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The target coordinate measurement system features an extensive range of key applications. In many highprecision measurement systems wide scope, high precision and multiple cameras are used. However, the objective of this paper is to enhance the measurement accuracy and range of a monocular target owing to its portability and convenience. A systematic simulation of linear, planar and stereo target structures was carried out to investigate target structures. Based on our simulation results, the 3D target is more accurate and robust to tilt due to rich information available from 3D locations of the markers. To overcome the limitation in the measurement range for the monocular target, ideas of coded stereo target are presented in this paper. The measured coordinates can be calculated from only part of the markers, effectively enlarging the measurement range at short object distances. A stereo coded target system is designed based on this method and is compared to an ordinary monocular target. Stability experiments were conducted under different object distances and poses, which have shown that the Z direction accuracy of the stereo target is at least 23.8% or 10% higher than that of the 1D or 2D target, respectively. Additionally, the ranging experiment revealed that the measurement accuracy of the coded stereo target is 23.5% or 59.2% higher than that of the non-coded 1D or 2D target when measuring the Z direction and the distance of the far field. [ABSTRACT FROM AUTHOR]

The MS6.8 earthquake occurred in Luding County, Ganzi Prefecture, Sichuan Province, China at 12:52 p.m. on Sept. 5, 2022, is preliminarily analyzed in terms of regional tectonics, historical earthquakes, sequence characteristics and focal mechanism solutions. The results show that: 1) The magnitude difference ΔM between the main shock and the maximum aftershock, the energy ratio ER of the main shock to the aftershocks, the p-value and the estimated Mmax-value indicate that the MS6.8 Luding earthquake sequence can be divided into the main shock-aftershock type (MAT). 2) The spatial distribution of the aftershocks, their corresponding b-value and expected maximum magnitude are obviously segmented, which reflect the complexity of the seismogenic tectonics. 3) According to the focal mechanisms obtained from the HASH program, the geometry distribution of the sequence, and the relationship between the sequence and the nearby faults, it can be inferred that the Moxi fault segment of the Xianshuihe fault zone is the seismogenic tectonics of the MS6.8 Luding earthquake sequence. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E294-302-specific T cells can account for 20-60% of the total CD8+ T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E294-302-specific TCRaßs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct aß paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8+ T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs. IMPORTANCE The immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8+ T cells. Our data show that CD8+ T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRa/ß clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRa/ß clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5, was found to be selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8+ T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8+ T cells after ZIKV infection in different IPOs. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions To investigate the effects of the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine at therapeutically relevant concentrations on beta‐cell mass and function.Viability was quantified in mouse insulinoma (MIN6) beta cells and mouse islets after 48‐h exposure to sertraline (1–10 μM) or paroxetine (0.01–1 μM) using the Trypan blue exclusion test. The effects of therapeutic concentrations of these SSRIs on insulin secretion were determined by static incubation and perifusion experiments, while islet apoptosis was investigated by Caspase‐Glo 3/7 assay, TUNEL staining and quantitative PCR analysis. Finally, proliferation of MIN6 and mouse islet beta cells was assessed by bromodeoxyuridine (BrdU) enzyme‐linked immunosorbent assay and immunofluorescence.Sertraline (0.1–1 μM) and paroxetine (0.01–0.1 μM) were well tolerated by MIN6 beta cells and islets, whereas 10 μM sertraline and 1 μM paroxetine were cytotoxic. Exposure to 1 μM sertraline and 0.1 μM paroxetine significantly potentiated glucose‐stimulated insulin secretion from mouse and human islets. Moreover, they showed protective effects against cytokine‐ and palmitate‐induced apoptosis of islets, they downregulated cytokine‐induced Stat1 and Traf1 mRNA expression, and they significantly increased proliferation of mouse beta cells.Our data demonstrate that sertraline and paroxetine act directly on beta cells to enhance glucose‐stimulated insulin secretion and stimulate beta‐cell mass expansion by increasing proliferation and decreasing apoptosis. These drugs are therefore likely to be appropriate for treating depression in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Gasdermin D (GSDMD) serves as a vital mediator of inflammasome-driven pyroptosis. In our study, we have identified NU6300 as a specific GSDMD inhibitor that covalently interacts with cysteine-191 of GSDMD, effectively blocking its cleavage while not affecting earlier steps such as ASC oligomerization and caspase-1 processing in AIM2-and NLRC4-mediated inflammation. On the contrary, NU6300 robustly inhibits these earlier steps in NLRP3 inflammasome, confirming a unique feedback inhibition effect in the NLRP3-GSDMD pathway upon GSDMD targeting. Our study reveals a previously undefined mechanism of GSDMD inhibitors: NU6300 impairs the palmitoylation of both full-length and N-terminal GSDMD, impeding the membrane localization and oligomerization of N-terminal GSDMD. In vivo studies further demonstrate the efficacy of NU6300 in ameliorating dextran sodium sulfate-induced colitis and improving survival in lipopolysaccharide-induced sepsis. Overall, these findings highlight the potential of NU6300 as a promising lead compound for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Phage therapy has shown great promise for the treatment of multidrugresistant bacterial infections. However, the lack of a thorough and organized understanding of phage-body interactions has limited its clinical application. Here, we administered different purified phages (Salmonella phage SE_SZW1, Acinetobacter phage AB_SZ6, and Pseudomonas phage PA_LZ7) intravenously to healthy animals (rats and monkeys) to evaluate the phage-induced host responses and phage pharmacokinetics with different intravenous (IV) doses in healthy animals. The plasma and the organs were sampled after different IV doses to determine the phage biodistribution, phage-induced cytokines, and antibodies. The potential side effects of phages on animals were assessed. A non-compartment model revealed that the plasma phage titer gradually decreased over time following a single dose. Repeated doses resulted in a 2-3 Log10 decline of the plasma phage titer at 5 min compared to the first dose, regardless of the type of phage administered in rats. Host innate immune responses were activated including splenic enlargement following repeated doses. Phage-specific neutralization antibodies in animals receiving phages were detected. Similar results were obtained from monkeys. In conclusion, the mammalian bodies were well-tolerant to the administered phages. The animal responses to the phages and the phage biodistribution profiles could have a significant impact on the efficacy of phage therapy. IMPORTANCE Phage therapy has demonstrated potential in addressing multidrugresistant bacterial infections. However, an insufficient understanding of phage-host interactions has impeded its broader clinical application. In our study, specific phages were administered intravenously (IV) to both rats and monkeys to elucidate phage-host interactions and evaluate phage pharmacokinetics (PK). Results revealed that with successive IV administrations, there was a decrease in plasma phage concentrations. Concurrently, these administrations elicited both innate and adaptive immune responses in the subjects. Notably, the observed immune responses and PK profiles exhibited variation contingent upon the phage type and the mammalian host. Despite these variations, the tested mammals exhibited a favorable tolerance to the IV-administered phages. This underscores the significance of comprehending these interactions for the optimization of phage therapy outcomes. [ABSTRACT FROM AUTHOR]