Simulation and analysis of chest loads on crews during Lunar-Earth re-entry returns.

The safety of crews is the primary concern in the manned lunar landing project, particularly during re-entry as the manned spacecraft returns from a direct Lunar-Earth trajectory. This paper analyzed the crew's chest biomechanical response to assess potential injuries caused by acceleration loads during the re-entry phase. Initially, a sophisticated finite element model of the chest was constructed, whose effectiveness was verified by experiments involving vertebral range of motion, rib lateral rupture, and chest frontal impact. The model was then subjected to the return re-entry loads simulating the Apollo and Chang'e 5 T1 (CE-5T1) test returner to specifically analyze the correlation between the acceleration load and the injury of the crew's chest tissues and organs. The results indicate that the biomechanical response of crew chest bone tissue under the two return missions is within the threshold value and will not directly cause damage. Compared to the Apollo mission, the CE-5T1 mission's load poses a higher risk to internal organs. These findings can enhance the crew's safety and provide reliable assurance for future space exploration.

Effects of different seat inclination angles on lumbar dynamic response and injury during lunar-earth reentry.

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 comparative study on the effects of human serum albumin and α-melanocyte-stimulating hormone fusion proteins on the anti-neuroinflammatory in the central nervous system of adult mice.

The immunomodulatory effects of α-melanocyte stimulating hormone (α-MSH) in the central nervous system (CNS) have been investigated for forty years. The clinical applications of α-MSH are limited due to its short half-life. Our previous study has indicated that the short half-life of α-MSH can be extended by fusion with carrier human serum albumin (HSA) and this fusion protein has also retained the anti-inflammatory effect on the CNS. This improvement is still far from the clinical requirements. Thus, we expected to enhance the half-life and activity of the fusion protein by optimizing the linker peptide to get closer to clinical requirements. In a previous study, we screened out two candidates in vitro experiments with a flexible linker peptide (fusion protein with flexible linker peptide, FPFL) and a rigid linker peptide (fusion protein with rigid linker peptide, FPRL), respectively. However, it was not sure whether the anti-inflammatory effects in vitro could be reproduced in vivo. Our results show that FPRL is the best candidate with a longer half-life compared to the traditional flexible linker peptides. Meanwhile, the ability of FPRL to penetrate the blood-brain barrier (BBB) was enhanced, and the inhibition of TNF-α and IL-6 was improved. We also found that the toxicity of FPRL was decreased. All of the results suggested that trying to choose the rigid linker peptide in some fusion proteins may be a potential choice for improving the unsatisfactory characteristics.

Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins.

The anti-inflammatory effect of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS) has been reported for 40 years. However, the short half-life of α-MSH limits its clinical applications. The previous study has shown that a fusion protein comprising protein transduction domain (PTD), human serum albumin (HSA), and α-MSH extends the half-life of α-MSH, but its anti-inflammatory effect is not satisfactory. In this study, optimization of the structures of fusion proteins was attempted by changing the linker peptide between HSA and α-MSH. The optimization resulted in the improvement of various important characteristics, especially the stability and anti-inflammatory bioactivity, which are important features in protein medicines. Compared to the original linker peptide L0, the 5-amino-acid rigid linker peptide L6 (PAPAP) is the best option for further investigation due to its higher expression (increased by 6.27%), improved purification recovery (increased by 60.8%), excellent thermal stability (Tm = 83.5°C) and better inhibition in NF-κB expression (increased by 81.5%). From this study, the significance of the design of linker peptides in the study of structure-activity relationship of fusion proteins was proved.

A pattern recognition receptor C-type lectin TcCTL14 contributes to immune response and development in the red flour beetle, Tribolium castaneum.

Evidence is accumulating that pattern recognition receptor (PRR) C-type lectins (CTL) play essential roles in recognition of pathogens. TcCTL14 (accession no. TC00871) contains the most domains among all CTL of Tribolium castaneum. Yet the biological function of TcCTL14 remains unclear. In this study, TcCTL14 exhibiting typical motif and domain of CTL was cloned from T. castaneum. The expression pattern analysis showed that TcCTL14 was highly expressed in late pupae and central nervous system, and was upregulated after treatment with Escherichia coli and Staphylococcus aureus, respectively. Analysis of binding affinity revealed that recombinant TcCTL14 not only could bind to lipopolysaccharide and peptidoglycan in a dose-dependent fashion, but possibly could bind to and agglutinate different bacteria in a Ca2+ -dependent fashion. Knockdown of TcCTL14 before injection with bacteria led to the downregulation of nuclear factor-κB transcription factors of Toll/IMD and 4 antimicrobial peptides. Knockdown of TcCTL14 also caused suppressed metamorphosis, reduced fecundity, and delayed embryogenesis of T. castaneum. Further observation discovered that knockdown of TcCTL14 inhibited the development of ovaries and embryos. The detection of signaling pathways revealed that TcCTL14 may be involved in metamorphosis and fecundity by impacting 20-hydroxyecdysone and vitellogenin, respectively. Overall, these results indicate that TcCTL14 may contribute to immune response by agglutination or regulating the expression of antimicrobial peptides by the Toll/IMD pathway, and is required for T. castaneum development including metamorphosis, fecundity, and embryogenesis. These findings will improve the functional cognition of PRR CTL in insects and provide the new strategy for pest control.

Three cytochrome P450 CYP4 family genes regulated by the CncC signaling pathway mediate phytochemical susceptibility in the red flour beetle, Tribolium castaneum.

BACKGROUND: Insect cytochrome P450 monooxygenases (P450s) play a crucial role in phytochemical metabolism and tolerance. Three P450 genes (TcCYP4Q3, TcCYP4Q5, and TcCYP4Q7) are associated with the response of eugenol in Tribolium castaneum. However, the responding mechanisms of these P450 genes to eugenol remain unknown. RESULTS: Here, spatiotemporal expression profiling revealed that TcCYP4Q3 and TcCYP4Q5 were most highly expressed in late adult, while TcCYP4Q7 was predominantly expressed in late larva; and all of these three P450 genes were mainly expressed in the fat body of larvae. Furthermore, the expressions of these three P450 genes were significantly up-regulated after exposure to eugenol, and depletion of them enhanced the susceptibility of beetles to eugenol. Interestingly, RNA interference (RNAi) against the CncC gene, a transcription factor of CncC signaling pathway associated with regulation of insect P450s in response to phytochemicals, reduced the transcripts of these three P450 genes following exposure to eugenol. Investigation of CncC signaling pathway showed that this pathway could be activated by eugenol. CONCLUSION: Altogether, the results indicate that these three P450 genes are regulated by CncC signaling pathway to participate in the susceptibility of Tribolium castaneum to phytochemicals. These findings will aid implications for the development of novel therapeutics to control pest. © 2022 Society of Chemical Industry.

Autophagy activation by Terminalia chebula Retz. reduce Aß generation by shifting APP processing toward non-amyloidogenic pathway in APPswe transgenic SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid ß plaques (Aß) is a central hallmark of AD. Accumulating evidence suggest that shifting amyloid precursor protein (APP) metabolism pathway to non-amyloidogenic ways and inducing autophagy play key roles in AD pathology. In published reports, there is no research on the APP metabolic process of Terminalia chebula Retz. (T. Chebula). PURPOSE: The study aims to assess the effects of T. Chebula in AD transgenic SH-SY5Y cells to determine its underlying mechanisms on reducing Aß level by regulating APP metabolic process. METHODS: The effects of T. Chebula water extract (TWE) on APPswe transgenic SH-SY5Y cells were analyzed by cell viability. ELISA used to quantify extracellular Aß1-40 and Aß1-42 generations. Western blot and RT-PCR assays were chosen to detect the expression of proteins and genes. The acridine orange (AO) stain was used to label autophagic-vesicles. RESULTS: Treatment with TWE significantly suppressed the Aß1-40 and Aß1-42 generations of APPswe transgenic cells. TWE inhibited amyloidogenic pathway by reducing BACE1 expression, and promote non-amyloidogenic pathway by inducing ADAM10 level of APP metabolism. Additionally, TWE induced autophagy in APPswe transgenic cells involved in APP metabolism to shift the balance to non-amyloidogenic pathway. CONCLUSION: In summary, our finding first time expounded that TWE can inhibit the generation of Aß1-40 and Aß1-42 in APPswe transgenic SH-SY5Y cells, which were regulated APP metabolism tends to non-amyloid metabolism pathway and mediated by autophagy. The results presented a novel finding for AD treatment of traditional natural medicines.

[Observation on therapeutic effect of acupuncture combined with drug for treatment of intestinal metaplasia of chronic atrophic gastritis].

OBJECTIVE: To search for an effective method for treatment of intestinal metaplasia of gastric mucosa in the patient of chronic atrophic gastritis. METHODS: Fifty-one cases of chronic atrophic gastritis with intestinal metaplasia were randomly divided into a treatment group (n = 26) and a control group (n = 25). The treatment group were treated with acupuncture at main acupoints: Zhongwan (CV 12), Zusanli (ST 36), Neiguan (PC 6), Gongsun (SP 4), and oral administration of modified Sijunzi Decoction, and the control group with the modified Sijunzi Decoction. After treatment for 3 months, clinical symptoms, results of gastroscopy and pathological changes of gastric mucosa were compared between the two groups. RESULTS: There was no significant difference in improvement of the clinical symptoms between the two groups (P > 0.05); the total effective rate of 88.46% for gastroscopy in the treatment group was better than 64.00% in the control group (P < 0.05); and the total effective rate of 84.62% for pathological improvement of intestinal metaplasia in the treatment group was superior to 64.00% in the control group (P < 0.05). CONCLUSION: Acupuncture combined with Chinese drug is a better therapy for intestinal metaplasia of gastric mucosa in the patient of chronic atrophic gastritis.