The “Angiogenic Switch” and Functional Resources in Cyclic Sports Athletes

Regular physical activity in cyclic sports can influence the so-called “angiogenic switch”, which is considered as an imbalance between proangiogenic and anti-angiogenic molecules. Disruption of the synthesis of angiogenic molecules can be caused by local changes in tissues under the influence of excessive physical exertion and its consequences, such as chronic oxidative stress and associated hypoxia, metabolic acidosis, sports injuries, etc. A review of publications on signaling pathways that activate and inhibit angiogenesis in skeletal muscles, myocardium, lung, and nervous tissue under the influence of intense physical activity in cyclic sports. Materials: We searched PubMed, SCOPUS, Web of Science, Google Scholar, Clinical keys, and e-LIBRARY databases for full-text articles published from 2000 to 2020, using keywords and their combinations. Results: An important aspect of adaptation to training loads in cyclic sports is an increase in the number of capillaries in muscle fibers, which improves the metabolism of skeletal muscles and myocardium, as well as nervous and lung tissue. Recent studies have shown that myocardial endothelial cells not only respond to hemodynamic forces and paracrine signals from neighboring cells, but also take an active part in heart remodeling processes, stimulating the growth and contractility of cardiomyocytes or the production of extracellular matrix proteins in myofibroblasts. As myocardial vascularization plays a central role in the transition from adaptive heart hypertrophy to heart failure, further study of the signaling mechanisms involved in the regulation of angiogenesis in the myocardium is important in sports practice. The study of the “angiogenic switch” problem in the cerebrovascular and cardiovascular systems allows us to claim that the formation of new vessels is mediated by a complex interaction of all growth factors. Although the lungs are one of the limiting systems of the body in cyclic sports, their response to high-intensity loads and other environmental stresses is often overlooked. Airway epithelial cells are the predominant source of several growth factors throughout lung organogenesis and appear to be critical for normal alveolarization, rapid alveolar proliferation, and normal vascular development. There are many controversial questions about the role of growth factors in the physiology and pathology of the lungs. The presented review has demonstrated that when doing sports, it is necessary to give a careful consideration to the possible positive and negative effects of growth factors on muscles, myocardium, lung tissue, and brain. Primarily, the “angiogenic switch” is important in aerobic sports (long distance running). Conclusions: Angiogenesis is a physiological process of the formation of new blood capillaries, which play an important role in the functioning of skeletal muscles, myocardium, lung, and nervous tissue in athletes. Violation of the “angiogenic switch” as a balance between proangiogenic and anti-angiogenic molecules can lead to a decrease in the functional resources of the nervous, musculoskeletal, cardiovascular, and respiratory systems in athletes and, as a consequence, to a decrease in sports performance.     

Molecular Mechanisms of the Deregulation of Muscle Contraction Induced by the R90P Mutation in Tpm3.12 and the Weakening of This Effect by BDM and W7

Point mutations in the genes encoding the skeletal muscle isoforms of tropomyosin can cause a range of muscle diseases. The amino acid substitution of Arg for Pro residue in the 90th position (R90P) in γ-tropomyosin (Tpm3.12) is associated with congenital fiber type disproportion and muscle weakness. The molecular mechanisms underlying muscle dysfunction in this disease remain unclear. Here, we observed that this mutation causes an abnormally high Ca²⁺-sensitivity of myofilaments in vitro and in muscle fibers. To determine the critical conformational changes that myosin, actin, and tropomyosin undergo during the ATPase cycle and the alterations in these changes caused by R90P replacement in Tpm3.12, we used polarized fluorimetry. It was shown that the R90P mutation inhibits the ability of tropomyosin to shift towards the outer domains of actin, which is accompanied by the almost complete depression of troponin’s ability to switch actin monomers off and to reduce the amount of the myosin heads weakly bound to F-actin at a low Ca²⁺. These changes in the behavior of tropomyosin and the troponin–tropomyosin complex, as well as in the balance of strongly and weakly bound myosin heads in the ATPase cycle may underlie the occurrence of both abnormally high Ca²⁺-sensitivity and muscle weakness. BDM, an inhibitor of myosin ATPase activity, and W7, a troponin C antagonist, restore the ability of tropomyosin for Ca²⁺-dependent movement and the ability of the troponin–tropomyosin complex to switch actin monomers off, demonstrating a weakening of the damaging effect of the R90P mutation on muscle contractility.     

Investigation of the Anti-Methicillin-Resistant Staphylococcus aureus Activity of (+)-Tanikolide- and (+)-Malyngolide-Based Analogues Prepared by Asymmetric Synthesis

Herein, we report antibacterial and antifungal evaluation of a series of previously prepared (+)-tanikolide analogues. One analogue, (4S,6S)-4-methyltanikolide, displayed promising anti-methicillin-resistant Staphylococcus aureus activity with a MIC of 12.5 µg/mL. Based on the antimicrobial properties of the structurally related (−)-malyngolide, two further analogues (4S,6S)-4-methylmalyngolide and (4R,6S)-4-methylmalyngolide bearing a shortened n-nonyl alkyl side chain were prepared in the present study using a ZrCl₄-catalysed deprotection/cyclisation as the key step in their asymmetric synthesis. When these were tested for activity against anti-methicillin-resistant Staphylococcus aureus, the MIC increased to 50 µg/mL.     

Highly Thermal Stable Polyimides Applied in Flexible Resistive Memory

Flexible memory devices are one of the most crucial elements in the wearable electronics. In this work, polyimides (PIs)-based flexible resistive memory devices with an excellent thermal and mechanical durability are demonstrated. Four kinds of functional PIs are derived from the heterocyclic diamines including 2,6-diaminodibenzo-p-dioxin (OODA) and 2,6-diaminothianthrene, and dianhydrides including 4,4′-(hexafluoroisopropylidene)diphthalic anhydride (6FDA) and 3,3′,4,4′-biphenyltetracarboxylic dianhydride. PI with diamine of OODA and dianhydride of 6FDA (PI(OODA_6FDA)) possesses outstanding thermal and mechanical properties with a high glass transition temperature of 352 °C, a low coefficient of thermal expansion of 28.1 ppm K⁻¹, and a high elongation at break of 10%. In addition, PI(OODA_6FDA)-based memory shows write-once-read-many behavior with a high on/off current ratio of 10⁶ and a stable data retention, attributed to the donor–acceptor charge transfer between the polymer chains. The retained current levels at a low resistive state can be observed even with thermal treatment at 200 °C for 24 h or 1000 times cyclic bending at a bending radius of 5 mm. These results demonstrate the potential of heterocyclic PIs for flexible resistive memory.     

Natural Polysaccharides as Multifunctional Components for One-Step 3D Printing Tough Hydrogels

Natural polysaccharides (NPS) are regarded as biomolecular and structural components for preparing high-performance tough hydrogels. But the one-step fabrication of NPS-containing hydrogels in seconds and the template-free design of complicated high-resolution structures are still significant challenges in this field. To meet these requirements, various NPS-containing tough hydrogels are fabricated and processed into 2D/3D structures via the combination of Ru(bpy)₃²⁺-mediated photochemistry and extrusion 3D printing technique. The whole fabrication process is one-step, completed in tens of seconds under visible light irradiation. It is found that the used NPS plays a key role in achieving the fabrication of high-performance structured tough hydrogels. The high reactivity of functional groups in the used NPS can shorten their gelation times. Long rigid chains of the used NPS, their hierarchical assemblies, and contrasting multinetworks benefit from the efficient dissipation of mechanical energy and enhancement of its operational stability. Strong supramolecular interactions enable hydrogel precursors to have high viscosities, therefore providing good controllability to design high-resolution and complicated tough hydrogel structures via extrusion 3D printing. It is anticipated that this straightforward fabrication strategy and findings will open new horizons for NPS-containing materials.     

Direct-Ink-Writing of Electroactive Polymers for Sensing and Energy Storage Applications

Considering the high levels of materials used in the fields of electronics and energy storage systems, it is increasingly necessary to take into consideration environmental impact. Thus, it is important to develop devices based on environmentally friendlier materials and/or processes, such as additive manufacturing techniques. In this work, poly(vinylidene fluoride) (PVDF) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) are prepared by direct-ink-writing (DIW) by varying solvent evaporation temperature and fill density percentage. Different morphologies for both polymers are obtained, including dense films and porous membranes, as well as different electroactive β-phase content, thermal and mechanical properties. The dielectric constant and piezoelectric d₃₃ coefficient for dense films reaches up to 16 at 1 kHz and 4 pC N⁻¹, respectively for PVDF-HFP with a fill density of 80 and a solvent evaporation temperature of 50 °C. Porous structures are developed for battery separator membranes in lithium-ion batteries, with a highest ionic conductivity value of 3.8 mS cm⁻¹ for the PVDF-HFP sample prepared with a fill density of 100 and a solvent evaporation temperature of 25 °C, the sample showing an excellent cycling performance. It is demonstrated that electroactive films and membranes can be prepared by direct-ink writing suitable for sensors/actuators and energy storage systems.     

3D Printing Conductive Composites with Poly(ionic liquid) as a Noncovalent Intermedia to Fabricate Carbon Circuits

In this study, a kind of imidazole type poly(ionic liquid) ([PEP-MIM]Cl) is synthesized, which can disperse carbon effectively. [PEP-MIM]Cl is used as an intermediate to coat carbon on the poly(acrylic acid)(PAA-co-MBA) via ion exchange to obtain conductive polymer composite (CPC). A series of characterizations are performed. Experiments show that carbon can be coated on the PAA-co-MBA uniformly, and compared with using carbon as filler, this method requires less carbon to achieve good conductive performance. The carbon layer on the polymer's surface is enriched via the swelling-shrinking properties of PAA-co-MBA according to the SEM images. Furthermore, in combination with 3D printing technology, PAA-co-MBA can be designed into different shapes to achieve various functions such as pressure-sensing element. Finally, a new type of CPC named carbon clad polymeric laminate (CCPL) is prepared by using the carbon coating method and 3D printing technology. It has the potential to replace copper clad laminate (CCL) and printed circuit board (PCB), to a certain extent. This technology expands the preparation method and application of the CPC such as flexible and wearable conductive fabrics.     

Preparation and Bioactivity of Iridium(III) Phenanthroline Complexes with Halide Ions and Pyridine Leaving Groups

A series of half-sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl⁻, Br⁻, I⁻) and pyridine leaving groups ([(η⁵-Cp^X)Ir(Phen)Z](PF₆)_n, Cp^x: electron-rich cyclopentadienyl group, Z: leaving group) have been prepared. Target complexes, especially the Cp^xbiph (biphenyl-substituted cyclopentadienyl)-based one, showed favourable anticancer activity against human lung cancer (A549) cells; the best one ( Ir8 ) was almost five times that of cisplatin under the same conditions. Compared with complexes involving halide ion leaving groups, the pyridine-based one did not display hydrolysis but effectively caused lysosomal damage, leading to accumulation in the cytosol, inducing an increase in the level of intracellular reactive oxygen species and apoptosis; this indicated an anticancer mechanism of oxidation. Additionally, these complexes could bind to serum albumin through a static quenching mechanism. The data highlight the potential value of half-sandwich iridium(III) phenanthroline complexes as anticancer drugs.     

Biowaste-derived hydroxyapatite reinforced with polyvinyl pyrrolidone/aloevera composite for biomedical applications

The present investigation focuses on the synthesis of crabshell-derived hydroxyapatite (CS-HAP)/ water-soluble synthetic polymer—polyvinylpyrrolidone(PVP)/aloevera(AV)—a natural biopolymer, as a composite for enhanced mechanical, antibacterial and biocompatible properties. The reinforcement of polymer has a significant function in increasing the mechanical property of the composite, whereas the incorporation of AV improves the antibacterial and biocompatibility. Phase composition, morphology, mechanical property, and hydrophilicity of CS-HAP/PVP/AV biocomposite with different concentrations of PVP and AV were examined by Fourier transform infrared spectroscopy (FTIR), X-Ray diffraction (XRD), scanning electron microscopy with energy dispersive X-ray (SEM-EDX), Vickers microhardness tests, contact angle, respectively. Furthermore, the antibacterial efficiency of the composite is assessed using Escherichia coli (E coli) and Staphylococcus aureus (S aureus). The biocompatibility of HOS MG 63 cells on the CS-HAP/PVP/AV composite is evaluated by MTT assay test. The obtained results evidence that the as-synthesized composite have appropriate mechanical, antibacterial and biocompatible properties. Overall, the combination of mechanical property of PVP, antibacterial and biocompatible property of AV in CS-HAP/PVP/AV, makes the composite a potential therapeutic material for various biomedical applications.     

Multicomponent Bioluminescence Imaging with Naphthylamino Luciferins

Bioluminescent tools have been used for decades to image processes in complex tissues and preclinical models. However, few distinct probes are available to probe multicellular interactions. We and others are addressing this limitation by engineering new luciferases that can selectively process synthetic luciferin analogues. In this work, we explored naphthylamino luciferins as orthogonal bioluminescent probes. Three analogues were prepared using an optimized synthetic route. The luciferins were found to be robust emitters with native luciferase in vitro and in cellulo. We further screened the analogues against libraries of luciferase mutants to identify unique enzyme-substrate pairs. The new probes can be used in conjunction with existing bioluminescent tools for multi-component imaging.