Nebulized Inhalation of Peptide-Modified DNA Origami To Alleviate Acute Lung Injury.

Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.

Self-Assembled DNA Composite-Engineered Mesenchymal Stem Cells for Improved Skin-Wound Repair.

The direct use of mesenchymal stem cells (MSCs) as therapeutics for skin injuries is a promising approach, yet it still faces several obstacles, including limited adhesion, retention, and engraftment of stem cells in the wound area, as well as impaired regenerative and healing functions. Here, DNA-based self-assembled composites are reported that can aid the adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound closure and re-epithelialization. Rolling-circle amplification (RCA)-derived DNA flowers, equipped with multiple copies of cyclic Arg-Gly-Asp (cRGD) peptides and anti-von Willebrand factor (vWF) aptamers, act as robust scavengers of reactive oxygen species (ROS) and enable synergistic recognition and adhesion to stem cells and damaged vascular endothelial cells. These DNA structure-aided stem cells are retained at localized wound sites, maintain repair function, and promote angiogenesis and growth factor secretion. In both normal and diabetes-prone db/db mice models with excisional skin injuries, facile topical administration of DNA flower-MSCs elicits rapid blood vessel formation and enhances the sealing of the wound edges in a single dose. DNA composite-engineered stem cells warrant further exploration as a new strategy for the treatment of skin and tissue damage.

Role of Polysaccharides from Marine Seaweed as Feed Additives for Methane Mitigation in Ruminants: A Critical Review.

Given the increasing concerns regarding greenhouse gas emissions associated with livestock production, the need to discover effective strategies to mitigate methane production in ruminants is clear. Marine algal polysaccharides have emerged as a promising research avenue because of their abundance and sustainability. Polysaccharides, such as alginate, laminaran, and fucoidan, which are extracted from marine seaweeds, have demonstrated the potential to reduce methane emissions by influencing the microbial populations in the rumen. This comprehensive review extensively examines the available literature and considers the effectiveness, challenges, and prospects of using marine seaweed polysaccharides as feed additives. The findings emphasise that marine algal polysaccharides can modulate rumen fermentation, promote the growth of beneficial microorganisms, and inhibit methanogenic archaea, ultimately leading to decreases in methane emissions. However, we must understand the long-term effects and address the obstacles to practical implementation. Further research is warranted to optimise dosage levels, evaluate potential effects on animal health, and assess economic feasibility. This critical review provides insights for researchers, policymakers, and industry stakeholders dedicated to advancing sustainable livestock production and methane mitigation.

Ecological stoichiometry influences phytoplankton alpha and beta diversity rather than the community stability in subtropical bay.

Numerous studies have shown that changes in environmental factors can significantly impact and shift the structure of phytoplankton communities in marine ecosystems. However, little is known about the association between the ecological stoichiometry of seawater nutrients and phytoplankton community diversity and stability in subtropical bays. Therefore, we investigated the relationship between the phytoplankton community assemblage and seasonal variation in the Beibu Gulf, South China Sea. In this study, we found that the abundance of Bacillariophyceae in spring was relatively greater than in other seasons, whereas the abundance of Coscinodiscophyceae was relatively low in spring and winter but greatly increased in summer and autumn. Values of the alpha diversity indices gradually increased from spring to winter, revealing that seasonal variations shifted the phytoplankton community structure. The regression lines between the average variation degree and the Shannon index and Bray-Curtis dissimilarity values showed significantly positive correlations, indicating that high diversity was beneficial to maintaining community stability. In addition, the ecological stoichiometry of nutrients exhibited significantly positive associations with Shannon index and Bray-Curtis dissimilarity, demonstrating that ecological stoichiometry can significantly influence the alpha and beta diversity of phytoplankton communities. The C:N:P ratio was not statistically significantly correlated with average variation degree, suggesting that ecological stoichiometry rarely impacted the community stability. Temperature, nitrate, dissolved inorganic phosphorous, and total dissolved phosphorus were the main drivers of the phytoplankton community assemblage. The results of this study provide new perspectives about what influences phytoplankton community structure and the association between ecological stoichiometry, community diversity, and stability in response to environmental changes.

Co-occurrence of chromophytic phytoplankton and the Vibrio community during Phaeocystis globosa blooms in the Beibu Gulf.

Accumulating research evidence has revealed that harmful algal blooms (HABs) can substantially affect the community structures of phytoplankton and heterotrophic bacteria in marine ecosystems. However, little is known about their species-specific interactions between phytoplankton and heterotrophic bacteria during the HABs period and about their interaction shifts in response to blooms. From this perspective, we investigated the co-occurrence of chromophytic phytoplankton and Vibrio during Phaeocystis globosa blooms in the Beibu Gulf. The results showed that Vibrio communities were distinct during the blooms, and P. globosa blooms resulted in a decline in phytoplankton alpha diversity, revealing that the blooms could affect their community compositions. The regression lines between the Shannon indices and Bray-Curtis distances of phytoplankton and Vibrio showed positive correlations with each other (p < 0.001), suggesting that they may have intrageneric symbiotic interactions overall. In addition, network analysis further demonstrated that relationships between phytoplankton and Vibrio were dominated by positive correlations, and more interaction modules were observed during the blooms, revealing that the blooms intensified synergistic association and mutual symbiotic interactions between them. Environmental factors (SiO32-, NH4+, NO3- and TN,) and P. globosa density more deeply affected network interactions between phytoplankton and Vibrio during the periods of P. globosa blooms than those before the blooms and after the blooms. This study provided new insight to elucidate community structure and interaction relationships between phytoplankton and Vibrio in response to P. globosa blooms and their ecological effects in marine ecosystems.

Spatial distribution and functional profile of the bacterial community in response to eutrophication in the subtropical Beibu Gulf, China.

In this study, we investigated the specific bacterial distribution and the response of bacterial communities to shifts in environmental factors in the subtropical Beibu Gulf, southern China. The abundances of Actinobacteria, Bacilli, Planctomycetia, Thermoleophilia, Anaerolineae, and Synechococcophycideae were significantly higher in high eutrophic samples than in medium eutrophic and oligotrophic samples. Bacterial alpha-diversity was found greater in high eutrophication samples than in the other samples. Besides, Ponticaulis koreensis, Nautella italic, Anaerospora hongkongensis, Candidatus Aquiluna rubra, and Roseovarius pacificus were sensitive to trophic variation and thus could be used as eco-markers. In addition, the relative abundances of functional genes involving carbohydrate and amino acid metabolism were very high among the samples. We also found temperature, Chl-a, TDN and NO3- were the main environmental drivers of bacterial community structure. Overall, this study provides new insight into the composition of bacterial community and function response to gradients of eutrophication in Beibu Gulf.

Dynamically enhancing plaque targeting via a positive feedback loop using multifunctional biomimetic nanoparticles for plaque regression.

A paradigm shift from preventive therapy to aggressive plaque regression and eventual eradication is much needed to address increasing atherosclerotic burden and risks. Herein, we report a biologically inspired dual-targeting multifunctional recombinant high-density lipoprotein (rHDL)-mimicking core-shell nanoplatform. It is composed of an ATP-responsive ternary polyplexes core for SR-A siRNA and catalase complexation, and a phosphatidylserine-modified rHDL-based outer shell for SR-BI and CD36 targeting, in which pitavastatin is packaged. We demonstrated that dual-targeting biomimetic core-shell nanoparticles dynamically enhanced macrophage CD36 targeting in the plaques by establishing a positive feedback loop via the reciprocal regulation of SR-A and CD36. Positive feedback-enabled accumulation of the nanoparticles in the atherosclerotic plaques increased by 3.3-fold following 4-week repeated administration. A 3-month dosage regimen of the dual-targeting rHDL-mimicking nanoparticles reduced plaque areas by 65.8%, and decreased macrophages by 57.3%. Collectively, this work shows that dynamically enhancing plaque targeting via a positive feedback loop and dual action of cholesterol deposition inhibition and efflux enhancement accomplished with our novel multifunctional biomimetic nanoparticles provides a new way to regress plaques and alleviate the atherosclerotic burden.

Rational Design of Lovastatin-Loaded Spherical Reconstituted High Density Lipoprotein for Efficient and Safe Anti-Atherosclerotic Therapy.

Reconstituted high density lipoprotein (rHDL) is a biomimetic nanoparticle with plaque targeting and anti-atherosclerotic efficacy. In this work, we report on a strategy to rational design of lovastatin (LOV)-loaded spherical rHDL (LOV-s-rHDL) for efficient and safe anti-atherosclerotic therapy. Briefly, three LOV-s-rHDLs were formulated with LOV/s-rHDL at ratios of 8:1, 10:1, and 15:1 upon their respective median-effect values ( Dm). The combined inhibitory effect between LOV and s-rHDL of different LOV-s-rHDL formulations on DiI-labeled oxLDL internalization was systemically investigated in RAW 264.7 cells based on the median-effect principle. Median-effect analysis demonstrated that the optimized LOV-s-rHDL was formulated with a ratio of 10:1 ( Dm LOV: Dm s-rHDL), in which LOV and s-rHDL carrier showed the best synergistic effect, presumably ascribed to their inhibitory effect on CD36 and SR-A expression according to the Western blot analysis. In vivo pharmacodynamics studies showed that the optimized LOV-s-rHDL displayed the most pronounced anti-atherosclerotic effect on decreasing plaque area and reducing the MMP level following an 8-week dosing regimen. In vivo atherosclerotic plaque targeting analysis revealed that s-rHDL had potent plaque targeting efficacy, probably owing to the interaction between apoA-I and scavenger receptor B-I. Furthermore, we observed that the optimized LOV-s-rHDL exhibited a favorable safety profile as evidenced by the results of a hemolysis assay, cell cytotoxicity study, and in vivo safety test. Collectively, the rational design of the biomimetic LOV-s-rHDL based on the median-effect analysis provides an efficient strategy to achieve a synergistic and safe anti-atherosclerotic therapy.

Recent advances in the development of polyethylenimine-based gene vectors for safe and efficient gene delivery.

INTRODUCTION: Despite the great therapeutic potential of gene therapy for treating critical diseases, the clinical application is limited by lack of safe and effective gene delivery vectors. Nonviral gene vectors have attracted tremendous attention due to the favorable loading capacity and facile manufacture. Among them, polyethylenimine-based gene vectors (PEIs) hold great promise for highly efficient gene delivery. AREAS COVERED: In this review, we outline the multiple biological barriers associated with gene delivery process and point out several challenges exist in the clinical usage of PEIs. We then provide an overview of the most impressive progresses made to overcome such challenges in recent years, including modifications of PEIs (i.e. to enhance biocompatibility, specific targeting effect, and buffering capacity) and stimuli-responsive strategies (i.e. endogenous and exogenous stimuli) for safe and efficient gene delivery. EXPERT OPINION: Rational modification of PEIs with diverse functionalized segments or the development of stimuli-responsive PEIs is an appealing strategy to meet some requirements involved in gene delivery. Nevertheless, further optimization by combining the two strategies is needed for the maximized transfection efficiency and minimized side effects, shedding new light on the development of nonviral gene delivery for clinical application.

[Analysis of the determinants of salt-restriction behavior among urban and rural residents in Beijing with health belief model].

OBJECTIVE: To investigate salt-restriction behavior and explore related determinants among Beijing residents, so as to provide scientific basis for salt-restriction intervention. METHODS: The health belief model (HBM) was applied in designing the questionnaire, in which respondents' demographic characteristics, salt-restriction behavior, knowledge on hypertension, perceived susceptibility to hypertension, perceived severity of hypertension, perceived benefits of salt-restriction, perceived subjective barriers of salt-restriction, perceived objective barriers of salt-restriction, self-efficacy and cues to action were measured. Altogether 799 residentsresponsible for cooking in Xicheng district (396 urban residents) and Shunyi district (403 rural residents) in Beijing were investigated by the questionnaire, salt intake follow up, and 24-hour urinary sodium (24HUNa) determination. RESULTS: In the study, 54.0% (214/396) of urban respondents and 26.3% (106/403) of rural respondents used a salt-restriction-spoon with high frequencies (everyday and often), while 27.5% (109/396) and 12.4% (50/403) used it correctly. The daily salt intake was (5.85±4.17) g and (7.74±4.67) g, and the 24HUNa was (113.70± 72.57) mmoL and (212.18±105.01) mmoL for urban and rural respondents, respectively. Perceived objective barriers of salt-restriction was animportant determinant of salt-restriction behavior for both the rural (OR=0.92; 95%CI: 0.88-0.96; P<0.01) and urban respondents (OR=0.87;95%CI: 0.83-0.91;P<0.01), which was perceived obviously more by rural respondents than by urban ones. Another important determinant of rural respondents' salt-restriction behavior was the owning status of salt-restriction-spoon (OR=2.18;95%CI: 1.04-4.57;P=0.04). CONCLUSION: It is necessary to improve current salt-restriction-spoon, enhance its owning rate,and popularize its correct way of using, especially among rural residents.

Determinants of salt-restriction-spoon using behavior in China: application of the health belief model.

BACKGROUND: The two-gram salt-restriction-spoons, which can be used to reduce the salt intake of people, had been handed out for free by the Chinese government to the citizens several years ago, but only a small fraction of residents use such a spoon currently. Since no studies have been conducted to investigate relevant influencing factors, this study was designed to explore the determinants of salt-restriction-spoon using behavior (SRB) in China. METHODS: This cross-sectional study was conducted in Beijing, China. Altogether 269 rural residents and 244 urban residents aged over 18 were selected by convenience sampling method in 2012. Variables measured in a questionnaire designed according to the Health Belief Model (HBM) included socio-demographics, perceived susceptibility, perceived severity, perceived benefits, perceived objective barriers, perceived subjective barriers, self-efficacy, knowledge of hypertension, cues to action, and SRB. Answers to the questionnaire were obtained from all the participants, and 24-hour urine samples were collected to determine the 24-hour urinary sodium excretion (24HUNa). Path analyses were used to explore the determinants of SRB. RESULTS: Approximately 22.7% and 45.3% of residents used a salt-restriction-spoon everyday in the rural and urban areas, respectively. The average 24HUNa was 211.19±98.39 mmol for rural residents and 109.22±58.18 mmol for urban residents. Path analyses shown that perceived objective barriers, perceived benefits, perceived severity, knowledge and age were related to SRB and 24HUNa for both rural and urban participants, among which perceived objective barrier (ß =  - 0.442 and ß =  - 0.543, respectively) was the most important determinant. CONCLUSION: Improvement of the current salt-restriction-spoon and education on the right usage of the salt-restriction-spoon, the severity of hypertension, and the benefit of salt reduction are necessary, especially among those who are relatively young but at risk of hypertension, those who have lower education levels, and those who live in the rural areas.

Salt-restriction-spoon improved the salt intake among residents in China.

OBJECTIVE: To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa). DESIGN: A community intervention study. SETTING: Two villages in Beijing. PARTICIPANTS: 403 local adult residents being responsible for home cooking. INTERVENTION: Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group. MAIN OUTCOME MEASURES: The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa. ANALYSIS: Covariance analyses, Chi-square tests, Student's t tests, and repeated measures analyses of variance. RESULTS: After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870). CONCLUSIONS: The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.