Notes

[Social stigma inside mental illness: An assessment of principles, methods and empirical evidence].
B cell development in bone marrow (BM) is a multi-staged process involving pro-B, pre-B, immature B, and mature B cells, among which pre-B cells undergo vigorous proliferation, differentiation, apoptosis, and gene rearrangement. While several signaling pathways participate in pre-B cell development have been clarified, detailed intrinsic mechanisms regulating pre-B cell proliferation and survival have not been fully understood. In the current study, we report that miR-582 regulates pre-B cell proliferation and survival. miR-582 is enriched in pre-B cells. Deletion of miR-582 in mice expanded the BM pre-B cell population in a cell-autonomous manner as shown by competitive BM transplantation. We show that forced miR-582 overexpression inhibited pre-B cell proliferation and survival, whereas downregulation of miR-582 by siRNA significantly promoted pre-B cell proliferation and survival in vitro. We identified that Hif1α and Rictor are authentic targets of miR-582 in pre-B cells as shown by reporter assays. Moreover, miR-582 overexpression reduced the expression of Hif1α and its downstream molecule Glut1, as well as Rictor and mTORC2 activity as shown by attenuated AKT and FoxO1 phosphorylation, while miR-582 knockdown showed opposite effects. miR-582 knockdown-induced increases in pre-B proliferation and survival was abrogated by Hif1α and Rictor inhibitors. Together, miR-582 functions as a negative regulator of pre-B cell proliferation and survival by simultaneously targeting Hif1α and mTORC2 signaling that regulates metabolism in early B cell development.In 2020, a group of experts officially suggested metabolic dysfunction associated with fatty liver disease "MAFLD" as a more appropriate overarching term than NAFLD, indicating the key role of metabolism in fatty liver disease. Bdh1, as the rate-limiting enzyme of ketone metabolism, acts as an important metabolic regulator in liver. However, the role of Bdh1 in MAFLD is unclear. In this study, we used the transgenic db/db mice as a MAFLD mouse model and observed the downregulated expression of Bdh1 in fatty liver. In addition, expression of Bdh1 was also reduced by palmitic acid (PA) treatment in LO2 cells. Bdh1 knockdown led to ROS overproduction and ROS-induced inflammation and apoptosis in LO2 cells, while Bdh1 overexpression protected LO2 cells from lipotoxicity by inhibiting ROS overproduction. Mechanistically, Bdh1-mediated βOHB metabolism inhibits ROS overproduction by activation of Nrf2 through enhancement of metabolic flux composed of βOHB-AcAc-succinate-fumarate. Notably, adeno-associated virus (AAV)-mediated Bdh1 overexpression successfully reversed the hepatic function indexes, fibrosis, inflammation, and apoptosis in fatty livers from db/db mice. In conclusion, our study revealed a Bdh1-mediated molecular mechanism in pathogenesis of metabolic dysfunction related liver disease and identified Bdh1 as a novel potential therapeutic target for MAFLD.Matrix computation, as a fundamental building block of information processing in science and technology, contributes most of the computational overheads in modern signal processing and artificial intelligence algorithms. Photonic accelerators are designed to accelerate specific categories of computing in the optical domain, especially matrix multiplication, to address the growing demand for computing resources and capacity. Photonic matrix multiplication has much potential to expand the domain of telecommunication, and artificial intelligence benefiting from its superior performance. Recent research in photonic matrix multiplication has flourished and may provide opportunities to develop applications that are unachievable at present by conventional electronic processors. In this review, we first introduce the methods of photonic matrix multiplication, mainly including the plane light conversion method, Mach-Zehnder interferometer method and wavelength division multiplexing method. We also summarize the developmental milestones of photonic matrix multiplication and the related applications. Then, we review their detailed advances in applications to optical signal processing and artificial neural networks in recent years. Finally, we comment on the challenges and perspectives of photonic matrix multiplication and photonic acceleration.Sphingosine kinase 1 (SphK1) expression and activity are elevated in human osteosarcoma (OS) and is a promising target of therapy. SKI-V is a non-competitive and highly-efficient non-lipid SphK1 inhibitor. The potential anti-OS cell activity by the SphK1 inhibitor was studied here. In primary OS cells and immortalized cell lines, SKI-V robustly suppressed cell survival, growth and proliferation as well as cell mobility, and inducing profound OS cell death and apoptosis. The SphK1 inhibitor was however non-cytotoxic nor pro-apoptotic in human osteoblasts. SKI-V robustly inhibited SphK1 activation and induced accumulation of ceramides, without affecting SphK1 expression in primary OS cells. The SphK1 activator K6PC-5 or sphingosine-1-phosphate partially inhibited SKI-V-induced OS cell death. We showed that SKI-V concurrently blocked Akt-mTOR activation in primary OS cells. A constitutively-active Akt1 (ca-Akt1, S473D) construct restored Akt-mTOR activation and mitigated SKI-V-mediated cytotoxicity in primary OS cells. In vivo, daily injection of SKI-V potently suppressed OS xenograft tumor growth in nude mice. In SKI-V-administrated OS xenograft tissues, SphK1 inhibition, ceramide increase and Akt-mTOR inhibition were detected. Together, SKI-V exerts significant anti-OS activity by inhibiting SphK1 and Akt-mTOR cascades in OS cells.Due to the self-renewal characteristics and tumorigenic abilities of cancer stem cells (CSCs), CSCs have been demonstrated to play vital roles in carcinogenesis and antitumor therapy. Our previous report found that Krüppel-like family members (KLFs) and zinc finger protein 32 (ZNF32) play oncogenic roles in carcinogenesis. However, the roles and mechanism of ZNF32 in CSCs are still unknown. Our study demonstrated that ZNF32 was highly expressed in colorectal CSCs, which promoted their self-renewal capacity and tumorigenicity. Overexpression of ZNF32 in colorectal cancer (CRC) cells increased their self-renewal capacity. Furthermore, we identified the leptin receptor (LEPR) as the downstream target gene of ZNF32 and verified that the ZNF32-mediated regulation of CRC self-renewal is achieved via the LEPR- signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ZNF32 regulated the expression of SOX2, a core transcription factor in stem cells. Finally, we demonstrated that ZNF32 and LEPR were positively correlated in CRC tissues. ZNF32 expression was negatively correlated with the prognosis of CRC patients. Therefore, therapeutically targeting the ZNF32-LEPR-STAT3 pathway in the clinic is tempting.Two-dimensional electron gases (2DEGs) with high mobility, engineered in semiconductor heterostructures host a variety of ordered phases arising from strong correlations, which emerge at sufficiently low temperatures. The 2DEG can be further controlled by surface gates to create quasi-one dimensional systems, with potential spintronic applications. Here we address the long-standing challenge of cooling such electrons to below 1 mK, potentially important for identification of topological phases and spin correlated states. The 2DEG device was immersed in liquid 3He, cooled by the nuclear adiabatic demagnetization of copper. The temperature of the 2D electrons was inferred from the electronic noise in a gold wire, connected to the 2DEG by a metallic ohmic contact. With effective screening and filtering, we demonstrate a temperature of 0.9 ± 0.1 mK, with scope for significant further improvement. This platform is a key technological step, paving the way to observing new quantum phenomena, and developing new generations of nanoelectronic devices exploiting correlated electron states.Radiocesium remediation is desirable for ecological protection, human health and sustainable development of nuclear energy. Effective capture of Cs+ from acidic solutions is still challenging, mainly due to the low stability of the adsorbing materials and the competitive adsorption of protons. check details Herein, the rapid and highly selective capture of Cs+ from strongly acidic solutions is achieved by a robust K+-directed layered metal sulfide KInSnS4 (InSnS-1) that exhibits excellent acid and radiation resistance. InSnS-1 possesses high adsorption capacity for Cs+ and can serve as the stationary phase in ion exchange columns to effectively remove Cs+ from neutral and acidic solutions. The adsorption of Cs+ and H3O+ is monitored by single-crystal structure analysis, and thus the underlying mechanism of selective Cs+ capture from acidic solutions is elucidated at the molecular level.Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.Sodium-based dual-ion batteries have received increased attention owing to their appealing cell voltage (i.e., >3 V) and cost-effective features. However, the development of high-performance anode materials is one of the key elements for exploiting this electrochemical energy storage system at practical levels. Here, we report a source-template synthetic strategy for fabricating a variety of nanowire-in-nanotube MSxTey@C (M = Mo, W, Re) structures with an in situ-grown carbon film coating, termed as nanocables. Among the various materials prepared, the MoS1.5Te0.5@C nanocables are investigated as negative electrode active material in combination with expanded graphite at the positive electrode and NaPF6-based non-aqueous electrolyte solutions for dual-ion storage in coin cell configuration. As a result, the dual-ion lab-scale cells demonstrate a prolonged cycling lifespan with 97% capacity retention over 1500 cycles and a reversible capacity of about 101 mAh g-1 at specific capacities (based on the mass of the anode) of 1.0 A g-1 and 5.0 A g-1, respectively.REV1 is the central member of the family of TLS polymerases, which participate in various DNA damage repair and tolerance pathways and play a significant role in maintaining genomic stability. However, the role of REV1 in tumors is rarely reported. In this study, we found that the expression of REV1 was significantly upregulated in lung cancer tissues compared with matched adjacent tissues and was associated with poor prognosis. Functional experiments demonstrated that REV1 silencing decreased the growth and proliferation capacity of lung cancer cells. Mechanistically, REV1 upregulated the expression of SERTAD2 in a Rad18-dependent manner, thereby promoting lung carcinogenesis. A novel REV1 inhibitor, JH-RE-06, suppressed lung tumorigenesis in vivo and in vitro and was shown to be safe and well tolerated. Our study confirmed that REV1 is a potential diagnostic marker and therapeutic target for lung cancer and that JH-RE-06 may be a safe and efficient therapeutic agent for NSCLC.
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