Search

Mechanical forces, including flow shear stress, govern fundamental cellular processes by modulating nucleocytoplasmic transport of transcription factors like Yes‐associated Protein (YAP). However, the underlying mechanical mechanism remains elusive. In this study, it is reported that unidirectional flow induces biphasic YAP transport with initial nuclear import, followed by nuclear export as actin cap formation and nuclear stiffening. Conversely, pathological oscillatory flow induces slight actin cap formation, nuclear softening, and sustained YAP nuclear localization. To elucidate the disparately YAP spatiotemporal distribution, a 3D mechanochemical model is developed, which integrates flow sensing, cytoskeleton organization, nucleus mechanotransduction, and YAP transport. The results unveiled that despite the significant localized nuclear stress imposed by the actin cap, its inherent stiffness counteracts the dispersed contractile stress exerted by conventional fibers on the nuclear membrane. Moreover, alterations in nuclear stiffness synergistically regulate nuclear deformation, thereby governing YAP transport. Furthermore, by expanding the single‐cell model to a collective vertex framework, it is revealed that the irregularities in actin cap formation within individual cells have the potential to induce topological defects and spatially heterogeneous YAP distribution in the cellular monolayer. This work unveils a unified mechanism of flow‐induced nucleocytoplasmic transport, providing a linkage between transcription factor localization and mechanical stimulation. [ABSTRACT FROM AUTHOR]

The existing identification (ID) and antimicrobial susceptibility testing (AST) method requires at least two to three days to detect blood infection, and a fast and accurate detection method is very necessary for sepsis patients or Intensive Care Unit (ICU) patients. Here, we describe a direct isolated bacteria from a positive blood culture bottle (PBCB), and rapid AST method by femtosecond stimulated Raman scattering (SRS) imaging of deuterium oxide (D2O) metabolism, which can determine the antimicrobial susceptibility of bacteria from PBCB in 5-6 hours. The positive blood culture sample is passed through a filter membrane and mixed with cell lysis, after through the centrifugal which can directly isolated bacterium in order to identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS), following by antibiotic susceptibility testing by SRS imaging within a day. Overall, this rapid and rapid process combination of MALDI-TOF MS and SRS imaging of deuterium oxide (D2O) metabolism can solve the direct identification and antibiotic susceptibility testing of pathogen in positive blood cultures.

Currently, the high -- quality fusion of SAR and optical images is a hot research topic. However, the significant radiation difference and weak gray correlation between SAR and optical images greatly reduce the fusion quality. In this regard, this study proposed a SAR and optical remote sensing image fusion algorithm that coupled non -- local self -- similarity and divergence. First, images were decomposed in the frequency domain. Then, the non -- local directional entropy and divergence were used as characteristic parameters to guide the fusion of low -- and high -- frequency components, respectively. Finally, the fusion components were reconstructed to obtain fusion images with clear structural features and rich spectral information. The comparative experiments verified the effectiveness of the proposed algorithm in fusing SAR with optical images and its superiority in maintaining structural features and reducing spectral distortion. [ABSTRACT FROM AUTHOR]

The RIIβ subunit of cAMP‐dependent protein kinase A (PKA) is expressed in the brain and adipose tissue. RIIβ‐knockout mice show leanness and increased UCP1 in brown adipose tissue. The authors have previously reported that RIIβ reexpression in hypothalamic GABAergic neurons rescues the leanness. However, whether white adipose tissue (WAT) browning contributes to the leanness and whether RIIβ‐PKA in these neurons governs WAT browning are unknown. Here, this work reports that RIIβ‐KO mice exhibit a robust WAT browning. RIIβ reexpression in dorsal median hypothalamic GABAergic neurons (DMH GABAergic neurons) abrogates WAT browning. Single‐cell sequencing, transcriptome sequencing, and electrophysiological studies show increased GABAergic activity in DMH GABAergic neurons of RIIβ‐KO mice. Activation of DMH GABAergic neurons or inhibition of PKA in these neurons elicits WAT browning and thus lowers body weight. These findings reveal that RIIβ‐PKA in DMH GABAergic neurons regulates WAT browning. Targeting RIIβ‐PKA in DMH GABAergic neurons may offer a clinically useful way to promote WAT browning for treating obesity and other metabolic disorders. [ABSTRACT FROM AUTHOR]

In order to study the equivalent relationship between the accelerated aging test and natural exposure test of the coatings on color steel plates for buildings, five cycles of accelerated aging test and five quarters of natural exposure test of zinc-coated steel plate with red, white, and blue coatings commonly used in Lanzhou City were carried out. The aging phenomena such as loss of luster, discoloration, chalking, and blistering appearing on the protective coatings of three colors at different acceleration cycles and exposure time were analyzed. The aging behaviors of the coatings on colored steel plates for buildings were analyzed based on the failure criteria of luster loss after accelerated aging test and natural exposure test. The results showed that accelerated aging test could reproduce the natural aging characteristics. Considering the multi-attributes and dynamic characteristics of aging of coating, a variety of fitting methods were used to analyze the data of the two tests for different color coatings. Three fitting methods were selected and the variation rules of the luster loss and aging characteristics with time were described with the correlation functions. The representation of equivalent acceleration relationship for the coating of each color was established. The equivalent relationship between accelerated aging test result and the natural outdoor exposure test result was determined as follows: 0.80 quarter/cycle for the red sample, 1.03 quarters/cycle for the white sample, and 0.93 quarter/cycle for the blue sample. [ABSTRACT FROM AUTHOR]

L-type Ca2+ (CaV1) channels transduce channel activities into nuclear signals critical to neuritogenesis. Also, standalone peptides encoded by CaV1 DCT (distal carboxyl-terminus) act as nuclear transcription factors reportedly promoting neuritogenesis. Here, by focusing on exemplary CaV1.3 and cortical neurons under basal conditions, we discover that cytosolic DCT peptides downregulate neurite outgrowth by the interactions with CaV1's apo-calmodulin binding motif. Distinct from nuclear DCT, various cytosolic peptides exert a gradient of inhibitory effects on Ca2+ influx via CaV1 channels and neurite extension and arborization, and also the intermediate events including CREB activation and c-Fos expression. The inhibition efficacies of DCT are quantitatively correlated with its binding affinities. Meanwhile, cytosolic inhibition tends to facilitate neuritogenesis indirectly by favoring Ca2+-sensitive nuclear retention of DCT. In summary, DCT peptides as a class of CaV1 inhibitors specifically regulate the channel activity-neuritogenesis coupling in a variant-, affinity-, and localization-dependent manner. When present in the cytosol, a variety of peptides encoded by the distal carboxyl-termini of the L-type CaV1 calcium channels downregulate channel activity and neurite outgrowth. [ABSTRACT FROM AUTHOR]

Rapid antimicrobial susceptibility testing (AST) is urgently needed for treating infections with appropriate antibiotics and slowing down the emergence of antibiotic‐resistant bacteria. Here, a phenotypic platform that rapidly produces AST results by femtosecond stimulated Raman scattering imaging of deuterium oxide (D2O) metabolism is reported. Metabolic incorporation of D2O into biomass in a single bacterium and the metabolic response to antibiotics are probed in as short as 10 min after culture in 70% D2O medium, the fastest among current technologies. Single‐cell metabolism inactivation concentration (SC‐MIC) is obtained in less than 2.5 h from colony to results. The SC‐MIC results of 37 sets of bacterial isolate samples, which include 8 major bacterial species and 14 different antibiotics often encountered in clinic, are validated by standard minimal inhibitory concentration blindly measured via broth microdilution. Toward clinical translation, stimulated Raman scattering imaging of D2O metabolic incorporation and SC‐MIC determination after 1 h antibiotic treatment and 30 min mixture of D2O and antibiotics incubation of bacteria in urine or whole blood is demonstrated. [ABSTRACT FROM AUTHOR]