Enhancing interfacial electron transfer through PANI electron bridge for tailoring dynamic reconstruction and achieving high-performance water oxidation.

Tailoring the dynamic reconstruction of transition metal compounds into highly active oxyhydroxides through surface electron state modification is crucial for advancing water oxidation, yet remains a formidable challenge. In this study, a unique polyaniline (PANI) electron bridge was integrated into the metal-organic frameworks (MOFs)/layer double hydroxides (LDHs) heterojunction to expedite electron transfer from MOFs to LDHs, facilitating electron accumulation at the metal sites within MOF and electron-deficient LDHs. This configuration promotes the surface dynamic reconstruction of LDHs into highly active oxyhydroxides while safeguarding the MOF from corrosion in harsh environments over extended periods. The optimized electronic structure modification of both MOFs and LDHs enhances reaction kinetics. The superior MIL-88B(Fe)@PANI@NiCo LDH catalyst achieved 10 mA∙cm-2 at an overpotential of 202 mV and demonstrated stable operation for 120 h at this current density. This research introduces an innovative approach for guiding electron transfer and dynamic catalyst reconstruction by constructing a PANI electron bridge, potentially paving the way for more efficient catalytic systems.

Macrophages in the infarcted heart acquire a fibrogenic phenotype, expressing matricellular proteins, but do not undergo fibroblast conversion.

Although some studies have suggested that macrophages may secrete structural collagens, and convert to fibroblast-like cells, macrophage to fibroblast transdifferentiation in infarcted and remodeling hearts remains controversial. Our study uses linage tracing approaches and single cell transcriptomics to examine whether macrophages undergo fibroblast conversion, and to characterize the extracellular matrix expression profile of myeloid cells in myocardial infarction. To examine whether infarct macrophages undergo fibroblast conversion, we identified macrophage-derived progeny using the inducible CX3CR1CreER mice crossed with the PDGFRαEGFP reporter line for reliable fibroblast identification. The abundant fibroblasts that infiltrated the infarcted myocardium after 7 and 28 days of coronary occlusion were not derived from CX3CR1+ macrophages. Infarct macrophages retained myeloid cell characteristics and did not undergo conversion to myofibroblasts, endothelial or vascular mural cells. Single cell RNA-seq of CSF1R+ myeloid cells harvested from control and infarcted hearts showed no significant expression of fibroblast identity genes by myeloid cell clusters. Moreover, infarct macrophages did not express significant levels of genes encoding structural collagens. However, infarct macrophage and monocyte clusters were the predominant source of the fibrogenic growth factors Tgfb1 and Pdgfb, and of the matricellular proteins Spp1/Osteopontin, Thbs1/Thrombospondin-1, Emilin2, and Fn1/fibronectin, while expressing significant amounts of several other matrix genes, including Vcan/versican, Ecm1 and Sparc. ScRNA-seq data suggested similar patterns of matrix gene expression in human myocardial infarction. In conclusion, infarct macrophages do not undergo fibroblast or myofibroblast conversion and do not exhibit upregulation of structural collagens but may contribute to fibrotic remodeling by producing several fibrogenic matricellular proteins.

Targeting SMYD2 promotes ferroptosis and impacts the progression of pancreatic cancer through the c-Myc/NCOA4 axis-mediated ferritinophagy.

BACKGROUND: Pancreatic cancer (PC) is characterized by a poor prognosis and limited treatment options. Ferroptosis plays an important role in cancer, SET and MYND domain-containing protein 2 (SMYD2) is widely expressed in various cancers. However, the role of SMYD2 in regulating ferroptosis in PC remains unexplored. This study aimed to investigate the role of SMYD2 in mediating ferroptosis and its mechanistic implications in PC progression. METHODS: The levels of SMYD2, c-Myc, and NCOA4 were assessed in PC tissues, and peritumoral tissues. SMYD2 expression was further analyzed in human PC cell lines. In BxPC3 cells, the expression of c-Myc, NCOA4, autophagy-related proteins, and mitochondrial morphology, was evaluated following transfection with si-SMYD2 and treatment with autophagy inhibitors and ferroptosis inhibitors. Ferroptosis levels were quantified using flow cytometry and ELISA assays. RNA immunoprecipitation was conducted to elucidate the interaction between c-Myc and NCOA4 mRNA. A xenograft mouse model was constructed to validate the impact of SMYD2 knockdown on PC growth. RESULTS: SMYD2 and c-Myc were found to be highly expressed in PC tissues, while NCOA4 showed reduced expression. Among the PC cell lines studied, BxPC3 cells exhibited the highest SMYD2 expression. SMYD2 knockdown led to decreased c-Myc levels, increased NCOA4 expression, reduced autophagy-related protein expression, mitochondrial shrinkage, and heightened ferroptosis levels. Additionally, an interaction between c-Myc and NCOA4 was identified. In vivo, SMYD2 knockdown inhibited tumor growth. CONCLUSIONS: Targeting SMYD2 inhibits PC progression by promoting ferritinophagy-dependent ferroptosis through the c-Myc/NCOA4 axis. These findings provide insights into potential diagnostic and therapeutic strategies for PC.

A global annual fractional tree cover dataset during 2000-2021 generated from realigned MODIS seasonal data.

Fractional tree cover facilitates the depiction of forest density and its changes. However, it remains challenging to estimate tree cover from satellite data, leading to substantial uncertainties in forest cover changes analysis. This paper generated a global annual fractional tree cover dataset from 2000 to 2021 with 250 m resolution (GLOBMAP FTC). MODIS annual observations were realigned at the pixel level to a common phenology and used to extract twelve features that can differentiate between trees and herbaceous vegetation, which greatly reduced feature dimensionality. A massive training data, consisting of 465.88 million sample points from four high-resolution global forest cover products, was collected to train a feedforward neural network model to predict tree cover. Compared with the validation datasets derived from the USGS circa 2010 global land cover reference dataset, the R2 value, MAE, and RMSE were 0.73, 10.55%, and 17.98%, respectively. This dataset can be applied for assessment of forest cover changes, including both abrupt forest loss and gradual forest gain.

Seasonal migration patterns of Siberian Rubythroat (Calliope calliope) facing the Qinghai-Tibet Plateau.

BACKGROUND: Small songbirds respond and adapt to various geographical barriers during their annual migration. Global flyways reveal the diverse migration strategies in response to different geographical barriers, among which are high-elevation plateaus. However, few studies have been focused on the largest and highest plateau in the world, the Qinghai-Tibet Plateau (QTP) which poses a significant barrier to migratory passerines. The present study explored the annual migration routes and strategies of a population of Siberian Rubythroats (Calliope calliope) that breed on the north-eastern edge of the QTP. METHODS: Over the period from 2021 to 2023, we applied light-level geolocators (13 deployed, seven recollected), archival GPS tags (45 deployed, 17 recollected), and CAnMove multi-sensor loggers (with barometer, accelerometer, thermometer, and light sensor, 20 deployed, six recollected) to adult males from the breeding population of Siberian Rubythroat on the QTP. Here we describe the migratory routes and phenology extracted or inferred from the GPS and multi-sensor logger data, and used a combination of accelerometric and barometric data to describe the elevational migration pattern, flight altitude, and flight duration. All light-level geolocators failed to collect suitable data. RESULTS: Both GPS locations and positions derived from pressure-based inference revealed that during autumn, the migration route detoured from the bee-line between breeding and wintering grounds, leading to a gradual elevational decrease. The spring route was more direct, with more flights over mountainous areas in western China. This different migration route during spring probably reflects a strategy for faster migration, which corresponds with more frequent long nocturnal migration flights and shorter stopovers during spring migration than in autumn. The average flight altitude (1856 ± 781 m above sea level) was correlated with ground elevation but did not differ between the seasons. CONCLUSIONS: Our finding indicates strong, season-dependent impact of the Qinghai-Tibet Plateau on shaping passerine migration strategies. We hereby call for more attention to the unexplored central-China flyway to extend our knowledge on the environment-migration interaction among small passerines.

Decellularized Matrices for the Treatment of Tissue Defects: from Matrix Origin to Immunological Mechanisms.

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-ß/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

Spatial dynamics of mammalian brain development and neuroinflammation by multimodal tri-omics mapping.

The ability to spatially map multiple layers of the omics information over different time points allows for exploring the mechanisms driving brain development, differentiation, arealization, and alterations in disease. Herein we developed and applied spatial tri-omic sequencing technologies, DBiT ARP-seq (spatial ATAC-RNA-Protein-seq) and DBiT CTRP-seq (spatial CUT&Tag- RNA-Protein-seq) together with multiplexed immunofluorescence imaging (CODEX) to map spatial dynamic remodeling in brain development and neuroinflammation. A spatiotemporal tri-omic atlas of the mouse brain was obtained at different stages from postnatal day P0 to P21, and compared to the regions of interest in the human developing brains. Specifically, in the cortical area, we discovered temporal persistence and spatial spreading of chromatin accessibility for the layer-defining transcription factors. In corpus callosum, we observed dynamic chromatin priming of myelin genes across the subregions. Together, it suggests a role for layer specific projection neurons to coordinate axonogenesis and myelination. We further mapped the brain of a lysolecithin (LPC) neuroinflammation mouse model and observed common molecular programs in development and neuroinflammation. Microglia, exhibiting both conserved and distinct programs for inflammation and resolution, are transiently activated not only at the core of the LPC lesion, but also at distal locations presumably through neuronal circuitry. Thus, this work unveiled common and differential mechanisms in brain development and neuroinflammation, resulting in a valuable data resource to investigate brain development, function and disease.

Caries-Prone Primary Teeth: A Hidden Reason and Prophylactic Treatment in the Viewpoint of Materials Science.

Dental caries, the most prevalent chronic disease across all age groups, has a high prevalence, particularly among children. However, there is no specific and effective treatment for the prevention of caries in primary teeth (Pr.T.), which stems from a lack of knowledge regarding the basic nature of the tooth surface. Herein, we observed that the adhesion energies of the caries-related bacteria Streptococcus mutans and Streptococcus sanguinis to Pr.T were approximately 10 and 5.5 times higher than those to permanent teeth (Pe.T). A lower degree of mineralization and more hydrophilic characteristics of the Pr.T enamel account for this discrepancy. Accordingly, we proposed that the on-target modification of both hydroxyapatite and organic components on Pr.T by dual modification would render a sufficient hydration layer. This resulted in an approximately 11-time decrease in bacterial adhesion energy after treatment. In contrast, a single hydroxyapatite modification on Pe.T and young permanent teeth (Y.Pe.T) was sufficient to achieve a similar effect. Theoretical simulation further verified the rationality of the approach. Our findings may help understand the reason for Pr.T being caries-prone and provide references for treatment using resin restorations. This strategy offers valuable insights into daily oral hygiene and dental prophylactic treatment in children.

Dexamethasone induces trabecular meshwork cell myofibroblast transdifferentiation through ARHGEF26.

Glucocorticoid use may cause elevated intraocular pressure, leading to the development of glucocorticoid-induced glaucoma (GIG). However, the mechanism of GIG development remains incompletely understood. In this study, we subjected primary human trabecular meshwork cells (TMCs) and mice to dexamethasone treatment to mimic glucocorticoid exposure. The myofibroblast transdifferentiation of TMCs was observed in cellular and mouse models, as well as in human trabecular mesh specimens. This was demonstrated by the cytoskeletal reorganization, alterations in cell morphology, heightened transdifferentiation markers, increased extracellular matrix deposition, and cellular dysfunction. Knockdown of Rho guanine nucleotide exchange factor 26 (ARHGEF26) expression ameliorated dexamethasone-induced changes in cell morphology and upregulation of myofibroblast markers, reversed dysfunction and extracellular matrix deposition in TMCs, and prevented the development of dexamethasone-induced intraocular hypertension. And, this process may be related to the TGF-ß pathway. In conclusion, glucocorticoids induced the myofibroblast transdifferentiation in TMCs, which played a crucial role in the pathogenesis of GIG. Inhibition of ARHGEF26 expression protected TMCs by reversing myofibroblast transdifferentiation. This study demonstrated the potential of reversing the myofibroblast transdifferentiation of TMCs as a new target for treating GIG.

Experimental Study on Damage Effect of Mid-Infrared Pulsed Laser on Charge Coupled Device (CCD) and HgCgTe Detectors.

As the weak link in electro-optical imaging systems, photodetectors have always faced the threat of laser damage. In this paper, we experimentally investigated the damage mechanism of the photodetector induced by the out-of-band laser. The damage thresholds of the mid-infrared pulsed laser for Charge Coupled Device (CCD) and HgCdTe detectors were determined through damage experiments. The analysis of the damage phenomena and data for both CCD and HgCdTe detectors clearly demonstrated that out-of-band mid-infrared pulsed lasers could entirely incapacitate CCD and HgCdTe detectors. Our analysis of the damage process and data revealed that the primary mechanism of damage to CCD and HgCdTe detectors by mid-infrared pulsed lasers was primarily thermal. This study serves as a reference for further research on the mid-infrared pulsed laser damage mechanisms of CCD and HgCdTe detectors, as well as for laser protection and performance optimization in imaging systems.

Biogeographical distribution and community assembly of Myxococcota in mangrove sediments.

BACKGROUND: Myxococcota, characterized by their distinct social lifestyles, are widely distributed micro-predators in global sediments. They can feed on a wide range of bacterial, archaeal, and fungal prey. Myxococcota are capable of producing diverse secondary metabolites, playing key roles in microbial food webs, and regulating the microbial community structures in different ecosystems. However, Myxococcota are rarely pure cultured due to the challenging and stringent culturing conditions. Their natural distribution, niche differentiation, and predator-prey relationships in a specific habitat are poorly understood. RESULTS: In this study, we conducted a comprehensive analysis of the 16S rRNA gene sequence data from public databases and our collection. We compared the abundance, diversity, and distribution patterns of Myxococcota in various habitats, with a specific focus on mangroves. We found that Myxococcota accounted for 1.45% of the total prokaryotes in global sediments based on the abundance of 16S rRNA genes. Myxococcota are abundant and diverse in mangrove sediments. They tend to be more generalistic in mangroves than in other habitats due to their wide niche breadth. Besides, the deterministic processes (variable selection) influenced the assembly of mangrove Myxococcota communities significantly more than stochastic processes. Further, we determined that environmental factors explained a greater amount of total community variation in mangrove Myxococcota than geographical variables (latitude and sediment depth). In the end, through the analysis of microbial co-occurrence networks, Myxococcota emerges as a key component and functions as a connector in the mangrove microbial community. CONCLUSIONS: Our study enhances comprehension of mangrove Myxococcota's biogeography, assembly patterns, driving factors, and co-occurrence relationships, as well as highlights their unique niche and ecological importance in mangrove sediments.

A paper-based lateral flow immunochromatographic sensor for the detection of tricyclazole in rice.

Tricyclazole is commonly used to prevent rice blast to meet the carbohydrate intake needs of half of the global population, and a large number of toxicological reports indicate that monitoring of tricyclazole is necessary. Here, we analyzed the structure of tricyclazole and designed different hapten derivatization strategies to prepare a high-performance monoclonal antibody (half inhibition concentration of 1.61 ng/mL), and then a lateral flow immunochromatographic sensor based on gold nanoparticles for the detection of tricyclazole in rice, with a limit of detection of 6.74 µg/kg and 13.58 µg/kg in polished and brown rice, respectively. The recoveries in rice were in the range of 84.6-107.4%, no complex pretreatment was required for comparison with LC-MS/MS, and the comparative analysis demonstrated that our method had good accuracy and precision. Therefore, the developed lateral flow immunochromatographic analysis was a reliable and rapid means for the on-site analysis of tricyclazole in rice.

Corrosion Properties and Passive Film Interface of Inconel 718 in NaNO3 Solution for Laser-Assisted Electrochemical Machining.

Laser-assisted electrochemical machining (ECM) is an ideal manufacturing method for Inconel 718 (IN718) because of the method's high efficiency and good surface quality, and the basis for and key to laser-assisted ECM is its anodic electrochemical dissolution behavior. In this study, IN718 in a 10 wt % NaNO3 solution was subjected to innovative electrochemical testing and laser-assisted ECM experiments to investigate its corrosion properties and the passive film characteristics formed on its surface. The passivation-related behaviors and structures of the passive film were investigated based on open-circuit potentials, dynamic polarization, potentiostatic polarization, and electrochemical impedance spectroscopy. It was found that there was obvious active-passive-transpassive transition behavior, and the structure of the passive film in laser-assisted ECM exhibited pores and defects, resulting in weak corrosion resistance, compared with IN718 under ECM without laser irradiation. The chemical composition of the passive film was obtained by X-ray photoelectron spectroscopy. The results showed that the passive film was composed mainly of a mixture of NiO, Ni(OH)2, Cr2O3, CrO3, Fe2O3, α-Fe2O3, α-FeOOH, Nb2O5, NbO, MoO3, MoO2, and TiO2. The passive film formed by laser-assisted ECM was rich in NiO and TiO2 and lacked Cr2O3 and MoO3, which validated its pores and defect structures. A corresponding schematic model was also proposed to characterize the interface structure between the IN718 substrate and the passive film. Laser-assisted ECM tests were performed under different current densities and machining times, and the corrosion morphology of IN718 was identified. Corrosion pits and a loose product layer appeared on the machined surface at low current densities, and the dissolution mechanism was pitting. The quantity and depth of the corrosion pits dispersed on the machined surface clearly decreased as the current density increased. Finally, a quantitative corrosion model was established to characterize the dissolution behavior of IN718 in NaNO3 solution during laser-assisted ECM.

Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

In Situ Growth of Columnar PEG on PEDOT and Its Antifouling Properties.

The antifouling properties of conductive polymers have received extensive attention for biosensor and bioelectronic applications. Polyethylene glycol (PEG) is a well-known antifouling material, but the controlled regulation of the surface topography of PEG without a template remains a challenge. Here, we show a columnar structure antifouling conductive polymer brush with enhanced antifouling properties and considerable conductivity. The method involves synthesizing the 3,4-ethylenedioxythiophene monomer modified with azide (EDOT-N3), the electropolymerization of PEDOT-N3, and the in situ growth of PEG polymer brushes on PEDOT through double-click reactions. The resultant columnar structure polymer brush exhibits high electrical conductivity (3.5 Ω·cm2), ultrahigh antifouling property, electrochemical stability (capacitance retention was 93.8% after 2000 cycles of CV scans in serum), and biocompatibility.

Flow to Candidate: Temporal Knowledge Graph Reasoning With Candidate-Oriented Relational Graph.

Reasoning over temporal knowledge graphs (TKGs) is a challenging task that requires models to infer future events based on past facts. Currently, subgraph-based methods have become the state-of-the-art (SOTA) techniques for this task due to their superior capability to explore local information in knowledge graphs (KGs). However, while previous methods have been effective in capturing semantic patterns in TKG, they are hard to capture more complex topological patterns. In contrast, path-based methods can efficiently capture relation paths between nodes and obtain relation patterns based on the order of relation connections. But subgraphs can retain much more information than a single path. Motivated by this observation, we propose a new subgraph-based approach to capture complex relational patterns. The method constructs candidate-oriented relational graphs to capture the local structure of TKGs and introduces a variant of a graph neural network model to learn the graph structure information between query-candidate pairs. In particular, we first design a prior directed temporal edge sampling method, which is starting from the query node and generating multiple candidate-oriented relational graphs simultaneously. Next, we propose a recursive propagation architecture that can encode all relational graphs in the local structures in parallel. Additionally, we introduce a self-attention mechanism in the propagation architecture to capture the query's preference. Finally, we design a simple scoring function to calculate the candidate nodes' scores and generate the model's predictions. To validate our approach, we conduct extensive experiments on four benchmark datasets (ICEWS14, ICEWS18, ICEWS0515, and YAGO). Experiments on four benchmark datasets demonstrate that our proposed approach possesses stronger inference and faster convergence than the SOTA methods. In addition, our method provides a relational graph for each query-candidate pair, which offers interpretable evidence for TKG prediction results.

Repair Effect of Umbilical Cord Mesenchymal Stem Cells Embedded in Hydrogel on Mouse Insulinoma 6 Cells Injured by Streptozotocin.

Umbilical cord mesenchymal stem cells (UC-MSCs) possess the capabilities of differentiation and immune modulation, which endow them with therapeutic potential in the treatment of type 2 diabetes mellitus (T2DM). In this study, to investigate the repair mechanism of UC-MSCs in hydrogel on pancreatic ß-cells in diabetes, mouse insulinoma 6 (MIN-6) cells damaged by streptozotocin (STZ) in vitro were used in co-culture with UC-MSCs in hydrogel (UC-MSCs + hydrogel). It was found that UC-MSCs + hydrogel had a significant repair effect on injured MIN-6 cells, which was better than the use of UC-MSCs alone (without hydrogel). After repair, the expression of superoxide dismutase (SOD) and catalase (CAT) as well as the total antioxidant capacity (T-AOC) of the repaired MIN-6 cells were increased, effectively reducing the oxidative stress caused by STZ. In addition, UC-MSCs + hydrogel were able to curb the inflammatory response by promoting the expression of anti-inflammatory factor IL-10 and reducing inflammatory factor IL-1ß. In addition, the expression of both nuclear antigen Ki67 for cell proliferation and insulin-related genes such as Pdx1 and MafA was increased in the repaired MIN-6 cells by UC-MSCs + hydrogel, suggesting that the repair effect promotes the proliferation of the injured MIN-6 cells. Compared with the use of UC-MSCs alone, UC-MSCs + hydrogel exhibit superior antioxidant stress resistance against injured MIN-6 cells, better proliferation effects and a longer survival time of UC-MSCs because the porous structure and hydrophilic properties of the hydrogel could affect the growth of cells and slow down their metabolic activities, resulting in a better repair effect on the injured MIN-6 cells.

The role of m6A methylation in targeted therapy resistance in lung cancer.

Targeted therapies have greatly improved clinical outcomes for patients with lung cancer (LC), but acquired drug resistance and disease relapse inevitably occur. Increasingly, the role of epigenetic mechanisms in driving acquired drug resistance is appreciated. In particular, N6-methyladenosine (m6A), one of the most prevalent RNA modifications, has several roles regulating RNA stability, splicing, transcription, translation, and destruction. Numerous studies have demonstrated that m6A RNA methylation can modulate the growth and invasion of cancer cells as well as contribute to targeted therapy resistance in LC. In this study, we outline what is known regarding the function of m6A in the acquisition of targeted therapy resistance in LC.

DNMT3A dysfunction promotes neuroinflammation and exacerbates acute ischemic stroke.

Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well-characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A-driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.