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Immunological priming-in the context of either prior infection or vaccination-elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4+ T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4+ T cell-depleted granulomas, we found that the presence of CD4+ T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8+ T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.
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BACKGROUND: Considerable studies show that ETS variant 4 (ETV4) plays an important roles in multitudinous tumor. This study investigated its function in cholangiocarcinoma (CCA) progression and revealed the underlying mechanisms. METHODS: The expression of ETV4 in CCA was evaluated using TCGA database and the single-cell analysis based on GSE189903 dataset. ETV4 expression in CCA human specimens was detected by reverse transcription-quantitative PCR, immunohistochemistry, and western blot. Cell Counting Kit-8, EdU, colony formation, wound healing, and Transwell assays were used to analyze the effects of ETV4. Extracellular acidification rate, oxygen consumption rate, glucose uptake, and lactate production were used to measure glycolysis in CAA cells. Western blot was performed to explore glycolysis-related proteins. Tumor growth was evaluated in mice xenograft tumors. RESULTS: ETV4 was up-regulated in CCA epithelial cells. The high-expression of ETV4 was associated with poor prognosis of patients with CCA. ETV4 overexpression enhanced the proliferation, migration, invasion, and glycolysis of CCA cells; ETV4 silencing led to the contrary effects. Mechanistically, ETV4 activates TGF-ß/Smad2/3 signaling pathway. In mice xenograft mode, ETV4 silencing inhibits the tumor growth, the expression of glycolysis-related proteins and TGF-ß/Smad2/3 pathway proteins. CONCLUSIONS: ETV4 functions as an essential factor in the roles of TGF-ß1 in CCA cells, and may be a promising target for TGF-ß1-mediated CCA progression.
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An intraductal papillary mucinous neoplasm of the biliary tract (BT-IPMN) in the caudate lobe of the liver is a rare tumor originating from the bile duct. Approximately 40% of the intraductal papillary neoplasms of the biliary tract (IPNB) secrete mucus and can grow in the intrahepatic or extrahepatic bile ducts. A 65-year-old woman presented with recurrent episodes of right upper pain. She developed her first episode 8 years ago, which resolved spontaneously. The frequency of symptoms has increased in the last 2 years. She underwent laparoscopic hepatectomy and choledochal exploration and was pathologically diagnosed with a rare BT-IPMN of the caudate lobe after admission. Here, we review studies on IPNB cases and systematically describe the pathological type, diagnosis, and treatment of IPNB to provide a valuable reference for hepatobiliary surgeons in the diagnosis and treatment of this disease.
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Nanomagnetic logic (NML) has attracted attention during the last two decades due to its promise of high energy efficiency combined with non-volatility. Data transmission in NML relies on Bennett clocking through dipole interaction between neighboring nanomagnetic bits. This paper uses a fully coupled finite element model to simulate Bennett clocking based on strain-mediated multiferroic system for Ni, CoFeB and Terfenol-D with perpendicular magnetic anisotropies. Simulation results demonstrate that Terfenol-D system has the highest energy efficiency, which is 2 orders of magnitude more efficient than Ni and CoFeB. However, the high efficiency is associated with switching incoherency due to its large magnetostriction coefficient. It is also suggested that the CoFeB clocking system has lower bit-density than in Ni or Terfenol-D systems due to its large dipole coupling. Moreover, we demonstrate that the precessional perpendicular switching and the Bennett clocking can be achieved using the same strain-mediated multiferroic architecture with different voltage pulsing. This study opens new possibilities to an all-spin in-memory computing system.
RESUMEN
We experimentally demonstrated Bessel-like beams utilizing digital micromirror device (DMD). DMD with images imitating the equivalent axicon can shape the collimated Gaussian beam into Bessel beam. We reconstructed the 3D spatial field of the generated beam through a stack of measured cross-sectional images. The output beams have the profile of Bessel function after intensity modulation, and the beams extend at least 50 mm while the lateral dimension of the spot remains nearly invariant. Furthermore, the self-healing property has also been investigated, and all the experimental results agree well with simulated results numerically calculated through beam propagation method. Our observations demonstrate that the DMD offers a simple and efficient method to generate Bessel beams with distinct nondiffracting and self-reconstruction behaviors. The generated Bessel beams will potentially expand the applications to the optical manipulation and high-resolution fluorescence imaging owing to the unique nondiffracting property.