KPNA3 regulates histone locus body formation by modulating condensation and nuclear import of NPAT.

The histone locus body (HLB) is a membraneless organelle that determines the transcription of replication-dependent histones. However, the mechanisms underlying the appropriate formation of the HLB in the nucleus but not in the cytoplasm remain unknown. HLB formation is dependent on the scaffold protein NPAT.

Imaging of Viral Genomic RNA Replication with Nanoprobes.

Viruses are a great threat to human life and health. Different viruses have its unique mechanism to efficiently infect cells, and the entry process and the nucleic acid replication using cell machine are two critical processes related to the fate of virus progeny. Real-time and long-term imaging techniques can be used to thoroughly investigate the viral infection events.

A single-dose intranasal live-attenuated codon deoptimized vaccine provides broad protection against SARS-CoV-2 and its variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) continues its significant health and economic impact globally. Despite the success of spike-protein vaccines in preventing severe disease, long-lasting protection against emerging variants and the prevention of breakthrough infections and transmission remain elusive. We generate an intranasal live-attenuated SARS-CoV-2 vaccine, CDO-7N-1, using codon deoptimization.

FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design.

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1.

VAPB-mediated ER-targeting stabilizes IRS-1 signalosomes to regulate insulin/IGF signaling.

The scaffold protein IRS-1 is an essential node in insulin/IGF signaling. It has long been recognized that the stability of IRS-1 is dependent on its endomembrane targeting. However, how IRS-1 targets the intracellular membrane, and what type of intracellular membrane is actually targeted, remains poorly understood.

Role of MXRA8 in Ross River Virus Disease Pathogenesis.

Arthritogenic alphaviruses such as Ross River virus (RRV) and Chikungunya virus (CHIKV) are responsible for large-scale epidemics that cause debilitating acute and chronic musculoskeletal diseases. MXRA8 was recently discovered as an entry receptor for multiple alphaviruses including CHIKV, RRV, Mayaro virus (MAYV), and O'nyong-nyong virus (ONNV). However, the role of MXRA8 in the development of alphavirus-induced musculoskeletal inflammation has not yet been fully studied.

CELLULAR SENESCENCE IMPLICATED IN SEPSIS-INDUCED MUSCLE WEAKNESS AND AMELIORATED WITH METFORMIN.

Background: Sepsis is a life-threatening medical emergency, frequently complicated with intensive care unit-acquired weakness syndrome (ICU-AW). ICU-AW patients display flaccid weakness of the limbs, especially in the proximal limb muscles. However, little is known regarding its pathogenesis.

Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes.

As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive.

PLX5622 Reduces Disease Severity in Lethal CNS Infection by Off-Target Inhibition of Peripheral Inflammatory Monocyte Production.

PLX5622 is a CSF-1R inhibitor and microglia-depleting reagent, widely used to investigate the biology of this central nervous system (CNS)-resident myeloid population, but the indirect or off-target effects of this agent remain largely unexplored. In a murine model of severe neuroinflammation induced by West Nile virus encephalitis (WNE), we showed PLX5622 efficiently depleted both microglia and a sub-population of border-associated macrophages in the CNS. However, PLX5622 also significantly depleted mature Ly6C monocytes in the bone marrow (BM), inhibiting their proliferation and lethal recruitment into the infected brain, reducing neuroinflammation and clinical disease scores.

AMPK-mediated phosphorylation enhances the auto-inhibition of TBC1D17 to promote Rab5-dependent glucose uptake.

Dysregulation of glucose homeostasis contributes to insulin resistance and type 2 diabetes. Whilst exercise stimulated activation of AMP-activated protein kinase (AMPK), an important energy sensor, has been highlighted for its potential to promote insulin-stimulated glucose uptake, the underlying mechanisms for this remain largely unknown. Here we found that AMPK positively regulates the activation of Rab5, a small GTPase which is involved in regulating Glut4 translocation, in both myoblasts and skeletal muscles.

Basic insights into Zika virus infection of neuroglial and brain endothelial cells.

Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain-Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood-brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood.

Zika virus encephalitis in immunocompetent mice is dominated by innate immune cells and does not require T or B cells.

Background: Until the end of the twentieth century, Zika virus (ZIKV) was thought to cause a mostly mild, self-limiting disease in humans. However, as the geographic distribution of ZIKV has shifted, so too has its pathogenicity. Modern-day ZIKV infection is now known to cause encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome in otherwise healthy adults.

Hsp90β interacts with MDM2 to suppress p53-dependent senescence during skeletal muscle regeneration.

Cellular senescence plays both beneficial and detrimental roles in embryonic development and tissue regeneration, while the underlying mechanism remains elusive. Recent studies disclosed the emerging roles of heat-shock proteins in regulating muscle regeneration and homeostasis. Here, we found that Hsp90β, but not Hsp90α isoform, was significantly upregulated during muscle regeneration.

Hsp70 Interacts with Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 To Regulate p38MAPK Stability and Myoblast Differentiation during Skeletal Muscle Regeneration.

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation.

Activation of AKT-mTOR Signaling Directs Tenogenesis of Mesenchymal Stem Cells.

Tendon repair is a clinical challenge because of the limited understanding on tenogenesis. The synthesis of type I collagen (Collagen I) and other extracellular matrix are essential for tendon differentiation and homeostasis. Current studies on tenogenesis focused mostly on the tenogenic transcriptional factors while the signaling controlling tenogenesis on translational level remains largely unknown.

Chiral nanoprobes for targeting and long-term imaging of the Golgi apparatus.

The Golgi apparatus is an essential subcellular organelle. Targeting and monitoring the Golgi change at the single-cell level over a long time scale are critical but are challenges that have not yet been tackled. Inspired by the precise Golgi positioning ability of galactosyltransferase and protein kinase D, due to their cysteine residues, we developed a method for long-term Golgi imaging.

Surface-engineered quantum dots/electrospun nanofibers as a networked fluorescence aptasensing platform toward biomarkers.

A membrane-based fluorescent sensing platform is a facile, point-of-care and promising technique in chemo/bio-analytical fields. However, the existing fluorescence sensing films for cancer biomarkers have several problems, with dissatisfactory sensitivity and selectivity, low utilization of probes encapsulated in films as well as the tedious design of membrane structures. In this work, a novel fluorescence sensing platform is fabricated by bio-grafting quantum dots (QDs) onto the surface of electrospun nanofibers (NFs).

A dynamic cell entry pathway of respiratory syncytial virus revealed by tracking the quantum dot-labeled single virus.

Studying the cell entry pathway at the single-particle level can provide detailed and quantitative information for the dynamic events involved in virus entry. Indeed, the viral entry dynamics cannot be monitored by static staining methods used in cell biology, and thus virus dynamic tracking could be useful in the development of effective antiviral strategies. Therefore, the aim of this work was to use a quantum dot-based single-particle tracking approach to monitor the cell entry behavior of the respiratory syncytial virus (RSV) in living cells.

Color resolution improvement of the dark-field microscopy imaging of single light scattering plasmonic nanoprobes for microRNA visual detection.

Imaging of light scattering plasmonic nanoparticles (PNPs) with the aid of the dark-field microscopy imaging (iDFM) technique has attracted wide attention owing to its high signal-to-noise ratio, but to improve the color resolution and contrast of dark-field microscopy (DFM) images of single light scattering PNPs in a small spectral variation environment is still a challenge. In this study, a new color analytical method for resolving the resolution and contrast in DFM images has been developed and further applied for colorimetric analysis using the digital image processing technique. The color of single light scattering PNP images is automatically coded at first with the hue values of the HSI color model, and then amplified using the MATLAB program even for marginal spectral changes, leading to significant improvement of the color resolution of DFM images and easy detection with the naked eye.

His-tag based in situ labelling of progeny viruses for real-time single virus tracking in living cells.

Tracking virus infection events in live cells is useful for understanding the mechanism of virus infection, and fluorescent labelling is a critical step. Herein a noninvasive strategy for labelling viruses with His-tags was developed by in situ modifying the cell surface proteins with polypeptides containing His-tags during progeny virus assembly. The His-tagged viruses were further conjugated with Ni-nitrilotriacetate complex modified quantum dots, and retained their infectivity for real-time single virus tracking in living cells.

HSI colour-coded analysis of scattered light of single plasmonic nanoparticles.

Single plasmonic nanoparticles (PNPs) analysis with dark-field microscopic imaging (iDFM) has attracted much attention in recent years. The ability for quantitative analysis of iDFM is critical, but cumbersome, for characterizing and analyzing the scattered light of single PNPs. Here, a simple automatic HSI colour coding method is established for coding dark-field microscopic (DFM) images of single PNPs with localized surface plasmon resonance (LSPR) scattered light, showing that hue value in the HSI system can realize accurate quantitative analysis of iDFM and providing a novel approach for quantitative chemical and biochemical imaging at the single nanoparticle level.

A magnetic nanoparticle-based aptasensor for selective and sensitive determination of lysozyme with strongly scattering silver nanoparticles.

Qualitative and quantitative determination of lysozyme concentrations in urine and serum with high selectivity and sensitivity is important for diagnosing the progression of several diseases. In this report, we devised an improved method for specifically detecting lysozyme by combining magnetic nanoparticles (for separation and enrichment), an aptamer (for selective binding of lysozyme) and strongly scattering silver nanoparticles (AgNPs, for detection by light scattering, but also providing another level of selectivity due to their electrostatic binding with lysozyme). In this system, 0.

Influence of the large-small split effect on strategy choice in complex subtraction.

Two main theories have been used to explain the arithmetic split effect: decision-making process theory and strategy choice theory. Using the inequality paradigm, previous studies have confirmed that individuals tend to adopt a plausibility-checking strategy and a whole-calculation strategy to solve large and small split problems in complex addition arithmetic, respectively. This supports strategy choice theory, but it is unknown whether this theory also explains performance in solving different split problems in complex subtraction arithmetic.