A bypass flow model to study endothelial cell mechanotransduction across diverse flow environments.

Disturbed flow is one of the pathological initiators of endothelial dysfunction in intimal hyperplasia (IH) which is commonly seen in vascular bypass grafts, and arteriovenous fistulas. Various in vitro disease models have been designed to simulate the hemodynamic conditions found in the vasculature. Nonetheless, prior investigations have encountered challenges in establishing a robust disturbed flow model, primarily attributed to the complex bifurcated geometries and distinctive flow dynamics. In the present study, we aim to address this gap by introducing an in vitro bypass flow model capable of inducing disturbed flow and other hemodynamics patterns through a pulsatile flow in the same model. To assess the model's validity, we employed computational fluid dynamics (CFD) to simulate hemodynamics and compared the morphology and functions of human umbilical venous endothelial cells (HUVECs) under disturbed flow conditions to those in physiological flow or stagnant conditions. CFD analysis revealed the generation of disturbed flow within the model, pinpointing the specific location in the channel where the effects of disturbed flow were observed. High-content screening, a single-cell morphological profile assessment, demonstrated that HUVECs in the disturbed flow area exhibited random orientation, and morphological features were significantly distinct compared to cells in the physiological flow or stagnant condition after a two days of flow exposure. Furthermore, HUVECs exposed to disturbed flow underwent extensive remodeling of the adherens junctions and expressed higher levels of endothelial cell activation markers compared to other hemodynamic conditions. In conclusion, our in vitro bypass flow model provides a robust platform for investigating the associations between disturbed flow pattern and vascular diseases.

Can Environmental Stressors Determine the Condition of Ecological Plant Groups?

There is still a need to investigate the relationships between glycophytes and halophytes and the many biotic and abiotic factors in their natural environments. Therefore, we study the effects of the type of environment on the ecophysiological responses and condition of the glycophyte Elder Sambucus nigra L., the macrophyte Common Reed Phragmites australis (Cav.) Trin. ex Steud., the facultative halophyte Weeping Alkaligrass Puccinellia distans (Jacq.) Parl, and the obligate halophyte Common Glasswort Salicornia europaea L. in a saline-disturbed anthropogenic region of central Poland. We analyzed the effects of salinity, acidity, and soil organic matter on shoot length, lipoperoxidation, and proline in roots and green parts, and evaluated plant responses to environmental disturbance, which allowed for the comparison of adaptation strategies. The studies were carried out in (1) "sodium production" (near sodium factories), (2) "anthropogenic environments" (waste dumps, agroecosystems, calcium deposits, post-production tanks), (3) "wetland environments" (near river channels and riparian areas), and (4) "control" (natural, unpolluted environments). Green parts of plants are better suited to indicate environmental stress than roots. Their higher structural MDA membrane damage is related to the transport of toxic ions to the shoots by a rapid transpiration stream in the xylem. We found high salinity to be the main factor inducing growth and found it to be correlated with the high pH effect on proline increase in glycophytes (Elder, Reed) and Weeping Alkaligrass, in contrast to Common Glasswort. We suggest that proline accumulation allows osmotic adjustment in the green parts of reeds and alkaligrasses, but may have another function (in Elder). Common Glasswort accumulates large amounts of Na+, which is energetically more effective than proline accumulation for osmotic adjustment. Organic matter affects plant growth and proline levels, but soil salinity and pH alter nutrient availability. Plant distribution along the salinity gradient indicates that Elder is the most salt-sensitive species compared to Reed, Alkaligrass, and Glasswort. Salinity and the lack of control of thick reeds, which compete with other plant groups, affect the distribution of halophytes in saline environments.

Using organic amendments in disturbed soil to enhance soil organic matter, nutrient content and turfgrass establishment.

Disturbed soils, including manufactured topsoils, often lack physical and chemical properties conducive to vegetation establishment. As a result, efforts to stabilize disturbed soils with vegetation are susceptible to failure. Urban organic waste products such as wood mulch, composted leaf and yard waste, and biosolids are widely distributed as organic amendments that enhance sustainability and plant establishment. Correct use can be determined by examining soil properties such as pH; the concentration of soluble salts (SS); and plant available nutrients - particularly N, C and P; as well as root and shoot growth. This research examined the effects of three typical organic amendments on fertility, establishment, and nutrient loss. A manufactured topsoil was used as the base soil for all treatments, including a control unamended soil (CUT), and soil amended with either mulch (MAT), composted leaf and yard waste (LAT), or biosolids (BAT). A 2 % organic matter concentration increase was sought but not achieved due to difficulty in reproducing lab results at a larger scale. Results showed that LAT improved soil fertility, particularly N-P-K concentrations while maintaining a good C:N ratio, pH, and SS concentration. BAT was the most effective at enhancing shoot growth but results suggest that improved growth rates could result in increased maintenance. Additionally, biosolids were an excellent source of nutrients, especially N-P-K and S, but diminished root growth and N leachate losses indicate that N was applied in excess of turfgrass requirements. Therefore, biosolids could be used as fertilizer, subject to recommended rates for turfgrass establishment to prevent poor root growth and waterborne N pollution. To ensure establishment efforts are successful, MAT is not recommended without a supplemental source of soluble N. Altogether, study results and conclusions could inform others seeking to improve specifications for disturbed soil where turfgrass establishment is needed to stabilize soil.

Ecological Groups of Coleoptera (Insecta) as Indicators of Habitat Transformation on Drained and Rewetted Peatlands: A Baseline Study from a Carbon Supersite, Kaliningrad, Russia.

A total of 281 coleopteran species from 41 families were recorded from different sites of an abandoned cut-over peatland designated as the Carbon Measurement Supersite in Kaliningrad Oblast. This beetle assemblage is considered a baseline (pre-impact) faunal assemblage for further investigations during the 'before-after' (BA) or 'before-after control-impact' (BACI) study on a peatland that is planned to be rewetted. The spontaneously revegetated peatland has a less specialised beetle assemblage than at an intact raised bog. Tyrphobiontic species are completely absent from the peatland, while some tyrphophiles (5.3% of the total beetle fauna) are still found as remnants of the former raised bog communities. The predominant coenotic coleopteran group is tyrphoneutral generalists from various non-bog habitats (72.9%). The species composition is associated with the vegetation structure of the disturbed peatland (fragmentary Sphagnum cover, lack of open habitats, and widespread birch coppice or tree stand), which does not correspond to that of a typical European raised bog. The sampled coleopteran assemblage is divided into several relative ecological groups, whose composition and peculiarities are discussed separately. Possible responses to the rewetting measurements in different coleopteran groups are predicted and briefly discussed. A complex assemblage of stenotopic peatland-specialised tyrphophiles (15 spp.) and the most abundant tyrphoneutral generalists (31 spp.) were assigned as indicators for the environmental monitoring of peatland development.

Disturbed fluid flow reinforces endothelial tractions and intercellular stresses.

Disturbed fluid flow is well understood to have significant ramifications on endothelial function, but the impact disturbed flow has on endothelial biomechanics is not well understood. In this study, we measured tractions, intercellular stresses, and cell velocity of endothelial cells exposed to disturbed flow using a custom-fabricated flow chamber. Our flow chamber exposed cells to disturbed fluid flow within the following spatial zones: zone 1 (inlet; length 0.676-2.027 cm): 0.0037 ± 0.0001 Pa; zone 2 (middle; length 2.027-3.716 cm): 0.0059 ± 0.0005 Pa; and zone 3 (outlet; length 3.716-5.405 cm): 0.0051 ± 0.0025 Pa. Tractions and intercellular stresses were observed to be highest in the middle of the chamber (zone 2) and lowest at the chamber outlet (zone 3), while cell velocity was highest near the chamber inlet (zone 1), and lowest near the middle of the chamber (zone 2). Our findings suggest endothelial biomechanical response to disturbed fluid flow to be dependent on not only shear stress magnitude, but the spatial shear stress gradient as well. We believe our results will be useful to a host of fields including endothelial cell biology, the cardiovascular field, and cellular biomechanics in general.

Dynamics of dissolved inorganic carbon (DIC) and stable C isotope ratios (δ13CDIC) in a tropical watershed with diversified land use in São Paulo State, Brazil.

The fluvial transport of dissolved inorganic carbon (DIC) is an important component of the global carbon cycle. Herein, we assessed the dynamics of DIC and the C stable isotopic composition (δ13CDIC) in a watershed with diversified land use in São Paulo State (Brazil), more specifically in the Sorocaba River basin (SRB) and considered the temporal and spatial scales. For this purpose, twelve fluvial samples at each sampling point (e.g., S1, S2, S3, S4 and S5) were collected in the SRB, from June 2009 to May 2010, which represented one complete hydrological cycle that included the extremes of the rainfall and discharge regimes. In addition, the δ13CDIC values were also characterized in the wet and dry season at all sampling points to verify their seasonal variability. The results reflected the seasonal variation in discharges, water temperatures, and electrical conductivities. Most of the DIC was transported in the wet season at all sampling points, where the less negative δ13CDIC values were characterized. The natural sources of DIC are associated with atmospheric/soil CO2 consumption. The anthropogenic impacts on both [DIC] and δ13CDIC are linked to untreated urban sewage that is discharged directly into the Sorocaba River, as well as to aquatic photosynthesis in the Itupararanga Reservoir. From 1970 to 2020, the modeling proposed in this study indicated that the annual flux of DIC (Friver) varied from 9.0 to 78.7 t km-2 a-1, confirming that the El Niño Southern Oscillation (ENSO) controlled Friver in the SRB, with higher and lower Friver values occurring during strong El Niño (EN) and La Niña (LN) years. The average Friver value was 20 t km-2 a-1, which is higher than those obtained in natural several temperate and tropical watersheds due to the influences of urban areas on [DIC] in the SRB.

Disturbed flow in the juxta-anastomotic area of an arteriovenous fistula correlates with endothelial loss, acute thrombus formation, and neointimal hyperplasia.

Clinical failure of arteriovenous neointimal hyperplasia (NIH) fistulae (AVF) is frequently due to juxta-anastomotic NIH (JANIH). Although the mouse AVF model recapitulates human AVF maturation, previous studies focused on the outflow vein distal to the anastomosis. We hypothesized that the juxta-anastomotic area (JAA) has increased NIH compared with the outflow vein. AVF was created in C57BL/6 mice without or with chronic kidney disease (CKD). Temporal and spatial changes of the JAA were examined using histology and immunofluorescence. Computational techniques were used to model the AVF. RNA-seq and bioinformatic analyses were performed to compare the JAA with the outflow vein. The jugular vein to carotid artery AVF model was created in Wistar rats. The neointima in the JAA shows increased volume compared with the outflow vein. Computational modeling shows an increased volume of disturbed flow at the JAA compared with the outflow vein. Endothelial cells are immediately lost from the wall contralateral to the fistula exit, followed by thrombus formation and JANIH. Gene Ontology (GO) enrichment analysis of the 1,862 differentially expressed genes (DEG) between the JANIH and the outflow vein identified 525 overexpressed genes. The rat jugular vein to carotid artery AVF showed changes similar to the mouse AVF. Disturbed flow through the JAA correlates with rapid endothelial cell loss, thrombus formation, and JANIH; late endothelialization of the JAA channel correlates with late AVF patency. Early thrombus formation in the JAA may influence the later development of JANIH.NEW & NOTEWORTHY Disturbed flow and focal endothelial cell loss in the juxta-anastomotic area of the mouse AVF colocalizes with acute thrombus formation followed by late neointimal hyperplasia. Differential flow patterns between the juxta-anastomotic area and the outflow vein correlate with differential expression of genes regulating coagulation, proliferation, collagen metabolism, and the immune response. The rat jugular vein to carotid artery AVF model shows changes similar to the mouse AVF model.

Disturbed flow regulates protein disulfide isomerase A1 expression via microRNA-204.

Redox processes can modulate vascular pathophysiology. The endoplasmic reticulum redox chaperone protein disulfide isomerase A1 (PDIA1) is overexpressed during vascular proliferative diseases, regulating thrombus formation, endoplasmic reticulum stress adaptation, and structural remodeling. However, both protective and deleterious vascular effects have been reported for PDIA1, depending on the cell type and underlying vascular condition. Further understanding of this question is hampered by the poorly studied mechanisms underlying PDIA1 expression regulation. Here, we showed that PDIA1 mRNA and protein levels were upregulated (average 5-fold) in the intima and media/adventitia following partial carotid ligation (PCL). Our search identified that miR-204-5p and miR-211-5p (miR-204/211), two broadly conserved miRNAs, share PDIA1 as a potential target. MiR-204/211 was downregulated in vascular layers following PCL. In isolated endothelial cells, gain-of-function experiments of miR-204 with miR mimic decreased PDIA1 mRNA while having negligible effects on markers of endothelial activation/stress response. Similar effects were observed in vascular smooth muscle cells (VSMCs). Furthermore, PDIA1 downregulation by miR-204 decreased levels of the VSMC contractile differentiation markers. In addition, PDIA1 overexpression prevented VSMC dedifferentiation by miR-204. Collectively, we report a new mechanism for PDIA1 regulation through miR-204 and identify its relevance in a model of vascular disease playing a role in VSMC differentiation. This mechanism may be regulated in distinct stages of atherosclerosis and provide a potential therapeutic target.

Disturbed flow impairs MerTK-mediated efferocytosis in aortic endothelial cells during atherosclerosis.

Background: MER proto-oncogene tyrosine kinase (MerTK) is a key receptor for efferocytosis, a process for the clearance of apoptotic cells. MerTK is mainly expressed in macrophages and immature dendritic cells. There are very limited reports focused on MerTK biology in aortic endothelial cells (ECs). It remains unclear for the role of blood flow patterns in regulating MerTK-mediated efferocytosis in aortic ECs. This study was designed to investigate whether endothelial MerTK and EC efferocytosis respond to blood flow patterns during atherosclerosis. Methods: Big data analytics, RNA-seq and proteomics combined with our in vitro and in vivo studies were applied to reveal the potential molecular mechanisms. Partial carotid artery ligation combined with AAV-PCSK9 and high fat diet were used to set up acute atherosclerosis in 4 weeks. Results: Our data showed that MerTK is sensitive to blood flow patterns and is inhibited by disturbed flow and oscillatory shear stress in primary human aortic ECs (HAECs). The RNA-seq data in HAECs incubated with apoptotic cells showed that d-flow promotes pro-inflammatory pathway and senescence pathway. Our in vivo data of proteomics and immunostaining showed that, compared with WT group, MerTK-/- aggravates atherosclerosis in d-flow areas through upregulation of endothelial dysfunction markers (e.g. IL-1ß, NF-κB, TLR4, MAPK signaling, vWF, VCAM-1 and p22phox) and mitochondrial dysfunction. Interestingly, MerTK-/-induces obvious abnormal endothelial thickening accompanied with decreased endothelial efferocytosis, promoting the development of atherosclerosis. Conclusions: Our data suggests that blood flow patterns play an important role in regulating MerTK-mediated efferocytosis in aortic ECs, revealing a new promising therapeutic strategy with EC efferocytosis restoration to against atherosclerosis.

Resilient exponential tracking for disturbed systems with communication links faults.

Resilience is to appraise the ability of disturbed systems to recover cooperative performance after suffering from failures or disturbances. In this paper, the improvement on the exponential tracking resilience for disturbed Euler-Lagrange systems is explored by settling the unknown time-variant faults imposed on the communication interaction between agents. First, we transform the resilient exponential tracking problem into designing the trajectory and velocity observers for leaders, and showcase that the proposed observers are resilient to communication interaction malfunctions. Second, a disturbance observer is manifested to estimate disturbances precisely, which is needless to know the upper bound of disturbance. The reliable observers and estimator are incorporated into the resilient tracking control frame. Further, the global exponential stabilization of the tracking systems is performed by utilizing the Lyapunov theory. Moreover, benefiting from feasible and reliable observation and estimation results, the proposed control framework enables to realize a satisfactory resilient exponential tracking performance even in the case of communication links faults (CLFs) and disturbances. Comprehensive studies are executed on a group of satellite systems, and the simulations results verify the effectiveness of the proposed resilient approaches in a time-variant tracking case.

Effect of expanding farmlands with domestication of animals in the vicinity of disturbed swamps and built-up farmland ponds on population dispersion and decline of locally adapted Mansonia vectors (Diptera: Culicidae).

Background and Objectives: The adaptive processes and resilience of Mansonia vectors responsible for bioindicators can change in response to climate, land use, and environmental changes. This study evaluated the effects of expanding farmlands with the domestication of animals in the vicinity of either disturbed swamps or built-up farmland ponds on the population dispersion and decline of locally adapted Mansonia faunas as a result of expanding farmlands in Thailand. Materials and Methods: Based on environmental surveys, four different geographically defined study sites were selected: I - the expanding farmlands with domestication of livestock and pet animals in the vicinity of low-lying swamp with habitat fragmentation and aquatic vegetation; II - the expanding farmlands with domestication of pet animals in the vicinity of elevated swamp with habitat destruction and aquatic vegetation; III - the expanding farmlands with domestication of livestock and pet animals in the vicinity of low-lying farmland ponds with restoration and aquatic vegetation; and IV - the expanding farmlands with domestication of pet animals in the vicinity of elevated farmland ponds with restoration and aquatic vegetation. Human landing catch collection method was used to periodically assess the species composition and abundance of Mansonia vectors. Results: Aggregated distributions and seasonal abundances of Mansonia faunas (Mansonia uniformis, Mansonia indiana, Mansonia annulifera, Mansonia annulata, Mansonia bonneae, and Mansonia dives) with variable proportions were observed at all the study sites. A decline in the population of Mansonia faunas, except for Ma. uniformis, was observed at study sites I and II. Conclusion: The anticipated effects of expanding farmlands affected the population dispersion and decline of locally adapted Mansonia faunas, thus representing a diverse assemblage of Mansonia species with different adaptations, ecological tolerances, and host exploitation strategies in life. These effects depended either on the function of disturbed swamps or on the development of farmland ponds, whether they provided a wide range of freshwater habitats, or on the domestication of animals, whether they provided animal blood meal sources.

Characterization of sensory and motor dysfunction and morphological alterations in late stages of type 2 diabetic mice.

Diabetic neuropathy is the most common complication of diabetes and lacks effective treatments. Although sensory dysfunction during the early stages of diabetes has been extensively studied in various animal models, the functional and morphological alterations in sensory and motor systems during late stages of diabetes remain largely unexplored. In the current work, we examined the influence of diabetes on sensory and motor function as well as morphological changes in late stages of diabetes. The obese diabetic Leprdb/db mice (db/db) were used for behavioral assessments and subsequent morphological examinations. The db/db mice exhibited severe sensory and motor behavioral defects at the age of 32 weeks, including significantly higher mechanical withdrawal threshold and thermal latency of hindpaws compared with age-matched nondiabetic control animals. The impaired response to noxious stimuli was mainly associated with the remarkable loss of epidermal sensory fibers, particularly CGRP-positive nociceptive fibers. Unexpectedly, the area of CGRP-positive terminals in the spinal dorsal horn was dramatically increased in diabetic mice, which was presumably associated with microglial activation. In addition, the db/db mice showed significantly more foot slips and took longer time during the beam-walking examination compared with controls. Meanwhile, the running duration in the rotarod test was markedly reduced in db/db mice. The observed sensorimotor deficits and motor dysfunction were largely attributed to abnormal sensory feedback and muscle atrophy as well as attenuated neuromuscular transmission in aged diabetic mice. Morphological analysis of neuromuscular junctions (NMJs) demonstrated partial denervation of NMJs and obvious fragmentation of acetylcholine receptors (AChRs). Intrafusal muscle atrophy and abnormal muscle spindle innervation were also detected in db/db mice. Additionally, the number of VGLUT1-positive excitatory boutons on motor neurons was profoundly increased in aged diabetic mice as compared to controls. Nevertheless, inhibitory synaptic inputs onto motor neurons were similar between the two groups. This excitation-inhibition imbalance in synaptic transmission might be implicated in the disturbed locomotion. Collectively, these results suggest that severe sensory and motor deficits are present in late stages of diabetes. This study contributes to our understanding of mechanisms underlying neurological dysfunction during diabetes progression and helps to identify novel therapeutic interventions for patients with diabetic neuropathy.

Steady Laminar Flow Decreases Endothelial Glycolytic Flux While Enhancing Proteoglycan Synthesis and Antioxidant Pathways.

Endothelial cells in steady laminar flow assume a healthy, quiescent phenotype, while endothelial cells in oscillating disturbed flow become dysfunctional. Since endothelial dysfunction leads to atherosclerosis and cardiovascular disease, it is important to understand the mechanisms by which endothelial cells change their function in varied flow environments. Endothelial metabolism has recently been proven a powerful tool to regulate vascular function. Endothelial cells generate most of their energy from glycolysis, and steady laminar flow may reduce endothelial glycolytic flux. We hypothesized that steady laminar but not oscillating disturbed flow would reduce glycolytic flux and alter glycolytic side branch pathways. In this study, we exposed human umbilical vein endothelial cells to static culture, steady laminar flow (20 dynes/cm2 shear stress), or oscillating disturbed flow (4 ± 6 dynes/cm2 shear stress) for 24 h using a cone-and-plate device. We then measured glucose and lactate uptake and secretion, respectively, and glycolytic metabolites. Finally, we explored changes in the expression and protein levels of endothelial glycolytic enzymes. Our data show that endothelial cells in steady laminar flow had decreased glucose uptake and 13C labeling of glycolytic metabolites while cells in oscillating disturbed flow did not. Steady laminar flow did not significantly change glycolytic enzyme gene or protein expression, suggesting that glycolysis may be altered through enzyme activity. Flow also modulated glycolytic side branch pathways involved in proteoglycan and glycosaminoglycan synthesis, as well as oxidative stress. These flow-induced changes in endothelial glucose metabolism may impact the atheroprone endothelial phenotype in oscillating disturbed flow.

Unveiling the resistance of native weed communities: insights for managing invasive weed species in disturbed environments.

Weed communities influence the dynamics of ecosystems, particularly in disturbed environments where anthropogenic activities often result in higher pollution. Understanding the dynamics existing between native weed communities and invasive species in disturbed environments is crucial for effective management and normal ecosystem functioning. Recognising the potential resistance of native weed communities to invasion in disturbed environments can help identify suitable native plants for restoration operations. This review aims to investigate the adaptations exhibited by native and non-native weeds that may affect invasions within disturbed environments. Factors such as ecological characteristics, altered soil conditions, and adaptations of native weed communities that potentially confer a competitive advantage relative to non-native or invasive weeds in disturbed environments are analysed. Moreover, the roles of biotic interactions such as competition, mutualistic relationships, and allelopathy in shaping the invasion resistance of native weed communities are described. Emphasis is given to the consideration of the resistance of native weeds as a key factor in invasion dynamics that provides insights for conservation and restoration efforts in disturbed environments. Additionally, this review underscores the need for further research to unravel the underlying mechanisms and to devise targeted management strategies. These strategies aim to promote the resistance of native weed communities and mitigate the negative effects of invasive weed species in disturbed environments. By delving deeper into these insights, we can gain an understanding of the ecological dynamics within disturbed ecosystems and develop valuable insights for the management of invasive species, and to restore long-term ecosystem sustainability.

The Population Dynamics and Parasitism Rates of Ceratitis capitata, Anastrepha fraterculus, and Drosophila suzukii in Non-Crop Hosts: Implications for the Management of Pest Fruit Flies.

Understanding the seasonal dynamics inherent to non-crop host-fruit fly-parasitoid interactions is vitally important for implementing eco-friendly pest control strategies. This study assessed the abundance and seasonal infestation levels of three pest fly species, Ceratitis capitata (Wiedemann), Anastrepha fraterculus (Wiedemann), Drosophila suzukii (Matsumura), as well as the related saprophytic drosophilids, and their natural parasitism in a disturbed wild habitat characterized by non-crop hosts in northwestern Argentina over 40 months. Juglans australis Griseb (walnut), Citrus aurantium L. (sour orange), Eriobotrya japonica (Thunb.) Lindley (loquat), Prunus persica (L.) Batsch (peach), and Psydium guajava L. (guava) were sampled throughout their fruiting seasons. Fruits were collected from both the tree canopies and the ground. The most abundant puparia was A. fraterculus, followed by C. capitata and D. suzukii. Drosophila species from the D. melanogaster group were highly abundant only in fallen fruits. Spatiotemporal overlaps of different host fruit availability provided suitable sources for pest proliferation throughout the year. The populations of both invasive pests peaked from December to January, and were related to the highest ripe peach availability, whereas the A. fraterculus population peaked from February to April, overlapping with the guava fruiting period. The three pest fly species were parasitized mainly by three generalist resident parasitoids, which are potential biocontrol agents to use within an integrated pest management approach.

Identification of KU-55933 as an anti-atherosclerosis compound by using a hemodynamic-based high-throughput drug screening platform.

Several compounds have been used for atherosclerosis treatment, including clinical trials; however, no anti-atherosclerotic drugs based on hemodynamic force-mediated atherogenesis have been discovered. Our previous studies demonstrated that "small mothers against decapentaplegic homolog 1/5" (Smad1/5) is a convergent signaling molecule for chemical [e.g., bone morphogenetic proteins (BMPs)] and mechanical (e.g., disturbed flow) stimulations and hence may serve as a promising hemodynamic-based target for anti-atherosclerosis drug development. The goal of this study was to develop a high-throughput screening (HTS) platform to identify potential compounds that can inhibit disturbed flow- and BMP-induced Smad1/5 activation and atherosclerosis. Through HTS using a Smad1/5 downstream target inhibitor of DNA binding 1 (Id-1) as a luciferase reporter, we demonstrated that KU-55933 and Apicidin suppressed Id-1 expression in AD-293 cells. KU-55933 (10 µM), Apicidin (10 µM), and the combination of half doses of each [1/2(K + A)] inhibited disturbed flow- and BMP4-induced Smad1/5 activation in human vascular endothelial cells (ECs). KU-55933, Apicidin, and 1/2(K + A) treatments caused 50.6%, 47.4%, and 73.3% inhibitions of EC proliferation induced by disturbed flow, respectively, whereas EC inflammation was only suppressed by KU-55933 and 1/2(K + A), but not Apicidin alone. Administrations of KU-55933 and 1/2(K + A) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in ECs in athero-susceptible regions, thereby suppressing endothelial proliferation and inflammation, with the attenuation of atherosclerotic lesions in these mice. A unique drug screening platform has been developed to demonstrate that KU-55933 and its combination with Apicidin are promising therapeutic compounds for atherosclerosis based on hemodynamic considerations.

Anthropogenic disturbance exacerbates resilience loss in the Amazon rainforests.

Uncovering the mechanisms that lead to Amazon forest resilience variations is crucial to predict the impact of future climatic and anthropogenic disturbances. Here, we apply a previously used empirical resilience metrics, lag-1 month temporal autocorrelation (TAC), to vegetation optical depth data in C-band (a good proxy of the whole canopy water content) in order to explore how forest resilience variations are impacted by human disturbances and environmental drivers in the Brazilian Amazon. We found that human disturbances significantly increase the risk of critical transitions, and that the median TAC value is ~2.4 times higher in human-disturbed forests than that in intact forests, suggesting a much lower resilience in disturbed forests. Additionally, human-disturbed forests are less resilient to land surface heat stress and atmospheric water stress than intact forests. Among human-disturbed forests, forests with a more closed and thicker canopy structure, which is linked to a higher forest cover and a lower disturbance fraction, are comparably more resilient. These results further emphasize the urgent need to limit deforestation and degradation through policy intervention to maintain the resilience of the Amazon rainforests.

Revealing symptom profiles: A pre-post analysis of docetaxel therapy in individuals with breast cancer.

PURPOSE: This study aimed to explore the symptom profiles and predominant symptoms in newly diagnosed breast cancer women before and after receiving docetaxel chemotherapy. METHODS: A pre-post study recruited adult women with stage I-III breast cancer undergoing docetaxel chemotherapy using convenience sampling. The 13-item symptom severity subscale of the M. D. Anderson Symptom Inventory-Taiwan Form was used to measure symptoms. The study employed latent profile analysis to identify subgroups based on symptom severity before and after docetaxel chemotherapy. Descriptive statistics, including mean and frequency, were used to compare and contrast the most prevalent and severe symptoms within each subgroup to confirm the predominant symptoms. RESULTS: The study identified four and two symptom profiles before and after docetaxel treatment, respectively. Disturbed sleep was identified as a prevalent symptom for all participants, regardless of their chemotherapy status. The predominant symptoms before treatment were disturbed sleep, dry mouth, difficulty remembering, and fatigue, while disturbed sleep and numbness were the predominant symptoms after treatment. CONCLUSION: The findings of this study are significant, as they contribute to the current understanding of the symptom experience of breast cancer individuals undergoing docetaxel chemotherapy. Healthcare professionals should prioritize assessing and managing these symptoms, including identifying contributing factors to poor sleep. Addressing symptom profiles related to sleep can improve the quality of life of breast cancer individuals undergoing docetaxel chemotherapy.

Examining the role of self-reported somatosensory sensations in body (dis)ownership: A scoping review and empirical study of patients with a disturbed sense of limb ownership.

Patients with a disturbed sense of limb ownership (DSO) offer a unique window of insight into the multisensory processes contributing to the sense of body ownership. A limited amount of past research has examined the role of sensory deficits in DSO, and even less is known regarding the role of patient self-reported somatosensory sensations in the pathogenesis of DSO. To address this lack of knowledge we first conducted a systematic scoping review following PRISMA-SR guidelines, examining current research into somatosensory deficits and patient self-reported somatosensory sensations in patients with DSO. Eighty studies, including 277 DSO patients, were identified. The assessment of sensory deficits was generally limited in scope and quality, and deficits in tactile sensitivity and proprioception were most frequently found. The reporting of somatosensory sensations was even less frequent, with instances of paraesthesia (pins-and-needles), stiffness/rigidity, numbness and warmth, coldness and heaviness amongst the deficits recorded. In a second part of the study, we sought to directly address the lack of evidence concerning the impact of patient self-reported somatosensory sensations in DSO by measuring DSO and self-reported somatosensory sensations in a large (n = 121) sample of right-hemisphere stroke patients including N = 65 with DSO and N = 56 hemiplegic controls. Results show that feelings of coldness and stiffness modulate DSO symptoms. Sense of heaviness and numbness are more frequent in patients with DSO but do not have a clear impact on disownership symptomology. Although preliminary, these results suggest a role of subjective sensations about the felt body in the sense of limb ownership.