The sphingosine 1-phosphate receptor agonist FTY720 interfered the distribution of dendritic cell and induced the maternal-fetal immune tolerance.

OBJECTIVE: The aim of this study was to investigate the effect of FTY720, an agonist of the sphingosine 1-phosphate (S1P) receptor, on the embryo loss rate in mice of spontaneous abortion model and the underlying mechanism. METHODS: The effect of intraperitoneal injection of FTY720 on the embryo loss rate in mice of spontaneous abortion model was observed. The expression of S1PR on the dendritic cell (DC) surface was detected by reverse transcription polymerase chain reaction. The quantity and maturation of DCs in peripheral blood and local tissues of pregnant mice, and the expression of CCL19 as well as its receptor C-C chemokine receptor 7 (CCR7) were detected by flow cytometry and immunohistochemistry. Chemotaxis assay was performed to verify the effect of FTY720 on the chemotaxis of DCs. RESULTS: (1) FTY720 had no significant effect on the embryo loss rate in normal pregnant rats. In contrast, adoptive transferring of FTY720 significantly reduced the embryo loss rate of the spontaneous abortion mouse model (P < 0.05). (2) S1PR was extensively expressed on DC surface. The S1P receptor agonist FTY720 reduced the expressions of DC surface chemokines and its receptor (P < 0.05), resulting in a significant reduction in the number of DCs that were chemoattracted to maternal-fetal interface flow cytometry (P < 0.05). (3) FTY720 had no significant effect on the differentiation and apoptosis rate of DCs (P > 0.05). CONCLUSION: We hypothesized that FTY720 may reduce the number of DCs that were chemoattracted to the maternal-fetal interface by downregulating the expression of CCR7, which ultimately induces maternal-fetal immune tolerance.

[Spatial and Temporal Characteristics of Fractional Vegetation Cover and Its Response to Urbanization in Beijing].

Exploration of the spatiotemporal changes in fractional vegetation cover （FVC） and its response characteristics to urbanization is of great significance for urban ecological protection and planning in Beijing. This study analyzed the spatiotemporal characteristics of vegetation cover changes in Beijing from 2000 to 2020 using the Theil-Sen Median and Mann-Kendall methods based on a long-term time series vegetation cover dataset. Then, this study used the urbanization index as a key indicator of spatial urbanization and utilized the transect line and global grid analysis methods to investigate the response characteristics of FVC to different urbanization gradients. The results indicated that： ① FVC changes showed spatial and temporal heterogeneity. From 2000 to 2020, Beijing was predominantly covered by high vegetation, accounting for 65.22% of the total area, which was mainly distributed in ecological conservation areas consistent with the Jundu, Xishan, and Yaji Mountain ranges. The FVC presented an overall positive development trend, with a decreasing trend of areas with low FVC. The increase in FVC was significant （by 28.68%）, mainly distributed in ecological conservation areas and within a range of 10-12 km in concentric circles centered around Tiananmen Square. The urbanization index and FVC change rate were relatively high in Haidian District, Chaoyang District, Fengtai District, Shijingshan District, and Changping District. ② The artificial land surface in 2000, 2010, and 2020 was 9.69%, 13.64%, and 21.19%, respectively, with significant spatial agglomeration and strong spatial heterogeneity. During the urbanization process in Beijing, the increase in artificial land surface reached 11.5%, with the conversion from arable land to artificial land surface accounting for 53.83% of the total land use conversion area. ③ There was a significant negative correlation between FVC and the urbanization index, indicating that urbanization had a negative impact on regional FVC. However, as the urbanization process stabilized, this negative correlation tended to gradually weaken. Although the central urban areas were mainly characterized by low FVC, there was a significant increasing trend in the FVC, indicating a positive development in the FVC and an improvement in regional ecological quality, which was closely related to the governance of the mountain-water-forest-field-lake-grass-sand system. The results of the study can provide a basis for the development of vegetation restoration programs and ecological management measures in Beijing.

[Establishment of an indicator system for comprehensive assessment on terrestrial biodiversity in China]. / ä¸­å›½é™†åŸŸç”Ÿç‰©å¤šæ ·æ€§ç»¼åˆè¯„ä¼°æŒ‡æ ‡ä½“ç³»æž„å»º.

The comprehensive evaluation of terrestrial biodiversity is a key basic work for biodiversity protection. Clarifying the status, trend, and driving factors of biodiversity is premise and necessary for formulating policies and measures of biodiversity protection. At present, there is no unified indicator system for the comprehensive assessment of terrestrial biodiversity in China. We constructed a comprehensive assessment indicator system of terrestrial biodiversity in China, by combining the Aichi biodiversity targets of the Convention on Biological Diversity and the sustainable development goals of the United Nations, learning from the development trend of biodiversity assessment in the world, and following the Pressure-State-Response framework. A total of 22 indicators were obtained, including eight status indicators, seven pressure indicators, and seven response indicators. The correlation and accessibility of the indicators were analyzed. These indicators could be applied to not only an independent assessment for biodiversity status, threatened and protection effectiveness, but also for the comprehensive assessment of terrestrial biodiversity to optimize and adjust priority protection areas and protection measures. Our results would provide a technical support for calculating green GDP and formulating regional ecological compensation policies.

DAP10 Predicted the Outcome of Pediatric B-Cell Acute Lymphoblastic Leukemia and Was Associated with the T-Cell Exhaustion.

B-cell acute lymphoblastic leukemia is the most common malignant tumor in children. About 10-15% of patients will relapse with a 5-year OS of 57.5% for the past 20 years. As tumor microenvironment plays an important role in the disease process, many types of immunotherapy are approached. New immunotherapies including CAR-T cells have been developed for refractory B-ALL treatment. However, CAR-T treatment faces several problems, including loss of the target antigen and in vivo T-cell persistence. Here, we analyzed the tumor microenvironment of pediatric B-ALL patients in TARGET database. Using Cox analysis and PPI network, we finally sorted out the DAP10 gene. We found that DAP10 was hardly expressed in leukemic B cells. DAP10 was downregulated in B-ALL compared with normal individuals, and low expression level of DAP10 predicted poor survival. Furthermore, we found the tumor microenvironment was different in DAP10 high and low expression children. The CD8+ T cells might be hard to activate and more likely to suffer from exhaustion in DAP10 lowly expressed children. In conclusion, our results showed that DAP10 was a well biomarker to indicate the prognosis and tumor microenvironment in pediatric B-ALL. The treatment strategy of immunotherapy for the leukemic children with DAP10 lowly expressed should be adjusted if needed.

Case Report: Macrophage Activation Syndrome and Widespread Neuroimaging Abnormality in Childhood-Onset Systemic Lupus Erythematosus.

Macrophage activation syndrome (MAS) and widespread brain lesions are rare and severe complications of childhood-onset systemic lupus erythematosus (SLE). We report an 11-year-old girl who presented with recurrent rashes for half a year and fever for 2 weeks. Clinical and laboratory features at admission pointed to the diagnosis of SLE and SLE-associated MAS. Cerebral magnetic resonance imaging taken on day 4 after admission showed abnormal signals. Glucocorticoid therapy was started on day 5. Two days later, the patient appeared weak and ill, then the next day she exhibited dizziness, drowsiness, apathia, and dysarthria. High-dose methylprednisolone, cyclophosphamide, and intravenous immunoglobulin were used to treat the patient, and intrathecal dexamethasone was given. The patient was discharged on day 30 after admission and showed complete clinical resolution and improved magnetic resonance imaging resolution.

Effect of baicalin on gestational hypertension-induced vascular endothelial cell damage.

OBJECTIVE: Baicalin is a compound extracted from the dried root of Scutellaria baicalensis Georgi. Studies have shown that baicalin has a protective effect on vascular endothelial cells, but whether baicalin could alleviate ascular endothelial cell damage in pregnancy-induced hypertensive patients remains unknown. MATERIALS AND METHODS: We established a hypertensive pregnant rat model to study vascular endothelial injury during pregnancy-induced hypertension. Plasma epoprostenol (PGI-2), thromboxane A2 (Txa-2), ß-human chorionic gonadotropin (ß-HCG), and estrogen levels in rats were detected using ELISA. Vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and C-reactive protein (CRP) expression were detected using western blotting and quantitative PCR (q-PCR). RESULTS: Results showed that baicalin alleviated symptoms of pregnancy-induced hypertension. CRP, Txa-2, and ß-HCG expression were significantly upregulated, while VEGF, eNOS, PGI-2, and estrogen expression was decreased in plasma and placental tissues of hypertensive rats. However, the levels of these injury indicators were significantly decreased after baicalin therapy, while the expression of protective indicators was significantly increased. CONCLUSION: Baicalin reversed vascular endothelial cell injury in pregnant hypertensive rats by promoting VEGF, eNOS, PGI-2, and estrogen expression.

Apigenin and Abivertinib, a novel BTK inhibitor synergize to inhibit diffuse large B-cell lymphoma in vivo and vitro.

Background: Apigenin, a flavonoid phytochemical extracted from fruits and vegetables, has shown anti-neoplastic effects in a variety of malignant tumors. DLBCL is the most common type of aggressive lymphoma in adults with a poor prognosis. Small-molecule inhibitors like BTK inhibitors have demonstrated extended period of disease control. Whereas the effects of the synergetic inhibition of the two have not been elucidated. Methods: We assessed the efficacy of Apigenin alone or combined with Abivertinib to inhibit DLBCL progression. Cell viability was examined using the cell proliferation cell proliferation assay (MTS). Apoptotic cells and cell cycle evaluation were detected by Annexin V-FITC and DNA staining solution respectively. Western blot was used to explore the potential mechanism, and the in vivo effects of the two drugs were performed by a DLBCL xenograft BALB/c nude mice model. Results: Our results demonstrated that Apigenin can inhibit the proliferation and clone forming of DLBCL cells. Apigenin also induces apoptosis by down-regulating BCL-XL and activating Caspase family. In addition, Apigenin down-regulates cell cycle proteins including CDK2/CDK4/CDK6/CDC2/p-RB to increase G2/M phase arrest. Mechanically, our data demonstrate that Apigenin leads to a significant reduction of the expression of pro-proliferative pathway PI3K/mTOR to inhibit DLBCL cells survival. Moreover, our in vitro and in vivo results show that Apigenin can synergize with Abivertinib, a novel BTK inhibitor, in treating DLBCL visa synergistically inducing apoptosis and inhibiting the p-GS3K-ß and its downstream targets. Conclusions: Collectively, our study suggests that Apigenin exerts improving anti-lymphoma effect of BTK inhibitors and provides hope to targeted therapy of those develop resistance.

Anti-IFN-γ autoantibodies underlie disseminated Talaromyces marneffei infections.

Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*16:02 and -DQB1*05:02 alleles in these patients. We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*16:02 and DQB1*05:02 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.

High drug-loading system of hollow carbon dots-doxorubicin: preparation, in vitro release and pH-targeted research.

Hollow carbon dots (HCDs), as drug carriers, and doxorubicin (DOX), as a model drug, were selected to prepare a HCDs-DOX-loading system. First, HCDs were prepared by a hydrothermal method and characterized by transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and nuclear magnetic resonance (13C NMR), UV-vis absorption, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopies (XPS). The HCDs were then used to load DOX. The drug-loading system of HCDs-DOX was characterized by zeta potential measurements, and UV-vis absorption and fluorescence spectroscopies. We then studied the drug loading, formation mechanism, cytotoxicity, in vitro release and pH-targeted properties. HCDs-DOX was found to have a high drug (DOX)-loading ratio (∼42.9%) and better sustained pH targeted-release and lower cytotoxicity than those of DOX. In the HCDs-DOX system, interactions between the HCDs and DOX were electrostatic resulting in the formation of -N[double bond, length as m-dash]C-via the coupling of -NH2 (on HCDs) and -C[double bond, length as m-dash]O (on DOX). In vitro release of HCDs-DOX conformed to the Weibull model and Fick diffusion, consistent with that of free DOX. We report, for the first time, that the: (i) functional groups on the HCD surfaces (not their hollow structure) play a key role in drug loading; (ii) the carrier (HCDs) did not change the in vitro release model or mechanism of DOX before and after loading by the HCDs.

In vitro assembly of the bacterial actin protein MamK from ' Candidatus Magnetobacterium casensis' in the phylum Nitrospirae.

Magnetotactic bacteria (MTB), a group of phylogenetically diverse organisms that use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field, play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have revealed that the bacterial actin protein MamK plays essential roles in the linear arrangement of magnetosomes in MTB cells belonging to the Proteobacteria phylum. However, the molecular mechanisms of multiple-magnetosome-chain arrangements in MTB remain largely unknown. Here, we report that the MamK filaments from the uncultivated 'Candidatus Magnetobacterium casensis' (Mcas) within the phylum Nitrospirae polymerized in the presence of ATP alone and were stable without obvious ATP hydrolysis-mediated disassembly. MamK in Mcas can convert NTP to NDP and NDP to NMP, showing the highest preference to ATP. Unlike its Magnetospirillum counterparts, which form a single magnetosome chain, or other bacterial actins such as MreB and ParM, the polymerized MamK from Mcas is independent of metal ions and nucleotides except for ATP, and is assembled into well-ordered filamentous bundles consisted of multiple filaments. Our results suggest a dynamically stable assembly of MamK from the uncultivated Nitrospirae MTB that synthesizes multiple magnetosome chains per cell. These findings further improve the current knowledge of biomineralization and organelle biogenesis in prokaryotic systems.

Secretory expression, functional characterization, and molecular genetic analysis of novel halo-solvent-tolerant protease from Bacillus gibsonii.

A novel protease gene from Bacillus gibsonii, aprBG, was cloned, expressed in B. subtilis, and characterized. High-level expression of aprBG was achieved in the recombinant strain when a junction was present between the promoter and the target gene. The purified recombinant enzyme exhibited similar N-terminal sequences and catalytic properties to the native enzyme, including high affinity and hydrolytic efficiency toward various substrates and a superior performance when exposed to various metal ions, surfactants, oxidants, and commercial detergents. AprBG was remarkably stable in 50% organic solvents and retained 100% activity and stability in 0-4 M NaCl, which is better than the characteristics of previously reported proteases. AprBG was most closely related to the high-alkaline proteases of the subtilisin family with a 57-68% identity. The secretion and maturation mechanism of AprBG was dependent on the enzyme activity, as analyzed by site-directed mutagenesis. Thus, when taken together, the results revealed that the halo-solvent-tolerant protease AprBG displays significant activity and stability under various extreme conditions, indicating its potential for use in many biotechnology applications.

Prolonged reversal of long-term potentiation that is N-methyl-D-aspartate receptor independent: implications for memory formation.

Reversal of long-term potentiation (LTP) by low-frequency stimulation (LFS) is often referred to as depotentiation (DP), a phenomenon that is time-dependent. The present study aimed to determine whether LTP could still be reversed when the stimulation was applied beyond the optimal time window in hippocampal slices from adult rats. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the strata radiatum in CA1, following stimulation of Schaffer collaterals. Theta-burst stimulation (TBS) induced LTP that could be reversed by repeated paired-pulse LFS (PP-LFS) after almost 3 h post-TBS. Only when synapse strength reached a plateau did application of PP-LFS trigger DP. In addition, it was surprising to observe that PP-LFS, which generally induces LTD in adult rats, evoked an LTP-like further strengthening in previously potentiationed synapses, even in the presence of APV, a competitive antagonist of N-methyl-D-aspartate receptors (NMDA-Rs). Our results suggest that LTP can be reversed NMDAR-independently more than 2 h after TBS by PP-LFS in adult hippocampus and that saturation of LTP is effective to promote this process.