Enantioselective transformation of phytoplankton-derived dihydroxypropanesulfonate by marine bacteria.

Chirality, a fundamental property of matter, is often overlooked in the studies of marine organic matter cycles. Dihydroxypropanesulfonate (DHPS), a globally abundant organosulfur compound, serves as an ecologically important currency for nutrient and energy transfer from phytoplankton to bacteria in the ocean. However, the chirality of DHPS in nature and its transformation remain unclear. Here, we developed a novel approach using chiral phosphorus-reagent labeling to separate DHPS enantiomers. Our findings demonstrated that at least one enantiomer of DHPS is present in marine diatoms and coccolithophores, and that both enantiomers are widespread in marine environments. A novel chiral-selective DHPS catabolic pathway was identified in marine Roseobacteraceae strains, where HpsO and HpsP dehydrogenases at the gateway to DHPS catabolism act specifically on R-DHPS and S-DHPS, respectively. R-DHPS is also a substrate for the dehydrogenase HpsN. All three dehydrogenases generate stable hydrogen bonds between the chirality-center hydroxyls of DHPS and highly conserved residues, and HpsP also form coordinate-covalent bonds between the chirality-center hydroxyls and Zn2+, which determines the mechanistic basis of strict stereoselectivity. We further illustrated the role of enzymatic promiscuity in the evolution of DHPS metabolism in Roseobacteraceae and SAR11. This study provides the first evidence of chirality's involvement in phytoplankton-bacteria metabolic currencies, opening a new avenue for understanding the ocean organosulfur cycle.

Higher dietary live microbe intake is associated with a lower risk of sarcopenia.

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.

GDF11 improves hippocampal neurogenesis and cognitive abilities in diabetic mice by reducing neural inflammation.

BACKGROUND: The cognitive decline associated with type 2 diabetes (T2D) is often attributed to compromised hippocampal neurogenesis and exacerbated neural inflammation. This study investigates the therapeutic potential of growth differentiation factor 11 (GDF11) in reversing these neurodegenerative processes in diabetic mice. RESULT: We utilized a murine model of T2D and examined the effects of GDF11 on learning, memory, neurogenesis, and neuroinflammatory markers. Our results indicate that diabetic mice exhibit significant deficits in cognitive function, mirrored by reduced hippocampal neurogenesis and increased neuroinflammation. Chronic administration of GDF11 was observed to significantly enhance cognitive abilities, as evidenced by improved performance in learning and memory tasks. Concurrently, GDF11 treatment restored neural activity and promoted the regeneration of new neurons within the hippocampus. Inflammatory profiling revealed a reduction in neuroinflammatory markers, which was further supported by reduced microglia numbers. To delineate the role of neuroinflammation, we pharmacologically depleted microglia, leading to a restoration of neurogenesis and cognitive functions in diabetic mice. CONCLUSION: These findings endorse the hypothesis that GDF11 exerts its beneficial effects by modulating neuroinflammatory pathways. Consequently, GDF11 represents a promising intervention to ameliorate diabetes-induced cognitive impairments and neural degeneration through its anti-inflammatory properties.

Development and advancements in rodent MRI-based brain atlases.

Rodents, particularly mice and rats, are extensively utilized in fundamental neuroscience research. Brain atlases have played a pivotal role in this field, evolving from traditional printed histology atlases to digital atlases incorporating diverse imaging datasets. Magnetic resonance imaging (MRI)-based brain atlases, also known as brain maps, have been employed in specific studies. However, the existence of numerous versions of MRI-based brain atlases has impeded their standardized application and widespread use, despite the consensus within the academic community regarding their significance in mice and rats. Furthermore, there is a dearth of comprehensive and systematic reviews on MRI-based brain atlases for rodents. This review aims to bridge this gap by providing a comprehensive overview of the advancements in MRI-based brain atlases for rodents, with a specific focus on mice and rats. It seeks to explore the advantages and disadvantages of histologically printed brain atlases in comparison to MRI brain atlases, delineate the standardized methods for creating MRI brain atlases, and summarize their primary applications in neuroscience research. Additionally, this review aims to assist researchers in selecting appropriate versions of MRI brain atlases for their studies or refining existing MRI brain atlas resources, thereby facilitating the development and widespread adoption of standardized MRI-based brain atlases in rodents.

Factor analysis of hydrologic services in water-controlled grassland ecosystems by InVEST model and geodetector.

Water conservation is highly important for a successful desert grassland ecosystem, but there was no comprehensive view on how to assess influencing factors in managing and addressing water yield and water conservation in desert steppe. The Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model, which is specifically used for the assessment of ecosystem services, was combined with geographic detectors to identify the priority areas for water conservation function and analyze the driving factors of water conservation in the Tabu River Basin, Inner Mongolia Autonomous Region, China, using different meteorological data sources. (i) The InVEST model has the advantage of modeling water yield and water conservation at spatial scales by fusion downscaling data. High water yield mainly occurs in the southern hilly mountainous areas, low water yield in the northern desert and grassland areas, and between the two in the central agro-pastoral areas; the multi-year average water conservation and water yield based on the InVEST model are 3.3 and 16 mm, respectively. (ii) Water yield and water conservation roughly show a transitional phenomenon of "high in the south and low in the north." The water yield and water conservation per unit area of the Tabu River Basin are relatively large for construction land, unused land, and cropland, relatively small for grassland and forestland, and basically zero for water bodies. Forest land has the strongest water conservation capacity, followed by grassland and farmland, while the order of water yield capacity is the opposite. (iii) Precipitation shows the strongest explanatory power for water yield (q = 0.427), followed by land use types (q = 0.411). The precipitation ∩ actual evapotranspiration has the strongest explanatory power for water yield (q = 0.87). The explanatory power of water yield on water conservation is the strongest (q = 0.752), followed by precipitation (q = 0.4), and the water yield ∩ soil has the greatest explanatory power on water conservation (q = 0.91). These findings are crucial for promoting regional hydrologic services and can provide a water resources management strategy for decision-makers.

Impacts of climate change on winter wheat net primary production: the regulatory role of crop management.

BACKGROUND: The Huang-Huai-Hai Plain (3HP) is the main agricultural area in China. Although climate change (CC) and crop management (CM) are considered factors affecting the winter wheat net primary production (NPP) in this region, their effects remain unclear. In the present study, we evaluated the relative contributions of CC and CM to winter wheat aboveground NPP (ANPP) in the 3HP and the relationships between climatic factors and ANPP using the first-order difference method from 2000 to 2020. RESULTS: CM had a greater influence on the ANPP of winter wheat than did CC. However, the relative contribution of CM to ANPP gradually decreased in humid and dry sub-humid regions with the development of winter wheat. Furthermore, in areas characterized by low temperatures and limited precipitation, CC became the dominant factor contributing to ANPP, indicating that varieties resilient to drought and cold should be selected in these regions. Minimum and average temperatures were the dominant factors driving spatiotemporal variations in ANPP during the early stage of winter wheat growth, whereas maximum temperature constrained growth throughout the winter wheat growth cycle. When winter wheat entered the vigorous growth stage, precipitation and solar radiation replaced temperature as the driving factors influencing winter wheat growth. CONCLUSION: The results of the present study provide guidance for optimizing winter wheat crop management in the 3HP. © 2023 Society of Chemical Industry.

Study on the relationship between regional soil desertification and salinization and groundwater based on remote sensing inversion: A case study of the windy beach area in Northern Shaanxi.

Soil desertification and salinization are important environmental concerns in arid regions, and their relationship with groundwater change must be further clarified. However, the relationships among soil desertification, salinization, and groundwater are difficult to investigate on a large spatiotemporal scale using traditional ground surveys. In the windy beach area in Northern Shaanxi (WBANS), desertification and salinization problems coexist; therefore, this area was selected as the study area. The feasibility of implementing large-scale remote sensing inversions to identify the degree of desertification and salinization was verified based on measured data, and the degree of influence of groundwater burial depth (GBD) on desertification and salinization was quantified using the geodetector and residual trend analysis methods. The results showed that the GBD in the WBANS presented an increasing trend and the degree of salinization showed a decreasing trend. Moreover, the joint influence of the unique natural environment and anthropogenic activities has led to increases in fractional vegetation cover and considerable improvements in the ecological environment. The intensity of desertification explained by GBD in the WBANS increased significantly (p < 0.01) at a rate of change of 0.0190/year, with high q-values above 0.66 for both Yuyang and Shenmu. The contribution rate of potential evapotranspiration and precipitation to salinization in Yuyang and Shenmu was >97 %, and the contribution rate of GBD to salinization in Dingbian, Jingbian, and Hengshan was 34.78 %, 31.15 %, and 29.41 %, respectively. Overall, the suitable GBD in the WBANS is 2-4 m. The study results provide a reference for research on the inversion, monitoring, and prevention of desertification and salinization dynamics on a large spatiotemporal scale and offer a scientific basis for rationally determining GBD.

Interactions between Helicobacter pylori infection and host metabolic homeostasis: A comprehensive review.

The microbiota actively and extensively participates in the regulation of human metabolism, playing a crucial role in the development of metabolic diseases. Helicobacter pylori (H. pylori), when colonizing gastric epithelial cells, not only induces local tissue inflammation or malignant transformation but also leads to systemic and partial changes in host metabolism. These shifts can be mediated through direct contact, toxic components, or indirect immune responses. Consequently, they influence various molecular metabolic events that impact nutritional status and iron absorption in the host. Unraveling the intricate and diverse molecular interaction links between H. pylori and human metabolism modulation is essential for understanding pathogenesis mechanisms and developing targeted treatments for related diseases. However, significant challenges persist in comprehensively understanding the complex association networks among H. pylori itself, the infected host's status, the host microbiome, and the immune response. Previous metabolomics research has indicated that H. pylori infection and eradication may selectively shape the metabolite and microbial profiles of gastric lesions. Yet, it remains largely unknown how these diverse metabolic pathways, including isovaleric acid, cholesterol, fatty acids, and phospholipids, specifically modulate gastric carcinogenesis or affect the host's serum metabolism, consequently leading to the development of metabolic-associated diseases. The direct contribution of H. pylori to metabolisms still lacks conclusive evidence. In this review, we summarize recent advances in clinical evidence highlighting associations between chronic H. pylori infection and metabolic diseases, as well as its potential molecular regulatory patterns.

Antioxidant-Engineered Milk-Derived Extracellular Vesicles for Accelerating Wound Healing via Regulation of the PI3K-AKT Signaling Pathway.

Inspired by the experience of relieving inflammation in infants with milk, antioxidant-engineered milk-derived extracellular vesicles (MEVs) are developed to evaluate their potential for accelerating wound healing. In this work, MEVs with polydopamines (PDA) are engineered using the co-extrusion method. Subsequently, the authors incorporated them into a Schiff-based crosslink hydrogel, forming a skin dosage form that could facilitate the wound healing process. The antioxidant properties of PDA assist in the anti-inflammatory function of engineered MEVs, while the gel provides better skin residency. The PDA@MEVs+GEL formulation exhibits excellent biocompatibility, pro-angiogenic capacity, and antioxidant ability in vitro. Furthermore, in vivo experiments demonstrate its efficacy in wound repair and inflammation inhibition. Mechanistically, PDA@MEVs+GEL simultaneously promotes the growth, migration, and anti-inflammation of 3T3 cells by activating PI3K-AKT pathway. Moreover, PDA@MEVs+GEL exhibits enhanced functionality in promoting wound healing in vivo, attributed to its ability to inhibit inflammation, stimulate angiogenesis, and promote collagen synthesis. In conclusion, this study delves into the mechanism of MEVs and underscores the improved efficacy of engineered extracellular vesicles. Additionally, the feasibility and prospect of engineered MEVs in treating skin wounds are verified, suggesting that antioxidant-engineered MEVs could be a promising therapeutic agent for wound healing applications.

Effects of urea solution concentration on soil hydraulic properties and water infiltration capacity.

Elucidating the effect of fertigation on soil hydraulic parameters and water-solute transportation is fundamental to the design of farmland irrigation systems and their sustainable utilization. Few studies have focused on soil hydraulic parameters or water infiltration characteristics or how they are influenced by urea solution concentration. In this study, the clay loam and sandy loam in Yangling District of Shaanxi Province, China, were used as test soil, and experiments involving seven urea solution concentrations (0.2, 0.4, 0.6, 0.8, 1, 3, and 5 g/L) and a control treatment (0 g/L) were conducted to explore the influence of the various urea solution concentrations on soil hydraulic parameters and water infiltration characteristics. The results indicated that the cumulative infiltration and wetting front migration depth increased with urea solution concentration, as accurately estimated using the Kostiakov model and a power function, respectively. In addition, the coefficients of the Kostiakov model and the power function increased with urea solution concentration. Treatment with multiple concentrations of urea solution resulted in an increase in the volume of macro pores in the soil but a reduction in the volume of mesopores and micro pores in the soil, leading to increases in the saturated water content, saturated hydraulic conductivity, soil water diffusivity, and infiltration capacity and a reduction in the water-holding capacity of the soil. The effect of urea solute potential on the inhibition of soil water movement is small, and this inhibitory effect is far weaker than the improvement effect of the urea solution on soil structure, and hence enhance the soil water infiltration capacity. Our results increase the understanding of soil hydrological mechanisms and may be usefully applied for improving the management of fertigation.

Effects of NSC in different organs and at different growth stages on the yield of oil peony Fengdan with different ages.

Non-structural carbohydrates (NSC) as resource reserves of plants play important roles in energy supply for normal growth and reproduction under environmental stress. The yield of perennial crops is mainly determined by the carbohydrate production and allocation in the current growth season, as well as the re-allocation of NSC reserves. However, the contribution of NSC to crop yield has not been fully determined. Fengdan (Paeonia ostii) is a variety of oil Peony that is newly developed in China. The effects of tree age and NSC on yield were examined by investigated the variations of biomass, soluble sugars, starch, and NSC in the organ and whole tree levels in the dormant and ripening stages of Fengdan populations with 4-, 6-, and 8-year-old in 2020 and 5-, 7-, and 9- year old in 2021. Results showed that the biomass, yield (seed biomass), soluble sugars, starch, and NSC reserve of Fengdan at the whole tree level increased with the increase in age. Although consistent correlations were observed between soluble sugars, starch and NSC storage, and yield among the plants with different ages, Fengdan showed allometric growth relationships between the accumulation of soluble sugars, starch, and NSC and yield and biomass (standardized major axis analyses slope b ≠ 1). Tree age significantly affected biomass and its allocation and NSC levels, especially the yield of Fengdan plants. The results of the investigation of the variations in the relationships between the yield and seasonal fluctuations of NSC and biomass indicate that roots is the key storage structure, whereas stems both serve as sink and/or source functions for the adult (7-9a) plants. NSC level, particularly the concentration of soluble sugars, in stems mainly influences Fengdan yield. These findings together provide new insights into the mechanisms underlying the yield formation of Fengdan and have implications for manipulating sink-source relationship to achieve high yield.

Multi-objective synchronous calibration and Pareto optimality of runoff and sediment parameters in an arid and semi-arid watershed.

Calibration methodologies must extract as much information as possible from available data, but it is not well understood in investigating the multi-objective synchronous calibration strategy by using multiple sources of information and by exploiting the data in better ways. The non-dominated sorting genetic algorithm II (NSGA-II) is introduced to study the calibration performance of runoff and sediment parameters under nine targeted scenarios, which considers the best choice to obtain high-cost performance results for decision makers through multi-objective optimization and the calculation of Pareto-optimal front with a high precision. (i) SWAT model has good adaptability in the runoff simulation of the Yanhe River watershed. Both the calibration results of NSGA-II and sequential uncertainty fitting approach-version 2 (SUFI-2) can meet the accuracy requirements of runoff simulation. Particularly, the NSGA-II based on multiple objective functions not only has strong applicability but also can better constrain the parameter process, making the calibrated model more in line with the physical conditions of the watershed. (ii) The two-site synchronous calibration of runoff or sediment can make full use of data information of different sites, reduce the impact of spatial heterogeneity on model parameters, and improve the calibration efficiency of the model. The single-site synchronous calibration of runoff and sediment based on NSGA-II not only has high calibration efficiency but also can avoid the tedious steps of calibrating runoff and sediment separately. (iii) The two-site synchronous calibration of runoff and sediment based on NSGA-II combines the advantages of the above synchronous calibration strategies, which can get Pareto-optimal front and represent the best trade-offs among different objectives, and its applicability is stronger than the traditional single-site or single-element calibration strategy. This study provides new and competing ways to evaluate hydrological models and their performance, and the multiple criteria approach for watershed modeling is one of the focuses in future research extensions.

MnO2@Au nanostructures supported colorimetric biosensing with duplex-specific nuclease-assisted DNA structural transition.

Manganese dioxide (MnO2) nanosheets are regarded as a new class of two-dimensional nanomaterials with several attractive properties with enormous progress in biomedical fields. Gold nanoparticles (AuNPs) are also important biocompatible nanomaterials with unusual optical properties. Hetero-nanostructure of MnO2 and AuNPs with the medium of DNA is an interesting topic. In this work, the protection of the hetero-nanostructure from salt-induced aggregation is systematically investigated including the effects of sequence length, reagents concentrations, incubation time and temperature. The MnO2@Au nanostructures are thus applied for the analysis of miRNA. Duplex-specific nuclease (DSN) catalyzed digestion, hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) are utilized for signal amplification. By finally analyzing the optical responses of the nanocomponents, highly sensitive analysis of target miRNA can be achieved. Excellent analytical performances are attributed to the unique features of MnO2@Au nanostructures and signal amplification designs. They are promising basis for the construction of novel biosensors for clinical applications.

Gamma-Aminobutyric Acid Promotes Beige Adipocyte Reconstruction by Modulating the Gut Microbiota in Obese Mice.

Given the increasing prevalence of obesity, the white-to-beige adipocyte conversion has attracted interest as a target for obesity treatment. Gamma-aminobutyric acid (GABA) treatment can reduce obesity, but the underlying mechanism remains unclear. Here, we aimed to investigate the mechanism by which GABA triggers weight loss by improving the beiging of inguinal white adipose tissue (iWAT) and the role of gut microbiota in this process. The results showed that GABA reduced body weight and adipose inflammation and promoted the expression of thermogenic genes in the iWAT. The 16S rRNA sequence analysis of gut microbiota showed that GABA treatment increased the relative abundance of Bacteroidetes, Akkermansia, and Romboutsia and reduced that of Firmicutes and Erysipelatoclostridium in obese mice. Additionally, serum metabolomic analysis revealed that GABA treatment increased 3-hydroxybutyrate and reduced oxidized lipid levels in obese mice. Spearman's correlation analysis showed that Akkermansia and Romboutsia were negatively associated with the levels of oxidized lipids. Fecal microbiota transplantation analysis confirmed that the gut microbiota was involved in the white-to-beige adipocyte reconstruction by GABA. Overall, our findings suggest that GABA treatment may promote iWAT beiging through the gut microbiota in obese mice. GABA may be utilized to protect obese people against metabolic abnormalities brought on by obesity and gut dysbiosis.

Increasing areas of aquaculture ponds and reservoirs reshape runoff coefficients: evidence from a subtropical catchment, China.

Detention pond is a key storm water management measure employed both to attenuate surface runoff and to regulate depression storage, yet the effects of aquaculture ponds and reservoirs on runoff coefficient are not well quantified in a subtropical humid monsoon climate zone, China. Here, a set of six subcatchments ranging in size from 0.7 hm2 to 10,000 hm2 were evaluated over the 2011-2015 period. (i) The annual average runoff coefficient differed with different subcatchments due to the spatial heterogeneity of landscape patterns, while the event-based runoff coefficient under the same catchment showed a decreasing trend with increasing rainfall intensity. (ii) The annual average and event-based runoff coefficients initially increased and then decreased with an increase in the area ratio of aquaculture ponds and reservoirs. The critical area ratio of aquaculture ponds and reservoirs for the maximum runoff coefficient in annual, light, and moderate rainfall intensity was about 4%; but this value would be transferred forward to the position of < 4% under the intensity of heavy rain, rainstorms, and heavy rainstorms. (iii) All runoff coefficients decreased with increasing forestland but increased with increasing paddy fields, and the decreasing rate was greater than the increasing rate. The trends of runoff coefficient for the annual and event-based rainfall are opposite between river development coefficient and watershed shape coefficient. The results provide underlying insights for decision-makers in aquaculture land-use planning and the sustainable utilization of water resources in the upstream and downstream systems of a catchment.

Sulfoquinovose is a widespread organosulfur substrate for Roseobacter clade bacteria in the ocean.

Sulfoquinovose (SQ) is one of the most abundant organosulfur compounds in the biosphere, and its biosynthesis and degradation can represent an important contribution to the sulfur cycle. To data, in marine environments, the microorganisms capable of metabolising SQ have remained unidentified and the sources of SQ are still uncertain. Herein, the marine Roseobacter clade bacteria (RCB) Dinoroseobacter shibae DFL 12 and Roseobacter denitrificans OCh 114 were found to grow using SQ as the sole source of carbon and energy. In the presence of SQ, we identified a set of highly up-regulated proteins encoded by gene clusters in these two organisms, of which four homologues to proteins in the SQ monooxygenase pathway of Agrobacterium fabrum C58 may confer the ability to metabolise SQ to these marine bacteria. The sulfite released from SQ desulfonation by FMN-dependent SQ monooxygenase (SmoC) may provide bacteria with reduced sulfur for assimilation, while proteins associated with sulfite production via assimilatory sulfate reduction were significantly down-regulated. Such SQ catabolic genes are restricted to a limited number of phylogenetically diverse bacterial taxa with the predominate genera belonging to the Roseobacter clade (Roseobacteraceae). Moreover, transcript analysis of Tara Oceans project and coastal Bohai Sea samples provided additional evidence for SQ metabolism by RCB. SQ was found to be widely distributed in marine phytoplankton and cyanobacteria with variable intracellular concentrations ranging from micromolar to millimolar levels, and the amounts of SQ on particulate organic matter in field samples were, on average, lower than that of dimethylsulfoniopropionate (DMSP) by one order of magnitude. Together, the phototroph-derived SQ actively metabolised by RCB represents a previously unidentified link in the marine sulfur cycle.

Optimization of sowing date for spring maize in China's loess plateau based on presowing temperature and soil water content.

BACKGROUND: The sowing date of spring maize in China's Loess Plateau is often restricted by the presowing temperature and soil water content (SWC). The effective measurement of the effects of presowing temperature and SWC on the sowing date is a major concern for agricultural production in this region. In this paper, we considered the average daily air temperature of ˃10 °C in the 7 days before sowing. The Decision Support System for Agrotechnology Transfer (DSSAT) model was used to simulate a spring maize yield under distinct combinations of SWC and sowing date for 51 years (1970-2020). Subsequently, through the cumulative probability distribution function, the contribution of presowing SWC to the spring maize yield was quantified, and the optimal sowing date of spring maize in each production location was determined. RESULTS: The results revealed that the daily average temperature of ˃10 °C for 7 days consecutively can be used effectively as the basis for the simulation of spring maize sowing date. The presowing SWC affected the spring maize yield but did not change the optimal sowing date. When the SWC of each study site is about 70% of the field capacity, Wenshui and Yuanping can properly delay sowing, and Lin county can sow early to obtain a higher yield. CONCLUSION: This study provides an effective approach for optimizing presowing soil moisture management and the sowing date of spring maize in the semiarid regions of the Loess Plateau. © 2023 Society of Chemical Industry.

Native and engineered exosomes for inflammatory disease.

Exosomes are extracellular vesicles which carry specific molecular information from donor cells and act as an intercellular communication vehicle, which have emerged as a novel cell-free strategy for the treatment of many diseases including inflammatory disease. Recently, rising studies have developed exosome-based strategies for novel inflammation therapy due to their biocompatibility and bioactivity. Researchers not only use native exosomes as therapeutic agents for inflammation, but also strive to make up for the natural defects of exosomes through engineering methods to improve and update the property of exosomes for enhanced therapeutic effects. The engineered exosomes can improve cargo-loading efficiency, targeting ability, stability, etc., to achieve combined and diverse treatment strategies in inflammation diseases. Herein, a comprehensive overview of the recent advances in application studies of native and engineered exosomes as well as the engineered methods is provided. Meanwhile, potential application prospects, possible challenges, and the development of clinical researches of exosome treatment strategy are concluded from plentiful examples, which may be able to provide guidance and suggestions for the future research and application of exosomes.

Dynamic tagging to drive arginine nano-assembly to metabolically potentiate immune checkpoint blockade therapy.

L-arginine metabolism is essential for the activation, survival, and effector function of the T lymphocytes and critical in eliminating tumors via T-cell-mediated immunotherapy, such as immune checkpoint blockade (ICB). Unfortunately, efficient delivery of hydrophilic L-arginine to the tumor microenvironment (TME) has met tremendous difficulties because of the limited loading efficacy and rapid diffusion. Inspired by the small-molecule prodrug nanoassemblies with ultrahigh drug-loading, we screen out aromatic aldehydes compounds to be used as dynamic tags to decorate L-arginine (reversible imine). Nano-Arginine (ArgNP, 104 nm) was created based on dynamic tag-mediated self-assembly. Molecular dynamics simulations indicate that the driving force of this self-assembly process is intermolecular hydrogen bonds, π-π stacking, and cation-π interactions. Notably, ArgNP metabolic synergy with anti-PD-L1 antibody (aPDL1) can promote tumor-infiltrating T cells (3.3-fold than aPDL1), resulting in a tumor inhibition ratio of 2.6-fold than aPDL1. Besides, such a strategy efficiently reduces the myeloid-derived suppressor cells, increases the M1-macrophages against the tumor, and induces the production of memory T cells. Furthermore, this synergistic therapy effectively restrains lung metastasis and prolongs mouse survival (60% survival ratio). The study highlights the dynamic tags strategy with facility and advance to deliver L-arginine that can metabolically promote ICB therapy.