Analysis of Prevalence and Related Factors of Cyberbullying-Victimization among Adolescents.

BACKGROUND/OBJECTIVES: Cyberbullying is an increasingly serious issue that negatively impacts the mental and physical health of adolescents. This study aims to report the prevalence rates of adolescent cyberbullying-victimization and its associated related factors, providing a scientific basis for targeted efforts to protect the mental and physical well-being of adolescents; Methods: From March to May 2019, there were 13 high schools and 33 middle schools in Yixing, with a student ratio of 2:1 between middle and high school. Using a random cluster sampling method, we selected four high schools and three middle schools based on this ratio, resulting in a total of 13,258 students. We conducted a survey using a self-designed questionnaire to investigate the experiences of adolescents with cyberbullying and victimization, comparing the differences in cyberbullying-victimization based on various demographic characteristics. Additionally, we employed a multifactorial logistic regression model to analyze the associated factors; Results: The rate of adolescents who declared themselves as cyberbully-victims is 2.9%. The results of the logistic regression analysis indicate that being male, having both parents working outside the home, experiencing occasional or large conflicts among family members, being subjected to punishment-and-abuse child discipline, always or often using social software (websites), enjoying playing single or multiplayer games, self-smoking, and self-drinking were associated with a higher likelihood of being a cyberbully-victim (p < 0.05); Conclusions: Adolescent cyberbullying-victimization is affected by personal, family, and social factors. Therefore, comprehensive strategies and measures are needed to intervene in this problem.

Sustainable food systems under environmental footprints: The delicate balance from farm to table.

In today's world, agriculture is not only about food production but also a critical factor in global environmental change, economic stability, and human health, among other aspects. With population growth and increasingly scarce resources, exploring sustainable development of food systems has become crucial. Achieving this goal requires striking a delicate balance among food security, economic development, ecological environment, and human health. Traditional approaches to sustainable agricultural development research often focus solely on singular domains, overlooking the inherent connections and interactions among environmental, socioeconomic, and health dimensions. This perspective limits our comprehensive understanding of food systems. Environmental footprint assessments can be integrated with economic, systemic, and decision models to analyze environmental, socioeconomic, and health issues within food systems. This integration accurately captures the diversity, overlap, accumulation, and heterogeneity of environmental pressures resulting from human and natural factors. Therefore, we propose an innovative conceptual framework that considers environmental, socioeconomic, and health dimensions as crucial components, with the environmental footprint indicators at its core, to link various stages from farm to table. This framework constructs an evidence gap map, integrating dispersed data and perspectives from existing literature, thus showing knowledge gaps across these domains. Such an interdisciplinary approach not only provides a more comprehensive perspective on the multidimensional complexity of sustainable food systems but also reveals potential synergies and conflicts among environmental, socioeconomic, and health domains, thereby guiding more comprehensive and cautious policy-making. Importantly, it provides direction for future research to achieve the sustainable development of food systems, emphasizing the necessity of a comprehensive, integrated research perspective, particularly in strengthening studies on composited footprints, viewing the entire farm-to-table continuum holistically. Stakeholders must collaborate and coordinate environmental, socioeconomic, and health objectives to drive the sustainable development of food systems.

Pharmacophylogenetic relationships of genus Dracocephalum and its related genera based on multifaceted analysis.

The Lamiaceae genus Dracocephalum, with over 30 species, is believed to have considerable medicinal properties and is widely used in Eurasian ethnomedicine. Numerous studies have researched on the geographical distribution, metabolite identification, and bioactivity of Dracocephalum species, especially amidst debates concerning the taxonomy of its closely related genera Hyssopus and Lallemantia. These discussions present an opportunity for pharmacophylogenetic studies of these medicinal plants. In this review, we collated extensive literature and data to present a multifaceted view of the geographical distribution, phylogenetics, phytometabolites and chemodiversity, ethnopharmacological uses, and pharmacological activities of Dracocephalum, Hyssopus, and Lallemantia. We found that these genera were concentrated in Europe, with species adapted to various climatic zones. These genera shared close phylogenetic relationships, with Dracocephalum and Hyssopus displaying intertwined patterns in the phylogenetic tree. Our review assessed more than 900 metabolites from these three genera, with terpenoids and flavonoids being the most abundant. Researchers have recently identified novel metabolites within Dracocephalum, expanding our understanding of its chemical constituents. Ethnopharmacologically, these genera have been traditionally used for treating respiratory, liver and gall bladder diseases. Extracts and metabolites from these genera exhibit a range of pharmacological activities such as hepatoprotective, anti-inflammation, antimicrobial action, anti-hyperlipidaemia, and anti-tumour properties. By integrating phylogenetic analyses with network pharmacology, we explored the intrinsic links between metabolite profiles, traditional efficacy, and modern pharmacology of Dracocephalum and its related genera. This study contributes to the discovery of potential medicinal value from closely related species of Dracocephalum and aids in the development and sustainable use of medicinal plant resources.

A virulent milRNA inhibits host immunity by silencing a host receptor-like kinase MaLYK3 and facilitates infection by Fusarium oxysporum f. sp. cubense.

MicroRNA-like RNAs (milRNAs) play a significant role in the infection process by plant-pathogenic fungi. However, the specific functions and regulatory mechanisms of fungal milRNAs remain insufficiently elucidated. This study investigated the function of Foc-milR138, an infection-induced milRNA secreted by Fusarium oxysporum f. sp. cubense (Foc), which is the causal agent of Fusarium wilt of banana. Initially, through precursor gene knockout and phenotypic assessments, we confirmed that Foc-milR138 acts as a virulent milRNA prominently upregulated during the early stages of Foc infection. Subsequent bioinformatic analyses and transient expression assays in Nicotiana benthamiana leaves identified a host receptor-like kinase gene, MaLYK3, as the direct target of Foc-milR138. Functional investigations of MaLYK3 revealed its pivotal role in triggering immune responses of N. benthamiana by upregulating a suite of resistance genes, bolstering reactive oxygen species (ROS) accumulation and callose deposition, thereby fortifying disease resistance. This response was markedly subdued upon co-expression with Foc-milR138. Expression pattern analysis further verified the specific suppression of MaLYK3 by Foc-milR138 during the early root infection by Foc. In conclusion, Foc secretes a virulent milRNA (Foc-milR138) to enter the host banana cells and inhibit the expression of the plant surface receptor-like kinase MaLYK3, subverting the disease resistance activated by MaLYK3, and ultimately facilitating pathogen invasion. These findings shed light on the roles of fungal milRNAs and their targets in resistance and pathogenicity, offering promising avenues for the development of disease-resistant banana cultivars.

Research on planting planning of Glycyrrhiza uralensis in Naiman Banner based on MaxEnt model and remote sensing technology.

Benefits of Glycyrrhiza uralensis include removing heat, detoxifying, and moistening the lungs, easing coughs, refueling the spleen, and balancing medications. In addition to providing theoretical guidance for the development of the G. uralensis industry and rural revitalization plan, it is anticipated that this paper will also provide basic data for the formulation of production layout of the G. uralensis industry at the county level, the control of cultivation industry direction, the establishment of high-quality G. uralensis cultivation technology system. The Maximum Entropy (MaxEnt) model was used to simulate the potential distribution of G. uralensis, a Chinese medicine resource, in Naiman Banner. By conducting a field inquiry and a broad assessment of the available Chinese medicine resources, the distribution information was acquired. The random forest technique was used to classify G. uralensis. The phenological cycle and development mode of vegetation, which exhibits diverse temporal traits and aids in identification, were elucidated through long-term series analysis. The random forest classification algorithm based on multiple features showed high accuracy in remote sensing (RS) recognition of G. uralensis. Comparative analysis of the MaxEnt and RS results showed that the planting area of G. uralensis was smaller than that of its potential distribution. The expansion to high-suitability areas planting should be prioritized. Based on the dual analysis of regional and remote sensing, it not only proved the great potential of using geographic information to predict the distribution of G. uralensis, but also verified the great potential of extracting the distribution of G. uralensis from GF-6 images. These results will guide the planting and development of G. uralensis in Naiman Banner and a scientific basis for the development of G. uralensis economy, conducive to optimizing the ecological environment and promoting rural revitalization programs.

Unlocking Auxetic Behavior in Recyclable Thermosetting Foams Enabled by Dynamic Disulfide Cross-linking Strategy.

Auxetic foams with a negative Poisson's ratio (NPR) have attracted considerable attention in material engineering due to their outstanding performance in seismic and energy absorption. Nevertheless, thermoplastic auxetic foams are compromised by weak non-covalent crosslinking that diminishes the mechanical strength and durability of foams. Conversely, thermosetting foams with chemical crosslinking, although mechanically robust, face challenges in elaborating auxetic structure and in achieving recyclability. Herein, an alternative approach is proposed to tackle this dilemma by incorporating dynamic disulfide bonds into the polymer network for preparing a thermosetting polyurethane foam with covalent adaptable network. By leveraging the unidirectional multi-effect compression technique, the topological network reorganization of foam is induced, transforming the initial circular open-cell structure into a re-entrant cell structure. This structural transformation endows the foam with stable NPR capability, achieving a minimum Poisson's ratio value of -0.4 within 30% compressive strain. Benefiting from its reinforced network structure, the foam also demonstrates high compressive strength (6.47 MPa) and tensile strength (1.67 MPa). Furthermore, it is recyclable and can be recompressed into thermosetting films. This work offers a straightforward approach to making auxetic thermosetting foams with good mechanical and recyclable properties, which is interesting for the development of high-performance auxetic materials.

The association of school bullying victimization and suicidal ideation among school-aged adolescents in Yixing City, China.

BACKGROUND: Research on the associations of type-specific bullying victimization and poly-bullying victimization with suicidal ideation is limited and contradictory. This study aimed to examine these associations among school-aged adolescents. METHODS: A total of 13,258 students from 3 middle schools and 4 high schools in a southern city in China completed a cross-sectional questionnaire in 2019. Multinomial logistic regressions were used to examine associations between type-specific bullying victimization and poly-victimization with suicidal ideation. RESULTS: The latent class analysis identified three subgroups of suicidal ideation: low (70.0 %), moderate (24.0 %), and high (6.0 %). Compared with non-bullying victimization in the past year, the corresponding adjusted odds ratios [aOR] (95 % CI) of moderate and high suicidal ideation for only physical victimization were 1.74 (1.15, 2.63) and 2.51 (1.18, 5.38), respectively, for only relational victimization were 1.26 (0.97, 1.62) and 2.48 (1.65, 3.71), respectively, for only verbal victimization were 1.45 (1.17, 1.78) and 1.42 (0.90, 2.22), respectively, for only property victimization were 1.30 (1.03, 1.65) and 1.31 (0.80, 2.16), respectively, and for sexual victimization were 1.38 (1.03, 1.83) and 2.45 (1.50, 3.99), respectively. Poly-bullying victimization was associated with moderate (aORtwo = 1.45 (1.24, 1.70); aORthree = 1.70 (1.41, 2.05), aORfour = 2.03 (1.61, 2.58), aORfive = 2.48 (1.74, 3.53)) and high suicidal ideation (aORtwo = 2.01 (1.49, 2.70), aORthree = 3.87 (2.86, 5.25), aORfour = 4.55 (3.20,6.46), aORfive = 7.90 (5.06, 12.33)). LIMITATIONS: The research design is cross-sectional, and relevant data was based on self-reports. CONCLUSIONS: Different types of bullying victimization were associated with suicidal ideation and poly-bullying victimization and suicidal ideation association shows a dose-response-relationship.

Effect of cruciferous vegetable intake on cancer: An umbrella review of meta-analysis.

Previous systematic evaluations and meta-analyses of the relationship between cruciferous vegetable (CV) intake and cancer risk have yielded inconsistent results. Herein, we summarize and evaluate the existing data and examine the relationship between CV intake and cancer risk. We searched four databases for cancer risk as a key outcome indicator. AMSTAR-2 was used to evaluate the methodological quality of the included systematic reviews, PRISMA 2020 was used to evaluate the report quality, and corrected coverage area analysis was used to evaluate the duplication rate of the original documents. Overall, 22 meta-analyses involving 175 independent cancer studies were included. Evidence on lung, gastric, prostate, breast, endometrial, and ovarian cancer, as well as renal cell carcinoma, suggests a potential association between cancer and CV intake, which influences the risk of various cancers. Future research should focus on improving methods and techniques, controlling influencing factors, elucidating underlying mechanisms, and improving evidence quality to demonstrate the association between CV intake and cancer. The potential role of dietary CVs in cancer control has implications for public health policies.

Virulence of banana wilt-causing fungal pathogen Fusarium oxysporum tropical race 4 is mediated by nitric oxide biosynthesis and accessory genes.

Fusarium wilt of banana, caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most damaging plant diseases known. Foc race 1 (R1) decimated the Gros Michel-based banana (Musa acuminata) trade, and now Foc tropical race 4 (TR4) threatens global production of its replacement, the Cavendish banana. Here population genomics revealed that all Cavendish banana-infecting Foc race 4 strains share an evolutionary origin distinct from that of R1 strains. Although TR4 lacks accessory chromosomes, it contains accessory genes at the ends of some core chromosomes that are enriched for virulence and mitochondria-related functions. Meta-transcriptomics revealed the unique induction of the entire mitochondrion-localized nitric oxide (NO) biosynthesis pathway upon TR4 infection. Empirically, we confirmed the unique induction of a NO burst in TR4, suggesting that nitrosative pressure may contribute to virulence. Targeted mutagenesis demonstrated the functional importance of fungal NO production and the accessory gene SIX4 as virulence factors.

Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.

Abdominal aortic aneurysm (AAA) is a degenerative disease that caused mortality in people aged >65. Senescence plays a critical role in AAA pathogenesis. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. Our Previous study found cyclic nucleotide phosphodiesterase 1C (PDE1C) exacerbate AAA through aggravate vascular smooth muscle cells (VSMCs) senescence by downregulating Sirtuin1 (SIRT1) expression and activity. Vinpocetine as a selective inhibitor of PDE1 and a clinical medication for cerebral vasodilation, it is unclear whether vinpocetine can rely on SIRT1 to alleviate AAA. This study showed that pre-treatment with vinpocetine remarkably prevented aneurysmal dilation and reduced aortic rupture in elastase-induced AAA mice. In addition, the elastin degradation, MMP (matrix metalloproteinase) activity, macrophage infiltration, ROS production, collagen fibers remodeling, and VSMCs senescence were decreased in AAA treated with vinpocetine. While these effects were unable to exert in VSMCs-specific SIRT1 knockout AAA mice. Accordingly, we revealed that vinpocetine suppressed migration, proliferation, and senescence in VSMCs. Moreover, vinpocetine reduced SIRT1 degradation by inhibiting lysosome-mediated autophagy. In conclusion, this study indicated that vinpocetine may be as a potential drug for therapy AAA through alleviate VSMCs senescence via the SIRT1-dependent pathway.

Traditional Use, Phytochemistry, Pharmacology, Toxicology and Clinical Applications of Persicae Semen: A Review.

Persicae Semen (Taoren), the seed of mature peaches consumed as both food and medicine, is native to the temperate regions of China, distributed in the provinces of North and East China, and currently cultivated worldwide. The primary components of Persicae Semen include volatile oil, protein, amino acids, amygdalin, and prunasin, all of which have pharmacological properties, such as anti-inflammatory, antioxidant, and immune regulatory effects, and are clinically used in the treatment of gynecological, cardiovascular, cerebrovascular, orthopedic, and digestive system diseases. This review provides a comprehensive perspective on the resource status, ethnopharmacology, phytochemistry, pharmacology, and toxicology, as well as the trend of Persicae Semen patent, global distribution, and clinical applications. This review will help facilitate the development and utilization of Persicae Semen in clinical settings.

Multifaceted insights into the environmental adaptability of Arnebia guttata under drought stress.

Introduction: Global warming has led to increased environmental stresses on plants, notably drought. This affects plant distribution and species adaptability, with some medicinal plants showing enhanced drought tolerance and increased medicinal components. In this pioneering study, we delve into the intricate tapestry of Arnebia guttata, a medicinal plant renowned for its resilience in arid environments. By fusing a rich historical narrative with cutting-edge analytical methodologies, this research endeavors to demystify the plant's intricate response to drought stress, illuminating its profound implications for medicinal valorization. Methods: The methodology includes a comprehensive textual research and resource investigation of A. guttata, regionalization studies, field sample distribution analysis, transcriptome and metabolome profiling, rhizosphere soil microbiome analysis, and drought stress experiments. Advanced computational tools like ArcGIS, MaxEnt, and various bioinformatics software were utilized for data analysis and modeling. Results: The study identified significant genetic variations among A. guttata samples from different regions, correlating with environmental factors, particularly precipitation during the warmest quarter (BIO18). Metabolomic analysis revealed marked differences in metabolite profiles, including shikonin content, which is crucial for the plant's medicinal properties. Soil microbial community analysis showed variations that could impact plant metabolism and stress response. Drought stress experiments demonstrated A. guttata's resilience and its ability to modulate metabolic pathways to enhance drought tolerance. Discussion: The findings underscore the complex interplay between genetic makeup, environmental factors, and microbial communities in shaping A. guttata's adaptability and medicinal value. The study provides insights into how drought stress influences the synthesis of active compounds and suggests that moderate stress could enhance the plant's medicinal properties. Predictive modeling indicates future suitable growth areas for A. guttata, aiding in resource management and conservation efforts. The research contributes to the sustainable development of medicinal resources and offers strategies for improving the cultivation of A. guttata.

An ethnobotanical survey on the medicinal and edible plants used by the Daur people in China.

BACKGROUND: The Daur people are one of the 55 minority ethnic groups in China and have lived in Northern China for 300 years. In traditional Daur medicine, medicinal and edible plants (MEPs) are utilised for health benefits and therapeutic purposes; however, related ethnobotanical knowledge is rarely reported, which is disadvantageous for the sustainable development of these MEPs. METHODS: Semi-structured interviews with 122 informants, six focus group discussions, and a resource survey were conducted in a Daur minority nationality area in Inner Mongolia from 2015 to 2020, and the data statistics were analysed. In this study, we simulated a system dynamics model aimed at understanding the multiple feedback mechanisms involved in the relationships between the cultural influences and socioeconomic factors, sustainable environment, and development of MEPs. RESULTS: A total of 52 species of MEPs were identified and relevant ethnobotanical knowledge was assessed using Daur medicinal species data from Inner Mongolia and the Xinjiang region, with the literature and Ewenki ethnic group data used for comparison. The most commonly used medicinal plant species by the Daur were found to be Betula pendula subsp. mandshurica, Artemisia integrifolia, Crataegus pinnatifida, Saposhnikovia divaricata, Artemisia argyi, and Jacobaea cannabifolia. The MEPs most frequently targeted the digestive and rheumatic immunity systems, as well as infectious diseases or parasitic infections and other common diseases and basic health issues. MEP knowledge was primarily limited to older generations; thus, the valuable ethnobotanical knowledge on traditional medicines must be protected from future losses. CONCLUSIONS: Our findings provide insights for future research aimed at exploiting the rich phytochemical diversity in traditional medicine and promote its use in modern lifestyles. Effective assessment and management of plant resources will lead to their application for the improvement of dietary diversity, nutrition, and health care.

Advances in research and utilization of botanical pesticides for agricultural pest management in Inner Mongolia, China.

Traditional Chinese herbal medicines not only cure human diseases, but also play an important role as insecticides. Compared with conventional chemical agents, traditional Chinese herbal medicines are characterized by low toxicity, low residues, and being eco-friendly, and they have become a research hotspot. Traditional Chinese herbal medicines have tremendous flexibility and indefinite potential. Therefore, this paper reviewed the types of insecticides belonging to traditional Chinese herbal medicines in Inner Mongolia, China, including their traditional uses, secondary metabolites, biological activities, action mechanisms, application methods, and development status. In addition, the most relevant issues involved in the development of traditional Chinese herbal medicines was discussed. We believe that traditional Chinese herbal medicines can be better implemented and developed; such that its other advantages, such as an insect repellent, can be promoted. Moreover, this study lays a solid foundation for further research on traditional Chinese herbal medicines in Inner Mongolia, China.

Exotic medicinal plants from the Silk Road promote the diversification of traditional Chinese medicines.

BACKGROUND: As a political, economic, and cultural exchange channel between ancient China and countries in Asia, Europe, and Africa, the Silk Road has promoted political, trade, and cultural exchanges between China and foreign countries in Chinese history and also promoted the development of traditional Chinese medicine. METHODS: This article summarizes the introduction of medicinal materials from the Han to Qing Dynasties, spanning approximately 2000 years. RESULTS: A total of 235 types of medicinal plant materials were imported. An analysis of 178 medicinal herbs of known origin, belonging to 72 families revealed their effectiveness in treating 20 diseases. The maximum number of medicinal herbs used to treat gastrointestinal and digestive disorders (GAS) was 122. The applications and origin of exotic medicinal materials, including draconis sanguis and olibanum have changed during the development of the Silk Road. Imported medicinal materials are affected by five factors, including local demand, adaptability, cultural exchange, scarcity, and medical theory. Five modes for introducing medicinal materials include the onshore Silk Road, the maritime Silk Road, diplomatic envoys and gifts, overseas Chinese, cultural exchange, and medical integration. The application of exotic medicinal materials expands the resources and application fields of traditional Chinese medicine, enriching the theory of traditional Chinese medicine. CONCLUSION: Traditional Chinese medicinal compounds introduced to China through the ancient Silk Road not only promoted their integration into foreign medicine but also had long-lasting impacts to date and over a wide range, thereby considerably affecting the pharmaceutical and general healthcare industries.

Mechanically Ultra-Robust Fluorescent Elastomer for Elaborating Auxetic Composite.

Fluorescent elastomers are predominantly fabricated through doping fluorescent components or conjugating chromophores into polymer networks, which often involves detrimental effects on mechanical performance and also makes large-scale production difficult. Inspired by the heteroatom-rich microphase separation structures assisted by intensive hydrogen bonds in natural organisms, an ultra-robust fluorescent polyurethane elastomer is reported, which features a remarkable fracture strength of 87.2 MPa with an elongation of 1797%, exceptional toughness of 678.4 MJ m-3 and intrinsic cyan fluorescence at 445 nm. Moreover, the reversible fluorescence variation with temperature could in situ reveal the microphase separation of the elastomer in real time. By taking advantage of mechanical properties, intrinsic fluorescence and hydrogen bonds-promoted interfacial bonding ability, this fluorescent elastomer can be utilized as an auxetic skeleton for the elaboration of an integrated auxetic composite. Compared with the auxetic skeleton alone, the integrated composite shows an improved mechanical performance while maintaining auxetic deformation in a large strain below 185%, and its auxetic process can be visually detected under ultraviolet light by the fluorescence of the auxetic skeleton. The concept of introducing hydrogen-bonded heteroatom-rich microphase separation structures into polymer networks in this work provides a promising approach to developing fluorescent elastomers with exceptional mechanical properties.

Litchi aspartic protease LcAP1 enhances plant resistance via suppressing cell death triggered by the pectate lyase PlPeL8 from Peronophythora litchii.

Plant cell death is regulated in plant-pathogen interactions. While some aspartic proteases (APs) participate in regulating programmed cell death or defense responses, the defense functions of most APs remain largely unknown. Here, we report on a virulence factor, PlPeL8, which is a pectate lyase found in the hemibiotrophic pathogen Peronophythora litchii. Through in vivo and in vitro assays, we confirmed the interaction between PlPeL8 and LcAP1 from litchi, and identified LcAP1 as a positive regulator of plant immunity. PlPeL8 induced cell death associated with NbSOBIR1 and NbMEK2. The 11 conserved residues of PlPeL8 were essential for inducing cell death and enhancing plant susceptibility. Twenty-three LcAPs suppressed cell death induced by PlPeL8 in Nicotiana benthamiana depending on their interaction with PlPeL8. The N-terminus of LcAP1 was required for inhibiting PlPeL8-triggered cell death and susceptibility. Furthermore, PlPeL8 led to higher susceptibility in NbAPs-silenced N. benthamiana than the GUS-control. Our results indicate the crucial roles of LcAP1 and its homologs in enhancing plant resistance via suppression of cell death triggered by PlPeL8, and LcAP1 represents a promising target for engineering disease resistance. Our study provides new insights into the role of plant cell death in the arms race between plants and hemibiotrophic pathogens.

A polyamino acid-based phosphatidyl polymer library for in vivo mRNA delivery with spleen targeting ability.

A qualified delivery system is crucial for the successful application of messenger RNA (mRNA) technology. While lipid nanoparticles (LNPs) are currently the predominant platform for mRNA delivery, they encounter challenges such as high inflammation and difficulties in targeting non-liver tissues. Polymers offer a promising delivery solution, albeit with limitations including low transfection efficiency and potential high toxicity. Herein, we present a poly(L-glutamic acid)-based phosphatidyl polymeric carrier (PLG-PPs) for mRNA delivery that combines the dual advantages of phospholipids and polymers. The PLGs grafted with epoxy groups were firstly modified with different amines and then with alkylated dioxaphospholane oxides, which provided a library of PLG polymers grafted with various phosphatidyl groups. In vitro studies proved that PLG-PPs/mRNA polyplexes exhibited a significant increase in mRNA expression, peaking 14 716 times compared to their non-phosphatidyl parent polymer. Impressively, the subset PA8-PL3 not only facilitated efficient mRNA transfection but also selectively delivered mRNA to the spleen instead of the liver (resulting in 69.73% protein expression in the spleen) once intravenously administered. This type of phosphatidyl PLG polymer library provides a novel approach to the construction of mRNA delivery systems especially for spleen-targeted mRNA therapeutic delivery.

Xanthoceras sorbifolium leaves alleviate hyperuricemic nephropathy by inhibiting the PI3K/AKT signaling pathway to regulate uric acid transport.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, Xanthoceras sorbifolium Bunge was first documented as "Wen Guan Hua" in the "Jiu Huang Ben Cao" in 1406 A.D. According to the "National Compilation of Chinese Herbal Medicine," X. sorbifolium leaves are sweet and flat in nature and can dispel wind and dampness, suggesting that their extract can be used to treat rheumatoid arthritis. X. sorbifolium Bunge has also been used to treat arteriosclerosis, hyperlipidemia, hypertension, chronic hepatitis, and rheumatism, complications associated with hyperuricemic nephropathy (HN), a condition characterized by kidney damage resulting from high levels of uric acid (UA) in the blood. AIM OF THE STUDY: The purpose of this study was to investigate the effects and underlying mechanisms of a 70% ethanol extract from X. sorbifolium leaves (EX) in alleviating HN. MATERIALS AND METHODS: A mouse model of hyperuricemia was established to initially evaluate the hypouricemic effects and determine the effective dose of EX. Phytochemical analyses were conducted using ultra high-performance liquid chromatography and liquid chromatography-mass spectroscopy. The potential key pathways of EX in the alleviation of HN were inferred using network pharmacology and bioinformatics. An HN rat model was then established, and experiments including biomarker detection, western blotting, reverse transcription quantitative polymerase chain reaction, immunohistochemical and Masson's trichrome staining, and transmission electron microscopy were conducted to evaluate the effect of EX on UA transporter expression in vitro. RESULTS: Network pharmacology and bioinformatics analyses revealed that the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was the key pathway for the alleviation of HN progression by EX. EX treatment reduced serum biomarkers in HN rats, downregulated the expression of p-PI3K, p-AKT, glucose transporter 9 (GLUT9), urate transporter 1 (URAT1), Collagen I, matrix metalloproteinase (MMP)-2, and MMP-9, and upregulated the expression of ATP binding cassette subfamily G member 2 (ABCG2) to improve renal interstitial fibrosis in HN rats. A high content of both quercitrin and cynaroside were identified in EX; their administration inhibited the increased expression of GLUT9 and URAT1 in damaged HK-2 cells. CONCLUSION: Our study provides evidence that EX alleviates HN. The potential mechanism underlying this effect may be the regulation of UA transporters, such as GLUT9 and URAT1, by limiting the activation of the PI3K/AKT signaling pathway to improve renal injury.