Notes

Single-cell transcriptomic examination associated with eutopic endometrium along with ectopic lesions on the skin of adenomyosis.
An exclusive feature of dendritic cells (DCs) is their capacity to present exogenous antigens by MHC class I molecules, called cross-presentation. Here, we show that protein antigen can be conserved in mature murine DCs for several days in a lysosome-like storage compartment, distinct from MHC class II and early endosomal compartments, as an internal source for the supply of MHC class I ligands. learn more Using two different uptake routes via Fcγ receptors and C-type lectin receptors, we could show that antigens were routed towards the same endolysosomal compartments after 48 h. The antigen-containing compartments lacked co-expression of molecules involved in MHC class I processing and presentation including TAP and proteasome subunits as shown by single-cell imaging flow cytometry. Moreover, we observed the absence of cathepsin S but selective co-localization of active cathepsin X with protein antigen in the storage compartments. This indicates cathepsin S-independent antigen degradation and a novel but yet undefined role for cathepsin X in antigen processing and cross-presentation by DCs. In summary, our data suggest that these antigen-containing compartments in DCs can conserve protein antigens from different uptake routes and contribute to long-lasting antigen cross-presentation.Leaf angle distribution (LAD) in forest canopies affects estimates of leaf area, light interception, and global-scale photosynthesis, but is often simplified to a single theoretical value. Here, we present TLSLeAF (Terrestrial Laser Scanning Leaf Angle Function), an automated open-source method of deriving LADs from terrestrial laser scanning. TLSLeAF produces canopy-scale leaf angle and LADs by relying on gridded laser scanning data. The approach increases processing speed, improves angle estimates, and requires minimal user input. Key features are automation, leaf-wood classification, beta parameter output, and implementation in R to increase accessibility for the ecology community. TLSLeAF precisely estimates leaf angle with minimal distance effects on angular estimates while rapidly producing LADs on a consumer-grade machine. We challenge the popular spherical LAD assumption, showing sensitivity to ecosystem type in plant area index and foliage profile estimates that translate to c. 25% and c. 11% increases in canopy net photosynthesis (c. 25%) and solar-induced chlorophyll fluorescence (c. 11%). TLSLeAF can now be applied to the vast catalog of laser scanning data already available from ecosystems around the globe. The ease of use will enable widespread adoption of the method outside of remote-sensing experts, allowing greater accessibility for addressing ecological hypotheses and large-scale ecosystem modeling efforts.SPI-62 is a selective and potent small-molecule inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (HSD-1). SPI-62 has demonstrated substantial and complex nonlinear pharmacokinetics (PK) in humans that is characterized by unusually low plasma exposure at low doses, dose-dependent volume of distribution, nonlinear PK following the first dose, and dose-proportional PK at steady state, as well as unusually high accumulation ratios at low doses. The most likely explanation for the observed nonlinearity of SPI-62 is the saturable binding of SPI-62 to its pharmacological target HSD-1, a phenomenon known as target-mediated drug disposition (TMDD). Because of the nonlinear and complex PK of SPI-62, the relationship among SPI-62 dose, exposure, and response is no longer intuitive and consequently dose selection can be challenging. To facilitate dose selection and clinical trial design, in the current study population PK analysis was performed to characterize SPI-62 dose-exposure relationship in humans quantitatively. SPI-62 PK was best characterized by a 2-compartment TMDD model with 3 transit absorption compartments. The model was successfully established to explain the substantial and unusual nonlinear PK of SPI-62 in humans, and it provided adequate fitting for both single- and multiple-dose data. Our modeling work has provided a strong foundation for dose selection in future SPI-62 clinical trials.Patients with hepatitis-associated aplastic anemia (HAA) who undergo living-donor liver transplantation (LDLT) have a poor prognosis with infections and bleeding complications. Rapid recovery of blood cells is critical for preventing these complications and improving the outcome. Immunosuppressive therapy (IST) combined with thrombopoietin receptor agonists is considered effective for aplastic anemia. However, there are no data on the benefits of adding thrombopoietin receptor agonists to IST for HAA. We present the case of a child with severe HAA who underwent LDLT, and who achieved rapid blood cell recovery with IST combined with romiplostim, a thrombopoietin receptor agonist. In addition, despite having undergone LDLT, the patient had no adverse events such as serious liver dysfunction or thrombosis. This case suggests that IST combined with thrombopoietin receptor agonists may be a promising treatment option for HAA patients undergoing LDLT.
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout China and worldwide. Little is known about the dynamic changes in the patient immune responses to SARS-CoV-2 and how different responses are correlated with disease severity and outcomes.

Seventy-four patients with confirmed COVID-19 were enrolled in this prospective research. The demographic information, medical history, symptoms, signs and laboratory results were analyzed and compared between severe and non-severe patients. The leukocytes, lymphocyte subsets and inflammatory cytokines were longitudinally collected.

Of the 74 patients included, 17 suffered from severe disease. The severe patients tended be older (65.29 ± 12.33years vs. 45.37 ± 18.66years) and had a greater degree of underlying disease (41.18% vs. 24.56%), lower baseline lymphocyte counts [0.64 (0.46-0.95) × 10
vs. 1.27 (0.95-1.70) × 10
], higher neutrophil-lymphocyte ratios [NLRs; 3.76 (3.
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