation at the finite speed of the interface advancing. To describe transformations within the diffuse interface, we use the phase-field model which allows us to follow steep but smooth changes of phase within the width of the diffuse interface.

Measuring nonequilibrium temperature of forced oscillators.

The meaning of temperature in nonequilibrium thermodynamics is considered by using a forced harmonic oscillator in a heat bath, where we have two effective temperatures for the position and the momentum, respectively. We propose a concrete model of a thermometer to testify the validity of these different temperatures from the operational point of view. It is found that the measured temperature depends on a specific form of interaction between the system and a thermometer, which means that the zeroth law of thermodynamics cannot be immediately extended to nonequilibrium cases.