Inflammatory arterial diseases differentially affect the compartments of the vessel wall. The intima and adventitia are commonly involved by the disease process, with luminal and microvascular ...endothelial cells playing a critical role in the recruitment and activation of leukocytes. In contrast, the avascular media is often spared by immune-mediated disorders. Surprisingly, vascular smooth muscle cells (VSMCs), the predominant and often exclusive cell type of the media, are capable of robust proinflammatory responses to diverse stressors. The multiple cytokines and chemokines produced within the media can profoundly affect macrophage and T cell function, thus amplifying and shaping innate and adaptive immune responses. On the other hand, VSMCs and the extracellular matrix that they produce also display significant anti-inflammatory properties. The balance between the pro- and anti-inflammatory effects of VSMCs and their extracellular matrix versus the strength of the inciting immunologic events determines the pattern of medial pathology. Limitations on the extent of medial infiltration and injury, defined as medial immunoprivilege, are typically seen in arteriosclerotic diseases, such as atherosclerosis and transplant vasculopathy. Conversely, breakdown of medial immunoprivilege that manifests as more intense leukocytic infiltrates, loss of VSMCs, and destruction of the extracellular matrix architecture is a general feature of certain aneurysmal diseases and vasculitides. In this review, we consider the inflammatory and immune functions of VSMCs and how they may lead to medial immunoprivilege or medial inflammation in arterial diseases.
Plastics are ubiquitous anthropogenic contaminants that are a growing concern in aquatic environments. The ecological implications of macroplastics pollution are well documented, but less is known ...about nanoplastics. The current study investigates the potential adverse effects of nanoplastics, which likely contribute to the ecological burden of plastic pollution. To this end, we examined whether a dietary exposure of adult zebrafish (Danio rerio) to polystyrene nanoparticles (PS NPs) could lead to the transfer of nanoplastics to the offspring, and whether nanoplastics exposure affects zebrafish physiology. Specifically, adult female and male zebrafish (F0 generation) were exposed to PS NPs via diet for one week and bred to produce the F1 generation. Four F1 groups were generated: control (unexposed females and males), maternal (exposed females), paternal (exposed males), and co-parental (exposed males and females). Co-parental PS NP exposure did not significantly affect reproductive success. Assessment of tissues from F0 fish revealed that exposure to PS NPs significantly reduced glutathione reductase activity in brain, muscle, and testes, but did not affect mitochondrial function parameters in heart or gonads. Assessment of F1 embryos and larvae revealed that PS NPs were present in the yolk sac, gastrointestinal tract, liver, and pancreas of the maternally and co-parentally exposed F1 embryos/larvae. Bradycardia was also observed in embryos from maternal and co-parental exposure groups. In addition, the activity of glutathione reductase and the levels of thiols were reduced in F1 embryos/larvae from maternal and/or co-parental exposure groups. Mitochondrial function and locomotor activity were not affected in F1 larvae. This study demonstrates that (i) PS NPs are transferred from mothers to offspring, and (ii) exposure to PS NPs modifies the antioxidant system in adult tissues and F1 larvae. We conclude that PS NPs could bioaccumulate and be passed on to the offspring, but this does not lead to major physiological disturbances.
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•Is parental transfer a relevant route of exposure to nanoplastics in fish?•Adult zebrafish were dietary exposed to nanopolystyrene and F1 embryos analyzed.•Nanoplastic uptake was detected in maternally and co-parentally exposed F1 embryos.•Plastic exposure affected the antioxidant system in both the F0 and F1 organisms.•Despite the low toxicity, nanoplastics can affect multiple generations of fish.
Solid organs transport fluids through distinct vascular networks that are biophysically and biochemically entangled, creating complex three-dimensional (3D) transport regimes that have remained ...difficult to produce and study. We establish intravascular and multivascular design freedoms with photopolymerizable hydrogels by using food dye additives as biocompatible yet potent photoabsorbers for projection stereolithography. We demonstrate monolithic transparent hydrogels, produced in minutes, comprising efficient intravascular 3D fluid mixers and functional bicuspid valves. We further elaborate entangled vascular networks from space-filling mathematical topologies and explore the oxygenation and flow of human red blood cells during tidal ventilation and distension of a proximate airway. In addition, we deploy structured biodegradable hydrogel carriers in a rodent model of chronic liver injury to highlight the potential translational utility of this materials innovation.
Even with many advances in treatment over the past decades, cancer still remains a leading cause of death worldwide. Despite the recognized relationship between metastasis and increased mortality ...rate, surprisingly little is known about the exact mechanism of metastatic progression. Currently available in vitro models cannot replicate the three-dimensionality and heterogeneity of the tumor microenvironment sufficiently to recapitulate many of the known characteristics of tumors in vivo Our understanding of metastatic progression would thus be boosted by the development of in vitro models that could more completely capture the salient features of cancer biology. Bioengineering groups have been working for over two decades to create in vitro microenvironments for application in regenerative medicine and tissue engineering. Over this time, advances in 3D printing technology and biomaterials research have jointly led to the creation of 3D bioprinting, which has improved our ability to develop in vitro models with complexity approaching that of the in vivo tumor microenvironment. In this Review, we give an overview of 3D bioprinting methods developed for tissue engineering, which can be directly applied to constructing in vitro models of heterogeneous tumor microenvironments. We discuss considerations and limitations associated with 3D printing and highlight how these advances could be harnessed to better model metastasis and potentially guide the development of anti-cancer strategies.
We used a mechanistic physical model to examine the effect of variability in dissolved organic carbon (DOC) concentrations on the physical properties of small temperate lakes. The model was validated ...on eight small (6 × 10−4 to 3.8 × 10−2 km²) lakes in Wisconsin and Michigan, with a standard error , 1°C for seven of eight lakes. Attenuation of photosynthetically active radiation (400-700 nm) in these lakes was regulated by DOC concentrations and was important in the vertical structuring of water temperatures. Heat exchange below the surface mixed layer was near the molecular rate, increasing the importance of water clarity as a control on the heat content of deeper waters. To understand the thermal effects of changing DOC concentrations, we applied scenarios of a 50% increase and 50% decrease in DOC concentrations for one lake (Trout Bog) and found water temperatures to vary in response, with the seasonally averaged temperatures in the increased DOC scenario being > 2°C colder than the reduced scenario. We found a nonlinear relationship between DOC and temperature, with clearer (lower DOC) simulations being more sensitive to climate variability, suggesting that DOC may act as a buffer against a warming climate. Our model showed that DOC also influenced epilimnetic depths, as nocturnal mixing (related to the vertical partitioning of heat) was more important than wind-driven mixing. Small lakes are globally important regulators of biogeochemical cycles and are structurally different from larger lakes. Important feedbacks to physical processes must be accounted for when understanding the effects of changing DOC and climate on small lakes.
A benchtop stable, bifunctional reagent for the redox-neutral cyclopropanation of olefins has been developed. Triethylammonium bis(catecholato)iodomethylsilicate can be readily prepared on ...multigram scale. Using this reagent in combination with an organic photocatalyst and visible light, cyclopropanation of an array of olefins, including trifluoromethyl- and pinacolatoboryl-substituted alkenes, can be accomplished in a matter of hours. The reaction is highly tolerant of traditionally reactive functional groups (carboxylic acids, basic heterocycles, alkyl halides, etc.) and permits the chemoselective cyclopropanation of polyolefinated compounds. Mechanistic interrogation revealed that the reaction proceeds via a rapid anionic 3-exo-tet ring closure, a pathway consistent with experimental and computational data.
The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized.
To define carefully the proportion of key anatomic and nonanatomic ...contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA.
Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway Pcrit) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA.
Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 -1.5 to 1.9 vs. -6.2 -12.4 to -3.6 cm H2O; P <0.01), 19% had a relatively noncollapsible upper airway similar to many of the control subjects (Pcrit, -2 to -5 cm H2O). In these patients, loop gain was almost twice as high as patients with a Pcrit greater than -2 cm H2O (-5.9 -8.8 to -4.5 vs. -3.2 -4.8 to -2.4 dimensionless; P = 0.01). A three-point scale for weighting the relative contribution of the traits is proposed. It suggests that nonanatomic features play an important role in 56% of patients with OSA.
This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
3D printing of conjugated polymers Jordan, Robert S.; Wang, Yue
Journal of polymer science. Part B, Polymer physics,
December 1, 2019, Letnik:
57, Številka:
23
Journal Article
The rapid growth of data in water resources has created new opportunities to accelerate knowledge discovery with the use of advanced deep learning tools. Hybrid models that integrate theory with ...state‐of‐the art empirical techniques have the potential to improve predictions while remaining true to physical laws. This paper evaluates the Process‐Guided Deep Learning (PGDL) hybrid modeling framework with a use‐case of predicting depth‐specific lake water temperatures. The PGDL model has three primary components: a deep learning model with temporal awareness (long short‐term memory recurrence), theory‐based feedback (model penalties for violating conversation of energy), and model pretraining to initialize the network with synthetic data (water temperature predictions from a process‐based model). In situ water temperatures were used to train the PGDL model, a deep learning (DL) model, and a process‐based (PB) model. Model performance was evaluated in various conditions, including when training data were sparse and when predictions were made outside of the range in the training data set. The PGDL model performance (as measured by root‐mean‐square error (RMSE)) was superior to DL and PB for two detailed study lakes, but only when pretraining data included greater variability than the training period. The PGDL model also performed well when extended to 68 lakes, with a median RMSE of 1.65 °C during the test period (DL: 1.78 °C, PB: 2.03 °C; in a small number of lakes PB or DL models were more accurate). This case‐study demonstrates that integrating scientific knowledge into deep learning tools shows promise for improving predictions of many important environmental variables.
Key Points
Process‐Guided Deep Learning (PGDL) models integrate advanced empirical techniques with process knowledge
We used PGDL to accurately predict lake water temperatures for various conditions
PGDL performance improved significantly when pretraining data included diverse conditions generated by an existing process‐based model
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