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Background Damage in the ischemic core and penumbra after stroke affects patient prognosis. Microglia immediately respond to ischemic insult and initiate immune inflammation, playing an important role in the cellular injury after stroke. However, the microglial heterogeneity and the mechanisms involved remain unclear. Methods We first performed single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) on middle cerebral artery occlusion (MCAO) mice from three time points to determine stroke-associated microglial subclusters and their spatial distributions. Furthermore, the expression of microglial subcluster-specific marker genes and the localization of different microglial subclusters were verified on MCAO mice through RNAscope and immunofluorescence. Gene set variation analysis (GSVA) was performed to reveal functional characteristics of microglia sub-clusters. Additionally, ingenuity pathway analysis (IPA) was used to explore upstream regulators of microglial subclusters, which was confirmed by immunofluorescence, RT-qPCR, shRNA-mediated knockdown, and targeted metabolomics. Finally, the infarct size, neurological deficits, and neuronal apoptosis were evaluated in MCAO mice after manipulation of specific microglial subcluster. Results We discovered stroke-associated microglial subclusters in the brains of MCAO mice. We also identified novel marker genes of these microglial subclusters and defined these cells as ischemic core-associated (ICAM) and ischemic penumbra-associated (IPAM) microglia, according to their spatial distribution. ICAM, induced by damage-associated molecular patterns, are probably fueled by glycolysis, and exhibit increased pro-inflammatory cytokines and chemokines production. BACH1 is a key transcription factor driving ICAM generation. In contrast, glucocorticoids, which are enriched in the penumbra, likely trigger IPAM formation, which are presumably powered by the citrate cycle and oxidative phosphorylation and are characterized by moderate pro-inflammatory responses, inflammation-alleviating metabolic features, and myelinotrophic properties. Conclusions ICAM could induce excessive neuroinflammation, aggravating brain injury, whereas IPAM probably exhibit neuroprotective features, which could be essential for the homeostasis and survival of cells in the penumbra. Our findings provide a biological basis for targeting specific microglial subclusters as a potential therapeutic strategy for ischemic stroke.

The triglyceride-glucose index (TyG) has been actively researched for predicting several diseases. However, high-quality evidence assessing its ability to predict stroke is lacking. We conducted a meta-analysis of high-quality studies examining if TyG can predict stroke in the general population. Embase, PubMed, CENTRAL, Web of Science, and Scopus databases were searched until 13th January 2025. Cohort studies on the general population, excluding those with baseline stroke or cardiovascular disease, with a minimum follow-up of four years and reporting an adjusted association between TyG and stroke were included. TyG was assessed as both a categorical and continuous variable. A total of 13 studies with 12,898,434 individuals were eligible. The overall incidence of stroke was 0.89%. Meta-analysis indicated a statistically significant increased risk of stroke between higher vs lower values of TyG (risk ratio (RR): 1.27 95% confidence interval (CI) [1.19-1.35]  = 66%). Per unit increase in TyG was also associated with a statistically significant increase in the risk of stroke (RR: 1.16 95% CI [1.07-1.27]  = 89%). Most results remained unchanged on subgroup analysis based on location, excluded population, stroke diagnosis, TyG data, and follow-up. Meta-regression using moderators sample size, age, male gender, diabetes mellitus, hypertension, TyG cut-off, stroke incidence, and follow-up also failed to reveal significant results. High TyG is associated with increased risk of stroke in the general population.

Both weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

White matter injury (WMI), which reflects myelin loss, contributes to cognitive decline or dementia caused by cerebral vascular diseases. However, because pharmacological agents specifically for WMI are lacking, novel therapeutic strategies need to be explored. It is recently found that adaptive myelination is required for homeostatic control of brain functions. In this study, adaptive myelination‐related strategies are applied to explore the treatment for ischemic WMI‐related cognitive dysfunction. Here, bilateral carotid artery stenosis (BCAS) is used to model ischemic WMI‐related cognitive impairment and uncover that optogenetic and chemogenetic activation of glutamatergic neurons in the medial prefrontal cortex (mPFC) promote the differentiation of oligodendrocyte precursor cells (OPCs) in the corpus callosum, leading to improvements in myelin repair and working memory. Mechanistically, these neuromodulatory techniques exert a therapeutic effect by inducing the secretion of Wnt2 from activated neuronal axons, which acts on oligodendrocyte precursor cells and drives oligodendrogenesis and myelination. Thus, this study suggests that neuromodulation is a promising strategy for directing myelin repair and cognitive recovery through adaptive myelination in the context of ischemic WMI. Optogenetic and chemogenetic activation of mPFC glutamatergic neurons after chronic ischemia upregulate the expression of neuron‐derived Wnt2, which acts on OPCs and promotes their differentiation toward oligodendrocytes, leading to myelin repair and improved cognitive function. The current finding highlights that neuromodulation is a promising strategy for directing adaptive myelination in the context of chronic ischemia.

Lactate plays diverse roles in brain pathophysiology, including ischemic stroke. Here, the role of lysine lactylation, an epigenetic modification of lactate, in cerebral ischemia is investigated. Using a mouse model of transient middle cerebral artery occlusion, increased brain lactate levels and global protein lactylation are observed. Proteomics analysis reveals significant lactylation of non‐histone proteins in the ischemic penumbra. Lactylation of MeCP2, a transcriptional regulator, is identified as a protective mechanism against stroke‐induced neuronal death. Inhibition of MeCP2 lactylation through chemical or genetic manipulation increases infarct volume and aggravates neurological deficits. Mechanistically, MeCP2 lactylation at K210/K249 represses the transcription of apoptosis‐associated genes, including Pdcd4 and Pla2g6, thereby attenuating neuronal apoptosis. Additionally, HDAC3 and p300 are identified as key enzymes that regulate MeCP2 lactylation post‐stroke. The findings suggest that MeCP2 lactylation offers a potential therapeutic target for alleviating neuronal damage and improving stroke outcomes. MeCP2 lactylation protects against ischemic stroke by reducing brain infarct volume and improving neurological outcomes. Lactylation at K210/K249 exerts neuroprotective effects by repressing the transcription of apoptosis‐associated genes, including Pdcd4 and Pla2g6. HDAC3 and p300 serve as key regulatory enzymes for MeCP2 lactylation following stroke.

The polymer industry is confronting an urgent sustainability trilemma: accelerating plastic pollution, substantial CO 2 emissions from production processes, and dependence on diminishing fossil resources. Upcycling CO 2 into polymers presents a promising solution to these interconnected issues; however, existing CO 2 -to-polymer technologies face significant challenges: dependence on concentrated CO 2 sources rather than direct air capture (DAC), reliance on complex catalysts and energy-intensive conditions (elevated temperatures/pressures), and generation of polymers with limited self-healing and recyclability. Herein, we propose a catalyst-free strategy of converting atmospheric CO 2 into carbonate ions (CO 3 2- ) as intermediates for the synthesis of dynamic covalent polymers. This approach is based on a dynamic bond system, termed the CO 3 2- -bridged dynamic covalent bond, enabling catalyst-free synthesis of polymers from ambient air at room temperature and pressure. The resultant polymers show excellent mechanical properties, rapid self-healing, and versatile circularity through three distinct pathways: thermal reprocessing, closed-loop chemical recycling via acid-triggered depolymerization at room temperature, and upcycling of mixed CO 2 -derived polymers into hybrid materials with enhanced properties. This study provides a platform for both low-energy-consuming CO 2 valorization and the development of sustainable polymers.

Lipid droplets (LDs) were reported to play an important role in the modulation of inflammation and various cellular processes among multiple cell types. However, LDs accumulation, its function and mechanisms of its formation during ischemic stroke remained poorly-identified. In this study, we observed increased LDs accumulation in microglia at the acute stage of ischemic stroke by immunofluorescence and flow cytometry. Transcriptomic analysis indicated that microglia accumulated with LDs were associated with inflammation and phagocytosis. Both inflammatory activation and phagocytosis of tissue debris in microglia could contribute to LDs formation. Moreover, through specific LDs depletion and overload experiments by pharmacological approaches, we proposed that LDs was critical for the maintenance of anti-inflammatory properties of microglia. Furthermore, Atglistatin, a specific adipose triglyceride lipase (ATGL) inhibitor, was shown to prevent proinflammatory cytokines production in primary microglia through decreased LDs lipolysis. After Atglistatin treatment, middle cerebral artery occlusion (MCAO) mice showed decreased infarct volume and improved neurobehavioral performance at the acute stage of stroke. Our findings provided a biological basis for microglial LDs regulation as a potential therapeutic strategy for acute ischemic stroke and uncovered the neuroprotective role of Atglistatin in the treatment of MCAO mice.

Aquaculture wastewater is one of the most important alternative water resources in arid regions where scarcity of fresh water is common. Irrigation with this kind of water may affect soil microbial functional diversity and community structure as changes of soil environment would be significant. Here, we conducted a field sampling to investigate these effects using Biolog and metagenomic methods. The results demonstrated that irrigation with aquaculture wastewater could dramatically reduce soil microbial functional diversity. The values of diversity indices and sole carbon source utilization were all significantly decreased. Increased soil salinity, especially Cl concentration, appeared primarily associated with the decreases. Differently, higher bacterial community diversity was obtained in aquaculture wastewater irrigated soils. More abundant phyla Actinobacteria, Chloroflexi, Acidobacteria, Gemmatimonadetes and fewer members of Proteobacteria, Bacteroidetes and Planctomycetes were found in this kind of soils. Changes in the concentration of soil Cl mainly accounted for the shifts of bacterial community composition. This research can improve our understanding of how aquaculture wastewater irrigation changes soil microbial process and as a result, be useful to manage soil and wastewater resources in arid regions.

The polymer industry is confronting an urgent sustainability trilemma: accelerating plastic pollution, substantial CO emissions from production processes, and dependence on diminishing fossil resources. Upcycling CO into polymers presents a promising solution to these interconnected issues; however, existing CO -to-polymer technologies face significant challenges: dependence on concentrated CO sources rather than direct air capture (DAC), reliance on complex catalysts and energy-intensive conditions (elevated temperatures/pressures), and generation of polymers with limited self-healing and recyclability. Herein, we propose a catalyst-free strategy of converting atmospheric CO into carbonate ions (CO ) as intermediates for the synthesis of dynamic covalent polymers. This approach is based on a dynamic bond system, termed the CO -bridged dynamic covalent bond, enabling catalyst-free synthesis of polymers from ambient air at room temperature and pressure. The resultant polymers show excellent mechanical properties, rapid self-healing, and versatile circularity through three distinct pathways: thermal reprocessing, closed-loop chemical recycling via acid-triggered depolymerization at room temperature, and upcycling of mixed CO -derived polymers into hybrid materials with enhanced properties. This study provides a platform for both low-energy-consuming CO valorization and the development of sustainable polymers.

Microglia-mediated neuroinflammation plays a crucial role in multiple neurological diseases. We have previously found that Atglistatin, the mouse Adipose Triglyceride Lipase (ATGL) inhibitor, could promote lipid droplets (LDs) accumulation and suppress LPS-induced neuroinflammation in mouse microglia. However, Atglistatin was species-selective, which limited its use in clinical settings. Here, we found that NG-497, a previously identified human ATGL inhibitor, significantly increased LDs accumulation and inhibited LPS-induced pro-inflammatory responses in human microglia. Moreover, NG-497 also protected human neurons against neurotoxic cytokines in a humanized in vitro model of neuroinflammation. However, the anti-inflammatory capacity of NG-497 was independent of its effect on ATGL. Instead, we revealed that NG-497 alleviated microglia-mediated neuroinflammation through elevating the protein level of melatonin receptor 1A (MTNR1A). Therefore, in this study, we uncovered a novel MTNR1A-targeting compound, which exhibited anti-inflammatory and neuroprotective effect, highlighting its potential in the treatment of neuroinflammation. Moreover, the MTNRs agonist, Ramelteon, exerts comparable anti-inflammation effects with NG-497.