Highlights Bioinformatics analysis of mouse mRNA expression dataset for presumptive SARS-CoV-2 targets. Induction of ISGs-Isg15, Oasl1, Usp18 and Ddx58 with no marked changes in the expression of IFNs. No induction of ACE2 and TMPRSS2, raising implications for host factor limitations. Identification of ceRNA network including miR-124-3p, Ddx58, lncRNA (Gm26917) and circRNAs (Ppp1r10, C330019G07RiK). Virus regulates the expression of lnc and circRNAs, acting as sponges for miR-124-3p targeting Ddx58.

In this study, we synthesized hierarchical CuO nanoleaves in large-quantity via the hydrothermal method. We employed different techniques to characterize the morphological, structural, optical properties of the as-prepared hierarchical CuO nanoleaves sample. An electrochemical based nonenzymatic glucose biosensor was fabricated using engineered hierarchical CuO nanoleaves. The electrochemical behavior of fabricated biosensor towards glucose was analyzed with cyclic voltammetry (CV) and amperometry (i–t) techniques. Owing to the high electroactive surface area, hierarchical CuO nanoleaves based nonenzymatic biosensor electrode shows enhanced electrochemical catalytic behavior for glucose electro-oxidation in 100 mM sodium hydroxide (NaOH) electrolyte. The nonenzymatic biosensor displays a high sensitivity (1467.32 μA/(mM cm2)), linear range (0.005–5.89 mM), and detection limit of 12 nM (S/N = 3). Moreover, biosensor displayed good selectivity, reproducibility, repeatability, and stability at room temperature over three-week storage period. Further, as-fabricated nonenzymatic glucose biosensors were employed for practical applications in human serum sample measurements. The obtained data were compared to the commercial biosensor, which demonstrates the practical usability of nonenzymatic glucose biosensors in real sample analysis.

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Macrophage migration inhibitory factor (MIF) activates CD74, whichl eads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions.M olecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between aresidue located at the opening of one end of the MIF solvent channel, previously thought to be ac onsequence of homotrimerization, and residues in ad istal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified apathway to this site via the MIF b-strands. The reported findings providef undamental insights on ad ynamic mechanism that controls the MIF-induced activation of CD74.MIF is ap ro-inflammatory cytokine with regulatory functions that control cell fate.I np athological conditions, such as cancer, MIF serves to manipulate the immune system to benefit malignant cells. [1] Thec ascade of signaling events that promote tumor growth and metastasis is initiated by the MIF-induced activation of the cell surface receptor CD74. [2] MIF is also an on-cognate,p artial agonist of CXCR2 and CXCR4. [3] Despite the extensive understanding of the MIF role in immune system physiology and pathology,westill lack af undamental understanding of all aspects of protein structure and activity.G eneration of ac o-crystal or NMR structure between MIF and its primary receptor CD74 has been difficult to obtain due to the increased flexibility of CD74. [4] However,i nsights into the MIF/CD74 interaction can be obtained using other methods that are focused on understanding the intermolecular mechanism of CD74 activation by MIF.N umerous crystal structures of wild-type and mutants of MIF have been determined, as well as MIF cocrystal structures with substrates,c ompetitive,n on-competitive,and covalent inhibitors. [5][6][7][8][9][10] No significant changes in the MIF tertiary or quaternary structures have been observed, other than movements of side chains.S uch findings give the impression that local flexibility [11] is important for regulation of MIF biological functions,i ncluding activation of the cell surface receptor CD74. TheMIF surface residues responsible for activation of CD74 were mapped by epitope scanning [12] and alanine-scanning mutagenesis. [9] To probe whether local flexibility of the MIF trimer has any role in CD74 activation, we employed atomistic molecular dynamics simulations of wild-type human MIF over 1 ms. Our findings show that the averaged root-mean-square fluctuation (RMSF) over all residues is 0.90 indicating that the system remains in at ightly clustered ensemble (Supporting Information, Figure S1a,b). Correlations between fluctuations in the displacement of Ca of pairs of residues i and j were identified with the generalized correlation matrix, with entries C ij . This approach provides an improvement over the calculation of covariance matrices and linear correlations. [13] Theapproximate threefold symmetry of the protein is reflected in the correlation plot where each boxed region repre...

BackgroundHaptic display technologies are well suited to relay proprioceptive, force, and contact cues from a prosthetic terminal device back to the residual limb and thereby reduce reliance on visual feedback. The ease with which an amputee interprets these haptic cues, however, likely depends on whether their dynamic signal behavior corresponds to expected behaviors—behaviors consonant with a natural limb coupled to the environment. A highly geared motor in a terminal device along with the associated high back-drive impedance influences dynamic interactions with the environment, creating effects not encountered with a natural limb. Here we explore grasp and lift performance with a backdrivable (low backdrive impedance) terminal device placed under proportional myoelectric position control that features referred haptic feedback.MethodsWe fabricated a back-drivable terminal device that could be used by amputees and non-amputees alike and drove aperture (or grip force, when a stiff object was in its grasp) in proportion to a myoelectric signal drawn from a single muscle site in the forearm. In randomly ordered trials, we assessed the performance of N=10 participants (7 non-amputee, 3 amputee) attempting to grasp and lift an object using the terminal device under three feedback conditions (no feedback, vibrotactile feedback, and joint torque feedback), and two object weights that were indiscernible by vision.ResultsBoth non-amputee and amputee participants scaled their grip force according to the object weight. Our results showed only minor differences in grip force, grip/load force coordination, and slip as a function of sensory feedback condition, though the grip force at the point of lift-off for the heavier object was significantly greater for amputee participants in the presence of joint torque feedback. An examination of grip/load force phase plots revealed that our amputee participants used larger safety margins and demonstrated less coordination than our non-amputee participants.ConclusionsOur results suggest that a backdrivable terminal device may hold advantages over non-backdrivable devices by allowing grip/load force coordination consistent with behaviors observed in the natural limb. Likewise, the inconclusive effect of referred haptic feedback on grasp and lift performance suggests the need for additional testing that includes adequate training for participants.

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Abstract. Functional near infrared spectroscopy (fNIR) is a noninvasive, portable optical imaging tool to monitor changes in hemodynamic responses (i.e., oxygenated hemoglobin (HbO)) within the prefrontal cortex (PFC) in response to sensory, motor or cognitive activation. We used fNIR for monitoring PFC activation during learning of simulated laparoscopic surgical tasks throughout 4 days of training and testing. Blocked (BLK) and random (RND) practice orders were used to test the practice schedule effect on behavioral, hemodynamic responses and relative neural efficiency (EFF rel-neural ) measures during transfer. Left and right PFC for both tasks showed significant differences with RND using less HbO than BLK. Cognitive workload showed RND exhibiting high EFF rel-neural across the PFC for the coordination task while the more difficult cholecystectomy task showed EFF rel-neural differences only in the left PFC. Use of brain activation, behavioral and EFF rel-neural measures can provide a more accurate depiction of the generalization or transfer of learning.

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