Functionalized γ-Boehmite Covalent Grafting Modified Polyethylene for Lithium-Ion Battery Separator.

In the field of lithium-ion batteries, the challenges posed by the low melting point and inadequate wettability of conventional polyolefin separators have increased the focus on ceramic-coated separators. This study introduces a highly efficient and stable boehmite/polydopamine/polyethylene (AlOOH-PDA-PE) separator. It is crafted by covalently attaching functionalized nanosized boehmite (γ-AlOOH) whiskers onto polyethylene (PE) surfaces. The presence of a covalent bond increases the stability at the interface, while amino groups on the surface of the separator enhance the infiltration of the electrolyte and facilitate the diffusion of lithium ions. The PE-PDA-AlOOH separator, when used in lithium-ion batteries, achieves a discharge capacity of 126 mAh g-1 at 5 C and retains 97.1% capacity after 400 cycles, indicating superior cycling stability due to its covalently bonded ceramic surface. Thus, covalent interface modification is a promising strategy to prevent delamination of ceramic coatings in separators.

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.

Comparative characterization of microRNA-71 of Echinococcus granulosus exosomes.

Cystic echinococcosis (CE) is a global zoonotic disease caused by Echinococcus granulosus, posing a great threat to human and animal health. MiRNAs are small regulatory noncoding RNA involved in the pathogenesis of parasitic diseases, possibly via exosomes. Egr-miR-71 has been identified as one of the miRNAs in the blood of CE patients, but its secretory characteristics and functions remains unclear. Herein, we studied the secretory and biological activity of exosomal egr-miR-71 and its immunoregulatory functions in sheep peripheral blood mononuclear cells (PBMCs). Our results showed that egr-miR-71 was enriched in the exosome secreted by protoscoleces with biological activity. These egr-miR-71-containing exosomes were easily internalized and then induced the dysregulation of cytokines (IL-10 and TNF-α), nitric oxide (NO) and key components (CD14 and IRF5) in the LPS/TLR4 pathway in the coincubated sheep PBMCs. Similarly, egr-miR-71 overexpression also altered the immune functions but exhibited obvious differences in regulation of the cytokines and key components, preferably inhibiting proinflammatory cytokines (IL-1α, IL-1ß and TNF-α). These results demonstrate that exosomal egr-miR-71 is bioactive and capacity of immunomodulation of PBMCs, potentially being involved in immune responses during E. granulosus infection.

Title: Caractérisation comparative du microARN-71 des exosomes d'Echinococcus granulosus. Abstract: L'échinococcose kystique (EK) est une maladie zoonotique mondiale causée par Echinococcus granulosus, représentant une grande menace pour la santé humaine et animale. Les miARN sont des petits ARN régulateurs non codants impliqués dans la pathogenèse des maladies parasitaires, éventuellement via les exosomes. Egr-miR-71 a été identifié comme l'un des miARN présents dans le sang des patients atteints d'EK, mais ses caractéristiques et fonctions sécrétoires restent floues. Ici, nous avons étudié l'activité sécrétoire et biologique du egr-miR-71 exosomal et ses fonctions immunorégulatrices dans les cellules mononucléées du sang périphérique (CMSP) de mouton. Nos résultats ont montré qu'egr-miR-71 était enrichi dans l'exosome sécrété par les protoscolex ayant une activité biologique. Ces exosomes contenant egr-miR-71 ont été facilement internalisés et ont ensuite induit la dérégulation des cytokines (IL-10 et TNF-α), de l'oxyde nitrique (NO) et des composants clés (CD14 et IRF5) de la voie LPS/TLR4 dans les CMSP de mouton co-incubées. De même, la surexpression d'egr-miR-71 a également modifié les fonctions immunitaires mais a montré des différences évidentes dans la régulation des cytokines et des composants clés, inhibant de préférence les cytokines pro-inflammatoires (IL-1α, IL-1ß et TNF-α). Ces résultats démontrent que l'egr-miR-71 exosomal est bioactif et possède une capacité d'immunomodulation des CMSP, potentiellement impliquée dans les réponses immunitaires lors d'une infection à E. granulosus.

Interplays of liver fibrosis-associated microRNAs: Molecular mechanisms and implications in diagnosis and therapy.

microRNAs (miRNAs) are a class of non-coding functional small RNA composed of 21-23 nucleotides, having multiple associations with liver fibrosis. Fibrosis-associated miRNAs are roughly classified into pro-fibrosis or anti-fibrosis types. The former is capable of activating hepatic stellate cells (HSCs) by modulating pro-fibrotic signaling pathways, mainly including TGF-ß/SMAD, WNT/ß-catenin, and Hedgehog; the latter is responsible for maintenance of the quiescent phenotype of normal HSCs, phenotypic reversion of activated HSCs (aHSCs), inhibition of HSCs proliferation and suppression of the extracellular matrix-associated gene expression. Moreover, several miRNAs are involved in regulation of liver fibrosis via alternative mechanisms, such as interacting between hepatocytes and other liver cells via exosomes and increasing autophagy of aHSCs. Thus, understanding the role of these miRNAs may provide new avenues for the development of novel interventions against hepatic fibrosis.

A Systematic Government-Driven Green Development Transformation Strategy with Chinese Characteristics: The Case Study of the Xining Metropolitan Area.

In the 21st century, the tension between economic growth, resources and the environment in countries around the world is increasing, and the sustainable development of the economy and society is under great pressure. Green development has become the only way for countries to promote sustainable development. Generally, capitalist countries achieve their green development goals through increasingly strict environmental protection regulations, technological upgrading, industrial upgrading and global transfer based on market mechanisms and legal environments. Evidently, this green development strategy relies on the core position of Western countries in the global technological leadership and the global division of labor. However, limited in terms of their economic strength and by technical barriers, how can developing countries, led by China, in the marginal position in the global market competition, carry out green development transformation? In line with the "high-quality development" strategy, governments at all levels in China are actively exploring green development strategies with their own characteristics. Based on the Second Tibetan Plateau Scientific Expedition and Research and the face-to-face interview method, this paper summarizes a new strategy of systematic government-driven green development combining internal and external factors in the underdeveloped areas of inland China, which has gradually formed in the Xining metropolitan area (XMA) in the past 20 years. This strategy has the following characteristics: Firstly, during the period of rapid growth, the XMA areas have promoted each other through new urbanization and new industrialization and jointly promoted the formation of a green development turn in the new era. Secondly, the government is the core actor and driving force of China's regional green development and has gradually formulated and implemented a series of policy systems during this development. Restricted by local economic backwardness and low industrial profits, the implementation of green government policies tends to be mandatory. The majority of urban residents and rural people support this transformation because they have benefited from the transformation process. Thirdly, this green development strategy is reflected in many aspects, such as industry, ecology, the environment, space and transportation, and is part of a systematic, green-oriented transformation. Fourthly, the advantages of the socialist system with Chinese characteristics are the guarantee of the green development strategy. It is noteworthy that this kind of green development transformation requires a large amount of "additional" investment and the "rapid" upgrade of the industry. Therefore, it requires more time and the understanding and assistance of all sectors of society.

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.

The Multiple Cooperative Mechanism and Globalization Path of Small Inland Cities in China: A Showcase Study of Dunhuang, China.

Currently, urbanization driven by global capital flows entails a main trend in many large cites in China, while global capital investment in small inland cities especially in western China is extremely scarce, where their globalization characters the powerful nationalization power and market activation. Dunhuang, a small inland city in western China, has transformed successfully from an agricultural county to an international tourist city, a platform for worldwide cultural communication, and a node city in the Belt and Road region because of its unique and brilliant resources: Mogao Grottoes and Dunhuangology. Therefore, this paper develops a conceptual framework of the multiple cooperative mechanisms and globalization path (MCMGP) of Dunhuang, elaborating the process of industrial transformation, urban globalization, and multiple cooperative mechanisms between government and market actors based on interviewing records and statistics. Findings show that the MCMGP features government-led intervention, resource orientation, and centralization that embodies the driver of state-owned enterprises (SOEs). Also, the MCM in Dunhuang's globalization contains the mechanism of enrolment, mobilization and action, governance and global marketing, distributed in the two phases. Equally important, in response to the Belt and Road Initiative (BRI) and Silk Road (Dunhuang) International Cultural Expo (SRDICE) from the state, the city government has significantly reinvested and refined cultural tourism via governance mechanisms, carving out a key node city in the Silk Road and elevating an international tourist city. Environmentally, Dunhuang's tourism internationalization enhances the process of the development of a sustainable shared mobility industry. Furthermore, its tourism development and social-ecology system maintain the synergistic relationships which international tourism promotes such as urban ecosystem and public welfare and in turn, social-ecological enhancement serve Dunhuang's international tourism well. Practical implications of how Dunhuang's experience may have lessons for others are discussed in China's peculiar socialist market economy discourse.

Machine learning based personalized promotion strategy of piglets weaned per sow per year in large-scale pig farms.

BACKGROUND: The purpose of this study was to analyze the relationship between different productive factors and piglets weaned per sow per year (PSY) in 291 large-scale pig farms and analyze the impact of the changes in different factors on PSY. We chose nine different algorithm models based on machine learning to calculate the influence of each variable on every farm according to its current situation, leading to personalize the improvement of the impact in the specific circumstances of each farm, proposing a production guidance plan of PSY improvement for every farm. According to the comparison of mean absolute error (MAE), 95% confidence interval (CI) and R2, the optimal solution was conducted to calculate the influence of 17 production factors of each pig farm on PSY improvement, finding out the bottleneck corresponding to each pig farm. The level of PSY was further analyzed when the bottleneck factor of each pig farm changed by 0.5 standard deviation (SD). RESULTS: 17 production factors were non-linearly related to PSY. The top five production factors with the highest correlation with PSY were the number of weaned piglets per litter (WPL) (0.6694), mating rate within 7 days after weaning (MR7DW) (0.6606), number of piglets born alive per litter (PBAL) (0.6517), the total number of piglets per litter (TPL) (0.5706) and non-productive days (NPD) (- 0.5308). Among nine algorithm models, the gradient boosting regressor model had the highest R2, smallest MAE and 95% CI, applied for personalized analysis. When one of 17 production factors of 291 large-scale pig farms changed by 0.5 SD, 101 pig farms (34.7%) can increase 1.41 PSY (compared to its original value) on average by adding the production days, and 60 pig farms (20.6%) can increase 1.14 PSY on average by improving WPL, 45 pig farms (15.5%) can increase 1.63 PSY by lifting MR7DW. CONCLUSIONS: The main productive factors related to PSY included WPL, MR7DW, PBAL, TPL and NPD. The gradient boosting regressor model was the optimal method to individually analyze productive factors that are non-linearly related to PSY.

How Does Family Intergenerational Relationships Affect the Life Satisfaction of Middle-Aged and Elderly Parents in Urban Only-Child Families in Chengdu, China.

Over the past 40 years, the implementation of the family planning policy in China has led to the creation of many only-child families. In the process of modernization and urbanization, it is critical to focus on the intergenerational relationships in only-child families and their associational mechanism on the life satisfaction of middle-aged and elderly parents, which has crucial implications for them staying active and healthy aging. Using the survey data from Chengdu, China, this study analyzed the characteristics of only-child parents' life satisfaction and family intergenerational relationships, and explored the associational mechanism of family intergenerational relationships on only-child parents' life satisfaction in urban families, as well as the possible moderating role of gender. The results indicate that there are gender differences in the life satisfaction of only-child parents in urban families, and men are more satisfied than women. Moreover, parents of sons and daughters differ in life satisfaction from the dual-gender perspective. Parents of daughters are likely to have higher life satisfaction, especially mothers. The only-child families have not moved toward nucleation in urban families, and intergenerational members maintain close contact and provide frequent mutual support to achieve individual and family development. There are significant gender differences in structural, associational, affectual, and functional solidarity among only-child. This study confirms that there are differences in the associational mechanism of family intergenerational relationships on life satisfaction in different dimensions. Affectual solidarity is the most influential factor of life satisfaction. In terms of normative and consensual solidarity, gender plays a moderating role. For men, normative and consensual solidarity is beneficial for improving life satisfaction, but it has an insignificant effect on women. The effects of structural solidarity, association solidarity, and functional solidarity are not significant.

Escherichia coli carrying IncI2 plasmid-mediated mcr-1 genes in crested ibis (Nipponia nippon).

Antimicrobial resistance is a quintessential One Health issue, among the most serious 21st century global threats in human and veterinary medicine. Wild animals are usually not directly exposed to clinically relevant antibiotics; however, antibacterial resistance in wild animals has been increasingly reported worldwide in parallel to the situation in human and veterinary medicine. In this work, we collected 100 fecal samples from the crested ibis protected areas. A total of eight Escherichia coli (E. coli) isolates positive for mcr-1 were obtained, and all of them were analyzed using WGS (whole genome sequencing). The WGS analysis showed that the isolates were assigned to four different sequence types (ST) overall. The antibiotic susceptibility profile showed that of eight E. coli isolates, six strains exhibited resistance to tetracycline and all mcr-1-positive E. coli (MCREC) strains showed resistance to colistin. Our findings importantly document the epidemic spread of MCREC in crested ibis in China.

Comparative Transcriptomic Analysis Reveals the Regulated Expression Profiles in Oreochromis niloticus in Response to Coinfection of Streptococcus agalactiae and Streptococcus iniae.

Tilapia (Oreochromis sp.) is one of the important economical fishes in the world. Streptococcosis is commonly found in tilapia, causing severe and devastating effects in tilapia cultures. Streptococcus agalactiae and Streptococcus iniae are the predominant pathogens causing tilapia streptococcosis. To understand the molecular mechanisms underlying differential streptococcal infection patterns, Nile tilapias (Oreochromis niloticus) were infected by 1 × 107 CFU/mL S. agalactiae, 1 × 107 CFU/mL S. iniae, and 1 × 107 CFU/mL S. agalactiae and S. iniae (1:1), respectively, and transcriptome analysis was conducted to the intestine samples of Nile tilapia (Oreochromis niloticus) at 6, 12, 24 h, and 7 days post-infection. A total of 6,185 genes that differentially expressed among groups were identified. Eight differentially expressed genes (DEGs) including E3 ubiquitin-protein ligase TRIM39-like, C-X-C motif chemokine 10-like(CXCL 10), C-C motif chemokine 19-like, interleukin-1 beta-like, IgM heavy chain VH region, partial, IgG Fc-binding protein, proteasome subunit beta type-8 (PSMB8), and ATP synthase F(0) complex subunit B1, mitochondrial that involved in the immune system were selected, and their expression levels in the coinfection group were significantly higher than those in either of the single infection groups. These genes were associated with four different KEGG pathways. Additionally, the differential expression of eight DEGs was validated by using the RT-qPCR approach, and their immunological importance was discussed. The results provided insights into the responses of tilapia against S. agalactiae and S. iniae at the transcriptome level, promoting our better understanding of immune responses for aquatic animal against Streptococcus.

The Coupling Coordination Degree of Economic, Social and Ecological Resilience of Urban Agglomerations in China.

This paper refines the fuzzy logic method, while constructing a theoretical model of the relationship between economic resilience, social resilience and ecological resilience, and evaluates the coupling coordination between the economic-social-ecological resilience of 197 prefecture-level cities in China's urban agglomerations in 2019. Findings include: (1) The mean ecological resilience of China's urban agglomerations in 2019 was the highest, followed by economic and social resilience. (2) Promoting urban agglomerations had higher resilience scores in the three dimensions, especially in the economic dimension. Growing urban agglomerations had low resilience values on the whole, especially economic resilience. (3) The mean coupling coordination degree of economic-social-ecological resilience ranged from near-incoordination to narrow balance. (4) The coupling coordination degree between the two coincided with the positioning of existing urban agglomerations. (5) Economic resilience had the most significant impact on the coupling coordination. Finally, we give differentiated countermeasures to improve the resilience of urban agglomerations. This study aims to contribute to the promotion of urban resilience research, and helps to plan and design more rational urban economic-social-ecological systems, thereby enhancing the ability of cities to cope with any uncertainties and contingencies.

Impacts of industrial agglomeration on industrial pollutant emissions: Evidence found in the Lanzhou-Xining urban agglomeration in western China.

Industrial agglomeration does not only promote economic and social prosperity of urban agglomeration, but also increases industrial pollution, which poses a health risk to the general public. The Lanzhou-Xining urban agglomeration in western China is characterized by industrial agglomeration and serious industrial pollution. Based on the county panel data of the Lanzhou-Xining urban agglomeration in western China from 2010 to 2018, a research of the impacts of industrial agglomeration on industrial pollutant emissions was conducted by using spatial analysis technology and spatial econometric analysis. The results indicate that industrial agglomeration is an important factor leading to an increase in industrial pollutant emissions. In addition, population density, economic level, and industrial structure are also important factors that lead to the increase in industrial pollutant emissions. However, technological level has led to the reduction in industrial pollutant emissions. Furthermore, industrial pollutant emissions are not only affected by the industrial agglomeration, population density, economic level, industrial structure, and technological level of the county but also by those same factors in the surrounding counties, owing to the spatial spillover effect. Joint development of green industries and control of industrial pollutant emissions is an inevitable result for the Lanzhou-Xining urban agglomeration in western China.

Re-emergence of H5N8 highly pathogenic avian influenza virus in wild birds, China.

In mid-November 2020, deaths of whooper swan were reported in the Yellow River Reservoir Area, China. In the present study, we describe the genetic characterizations and phylogenetic relationships of four clade 2.3.4.4b H5N8 highly avian influenza viruses (HPAIVs) identified from a sick whooper swan and environmental samples collected in the Yellow River Reservoir Area in late November 2020. They were closely related to recent H5Nx HPAIVs causing outbreaks in Eurasia in the 2020-2021 influenza season, suggesting these isolates might be imported into China via migratory birds. The newly identified H5N8 HPAIVs possessed Q226 and G228 (H3 numbering), indicating that they prefer to avian-like receptors. However, they had three mutations falling within known antigenic regions, including T144A in antigenic region A, T192I in antigenic region B, and N240D in antigenic region D. Our study highlights the risk of the rapid global spread of H5N8 HPAIVs and the necessity for continuous monitoring of avian influenza viruses in wild birds.

Intergenerational Factors Influencing Household Cohabitation in Urban China: Chengdu.

Family composition impacts individual consumption habits, which may potentially transform urban integral space structure. Due to the reform in the housing system at the end of the 1990s and increases in residents' income, houses became more affordable, and intergenerational household cohabitation is no longer the primary pattern. Nonetheless, as families change, it still remains an important form of family composition. Intergenerational support is important in household habitation. This study examines the temporal changes and the structure of intergenerational household cohabitation. Moreover, intergenerational factors in groups of all genders and ages are analyzed. We found that intergenerational household cohabitation in Chengdu comprises three structures: elders living with married children, elders living with unmarried children, and elders living with grandchildren. According to multiple logistic regression, we can see that inadequate housing, economy of costs, cases of emergency, fear of loneliness, care of grandchildren, and poor health have marked effects on household cohabitation, and the positive or negative effects are distinct regarding different structures. To be more specific, the significance of financial support in family composition decreases, and that of support in daily care increases with age. The influence of financial support, daily care support, and emotional support peaks among those aged between 35-60, followed by individuals under 35, and those aged over 60. Financial support is comparatively important for individuals under 35, and females attach more importance to emotional support in intergenerational household cohabitation. The findings provide a basis for subsequent studies of family composition.

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.

Insight into Medicinal Chemistry Behind Traditional Chinese Medicines: p-Hydroxybenzyl Alcohol-Derived Dimers and Trimers from Gastrodia elata.

From an aqueous extract of "tian ma" (the steamed and dried rhizomes of Gastrodia elata), ten new compounds gastrodibenzins A-D (1-4) and gastrotribenzins A-F (5-10), along with known analogues (11-20), having structure features coupling between two and three p-hydroxybenzyl-derived units via carbon- and/or ether-bonds, were isolated and characterized by spectroscopic data analysis. Meanwhile, the new compounds 5a, 6a, 8a, 22, and 23, as well as the known derivatives 13a, 14a, 15, 17-21, 24, 25, and p-hydroxybenzyl aldehyde were isolated and identified from a refluxed aqueous solution of p-hydroxybenzyl alcohol. Methylation of 5a and 6a in methanol and ethylation of 6a, 8a, 13a, and 14a in ethanol produced 5 and 6 and 7, 8, 13, and 14, respectively. using ultra-performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UPLC-HRESIMS) analysis of the refluxed solutions of p-hydroxybenzyl alcohol and the refluxed extracts of the fresh G. elata rhizome and "tian ma" extracts indicated consistent production and variation of the dimeric and trimeric derivatives of p-hydroxybenzyl alcohol upon extracting solvents and refluxing time. In various assays, the dimeric and trimeric derivatives showed more potent activities than p-hydroxybenzyl alcohol itself and gastrodin, which are the main known active constituents of "tian ma". These results revealed for the first time that the more effective dimers and trimers can be produced through condensation of the co-occurring p-hydroxybenzyl alcohol during processing and decocting of the G. elata rhizomes, demonstrating insights into medicinal chemistry behind application protocols of traditional Chinese medicines.

Dominant subtype switch in avian influenza viruses during 2016-2019 in China.

We have surveyed avian influenza virus (AIV) genomes from live poultry markets within China since 2014. Here we present a total of 16,091 samples that were collected from May 2016 to February 2019 in 23 provinces and municipalities in China. We identify 2048 AIV-positive samples and perform next generation sequencing. AIV-positive rates (12.73%) from samples had decreased substantially since 2016, compared to that during 2014-2016 (26.90%). Additionally, H9N2 has replaced H5N6 and H7N9 as the dominant AIV subtype in both chickens and ducks. Notably, novel reassortants and variants continually emerged and disseminated in avian populations, including H7N3, H9N9, H9N6 and H5N6 variants. Importantly, almost all of the H9 AIVs and many H7N9 and H6N2 strains prefer human-type receptors, posing an increased risk for human infections. In summary, our nation-wide surveillance highlights substantial changes in the circulation of AIVs since 2016, which greatly impacts the prevention and control of AIVs in China and worldwide.

Mycobacterial PPE13 activates inflammasome by interacting with the NATCH and LRR domains of NLRP3.

Pathogenic mycobacteria, such as Mycobacterium tuberculosis, Mycobacterium bovis, and Mycobacterium marinum, can trigger NLRP3 inflammasome activation leading to maturation and secretion of interleukin 1ß (IL-1ß). However, the mycobacterial factors involved in the activation of NLRP3 inflammasome are not fully understood. Here, we identified that the PPE family protein PPE13 was responsible for the induction of IL-1ß secretion in a NLRP3 inflammasome-dependent manner. We found that the recombinant Mycobacterium smegmatis expressing PPE13 activates NLRP3 inflammasome, thereby inducing caspase-1 cleavage and IL-1ß secretion in J774A.1, BMDMs, and THP-1 macrophages. To examine whether this inflammasome activation was triggered by PPE13 rather than components of M. smegmatis, PPE13 was introduced into the aforementioned macrophages by lentivirus as a delivery vector. Similarly, this led to the activation of NLRP3 inflammasome, indicating that PPE13 is a direct activator of NLRP3 cascade. We further demonstrated that the NLRP3 complex activated the inflammasome cascade, and the assembly of this complex was facilitated by PPE13 through interacting with the LRR and NATCH domains of NLRP3. Finally, we found that all PPE13 proteins isolated from M. tuberculosis, M. bovis, and M. marinum can activate NLRP3 inflammasome through binding to NLRP3, which requires C-terminal repetitive MPTR domain of PPE13. Thus, we, for the first time, revealed that PPE13 triggers the inflammasome-response by interacting with the MPTR domain of PPE13 and the LRR and NATCH domains of NLRP3. These findings provide a novel perspective on the function of PPE proteins in the immune system during mycobacteria invasion.