Explore the vast range of titles available.

The composition and configuration of landscapes are critical important to design effective approaches to mitigate urban thermal environment in the urbanization process. In this research, land use maps and land surface temperature (LST) retrieval were derived in Nanchang city of central China based on product datasets and the thermal infrared band of Landsat. The results showed that the thermal environment of Nanchang had become worse over the past two decades, that is, the proportion of area of the extremely low temperature zone (ELTZ) decreased from 4.39 to 0.77% from 2001 to 2020, and that of medium temperature zone (MTZ) reduced by 20%, whereas those of the high temperature zone (HTZ) and the extremely high temperature zone (EHTZ) increased sharply after 2001, and by 2020, the area ratio increased by 11% and 7.16%, respectively. The agricultural land (AL) area decreased from 68.44 to 49.69%, was gradually replaced by construction land (CL). The CL occupied the largest proportion in EHTZ, HTZ and slight high temperature zone (SHTZ); water landscape (WL) and green land (GL) occupied the largest proportion in ELTZ, low temperature zone (LTZ); and AL occupied the largest proportion in SHTZ, MTZ, and slight low temperature zone (SLTZ). Landscape configuration also obviously impacted on LST. The model fitting was well (R = 0.87) between land use area and LST by multiple regression analysis. The significant correlation between LST and six landscape pattern indices of CL ( p  < 0.01) indicated that the larger percent (PLANT, R = 0.78) and the more concentrate (LPI, R = 0.73) of CL implied the higher LST, while the more fragment (NP, R = − 0.45), dispersed and complex shape (R = − 0.35) were benefit to relieve LST. Contrastively, the larger percent and the more concentrated and complex shape distribution of AL, GL and WL, the lower LST ( p  < 0.01). In addition, LST had closely correlation with landscape level indices such as aggregation degree (AI, R = 0.44) and diversity (SHDI, R = − 0.60) ( p  < 0.01).

Background In the central nervous system (CNS), connexin 43 (Cx43) is mainly expressed in astrocytes and regulates astrocytic network homeostasis. Similar to Cx43 overexpression, abnormal excessive opening of Cx43 hemichannels (Cx43Hcs) on reactive astrocytes aggravates the inflammatory response and cell death in CNS pathologies. However, the role of excessive Cx43Hc opening in intracerebral hemorrhage (ICH) injury is not clear. Methods Hemin stimulation in primary cells and collagenase IV injection in C57BL/6J (B6) mice were used as ICH models in vitro and in vivo. After ICH injury, the Cx43 mimetic peptide Gap19 was used for treatment. Ethidium bromide (EtBr) uptake assays were used to measure the opening of Cx43Hcs. Western blotting and immunofluorescence were used to measure protein expression. qRT-PCR and ELISA were used to determine the levels of cytokines. Coimmunoprecipitation (Co-IP) and the Duolink in situ proximity ligation assay (PLA) were applied to measure the association between proteins. Results In this study, Cx43 expression upregulation and excessive Cx43Hc opening was observed in mice after ICH injury. Delayed treatment with Gap19 significantly alleviated hematoma volume and neurological deficits after ICH injury. In addition, Gap19 decreased inflammatory cytokine levels in the tissue surrounding the hematoma and decreased reactive astrogliosis after ICH injury in vitro and in vivo. Intriguingly, Cx43 transcriptional activity and expression in astrocytes were significantly increased after hemin stimulation in culture. However, Gap19 treatment downregulated astrocytic Cx43 expression through the ubiquitin-proteasome pathway without affecting Cx43 transcription. Additionally, our data showed that Gap19 increased Yes-associated protein (YAP) nuclear translocation. This subsequently upregulated SOCS1 and SOCS3 expression and then inhibited the TLR4-NFκB and JAK2-STAT3 pathways in hemin-stimulated astrocytes. Finally, the YAP inhibitor, verteporfin (VP), reversed the anti-inflammatory effect of Gap19 in vitro and almost completely blocked its protective effects in vivo after ICH injury. Conclusions This study provides new insight into potential treatment strategies for ICH injury involving astroglial Cx43 and Cx43Hcs. Suppression of abnormal astroglial Cx43 expression and Cx43Hc opening by Gap19 has anti-inflammatory and neuroprotective effects after ICH injury.

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.

Microglia-mediated neuroinflammation is involved in various neurological diseases, including ischemic stroke, but the endogenous mechanisms preventing unstrained inflammation is still unclear. The anti-inflammatory role of transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) in macrophages and microglia has previously been identified. However, the endogenous mechanisms that how NR4A1 restricts unstrained inflammation remain elusive. Here, we observed that NR4A1 is up-regulated in the cytoplasm of activated microglia and localizes to processing bodies (P-bodies). In addition, we found that cytoplasmic NR4A1 functions as an RNA-binding protein (RBP) that directly binds and destabilizes Tnf mRNA in an N6-methyladenosine (m 6 A)-dependent manner. Remarkably, conditional microglial deletion of Nr4a1 elevates Tnf expression and worsens outcomes in a mouse model of ischemic stroke, in which case NR4A1 expression is significantly induced in the cytoplasm of microglia. Thus, our study illustrates a novel mechanism that NR4A1 posttranscriptionally regulates Tnf expression in microglia and determines stroke outcomes.

Chrysin is one of the natural flavonoid compounds Sourced from various plant source, mainly in propolis and honey, demonstrates effective Cancer-suppressing properties, particularly in Breast cancer (BC). However, the specific molecular mechanisms underlying its efficacy in breast cancer treatment have remained elusive. This study employed network pharmacology combined with a molecular docking approach to uncover the intricate details of Chrysin’s impact on breast cancer. Utilizing databases such as GeneCards, and disgenet, Pharmmapper, ctd database, Chrysin and potential breast cancer targets were meticulously curated. Through a strategic process of mapping and screening, core targets essential for Chrysin’s efficacy in breast cancer treatment were identified. Further refinement through Venn diagram analysis, considering 1350 breast cancer target genes and 433 Chrysin-related targets, identified 140 intersection targets. Subsequent construction of protein–protein interaction networks of 140 intersecting using the STRING and Cytoscape software highlighted these ten targets as core candidates. Functional annotation and pathway analysis, performed using the ShinyGO database, unveiled that the key targets were significantly associated with the Prostate cancer pathways and IL17 signaling pathways. Molecular docking results underscored Chrysin’s effective binding to these ten key targets, forming stable protein–ligand complexes. Molecular docking analyses were then conducted to evaluate the impact of Chrysin in the key targets, revealing TP53, JUN, HIF1A, ALB, CASP3, STAT3, BCL2, TNF, AKT1, and IL6 as pivotal players. In summary, this investigation provides valuable revelations into the essential targets and molecular processes through which Chrysin exerts its anti-breast cancer effects. These findings not only enhance our understanding of Chrysin’s pharmacological actions in breast cancer but also lay a theoretical groundwork for future investigations into the therapeutic mechanisms of Chrysin in this context.

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.

Background Ischemic stroke triggers excessive microglial activation and sustained neuroinflammation, driving secondary neuronal injury. Recent evidence suggests that dysfunction of the autophagy-lysosome system may be a crucial factor sustaining microglial pro-inflammatory responses, yet the underlying regulatory mechanisms remain unclear. NOD-like receptor family caspase recruitment domain-containing protein 5 (NLRC5) has been widely studied in various immune and inflammatory diseases and exhibits functional heterogeneity under different pathological conditions. However, the role of NLRC5 in modulating post-stroke neuroinflammation remains unclear. Methods NLRC5 expression and localization was examined in a mouse transient middle cerebral artery occlusion (tMCAO) model and postmortem brain tissue from stroke patients. A microglia-specific Nlrc5 knockout (mCKO) mice line was generated to evaluate the effects of Nlrc5 deletion on neurological function, infarct volume, neuronal apoptosis, and inflammatory response after ischemic stroke. Proteomics, mass spectrometry, and molecular biology assays were conducted to elucidate the mechanisms. Results NLRC5 expression was upregulated in the ischemic penumbra of mouse models and appeared higher in postmortem brain tissues from stroke patients, specifically in activated microglia. Strikingly, mCKO mice exhibited significantly improved neurological outcomes, reduced infarct volumes, and attenuated neuronal apoptosis post-stroke. In vitro studies demonstrated that NLRC5 induction by various stimuli, including oxygen-glucose deprivation/reperfusion (OGD/R), lipopolysaccharide (LPS), as well as neuronal debris and supernatant, promoted pro-inflammatory cytokine release and microglia-mediated neurotoxicity, whereas Nlrc5 deletion exerted protective effects. Mechanistically, NLRC5 did not influence autophagosome formation but profoundly disrupted autophagic flux by impairing lysosomal function. Proteomic and biochemical analyses revealed that NLRC5 binds interferon-stimulated gene 15 (ISG15) via its CARD domain, shielding ISG15 from autophagy-lysosomal degradation. Furthermore, NLRC5-induced lysosomal defects and inflammatory responses were abolished in the absence of Isg15 . Conclusion NLRC5 promotes microglial inflammation and exacerbates post-stroke brain injury by stabilizing ISG15 and disrupting lysosomal function and autophagic flux. NLRC5-ISG15 axis is a therapeutic target for immune modulation in ischemic stroke.

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.

Microglia are the resident macrophages in the brain, which play a critical role in post-stroke neuroinflammation. Accordingly, targeting neuroinflammation could be a promising strategy to improve ischemic stroke outcomes. Ethyl ferulate (EF) has been confirmed to possess anti-inflammatory properties in several disease models, including acute lung injury, retinal damage and diabetes-associated renal injury. However, the effects of EF on microglial activation and the resolution of post-stroke neuroinflammation remains unknown. Here, we found that EF suppressed pro-inflammatory response triggered by lipopolysaccharide (LPS) stimulation in primary microglia and BV2 cell lines, as well as post-stroke neuroinflammation in an in vivo transient middle cerebral artery occlusion (tMCAO) stroke model in C57BL/6 mice, consequently ameliorating ischemic brain injury. Furthermore, EF could directly bind and inhibit the activity of monoamine oxidase B (MAO-B) to reduce pro-inflammatory response. Taken together, our study identified a MAO-B inhibitor, Ethyl ferulate, as an active compound with promising potentials for suppressing post-stroke neuroinflammation.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are two homologous transcriptional coactivators and the final effectors of the Hippo signaling transduction pathway. The transcriptional activity of YAP/TAZ is dependent on their recruitment to the nucleus, which promotes binding to the transcription factor of TEA domain family members 1-4 (TEAD1-4). In Hippo-signaling pathway, YAP/TAZ is inactivated and its translocation to the nucleus is blocked via a core kinase cascade stimulated by a variety of upstream signals, such as G-protein-coupled receptor signaling, mechanical pressure, and adherens junction signaling. This pathway plays a very important role in regulating organ size, tissue homeostasis, and tumor development. In recent years, many studies have reported upregulation or nuclear localization of YAP/TAZ in a number of human malignancies, such as breast cancer, melanoma, lung cancer, especially squamous cell carcinoma in different organs. A large number of experiments demonstrate that YAP/TAZ activation promotes cancer formation, progression, and metastasis. Therefore, in this review, we summarize the evidence of regulation and function of YAP/TAZ and discuss its role in squamous cell carcinoma. Collectively, this summary strongly suggests that targeting aberrant YAP/TAZ activation is a promising strategy for the suppression of squamous cell carcinoma.