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The inclination angle of the spacecraft seat is related to the astronaut’s reentry angle, which in turn affects the safety of the astronauts. This study quantitatively analyzed the effects of different seat inclination angles on astronauts’ lumbar spine injuries using the finite element method during the Lunar-Earth reentry. Firstly, a finite element model of the astronaut’s lumbar spine was constructed based on reverse engineering technology, and the effectiveness of the model was verified through mesh sensitivity, vertebral range of motion, and spinal impact experiments. Then, simulation calculations were carried out for different seat inclination angles (0°, 10°, 20°, and 30°) under the typical reentry return loads of Chang’e 5T1 (CE-5T1) and Apollo 10, and the prediction and evaluation of lumbar spine injuries were conducted in conjunction with the biological tissue injury criteria. The results indicated that the stress on the vertebrae and annulus fibrosus increased under both reentry loads with the rise of the seat inclination angle, but the increasing rates decreased. When the acceleration peak of CE-5T1 approached 9G, the risk of tissue injury was higher under the seat angle exceeded 20°. According to the Multi-Axis Dynamic Response Criteria for spinal injury, neither of the two load conditions would directly cause injury to the astronauts’ lumbar spine when the seat inclination angle was below 30°. The study findings provide a numerical basis for designing and improving the spacecraft’s inclination angle in crewed lunar missions, ensuring the safety of astronauts.

A dysregulated immune microenvironment at the maternal-fetal interface in early pregnancy may lead to early pregnancy loss, fetal growth restriction, and preeclampsia. However, major questions about how epigenetic modifications regulate the immune microenvironment during the decidualization process and embryo implantation remain unanswered. DNA methylation, the main epigenetic mechanism involved in the endometrial cycle, is crucial for specific transcriptional networks associated with endometrial stromal cell (ESC) proliferation, hormone response, decidualization, and embryo implantation. Ten-eleven translocation (TET) enzymes, responsible for catalyzing the conversion of 5-methylcytosine to 5-hydroxymethylcyosine, 5-formylytosine, and 5-carboxylcyosine to achieve the DNA demethylation process, appear to play a critical role in decidualization and embryo implantation. Here, we provide a comprehensive view of their structural similarities and the common mechanism of regulation in the microenvironment at the maternal-fetal interface during decidualization and early pregnancy. We also discuss their physiological role in the decidual immune microenvironment. Finally, we propose a key hypothesis regarding TET enzymes at the maternal-fetal interface between decidual immune cells and ESCs. Future work is needed to elucidate their functional role and examine therapeutic strategies targeting these enzymes in pregnancy-related disease preclinical models, which would be of great value for future implications in disease diagnosis or treatment.

We present a method utilizing the coupling between a pre-bunched electron beam and a silicon subwavelength grating to generate coherent terahertz waves. The grating that is connected to two opposite-traveling in-plane waveguides functions as a resonator. An example operating around 2 THz shows that, when the velocity and repetition frequency of the electron bunches respectively match the phase velocity and resonant frequency of the Bragg resonance in the grating, the strong electron-wave coupling leads to coherent radiation through the waveguide. The repetition frequency of the electron bunches can be halved by using its second harmonic to match the resonant frequency. This study might offer a potential approach for on-chip terahertz sources.

BackgroundExtracorporeal membrane oxygenation (ECMO) is widely used for refractory cardiopulmonary failure treatment. The disadvantage of ECMO is its higher risk profile and clinical resource consumption. This observation examines the role of serum total bilirubin (TBIL) as a predictor of adult patient outcomes on ECMO support.MethodsThis retrospective observation reports a single-center experience with adults on ECMO support between 2018 and 2021. Data were collected regarding demographics, ECMO details, laboratory parameters, and outcomes. We examined the elevation of TBIL to predict survival and variables associated with hyperbilirubinemia.ResultsThe patients who died within 28 days had a twofold higher peak level of TBIL than those who survived [73.10 (38.60, 98.64) vs. 34.50 (24.03, 54.85); P = 0.003]. Univariate logistic regression analyses demonstrated that high TBIL was remarkably associated with an elevated risk of 28-day mortality (OR: 7.25; 95% CI: 2.31–25.49; P = 0.001) and total mortality (OR: 5.71; 95% CI: 1.82–20.66; P = 0.001). The TBIL value was 65 μmol/L as the best cut-off value, and the observation group was divided into a high TBIL subgroup (n = 21) or a low TBIL subgroup (n = 39). The demographic and clinical features did not show a difference, whereas Sequential Organ Failure Assessment (SOFA) and APACHE II scores and ALT, AST, and LAC before ECMO initiation correlated with high or low TBIL (P < 0.05). For coagulation function at the time of TBIL peak, the levels of prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin time activity (PTA), and fibrinogen (FIB) were different between the two subgroups (P < 0.05). The SOFA score was potentially associated with hyperbilirubinemia after ECMO initiation, and the prediction accuracy was 0.800.ConclusionSerum total bilirubin elevation appears after ECMO initiation and correlates with survival, while other markers of liver injury do not. Serum total bilirubin is an easy-to-measure biomarker to be a predictor of survival after ECMO initiation.

Background: Anti-PD-1/PD-L1 immunotherapy has achieved impressive responses in multiple types of malignancies in recent years. However, immune-related adverse events (irAEs) occur and limit their continuous clinical use. Among these irAEs, acquired amegakaryocytic thrombocytopenia (AAT) is rare but often clinically serious, life-threatening and refractory to multiple treatment approaches.Case summary: We reported for the first time the successful treatment of avatrombopag in two cases of anti-PD1 antibody-induced AAT (in particular, one case had progressed to aplastic anemia), which was refractory or intolerant to glucocorticoids, ciclosporin, intravenous immunoglobulin (IVIG), recombinant human thrombopoietin (rh-TPO) and even TPO receptor agonist (TPO-RA) eltrombopag. To date, the two cases manifested as normal platelet counts and are independent of transfusion.Conclusion: Anti-PD1 antibody-induced AAT occurs with low frequency but is often serious and difficult to manage, for which this study proposed vatrombopag as a potential curative and safe approach.

Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by a high prevalence of autoantibodies and lymphocyte-mediated exocrine gland damage. To enhance our understanding of the mechanisms underlying the progression of the disease and to discover potential biomarkers for the early diagnosis of pSS, we applied RNA sequencing to compare the gene expression patterns in minor salivary glands between pSS patients and non-pSS. A total of 293 differentially expressed genes (DEGs) were detected in pSS vs. non-pSS (FDR < 0.05, fold changes > 2). Of these DEGs, 285 (97.26%) were up-regulated, with most being involved in immune system activation, especially in the formation of the immunological synapse. Significantly elevated CCL19/CCR7 expression in the salivary gland was found to be related to anti-Sjögren's syndrome-related antigen A (SSA) antibody and IgG levels in pSS patients, which was further confirmed in a larger cohort. Up-regulated gene expression showed strong discriminatory accuracy in identifying pSS with area under the curve of 0.98 using receiver operating characteristic curve analysis. In conclusion, gene expression changes in pSS include strong markers of immunological activation and have good discriminatory power in identifying patients with pSS.

Our previous investigations indicated that in vitro polarization of mouse macrophages by Toxoplasma gondii type II strain dense granule protein 15 (GRA15II), one of the genotype-associated effectors of T. gondii, induced the phenotypes of classically activated macrophage (M1). Transfusion of the cells to mice may effectively alleviated hepatic fibrosis caused by schistosomiasis. The purpose of the study was to identify whether liver macrophages can be in vivo driven to M1 macrophages by lentiviral vector (LV) carrying GRA15II gene (LV-gra15II) and to explore the potential mechanism by which the LV-gra15II-activated liver macrophage (LV-gra15II-M) ameliorates the hepatic fibrosis in schistosomiasis. The mice were treated with LV-gra15II by hydrodynamic injection via the tail vein followed by challenge of Schistosoma japonicum (S. japonicum). Our experiments showed that LV-gra15II was successfully delivered to liver macrophages and GRA15II was persistently expressed in the macrophages of mice for at least 2 months. Furthermore, the LV-gra15II infected macrophages were polarized to M1 macrophages in vivo. Consequently, mice with schistosomiasis receiving LV-gra15II injection displayed a remarkable amelioration of liver granuloma formation and collagen deposition in association with downregulated expression of transforming growth factor-beta1, arginase 1 (Arg-1), α-smooth muscle actin, and an increased expression of matrix metalloproteinase 13 (MMP13). Simultaneously, no negative effects of liver function and vitality of mice were noted. The in vitro experiments indicated that the C-C motif chemokine ligand 2 and nitric oxide level were elevated in LV-gra15II-M cultural supernatants; hepatocyte growth factor expression was enhanced in LV-gra15II-M. In addition, LV-gra15II-M not only secreted MMP13, which greatly degraded type I collagen, but also induced murine hepatic stellate cell (HSC) line (JS1) apoptosis in the co-culture system. Taken together, we identified for the first time that LV-gra15II may in vivo drive liver macrophages to M1 macrophage phenotypes, which helps for alteration of the liver fibrotic microenvironment with collagen dissolution, HSC deactivation, apoptosis and hepatocyte protection. Our study gives an insight into the use of gene delivery with parasite-derived immunomodulatory factor as a potential immune cell activating agent to re-equilibrate the other pathogen-induced immune response in some chronic diseases.