[TFEB activator 1 enhances autophagic degradation of oligomeric amyloid-ß in microglia].

The purpose of the study was to investigate the mechanism of TFEB activator 1 (TA1) improving the autophagic degradation of oligomeric amyloid-ß (oAß) in microglia, and to explore the therapeutic effect of TA1 on an in vitro model of microglia in Alzheimer's disease (AD). Primary microglia were exposed to 1 µmol/L oAß for 0, 3, 12, and 24 h respectively to construct the in vitro model of microglia in AD. In order to explore the therapeutic effect of TA1, primary microglia were co-treated with 1 µmol/L oAß and 1 µmol/L TA1 for 12 h. To determine the autophagy flux, the above cells were further treated with 100 nmol/L Bafilomycin A1 for 1 h before fixation. Fluorescent probes were used to detect the endocytosis or degradation of oAß1-42 by microglia. The autophagic flux was determined by infection of lentivirus mCherry-EGFP-LC3. The nuclear TFEB intensity, the autophagosomes number, and the colocalization ratio of oAß1-42 with lysosome-associated membrane protein 1 (LAMP1) or microtubule-associated protein light chain 3 (LC3), were detected by immunofluorescence assay. Expressions of autophagy-related-genes, including Lamp1, Atg5, and Map1lc3b, were detected by qRT-PCR. Results showed that prolonged oAß exposure inhibited the endocytosis and degradation of oAß by microglia. Meanwhile, the number of autophagosomes and autophagy flux in microglia decreased after 12 h of oAß treatment. We further found that the nuclear expression of autophagy regulator TFEB decreased after 12 h of oAß exposure, resulting in the decrease of autophagy genes, thus leading to the damage of autophagic degradation of oAß. Therefore, long-term oAß exposure was considered to construct the in vitro model of microglia in AD. After TA1 treatment, the nuclear expression of TFEB in cells was obviously upregulated. TA1 treatment upregulated the expressions of autophagy-related genes, leading to the recovery of autophagy flux. TA1 also recovered the endocytosis and degradation of oAß by microglia. In conclusion, TA1 could improve oAß clearance by microglia in AD by upregulating microglial TFEB-mediated autophagy, suggesting TA1 as a potential therapeutic drug for AD.

[Spatiotemporal Dynamic Evolution and Gravity Center Migration of Carbon Emissions in the Main Urban Area of Chongqing over the Past 20 Years].

Global warming caused by carbon emissions is an environmental issue that is of great concern to all walks of life. Dynamic monitoring of the spatiotemporal evolution of urban carbon emissions is an important part of achieving the regional double-carbon goals. Taking the main urban area of Chongqing as an example, based on the data of land use and energy consumption, this study estimated the carbon emissions of 153 townships and streets in the main urban area of Chongqing from 2000 to 2020 by using the carbon emission coefficient method. Additionally, using the ESTDA framework to pass the LISA time path, spatiotemporal transition, and the standard deviation ellipse model from the perspective of spatiotemporal interaction, the spatiotemporal dynamic evolution of carbon emissions in the main urban area and the shift in the center of gravity over the past 20 years were analyzed. The results showed that: ① in the past 20 years, the carbon emissions in the main urban and rural areas have had a significant positive spatial correlation, and the spatial convergence showed a trend of first decreasing and then increasing. ② In the past 20 years, there were 126 township streets with low and medium relative lengths (accounting for 82%), indicating that the local spatial structure of township carbon emissions in the main urban area had strong stability; the total number of township streets with low and medium curvatures was 138 (accounting for 90%), indicating that the volatility of the main urban and rural carbon emissions in the direction of spatial dependence was relatively stable; there were 113 township streets (accounting for 74%) of the synergistic growth type, indicating that the main urban and rural carbon emissions were relatively stable. The emission pattern had strong spatial integration. ③ In the past 20 years, the spatiotemporal agglomeration index was greater than 70%, indicating that the local spatial correlation pattern and agglomeration characteristics of carbon emissions in the main urban and rural areas had strong stability. 4 In the past 20 years, the center of carbon emission in the main urban area had been distributed between 106°30'43″-106°32'42″E, 29°33'34″-29°35'56″N, and the center of gravity shifted to the northeast as a whole. The spatial distribution changed from the "northwest-southeast" pattern to the "northeast-southwest" pattern. These results can provide reference for the green and low-carbon sustainable development of Chongqing and the formulation of differentiated emission reduction policies, as well as provide reference for other similar mountain cities in western China.

Lipid Dynamics, Identification, and Expression Patterns of Fatty Acid Synthase Genes in an Endoparasitoid, Meteorus pulchricornis (Hymenoptera: Braconidae).

In insect parasitoids, fatty acid synthases (FASs) have received less attention and their roles associated with lipogenesis loss are far from clear. Meteorus pulchricornis is a solitary endoparasitoid wasp of many larvae of lepidopteran pests. The lipid content during developmental stages of M. pulchricornis was measured; it was higher in the larval and pupal stages but declined from six-day-old pupae. Lipid accumulation constantly decreased in the adult stage, even after feeding on honey solutions. To investigate the roles of FASs in lipid synthesis in M. pulchricornis, four FAS genes (MpulFAS1~4) were identified from the transcriptome database of M. pulchricornis. All FAS genes included full-length open reading frames and shared 72-79% similarity with the sequences of Microplitis demolitor. qRT-PCR validation showed that all four FASs had the highest expression after the adult wasps were fed on honey diets. MpulFAS1 and MpulFAS2 reached their expression peaks at the adult stage but MpulFAS3 and MpulFAS4 peaked at the larval stage. To further study the function of FASs, dsRNA injection knocked down the expression of four MpulFASs and resulted in a significant decline of lipid content at the adult stage in M. pulchricornis. Results from this study suggest that M. pulchricornis adults cannot accumulate lipid content effectively and FASs may still contribute to lipid synthesis in the adult stage. This broadens the knowledge on the ability of lipid synthesis in parasitoid wasps and provides insight into the roles of FASs in insects with parasitic life-history traits.