Biodistribution and Non-linear Gene Expression of mRNA LNPs Affected by Delivery Route and Particle Size.

PURPOSE: Lipid nanoparticles (LNPs) are widely utilized as means to deliver mRNA molecules. However, metric connections between biodistribution and pharmacokinetics (PK) of the nanoparticle carrier and transgene expression dynamics remain largely unknown. METHODS: LNPs containing mRNAs encoding the firefly luciferase gene were prepared with varying sizes. Biodistributions of injected LNPs in mice were measured by fluorescence bioimaging or liquid chromatography with tandem mass spectrometry. In addition, luciferase expression levels were determined by bioluminescence imaging and enzyme activity assays. RESULTS: Some intramuscularly injected LNPs were found circulating in the system, resulting in accumulation in the liver and spleen, especially when the LNP sizes were relatively small. Bigger LNPs were more likely to remain at the injection site. Transgene expression in the liver was found most prominent compared with other organs and tissues. CONCLUSIONS: Biomolecules such as mRNAs encapsulated in locally injected LNPs can reach other organs and tissues via systemic circulation. Gene expression levels are affected by the LNP biodistribution and pharmacokinetics (PK), which are further influenced by the particle size and injection route. As transfection efficiency varies in different organs, the LNP exposure and mRNA expression are not linearly correlated.

Does the Emission Trading Scheme achieve the dual dividend of reducing pollution and improving energy efficiency? Micro evidence from China.

Resolving the negative externality of environmental pollution has always been a concern in both the theoretical and practical space. To stimulate enterprises to participate in environmental governance actively, China has implemented a series of environmental regulation policies. The Emission Trading Pilot Scheme (ETPS) is an example of such policies implemented to ensure the gradual transition toward marketization. From a micro-enterprise perspective, the study examines how this policy achieves the dual effects of reducing emissions and promoting energy efficiency. We further explore potential channels through which this policy influences the dual effects. We empirically find ETPS to reduce the pollution emissions of enterprises significantly. However, the pollution reduction effect is mainly achieved by encouraging enterprises to strengthen cleaner production rather than through end governance. In addition to bringing environmental dividends, we observe ETPS to improve fossil energy efficiency by about 7.5% indirectly. We conclude by urging policy makers and participants to optimize energy structures and adjust intermediate input as they serve as significant pathways through which ETPS can affect fossil energy efficiency. The ETPS can encourage enterprises to actively step out of their "comfort zone" of environmental governance to be viewed as an effective environmental regulation policy.

Comparative Evaluation of Mechanical Properties and Color Stability of Dental Resin Composites for Chairside Provisional Restorations.

Resin composites have become the preferred choice for chairside provisional dental restorations. However, these materials may undergo discoloration, changes in surface roughness, and mechanical properties with aging in the oral cavity, compromising the aesthetics, functionality, and success of dental restorations. To investigate the color and mechanical stability of chairside provisional composite resins, this study evaluated the optical, surface, and mechanical properties of four temporary restoration resin materials before and after aging, stimulated by thermal cycling in double-distilled water. Measurements, including CIE LAB color analysis, three-point bending test, nanoindentation, scanning electron microscopy (SEM), and atomic force microscopy (AFM), were conducted (n = 15). Results showed significant differences among the materials in terms of optical, surface, and mechanical properties. Revotek LC (urethane dimethacrylate) demonstrated excellent color stability (ΔE00 = 0.53-Black/0.32-White), while Artificial Teeth Resin (polymethyl methacrylate) exhibited increased mechanical strength with aging (p < 0.05, FS = 68.40 MPa-non aging/87.21 MPa-aging). Structur 2 SC (Bis-acrylic) and Luxatemp automix plus (methyl methacrylate bis-acrylate) demonstrated moderate stability in optical and mechanical properties (Structur 2 SC: ΔE00 = 1.97-Black/1.38-White FS = 63.20 MPa-non aging/50.07 MPa-aging) (Luxatemp automix plus: ΔE00 = 2.49-Black/1.77-White FS = 87.72 MPa-non aging/83.93 MPa-aging). These results provide important practical guidance for clinical practitioners, as well as significant theoretical and experimental bases for the selection of restorative composite resins.

Impacts of aquaculture on the area and soil carbon stocks of mangrove: A machine learning study in China.

Mangrove is an important carbon sink, as it can achieve climate regulation by sequestering carbon dioxide in the atmosphere. However, 50 % of mangrove species are threatened with extinction in China, and the carbon stocks in vegetation has also dropped by 53.1 %. Here, we couple remote sensing data with Random Forests, Support Vector Machines, and XGBoost to analyse mangroves in mainland China from 1986 to 2019. We find that aquaculture has crucial impacts on mangroves and prediction error. Future predictions indicate that the changes of mangroves in different cities range from -5.09E+06 m2 to 2.30E+06 m2, and soil carbon(C) stocks is "-1.90E+05 Mg ~ 8.57E+04 Mg". To protect mangroves, exploring the balance between aquaculture and mangroves and paying attention to the sustainable transformation of aquaculture are urgently required. In this way, mangroves can fully play the role of carbon sequestration and contribute to China's dual carbon goals.

A multi-constraint and multi-objective optimization layout method for a mine water inrush monitoring network.

Mine water inrush can cause property losses and casualties, but current theoretical and technological approaches cannot accurately predict such events. Through the networked deployment of water level sensors along a mine roadway, a mine water inrush monitoring network was developed, and a multi-constraint and multi-objective optimal deployment method was established. By setting practical constraints of the mining area, water inrush risk level, and installation at specified locations, and considering two objective functions of minimum total cost and minimum average monitoring time, a mathematical model was established. The non-dominated sorting genetic algorithm II (NSGA-II) was designed to solve the model. The method temporally and spatially optimized the network, which was then verified in the Beiyangzhuang coal mine in north China. The average response time of the monitoring network was 916 s using only 28 water level sensors. The higher the water inrush risk level, the shorter the monitoring network response time. Under the 2, 3, and 4 risk levels, the network's response time to simulated water inrush accidents was less than 3000, 2100, and 900 s, respectively. The multi-constraint and multi-objective optimization layout method further enhanced the effectiveness of the network, providing a novel system for the early warning of mine water inrush.

Microbial composition and nitrogen removal pathways in a novel sequencing batch reactor integrated with semi-fixed biofilm carrier: evidence from a pilot study for low- and high-strength sewage treatment.

The sequencing batch reactor (SBR) activated sludge process is a well-established technology for sewage treatment. One of the drawbacks of SBRs, however, total nitrogen (TN) removals is insufficient. By means of introducing four improvements, including semi-fixed biofilm carrier, sludge elevation mixing and change for the mode of influent and effluent, compliant standard for TN discharge was obtained in this novel SBR configuration during low- and high-strength sewage load. To illustrate the microbial compositions and functions of the attached biofilm on semi-fixed carrier and the suspended aggregates, as well as the nitrogen removal pathway, high throughput 16S rRNA gene amplicon sequencing, PICRUSt2 algorithm, and KEGG database were applied. The results revealed that (i) the microbial communities from suspended aggregates and biofilm samples were significantly different from each other; (ii) during low-strength sewage loads, TN removal was mainly by nitrification-denitrification. The suspended aggregates was responsible for denitrification, while the biofilm was focused on ammonium oxidation; (iii) during high-strength sewage loads, function of nitrate reductase from suspended aggregates was faded, and anammox and N assimilation by biofilm became dominant. Meanwhile, TN removal referring to the formation of L-glutamine via assimilation was the main pathway.

Optimal location of water level sensors for monitoring mine water inrush based on the set covering model.

Water inrush is one of the major mining disasters that may lead to numerous casualties. The development of information techniques makes it possible to monitor the occurrence and evolution of water inrush. Then, locating monitors for water inrush becomes a primary problem. This study presents a method of optimal location of water level sensors by constructing a set covering model. The monitoring scope of the water level sensor at each location in a given time is computed first based on the numerical simulation of water spreading along mine tunnels. In this simulation, the water inrush quantity is assigned using the mine drainage capability over which an accident may occur. Then the greedy algorithm is used to optimize the number and positions of water level sensors. As results, a mine water disaster can be monitored in the given time after it happened. The proposed method is then verified in the Beiyangzhuang coal mine in the North China. The results show that at least 22, 36, 42, 64 and 106 water level sensors are needed to monitor water disasters in the whole mine within 60, 30, 20, 10 and 5 min, respectively.

Effects of ultrasound on invasive golden mussel Limnoperna fortunei mortality and tissue lesions.

Biofouling by the invasive golden mussel Limnoperna fortunei deleteriously affects artificial water systems, but few effective, environmentally friendly antifouling strategies exist. We propose ultrasound for control of this invasive mussel and report minimum exposure times to kill juveniles and adults at ultrasonic powers ranging 300-600 W from a fixed distance of 8.5 cm. Analysis using a PMA + RT-qPCR assay revealed the formation of tissue lesions in response to ultrasound, with gill tissue more prone to injury than adductor muscle tissue. Shell microstructure determined using scanning electron microscopy (SEM) + energy dispersive X-ray spectroscopy (EDS) is plywood-like, with a thicker shell and increased numbers of prism and nacre layers in adult mussels that provide greater resistance to ultrasound, reducing mortality and tissue lesions. Our results suggest L. fortunei biomass could be effectively reduced by ultrasound, especially for early life-history stages without, or with only immature shells.

UV dose effects on the revival characteristics of microorganisms in darkness after UV disinfection: Evidence from a pilot study.

Ultraviolet (UV) disinfection during water supply treatment aims to reduce the number of bacteria. Although UV disinfection is effective at inactivating most microorganisms, some microbe species may be entirely impervious. A pilot study was conducted to compare the quantity and community component of bacteria in surface water collected from filtration effluent before UV disinfection with different doses of UV, and those 1 and 2 days afterwards, in darkness. The aim was to elucidate the relationship between the UV dose and the total revived microorganisms in darkness after UV disinfection. In the filtration effluent samples, Gammaproteobacteria, Bacilli, Actinobacteria, and Alphaproteobacteria were the predominant classes. After storage in the dark at a constant temperature of 19 °C, the UV-disinfected samples showed a considerable increase in Bacilli, while Gammaproteobacteria remained the predominant population. Genera such as Exiguobacterium, Citrobacter, Acinetobacter, and Pseudomonas presented a selective advantage in terms of revival in darkness after UV disinfection, irrespective of the UV dose and storage time. The lowest rate of microbial revival (5% day-1) was noted at a UV dose of 266.10 mJ m-2 (with an average UV illumination time of 124.4 s and an average intensity of 86.61 W m-2). Our results suggest that higher UV intensity and lower illumination time are key factors in minimizing the revival of microorganisms in darkness.

[Formation and characterization of aerobic granules in a pilot-scale reactor for real wastewater treatment].

Microbial granules were successfully developed in a pilot-scale sequencing batch reactor (SBR) for the treatment of real municipal wastewater. The aerobic granules developed had good settleability with a settling velocity of > 21 mh-1. The mature granular sludge was capable of simultaneous removal of chemical oxygen demand (COD), nitrogen (N) and phosphorus (P). With the cycle of 3 h, the effluent COD, ammonium nitrogen (NH+4 -N) and total nitrogen (TN) concentrations were <50 mg L-1, <5. 0 mg L-1, and <15 mgL-1, respectively. The removal efficiency for TN and total phosphorus (TP) was about 50%. Examinations by confocallaser scanning microscopy (CLSM) showed that extracellular polymeric substances (EPS) were uniformly distributed throughout the granules, forming the granule structure matrix. X-ray diffraction (XRD) analysis indicated the presence of SiO2 and other metal oxides inside aerobic granules, implying that minerals in real wastewater might function as the seed in the initial stage of aerobic granulation.