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"Zhang, Honglu"
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Lifestyle factors, glycemic traits, and lipoprotein traits and risk of liver cancer: a Mendelian randomization analysis
2024
The current state of knowledge on the relationship between lifestyle factors, glycemic traits, lipoprotein traits with liver cancer risk is still uncertain despite some attempts made by observational studies. This study aims to investigate the causal genetic relationship between factors highly associated with liver cancer incidence by using Mendelian randomization (MR) analysis. Employing MR analysis, this study utilized previously published GWAS datasets to investigate whether lifestyle factors, glycemic traits, and lipoprotein traits would affect the risk of liver cancer. The study utilized three MR methods, including inverse variance-weighted model (IVW), MR Egger, and weighted median. Furthermore, MR-Egger analyses were performed to detect heterogeneity in the MR results. The study also conducted a leave-one-out analysis to assess the potential influence of individual SNPs on the MR analysis results. MR-PRESSO was used to identify and remove SNP outliers associated with liver cancer. MR analyses revealed that 2-h glucose (odds ratio, OR 2.33, 95% confidence interval, CI 1.28–4.21), type 2 diabetes mellitus (T2DM, OR 1.67, 95% CI 1.18–2.37), body mass index (BMI, OR 1.67, 95% CI 1.18–2.37), waist circumference (OR 1.78, 95% CI 1.18–2.37) were associated with increased risk of liver cancer. On the contrary, apolipoproteins B (APOB, OR 0.67, 95% CI 0.47–0.97), and low-density lipoprotein (LDL, OR 0.62, 95% CI 0.42–0.92) were negatively related to liver cancer risk. Additionally, after adjusting for BMI, apolipoproteins A-I (APOA-I, OR 0.56, 95% CI, 0.38–0.81), total cholesterol (TC, OR 0.72, 95% CI, 0.54–0.94), and total triglycerides (TG, OR 0.57, 95% CI, 0.40–0.78) exhibited a significant inverse correlation with the risk of liver cancer. This study supports a causal relationship between 2-h glucose, T2DM, BMI, and waist circumference with the increased risk of liver cancer. Conversely, the study reveals a cause-effect relationship between TC, TG, LDL, APOA-I, and APOB with a decreased risk of liver cancer.
Journal Article
Nanoparticle-assembled bioadhesive coacervate coating with prolonged gastrointestinal retention for inflammatory bowel disease therapy
A key challenge for the effective treatment of gastrointestinal diseases including inflammatory bowel disease is to develop an orally administered drug delivery system capable of prolonged retention in the gastrointestinal tract. Herein we report a bioadhesive liquid coacervate based on hydrogen bonding-driven nanoparticle assembly. Free from electrostatic interactions, our fluid nanoparticle-assembled coacervate demonstrates significant pH- and salt-independent structural stability and forms a physically adhesive coating on a large surface area of intestinal tract with an extended residence time of more than 2 days to mediate the sustained release of preloaded water-soluble small molecule drugs in vivo. The orally administered drug-laden nanoparticle-assembled coacervate significantly mitigates the symptoms of inflammatory bowel disease, restores the diversity of gut microbiota, reduces systemic drug exposure, and improves the therapeutic efficacy in a rat acute colitis model compared with the oral administration of the same amount of drug in solution form. We suggest that the nanoparticle-assembled coacervate provides a promising drug delivery platform for management and treatment of numerous gastrointestinal diseases where controlled drug release with extended residence time is desired.
The development of a drug delivery system capable of prolonged retention in the gastrointestinal tract remains a clinical challenge. Here the authors present a bio-adhesive liquid coacervate coating on the intestinal tract that acts as a flowable drug carrier, mediates the sustained release of diverse drugs, and potentially enhances therapeutic efficacy against gastrointestinal diseases.
Journal Article
DNA nanostructures coordinate gene silencing in mature plants
by
Zhang, Huan
,
Cunningham, Francis J.
,
Aditham, Abhishek J.
in
Agrobacterium
,
Barriers
,
BASIC BIOLOGICAL SCIENCES
2019
Delivery of biomolecules to plants relies on Agrobacterium infection or biolistic particle delivery, the former of which is amenable only to DNA delivery. The difficulty in delivering functional biomolecules such as RNA to plant cells is due to the plant cell wall, which is absent in mammalian cells and poses the dominant physical barrier to biomolecule delivery in plants. DNA nanostructure-mediated biomolecule delivery is an effective strategy to deliver cargoes across the lipid bilayer of mammalian cells; however, nanoparticle-mediated delivery without external mechanical aid remains unexplored for biomolecule delivery across the cell wall in plants. Herein, we report a systematic assessment of different DNA nanostructures for their ability to internalize into cells of mature plants, deliver siRNAs, and effectively silence a constitutively expressed gene in Nicotiana benthamiana leaves. We show that nanostructure internalization into plant cells and corresponding gene silencing efficiency depends on the DNA nanostructure size, shape, compactness, stiffness, and location of the siRNA attachment locus on the nanostructure. We further confirm that the internalization efficiency of DNA nanostructures correlates with their respective gene silencing efficiencies but that the endogenous gene silencing pathway depends on the siRNA attachment locus. Our work establishes the feasibility of biomolecule delivery to plants with DNA nanostructures and both details the design parameters of importance for plant cell internalization and also assesses the impact of DNA nanostructure geometry for gene silencing mechanisms.
Journal Article
Engineering DNA nanostructures for siRNA delivery in plants
by
Zhang, Huan
,
Landry, Markita P.
,
Zhang, Honglu
in
631/61/350/354
,
631/61/447/2311
,
Agrochemicals
2020
Targeted downregulation of select endogenous plant genes is known to confer disease or pest resistance in crops and is routinely accomplished via transgenic modification of plants for constitutive gene silencing. An attractive alternative to the use of transgenics or pesticides in agriculture is the use of a ‘green’ alternative known as RNAi, which involves the delivery of siRNAs that downregulate endogenous genes to confer resistance. However, siRNA is a molecule that is highly susceptible to enzymatic degradation and is difficult to deliver across the lignin-rich and multi-layered plant cell wall that poses the dominant physical barrier to biomolecule delivery in plants. We have demonstrated that DNA nanostructures can be utilized as a cargo carrier for direct siRNA delivery and gene silencing in mature plants. The size, shape, compactness and stiffness of the DNA nanostructure affect both internalization into plant cells and subsequent gene silencing efficiency. Herein, we provide a detailed protocol that can be readily adopted with standard biology benchtop equipment to generate geometrically optimized DNA nanostructures for transgene-free and force-independent siRNA delivery and gene silencing in mature plants. We further discuss how such DNA nanostructures can be rationally designed to efficiently enter plant cells and deliver cargoes to mature plants, and provide guidance for DNA nanostructure characterization, storage and use. The protocol described herein can be completed in 4 d.
This protocol describes how to engineer DNA nanostructures with different sizes, shapes and mechanical properties; load them with a siRNA cargo; and evaluate their ability to silence genes in mature tobacco plants.
Journal Article
Coupling SAR and optical remote sensing data for soil moisture retrieval over dense vegetation covered areas
2025
Soil moisture is a key parameter for the exchange of substance and energy at the land-air interface, timely and accurate acquisition of soil moisture is of great significance for drought monitoring, water resource management, and crop yield estimation. Synthetic aperture radar (SAR) is sensitive to soil moisture, but the effects of vegetation on SAR signals poses challenges for soil moisture retrieval in areas covered with vegetation. In this study, based on Sentinel-1 SAR and Sentinel-2 optical remote sensing data, a coupling approach was employed to retrieval surface soil moisture over dense vegetated areas. Different vegetation indices were extracted from Sentinel-2 data to establish the vegetation water content (VWC) estimation model, which was integrated with the Water Cloud Model (WCM) to distinguish the contribution of vegetation layer and soil layer to SAR backscattering signals. Subsequently, the Oh model and the Look-Up Table (LUT) algorithm were used for soil moisture retrieval, and the accuracy of the result was compared with the traditional direct retrieval method. The results indicate that, for densely vegetated surfaces, VWC can be better reflected by multiple vegetation indices including NDVI, NDWI2, NDGI and FVI, the R 2 and RMSE of VWC estimation result is 0.709 and 0.30 kg·m -2 . After vegetation correction, the correlation coefficient increased from 0.659 to 0.802 for the VV polarization, and from 0.398 to 0.509 for the VH polarization. Satisfactory accuracy of soil moisture retrieval result was obtained with the Oh model and the LUT algorithm, VV polarization is found to be more suitable for soil moisture retrieval compared to VH polarization, with an R 2 of 0.672 and an RMSE of 0.048m 3 ·m -3 , the accuracy is higher than that of the direct retrieval method. The results of the study preliminarily verified the feasibility of the coupling method in soil moisture retrieval over densely veg etated surfaces.
Journal Article
Programming chain-growth copolymerization of DNA hairpin tiles for in-vitro hierarchical supramolecular organization
2019
Formation of biological filaments via intracellular supramolecular polymerization of proteins or protein/nucleic acid complexes is under programmable and spatiotemporal control to maintain cellular and genomic integrity. Here we devise a bioinspired, catassembly-like isothermal chain-growth approach to copolymerize DNA hairpin tiles (DHTs) into nanofilaments with desirable composition, chain length and function. By designing metastable DNA hairpins with shape-defining intramolecular hydrogen bonds, we generate two types of DHT monomers for copolymerization with high cooperativity and low dispersity indexes. Quantitative single-molecule dissection methods reveal that catalytic opening of a DHT motif harbouring a toehold triggers successive branch migration, which autonomously propagates to form copolymers with alternate tile units. We find that these shape-defined supramolecular nanostructures become substrates for efficient endocytosis by living mammalian cells in a stiffness-dependent manner. Hence, this catassembly-like in-vitro reconstruction approach provides clues for understanding structure-function relationship of biological filaments under physiological and pathological conditions.
Formation of biological filaments via intracellular supramolecular polymerization of proteins occurs under programmable and spatiotemporal control to maintain integrity. Here the authors devise a bioinspired isothermal chain-growth approach to programmably copolymerize DNA hairpin tiles into 1D nanofilaments.
Journal Article
Analysis of influencing factors and paths of synergistic development of water resources-economic society-ecological environment based on DIM modeling
2025
The intersection of climate change and human activities exacerbates the prominent contradiction between environmental resources and economic development. The synergistic development of water resources, economy and society, and ecological environment is particularly urgent. Therefore, accurately identifying its influencing factors and related pathways holds significant practical importance in resolving the contradiction between resources and economic development. This study constructs a system of influencing factors for the synergistic development of “water resources, economic society and ecological environment” from three dimensions, reveals the influencing relationship between indicators through the Decision Making Trial and Evaluation Laboratory (DEMATEL), determines the hierarchical structure of the influencing factors and the related paths through the Interpretive Structural Model (ISM), and classifies the influencing factors through the Matrix Multiplication Method of Cross Influence Matrix Multiplication (MICMAC). The results show that water resource factors are important cause factors and economic, social and ecological factors are essential effect factors. The factors influencing the synergistic development of “water resources, economic society and ecological environment” can be divided into four levels, of which the total water resources, precipitation and NDVI are at the bottom and are the most fundamental factors. The percentage of groundwater supply, total water supply, water resource utilization rate and energy consumption of 10,000 yuan of GDP are the deep core elements. Total grain output, water resources per capita, and water use per capita are the direct influencing factors. Finally, taking the Central Plains Urban Agglomeration as an example, selecting the identified important influencing factors and analyzing the level of synergistic development of its coupled system found that the degree of coupling coordination increased from 0.324 in 2011 to 0.978 in 2020. The water resources system showed a fluctuating change, and it is still the key to synergistic development. Analyzing the relationship between subsystems and clarifying the key factors for synergistic development of coupled systems are important for policy formulation, improving environmental governance and promoting high-quality economic development.
Journal Article
Investigation into the temporal impacts of drought on vegetation dynamics in China during 2000 to 2022
Quantifying vegetation’s response to drought and understanding its mechanisms is crucial for mitigating the adverse effects of drought disasters. The asymmetric cumulative and lag effects of drought on vegetation growth are widespread, yet the responses of different vegetation types, climate zones, and elevations in China remain unclear. This study used the Standardized Precipitation Evapotranspiration Index (SPEI) and Normalized Difference Vegetation Index (NDVI) to analyze vegetation status and drought trends from 2000 to 2022, examining the differentiation and mechanisms of cumulative (CED) and lag effect of drought (LED) under various conditions. The main findings are as follows: (1) 85.1% of the study area is becoming greener, with an overall growth rate of 0.026 per decade. Annual drought levels fluctuate, with increasingly severe conditions in parts of southwestern and northwestern China. (2) CED affects 35.94% of vegetated areas, with 77.44% showing a positive correlation between SPEI and NDVI. Grasslands have the longest CED (5.90 months), while forests have the shortest (4.72 months). Temperate and Arid climate zones show higher CED, at 6.91 months and 6.77 months, respectively. The highest CED is found at elevations of 2000–2500 m (6.34 months), and the lowest at 3000–3500 m (4.28 months). (3) LED affects a larger area (39.22%) with an average duration of 6.42 months, greater than the average CED (5.56 months). Grasslands have the longest LED (7.72 months), while forests (6.78 months) and shrublands (6.48 months) are shorter. The Arid climate zone has the highest LED (8.35 months), and the Tropical zone the lowest (4.82 months). LED shows significant elevation differences, being smallest at low elevations (6.48 months). (4) Climate type and potential evapotranspiration explain 0.269 and 0.259 of CED, respectively. For LED, temperature and potential evapotranspiration are dominant (0.173 and 0.167). The combination of factors significantly enhances the explanatory power of temporal effects. (5) NDVI stability is negatively influenced by CED. This study enhances understanding of the vegetation-drought relationship in China and provides theoretical support for addressing drought risks under climate change.
Journal Article
Changes in muscle strength and risk of cardiovascular disease among middle-aged and older adults in China: Evidence from a prospective cohort study
2024
Abstract
Background:
Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear.
Methods:
The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal–Normal, Low–Normal, Normal–Low, and Low–Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal–Normal group as the reference.
Results:
A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low–Normal (HR = 1.20, 95% CI: 1.01–1.43), the Normal–Low (HR = 1.35, 95% CI: 1.14–1.60), and the Low–Low (HR = 1.76, 95% CI: 1.49–2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories.
Conclusions:
The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.
Journal Article
Imaging tools for plant nanobiotechnology
2022
The successful application of nanobiotechnology in biomedicine has greatly changed the traditional way of diagnosis and treating of disease, and is promising for revolutionizing the traditional plant nanobiotechnology. Over the past few years, nanobiotechnology has increasingly expanded into plant research area. Nanomaterials can be designed as vectors for targeted delivery and controlled release of fertilizers, pesticides, herbicides, nucleotides, proteins, etc. Interestingly, nanomaterials with unique physical and chemical properties can directly affect plant growth and development; improve plant resistance to disease and stress; design as sensors in plant biology; and even be used for plant genetic engineering. Similarly, there have been concerns about the potential biological toxicity of nanomaterials. Selecting appropriate characterization methods will help understand how nanomaterials interact with plants and promote advances in plant nanobiotechnology. However, there are relatively few reviews of tools for characterizing nanomaterials in plant nanobiotechnology. In this review, we present relevant imaging tools that have been used in plant nanobiotechnology to monitor nanomaterial migration, interaction with and internalization into plants at three-dimensional lengths. Including: 1) Migration of nanomaterial into plant organs 2) Penetration of nanomaterial into plant tissues (iii)Internalization of nanomaterials by plant cells and interactions with plant subcellular structures. We compare the advantages and disadvantages of current characterization tools and propose future optimal characterization methods for plant nanobiotechnology.
Journal Article