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Microglia play a key role in regulating synaptic remodeling in the central nervous system. Activation of classical complement pathway promotes microglia-mediated synaptic pruning during development and disease. CD47 protects synapses from excessive pruning during development, implicating microglial SIRPα, a CD47 receptor, in synaptic remodeling. However, the role of microglial SIRPα in synaptic pruning in disease remains unclear. Here, using conditional knock-out mice, we show that microglia-specific deletion of SIRPα results in decreased synaptic density. In human tissue, we observe that microglial SIRPα expression declines alongside the progression of Alzheimer’s disease. To investigate the role of SIRPα in neurodegeneration, we modulate the expression of microglial SIRPα in mouse models of Alzheimer’s disease. Loss of microglial SIRPα results in increased synaptic loss mediated by microglia engulfment and enhanced cognitive impairment. Together, these results suggest that microglial SIRPα regulates synaptic pruning in neurodegeneration. Microglial SIRPα regulates synaptic pruning during development. Its role in neurodegeneration is unclear. Here, the authors show microglial SIRPα declines in the model of Alzheimer’s disease, leading to excessive microglia mediated synapse elimination as well as impaired cognitive function.

Advancing a metal‐free room temperature phosphorescent (RTP) material that exhibits multicolor emission, remarkable RTP lifetime, and high quantum yield still faces the challenge of achieving intersystem crossing between singly and triplet excited states, as well as the rapid decay of triplet excited states due to nonradiative losses. In this study, a novel strategy is proposed to address these limitations by incorporating o‐phenylenediamine, which generates multiple luminescent centers, and long‐chain polyacrylic acid to synthesize carbonized polymer dots (CPDs). These CPDs are then embedded in a rigid B2O3 matrix, effectively limiting nonradiative losses through the synergistic effects of polymer cross‐linking and the rigid matrix. The resulting CPD‐based materials exhibit remarkable ultralong phosphorescence in shades of blue and lime green, with a visible lifetime of up to 49 s and a high phosphorescence quantum yield. Simultaneously, this study demonstrates the practical applicability of these excellent material properties in anti‐counterfeiting and information encryption. Developing room‐temperature phosphorescent carbon dots with extended afterglow and multicolor emission is challenging. This work proposes a novel strategy using o‐phenylenediamine and polyacrylic acid to synthesize carbonized polymer dots embedded in B2O3 matrix. The resulting materials exhibit dual‐emitting ultralong phosphorescence in blue and lime green shades under different UV excitations, with a remarkable phosphorescence lifetime of up to 49 s and potential applications in anticounterfeiting and information encryption.

Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression, but the absorption mechanism remains unknown. Here, we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs. SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs. Notably, we identified the stomach as the primary site for dietary microRNA absorption, which is dramatically attenuated in the stomachs of SIDT1-deficient mice. Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent. Furthermore, oral administration of plant-derived miR2911 retards liver fibrosis, and this protective effect was abolished in SIDT1-deficient mice. Our findings reveal a major mechanism underlying the absorption of dietary microRNAs, uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.

It has been reported that increasingly microRNAs are associated with diseases. However, the patterns among the microRNA-disease associations remain largely unclear. In this study, in order to dissect the patterns of microRNA-disease associations, we performed a comprehensive analysis to the human microRNA-disease association data, which is manually collected from publications. We built a human microRNA associated disease network. Interestingly, microRNAs tend to show similar or different dysfunctional evidences for the similar or different disease clusters, respectively. A negative correlation between the tissue-specificity of a microRNA and the number of diseases it associated was uncovered. Furthermore, we observed an association between microRNA conservation and disease. Finally, we uncovered that microRNAs associated with the same disease tend to emerge as predefined microRNA groups. These findings can not only provide help in understanding the associations between microRNAs and human diseases but also suggest a new way to identify novel disease-associated microRNAs.

Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.

Given the complex nature of ulcerative colitis, combination therapy targeting multiple pathogenic genes and pathways of ulcerative colitis may be required. Unfortunately, current therapeutic strategies are usually based on independent chemical compounds or monoclonal antibodies, and the full potential of combination therapy has not yet been realized for the treatment of ulcerative colitis. Here, we develop a synthetic biology strategy that integrates the naturally existing circulating system of small extracellular vesicles with artificial genetic circuits to reprogram the liver of male mice to self-assemble multiple siRNAs into secretory small extracellular vesicles and facilitate in vivo delivery siRNAs through circulating small extracellular vesicles for the combination therapy of mouse models of ulcerative colitis. Particularly, repeated injection of the multi-targeted genetic circuit designed for simultaneous inhibition of TNF-α, B7-1 and integrin α4 rapidly relieves intestinal inflammation and exerts a synergistic therapeutic effect against ulcerative colitis through suppressing the pro-inflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we design an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4 through only a single injection. Overall, this study establishes a feasible combination therapeutic strategy for ulcerative colitis, which may offer an alternative to conventional biological therapies requiring two or more independent compounds or antibodies. Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.

Cyclotides are plant cyclic peptides with exceptional stability and diverse bioactivity, making them promising candidates for biomedical applications. Therefore, the study of cyclotides has attracted increasing attention in recent years. However, the existing cyclotide detection methods face limitations in sensitivity, accuracy, and reliability. To address these challenges, we developed an integrated strategy using a combination of strong cation exchange chromatography techniques for removing interfering small molecules, Orbitrap Exploris 480 mass spectrometry (OEMS); this is a detection and database searching-based method for cyclotide verification, which greatly improved the sensitivity, accuracy, and reliability of cyclotide identification. This strategy was subsequently employed for cyclotide mapping in Viola with a minute amount of starting tissue, resulting the identification of 65 known and 18 potentially novel cyclotides, which is the largest dataset of cyclotides for Viola philippica. This strategy provided valuable insights into the cyclotide diversity and distribution in V. philippica, with potential applications in drug discovery and other biomedical fields.

The accuracy of drought monitoring models is crucial for drought monitoring and early warning. Random forest (RF) is being used widely in the field of artificial intelligence. Nonetheless, the application of a random forest model in grassland drought monitoring research is yet to be further explored. In this study, various drought hazard factors were integrated based on remote sensing data, including from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Global Precipitation Measurement (GPM), as multisource remote sensing data. Based on the RF, a comprehensive grassland drought monitoring model was constructed and tested in Inner Mongolia, China, as an example. The critical issue addressed is the construction of a grassland drought disaster monitoring model based on meteorological data and multisource remote sensing data by using an RF model, and the verification of the accuracy and reliability of its monitoring results. The results show that the grassland drought monitoring model could quantitatively monitor the drought situation in Inner Mongolia grasslands. There was a significantly positive correlation between the drought indicators output by the model and the standardized precipitation evapotranspiration index (SPEI) measured in the field. The correlation coefficients (R) between the drought degree were 0.9706 and 0.6387 for the training set and test set, respectively. The consistent rate between the model drought index and the SPEI reached 87.90%. Drought events in Inner Mongolia were monitored from April to September in wet years, normal years, and dry years using the constructed model. The monitoring results of the model constructed in this study were in accordance with the actual drought conditions, reflecting the development and spatial evolution of drought conditions. This study provides a new application method for the comprehensive assessment of grassland drought.

Anxiety commonly co-occurs with obsessive-compulsive disorder (OCD). Both of them are closely related to stress. However, the shared neurobiological substrates and therapeutic targets remain unclear. Here we report an amelioration of both anxiety and OCD via the histamine presynaptic H3 heteroreceptor on glutamatergic afferent terminals from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core, a vital node in the limbic loop. The NAc core receives direct hypothalamic histaminergic projections, and optogenetic activation of hypothalamic NAc core histaminergic afferents selectively suppresses glutamatergic rather than GABAergic synaptic transmission in the NAc core via the H3 receptor and thus produces an anxiolytic effect and improves anxietyand obsessive-compulsive-like behaviors induced by restraint stress. Although the H3 receptor is expressed in glutamatergic afferent terminals from the PrL, basolateral amygdala (BLA), and ventral hippocampus (vHipp), rather than the thalamus, only the PrL– and not BLA– and vHipp–NAc core glutamatergic pathways among the glutamatergic afferent inputs to the NAc core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Furthermore, activation of the H3 receptor ameliorates anxiety and obsessive-compulsive-like behaviors induced by optogenetic excitation of the PrL–NAc glutamatergic afferents. These results demonstrate a common mechanism regulating anxiety- and obsessive-compulsive-like behaviors and provide insight into the clinical treatment strategy for OCD with comorbid anxiety by targeting the histamine H3 receptor in the NAc core.

To achieve the goals of “carbon peaking and carbon neutrality”, this paper puts forward the connotation and measurement method for the carbon emission intensity of urban industrial land and conducts an empirical study with the Yangtze River Economic Belt (YREB) as an example. We defined the carbon intensity of urban industrial land as the industrial carbon emissions per unit area of land, which is a spatial mapping of urban industrial economic development and carbon spillover and a key indicator for urban and territorial spatial planning oriented towards the “dual carbon” goal. Findings: The carbon emission density of industrial land in the YREB varied greatly between cities and exhibited significant positive spatial autocorrelation. In addition, the geographical pattern and spatio-temporal evolution model of the urban industrial land carbon emission density had a very complex driving mechanism, and different factors had significant synergistic effects. Therefore, it is suggested that while striving towards the goal of “dual carbon”, the government should incorporate the carbon emission density indicator of urban industrial land into the urban and territorial spatial planning system, and based on the threshold of the medium suitable density, they should design differentiated management policies according to concrete urban policies and encourage cooperation among cities to jointly promote carbon emission management of urban industrial land. In policy design, emphasis should also be placed on highlighting the interactive effects of foreign direct investment, fiscal expenditure, and the number of patent authorizations as well as constructing a combination of policies centered around them to better leverage the impacts of globalization, government intervention, and innovation.