Oil-recovery performance of a superhydrophobic sponge-covered disc skimmer.

Frequent oil spill accidents caused by transportation, storage and usage may lead to severe damage on aquatic and ecological environments. Effective methods for rapid oil recovery are urgently in demand. Polyvinyl chloride, hydrophobic nano-SiO2, expanded graphite were separately applied to polyurethane and melamine sponge to fabricate superhydrophobic sponge material. The selected superhydrophobic sponge was introduced to establish sponge - covered disc skimmer. Oil recovery tests of the device were conducted to determine the optimum parameters. The examined operating conditions encompassed sponge thickness, immersion depth, rotational speed, oil slick thickness, operation time. The results showed that the melamine sponge modified by both polyvinyl chloride and hydrophobic nano-SiO2 exhibits super-hydrophobicity with a water contact angle of 150.3°. The absorption capacity for diesel oil can reach 53.89 g/g. The absorption capacity can still achieve 90 % of its initial capacity even after 500 extrusion-absorption separation tests. The results indicate the superiority of the superhydrophobic sponge covered surface in oil recovery over the standard steel surface regardless of the operating conditions. The recovery rate of the device can still achieve 96.4 % of its initial capacity with 95 % efficiency even after 85 h operation. The results suggest the superhydrophobic sponge - covered disc skimmer may have great application perspectives in oil spill recovery.

Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Secreted insulin-like growth factor binding protein 5 functions as a tumor suppressor and chemosensitizer through inhibiting insulin-like growth factor 1 receptor/protein kinase B pathway in acute myeloid leukemia.

BACKGROUND: In addition to being secreted into the intercellular spaces by exocytosis, insulin-like growth factor binding protein 5 (IGFBP5) may also remain in the cytosol or be transported to the nucleus. Depending on the different cellular context and subcellular distribution, IGFBP5 can act as a tumor suppressor or promoter through insulin-like growth factor -dependent or -independent mechanisms. Yet, little is known about the impacts of IGFBP5 on acute myeloid leukemia (AML) and its underlying mechanism. METHODS: Here we investigated the roles of IGFBP5 in human AML by using recombinant human IGFBP5 (rhIGFBP5) protein and U937 and THP1 cell lines which stably and ectopically expressed IGFBP5 or mutant IGFBP5 (mtIGFBP5) with the lack of secretory signal peptide. Cell counting kit-8 and flow cytometry assay were conducted to assess the cell viability, cell apoptosis and cell cycle distribution. Cytotoxicity assay was used to detect the chemosensitivity. Leukemia xenograft model and hematoxylin-eosin staining were performed to evaluate AML progression and extramedullary infiltration in vivo. RESULTS: In silico analysis demonstrated a positive association between IGFBP5 expression and overall survival of the AML patients. Both IGFBP5 overexpression and extrinsic rhIGFBP5 suppressed the growth of THP1 and U937 cells by inducing cell apoptosis and arresting G1/S transition and promoted the chemosensitivity of U937 and THP1 cells to daunorubicin and cytarabine. However, overexpression of mtIGFBP5 failed to demonstrate these properties. An in vivo xenograft mouse model of U937 cells also indicated that overexpression of IGFBP5 rather than mtIGFBP5 alleviated AML progression and extramedullary infiltration. Mechanistically, these biological consequences depended on the inactivation of insulin-like growth factor 1 receptor -mediated phosphatidylinositol-3-kinase/protein kinase B pathway. CONCLUSIONS: Our findings revealed secreted rather than intracellular IGFBP5 as a tumor-suppressor and chemosensitizer in AML. Upregulation of serum IGFBP5 by overexpression or addition of extrinsic rhIGFBP5 may serve as a suitable therapeutic approach for AML.

Deletion of Mettl3 in mesenchymal stem cells promotes acute myeloid leukemia resistance to chemotherapy.

Acute myeloid leukemia (AML) cell survival and chemoresistance are influenced by the existence of bone marrow mesenchymal stem cells (BMMSCs); however, the pathways by which BMMSCs contribute to these processes remain unclear. We earlier revealed that methyltransferase-like 3 (METTL3) expression is significantly reduced in AML BMMSCs and that METTL3 mediates BMMSC adipogenesis to promote chemoresistance in human AML cell lines in vitro. In this investigation, we evaluated the METTL3 function in vivo. Mice exhibiting a conditional removal of Mettl3 in BMMSCs were developed by mating Prrx1-CreERT2;Mettl3fl/+ mice with Mettl3fl/fl mice using the CRISPR-Cas9 system. The Mettl3 deletion increased bone marrow adiposity, enhanced disease progression in the transplantation-induced MLL-AF9 AML mouse model, and chemoresistance to cytarabine. The removal of Mettl3 in BMMSCs resulted in a significant increase in BMMSC adipogenesis. This effect was attributed to the downregulation of AKT1 expression, an AKT serine/threonine kinase 1, in an m6A-dependent manner. The development of chemoresistance in AML is linked to the promoted adipogenesis of BMMSCs. We conclude that METTL3 expression in BMMSCs has a critical function in limiting AML progression and chemoresistance, providing a basis for the progression of therapeutic approaches for AML.

[Relationship Between Carbon Emissions and Economic Development of Industrial Parks Based on Decoupling Index].

Industrial parks are the main carriers of industrial activities and are also key areas for carbon emissions. To deeply explore the decoupling state of carbon emissions and economic development of industrial parks and the driving forces, Zhengzhou Economic Development Zone were taken as example, based on the energy consumption data of industrial enterprises above a designated size from 2011 to 2020, the IPCC carbon emission accounting method, Tapio decoupling model, and logarithmic mean Divisia index decomposition method were used to analyze the characteristics of carbon emissions from energy consumption in the park, the relationship between carbon emissions and economic development, and the driving factors of decoupling. The results showed that:① in terms of carbon emission characteristics, the carbon emissions of energy consumption in Zhengzhou Economic Development Zone were mainly indirect carbon emissions, and the total carbon emissions showed a trend of rapid growth in the early stage, slowing down in the medium term, and negative growth in the later stage. The carbon emission intensity was decreasing annually. ② From the perspective of decoupling, the decoupling index between total carbon emissions and economic development in Zhengzhou Economic Development Zone from 2011 to 2016 was 1.021, which was in a state of growth linkage, and the decoupling index decreased to 0.089 from 2016 to 2020, turning into a weak decoupling state. ③ From the analysis of driving factors, from 2011 to 2016, four factors, namely carbon emission coefficient, energy efficiency, industrial structure, and economic level, all had a restraining effect on the decoupling of carbon emissions in Zhengzhou Economic Development Zone, and from 2016 to 2020, they all turned into promotion except for the economic level. This study showed that among the factors for the decoupling of carbon emissions in the Zhengzhou Economic Development Zone, the economic level played a major inhibitory role, and energy efficiency played a major role in promoting it. The results of this study can provide a reference for the industry-city integrated industrial park represented by Zhengzhou Economic Development Zone to formulate corresponding carbon emission reduction policies and achieve the carbon peaking and carbon neutrality goals.

Effects of mental rotation on map representation in orienteers-behavioral and fNIRS evidence.

Objective: Taking orienteering as an example, this study aimed to reveal the effects of mental rotation on orienteers' map representation and their brain processing characteristics. Methods: Functional near-infrared spectroscopic imaging (fNIRS) was used to explore the behavioral performance and cortical oxyhemoglobin concentration changes of map-represented cognitive processing in orienteering athletes under two task conditions: normal and rotational orientation. Results: Compared to that in the normal orientation, athletes' task performance in the rotated orientation condition was significantly decreased, as evidenced by a decrease in correct rate and an increase in reaction time; in the normal orientation condition, blood oxygen activation in the dorsolateral prefrontal lobe was significantly greater than that in the ventral prefrontal lobe, which was significantly correlated with the correct rate. With rotating orientation, the brain oxygen average of each region of interest was enhanced, and the brain region specifically processed was the ventral prefrontal lobe, specifically correlating with the correct rate. Conclusions: Mental rotation constrains the map representation ability of athletes, and map representation in rotational orientation requires more functional brain activity for information processing. Ventral lateral prefrontal lobe activation plays an important role in the map representation task in rotational orientation.

Interleukin-6 Facilitates Acute Myeloid Leukemia Chemoresistance via Mitofusin 1-Mediated Mitochondrial Fusion.

Acute myeloid leukemia (AML), an aggressive hematopoietic malignancy, exhibits poor prognosis and a high recurrence rate largely because of primary and secondary drug resistance. Elevated serum IL6 levels have been observed in patients with AML and are associated with chemoresistance. Chemoresistant AML cells are highly dependent on oxidative phosphorylation (OXPHOS), and mitochondrial network remodeling is essential for mitochondrial function. However, IL6-mediated regulation of mitochondrial remodeling and its effectiveness as a therapeutic target remain unclear. We aimed to determine the mechanisms through which IL6 facilitates the development of chemoresistance in AML cells. IL6 upregulated mitofusin 1 (MFN1)-mediated mitochondrial fusion, promoted OXPHOS, and induced chemoresistance in AML cells. MFN1 knockdown impaired the effects of IL6 on mitochondrial function and chemoresistance in AML cells. In an MLL::AF9 fusion gene-induced AML mouse model, IL6 reduced chemosensitivity to cytarabine (Ara-C), a commonly used antileukemia drug, accompanied by increased MFN1 expression, mitochondrial fusion, and OXPHOS status. In contrast, anti-IL6 antibodies downregulated MFN1 expression, suppressed mitochondrial fusion and OXPHOS, enhanced the curative effects of Ara-C, and prolonged overall survival. In conclusion, IL6 upregulated MFN1-mediated mitochondrial fusion in AML, which facilitated mitochondrial respiration, in turn, inducing chemoresistance. Thus, targeting IL6 may have therapeutic implications in overcoming IL6-mediated chemoresistance in AML. IMPLICATIONS: IL6 treatment induces MFN1-mediated mitochondrial fusion, promotes OXPHOS, and confers chemoresistance in AML cells. Targeting IL6 regulation in mitochondria is a promising therapeutic strategy to enhance the chemosensitivity of AML.

Unhealthy lifestyles and clusters status among 3637 adolescents aged 11-23 years: a school-based cross-sectional study in China.

BACKGROUND: Unhealthy lifestyles are risk factors for non-communicable diseases (NCDs) and tend to be clustered, with a trajectory that extends from adolescence to adulthood. This study investigated the association of diets, tobacco, alcohol, physical activity (PA), screen time (ST) and sleep duration (SD) in a total of six lifestyles, separately and as cumulative lifestyle scores, with sociodemographic characteristics among school-aged adolescents in the Chinese city of Zhengzhou. METHODS: In the aggregate, 3,637 adolescents aged 11-23 years were included in the study. The questionnaire collected data on socio-demographic characteristics and lifestyles. Healthy and unhealthy lifestyles were identified and scored, depending on the individual score (0 and 1 for healthy and unhealthy lifestyles respectively), with a total score between 0 and 6. Based on the sum of the dichotomous scores, the number of unhealthy lifestyles was calculated and divided into three clusters (0-1, 2-3, 4-6). Chi-square test was used to analyze the group difference of lifestyles and demographic characteristics, and multivariate logistic regression was used to explore the associations between demographic characteristics and the clustering status of unhealthy lifestyles. RESULTS: Among all participants, the prevalence of unhealthy lifestyles was: 86.4% for diet, 14.5% for alcohol, 6.0% for tobacco, 72.2% for PA, 42.3% for ST and 63.9% for SD. Students who were in university, female, lived in country (OR = 1.725, 95% CI: 1.241-2.398), had low number of close friends (1-2: OR = 2.110, 95% CI: 1.428-3.117; 3-5: OR = 1.601, 95% CI: 1.168-2.195), and had moderate family income (OR = 1.771, 95% CI: 1.208-2.596) were more likely to develop unhealthy lifestyles. In total, unhealthy lifestyles remain highly prevalent among Chinese adolescents. CONCLUSION: In the future, the establishment of an effective public health policy may improve the lifestyle profile of adolescents. Based on the lifestyle characteristics of different populations reported in our findings, lifestyle optimization can be more efficiently integrated into the daily lives of adolescents. Moreover, it is essential to conduct well-designed prospective studies on adolescents.

Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma.

ITGA5, a fibronectin receptor was highly expressed in laryngeal squamous cell carcinoma (LSCC) samples and was related to poor survival. However, the potential mechanism remains unclear. To elucidate the regulatory role of ITGA5 in LSCC progression, we investigated the effect of ITGA5 expression on lymphangiogenesis, migration, and invasion of LSCC cells in vitro and in vivo using immunohistochemistry, siRNA transfection, qRT-PCR, western blotting, enzyme-linked immunosorbent assay, flow cytometry, transwell co-culture, tube formation, cell migration, and invasion assays, and a subcutaneous graft tumor model. The expression of ITGA5 was higher in the LSCC tissues and linked to lymph node metastasis and T staging. Moreover, ITGA5 expression was significantly positively correlated with VEGF-C expression, and the lymphatic vessel density of patients with high ITGA5 expression was noticeably higher than that of patients with low ITGA5 expression. Additionally, it was found in vitro that downregulation of ITGA5 expression not only inhibited the expression and secretion of VEGF-C, but also suppressed the tube-forming ability of human lymphatic endothelial cells (HLECs) and the migration and invasion ability of LSCC cells, while exogenous VEGF-C supplementation reversed these phenomena. Furthermore, a tumor xenograft assay showed that si-ITGA5 restrained the growth and metastasis of TU212-derived tumors in vivo. Our findings suggested that ITGA5 induces lymphangiogenesis and LSCC cell migration and invasion by enhancing VEGF-C expression and secretion.

Symptoms of depression and anxiety in Chinese adolescents: heterogeneity and associations with executive function.

BACKGROUND: Depression and anxiety are common symptoms associated with significant morbidity in adolescents. Few studies have explored the relationship between latent profiles of adolescent depression-anxiety symptoms and executive function (EF), which is also a major pediatric public health concern. METHODS: The sample included 1,306 participants who were recruited from two schools in Ningxia. The Depression Self-Rating Scale for Children (DSRSC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess the level of depression-anxiety symptoms in adolescents, and their executive function state was assessed using the Behavior Rating Inventory of Executive Function-Self-Report version (BRIEF-SR). Latent profile analysis (LPA) was carried out using Mplus 7.0 to explore the most likely number of profiles based on the subscales of DSRSC and SCARED. The relationship between adolescents' executive function and depression-anxiety symptoms were analyzed by multivariable logistic regression, and the odds ratio were used to test the impact of this relationship. RESULTS: The LPA results show that the three-profile model was the best-fitting model for adolescent depression and anxiety symptoms. The proportions of Profile-1 ("Healthy Group"), Profile-2 ("Anxiety Disorder Group"), and Profile-3 ("Depression-Anxiety Disorder Group") were 61.4%, 23.9%, and 14.7%, respectively. Additional analyses using multivariable logistic regression suggested that poor shifting capacity and emotional control were significantly more likely to be classified into the depression and/or anxiety groups, and worse working memory, task completion, and better inhibition were significantly more likely to be classified into the anxiety group. CONCLUSIONS: The findings contribute to our understanding of the heterogeneity of adolescents' depression-anxiety symptoms and highlight the important role of executive function in influencing mental health outcomes. These findings will guide the improvement and delivery of interventions for the treatment of anxiety and depression in adolescents, mitigating functional impairments in patients and reducing disease risk.

Real-World Efficacy and Safety of Thoracic Radiotherapy after First-Line Chemo-Immunotherapy in Extensive-Stage Small-Cell Lung Cancer.

(1) Background: At present, the efficacy and safety of thoracic radiotherapy (TRT) after chemo-immunotherapy (CT-IT) in patients with extensive-stage small-cell lung cancer (ES-SCLC) still remain unclear. The purpose of this study was to evaluate the role of TRT after CT-IT in patients with ES-SCLC. (2) Methods: From January 2020 to October 2021, patients with ES-SCLC treated with first-line anti-PD-L1 antibody plus platinum-etoposide chemotherapy were enrolled retrospectively. The survival data and adverse events data of patients treated with or without TRT after CT-IT were collected for analysis. (3) Results: A total of 118 patients with ES-SCLC treated with first-line CT-IT were retrospectively enrolled, with 45 patients with TRT and 73 patients without TRT after CT-IT. The median PFS and OS in the CT-IT + TRT group and CT-IT only group were 8.0 months versus 5.9 months (HR = 0.64, p = 0.025) and 22.7 months versus 14.7 months (HR = 0.52, p = 0.015), respectively. The median PFS and OS in all 118 patients treated with first-line CT-IT were 7.2 and 19.8 months with an ORR of 72.0%. In multivariate analyses, liver metastasis and response to CT-IT were shown to be independent prognostic factors of PFS (p < 0.05), while liver metastasis and bone metastasis were independent predictive factors of OS (p < 0.05). Although TRT was significantly associated with better PFS and OS in univariate analysis, the association of TRT and OS failed to reach statistical significance (HR = 0.564, p = 0.052) in multivariate analysis. There was no significant difference in adverse events (AEs) between two treatment groups (p = 0.58). (4) Conclusions: ES-SCLC patients treated with TRT after first-line CT-IT had prolonged PFS and OS with an acceptable safety profile. Further prospective randomized studies are necessary to explore the efficacy and safety of this treatment modality for ES-SCLC in future.

Microbial community structure dynamics of invasive bullfrog with meningitis-like infectious disease.

Meningitis-like infectious disease (MID) (also known as frog cataract and torticollis) is a disease prone to occur in amphibians and reptiles. It is highly contagious and has a high mortality rate. In this study, we sampled and sequenced microbiomes from oral and intestinal samples of five normal and five diseased bullfrogs. The analysis found that the richness, uniformity, and abundance of the microbial community of the diseased bullfrogs were significantly higher than those of the normal bullfrogs in both the oral cavity and the gut. In the diseased group, the abundance of Elizabethkingia significantly increased and that of Lactococcus significantly decreased. It showed that the structure of the microbial community had changed a lot in diseased frogs. After the pathogenic bacteria infected the body, it might be make the decline in the immune function of the body declined, and resulting in some conditional pathogenic bacteria in the water body further infecting the body. As a result, the richness and composition of the microbial community significantly changed. This study can provide a theoretical basis for the control of MID of bullfrogs.

Soil arthropods promote litter enzyme activity by regulating microbial carbon limitation and ecoenzymatic stoichiometry in a subalpine forest.

Soil arthropods are crucial decomposers of litter at both global and local scales, yet their functional roles in mediating microbial activity during litter decomposition remain poorly understood. Here, we conducted a two-year field experiment using litterbags to assess the effects of soil arthropods on the extracellular enzyme activities (EEAs) in two litter substrates (Abies faxoniana and Betula albosinensis) in a subalpine forest. A biocide (naphthalene) was used to permit (nonnaphthalene) or exclude (naphthalene application) the presence of soil arthropods in litterbags during decomposition. Our results showed that biocide application was effective in reducing the abundance of soil arthropods in litterbags, with the density and species richness of soil arthropods decreasing by 64.18-75.45 % and 39.19-63.30 %, respectively. Litter with soil arthropods had a greater activity of C-degrading (ß-glucosidase, cellobiohydrolase, polyphenol oxidase, peroxidase), N-degrading (N-acetyl-ß-D-glucosaminidase, leucine arylamidase) and P-degrading (phosphatase) enzymes than litter from which soil arthropods were excluded. The contributions of soil arthropods to C-, N- and P-degrading EEAs in the fir litter were 38.09 %, 15.62 % and 61.69 %, and those for the birch litter were 27.97 %, 29.18 % and 30.40 %, respectively. Furthermore, the stoichiometric analyses of enzyme activity indicated that there was potential C and P colimitation in both the soil arthropod inclusion and exclusion litterbags, and the presence of soil arthropods decreased C limitation in the two litter species. Our structural equation models suggested that soil arthropods indirectly promoted C-, N- and P-degrading EEAs by regulating the litter C content and litter stoichiometry (e.g., N/P, LN/N and C/P) during litter decomposition. These results demonstrate that soil arthropods play an important functional role in modulating EEAs during litter decomposition.

Grapevine bZIP transcription factor bZIP45 regulates VvANN1 and confers drought tolerance in Arabidopsis.

Drought is a severe environmental condition that restricts the vegetative growth and reduces the yield of grapevine (Vitis vinifera L.). However, the mechanisms underlying grapevine response and adaptation to drought stress remain unclear. In the present study, we characterized an ANNEXIN gene, VvANN1, which plays a positive role in the drought stress response. The results indicated that VvANN1 was significantly induced by osmotic stress. Expression of VvANN1 in Arabidopsis thaliana enhanced osmotic and drought tolerance through modulating the level of MDA, H2O2, and O2 ·- at the seedling stage, implying that VvANN1 might be involved in the process of ROS homeostasis under drought or osmotic stress conditions. Moreover, we used yeast one-hybridization and chromatin immunoprecipitation assays to show that VvbZIP45 could regulate VvANN1 expression by directly binding to the promoter region of VvANN1 in response to drought stress. We also generated transgenic Arabidopsis that constitutively expressed the VvbZIP45 gene (35S::VvbZIP45) and further produced VvANN1Pro::GUS/35S::VvbZIP45 Arabidopsis plants via crossing. The genetic analysis results subsequently indicated that VvbZIP45 could enhance GUS expression in vivo under drought stress. Our findings suggest that VvbZIP45 may modulate VvANN1 expression in response to drought stress and reduce the impact of drought on fruit quality and yield.

The association of cortisol/testosterone ratio and sleep quality with coronary heart disease: A case-control study in Chinese rural population.

PURPOSE: There were limited studies that have probed into the combined effect of the cortisol/testosterone (C/T) ratio as a biomarker of stress and Pittsburgh Sleep Quality Index (PSQI) on coronary heart disease (CHD). This research aimed to explore the association of C/T ratio and PSQI with the risk of CHD in a rural Chinese population, as well as the interaction and combined effect between C/T ratio and PSQI on CHD. METHODS: A case-control study was performed including 307 individuals without CHD and 307 patients drawn from Henan Rural Cohort. Logistic regression was utilized to survey the independent and joint effects of the C/T ratio and PSQI on CHD. To estimate the interaction impact of the C/T ratio and sleep quality (PSQI) on CHD, a cross-product term was introduced in the generalized linear model. RESULTS: Higher C/T ratio and PSQI index scores are related to increased odds ratio for CHD (Odds ratios (ORs) and 95 % confidence interval (CI) were 1.17 (1.07, 1.29), p-trend < 0.001; 1.16 (1.09, 1.22), respectively). The odds ratio of C/T ratio for CHD increased with increasing PSQI in women (pinteraction = 0.018) and total population (pinteraction = 0.033). The combined group of high C/T ratio and high PSQI had the highest risk of CHD (Total: OR = 7.53, 95 % CI: 4.12-13.76). CONCLUSIONS: The risk of CHD was associated with low testosterone levels, high C/T ratios, and high PSQI scores. Additionally, poor sleep quality aggravated the effect of high C/T ratio on coronary heart disease.

Lkb1 loss in regulatory T cells leads to dysregulation of hematopoietic stem cell expansion and differentiation in bone marrow.

The tumor suppressor Lkb1 is known to regulate the expression of forkhead box P3 (Foxp3), thereby maintaining the levels of Foxp3+ regulatory T cells (Treg) that play a crucial role in self-tolerance. However, the effect of Lkb1 in Treg on hematopoietic stem cells (HSCs) in the bone marrow (BM) remains obscure. Here, we demonstrated that conditional deletion of Lkb1 in Treg causes loss of Treg in the BM, which leads to failure of HSC homeostasis and the abnormal expansion. Moreover, the loss of BM Treg results in dysregulation of other developing progenitors/stem cell populations, leading to the defective differentiation of T cells and B cells. In addition, HSC from the BM with Treg loss exhibited poor engraftment efficiency, indicating that loss of Treg leads to irreversible impairment of HSC. Collectively, these results demonstrated the essential role of Lkb1 in Treg for maintaining HSC homeostasis and differentiation in mice. These findings provide insight into the mechanisms of HSC regulation and guidance for a strategy to improve the outcomes and reduce complications of HSC transplantation.

m6A RNA methylation regulators predict prognosis and indicate characteristics of tumour microenvironment infiltration in acute myeloid leukaemia.

Patients with acute myeloid leukaemia (AML) have poor prognoses and low overall survival (OS) rates owing to its heterogeneity and the complexity of its tumour microenvironment (TME). N6-methyladenosine (m6A) modification plays a key role in the initiation and progression of haematopoietic malignancies. However, the underlying function of m6A regulators in AML remains elusive. This study thoroughly analysed the m6A modification features of 177 AML patients based on 22 m6A regulators. Utilizing unsupervised clustering, we determined three distinct m6A modification patterns related to different biological functions, TME cell-infiltrating characteristics and clinical outcomes. Additionally, a risk score was constructed based on six m6A regulators-associated prognostic signatures and was validated as an independent and valuable prognostic factor for AML. Patients with a low-risk score exhibited better survival than those with a high-risk score. Many m6A regulators were aberrantly expressed in AML, among which METTL14, YTHDC2, ZC3H13 and RBM15 were observed to be associated with the OS of AML. In addition, these four m6A regulators were found to be noticeably related to the immune checkpoint inhibitor (ICI) treatments. Finally, we verified the expression levels of these four m6A regulators in AML and healthy samples and three groups of AML patients with different risk categories. Collectively, our study indicates that the m6A modification pattern is involved in TME immune-infiltrating characteristics and prognosis in AML. A better understanding of the m6A modification pattern will help enhance our knowledge of the molecular mechanisms of AML and develop potential prognosis prediction indicators and more effective immunotherapeutic strategies.