Stressed soft materials commonly present viscoelastic signatures in the form of power-law or exponential decay. Although exponential responses are the most common, power-law time dependencies arise ...peculiarly in complex soft materials such as living cells. Understanding the microscale mechanisms that drive rheologic behaviors at the macroscale shall be transformative in fields such as material design and bioengineering. Using an elastic network model of macromolecules immersed in a viscous fluid, we numerically reproduce those characteristic viscoelastic relaxations and show how the microscopic interactions determine the rheologic response. The macromolecules, represented by particles in the network, interact with neighbors through a spring constant k and with fluid through a non-linear drag regime. The dissipative force is given by γvα, where v is the particle's velocity, and γ and α are mesoscopic parameters. Physically, the sublinear regime of the drag forces is related to micro-deformations of the macromolecules, while α ≥ 1 represents rigid cases. We obtain exponential or power-law relaxations or a transitional behavior between them by changing k, γ, and α. We find that exponential decays are indeed the most common behavior. However, power laws may arise when forces between the macromolecules and the fluid are sublinear. Our findings show that in materials not too soft not too elastic, the rheological responses are entirely controlled by α in the sublinear regime. More specifically, power-law responses arise for 0.3 ⪅ α ⪅ 0.45, while exponential responses for small and large values of α, namely, 0.0 ⪅ α ⪅ 0.2 and 0.55 ⪅ α ⪅ 1.0.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the ...potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m
/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma.
Beaches combined with sloping structures are frequently the first element of defense to protect urban areas from the impact of extreme coastal flooding events. However, these structures are rarely ...designed for null wave overtopping discharges, accepting that waves can pass above the crest and threat exposed elements in hinterland areas, such as pedestrians, urban elements and buildings, and vehicles. To reduce risks, Early Warning Systems (EWSs) can be used to anticipate and minimize the impacts of flooding episodes on those elements. A key aspect of these systems is the definition of non-admissible discharge levels that trigger significant impacts. However, large discrepancies in defining these discharge levels and the associated impacts are found among the existing methods to assess floodings. Due to the lack of standardization, a new conceptual and quantitative four-level (from no-impact to high-impact) categorization of flood warnings (EW-Coast) is proposed. EW-Coast integrates and unifies previous methods and builds on them by incorporating field-based information. Thus, the new categorization successfully predicted the impact level on 70%, 82%, and 85% of the overtopping episodes affecting pedestrians, urban elements and buildings, and vehicles, respectively. This demonstrates its suitability to support EWSs in areas vulnerable to wave-induced flooding.
Pretargeted imaging has emerged as an effective multistep strategy aiming to improve imaging contrast and reduce patient radiation exposure through decoupling of the radioactivity from the targeting ...vector. The inverse electron-demand Diels–Alder (IEDDA) reaction between a trans-cyclooctene (TCO)-conjugated antibody and a labeled tetrazine holds great promise for pretargeted imaging applications due to its bioorthogonality, rapid kinetics under mild conditions, and formation of stable products. Herein, we describe the use of functionalized carbonylacrylic reagents for site-specific incorporation of TCO onto a human epidermal growth factor receptor 2 (HER2) antibody (THIOMAB) containing an engineered unpaired cysteine residue, generating homogeneous conjugates. Precise labeling of THIOMAB–TCO with a fluorescent or radiolabeled tetrazine revealed the potential of the TCO-functionalized antibody for imaging the HER2 after pretargeting in a cellular context in a HER2 positive breast cancer cell line. Control studies with MDA–MD-231 cells, which do not express HER2, further confirmed the target specificity of the modified antibody. THIOMAB–TCO was also evaluated in vivo after pretargeting and subsequent administration of an 111In-labeled tetrazine. Biodistribution studies in breast cancer tumor-bearing mice showed a significant activity accumulation on HER2+ tumors, which was 2.6-fold higher than in HER2– tumors. Additionally, biodistribution studies with THIOMAB without the TCO handle also resulted in a decreased uptake of 111In–DOTA–Tz on HER2+ tumors. Altogether, these results clearly indicate the occurrence of the click reaction at the tumor site, i.e., pretargeting of SK-BR-3 HER2-expressing cells with THIOMAB–TCO and reaction through the TCO moiety present in the antibody. The combined advantages of site-selectivity and stability of TCO tagged-antibodies could allow application of biorthogonal chemistry strategies for pretargeting imaging with minimal side-reactions and background.
Twin studies are becoming popular to investigate risk factors for low back pain (LBP) because they consider the genetic factor and allow for more precise estimates of risks. We aimed to identify and ...summarize the results of studies based on twin samples investigating risk factors for LBP. The MEDLINE, CINAHL, LILACS, Web of Science and EMBASE databases were searched. Prospective and cross‐sectional observational studies of LBP involving twins were included. The exposure factors could be genetics (heritability) or environmental such as smoking, alcohol consumption, body mass index and medical history. Pooling was attempted using an inverse variance weighting and fixed effects model. Twenty‐seven studies were included. Estimates of heritability effects ranged from 21% to 67%. The genetic component was higher for more chronic and disabling LBP than acute and less disabling LBP. Smoking was significantly associated with LBP pooled odds ratio (OR) = 3.0; 95% confidence interval (CI) 2.8–3.3 with a longitudinal and a cross‐sectional study also identifying a dose–response relationship in people with chronic LBP. Obesity was associated with LBP (pooled OR = 1.9; 95% CI 1.6–2.2) with a cross‐sectional study identifying a dose–response relationship. No association between alcohol consumption and LBP was identified. Co‐morbidities such as asthma, diabetes and osteoarthritis were associated with LBP (pooled OR ranging from 1.6 to 4.2). The contribution of genetics to LBP appears to be dependent on the severity of the condition. Twin studies could be better used to explore possible causation paths between lifestyle factors, co‐morbidities and LBP.
Chemotherapy has limited success in the treatment of malignant melanoma due to fast development of drug resistance and the low bioavailability of chemotherapeutic drugs. Resveratrol (RES) is a ...natural polyphenol with recognized preventive and therapeutic anti-cancer properties. However, poor RES solubility hampers its bioactivity, thus creating a demand for suitable drug delivery systems to improve it. This work aimed to assess the potential of RES-loaded mesoporous silica nanoparticles (MSNs) for human melanoma treatment. RES was efficiently loaded (efficiency > 93%) onto spheroidal (size~60 nm) MSNs. The encapsulation promoted the amorphization of RES and enhanced the release in vitro compared to non-encapsulated RES. The RES release was pH-dependent and markedly faster at pH 5.2 (acid environment in some tumorous tissues) than at pH 7.4 in both encapsulated and bulk forms. The RES release from loaded MSNs was gradual with time, without a burst effect, and well-described by the Weibull model. In vitro cytotoxicity studies on human A375 and MNT-1 melanoma cellular cultures showed a decrease in the cell viability with increasing concentration of RES-loaded MSNs, indicating the potent action of the released RES in both cell lines. The amelanotic cell line A375 was more sensitive to RES concentration than the melanotic MNT-1 cells.
OBJECTIVES: The aim of the present study was to examine the prevalence and factors associated with sarcopenia in older residents in São Paulo, Brazil. DESIGN: Cross-sectional study. SETTING: São ...Paulo, Brazil. PARTICIPANTS: 1,149 older individuals from the second wave of the Saúde, Bem-Estar e Envelhecimento (SABE) study from 2006. MEASUREMENTS: The definition of sarcopenia was based on the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP), which include three components: low muscle mass, assessed by a skeletal muscle mass index of ≤8.90kg/m² for men and ≤6.37kg/m² for women; low muscle strength, assessed by handgrip strength <30kg for men and <20kg for women; and low physical performance, assessed by gait speed <0.8m/s. Diagnosis of sarcopenia required presence of low muscle mass plus low muscle strength or low physical performance. Socio-demographic and behavioral characteristics, medical conditions and nutritional status were considered as independent variables to determine the associated factors using a logistic regression model. RESULTS: The prevalence of sarcopenia was 16.1% in women and 14.4% in men. Advanced age with a dose response effect, cognitive impairment, lower income, smoking, undernutrition and risk for undernutrition (p<0.05) were factors associated with sarcopenia. CONCLUSIONS: The EWGSOP algorithm is useful to define sarcopenia. The prevalence of sarcopenia in the Brazilian elderly population is high and several associated factors show that this syndrome is affected by multiple domains. No differences were observed by gender in any age groups.
In this work, hybrid materials within the polydimethylsiloxane-silica (PDMS-SiO
) system, synthesized via the sol-gel method, were developed and characterized for their potential to incorporate and ...release the bioactive compound resveratrol (RES). RES was incorporated into the materials with a high loading efficiency (>75%) using the rotary evaporator technique. This incorporation induced the amorphization of RES, resulting in enhanced solubility and
release when compared to the free polyphenolic compound. The release profiles displayed pH dependence, exhibiting notably faster release at pH 5.2 compared to pH 7.4. The gradual release of RES over time demonstrated an initial time lag of approximately 4 h, being well described by the Weibull model.
cytotoxicity studies were conducted on human osteosarcoma cells (MG-63), revealing a concentration-dependent decrease in cell viability for RES-loaded samples (for concentrations >50 µg mL
).
To understand why and when areas of endemism (provinces) of the tropical Atlantic Ocean were formed, how they relate to each other, and what processes have contributed to faunal enrichment. Atlantic ...Ocean. The distributions of 2605 species of reef fishes were compiled for 25 areas of the Atlantic and southern Africa. Maximum-parsimony and distance analyses were employed to investigate biogeographical relationships among those areas. A collection of 26 phylogenies of various Atlantic reef fish taxa was used to assess patterns of origin and diversification relative to evolutionary scenarios based on spatio-temporal sequences of species splitting produced by geological and palaeoceanographic events. We present data on faunal (species and genera) richness, endemism patterns, diversity buildup (i.e. speciation processes), and evaluate the operation of the main biogeographical barriers and/or filters. Phylogenetic (proportion of sister species) and distributional (number of shared species) patterns are generally concordant with recognized biogeographical provinces in the Atlantic. The highly uneven distribution of species in certain genera appears to be related to their origin, with highest species richness in areas with the greatest phylogenetic depth. Diversity buildup in Atlantic reef fishes involved (1) diversification within each province, (2) isolation as a result of biogeographical barriers, and (3) stochastic accretion by means of dispersal between provinces. The timing of divergence events is not concordant among taxonomic groups. The three soft (non-terrestrial) inter-regional barriers (mid-Atlantic, Amazon, and Benguela) clearly act as 'filters' by restricting dispersal but at the same time allowing occasional crossings that apparently lead to the establishment of new populations and species. Fluctuations in the effectiveness of the filters, combined with ecological differences among provinces, apparently provide a mechanism for much of the recent diversification of reef fishes in the Atlantic. Our data set indicates that both historical events (e.g. Tethys closure) and relatively recent dispersal (with or without further speciation) have had a strong influence on Atlantic tropical marine biodiversity and have contributed to the biogeographical patterns we observe today; however, examples of the latter process outnumber those of the former.
Aim To investigate how reef fish trophic structure responds to latitudinal changes, using a simple model: the extensive Brazilian coast. Location Six Brazilian tropical and subtropical coral and ...rocky coastal reefs, and the oceanic island of Atol das Rocas, between latitudes 0° and 27° S. Methods Underwater visual census data collected by the authors (five locations) or obtained from the literature (two locations) were used to estimate the relative abundance of 123 fish species belonging to 33 reef-associated families. Cryptic species were excluded from the analysis. Fishes were grouped in eight trophic categories: roving herbivores, territorial herbivores, mobile invertebrate feeders, sessile invertebrate feeders, omnivores, planktivores, piscivores and carnivores. After a series of detailed predictions based on phylogeny, physiological constraints and anthropogenic impacts was established, the community trophic structure was analysed along a latitudinal gradient and among coastal, mid-shore and oceanic sites. Results The trophic structure of Brazilian reef fish assemblages clearly changed with latitude. Roving herbivores such as scarids and acanthurids were proportionally more abundant at low latitudes. The browsing herbivores kyphosids followed an opposite latitudinal pattern. The parrotfish genus Sparisoma, more plastic in its feeding habits than Scarus, presented wider distribution. The relative abundance of territorial herbivores did not decrease towards higher latitudes. Mobile invertebrate feeders were the most important (in low latitudes) or the second most important trophic guild (in high latitudes) at all coastal sites. Sessile invertebrate feeders did not show any clear latitudinal trend, despite an expected increase in abundance towards low latitudes. Omnivores dominated high latitude reefs (27° S) and planktivores the oceanic island Atol das Rocas. Piscivores and carnivores were proportionally better represented in high latitudes. Main conclusions Latitudinal patterns seem to be influenced by phylogeny, physiological constraints (mainly related to temperature), and also by anthropogenic impacts. Grazing scarids and acanthurids are largely restricted to tropical reefs and show an abrupt decline beyond 23° S. This does not reflect the amount of algae present, but probably temperature-dependent physiological constraints. Other herbivores seem to overcome this through symbiotic microbial digestive processes (kyphosids), manipulating the structure of algal turfs or increasing animal protein from within the territory (pomacentrids). Omnivores dominate the southern sites Arraial do Cabo and Arvoredo, being more adapted to environment constraints related to seasonal and/or stochastic shifts. Large carnivores (including piscivores) extend farther into high-latitude habitats, apparently not constrained by thermal thresholds that limit the herbivores. Overfishing and/or ornamental harvesting certainly has been modifying local fish communities, but could not be detected properly at the large-scale patterns found in this study. The data presented put in evidence for the first time how reef fish trophic structure behave in the extensive south-western Atlantic latitudinal gradient.
PDF
