No abstract

Caprin-1 plays roles in many important biological processes, including cellular proliferation, innate immune response, stress response and synaptic plasticity. Caprin-1 has been implicated in several human diseases, including osteosarcoma, breast cancer, viral infection, hearing loss and neurodegenerative disorders. The functions of Caprin-1 depend on its molecular-interaction network. Direct interactions have been established between Caprin-1 and the fragile X mental retardation protein (FMRP), Ras GAP-activating protein-binding protein 1 (G3BP1) and the Japanese encephalitis virus (JEV) core protein. Here, crystal structures of a fragment (residues 132-251) of Caprin-1, which adopts a novel all-α-helical fold and mediates homodimerization through a substantial interface, are reported. Homodimerization creates a large and highly negatively charged concave surface suggestive of a protein-binding groove. The FMRP-interacting sequence motif forms an integral α-helix in the dimeric Caprin-1 structure in such a way that the binding of FMRP would not disrupt the homodimerization of Caprin-1. Based on insights from the structures and existing biochemical data, the existence of an evolutionarily conserved ribonucleoprotein (RNP) complex consisting of Caprin-1, FMRP and G3BP1 is proposed. The JEV core protein may bind Caprin-1 at the negatively charged putative protein-binding groove and an adjacent E-rich sequence to hijack the RNP complex.

Fast and accurate diagnosis and the immediate isolation of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are regarded as the most effective measures to restrain the coronavirus disease 2019 (COVID-19) pandemic. Here, we present a high-throughput, multi-index nucleic acid isothermal amplification analyzer (RTisochip™-W) employing a centrifugal microfluidic chip to detect 19 common respiratory viruses, including SARS-CoV-2, from 16 samples in a single run within 90 min. The limits of detection of all the viruses analyzed by the RTisochip™-W system were equal to or less than 50 copies·μL −1 , which is comparable to those of conventional reverse transcription polymerase chain reaction. We also demonstrate that the RTisochip™-W system possesses the advantages of good repeatability, strong robustness, and high specificity. Finally, we analyzed 201 cases of preclinical samples, 14 cases of COVID-19-positive samples, 25 cases of clinically diagnosed samples, and 614 cases of clinical samples from patients or suspected patients with respiratory tract infections using the RTisochip™-W system. The test results matched the referenced results well and reflected the epidemic characteristics of the respiratory infectious diseases. The coincidence rate of the RTisochip™-W with the referenced kits was 98.15% for the detection of SARS-CoV-2. Based on these extensive trials, we believe that the RTisochip™-W system provides a powerful platform for fighting the COVID-19 pandemic.

BackgroundPsychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter.MethodsTwenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis.ResultsPost-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe.ConclusionsAt an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the “top-down” mechanism of psychotherapy.

To control the ongoing coronavirus disease‐2019 (COVID‐19) pandemic, CoronaVac (Sinovac), an inactivated vaccine, has been granted emergency use authorization by many countries. However, the underlying mechanisms of the inactivated COVID‐19 vaccine‐induced immune response remain unclear, and little is known about its features compared to (Severe acute respiratory syndrome coronavirus 2) SARS‐CoV‐2 infection. Here, we implemented single‐cell RNA sequencing (scRNA‐seq) to profile longitudinally collected PBMCs (peripheral blood mononuclear cells) in six individuals immunized with CoronaVac and compared these to the profiles of COVID‐19 infected patients from a Single Cell Consortium. Both inactivated vaccines and SARS‐CoV‐2 infection altered the proportion of different immune cell types, caused B cell activation and differentiation, and induced the expression of genes associated with antibody production in the plasma. The inactivated vaccine and SARS‐COV‐2 infection also caused alterations in peripheral immune activity such as interferon response, inflammatory cytokine expression, innate immune cell apoptosis and migration, effector T cell exhaustion and cytotoxicity, however, the magnitude of change was greater in COVID‐19 patients, especially those with severe disease, than in immunized individuals. Further analyses revealed a distinct peripheral immune cell phenotype associated with CoronaVac immunization (HLA class II upregulation and IL21R upregulation in naïve B cells) versus SARS‐CoV‐2 infection (HLA class II downregulation and IL21R downregulation in naïve B cells from severe disease individuals). There were also differences in the expression of important genes associated with proinflammatory cytokines and thrombosis. In conclusion, this study provides a single‐cell atlas of the systemic immune response to CoronaVac immunization and revealed distinct immune responses between inactivated vaccines and SARS‐CoV‐2 infection.

Regenerative medicine represented by stem cell technology has become one of the pillar medical technologies for human disease treatment. Cytoskeleton plays important roles in maintaining cell morphology, bearing external forces, and maintaining the effectiveness of cell internal structure, among which cytoskeleton related proteins are involved in and play an indispensable role in the changes of cytoskeleton. PDLIM5 is a cytoskeleton-related protein that, like other cytoskeletal proteins, acts as a binding protein. PDZ and LIM domain 5 (PDLIM5), also known as ENH (Enigma homolog), is a cytoplasmic protein with a molecular mass of about 63 KDa that consists of a PDZ domain at the N-terminus and three LIM domains at the C-terminus. PDLIM5 binds to the cytoskeleton and membrane proteins through its PDZ domain and interacts with various signaling molecules, including protein kinases and transcription factors, through its LIM domain. As a cytoskeleton-related protein, PDLIM5 plays an important role in regulating cell proliferation, differentiation and cell fate decision in multiple tissues and cell types. In this review, we briefly summarize the state of knowledge on the PDLIM5 gene, structural properties, and molecular functional mechanisms of the PDLIM5 protein, and its role in cells, tissues, and organ systems, and describe the possible underlying molecular signaling pathways. In the last part of this review, we will focus on discussing the limitations of existing research and the future prospects of PDLIM5 research in turn.

The influences of the Li+/Ni2+ replacement modulated by minor Co dopant on cyclic capacity and rate performance of lithium-rich cathode material Li1.2Ni0.2−z/2Mn0.6−z/2CozO2 (z = 0, 0.02, 0.04, 0.10) were investigated from the microstructural point of view by comprehensive techniques of HRTEM, EELS, SAED, and XRD.

Using comprehensive transmission electron microscopy (TEM) techniques, the associations between the Mn dopant content, microstructure and improved rate performance of LiFe (1Àx) Mn x PO 4 (0 # x # 0.5) were well established. Via the synergistic mechanism including both templating and chelating effects contributed by cetyltrimethyl ammonium bromide (CTAB) and citric acid, a series of LiFe (1Àx) Mn x PO 4 (0 # x # 0.5) olivine crystals with adjustable Mn doping content were synthesized. No impurity phase was detected. Accidentally, a novel type of roughness phenomenon at the particle boundaries of LiFe (1Àx) Mn x PO 4 particles was observed, which depended on citric acid chelation. At the atomic level, the Mn ions were confirmed to be homogeneously substituted at the iron sites, which were furthermore examined by the combined analysis of electron energy loss spectroscopy (EELS), high angle annular dark-field (HAADF) imaging, magnetic susceptibility measurements and X-ray diffraction (XRD).Li/Fe antisite defects were found in the doped LiFe (1Àx) Mn x PO 4 rather than in pure LiFePO 4 by HAADF-EELS acquired from a single-atom column at high spatial resolution. The rate performance of LiFe 0.9 Mn 0.1 PO 4 and LiFe 0.8 Mn 0.2 PO 4 was improved compared to that of LiFePO 4 . Our findings might provide new insights into the understanding of Li-ion battery cathode materials with Mn dopant from a microstructural point of view.