Interferometers are widely used in imaging technologies to achieve enhanced spatial resolution, but require that the incoming photons be indistinguishable. In previous work, we built and analyzed ...color erasure detectors, which expand the scope of intensity interferometry to accommodate sources of different colors. Here we demonstrate experimentally how color erasure detectors can achieve improved spatial resolution in an imaging task, well beyond the diffraction limit. Utilizing two 10.9-mm-aperture telescopes and a 0.8 m baseline, we measure the distance between a 1063.6 and a 1064.4 nm source separated by 4.2 mm at a distance of 1.43 km, which surpasses the diffraction limit of a single telescope by about 40 times. Moreover, chromatic intensity interferometry allows us to recover the phase of the Fourier transform of the imaged objects-a quantity that is, in the presence of modest noise, inaccessible to conventional intensity interferometry.
A novel multifunctional nanotheranostic agent with targeting, redox‐responsive ultrasound imaging and ultrasound imaging‐guided high‐intensity focused ultrasound (HIFU) therapy (MSNC‐PEG‐HASS‐PFH, ...abbreviated as MPHSS‐PFH) capabilities is developed. The redox‐responsive guest molecule release and ultrasound imaging functions can be both integrated in such a “smart” theranostic agent, which is accomplished by the redox‐triggered transition from the crosslinking state to retrocrosslinking state of the grafted polyethylene glycol‐disulfide hyaluronic acid molecules on the particle surface when reaching a reducing environment in vitro. More importantly, under the tailored ultrasound imaging guiding, in vivo Hela tumor‐bearing nude mice can be thoroughly and spatial‐accurately ablated during HIFU therapy, due to the targeted accumulation, responsive ultrasound imaging guidance and the synergistic ablation functions of nanotheranostic agent MPHSS‐PFH in the tumors. This novel multifunctional nano‐platform can serve as a promising candidate for further studies on oncology therapy, due to its high stability, responsive and indicative ultrasound imaging of tumors, and enhanced HIFU therapeutic efficiency and spatial accuracy under ultrasound‐guidance.
Can a nanosized agent efficiently respond to ultrasound? A multifunctional redox‐responsive complex decorated, ultrasound sensitive PFH encapsulated nanotheranostic agent has been successfully constructed, which can be activated by the internal reducing environment and the external HIFU stimulus to enable tailored ultrasound guided synergistic HIFU therapy duo to its redox‐responsive ultrasound imaging and PFH bubble cavitations/thermal effects.
•Long chain fatty acid inhibited methanogenesis by limiting substrates utilization.•Anaerobic granular sludge absorbed long chain fatty acids.•Long chain fatty acid enhanced bubble separation from ...anaerobic granules.•Long chain fatty acid reduced the bubble-bubble coalescence probability.•Long chain fatty acid changed adhesion forces between bubble and bubble.
Anaerobic digestion of lipid-rich wastewater generally suffers from foaming induced by long chain fatty acid (LCFA). However, a systematic understanding of LCFA inhibition, especially the physical inhibition on interfacial interaction still remains unclear. Here, we combined bubble probe atomic force microscope and impinging-jet technique to unravel the interfacial interactions controlled by long chain fatty acids in anaerobic digestion. We showed that LCFA had a significant inhibition on methane production in anaerobic reactors for the inhibition of the conversion of VFAs to methane. By measuring the LCFA influence on methanogenic archaea Methanosarcina acetivorans C2A, the results demonstrated that methanogenesis was limited for substrates utilization but not metabolic pathways. The impinging-jet technique results indicated that LCFA enhanced bubble separation from anaerobic granules and reduced the bubble-bubble coalescence probability. In addition, the bubble probe atomic force microscope (AFM) revealed that LCFA enhanced the adhesion force between bubbles by enhancing electrical double layer (EDL) repulsion and decreasing hydrophobic interactions. Overall, these results complement framework of LCFA inhibition in anerobic digestion and provide a nanomechanical insight into the fundamental interfacial interactions related to bubbles in anaerobic reactors.
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Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of ...COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days with severe weight loss, morbidity, and failure to thrive. We demonstrate that there is metabolic suppression of oxidative phosphorylation and the tricarboxylic acid (TCA) cycle in multiple organs with neutrophilia, lymphopenia, and splenic atrophy, mirroring human COVID-19 phenotypes. Animals had a significantly lower heart rate, and electron microscopy demonstrated myofibrillar disarray and myocardial edema, a common pathogenic cardiac phenotype in human COVID-19. We performed metabolomic profiling of peripheral blood and identified a panel of TCA cycle metabolites that served as biomarkers of depressed oxidative phosphorylation. Finally, we observed that SARS-CoV-2 induces epigenetic changes of DNA methylation, which affects expression of immune response genes and could, in part, contribute to COVID-19 pathogenesis. Our model suggests that SARS-CoV-2-induced metabolic reprogramming and epigenetic changes in internal organs could contribute to systemic toxicity and lethality in COVID-19.
CULLIN3‐based E3 ubiquitin ligase substrate‐binding adaptor gene SPOP is frequently mutated in prostate cancer (PCa). PCa harboring SPOP hotspot mutants (e.g., F133V) are resistant to BET inhibitors ...because of aberrant elevation of BET proteins. Here, we identified a previously unrecognized mutation Q165P at the edge of SPOP MATH domain in primary and metastatic PCa of a patient. The Q165P mutation causes structural changes in the MATH domain and impairs SPOP dimerization and substrate degradation. Different from F133V hotspot mutant tumors, Q165P mutant patient‐derived xenografts (PDXs) and organoids were modestly sensitive to the BET inhibitor JQ1. Accordingly, protein levels of AR, BRD4 and downstream effectors such as RAC1 and phosphorylated AKT were not robustly elevated in Q165P mutant cells as in F133V mutant cells. However, NEO2734, a novel dual inhibitor of BET and CBP/p300, is active in both hotspot mutant (F133V) and non‐hotspot mutant (Q165P) PCa cells in vitro and in vivo. These data provide a strong rationale to clinically investigate the anti‐cancer efficacy of NEO2734 in SPOP‐mutated PCa patients.
Synopsis
While patient‐derived xenografts (PDXs) and organoids harboring the novel SPOP mutant Q165P respond modestly to the BET inhibitor JQ1, both Q165P mutant and JQ1‐resistant SPOP hotspot mutant prostate cancer cells are sensitive to the BET and CBP/p300 dual inhibitor NEO2734 in vitro and in vivo.
Identification of a novel SPOP Q165P heterozygous mutation in primary and homozygous mutation in metastatic prostate cancer.
Q165P likely causes structural changes in the MATH domain and impairs SPOP dimerization and substrate degradation.
Q165P mutant patient‐derived xenografts (PDXs) and organoids respond modestly to JQ1 and robustly to the BET and CBP/p300 dual inhibitor NEO2734.
JQ1‐resistant SPOP hotspot mutant prostate cancer cells are sensitive to NEO2734 in vitro and in vivo.
While patient‐derived xenografts (PDXs) and organoids harboring the novel SPOP mutant Q165P respond modestly to the BET inhibitor JQ1, both Q165P mutant and JQ1‐resistant SPOP hotspot mutant prostate cancer cells are sensitive to the BET and CBP/p300 dual inhibitor NEO2734 in vitro and in vivo.
Oxidative stress is a common cause of neurodegeneration and plays a central role in retinal degenerative diseases. Heme oxygenase-1 (HMOX1) is a redox-regulated enzyme that is induced in ...neurodegenerative diseases and acts against oxidative stress but can also promote cell death, a phenomenon that is still unexplained in molecular terms. Here, we test whether HMOX1 has opposing effects during retinal degeneration and investigate the molecular mechanisms behind its pro-apoptotic role.
Basal and induced levels of HMOX1 in retinas are examined during light-induced retinal degeneration in mice. Light damage-independent HMOX1 induction at two different expression levels is achieved by intraocular injection of different doses of an adeno-associated virus vector expressing HMOX1. Activation of Müller glial cells, retinal morphology and photoreceptor cell death are examined using hematoxylin-eosin staining, TUNEL assays, immunostaining and retinal function are evaluated with electroretinograms. Downstream gene expression of HMOX1 is analyzed by RNA-seq, qPCR examination and western blotting. The role of one of these genes, the pro-apoptotic DNA damage inducible transcript 3 (Ddit3), is analyzed in a line of knockout mice.
Light-induced retinal degeneration leads to photoreceptor degeneration and concomitant HMOX1 induction. HMOX1 expression at low levels before light exposure prevents photoreceptor degeneration but expression at high levels directly induces photoreceptor degeneration even without light stress. Photoreceptor degeneration following high level expression of HMOX1 is associated with a mislocalization of rhodopsin in photoreceptors and an increase in the expression of DDIT3. Genetic deletion of Ddit3 in knockout mice prevents photoreceptor cell degeneration normally resulting from high level HMOX1 expression.
The results reveal that the expression levels determine whether HMOX1 is protective or deleterious in the retina. Furthermore, in contrast to the protective low dose of HMOX1, the deleterious high dose is associated with induction of DDIT3 and endoplasmic reticulum stress as manifested, for instance, in rhodopsin mislocalization. Hence, future applications of HMOX1 or its regulated targets in gene therapy approaches should carefully consider expression levels in order to avoid potentially devastating effects.
Domain of unknown function 4228 (DUF4228) proteins are a class of proteins widely found in plants, playing an important role in response to abiotic stresses. However, studies on the DUF4228 family in ...soybean (
L.) are sparse. In this study, we identified a total of 81
genes in soybean genome, named systematically based on their chromosome distributions. Results showed that these genes were unevenly distributed on the 20 chromosomes of soybean. The predicted soybean DUF4228 proteins were identified in three groups (Groups I-III) based on a maximum likelihood phylogenetic tree. Genetic structure analysis showed that most of the
genes contained no introns. Expression profiling showed that
genes were widely expressed in different organs and tissues in soybean. RNA-seq data were used to characterize the expression profiles of
genes under the treatments of drought and salt stresses, with nine genes showing significant up-regulation under both drought and salt stress further functionally verified by promoter (
-acting elements) analysis and quantitative real-time PCR (qRT-PCR). Due to its upregulation under drought and salt stresses based on both RNA-seq and qRT-PCR analyses,
was selected for further functional analysis in transgenic plants. Under drought stress, the degree of leaf curling and wilting of the
-overexpressing (
-OE) line was lower than that of the empty vector (EV) line.
-OE lines also showed increased proline content, relative water content (RWC), and chlorophyll content, and decreased contents of malondialdehyde (MDA), H
O
, and O
. Under salt stress, the changes in phenotypic and physiological indicators of transgenic plants were the same as those under drought stress. In addition, overexpression of the
gene promoted the expression of marker genes under both drought and salt stresses. Taken together, the results indicated that
genes play important roles in response to abiotic stresses in soybean.
Background To mitigate uncertainty that may arise in the judgment of emergency medical technicians when relying on a prehospital stroke scale at the scene, we propose a hospital selection protocol ...that considers the uncertainty of a prehospital stroke scale and the actual door-to-treatment durations, and we have developed a web-based system to be used with mobile devices. Methods and Results This hospital selection protocol incorporates real-time, estimated transport time obtained from Google Maps, historical median door-to-treatment duration at hospitals that only provide the standard intravenous thrombolysis treatment, and at hospitals with endovascular thrombectomy for probable large-vessel occlusion cases. We have validated the efficiency of the proposed protocol and compared it with other strategies used by emergency medical technicians when deciding on a receiving hospital. Using the proposed protocol for the triage reduces the time from onset to receiving definitive treatment by nearly 11 minutes. We found that the nearest endovascular thrombectomy-capable hospital from the scene may not be the most ideal if the door-to-treatment durations are discriminative. The results show that, when the tolerable bypass transport threshold and administration time are reduced to 9 minutes and 30.5 minutes, respectively, 228 patients out of 7678 cases, whose receiving hospitals were changed to endovascular thrombectomy-capable hospitals, received definitive treatment in a shorter time. The results of our analysis give recommendations for appropriate allowable bypass transport time for regional planning. Conclusions By applying almost-real value parameters, we have validated a web-based model, which can be universally adapted for optimal, time-saving hospital selection for patients with stroke.
Little research was focused on the anerobic degradation of refractory para-toluic acid at present. Thus, temperature-regulated anaerobic system of para-toluic acid fed as sole substrate was built and ...investigated via microbiota, metabolism intermediates, and function prediction in this study. Results showed that low methane yield was produced in para-toluic acid anaerobic system at alkaline condition. And the causes were owing to anaerobic methane oxidation and potentially H2S production at 37 °C, N2 production by denitrification before starvation and propionic acid occurrence after starvation at 27 °C, and production of N2 and free ammonia, and accumulation of acetic acid at 52 °C. Simultaneously, hydrogenotrophic methanogenesis dependent on syntrophic acetate oxidation (SAO) was predominant, facilitating the removal of para-toluic acid at 52 °C. Moreover, the key intermediate changed from phthalic acid of 37 °C and 27 °C before starvation to terephthalic acid of 52 °C. Starvation promoted removal of para-toluic acid through benzoyl-CoA pathway by Syntrophorhabdus, enrichment of syntrophic propionate degraders of Bacteroidetes and Ignavibacteriaceae, and increase of methylotrophic methanogens.
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•Temperature variation and starvation changed para-toluic acid metabolic pathway.•Temperature variation and starvation also changed dominant methanogens type.•The key intermediate was phthalic acid at 37 °C and terephthalic acid at 52 °C.•Benzoate and fatty acid metabolism were facilitated at 27 °C.
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•Our theoretical work is innovative, combining anisotropic two-dimensional materials, hyperbolic metamaterials and light field concentration.•Our biaxial hyperbolic metamaterial ...structure consisting of anisotropic monolayer black phosphorus can achieve topological transition from an elliptical dispersion to a hyperbolic dispersion based on effective medium theory.•Our absorber achieves an average absorption of up to 93.4%, omnidirectionality (up to 70°), and polarization sensitivity from 30 to 90 μm (3.3 to 10 terahertz). It's optimal as far as we know.•Moreover, unlike the physical mechanism of common multilayer metal/dielectric sawtooth absorbers, which is related to slow-light effect, the absorption of our proposed absorber is attributed to the localized surface plasmon resonance, bulk plasmon polaritons and moth-eye effect.
We propose a biaxial hyperbolic metamaterials (HMMs) sawtooth absorber using anisotropic black phosphorus (BP) and demonstrate that it can achieve a topological transition from an elliptical dispersion to a hyperbolic dispersion. We also show the material to be an epsilon-near-zero HMM and validate an effective medium theory. Due to BP’s anisotropic permittivity and light confinement, our absorber achieves an average absorption of up to 93.4%, omnidirectionality (up to 70°), and polarization sensitivity from 30 to 90 μm. We gain physical insights about the high absorption using electric field distributions and absorbed power distribution. Unlike the physical mechanism of common multilayer metal/dielectric sawtooth absorbers, which is related to slow-light effect, the absorption of our proposed absorber is attributed to the localized surface plasmon resonance, plasmon polaritons. Our proposed HMM can be applied in the infrared to terahertz region and we conclude by providing practical guidelines for future research on biaxial hyperbolic metamaterials and anisotropic two-dimensional materials.
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