Electroacupuncture regulates macrophage, neutrophil, and oral microbiota to alleviate alveolar bone loss and inflammation in experimental ligature-induced periodontitis.

AIM: Electroacupuncture (EA) regulates distant body physiology through somatic sensory autonomic reflexes, balances the microbiome, and can promote the release of immune cells into bloodstream, thereby inhibiting severe systemic inflammation. This makes it possible to use EA as an integrated treatment for periodontitis. MATERIALS AND METHODS: In this study, EA was applied to the ST36 acupoints in a ligature-induced periodontitis (LIP) mouse model. Then the effects of EA on periodontal myeloid cells, cytokines, and the microbiome were comprehensively analysed using flow cytometry, quantitative Polymerase Chain Reaction (PCR), and 16 S sequencing. RESULTS: Results demonstrated that EA could significantly relieve periodontal bone resorption. EA also suppressed the infiltration of macrophages and neutrophils, reduced gene expression of the pro-inflammatory cytokines IL-1ß, IL-6, IL-17 and TNF-α, and increased expression of the anti-inflammatory factors IL-4 and IL-10 in periodontal tissues. Moreover, composition of the periodontal microbiome was regulated by EA, finding that complex of microbiota, including supragingival Veillonella, subgingival Streptococcus, and subgingival Erysipelatoclostridium, were significantly reduced. Meanwhile, nitrate and nitrate-related activities of subgingival microbiota were reversed. Network analysis revealed close relationships among Veillonella, Streptococcus, and Bacteroides. CONCLUSIONS: Our study indicates that EA can effectively alleviate inflammation and bone resorption in LIP mice, potentially via the regulation of myeloid cells, cytokines, and periodontal microbiome.

The transmission network and spatial-temporal distributions of COVID-19: A case study in Lanzhou, China.

Public emergencies exert substantial adverse effects on the socioeconomic development of cities. Investigating the transmission characteristics of COVID-19 can lead to evidence-based strategies for future pandemic intervention and prevention. Drawing upon primary COVID-19 data collected at both the street level and from individuals with confirmed cases in Lanzhou, China, our study examined the spatial-temporal distribution of the pandemic at a detailed level. First, we constructed transmission networks based on social relationships and spatial behavior to elucidate the actual natural transmission chain of COVID-19. We then analyze key information regarding pandemic spread, such as superspreaders, superspreading places, and peak hours. Furthermore, we constructed a space-time path model to deduce the spatial transmission trajectory of the pandemic while validating it with real activity trajectory data from confirmed cases. Finally, we investigate the impacts of pandemic prevention and control policies. The progression of the pandemic exhibits distinct stages and spatial clustering characteristics. People with complex social relationships and daily life trajectories and places with high pedestrian flow and commercial activity venues are prone to becoming superspreaders and superspreading places. The transmission path of the pandemic showed a pattern of short-distance and adjacent transmission, with most areas not affected. Early-stage control measures effectively disrupt transmission hotspots and impede the spatiotemporal trajectory of pandemic propagation, thereby enhancing the efficacy of prevention and control efforts. These findings elucidate the characteristics and transmission processes underlying pandemics, facilitating targeted and adaptable policy formulation to shape sustainable and resilient cities.

Study on Urban Resilience from the Perspective of the Complex Adaptive System Theory: A Case Study of the Lanzhou-Xining Urban Agglomeration.

In the context of global environmental change and continuous urbanization, enhancing urban resilience is an important way to improve urban emergency management capacity and achieve sustainable development of urban systems. It is of great significance to clarify the mechanisms and effects of urban resilience and carry out resilience measurement to improve the level of urban system resilience and alleviate the pressure of environmental disturbances on the stable operation of urban systems. As an important part of the "Belt and Road" Initiative and one of the few leading economic regions in western China, promoting the high-quality development of the Lanzhou-Xining urban agglomeration is of profound significance for strengthening ethnic unity and stabilizing the northwest and southwest regions. Based on the complex adaptive system (CAS) theory and the adaptive cycle model, this study understands urban resilience as the comprehensive result of urban system stability, self-organization, learning adaptability and transformability, constructs a multi-level open index evaluation system, and analyzes the spatio-temporal evolution characteristics of urban resilience of the Lanzhou-Xining urban agglomeration from the proposed design to the formal planning in 2010-2017. The findings are as follows: (1) Research on the urban resilience of the Lanzhou-Xining urban agglomeration verifies the applicability of the evolutionary urban resilience analysis framework and makes preliminary findings on urban resilience based on CAS theory, which provide a certain theoretical reference for the research on the spatio-temporal evolution of urban resilience. (2) From 2010 to 2017, significant differences are observed between various urban attributes. Resilience exhibits an overall upward trend, and spatial evolution changes from a double core (Lanzhou and Xining) to three cores (Lanzhou, Xining and Haidong) and polycentric modes. (3) Based on urban resilience characteristics and an urban system adaptability cycle model, this paper divides the Lanzhou-Xining urban agglomeration cities into four types (exploitation-reorganization, conservation-release, conservation-exploitation and exploitation), and proposes corresponding adaptive management countermeasures. These could be adopted as a reference to promote the high-quality development of the Lanzhou-Xining urban agglomeration.

Novel shikonin derivatives suppress cell proliferation, migration and induce apoptosis in human triple-negative breast cancer cells via regulating PDK1/PDHC axis.

AIMS: PDK1 is one of the key enzymes in the glucose metabolism pathway, which is abnormally high expressed in breast cancer tissues and can promote tumor proliferation and metastasis. PDK1 and the PDHC/PDK axis are important targets for regulating glucose metabolism and anti-tumor activity. In this study, we evaluated the anti-tumor activities of a series of semi-synthesized shikonin (SK) derivatives against human breast cancer cells. MAIN METHODS: The anti-proliferation activity of SK derivatives against human breast cancer cell lines was tested by CCK-8 and EdU assay. Flow cytometry was utilized to evaluate cell apoptosis, reactive oxygen species and cell cycle distribution. Cell migration ability was determined by wound healing and trans-well assay. PDK1 targeting effect was confirmed by western bolting, molecular docking, bio-layer interferometry and PDK1 enzyme activity assay. Nude-mouse transplanted tumor model was used to evaluate their anti-tumor effect in vivo. KEY FINDINGS: Findings revealed that SK derivatives had good anti-proliferation ability against MDA-MB-231 cell. They induced cell apoptosis by regulating the mitochondrial apoptosis and death receptor pathway. They also inhibited cell migration by suppressing EMT progression. Molecular docking, PDK1 affinity and enzyme activity demonstrated their PDK1 targeting. In vivo antitumor experiment showed that E2 could significantly inhibit tumor growth with lower side-effect on mice than SK. SIGNIFICANCE: In conclusion, the novel SK derivatives E2 and E5 inhibited tumor glycolysis by targeting PDK1 and ultimately induced apoptosis. Our data demonstrated that E2 would be a good lead compound for the treatment of human TNBC as a novel PDK1 inhibitor.

Genome-Wide Identification of LeBAHDs in Lithospermum erythrorhizon and In Vivo Transgenic Studies Confirm the Critical Roles of LeBAHD1/LeSAT1 in the Conversion of Shikonin to Acetylshikonin.

The BAHD acyltransferase family is a unique class of plant proteins that acylates plant metabolites and participates in plant secondary metabolic processes. However, the BAHD members in Lithospermum erythrorhizon remain unknown and uncharacterized. Although the heterologously expressed L. erythrorhizon BAHD family member LeSAT1 in Escherichia coli has been shown to catalyze the conversion of shikonin to acetylshikonin in vitro, its in vivo role remains unknown. In this study, the characterization, evolution, expression patterns, and gene function of LeBAHDs in L. erythrorhizon were explored by bioinformatics and transgenic analysis. We totally identified 73 LeBAHDs in the reference genome of L. erythrorhizon. All LeBAHDs were phylogenetically classified into five clades likely to perform different functions, and were mainly expanded by dispersed and WGD/segmental duplication. The in vivo functional investigation of the key member LeBAHD1/LeSAT1 revealed that overexpression of LeBAHD1 in hairy roots significantly increased the content of acetylshikonin as well as the conversion rate of shikonin to acetylshikonin, whereas the CRISPR/Cas9-based knockout of LeBAHD1 in hairy roots displayed the opposite trend. Our results not only confirm the in vivo function of LeBAHD1/LeSAT1 in the biosynthesis of acetylshikonin, but also provide new insights for the biosynthetic pathway of shikonin and its derivatives.

Coupling coordination and interaction between urbanization and eco-environment in Cheng-Yu urban agglomeration, China.

We built a comprehensive evaluation index system of urbanization in Chengdu-Chongqing (Cheng-Yu) urban agglomeration from four subsystems, including the economic, social, ecological, and urban and rural coordination. The comprehensive evaluation index system of eco-environment was constructed by combining ecological environment carrying capacity and ecological flexibi-lity. The coupling coordination degree model was applied to quantify the coupling coordination degree between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglo-meration from 2005 to 2018. With GIS spatial analysis, phenomenon analysis and Tapio model, we analyzed the interaction type, evolution path and path of decoupling between urbanization and eco-environment in the prefecture-level cities of Cheng-Yu urban agglomeration. The results showed that the urbanization quality of Cheng-Yu urban agglomeration showed a trend of fluctuation and rise during the study period. Both Chengdu and Chongqing as high value areas showed "double-core" radia-ting to the surrounding areas. The eco-environment quality showed a slowly rising trend. The spatial pattern was a " U " shape with a north opening, high perimeter and low center. The degree of coupling coordination between the urbanization system and the eco-environment system was rising, with a spatial pattern of low in the middle and high in the east and west. The overall level of coupling coordination was relatively high. The type of coupling coordination degree was gradually evolving from near-disorder and reluctant coordination to moderate coordination. The evolution paths of urbanization and eco-environmental interaction were divided into two categories: stable and changing. The stable type included 20 cities in 5 subcategories, with Chengdu, Deyang, Mianyang, etc. being always well-coordination. The change type included 16 cities in 9 subcategories. The coordination degree of Chongqing main urban area, Tongliang and most other cities was improved, showing "rising" development. Hechuan, Zigong and a few other cities showed "sinking" development. The growth rates of both ecological environment and urbanization were positive. The decoupling state of urbanization and ecological environment was mainly characterized by weak decoupling and expansion connection.

Resequencing 200 Flax Cultivated Accessions Identifies Candidate Genes Related to Seed Size and Weight and Reveals Signatures of Artificial Selection.

Seed size and weight are key traits determining crop yield, which often undergo strongly artificial selection during crop domestication. Although seed sizes differ significantly between oil flax and fiber flax, the genetic basis of morphological differences and artificial selection characteristics in seed size remains largely unclear. Here we re-sequenced 200 flax cultivated accessions to generate a genome variation map based on chromosome assembly reference genomes. We provide evidence that oil flax group is the ancestor of cultivated flax, and the oil-fiber dual purpose group (OF) is the evolutionary intermediate transition state between oil and fiber flax. Genome-wide association studies (GWAS) were combined with LD Heatmap to identify candidate regions related to seed size and weight, then candidate genes were screened based on detailed functional annotations and estimation of nucleotide polymorphism effects. Using this strategy, we obtained 13 candidate genes related to seed size and weight. Selective sweeps analysis indicates human-involved selection of small seeds during the oil to fiber flax transition. Our study shows the existence of elite alleles for seed size and weight in flax germplasm and provides molecular insights into approaches for further improvement.

[Community structure characteristics of phytoplankton and related affecting factors in Hengshan Reservoir, Zhejiang, China].

In order to reveal the community structure characteristics of phytoplankton and the relationships with environmental factors in Hengshan Reservoir, the phytoplankton species composition, abundance, biomass and 12 environmental factors at 4 sampling sites were analyzed from March 2011 to February 2012. A total of 246 phytoplankton species were identified, which belong to 78 genera and 7 phyla. The dominant species were Melosira varians, M. granulate, Cyclotella meneghiniana, Asterianella formosa, Synedra acus, Achnanthes exigua, Ankistrodesmus falcatus, Oscillatoria lacustris, Cryptomonas erosa, Chroomonas acuta, Phormidium tenue and Microcystis aeruginosa, etc. Seasonal variations of species were obvious. The annual abundance and biomass of the phytoplankton were 0.51 x 10(5)-14.22 x 10(5) ind x L(-1) and 0.07-1.27 mg x L(-1), respectively. The values of the Margelef index, Pielou index and Shannon index of the phytoplankton community were 1.10-3.33, 0.26-0.81 and 0.51-2.38, respectively. The phytoplankton community structure was of Bacillariophyta-Cryptophyta type in spring and winter, of Chlorophyta-Cyanophyta type in summer, and of Bacillariophyta type in autumn. Canonical correlation analysis (CCA) showed that temperature, transparency, chemical oxygen demand and pH had the closest relationships with the phytoplankton community structure in the reservoir. Water quality evaluation showed that Hengshan Reservoir was in a secondary pollution with a meso-trophic level.