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1.
Polymers (Basel) ; 16(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38543355

RESUMO

The objective of this research was to predict the fatigue behavior of polyetherimide-based composites loaded with short carbon fibers 200 µm long under cyclic loads. The weight fraction of the filler was 10, 20, and 30 wt.%, while the maximum stress in a cycle was 55, 65, and 75 MPa. A modified fatigue model based on the obtained experimental results and Basquin equation was developed. The novelty of the results is related to developing a model on the structure-property relationship, which accounts for both the maximum stress in a cycle and the carbon fiber content in the composites. In addition, an "algorithm" for designing such composites according to the fatigue life criterion was proposed. The approach to determine relationships between the composition, structure, and properties of PCMs described in this study can be applied to further expand the model and to improve its versatility in the use of other thermoplastic matrices and fillers. The results of this study can be applied for the design of composites for structural applications with designated fatigue properties.

2.
Polymers (Basel) ; 16(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475400

RESUMO

Carbon fiber-reinforced composites are popular due to their high strength and light weight; thus, the structures demonstrate high performance and specific strength. However, these composites are susceptible to impact damage. The objective of this research was to study the behavior of carbon fiber-reinforced laminates based on a polyetheretherketone (PEEK) matrix with six stacking sequences under static and impact loading. Four-point bending, short-beam bending, drop weight impact, and compression after impact tests were carried out. The results were complemented with digital shearography to estimate the damaged areas. Finite element modeling served to assess the failure mechanisms, such as fiber and matrix failure, in different layers due to tension of compression. Three behavior pattern of layups under drop-weight impact were found: (i)-energy redistribution due to mostly linear behavior (like a trampoline) and thus lower kinetic energy absorption for damage initiation, (ii)-moderate absorption of energy with initiation and propagation of concentrated damage with depressed redistribution of energy in the material, (iii)-moderate energy absorption with good redistribution due to initiation of small, dispersed damage. The results can be used to predict the mechanical behavior of composites with different stacking sequences in materials for proper structural design.

3.
Front Oncol ; 14: 1342802, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38390269

RESUMO

Tumor acidity has been identified as a key factor in promoting cancer progression, metastasis, and resistance. Tumor alkalization therapy has emerged as a potential strategy for cancer treatment. This article provides preclinical and clinical evidence for tumor alkalization therapy as a promising cancer treatment strategy. The potential of tumor alkalization therapy using sodium bicarbonate in the treatment of malignant ascites was studied. The concept of intraperitoneal perfusion with an alkalizing solution to increase the extracellular pH and its antitumor effect were explored. The significant extension in the overall survival of the Ehrlich ascites carcinoma mice treated with sodium bicarbonate solution compared to those treated with a sodium chloride solution was observed. In the sodium bicarbonate group, mice had a median survival of 30 days after tumor cell injection, which was significantly (p<0.05) different from the median survival of 18 days in the sodium chloride group and 14 days in the intact group. We also performed a case study of a patient with ovarian cancer malignant ascites resistant to previous lines of chemotherapy who underwent intraperitoneal perfusions with a sodium bicarbonate solution, resulting in a significant drop of CA-125 levels from 5600 U/mL to 2200 U/mL in and disappearance of ascites, indicating the potential effectiveness of the treatment. The preclinical and clinical results obtained using sodium bicarbonate perfusion in the treatment of malignant ascites represent a small yet significant contribution to the evolving field of tumor alkalization as a cancer therapy. They unequivocally affirm the good prospects of this concept.

4.
J Am Chem Soc ; 146(9): 6157-6167, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38393979

RESUMO

Fluorine electron-nuclear double resonance (19F ENDOR) has recently emerged as a valuable tool in structural biology for distance determination between F atoms and a paramagnetic center, either intrinsic or conjugated to a biomolecule via spin labeling. Such measurements allow access to distances too short to be measured by double electron-electron resonance (DEER). To further extend the accessible distance range, we exploit the high-spin properties of Gd(III) and focus on transitions other than the central transition (|-1/2⟩ ↔ |+1/2⟩), that become more populated at high magnetic fields and low temperatures. This increases the spectral resolution up to ca. 7 times, thus raising the long-distance limit of 19F ENDOR almost 2-fold. We first demonstrate this on a model fluorine-containing Gd(III) complex with a well-resolved 19F spectrum in conventional central transition measurements and show quantitative agreement between the experimental spectra and theoretical predictions. We then validate our approach on two proteins labeled with 19F and Gd(III), in which the Gd-F distance is too long to produce a well-resolved 19F ENDOR doublet when measured at the central transition. By focusing on the |-5/2⟩ ↔ |-3/2⟩ and |-7/2⟩ ↔ |-5/2⟩ EPR transitions, a resolution enhancement of 4.5- and 7-fold was obtained, respectively. We also present data analysis strategies to handle contributions of different electron spin manifolds to the ENDOR spectrum. Our new extended 19F ENDOR approach may be applicable to Gd-F distances as large as 20 Å, widening the current ENDOR distance window.


Assuntos
Elétrons , Flúor , Espectroscopia de Ressonância de Spin Eletrônica , Proteínas/química , Marcadores de Spin
5.
Biochimie ; 221: 1-12, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38215931

RESUMO

Gene silencing through RNA interference (RNAi) is a promising therapeutic approach for a wide range of disorders, including cancer. Non-viral gene therapy, using specific siRNAs against BCR-ABL1, can be a supportive or alternative measure to traditional chronic myeloid leukemia (CML) tyrosine kinase inhibitor (TKIs) therapies, given the prevalence of clinical TKI resistance. The main challenge for such approaches remains the development of the effective delivery system for siRNA tailored to the specific disease model. The purpose of this study was to examine and compare the efficiency of endosomolytic cell penetrating peptide (CPP) EB1 and PEG2000-decorated cationic liposomes composed of polycationic lipid 1,26-bis(cholest-5-en-3-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2Ð¥3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) for anti-bcr-abl siRNA delivery into the K562 human CML cell line. We show that both EB1 and 2Ð¥3-DOPE-DSPE-PEG2000 (0.62 % mol.) liposomes effectively deliver siRNA into K562 cells by endocytic mechanisms, and the use of liposomes leads to more effective inhibition of expression of the targeted gene (BCR-ABL1) and cancer cell proliferation. Taken together, these findings suggest that PEG-decorated cationic liposomes mediated siRNA delivery allows an effective antisense suppression of certain oncogenes, and represents a promising new class of therapies for CML.

6.
Pharmaceutics ; 16(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38276518

RESUMO

Antimicrobial peptides (AMPs) have recently attracted attention as promising antibacterial agents capable of acting against resistant bacterial strains. In this work, an approach was applied, consisting of the conjugation of a peptide related to the sequences of bactenecin 7 (Bac7) and oncocin (Onc112) with the alkyl(triphenyl)phosphonium (alkyl-TPP) fragment in order to improve the properties of the AMP and introduce new ones, expand the spectrum of antimicrobial activity, and reduce the inhibitory effect on the eukaryotic translation process. Triphenylphosphonium (TPP) derivatives of a decapeptide RRIRPRPPYL were synthesized. It was comprehensively studied how the modification of the AMP affected the properties of the new compounds. It was shown that while the reduction in the Bac7 length to 10 a.a. residues dramatically decreased the affinity to bacterial ribosomes, the modification of the peptide with alkyl-TPP moieties led to an increase in the affinity. New analogs with structures that combined a decapeptide related to Bac7 and Onc112-Bac(1-10, R/Y)-and TPP attached to the C-terminal amino acid residue via alkylamide linkers, inhibited translation in vitro and were found to be more selective inhibitors of bacterial translation compared with eukaryotic translation than Onc112 and Bac7. The TPP analogs of the decapeptide related to Bac7 and Onc112 suppressed the growth of both Gram-negative bacteria, similar to Onc112 and Bac7, and Gram-positive ones, similar to alkyl-TPP derivatives, and also acted against some resistant laboratory strains. Bac(1-10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, was transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1-10, R/Y) containing either a decylamide or ethylamide linker caused B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1-10, R/Y)-C2-TPP analog was proven to be non-toxic for mammalian cells using the MTT test.

7.
Biochemistry (Mosc) ; 88(6): 792-800, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37748875

RESUMO

Stacking interactions of heterocyclic bases of ribonucleotides are one of the most important factors in the organization of RNA secondary and tertiary structure. Most of these (canonical) interactions are formed between adjacent residues in RNA polynucleotide chains. However, with the accumulation of data on the atomic tertiary structures of various RNAs and their complexes with proteins, it has become clear that nucleotide residues that are not adjacent in the polynucleotide chains and are sometimes separated in the RNA primary structure by tens or hundreds of nucleotides can interact via (non-canonical) base stacking. This paper presents an exhaustive database of such nonadjacent base-stacking elements (NA-BSEs) and their environment in the macromolecules of natural and synthetic RNAs. Analysis of these data showed that NA-BSE-forming nucleotides, on average, account for about a quarter of all nucleotides in a particular RNA and, therefore, should be considered as bona fide motifs of the RNA tertiary structure. We also classified NA-BSEs by their location in RNA macromolecules. It was shown that the structure-forming role of NA-BSEs involves compact folding of single-stranded RNA loops, transformation of double-stranded bulges into imperfect helices, and binding of RNA regions distant in the primary and secondary RNA structure.


Assuntos
Nucleotídeos , RNA , RNA/química , Conformação de Ácido Nucleico , Polinucleotídeos
8.
Int J Mol Sci ; 24(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37569365

RESUMO

The versatile functions of fluorescent proteins (FPs) as fluorescence biomarkers depend on their intrinsic chromophores interacting with the protein environment. Besides X-ray crystallography, vibrational spectroscopy represents a highly valuable tool for characterizing the chromophore structure and revealing the roles of chromophore-environment interactions. In this work, we aim to benchmark the ground-state vibrational signatures of a series of FPs with emission colors spanning from green, yellow, orange, to red, as well as the solvated model chromophores for some of these FPs, using wavelength-tunable femtosecond stimulated Raman spectroscopy (FSRS) in conjunction with quantum calculations. We systematically analyzed and discussed four factors underlying the vibrational properties of FP chromophores: sidechain structure, conjugation structure, chromophore conformation, and the protein environment. A prominent bond-stretching mode characteristic of the quinoidal resonance structure is found to be conserved in most FPs and model chromophores investigated, which can be used as a vibrational marker to interpret chromophore-environment interactions and structural effects on the electronic properties of the chromophore. The fundamental insights gained for these light-sensing units (e.g., protein active sites) substantiate the unique and powerful capability of wavelength-tunable FSRS in delineating FP chromophore properties with high sensitivity and resolution in solution and protein matrices. The comprehensive characterization for various FPs across a colorful palette could also serve as a solid foundation for future spectroscopic studies and the rational engineering of FPs with diverse and improved functions.


Assuntos
Análise Espectral Raman , Análise Espectral Raman/métodos , Proteínas de Fluorescência Verde/metabolismo , Domínio Catalítico
9.
Chemistry ; 29(43): e202301250, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37194969

RESUMO

A new type of neutral mixed-valence system was synthesized using a facile one-pot procedure. The spiro-conjugated framework is additionally "fastened" with a biphenyl bridge, which does not directly participate in spin delocalization but makes the molecule stable and influences the reorganization energy and the energy barrier of the intramolecular electron transfer. The in-depth experimental and quantum-chemical study allowed determining the radicals as the Class II Robin-Day-mixed-valence systems. The structure of the radicals was confirmed by the X-ray data, which are relatively rare for Class II MV molecules. Advanced properties of the radicals, such as an ambipolar redox behavior and panchromatic absorption in the visible and NIR regions, along with their stability, make them of interest for materials science. All radicals demonstrate the SOMO-HOMO inversion phenomenon, which was supported by the DFT and the experimental study.

10.
Int J Mol Sci ; 24(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37047378

RESUMO

The rapid development of new microscopy techniques for cell biology has exposed the need for genetically encoded fluorescent tags with special properties. Fluorescent biomarkers of the same color and spectral range and different fluorescent lifetimes (FLs) became useful for fluorescent lifetime image microscopy (FLIM). One such tag, the green fluorescent protein BrUSLEE (Bright Ultimately Short Lifetime Enhanced Emitter), having an extremely short subnanosecond component of fluorescence lifetime (FL~0.66 ns) and exceptional fluorescence brightness, was designed for FLIM experiments. Here, we present the X-ray structure and discuss the structure-functional relations of BrUSLEE. Its development from the EGFP (enhanced green fluorescent proteins) precursor (FL~2.83 ns) resulted in a change of the chromophore microenvironment due to a significant alteration in the side chain conformations. To get further insight into molecular details explaining the observed differences in the photophysical properties of these proteins, we studied their structural, dynamic, and electric properties by all-atom molecular-dynamics simulations in an aqueous solution. It has been shown that compared to BrUSLEE, the mobility of the chromophore in the EGFP is noticeably limited by nonbonded interactions (mainly H-bonds) with the neighboring residues.


Assuntos
Corantes , Fluorescência , Proteínas de Fluorescência Verde/metabolismo , Microscopia de Fluorescência/métodos
11.
J Magn Reson ; 351: 107447, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37119743

RESUMO

Half-Integer High Spin (HIHS) systems with zero-field splitting (ZFS) parameters below 1 GHz are generally dominated by the spin |─1/2>→|+1/2 > central transition (CT). Accordingly, most pulsed Electron Paramagnetic Resonance (EPR) experiments are performed at this position for maximum sensitivity. However, in certain cases it can be desirable to detect higher spin transitions away from the CT in such systems. Here, we describe the use of frequency swept Wideband, Uniform Rate, Smooth Truncation (WURST) pulses for transferring spin population from the CT, and other transitions, of Gd(III) to the neighbouring higher spin transition |─3/2>→|─1/2 > at Q- and W-band frequencies. Specifically, we demonstrate this approach to enhance the sensitivity of 1H Mims Electron-Nuclear Double Resonance (ENDOR) measurements on two model Gd(III) aryl substituted 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) complexes, focusing on transitions other than the CT. We show that an enhancement factor greater than 2 is obtained for both complexes at Q- and W-band frequencies by the application of two polarising pulses prior to the ENDOR sequence. This is in agreement with simulations of the spin dynamics of the system during WURST pulse excitation. The technique demonstrated here should allow more sensitive experiments to be measured away from the CT at higher operating temperatures, and be combined with any relevant pulse sequence.

12.
Materials (Basel) ; 16(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36903230

RESUMO

The optimal mode for ultrasonic welding (USW) of the "PEEK-ED (PEEK)-prepreg (PEI impregnated CF fabric)-ED (PEEK)-PEEK" lap joint was determined by artificial neural network (ANN) simulation, based on the sample of the experimental data expanded with the expert data set. The experimental verification of the simulation results showed that mode 10 (t = 900 ms, P = 1.7 atm, τ = 2000 ms) ensured the high strength properties and preservation of the structural integrity of the carbon fiber fabric (CFF). Additionally, it showed that the "PEEK-CFF prepreg-PEEK" USW lap joint could be fabricated by the "multi-spot" USW method with the optimal mode 10, which can resist the load per cycle of 50 MPa (the bottom HCF level). The USW mode, determined by ANN simulation for the neat PEEK adherends, did not provide joining both particulate and laminated composite adherends with the CFF prepreg reinforcement. The USW lap joints could be formed when the USW durations (t) were significantly increased up to 1200 and 1600 ms, respectively. In this case, the elastic energy is transferred more efficiently to the welding zone through the upper adherend.

13.
Polymers (Basel) ; 15(5)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36904475

RESUMO

Since the inelastic strain development plays an important role in the low-cycle fatigue (LCF) of High-Performance Polymers (HPPs), the goal of the research was to study the effect of an amorphous polymer matrix type on the resistance to cyclic loading for both polyimide (PI)- and polyetherimide (PEI)-based composites, identically loaded with short carbon fibers (SCFs) of various lengths, in the LCF mode. The fracture of the PI and PEI, as well as their particulate composites loaded with SCFs at an aspect ratio (AR) of 10, occurred with a significant role played by cyclic creep processes. Unlike PEI, PI was less prone to the development of creep processes, probably because of the greater rigidity of the polymer molecules. This increased the stage duration of the accumulation of scattered damage in the PI-based composites loaded with SCFs at AR = 20 and AR = 200, causing their greater cyclic durability. In the case of SCFs 2000 µm long, the length of the SCFs was comparable to the specimen thickness, causing the formation of a spatial framework of unattached SCFs at AR = 200. The higher rigidity of the PI polymer matrix provided more effective resistance to the accumulation of scattered damage with the simultaneously higher fatigue creep resistance. Under such conditions, the adhesion factor exerted a lesser effect. As shown, the fatigue life of the composites was determined both by the chemical structure of the polymer matrix and the offset yield stresses. The essential role of the cyclic damage accumulation in both neat PI and PEI, as well as their composites reinforced with SCFs, was confirmed by the results of XRD spectra analysis. The research holds the potential to solve problems related to the fatigue life monitoring of particulate polymer composites.

14.
Angew Chem Int Ed Engl ; 62(20): e202218780, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-36905181

RESUMO

Studies of protein structure and dynamics are usually carried out in dilute buffer solutions, conditions that differ significantly from the crowded environment in the cell. The double electron-electron resonance (DEER) technique can track proteins' conformations in the cell by providing distance distributions between two attached spin labels. This technique, however, cannot access distances below 1.8 nm. Here, we show that GdIII -19 F Mims electron-nuclear double resonance (ENDOR) measurements can cover part of this short range. Low temperature solution and in-cell ENDOR measurements, complemented with room temperature solution and in-cell GdIII -19 F PRE (paramagnetic relaxation enhancement) NMR measurements, were performed on fluorinated GB1 and ubiquitin (Ub), spin-labeled with rigid GdIII tags. The proteins were delivered into human cells via electroporation. The solution and in-cell derived GdIII -19 F distances were essentially identical and lie in the 1-1.5 nm range revealing that both, GB1 and Ub, retained their overall structure in the GdIII and 19 F regions in the cell.


Assuntos
Elétrons , Gadolínio , Humanos , Espectroscopia de Ressonância de Spin Eletrônica , Gadolínio/química , Proteínas/química , Marcadores de Spin , Ubiquitina , Flúor/química
15.
Org Biomol Chem ; 21(2): 375-385, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36524609

RESUMO

Nitroxides are a unique class of persistent radicals finding a wide range of applications, from spin probes to polarizing agents, and recently bis-nitroxides have been used as proof-of-concept molecules for quantum information processing. Here we present the syntheses of pyrroline-based nitroxide (NO) radicals and give a comparision of two possible synthetic routes to form two key intermediates, namely 2,2,5,5-tetramethylpyrroline-1-oxyl-3-acetylene (TPA) and 1-oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic acid (TPC). TPC and TPA were then used as precursors for the synthesis of three model compounds featuring two distant NO groups with a variable degree of conjugation and thus electronic communication between them. Using relatively facile synthetic routes, we produced a number of mono- and bis-nitroxides with the structures of multiple compounds unambiguously characterized by X-ray crystallography, while Continuous Wave Electron Paramagnetic Resonance (CW-EPR) allowed us to quantify the electronic communication in the bis-nitroxides. Our study expands the repertoire of mono- and bis-nitroxides with possibilities of exploiting them for studying quantum coherence effects and as polarizing agents.


Assuntos
Óxidos de Nitrogênio , Óxidos de Nitrogênio/química , Espectroscopia de Ressonância de Spin Eletrônica , Marcadores de Spin
16.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361706

RESUMO

The real-time monitoring of the intracellular pH in live cells with high precision represents an important methodological challenge. Although genetically encoded fluorescent indicators can be considered as a probe of choice for such measurements, they are hindered mostly by the inability to determine an absolute pH value and/or a narrow dynamic range of the signal, making them inefficient for recording the small pH changes that typically occur within cellular organelles. Here, we study the pH sensitivity of a green-fluorescence-protein (GFP)-based emitter (EGFP-Y145L/S205V) with the alkaline-shifted chromophore's pKa and demonstrate that, in the pH range of 7.5-9.0, its fluorescence lifetime changes by a factor of ~3.5 in a quasi-linear manner in mammalian cells. Considering the relatively strong lifetime response in a narrow pH range, we proposed the mitochondria, which are known to have a weakly alkaline milieu, as a target for live-cell pH measurements. Using fluorescence lifetime imaging microscopy (FLIM) to visualize the HEK293T cells expressing mitochondrially targeted EGFP-Y145L/S205V, we succeeded in determining the absolute pH value of the mitochondria and recorded the ETC-uncoupler-stimulated pH shift with a precision of 0.1 unit. We thus show that a single GFP with alkaline-shifted pKa can act as a high-precision indicator that can be used in a specific pH range.


Assuntos
Corantes , Corantes Fluorescentes , Animais , Humanos , Fluorescência , Células HEK293 , Proteínas de Fluorescência Verde/genética , Microscopia de Fluorescência/métodos , Concentração de Íons de Hidrogênio , Mamíferos
17.
Curr Treat Options Oncol ; 23(12): 1664-1698, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36269457

RESUMO

OPINION STATEMENT: MET-driven tumors are a heterogenous group of non-small cell lung cancers (NSCLC) with activating mutations. Pathologic activation of MET can be achieved with increased number of gene copies overexpression, or decreased protein degradation through several mechanisms, including mutations, amplifications, or fusions. Besides its role as primary driver, MET activation might also mediate resistance to kinase inhibitors in NSCLC with various other actionable alterations. While checkpoint inhibitors have modest efficacy in MET-driven tumors, several approaches of targeted blockade are available. Among them the most promising are small tyrosine kinase inhibitors, antibody-drug conjugates, and bispecific antibodies. Unfortunately, resistance is virtually inevitable. Resistance to small kinase inhibitors might be mediated by kinase domain mutations or activation of shunting cascades. Various resistance mechanisms might be present in one patient, making it overcoming an unresolved problem.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Receptores ErbB , Resistencia a Medicamentos Antineoplásicos/genética , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met , Mutação
18.
Front Oncol ; 12: 979154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36106097

RESUMO

Tumor acidity is one of the cancer hallmarks and is associated with metabolic reprogramming and the use of glycolysis, which results in a high intracellular lactic acid concentration. Cancer cells avoid acid stress major by the activation and expression of proton and lactate transporters and exchangers and have an inverted pH gradient (extracellular and intracellular pHs are acid and alkaline, respectively). The shift in the tumor acid-base balance promotes proliferation, apoptosis avoidance, invasiveness, metastatic potential, aggressiveness, immune evasion, and treatment resistance. For example, weak-base chemotherapeutic agents may have a substantially reduced cellular uptake capacity due to "ion trapping". Lactic acid negatively affects the functions of activated effector T cells, stimulates regulatory T cells, and promotes them to express programmed cell death receptor 1. On the other hand, the inversion of pH gradient could be a cancer weakness that will allow the development of new promising therapies, such as tumor-targeted pH-sensitive antibodies and pH-responsible nanoparticle conjugates with anticancer drugs. The regulation of tumor pH levels by pharmacological inhibition of pH-responsible proteins (monocarboxylate transporters, H+-ATPase, etc.) and lactate dehydrogenase A is also a promising anticancer strategy. Another idea is the oral or parenteral use of buffer systems, such as sodium bicarbonate, to neutralize tumor acidity. Buffering therapy does not counteract standard treatment methods and can be used in combination to increase effectiveness. However, the mechanisms of the anticancer effect of buffering therapy are still unclear, and more research is needed. We have attempted to summarize the basic knowledge about tumor acidity.

19.
Sensors (Basel) ; 22(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36015792

RESUMO

(1) Background: this study deals with design of an automated laboratory facility based on a servo-hydraulic testing machine for estimating parameters of mechanical hysteresis loops by means of the digital image correlation (DIC) method. (2) Methods: the paper presents a description of the testing facility, describes the grounds for calculating the elastic modulus, the offset yield strength (OYS) and the parameters of the mechanical hysteresis loops by the DIC method. (3) Results: the developed hardware-software facility was tested by studying the fatigue process in neat polyimide (PI) under various amplitude tension-tension loadings. It was found that the damage accumulation was accompanied by the decrease in the loop areas, while failure occurred when it reduced by at least ~5 kJ/m3. (4) Conclusions: it was shown that lowering the loop area along with changing the secant modulus value makes it possible to estimate the level of the scattered damage accumulation (mainly at the stresses above the OYS level). It was revealed that fractography data, namely the pattern and sizes of the fatigue crack initiation and propagation zones, did not correlate well with the dependences of the parameters of the hysteresis loops.

20.
Materials (Basel) ; 15(13)2022 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-35806781

RESUMO

The fatigue properties of neat polyimide and the "polyimide + 10 wt.% milled carbon fibers + 10 wt.% polytetrafluoroethylene" composite were investigated under various cyclic loading conditions. In contrast to most of the reported studies, constructing of hysteresis loops was performed through the strain assessment using the non-contact 2D Digital Image Correlation method. The accumulation of cyclic damage was analyzed by calculating parameters of mechanical hysteresis loops. They were: (i) the energy losses (hysteresis loop area), (ii) the dynamic modulus (proportional to the compliance/stiffness of the material) and (iii) the damping capacity (calculated through the dissipated and total mechanical energies). On average, the reduction in energy losses reached 10-18% at the onset of fracture, whereas the modulus variation did not exceed 2.5% of the nominal value. The energy losses decreased from 20 down to 18 J/m3 (10%) for the composite, whereas they reduced from 30 down to 25 J/m3 (17%) for neat PI in the low-cycle fatigue mode. For high-cycle fatigue, energy losses decreased from 10 to 9 J/m3 (10%) and from 17 to 14 J/m3 (18%) for neat PI and composite, respectively. For this reason, the changes of the energy losses due to hysteresis are of prospects for the characterization of both neat PI and the reinforced PI-based composites.

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