Drops on soft solids: Free energy and double transition of contact angles

The equilibrium shape of liquid drops on elastic substrates is determined by minimising elastic and capillary free energies, focusing on thick incompressible substrates. The problem is governed by three length scales: the size of the drop $R$, the molecular size $a$, and the ratio of surface tension to elastic modulus $\gamma/E$. We show that the contact angles undergo two transitions upon changing the substrates from rigid to soft. The microscopic wetting angles deviate from Young's law when $\gamma/Ea \gg 1$, while the apparent macroscopic angle only changes in the very soft limit $\gamma/ER \gg 1$. The elastic deformations are worked out in the simplifying case where the solid surface energy is assumed constant. The total free energy turns out lower on softer substrates, consistent with recent experiments

Differences in mental health problems, coping self-efficacy and social support between adults victimised before and adults victimised after the COVID-19 outbreak:Population-based prospective study

Background Victims of violence, accidents and threats are at risk for mental health problems. Lower coping self-efficacy and social support levels increase this risk. Although highly relevant, it is unknown if the coronavirus disease 2019 (COVID-19) pandemic amplifies these risks. Aims To examine if the prevalence, incidence and/or mean scores for post-traumatic stress disorder (PTSD), anxiety and depression symptoms, general mental health problems, coping self-efficacy, lack of emotional support and social acknowledgement are higher among adults victimised in the year after the COVID-19 outbreak compared with adults victimised in a similar period before the outbreak. Also, to compare symptoms, problems and support within non-victims during the same period. Method Data was extracted from four surveys of the VICTIMS study (March 2018, 2019, 2020, 2021), based on a random sample of the Dutch population. Multivariate logistic regression analyses and mixed-effects models were used to examine differences between the two victim groups (2019: n = 421, 2021: n = 319) and non-victims (n = 3245). Results Adults victimised after the outbreak more often had PTSD, anxiety and depression symptoms, general mental health problems and lower coping self-efficacy than those victimised before. They did not differ in lack of support and acknowledgement. Both victim groups differed from non-victims, where mental health problems and lack of support levels were much lower and almost stable. Conclusions The COVID-19 pandemic had a negative impact on the mental health and coping self-efficacy levels of victims, whereas mental health problems among non-victims remained virtually stable. Mental healthcare workers, general practitioners and victim services should take this impact into account

Melanomas prevent endothelial cell death under restrictive culture conditions by signaling through AKT and p38 MAPK/ ERK-1/2 cascades

Although melanoma progression and staging is clinically well characterized, a large variation is observed in pathogenesis, progression, and therapeutic responses. Clearly, intrinsic characteristics of melanoma cells contribute to this variety. An important factor, in both progression of the disease and response to therapy, is the tumor-associated vasculature. We postulate that melanoma cells communicate with endothelial cells (ECs) in order to establish a functional and supportive blood supply. We investigated the angiogenic potential of human melanoma cell lines by monitoring the survival of ECs upon exposure to melanoma conditioned medium (CM), under restrictive conditions. We observed long-term (up to 72 h) EC survival under hypoxic conditions upon treatment with all melanoma CMs. No such survival effect was observed with the CM of melanocytes. The CM of pancreatic and breast tumor cell lines did not show a long-term survival effect, suggesting that the survival factor is specific to melanoma cells. Furthermore, all size fractions (up to < 1 kDa) of the melanoma CM induced long-term survival of ECs. The survival effect observed by the < 1 kDa fraction excludes known pro-angiogenic factors. Heat inactivation and enzymatic digestion of the CM did not inactivate the survival factor. Global gene expression and pathway analysis suggest that this effect is mediated in part via the AKT and p38 MAPK/ ERK-1/2 signaling axis. Taken together, these data indicate the production of (a) survival factor/s (< 1 kDa) by melanoma cell lines, which enables long-term survival of ECs and promotes melanoma-induc

An element through the looking glass: Exploring the Au-C, Au-H and Au-O energy landscape

Gold, the archetypal “noble metal”, used to be considered of little interest in catalysis. It is now clear that this was a misconception, and a multitude of gold-catalysed transformations has been reported. However, one consequence of the long-held view of gold as inert metal is that its organometallic chemistry contains many “unknowns”, and catalytic cycles devised to explain gold's reactivity draw largely on analogies with other transition metals. How realistic are such mechanistic assumptions? In the last few years a number of key compound classes have been discovered that can provide some answers. This Perspective attempts to summarise these developments, with particular emphasis on recently discovered gold(III) complexes with bonds to hydrogen, oxygen, alkenes and CO ligands

Computer-assisted detection of pulmonary embolism: evaluation of pulmonary CT angiograms performed in an on-call setting

Item does not contain fulltextPURPOSE: The purpose of the study was to assess the stand-alone performance of computer-assisted detection (CAD) for evaluation of pulmonary CT angiograms (CTPA) performed in an on-call setting. METHODS: In this institutional review board-approved study, we retrospectively included 292 consecutive CTPA performed during night shifts and weekends over a period of 16 months. Original reports were compared with a dedicated CAD system for pulmonary emboli (PE). A reference standard for the presence of PE was established using independent evaluation by two readers and consultation of a third experienced radiologist in discordant cases. RESULTS: Original reports had described 225 negative studies and 67 positive studies for PE. CAD found PE in seven patients originally reported as negative but identified by independent evaluation: emboli were located in segmental (n = 2) and subsegmental arteries (n = 5). The negative predictive value (NPV) of the CAD algorithm was 92% (44/48). On average there were 4.7 false positives (FP) per examination (median 2, range 0-42). In 72% of studies or=10 FP. CONCLUSION: CAD identified small emboli originally missed under clinical conditions and found 93% of the isolated subsegmental emboli. On average there were 4.7 FP per examination.1 april 201

Current challenges and future directions for engineering extracellular vesicles for heart, lung, blood and sleep diseases.

Extracellular vesicles (EVs) carry diverse bioactive components including nucleic acids, proteins, lipids and metabolites that play versatile roles in intercellular and interorgan communication. The capability to modulate their stability, tissue-specific targeting and cargo render EVs as promising nanotherapeutics for treating heart, lung, blood and sleep (HLBS) diseases. However, current limitations in large-scale manufacturing of therapeutic-grade EVs, and knowledge gaps in EV biogenesis and heterogeneity pose significant challenges in their clinical application as diagnostics or therapeutics for HLBS diseases. To address these challenges, a strategic workshop with multidisciplinary experts in EV biology and U.S. Food and Drug Administration (USFDA) officials was convened by the National Heart, Lung and Blood Institute. The presentations and discussions were focused on summarizing the current state of science and technology for engineering therapeutic EVs for HLBS diseases, identifying critical knowledge gaps and regulatory challenges and suggesting potential solutions to promulgate translation of therapeutic EVs to the clinic. Benchmarks to meet the critical quality attributes set by the USFDA for other cell-based therapeutics were discussed. Development of novel strategies and approaches for scaling-up EV production and the quality control/quality analysis (QC/QA) of EV-based therapeutics were recognized as the necessary milestones for future investigations.Funding information: National Heart, Lung, and Blood Institute, Grant/Award Numbers: HL 122596, HL124021, HL124074, HL128297, HL141080, HL155346-01, R35HL150807, R56HL141206 Prithu Sundd was supported by NIH-NHLBI R01 grants (HL128297 and HL141080) and 18TPA34170588 from American Heart Association. Stephen Y. Chan was supported by NIH grants R01 HL124021 and HL 122596 as well as AHA grant 18EIA33900027. SuamyaDaswas supported by NIH grants R35HL150807, UH3 TR002878 andAHASFRN35120123. ZhenjiaWangwas supported by NIH grant (R01EB027078). Pilar Martín was supported by MCIN-ISCIII-Fondo de Investigación Sanitaria grant PI22/01759. KennethW.Witwer was supported in part by NIH grants R01AI144997, R01DA047807, R33MH118164 andUH3CA241694. Tianji Chen was supported by AHA Career Development Award 18CDA34110301, Gilead Sciences Research Scholars Program in PAH, NIH-NHLBI grant R56HL141206 and Chicago Biomedical ConsortiumCatalyst Award. EduardoMarbán was supported byNIH R01 HL124074 and HL155346-01.S

RNAi-mediated inhibition of HIV-1 by targeting partially complementary viral sequences

Potent antiviral RNAi can be induced by intracellular expression of short hairpin RNAs (shRNAs) and artificial microRNAs (miRNAs). Expression of shRNA and miRNA results in target mRNA degradation (perfect base pairing) or translational repression (partial base pairing). Although efficient inhibition can be obtained, error-prone viruses such as human immunodeficiency virus type 1 (HIV-1) can escape from RNAi-mediated inhibition by mutating the target sequence. Recently, artificial miRNAs have been shown to be potent RNAi inducers due to their efficient processing by the RNAi machinery. Furthermore, miRNAs may be more proficient in suppressing imperfect targets than shRNAs. In this study, we tested the knockdown efficiency of miRNAs and shRNAs against wild-type and RNAi-escape HIV-1 variants with one or two mutations in the target sequence. ShRNAs and miRNAs can significantly inhibit the production of HIV-1 variants with mutated target sequences in the open reading frame. More pronounced mutation-tolerance was measured for targets in the 3′ untranslated region (3′ UTR). Partially complementary sequences within the 3′ UTR of the HIV-1 RNA genome efficiently act as target sites for miRNAs and shRNAs. These data suggest that targeting imperfect target sites by antiviral miRNAs or shRNAs provides an alternative RNAi approach for inhibition of pathogenic viruses

Crucial Role of miR-433 in Regulating Cardiac Fibrosis

Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes. Conversely, inhibition of miR-433 exhibited opposite results. AZIN1 and JNK1 were identified as two target genes of miR-433. Decreased level of AZIN1 activated TGF-β1 while down-regulation of JNK1 resulted in activation of ERK and p38 kinase leading to Smad3 activation and ultimately cardiac fibrosis. Importantly, systemic neutralization of miR-433 or adeno-associated virus 9 (AAV9)-mediated cardiac transfer of a miR-433 sponge attenuated cardiac fibrosis and ventricular dysfunction following myocardial infarction. Thus, our work suggests that miR-433 is a potential target for amelioration of cardiac fibrosis