Integrating animal experiments, mass spectrometry and network-based approach to reveal the sleep-improving effects of Ziziphi Spinosae Semen and γ-aminobutyric acid mixture.

BACKGROUND: Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. METHODS: Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. RESULTS: ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice (P < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF-MS. Also, we have constructed an online computation platform. CONCLUSION: Our data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

Reclamation and Ecological Service Value Evaluation of Coastal Wetlands Using Multispectral Satellite Imagery.

There are special locational value and natural resources in coastal wetlands. Studying their changes and evaluating their ecosystem service value (ESV) is beneficial for protecting the ecology of coastal wetlands and for maintaining sustainable human development. In this paper, the coastal wetland of Jiaozhou Bay is selected as the research area, an object-oriented method is used to extract shoreline and wetland information, and the coastal wetland reclamation process in Jiaozhou Bay is evaluated. The value equivalent method and market value method are used to evaluate the service value of wetland ecosystems from the perspective of ecological economics. The results show that the reclamation area of Jiaozhou Bay reached 75.2 km2 in 40 years, with nearly 23% of the bay area eroding. Reclamation engineering, estuary engineering, policy implementation and urbanization are the main factors affecting the changes in the Jiaozhou Bay wetland, and the main direction of wetland succession is natural wetlands→artificial wetlands→nonwetlands. Wetland reclamation in Jiaozhou Bay has led to the continuous extension of the coastline to the sea, especially during the 2005-2020 period, and the wetland area has declined in area by 116 km2. The changes in the wetland in the past 40 years have affected the changes in the ESV of Jiaozhou Bay, and there have been different synergistic/trade-off relationships in different periods. This research provides data to support the comprehensive ecological management of coastal areas, which is conducive to maximizing the utilization value of wetlands and promoting wetland protection.

Role and Mechanism of lncRNA-pvt1 in the Pathogenesis of Acute Lymphoblastic Leukemia in Children.

Objective: To investigate the role and mechanism of lncRNA-pvt1 in the pathogenesis of childhood acute lymphoblastic leukemia (ALL). Methods: The expression of lncRNA-pvt1 in bone marrow tissues of ALL patients after initial diagnosis and complete remission was detected by RT-PCR to explore its possible involvement in the pathogenesis of ALL. The proliferation and apoptosis of Jurkat cells transfected with lncRNA-pvt1 were observed by MTT and flow cytometry. Results: lncRNA-pvt1 expression was upregulated in bone marrow of ALL patients. Knockdown of lncRNA-pvt1 inhibited Jurkat cell proliferation and increased its apoptosis rate. Conclusion: Silencing lncRNA-pvt1 expression can inhibit the development of ALL.

PD-1 blockade inhibits lymphocyte apoptosis and restores proliferation and anti-viral immune functions of lymphocyte after CP and NCP BVDV infection in vitro.

Bovine viral diarrhea virus (BVDV) is an important virus that can cause extensive economic losses in both dairy and beef industry worldwide. Acute infection with BVDV results in peripheral blood lymphopenia, apoptosis and immunosuppression. Up-regulated programmed death-1 (PD-1) expression induces functional exhaustion of lymphocytes, inhibition of proliferation and apoptosis of lymphocytes during acute and chronic viral infections, such as HIV and HCV. However, there are no reports showing the role of PD-1 in peripheral blood lymphopenia, apoptosis and immunosuppression after acute BVDV infection. Accordingly, we measured the mRNA and protein expression of PD-1 and programmed death-ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMCs) infected with BVDV, and analyzed the effects of PD-1 blockade on immune-associated function and activity in peripheral blood lymphocytes (PBLs). The results showed that both cytopathic (CP) BVDV (strain NADL) and non-cytopathic (NCP) BVDV (strain KD) infection stimulated the mRNA and protein expression of PD-1 and PD-L1 significantly. The upregulation of PD-1/PD-L1 was accompanied by the decreased PBLs proliferation and increased apoptosis. Additionally, PD-1 blockade restored proliferation, inhibited apoptosis, increased IFN-γ production and decreased BVDV load. Remarkably, the PD-1/PD-L1 interaction has a more substantial effect on the immunoregulation of inhibiting proliferation induced by CP BVDV infection. Our findings confirm that PD-1 plays a vital role in peripheral blood lymphopenia and apoptosis caused by acute BVDV infection, and provide new insights into exploring the immunopathological mechanisms of BVDV or other members of the Flaviviridae family, and a potential therapeutic strategy to control BVDV infection.

Simulation of Jetting in Injection Molding Using a Finite Volume Method.

In order to predict the jetting and the subsequent buckling flow more accurately, a three dimensional melt flow model was established on a viscous, incompressible, and non-isothermal fluid, and a control volume-based finite volume method was employed to discretize the governing equations. A two-fold iterative method was proposed to decouple the dependence among pressure, velocity, and temperature so as to reduce the computation and improve the numerical stability. Based on the proposed theoretical model and numerical method, a program code was developed to simulate melt front progress and flow fields. The numerical simulations for different injection speeds, melt temperatures, and gate locations were carried out to explore the jetting mechanism. The results indicate the filling pattern depends on the competition between inertial and viscous forces. When inertial force exceeds the viscous force jetting occurs, then it changes to a buckling flow as the viscous force competes over the inertial force. Once the melt contacts with the mold wall, the melt filling switches to conventional sequential filling mode. Numerical results also indicate jetting length increases with injection speed but changes little with melt temperature. The reasonable agreements between simulated and experimental jetting length and buckling frequency imply the proposed method is valid for jetting simulation.

RHD gene polymorphism among RhD-negative Han Chinese.

OBJECTIVE: To evaluate the status of eight RHD specific exons in 131 Han Chinese blood donors who were classified as RhD-negative by serological methods and explore the genomic structure of RHD gene among the Han Chinese. The Rh blood group system has the highest prevalence of polymorphisms among human blood group systems and is clinically significant in transfusion medicine. The Rh antigens are expressed on polypeptides encoded by two highly homologous genes, RHD and RHCE. Recent molecular studies have shown that the RhD-negative trait could be generated by multiple genetic mechanisms and is ethnic group-dependent. METHODS: The polymerase chain reaction using-sequence specific primers (PCR-SSP) was used to amplify exons 2, 3, 4, 5, 6, 7, 9 and 10 of RHD gene and exons 1, 2 and 5 of RHCE gene, as well as intron 4 in each of them. RESULTS: The 131 cases of RhD-negative phenotypes consisted of 60 ccee, 58 Ccee, 5 ccEe, 5 CcEe and 3 CCee. Among them, 83 with the Rh ccee or ccEe phenotypes (63.4%) lacked the eight RHD exons indicated above, while 26 cases with the Rh Ccee, CCee, CcEe phenotypes (19.9%) had all the RHD exons examined. Twenty-two individuals with the Ccee, CCee, CcEe phenotypes (16.8%) carried at least one RHD exon. The phenotypes of the RhD negative individuals carrying the RHD gene were Rh CC or Cc, but not cc. CONCLUSIONS: Three classes of RhD-negative polymorphisms among a population of Han Chinese were observed. Antigen association analysis suggested the existence of a novel class of RhD-negative associated haplotype in Han Chinese. This haplotype consisted of a normal RHCE allele and a nonfunctional RHD gene. It may be beneficial to redefine the RhD-negative blood group among Chinese populations upon clarification of the mechanisms of RHD gene expression and RhD antigen immunization.