As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks of premature death and other medical conditions for patients. Neuroinflammation is ...the abnormal immune response in the brain, and its correlation with MDD is receiving increasing attention. Neuroinflammation has been reported to be involved in MDD through distinct neurobiological mechanisms, among which the dysregulation of neurogenesis in the dentate gyrus (DG) of the hippocampus (HPC) is receiving increasing attention. The DG of the hippocampus is one of two niches for neurogenesis in the adult mammalian brain, and neurotrophic factors are fundamental regulators of this neurogenesis process. The reported cell types involved in mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, and peripheral immune cells which selectively penetrate the blood-brain barrier and infiltrate into inflammatory regions. This review summarizes the functions of the hippocampus affected by neuroinflammation during MDD progression and the corresponding influences on the memory of MDD patients and model animals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The activation of retinoic acid-inducible gene 1 (RIG-I), a cytoplasmic innate sensor for viral RNA, is tightly regulated to maintain immune homeostasis properly and prevent excessive inflammatory ...reactions other than initiation of antiviral innate response to eliminate RNA virus effectively. Posttranslational modifications, particularly ubiquitination, are crucial for regulation of RIG-I activity. Increasing evidence suggests that E3 ligases play important roles in various cellular processes, including cell proliferation and antiviral innate signaling. Here we identify that E3 ubiquitin ligase RING finger protein 122 (RNF122) directly interacts with mouse RIG-I through MS screening of RIG-I–interacting proteins in RNA virus-infected cells. The transmembrane domain of RNF122 associates with the caspase activation and recruitment domains (CARDs) of RIG-I; this interaction effectively triggers RING finger domain of RNF122 to deliver the Lys-48–linked ubiquitin to the Lys115 and Lys146 residues of RIG-I CARDs and promotes RIG-I degradation, resulting in a marked inhibition of RIG-I downstream signaling. RNF122 is widely expressed in various immune cells, with preferential expression in macrophages. Deficiency of RNF122 selectively increases RIG-I–triggered production of type I IFNs and proinflammatory cytokines in macrophages. RNF122-deficient mice exhibit more resistance against lethal RNA virus infection, with increased production of type I IFNs. Thus, we demonstrate that RNF122 acts as a selective negative regulator of RIG-I–triggered antiviral innate response by targeting CARDs of RIG-I and mediating proteasomal degradation of RIG-I. Our study outlines a way for E3 ligase to regulate innate sensor RIG-I for the control of antiviral innate immunity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The issue of security and privacy plays an important role in the Internet of Things (IoT) and directly affects its wide applications. In order to meet the security requirements in the IoT ...environment, a series of lightweight encryption schemes have been proposed. Meanwhile, cryptanalysis against these schemes is critical to the security of IoT. In this paper, a practical distinguishing attack on an IoT‐friendly lightweight cipher ALLPC is presented. Specifically, it is found that there exists a fixed point in the differential of ALLPC's S‐box, then a differential trail with a period of 14‐round has been proposed. By connecting to the periodic differential trail, a differential trail is constructed for the full‐round ALLPC with a probability of 2−24. Applying such property, one can distinguish the full‐round ALLPC block cipher from a random permutation in about 10 min on a laptop.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Conventional reconnaissance camera systems have been flown on manned aircraft, where the weight, size, and power requirements are not stringent. However, today, these parameters are important for ...unmanned aerial vehicles (UAVs). This article provides a solution to the design of airborne large aperture infrared optical systems, based on a monocentric lens that can meet the strict criteria of aerial reconnaissance UAVs for a wide field of view (FOV) and lightness of airborne electro-optical pod cameras. A monocentric lens has a curved image plane, consisting of an array of microsensors, which can provide an image with 368 megapixels over a 100° FOV. We obtained the initial structure of a five-glass (5GS) asymmetric monocentric lens with an air gap, using ray-tracing and global optimization algorithms. According to the design results, the ground sampling distance (GSD) of the system is 0.33 m at 3000 m altitude. The full-field modulation transfer function (MTF) value of the system is more than 0.4 at a Nyquist frequency of 70 lp/mm. We present a primary thermal control method, and the image quality was steady throughout the operating temperature range. This compactness and simple structure fulfill the needs of uncrewed airborne lenses. This work may facilitate the practical application of monocentric lens in UAVs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Infantile pneumonia (IP) is an acute lower respiratory infection that imposes a heavy burden on children's health. Increasing evidence has demonstrated that long non-coding RNA (lncRNA) LINC00707 ...participates in the regulation of the pneumonia process. Cell proliferative ability and apoptosis were measured using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Bcl-2 related X protein (Bax), NF-kB activating protein (NKAP), p-P65, P65, p-IκBα, and IκBα protein levels were detected using western blot assay. The binding between miR-382-5p and LINC00707 or NKAP was predicted by starBase v2.0 and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. LINC00707 and NKAP levels were increased, and miR-382-5p was decreased in LPS-stimulated WI-38 cells. Furthermore, the silencing of LINC00707 could abrogate LPS-engendered WI-38 cell proliferation, apoptosis, and oxidative stress. LINC00707 deficiency could relieve LPS-triggered WI-38 cell damage by regulating the miR-382-5p/NKAP axis, providing a new therapeutic strategy for IP treatment.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
CD4+ T cells play predominant roles in protective immunity against blood-stage Plasmodium infection, both for IFN-γ-dependent effector mechanisms and providing B cell helper signals. Neddylation, an ...ubiquitination-like process triggered by covalent conjugation of NEDD8 to specific targets, has emerged as a potential regulator of T cell activities to TCR engagement. However, its contribution to T cell-mediated immunity to blood-stage malaria remains unclear. Here using an experimental model induced by Plasmodium yoelii 17XNL, and conditional knockout mice with T cell-specific deficiency of crucial components of neddylation pathway, we demonstrate activation of neddylation in T cells during blood-stage Plasmodium infection is essential for parasite control and host survival. Mechanistically, we show that apart from promoting CD4+ T cell activation, proliferation, and development of protective T helper 1 (Th1) cell response as suggested previously, neddylation is also required for supporting CD4+ T cell survival, mainly through B-cell lymphoma-2 (Bcl-2) mediated suppression of the mitochondria-dependent apoptosis. Furthermore, we provide evidence that neddylation contributes to follicular helper T (Tfh) cell differentiation, probably via augmenting the ubiquitin ligase Itch activity and proteasomal degradation of FoxO1, thereby facilitating germinal center (GC) formation and parasite-specific antibody production. This study identifies neddylation as a positive regulator of anti-Plasmodium immunity and provides insight into an involvement of such pathway in host resistance to infectious diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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Intranasal inoculation of Ad5 expressing SARS-CoV-2 N aggravates lung pathology.
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Enhanced infiltration of T cells in Ad5-N group.
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More T cells and granulocytes undergo necroptosis in Ad5-N ...group.
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Accumulated T cells are antigen-experienced and express more IFN-γ.
Preclinical studies indicate that SARS-CoV-2 nucleocapsid (N)-based vaccines, along with other viral protein(s), confer protection in various animal models against infection by SARS-CoV-2 ancestral virus and variants of concern. However, the optimal vaccination procedure and the role of N-specific host adaptive immune responses remain elusive. Here, we report that intranasal inoculation with replication-deficient human adenovirus type 5 expressing SARS-CoV‐2 N protein (Ad5-N) conferred no protection in the lung of female BALB/c mice upon re-encountering the antigen, either by 10-fold Ad5-N re-exposure or sublethal infection of mouse-adapted SARS-CoV-2. By contrast, this procedure led to aggravated lung pathology with more necroptotic CD3
+
T cells and Ly6G
+
granulocytes, which was associated with the accumulation of IFN‐γ‐expressing antigen-experienced CD4
+
and CD8
+
T cells. These findings pre-caution the clinical application of this vaccination procedure. Furthermore, our data suggest that excessive host adaptive immune responses against N protein contributes to COVID-19 pathogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In obesity, macrophages drive a low-grade systemic inflammation (LSI) and insulin resistance (IR). The ribosome biosynthesis protein NOC4 (NOC4) mediates 40 S ribosomal subunits synthesis in yeast. ...Hereby, we reported an unexpected location and function of NOC4L, which was preferentially expressed in human and mouse macrophages. NOC4L was decreased in both obese human and mice. The macrophage-specific deletion of Noc4l in mice displayed IR and LSI. Conversely, Noc4l overexpression by lentivirus treatment and transgenic mouse model improved glucose metabolism in mice. Importantly, we found that Noc4l can interact with TLR4 to inhibit its endocytosis and block the TRIF pathway, thereafter ameliorated LSI and IR in mice.
Laser-irradiated metallic foils were considered as x-ray sources for extended x-ray absorption fine structure (EXAFS) measurements and confirmed by experiments on the SGIII prototype facility. The Au ...foils were irradiated by laser beams with a total energy of 2.77 kJ and full width at half maximum (FWHM) of 1 ns to create an x-ray source. The x-ray emission was spectrally smooth in the energy range of Ti EXAFS, the FWHM of Au foil x-ray radiation pulse in the energy range of 0.1–4000 eV was 0.99 ns, and the FWHM of x-ray pulse in the energy range of 5000–6000 eV was deduced to be 0.55 ns according to simulation results. A shaped laser pulse was designed to achieve the Ti sample’s laser-direct-driven ramp compression process. By creating a quasi-stable state lasting longer than 1 ns as the probing window during the compression process, the demand for temporal resolution was reduced. EXAFS spectra of compressed Ti in α and ω-phase were obtained and compared, and structural phase transition was verified by EXAFS pattern changes. The velocity of the back interface of the Ti sample was measured by the velocity interferometer system for any reflector, and the maximum of the deduced pressure in the middle of the Ti sample was 8.2 GPa, which is consistent with the α-ω phase transition.
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