Combinatorial design of ionizable lipid nanoparticles for muscle-selective mRNA delivery with minimized off-target effects.

Ionizable lipid nanoparticles (LNPs) pivotal to the success of COVID-19 mRNA (messenger RNA) vaccines hold substantial promise for expanding the landscape of mRNA-based therapies. Nevertheless, the risk of mRNA delivery to off-target tissues highlights the necessity for LNPs with enhanced tissue selectivity. The intricate nature of biological systems and inadequate knowledge of lipid structure-activity relationships emphasize the significance of high-throughput methods to produce chemically diverse lipid libraries for mRNA delivery screening. Here, we introduce a streamlined approach for the rapid design and synthesis of combinatorial libraries of biodegradable ionizable lipids. This led to the identification of iso-A11B5C1, an ionizable lipid uniquely apt for muscle-specific mRNA delivery. It manifested high transfection efficiencies in muscle tissues, while significantly diminishing off-targeting in organs like the liver and spleen. Moreover, iso-A11B5C1 also exhibited reduced mRNA transfection potency in lymph nodes and antigen-presenting cells, prompting investigation into the influence of direct immune cell transfection via LNPs on mRNA vaccine effectiveness. In comparison with SM-102, while iso-A11B5C1's limited immune transfection attenuated its ability to elicit humoral immunity, it remained highly effective in triggering cellular immune responses after intramuscular administration, which is further corroborated by its strong therapeutic performance as cancer vaccine in a melanoma model. Collectively, our study not only enriches the high-throughput toolkit for generating tissue-specific ionizable lipids but also encourages a reassessment of prevailing paradigms in mRNA vaccine design. This study encourages rethinking of mRNA vaccine design principles, suggesting that achieving high immune cell transfection might not be the sole criterion for developing effective mRNA vaccines.

Effects of cascade dams on the occurrence and distribution of microplastics in surface sediments of Wujiang river basin, Southwestern China.

The influence of cascade dams on the migration of microplastics (MPs) was conducted by analyzing the spatial distribution of MPs in sediments of the Wujiang river basin (Wujiang river basin) in Southwest China. The results showed that the abundance of MPs in Wujiang river basin sediments ranged from 310 to 2620 items/kg dw (mean: 1354 items/kg dw, a high level compared with aquatic sediments worldwide). The main chemical components of these MPs were polypropylene and polyethylene. High abundance of MPs in tributary sediments suggested that tributary inputs contributed to the main stream and reservoirs. Statistical analysis showed that gross domestic product (GDP) and the basin area of cascade reservoirs, rather than hydraulic retention time and reservoir age, were the dominating factors in the distribution of MPs in the Wujiang river basin. The accumulation of MPs in cascade reservoirs implied the interception effect of cascade dams. The rapid development of cascade dam systems and the interception effect of dams should be taken into account when predicting the flux of MPs from rivers to the ocean. Heavy metals found on the surface of the MPs showed the compound pollution of MPs and heavy metals in dammed rivers and cascade reservoirs. Our results deepen the understanding of the migration of MPs in rivers alongside intensive cascade hydropower development.

Behavioral sensitization induced by methamphetamine causes differential alterations in gene expression and histone acetylation of the prefrontal cortex in rats.

BACKGROUND: Methamphetamine (METH) is one of the most widely abused illicit substances worldwide; unfortunately, its addiction mechanism remains unclear. Based on accumulating evidence, changes in gene expression and chromatin modifications might be related to the persistent effects of METH on the brain. In the present study, we took advantage of METH-induced behavioral sensitization as an animal model that reflects some aspects of drug addiction and examined the changes in gene expression and histone acetylation in the prefrontal cortex (PFC) of adult rats. METHODS: We conducted mRNA microarray and chromatin immunoprecipitation (ChIP) coupled to DNA microarray (ChIP-chip) analyses to screen and identify changes in transcript levels and histone acetylation patterns. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed to analyze the differentially expressed genes. We then further identified alterations in ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) and POU3F2 (POU domain, class 3, transcription factor 2) using qPCR and ChIP-PCR assays. RESULTS: In the rat model of METH-induced behavioral sensitization, METH challenge caused 275 differentially expressed genes and a number of hyperacetylated genes (821 genes with H3 acetylation and 10 genes with H4 acetylation). Based on mRNA microarray and GO and KEGG enrichment analyses, 24 genes may be involved in METH-induced behavioral sensitization, and 7 genes were confirmed using qPCR. We further examined the alterations in the levels of the ANP32A and POU3F2 transcripts and histone acetylation at different periods of METH-induced behavioral sensitization. H4 hyperacetylation contributed to the increased levels of ANP32A mRNA and H3/H4 hyperacetylation contributed to the increased levels of POU3F2 mRNA induced by METH challenge-induced behavioral sensitization, but not by acute METH exposure. CONCLUSIONS: The present results revealed alterations in transcription and histone acetylation in the rat PFC by METH exposure and provided evidence that modifications of histone acetylation contributed to the alterations in gene expression caused by METH-induced behavioral sensitization.

Method for phosphate oxygen isotopes analysis in water based on in situ enrichment, elution, and purification.

The phosphate oxygen isotope (δ18OP) ratio has been proven to be an effective tool to trace the sources and biogeochemical cycles of phosphorus (P) in aquatic ecosystems. However, the enrichment of phosphate (PO4) and the removal of impurities are quite complex and easy to cause PO4 loss in current δ18OP analytical methods. Moreover, the δ18OP value obtained by the commonly-used instantaneous sampling method is more of the instantaneous information of P, which is accidental or uncertain for accurate identification of the P source. In this study, a new method of in situ enrichment, elution, and purification of PO4 (ISEEP) was developed for δ18OP analysis in waters. This method utilized a PO4 binding phase (Zr-Oxide gel) to selectively in situ adsorb PO4 in water and exhibited an adsorption capacity per unit area of up to 789.3 µg P/cm2. The PO4 on the gel was eluted easily with a 1 M NaOH solution. More than 99.7% of the common anions, cations, and dissolved organic matter (DOM), as well as more than 90% of the trace elements were removed synchronously after adsorption and elution of PO4. The recovery rate of PO4 in the whole procedure was as high as 92.8%. The XRD and SEM examinations showed that the ISEEP can obtain high-purity Ag3PO4 solid for the δ18OP measurement. The reliability of the ISEEP method is confirmed by the measured δ18OP value and standard deviation of parallel samples from different types of natural waters obtained by both the ISEEP and the current popular McLaughlin (2004) method. It provides a good prospect of this new method for tracing the P sources and their biogeochemical cycling in aquatic ecosystems.

Carbon and phosphorus transformation during the deposition of particulate matter in the large deep reservoir.

As the running time of reservoirs is increasing, a large number of reservoirs are becoming eutrophicated. Organic phosphorus (OP) is a key factor in eutrophication. However, the mechanism and extent to which organic matter degradation affects P recycling in water column of large deep reservoirs are unclear, especially for the newly-built ones. In this study, different forms of carbon (C) and P in the water column of Hongjiadu Reservoir were investigated. The contents of particulate organic carbon (POC) and particulate organic phosphorus (POP) both decreased with depth in summer, indicating that organic matter was degraded during the deposition of particulates. In contrast, the contents of POC and POP varied slightly with depth in winter. This difference may result from the double thermal stratification and the corresponding double oxygen stratification in summer. The POC/POP ratios were lower in the epilimnion and increased with depth, suggesting that P was preferentially regenerated relative to C during organic matter degradation. The contents of particulate inorganic phosphorus (PIP) and POP were significantly negatively correlated, indicating that POP transformed into PIP in deeper water. The double thermoclines and oxyclines in Hongjiadu Reservoir lead to very low dissolved oxygen (DO) concentrations in the hypolimnion, which should receive sufficient attention. If water becomes hypoxic, enhanced P release during organic matter degradation will promote phytoplankton growth, leading to higher phytoplankton biomass and more severe DO depletion. Thus, a positive feedback loop may form among hypoxia, enhanced P release, higher primary productivity, and more severe hypoxia, accelerating P recycling in large deep reservoirs. Once if eutrophication occurs in these reservoirs, it will be very difficult to restore the water ecosystem. Thus, it is particularly important to prevent the occurrence of eutrophication and the formation of positive feedback loop as early as possible. This highlights the importance of both reducing external loading and improving DO level in large deep reservoirs.

Evolutionary analysis and structural characterization of Aquilaria sinensis sesquiterpene synthase in agarwood formation: A computational study.

Agarwood originating from Aquilaria sinensis contains sesquiterpenoids that have tremendous commercial value in the pharmaceutical and fragrance industries. Aquilaria sinensis sesquiterpene synthase (AsSTS) is the key enzyme in the agarwood biosynthesis pathway, and its activity directly affects the chemical composition of agarwood; however, its role in species evolution remains unclear. In this study, we performed an evolutionary analysis based on 68 plant sesquiterpene synthase (STS) genes and further structural characterization of the gene encoding AsSTS to explore its molecular evolution. The phylogenetic tree indicated that these STS genes included three subfamilies. Additionally, 23 positively selected sites were detected, and no influence of recombination was found. Furthermore, the protein structure of AsSTS was characterized using primary sequence and structural analyses as having a functional active site lid domain, a substrate binding site, two post-translational modification sites and four conserved motifs. Finally, most virtual mutations of positively selected sites could be stabilized against thermal denaturation by a decrease in free energy, and three virtual mutations (D403R, G470Q and S538K) were shown to play important roles in the function and stability of AsSTS. The molecular evolutionary analysis of plant STSs provides essential clues for further experimental site-directed mutagenesis and molecular modification of AsSTS.

Bound PAHs in Sediment and Related Environmental Significance.

Extractable polycyclic aromatic hydrocarbons (EPAHs) and bound PAHs (BPAHs) were measured in a sediment core using conventional Soxhlet extraction and a more astringent extraction method, with the objectives of determining the influence of BPAHs on the historical reconstruction of PAHs and exploring the formation of BPAHs and long-term behaviors of PAHs in sediment. The results indicated that the formation of BPAHs was clearly sediment-depth and molecular-size dependent. BPAHs represents an important portion of PAHs in sediment and cannot be extracted by conventional Soxhlet extraction. This suggests that the previously developed vertical profile of PAHs is not the real chronology of PAHs and the plausible interpretation derived from the sedimentary records of PAHs needs reexamination. Based on the previous findings, a biphase model was proposed and the formation of BPAHs was predicted. Due to the different nature of geosorbents in sediment, redistribution of PAHs among these geosorbents logically leads to the formation of BPAHs and is kinetically favorable for smaller molecular PAHs. This is consistent with the obtained results. Many factors may influence the formation of BPAHs, such as the physicochemical structure of sediment and environmental conditions. There is still a long way to reveal the thermodynamical characteristics in action during the formation of BPAHs.

Molecular insights into the microbial degradation of sediment-derived DOM in a macrophyte-dominated lake under aerobic and hypoxic conditions.

The mineralization of dissolved organic matter (DOM) in sediments is an important factor leading to the eutrophication of macrophyte-dominated lakes. However, the changes in the molecular characteristics of sediment-derived DOM during microbial degradation in macrophyte-dominated lakes are not well understood. In this study, the microbial degradation process of sediment-derived DOM in Lake Caohai under aerobic and hypoxic conditions was investigated using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and metagenomics. The results revealed that the microbial degradation of sediment-derived DOM in macrophyte-dominated lakes was more intense under aerobic conditions. The microorganisms mainly metabolized the protein-like substances in the macrophyte-dominated lakes, and the carbohydrate-active enzyme genes and protein/lipid-like degradation genes played key roles in sediment-derived DOM degradation. Organic compounds with high H/C ratios such as lipids, carbohydrates, and protein/lipid-like compounds were preferentially removed by microorganisms during microbial degradation. Meanwhile, there was an increase in the abundance of organic molecular formula with a high aromaticity such as tannins and unsaturated hydrocarbons with low molecular weight and low double bond equivalent. In addition, aerobic/hypoxic environments can alter microbial metabolic pathways of sediment-derived DOM by affecting the relative abundance of microbial communities (e.g., Gemmatimonadetes and Acidobacteria) and functional genes (e.g., ABC.PE.P1 and ABC.PE.P) in macrophyte-dominated lakes. The abundances of lipids, unsaturated hydrocarbons, and protein compounds in aerobic environments decreased by 58 %, 50 %, and 44 %, respectively, compared to in hypoxic environments under microbial degradation. The results of this study deepen our understanding of DOM biodegradation in macrophyte-dominated lakes under different redox environments and provide new insights into nutrients releases from sediment and continuing eutrophication in macrophyte-dominated lakes.

Phosphorus resource partitioning underpins diversity patterns and assembly processes of microbial communities in plateau karst lakes.

Eutrophication triggered by internal phosphorus (P) poses a substantial threat to the biodiversity of organisms in freshwater ecosystems. However, little is known about the linkages between P resource partitioning and microbial succession, especially in karst sediments. Here, we studied the diversity patterns and assembly processes of bacterial and archaeal communities in sediment cores from two historically hyper-eutrophicated karst lakes, Hongfeng Lake and Aha Lake, and investigated the relative contribution of P fractions to them. Our null and neutral models consistently indicated that bacterial and archaeal community assembly was judged to be deterministic rather than stochastic. We found a monotonically decreasing pattern for bacterial Shannon diversity toward deep sediments in Aha Lake, but U- or hump-shaped patterns for archaea in Hongfeng and Aha Lakes. Intriguingly, the community dissimilarity Bray-Curtis of bacteria and archaea consistently increased with increasing depth distance, with slopes of 0.0080 and 0.0069 in Hongfeng Lake and 0.0078 and 0.0087 in Aha Lake, respectively. Such cross-taxon congruence was well-supported by equivalent ecological processes (i.e., environmental selection). For bacteria and archaea, Shannon diversity was primarily affected by the total P (TP) fractions such as the loosely adsorbed TP or calcium-bound TP and sediment TP. Their community composition was significantly (P < 0.05) affected by calcium-bound inorganic P (Pi), loosely adsorbed Pi and reductant-soluble Pi. Although sediment properties were important, bacterial and archaeal diversity or community composition were well-explained by the Pi fractions, with high direct or indirect effects. In particular, Pi fractions exhibited stronger effects on bacterial and archaeal characteristics than organic P fractions. Taken together, our study provides novel insights into the ecological importance of P resource partitioning to microbial succession, which has crucial implications for disentangling the biogeochemical processes of P cycling in aquatic ecosystems.

Corn stigma ameliorates hyperglycemia in zebrafish and GK rats of type 2 diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornstigma (CS), derived from the stigma and style of gramineous plant Zeamays. The medicinal use of CS can be traced back to DianNanMateriaMedica. LingnanMedicinalPlantsCompendium records its effectiveness in ameliorating diabetes. Diabetes is a metabolic disorder characterized by hyperglycemia and the consequent chronic complications of kidney, heart, brain and other organs, which pose a significant threat to human health. CS has shown great potential in relieving hyperglycemia associated with diabetes. However, the mechanism of CS in treating diabetes remains unclear. AIM OF THE STUDY: To explore the pathogenesis of diabetes and the mechanism of CS improving hyperglycemia in diabetes. MATERIALS AND METHODS: We measured apigenin and luteolin contents in CS by UPLC/MS/MS method. Selecting Wistar rats as normal group, and GK rats as model group. For rats, we detected glucose and lipid metabolism indicators, including GHb, AST, ALT, U-Glu, UA, U-TP, U-ALB, and ACR after treatment. For zebrafish, we utilized alloxan and sucrose to establish the diabetes model. Measuring zebrafish blood glucose is employed to evaluate the hypoglycemic capability of CS. In order to explore the mechanism of CS in treating diabetes, we sequenced the transcriptome of zebrafish, compared differentially expressed genes of normal, diabetic, and CS-treated group, and validated multiple enrichment pathways by PCR. RESULTS: CS can improve blood glucose levels in both GK rats and diabetic zebrafish. For rats, CS partially restored glucose and lipid metabolism indicators. Transcriptome data from zebrafish showed a close correlation with steroid biosynthesis. The RNA-Sequencing was consistent with PCR results, indicating that CS downregulated gene (fdft1,lss,cyp51) expression concerned with steroid biosynthesis pathway in the diabetes model. CONCLUSION: CS effectively improved blood glucose levels, regulated glucose and lipid metabolism by suppressing gene expression in steroid biosynthesis pathway, and ameliorated hyperglycemia. Our research provides valuable insights for CS in the treatment of diabetes, and proposes a new strategy for selecting clinical medications for diabetes.

Evaluating impacts of climate and management on reservoir water quality using environmental fluid dynamics code.

Climate change and human interference, notably nutrient input, affect the water quality. Nitrogen (N) and phosphorus (P) are pivotal in managing eutrophication. This study investigated the effects of water dynamics and chemical constituents on water quality in Hongfeng Lake, a typical weakly stratified reservoir suffering from algae blooms in Southwest China, using the Environmental Fluid Dynamics Code. Leveraging climate, hydrological, and water quality data, we constructed, calibrated, and validated the temperature-hydrodynamics-water quality-sediment model. Various scenarios were analyzed, including wind speed, air temperature, solar radiation, rainfall, water discharge, N and P external input, and internal release. The findings revealed that no rain and warming increased trophic state index (TSI) and chlorophyll-a (Chl-a) concentration, and no solar radiation initially elevated nitrate concentration, followed by an increase in ammonium concentration. Besides, no solar radiation and changes in rainfall significantly increased total phosphate concentration. The management scenarios of N and P reduction, halving tributary, and mainstream flow scenarios improved water quality and reduced eutrophication. The wind speed under the N and P reduced scenarios showed that a doubling in wind led to increased concentrations of the particulate organic matter, Chl-a, and dissolved oxygen, alongside decreased ammonium and nitrate, while TSI exhibited minimal change. However, 5- and 10-times wind speed scenarios amplified TSI in shallow water, potentially due to a substantial rise in internal nutrient release. The degradation trend observed in drinking water quality amid climate change (warming and flooding) raises concerns regarding health-related risks. These simulations provided the quantified influence of climate change and environmental management strategies on water quality in the weakly stratified reservoir, notably highlighting the looming threat of exacerbated eutrophication due to warming, necessitating more stringent N and P reduction measures compared to current practices.

A novel pretreatment method for analysis the oxygen isotopic compositions of inorganic phosphorus pools in freshwater sediment.

Identifying the sources and cycling of phosphorus (P) is particularly important for formulating effective P management strategies in inland water. The oxygen isotopic compositions of phosphate (δ18OP) are recognized as a promising tool to solve this problem. However, the application of δ18OP in freshwater sediment is currently constrained by multiple difficulties. In this study, we presented a novel pretreatment method for δ18OP analysis of sediment inorganic P pools. Our results showed that the new method has advantages of simple operation, less time-consuming, and high P recovery rates. Specifically, we replaced the traditional Mg-induced co-precipitation (MAGIC) method by introducing Zr-Oxides gels with high selective adsorption function for phosphate. This made subsequent processing simpler and reduced the time consumption to ∼10 days, and the range of P recovery rates were from 88 % to 104 %. Furthermore, we emphasized the necessity of vacuum roasting following lyophilized Ag3PO4 to eliminate residual oxygen-containing impurities (e.g., NO3-, Ag2O, and organic matter). Additionally, evidences from microscopy and spectroscopy confirmed that this method ultimately yielded high-purity Ag3PO4 with the Ag:P molar ratios of 3.35:1. Importantly, combining direct synthesis Ag3PO4 between KH2PO4 and AgNO3 with the Ag3PO4 obtained by the method revealed no stark oxygen isotopic fractionation of phosphate during the pretreatment processes. The newly established δ18OP pretreatment methods here can also be extended to broader studies of the biogeochemical cycling of P in aquatic ecosystems, potentially advancing the understanding of the global P cycle.

Tumor-Tailored Ionizable Lipid Nanoparticles Facilitate IL-12 Circular RNA Delivery for Enhanced Lung Cancer Immunotherapy.

The advancement of message RNA (mRNA) -based immunotherapies for cancer is highly dependent on the effective delivery of RNA (Ribonucleic) payloads using ionizable lipid nanoparticles (LNPs). However, the clinical application of these therapies is hindered by variable mRNA expression among different cancer types and the risk of systemic toxicity. The transient expression profile of mRNA further complicates this issue, necessitating frequent dosing and thus increasing the potential for adverse effects. Addressing these challenges, a high-throughput combinatorial method is utilized to synthesize and screen LNPs that efficiently deliver circular RNA (circRNA) to lung tumors. The lead LNP, H1L1A1B3, demonstrates a fourfold increase in circRNA transfection efficiency in lung cancer cells over ALC-0315, the industry-standard LNPs, while providing potent immune activation. A single intratumoral injection of H1L1A1B3 LNPs, loaded with circRNA encoding interleukin-12 (IL-12), induces a robust immune response in a Lewis lung carcinoma model, leading to marked tumor regression. Immunological profiling of treated tumors reveals substantial increments in CD45+ leukocytes and enhances infiltration of CD8+ T cells, underscoring the ability of H1L1A1B3 LNPs to modulate the tumor microenvironment favorably. These results highlight the potential of tailored LNP platforms to advance RNA drug delivery for cancer therapy, broadening the prospects for RNA immunotherapeutics.

AGILE platform: a deep learning powered approach to accelerate LNP development for mRNA delivery.

Ionizable lipid nanoparticles (LNPs) are seeing widespread use in mRNA delivery, notably in SARS-CoV-2 mRNA vaccines. However, the expansion of mRNA therapies beyond COVID-19 is impeded by the absence of LNPs tailored for diverse cell types. In this study, we present the AI-Guided Ionizable Lipid Engineering (AGILE) platform, a synergistic combination of deep learning and combinatorial chemistry. AGILE streamlines ionizable lipid development with efficient library design, in silico lipid screening via deep neural networks, and adaptability to diverse cell lines. Using AGILE, we rapidly design, synthesize, and evaluate ionizable lipids for mRNA delivery, selecting from a vast library. Intriguingly, AGILE reveals cell-specific preferences for ionizable lipids, indicating tailoring for optimal delivery to varying cell types. These highlight AGILE's potential in expediting the development of customized LNPs, addressing the complex needs of mRNA delivery in clinical practice, thereby broadening the scope and efficacy of mRNA therapies.

Cardiac tissue model of immune-induced dysfunction reveals the role of free mitochondrial DNA and the therapeutic effects of exosomes.

Despite tremendous progress in the development of mature heart-on-a-chip models, human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip with circulating immune cells to model severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced acute myocarditis. We observed hallmarks of coronavirus disease (COVID-19)-induced myocardial inflammation, as the presence of immune cells augmented the secretion of proinflammatory cytokines, triggered progressive impairment of contractile function, and altered intracellular calcium transients. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the heart-on-a-chip and then validated in COVID-19 patients with low left ventricular ejection fraction, demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation-induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2-induced myocardial inflammation, we established that administration of endothelial cell-derived exosomes effectively rescued the contractile deficit, normalized calcium handling, elevated the contraction force, and reduced the ccf-mtDNA and cytokine release via Toll-like receptor-nuclear factor κB signaling axis.

Extensive abundances and characteristics of microplastic pollution in the karst hyporheic zones of urban rivers.

Cities are potential areas for microplastic pollution due to large-scale production and the use of plastic products. The karst ecosystem in southwestern China is fragile, and pollutants are more likely to be transported over long distance, resulting in higher pollution risks. Understanding the abundance and composition of microplastics in karst urban water systems is crucial for microplastic pollution management in a karst region. This study investigates the abundances and characteristics of microplastics typically found in river sediments in 10 cities in karst regions of Southwest China. The results show that the abundance of microplastics in sediments ranged from 800 items·kg-1 to 4400 items·kg-1, with an average of 2273 ± 775 items·kg-1 (n = 30), indicating high abundance. Polyamide (PA) was the most common plastic polymer types in all sediment samples. The abundance of microplastics in the downstream (2527 ± 698 items·kg-1) was higher than that in the midstream (2350 ± 999 items·kg-1) and upstream areas (1943 ± 370 items·kg-1), indicating a gradual accumulation effect in the karst water systems. Microplastic abundance in cities (2119 ± 838 items·kg-1) was lower than in counties (2427 ± 671 items·kg-1). No significant correlation was found between microplastic abundance in rivers of urban areas and the level of regional population and economy, but significantly negatively correlated with the efficiency of urban sewage treatment. The results obtained from this study provided insights into the management of microplastic pollution in urban river of a karst region.

Sedimentary records of polycyclic aromatic hydrocarbons from three enclosed lakes in China: Response to energy structure and economic development.

Historical polycyclic aromatic hydrocarbon (PAH) pollution was explored through the sedimentary records of three lakes: Huguangyan Maar Lake (HGY) in South China, Mayinghai Lake (MYH) in North China, and Sihailongwan Lake (SHLW) in Northeast China. In these three lakes, the PAH concentrations in sediments are still rising, showing the different trend to lakes in developed countries. PAH pollution in South China occurred from 1850, much earlier than the increases since 1980 observed in North and Northeast China. The temporal trends of PAH concentrations in lake sediments are highly correlated with local economic development. Spatially, although the region where HGY is located has the highest gross domestic product, higher fluxes of PAHs were found in MYH sediments, indicating that atmospheric PAH pollution in North China might be more serious, and that PAH pollution is not fully correlated with economic development. Source analysis suggested that the PAHs in lake sediments are mainly derived from oil leaks, coal and biomass combustion, vehicle emissions, and diagenesis. Positive matrix factorization (PMF) model revealed that the contribution of vehicle emissions and coal combustion to PAHs has increased significantly in the past 40 years. Benzo(a)pyrene equivalent (BaPE) in the surface sediments of MYH and SHLW were similar and higher than in HGY. In HGY, vehicle emissions posed the highest toxic risk, followed by coal combustion. However, in MYH, the toxicity risk of vehicle emissions was close to that of coal and biomass combustion due to the highly developed coal industry in Shanxi Province. In SHLW, the contribution of fossil fuel combustion to BaPE was significantly higher than that of biomass combustion. This study provides important information for understanding PAH pollution affected by anthropogenic activities in the Anthropocene and provides a scientific basis for formulating PAH pollution control strategies.

Antimony isotope fractionation and the key controls in the soil profiles of an antimony smelting area.

The controlling factors of antimony migration and transformation in soil profiles are still unclear. Antimony isotopes might be a useful tool to trace it. In this paper, antimony isotopic compositions of plant and smelter-derived samples, and two soil profiles were measured for the first time. The δ123Sb values of the surface and bottom layers of the two soil profiles varied in 0.23‰-1.19‰ and 0.58‰-0.66‰, respectively, while δ123Sb of the smelter-derived samples varied in 0.29‰-0.38‰. The results show that the antimony isotopic compositions in the soil profiles are affected by post-depositional biogeochemical processes. The enrichment and loss of light isotopes at 0-10 cm and 10-40 cm layers of the contrasted soil profile may be controlled by plant uptake process. The loss and enrichment of heavy isotopes in the 0-10 cm and 10-25 cm layers of the antimony from smelting source in the polluted soil profile may be controlled by the adsorption process, while the enrichment of light isotopes in the 25-80 cm layer may be related to the reductive dissolution process. The conclusion emphasizes that the promotion of the Sb isotope fractionation mechanism will play a crucial role in understanding the migration and transformation behaviors of Sb in soil systems.

External Application of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Hyaluronic Acid Gel Repairs Foot Wounds of Types I and II Diabetic Rats Through Paracrine Action Mode.

Diabetic foot ulcer (DFU) is a main diabetic complication with unmet treatment needs. This study applied human umbilical cord-derived mesenchymal stem cells-hyaluronic acid (hucMSCs-HA) gel to treat DFU in a noninvasive external way and investigated its paracrine action and mechanism. In this study, after analyzing the physical and biological properties of HA gel, hucMSCs-HA gel was applied in 2 in vivo models (types I and II DFU), and a molecular mechanism was investigated. To evaluate the paracrine action of hucMSCs, hucMSCs-conditional medium (MSC-CM) was collected to treat 1 in vivo model (type I DFU) and 2 in vitro models (high glucose (HG)-injured human umbilical vein endothelial cells (HUVECs) and human skin fibroblasts (HSFs)). The results indicated that HA gel with a porous microstructure underwent over 90% degradation and swelled to the maximum value within 48 h. In vivo, hucMSCs-HA gel accelerated wound healing of DFU rats by improving re-epithelialization, collagen deposition, and angiogenesis, in which a paracrine action of hucMSCs was confirmed and the phosphorylation of p38, ERK1/2, JNK, and Akt was increased. In vitro, MSC-CM improved cell viability, wound healing, migration, tube formation, cell senescence, and abnormal expressions (TNF-α, IL-1ß, IL-6, ET-1, p16 genes, and PCNA protein) of HUVECs, also improved cell viability, wound healing, antioxidant stress, and abnormal expressions (COL1, COL3, COL4, SOD1, SOD2 genes, and PCNA protein) of HSFs. Summarily, noninvasive external application of hucMSCs-HA gel shows great perspective against DFU and exerts wound healing effects through the MAPK and Akt pathways-mediated paracrine mechanism.

Application of two-dimension, high-resolution evidences to reveal the biogeochemical process patterns of trace metals in reservoir sediments.

Pollutions of trace metals (TMs) in reservoirs are blooming due to TMs were trapped efficiently in reservoir sediments by dams. Despite the mobilization of TMs in sediments have been well-documented, the patterns of biogeochemical processes occurred in sediments remain poorly understanding. Herein, a deep reservoir was selected to investigate the patterns of TMs biogeochemical processes in sediments by using high-resolution ZrO-Chelex-AgI diffusive gradient in thin films technique (HR-ZCA DGT) and the laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). 2-dimension high-resolution (2D-HR) images showed significant differential spatial enrichment of TMs (V, Mn, Fe, Co, Zn and Sb) in sediments, indicating strong heterogeneity in sediments. Correlations of TMs within microniches (diameter < 1 mm) in horizontal were usually different even contrast with that in vertical profile, suggesting distinct biogeochemical process patterns occurred in vertical vs. in horizontal. Further analyses from 2D-HR images showed the distributions of TMs in microniches reflected their mobilization that was driven by microenvironmental conditions. In contrast, distributions in sediment vertical profile recorded the diagenesis in different deposition depth. The diagenesis in sediment vertical is continuously accumulated by the discrete, microniches mobilization of TMs in horizontal. Collectively, our findings evidenced that 2D-HR data is an update complement to 1-dimension data for better interpret the biogeochemical process patterns of TMs in sediments, that have implication for water management to metals pollution in reservoir ecosystems.