Acute ischemic stroke (AIS) remains a devastating neurological disorder with limited therapeutic options, in which ischemia/reperfusion-induced oxidative stress, hypoxia, impaired cerebral perfusion, and neuronal injury jointly contribute to disease progression. Here, we report a reactive oxygen species (ROS)-responsive carrier-free nanodrug constructed through microwave-assisted coordination assembly of ruthenium (Ru), L-arginine (L-Arg), and curcumin (Cur), termed RAC. Unlike a simple physical mixture of the three components, RAC represents a coordination-driven carrier-free nanoassembly that integrates multiple therapeutic functions within a single platform, including Ru-associated H2O2-responsive oxygen generation, L-Arg-associated nitrite/NO-related signaling, and Cur-mediated antioxidant neuroprotection. RAC formed a distinct supramolecular nanostructure and remained relatively stable under physiological conditions, while undergoing ROS/acidosis-responsive disassembly and Cur release in ischemia/reperfusion-relevant microenvironments. In vitro, RAC exhibited broad ROS-scavenging capability, improved Cur-associated cellular delivery, reduced intracellular ROS and superoxide accumulation, preserved mitochondrial membrane potential, restored redox homeostasis, and attenuated apoptosis in N2a neuronal cells under OGD/R conditions more effectively than the corresponding physical mixture. In vivo fluorescence imaging showed enhanced brain accumulation of RAC after systemic administration. In a tMCAO/R mouse model, RAC promoted cerebral blood flow recovery, reduced infarct volume, preserved cortical neuronal integrity, and improved neurological outcomes compared with both the model and Mix groups. These findings demonstrate that the coordination-driven nanoassembly of RAC contributes to assembly-dependent therapeutic amplification beyond a simple combination of its individual components. This study provides a promising strategy for AIS therapy through the rational design of ROS-responsive, carrier-free nanodrugs integrating free radical scavenging, oxygen generation, NO-related perfusion support, and neuroprotection.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition predominantly affecting children, characterized by hyperinflammation and high early mortality. While the HScore criteria, developed by Fardet et al. in 2014, have been widely used to diagnose HLH, recent studies have also explored its potential to predict disease severity in COVID-19 patients, with findings indicating that higher HScore values correlate with increased mortality risk and may identify patients who could benefit from immunomodulatory treatment.However, the potential of HScore-related indicators in predicting early prognosis in patients with HLH has not been reported. This study aimed to investigate the association between HScore scores and related indicators and early mortality in children with Hemophagocytic Lymphohistiocytosis (HLH), and to develop a Cox prediction model for early mortality based on optimized HScore parameters to assist medical professionals in better risk stratification at the time of diagnosis. This retrospective study included 624 children diagnosed with HLH admitted to the Children's Hospital of Chongqing Medical University between January 2006 and December 2022. Five Cox prediction models were developed: Model 1 used HScore values; Model 2 used original HScore grouping criteria; Model 3 used raw HScore parameters; Model 4 grouped HScore parameters by optimal cut-offs; Model 5 combined optimized HScore parameters with common prognostic indicators (total protein, TC, APTT, BUN, ferritin). Model performance was assessed using AUC and calibration curves. An interactive web application was developed using R and Shiny for clinical use. The optimal cut-off value for the HScore was determined to be 223, which stratified children into high-risk and low-risk groups. The estimated 30-day survival rates were 77.9% (95% CI: 73.6%-82.5%) for the low-risk group and 65.8% (95% CI: 60.5%-71.7%) for the high-risk group (P < 0.001). Model 5 demonstrated the highest AUC on both training and validation datasets, with values of 0.881 (95% CI: 0.818-0.942) and 0.813 (95% CI: 0.747-0.881), respectively. Factors associated with increased early mortality risk included hemoglobin levels <61 g/L, platelet counts <31×10^9/L, ferritin levels ≥1318 ng/mL, total protein levels ≥52.3 g/L, AST levels >460 U/L, total cholesterol levels <3.23 mmol/L, APTT levels >60.2s, and bone marrow phagocytosis. To facilitate clinical application, we developed a free online calculator tool (https://ranwyr.shinyapps.io/DynNomapp/) based on the optimal model results. The HScore alone is insufficient for accurately predicting early mortality risk in children with HLH. Our study provides a novel early mortality prediction tool based on optimized HScore parameters, which may aid clinicians in better risk stratification and decision-making at the time of diagnosis.

Hippocampal neural stem cells (NSCs) have attracted significant attention due to their essential role in maintaining cognitive functions, such as memory and spatial orientation through neurogenesis. Cognitive impairment is a common and debilitating complication of traumatic brain injury (TBI), yet its underlying mechanisms remain poorly understood and effective clinical interventions are lacking. In this study, we observed persistent cognitive deficits in a mouse model of TBI, a phenomenon that has been widely documented in previous studies, and importantly, we found that these impairments were closely associated with increased hippocampal NSCs (H-NSCs) senescence. To investigate the cause of NSCs' senescence, we analyzed cerebrospinal fluid samples from TBI patients and hippocampal tissues from TBI mice and identified persistently elevated levels of IL-1β post TBI. In vitro, IL-1β successfully induced NSCs' senescence and suppressed neurogenesis. Induced pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) reversed IL-1β-induced senescence and restored neurogenic potential in H-NSCs. In vivo, iPSC-sEVs alleviated cognitive deficits and H-NSC senescence after TBI. Integrated proteomic and NSC cell transcriptomic analyses revealed that the β-catenin/ID2/CDKN2B (p15INK4b) signaling axis plays a critical role in regulating H-NSC senescence, which was further validated through inhibitor experiments. In summary, our findings demonstrate that iPSC-sEVs attenuate NSC senescence and improve cognitive function following TBI via modulation of the β-catenin/ID2/CDKN2B (p15INK4b) axis.

Salt is a major abiotic factor significantly affecting plant growth and development. Alfalfa (Medicago sativa L.), a crucial perennial crop for livestock feed, shows significant differences in salt tolerance among different varieties. This study aimed to comprehensively evaluate the salt tolerance of 30 varieties of alfalfa under salt stress (0, 150, and 300 mmol L-1 NaCl). It showed that shoot height (SH), root length (RL), shoot fresh weight (SFW), and root fresh weight (RFW) were decreased by 37.68%, 35.83%, 43.79% and 48.86%, respectively, under high salt stress. Photosynthesis-related parameters, including chlorophyll a (Chl a), chlorophyll b (Chl b), total chlorophyll (TChl), and carotenoids (Car) contents of all varieties were decreased by 50.13%, 43.73%, 48.17% and 60.86%, respectively, and minimum inhibition of photosynthetic pigment contents was observed in the variety Salsa. The changes of antioxidant enzymes in different alfalfa varieties were also found under salt stress. For example, the APX of Sardi 7 decreased by 641.84%, while the APX of Phabulous decreased by 88.33% compared to the non-treated controls. Principal component analysis (PCA) identified five major variables: Car, TChl, APX, Chl a, and POD. Finally, each variety's comprehensive tolerance membership function values were calculated by the membership function method, and the 30 varieties were classified into four categories by cluster analysis. Our findings indicate that Sardi 7, Salsa, Gannong No.8, Daye, and Instinct are alfalfa salt-tolerant varieties. Our study provided baseline information on the response of alfalfa varieties to different salinity levels, which will help select or breed salt-tolerant varieties.

Background: Pediatric acute myeloid leukemia (pAML) is the second most common type of childhood leukemia, behind acute lymphoblastic leukemia. High-throughput technologies have enabled the identification of increasing molecular alterations linked to AML prognosis, revealing genomic heterogeneity among individual patients and providing clinically valuable diagnostic and prognostic information. This study systematically analyzed the correlation between high-frequency mutated genes and prognosis in pAML by performing whole-transcriptome sequencing (WTS) of bone marrow samples from newly diagnosed AML children in Southwest China and mapping their genetic profiles. Methods: pAML patients treated at the Department of Hematology and Oncology, Children’s Hospital of Chongqing Medical University, from January 2015 to October 2024, were enrolled, and WTS was performed. The study described the frequency, pathogenicity classification, and risk stratification of mutation genes and fusion genes, and constructed a genetic landscape. For high-frequency pAML mutations, the impact on early induction remission rate (CR) and long-term event-free survival (EFS) was evaluated. Results: A total of 134 pediatric AML patients from Southwest China were included, with a male-to-female ratio of 74:60 and a median diagnosis age of 5.96 years. Based on pathogenicity classification using WTS, fusion genes were categorized into level 1, level 2, and level 3 genes, as well as mutation genes. The study identified five fusion genes of level 1, the most frequent being RUNX1::RUNX1T1 (32/134, 23.88%), KMT2A rearrangements (29/134, 21.64%), and CBFB::MYH11 (13/134, 9.7%). Sixteen mutation genes of level 1 were detected, seven of which recurred in over 5% of patients, including NRAS (31/134, 23.13%), FLT3 (25/134, 18.66%), KIT (24/134, 17.91%), CEBPA (14/134, 10.45%), WT1 (13/134, 9.7%), KRAS (11/134, 8.2%), and PTPN11 (7/134, 5.22%). Sex-based analysis revealed that PTPN11 mutations were significantly more frequent in males (9.45% vs. 0%, p = 0.023), as were KIT mutations (24.32% vs. 10.00%, p = 0.044). Risk-stratified analysis showed that WT1 mutations (14.13% vs. 0%, p = 0.031) and FLT3-ITD mutations (13.19% vs. 0%, p = 0.042) were enriched in intermediate- and high-risk groups, whereas CEBPA (25.64% vs. 5.43%, p = 0.012), KIT (35.90% vs. 10.87%, p = 0.003), and KIT-E8 (20.51% vs. 1.10%, p < 0.001) mutations were more prevalent in low-risk groups. Prognostic analysis indicated that PTPN11 and KIT mutations did not affect CR or EFS across sexes, nor did WT1, CEBPA, or KIT mutations influence outcomes by risk stratification. However, FLT3-ITD-positive patients had significantly lower CRs (χ2 value = 11.965, p = 0.007), although EFS differences were nonsignificant. In contrast, WT1 mutations were associated with inferior EFS compared to wild-type (p = 0.036). Furthermore, the univariate and multivariate Cox regression revealed consistent results with the above findings, indicating that WT1 mutation was an independent adverse prognostic factor for EFS (HR = 2.400, 95% CI: 1.101–5.233, p = 0.028). The results of univariate and multivariate logistic regression analyses also confirmed that FLT3-ITD mutation was an independent predictor of initial treatment response in our cohort (OR = 10.699, 95% CI: 2.108–54.302, p = 0.004). Conclusions: This study delineated the genetic landscape of pAML in Southwest China and explored the prognostic value of gene fusions and mutations in early and long-term outcomes. These findings provide a foundation for understanding the genetic heterogeneity of pAML and offer evidence for the development of precision medicine approaches.

Cadmium (Cd), a non-essential toxic heavy metal, presents severe threats to agricultural productivity, plant development, and human health through food chain contamination. Although Elymus nutans Griseb. (E. nutans) exhibits substantial potential for phytoremediation of Cd-contaminated soils, its molecular Cd-tolerance mechanisms remain poorly characterized. This study employed integrated morphological, physiological, ultrastructural, transcriptomic, and metabolomic analyses to systematically investigate Cd stress responses in E. nutans. Results demonstrated that Cd stress significantly inhibited growth and photosynthesis, activated antioxidant system, and induced lipid peroxidation in E. nutans seedlings. Notably, cellular ultrastructural damage coincided with disrupted energy metabolism and substantial accumulation of reactive oxygen species (ROS), which ultimately triggered programmed cell death (PCD). Transcriptomic analysis revealed differentially expressed genes (DEGs) enriched in Plant hormone signal transduction and Carbon metabolism pathways. Metabolomic profiling identified 128 differentially expressed metabolites (DEMs) associated with ABC transporters and Isoquinoline alkaloid biosynthesis. Integrated multi-omics analysis demonstrated that glutathione metabolism and photosynthetic carbon fixation pathways regulate E. nutans response to Cd by modulating photosynthesis, antioxidant defense, and energy metabolism. This study reveals phytoremediation mechanisms of E. nutans under Cd stress, offering a scientific foundation for restoring soil health and ecological functions in high-altitude contaminated areas through sustainable soil management strategies.

BackgroundThe genetic variations in aplastic anemia (AA) patients are closely related to clonal hematopoiesis, but there is limited research on this topic in children with AA. The aim of this study is to investigate the molecular classification and outcomes of children with AA combined with myeloid neoplasm-associated gene variants.MethodsThe clinical features, types of gene variants, mechanisms of action of the mutated genes, and correlations between gene variants and the outcomes of AA patients with myeloid neoplasm-associated gene variants were retrospectively analyzed.ResultsForty-six AA patients with myeloid neoplasm-associated gene variants were included, and a total of 20 gene variants were identified. The most frequent variant affected TET2 (9 patients, 19.6%), followed by ASXL1 (5 patients, 10.9%) and MPL (5 patients, 10.9%). Other variants, in descending order, affected TERT (4 patients); SH2B3, FLT3, ETV6, and JAK2 (3 patients each); BCOR, BCORL1, TP53, KIT, and SF3B1 (2 patients each); and CALR, GATA2, RUNX1, CBL, IDH1, IDH2, and WT1 (1 patient each). Six patients had 2 gene variants. The original mechanisms of action of the mutated genes mainly involved epigenetics and signal transduction pathways; both groups of genes were affected in 39.1% (18/46) of the patients. The difference in the efficacy of immunosuppressive therapy (IST) among the different gene groups was not significant. Disease severity (P = 0.046) and hematological response at 3 months (P = 0.002), 6 months (P = 0.001), 9 months (P = 0.001), and 1 year (P = 0.001) were important factors affecting survival time, but genotype was not. None of the patients experienced clonal evolution by the end of the follow-up cut-off time.ConclusionIn patients with AA combined with myeloid tumor neoplasm-associated gene variants, TET2, ASXL1 and MPL variants were the most frequently observed and primarily involved epigenetics and signal transduction pathways. There was no significant difference in the efficacy of IST among patients with different gene variants. Survival time was associated with disease severity, and the development of a hematological response—particularly when achieved at 3 months—was an independent key factor, whereas genotype was not.

"Nanophytovirology" is a potential management approach to combat plant viral diseases. Herein, the impact of foliar application of CeO2 nanoparticles (CeO2-NPs) on the growth, plant cell ultrastructure, and physiology of alfalfa mosaic virus (AMV)-infected alfalfa seedlings was explored at different concentrations and application strategies. In a solar greenhouse, 20 mL of CeO2-NP suspensions of 50, 100, 200, and 500 mg/L was sprayed onto the plant surface every other day for 9 days. As a result, the total volume applied per pot was 100 mL. It showed that the beneficial effects of CeO2-NPs on infected alfalfa seedlings were dependent on the concentration and application period. Compared to the infected control, foliar application with 100 mg/L CeO2-NPs before AMV infection (CeO2-NPs-BVI) showed the greatest virus suppression efficacy; significantly reduced the disease indices by 58.87%; improved growth, yield, and nutritional quality; and significantly increased plant height, plant dry biomass, crude protein, and crude fat contents and relative feeding value by 15.17, 37.12, 18.77, 71.19, and 10.09%, respectively. Moreover, CeO2-NPs-BVI maintained the chloroplast quantity and structure of leaf cells and significantly enhanced the chlorophyll content and photosynthesis rate of alfalfa leaves by 36.14 and 40.13%, respectively, as compared to infected control. Mechanistically, cell ultrastructure, physiology, and transcriptomic analyses revealed that (1) CeO2-NPs effectively mitigated AMV-induced chloroplast structure damage, subsequently enhancing photosynthesis and carbon fixation in photosynthetic organisms, providing sufficient energy and antiviral activities for maintaining plant growth and development; (2) CeO2-NPs reduced the AMV's ability to bind to host receptors and evade host immune recognition, significantly activating and boosting plant systemic immunity by down-regulating ABA and ETH levels and upregulating SA, IAA, and BR levels; (3) CeO2-NPs activated the plant antioxidative systems to eliminate excess reactive oxygen species. These findings provide significant insight into the potential of CeO2-NPs as highly efficient antiviral agent.

BackgroundTumor lysis syndrome (TLS) often occurs early after induction chemotherapy for acute lymphoblastic leukemia (ALL) and can rapidly progress. This study aimed to construct a machine learning model to predict the risk of TLS using clinical indicators at the time of ALL diagnosis.MethodsThis observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data were collected from pediatric ALL patients diagnosed between December 2008 and December 2021. Four machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction.ResultsThe study included 2,243 pediatric ALL patients, and the occurrence of TLS was 8.87%. A total of 33 indicators with missing values ≤30% were collected, and 12 risk factors were selected through LASSO regression analysis. The CatBoost model with the best performance after feature screening was selected to predict the TLS of ALL patients. The CatBoost model had an AUC of 0.832 and an accuracy of 0.758. The risk factors most associated with TLS were the absence of potassium, phosphorus, aspartate transaminase (AST), white blood cell count (WBC), and urea levels.ConclusionWe developed the first TLS prediction model for pediatric ALL to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200060616).Clinical trial registrationhttps://www.chictr.org.cn/, identifier ChiCTR2200060616.

OBJECTIVES:To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence. METHODS:A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed. RESULTS:Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group (P>0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage (n=62, 42.5%) and the early stage (n=46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene (HR=4.177, 95%CI: 2.086-8.364, P<0.001) and minimal residual disease≥0.01% on day 46 (HR=2.013, 95%CI: 1.163-3.483, P=0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol. CONCLUSIONS:There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Clostridial fermentation is the determining process causing the spoilage of direct-cut alfalfa silage, and the application of lactic acid bacteria (LAB) inoculant is considered as the most promising technology for inhibiting clostridial fermentation. In order to screen target-based LAB strains, identification and correlation analysis of key Clostridia and LAB species in alfalfa silage were conducted in this study. Three alfalfa cultivars (Sanditi, SD; Celsius, CE; SW5909, SW) were harvested at the early bloom stage and ensiled without (CK) or with LAB inoculant (LB) and sucrose (SC) for 60 d. Single-molecule real-time sequencing was used to identify dominant Clostridia and LAB species, and LAB with significant inhibitory effects on dominant Clostridia was screened via correlation network analysis. The results showed that silages CK and LB encountered severe clostridial fermentation as indicated by large amounts of butyric acid (BA) and ammoniacal nitrogen (NH3-N) production. Compared to silages CK and LB, SC treatment decreased (p < 0.05) BA and NH3-N concentrations, as well as decreasing (p < 0.05) the bacterial community indexes of Shannon and Chao1. Lactiplantibacillus pentosus was the first dominant LAB in silage CK of alfalfa SD and CE. The first dominant LAB in silage LB was also identified as L. pentosus, rather than Lentilactobacillus buchneri and Lactiplantibacillus plantarum in the used inoculant. L. buchneri became more abundant in silage SC of alfalfa SD and CE, accounting for the high fermentation quality of these silages. Clostridium tyrobutyricum, Clostridium luticellarii, Garciella sp._GK3, Clostridium sporogenes, Clostridium perfringens, and Clostridium sp._BTY5 were the most dominant Clostridia species in alfalfa silage. Furthermore, Enterococcus faecalis, L. buchneri, and L. pentosus exhibited significant (p < 0.05) inhibitory effects on C. tyrobutyricum, C. luticellarii, and Garciella sp._GK3, respectively, which were the top three Clostridia species associated with clostridial fermentation. In conclusion, E. faecalis, L. buchneri, and L. pentosus were screened and can be used as potential LAB inoculants for the targeted inhibition of clostridial fermentation.

Objective:To explore the gene mutations of Langerhans cell histiocytosis in children,and to analyze the correlation of BRAF V600E mutation with clinical features and prognosis of LCH,so as to provide reference for clinical diagnosis and treatment. Methods:Fluorescence PCR was used to detect gene mutations in paraffin-embedded tissue samples from 78 children with LCH,and the correlation of BRAF V600E mutation with clinical characteristics and prognosis of LCH in children was analyzed. Results:Among the 78 children,41 cases (52.6％) had BRAF V600E mutation,8 cases (10.3％) had MAP2K1 mutation,1 case (1.3％) had BRAF Exon 12 mutation,1 case (1.3％) had ARAF mutation,and 1 case (1.3％) had PIK3CA mutation. BRAF V600E mutation was not significantly correlated with sex,age,multisystem involvement,risk-organ involvement,CNS-risk lesions,and early treatment response in children with LCH (P>0.05),and it was also not significantly correlated with the recurrence and event-free survival (EFS) of children with LCH (P>0.05). Conclusion:LCH is an inflammatory myeloid tumor. BRAF V600E mutation is not correlated with clinical features,early treatment response,recurrence and prognosis of LCH.

Nanoparticle (NP) pollution has negative impacts and is a major global environmental problem. However, the molecular response of alfalfa (Medicago sativa L.) to titanium dioxide nanoparticles (TiO2 NPs) is limited. Herein, the dual effects of TiO2 NPs (0-1000 mg L-1) on carbon (C) and nitrogen (N) metabolisms in alfalfa were investigated. The results showed that 500 mg L-1 TiO2 NPs (Ti-500) had the highest phytotoxicity in the C/N metabolizing enzymes; and it significantly increased total soluble sugar, starch, sucrose, and sucrose-phosphate synthase. Furthermore, obvious photosynthesis responses were found in alfalfa exposed to Ti-500. By contrast, 100 mg L-1 TiO2 NPs (Ti-100) enhanced N metabolizing enzymes. RNA-seq analyses showed 4265 and 2121 differentially expressed genes (DEGs) in Ti-100 and Ti-500, respectively. A total of 904 and 844 differentially expressed proteins (DEPs) were identified in Ti-100 and Ti-500, respectively. Through the physiological, transcriptional, and proteomic analyses, the DEGs and DEPs related to C/N metabolism, photosynthesis, chlorophyll synthesis, starch and sucrose metabolism, and C fixation in photosynthetic organisms were observed. Overall,

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe3O4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe3O4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe3O4, and co-treatment with nano-Fe3O4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe3O4. The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe3O4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe3O4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe3O4.

The outcomes of children with acute lymphoblastic leukemia (ALL) have been incrementally improved with risk-directed chemotherapy but therapy responses remain heterogeneous. Parameters with added prognostic values are warranted to refine the current risk stratification system and inform appropriate therapies. CD9, implicated by our prior single-center study, holds promise as one such parameter. To determine its precise prognostic significance, we analyzed a nationwide, multicenter, uniformly treated cohort of childhood ALL cases, where CD9 status was defined by flow cytometry on diagnostic samples of 3781 subjects. CD9 was expressed in 88.5% of B-ALL and 27.9% of T-ALL cases. It conferred a lower 5-year EFS and a higher CIR in B-ALL but not in T-ALL patients. The prognostic impact of CD9 was most pronounced in the intermediate/high-risk arms and those with minimal residual diseases, particularly at day 19 of remission induction. The adverse impact of CD9 was confined to specific cytogenetics, notably BCR::ABL1 + rather than KMT2A -rearranged leukemia. Multivariate analyses confirmed CD9 as an independent predictor of both events and relapse. The measurement of CD9 offers insights into patients necessitating intervention, warranting its seamless integration into the diagnostic marker panel to inform risk level and timely introduction of therapeutic intervention for childhood ALL.

Cadmium (Cd) poses a significant threat to plant growth and the environment. Nano-Fe3O4 is effective in alleviating Cd stress in plants. Elymus nutans Griseb. is an important fodder crop on the Qinghai-Tibetan Plateau (QTP). However, the potential mechanism by which nano-Fe3O4 alleviates Cd stress in E. nutans is not well understood. E. nutans were subjected to single Cd, single nano-Fe3O4, and co-treatment with nano-Fe3O4 and Cd, and the effects on morphology, Cd uptake, antioxidant enzyme activity, reactive oxygen species (ROS) levels and programmed cell death (PCD) were studied to clarify the regulatory mechanism of nano-Fe3O4. The results showed that Cd stress significantly decreased the germination percentage and biomass of E. nutans. The photosynthetic pigment content decreased significantly under Cd stress. Cd stress also caused oxidative stress and lipid peroxidation, accumulation of excessive ROS, resulting in PCD, but the effect of nano-Fe3O4 was different. Seed germination, seedling growth, and physiological processes were analyzed to elucidate the regulatory role of nano-Fe3O4 nanoparticles in promoting photosynthesis, reducing Cd accumulation, scavenging ROS, and regulating PCD, to promote seed germination and seedling growth in E. nutans. This report provides a scientific basis for improving the tolerance of Elymus to Cd stress by using nano-Fe3O4.

The polarization of microglia plays an important role in the outcome of ischemic stroke (IS). In the aged population, senescent microglia show a predominant pro-inflammatory phenotype, which leads to worse outcomes in aged ischemic stroke compared to young ischemic stroke. Recent research demonstrated that inducible pluripotent stem cell-derived small extracellular vesicles (iPSC-sEVs) possess the significant anti-ageing ability. We hypothesized that iPSC-sEVs could alleviate microglia senescence to regulate microglia polarization in aged ischemic stroke. In this study, we showed that treatment with iPSC-sEVs significantly alleviated microglia senescence as indicated by the decreased senescence-associated proteins including P16, P21, P53, and γ-H2AX as well as the activity of SA-β-gal, and inhibited pro-inflammatory activation of microglia both in vivo and in vitro. Furthermore, iPSC-sEVs shifted microglia from pro-inflammatory phenotype to anti-inflammatory phenotype, which reduced the apoptosis of neurons, and improved the outcome of aged stroke mice. Mechanism studies showed that iPSC-sEVs reversed the loss of Rictor and downstream p-AKT (s473) in senescent microglia, which was involved in the senescence and pro-inflammatory phenotype regulation of microglia. Inhibition of Rictor abolished the iPSC-sEVs-afforded phosphorylation of AKT and alleviation of inflammation of senescent microglia. Proteomics results indicated that iPSC-sEVs carried transforming growth factor-β1 (TGF-β1) to upregulate Rictor and p-AKT in senescent microglia, which could be hindered by blocking TGF-β1. Taken together, our work demonstrates iPSC-sEVs reverse the senescent characteristic of microglia in aged brains and therefore improve the outcome after stroke, at least, via delivering TGF-β1 to upregulate Rictor and p-AKT. Our data suggest that iPSC-sEVs might be a novelty therapeutic method for aged ischemic stroke and other diseases involving senescent microglia.

Background: Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening disease in children, with a high early mortality rate. This study aimed to construct machine learning model to predict the risk of early death using clinical indicators at the time of HLH diagnosis. Methods: This observational cohort study was conducted at the National Clinical Research Center for Child Health and Disease. Data was collected from pediatric HLH patients diagnosed by the HLH-2004 protocol between January 2006 and December 2022. Six machine learning models were constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) to select key clinical indicators for model construction. Results: The study included 587 pediatric HLH patients, and the early mortality rate was 28.45 %. The logistic and XGBoost model with the best performance after feature screening were selected to predict early death of HLH patients. The logistic model had an AUC of 0.915 and an accuracy of 0.863, while the XGBoost model had an AUC of 0.889 and an accuracy of 0.829. The risk factors most associated with early death were the absence of immunochemotherapy, decreased TC levels, increased BUN and total bilirubin, and prolonged TT. We developed an online calculator tool for predicting the probability of early death in children with HLH. Conclusions: We developed the first web-based early mortality prediction tool for pediatric HLH to assist clinicians in risk stratification at diagnosis and in developing personalized treatment protocols. This study is registered on the China Clinical Trials Registry platform (ChiCTR2200061315).

Objective To investigate the genomic signatures and prognosis of advanced-stage T cell lymphoblastic lymphoma (T-LBL) and to examine the relationship between T-LBL and T cell acute lymphoblastic leukemia (T-ALL). Methods 35 Chinese T-LBL children with stage III or IV disease were recruited for this study. They were treated with combination chemotherapy and whole exome sequencing. The relationship of the clinical features, prognosis and specific gene mutations was researched. Gene chips of T-LBL and T-ALL were downloaded from a database, and differential gene expression was analyzed. Results Germline causal gene mutations (CARS or MAP2K2) were detected in 2 patients; 3.06 ± 2.21 somatic causal gene mutations were identified in the 35 patients, and somatic mutations were observed in the NOTCH1, FBXW7, PHF6 and JAK3 genes. NOTCH1 mutations were significantly associated with FBXW7 mutations, and the age at diagnosis of patients with NOTCH1-FBXW7 mutations was less than that of patients without such mutations ( P < 0.05). 32 patients achieved complete remission (CR), and 14 and 18 patients were classified into the intermediate risk (IR) group and high risk (HR) group. During a median follow-up of 44 months, 3 patients relapsed. Three-year prospective event free survival (pEFS) was 82.286%, and no significant differences of pEFS were found for different sexes, ages, or statuses of NOTCH1-FBXW7 mutations, ( P > 0.05); however, the mean survival time of the IR group was longer than that of the HR group ( P < 0.05). Differential expression of genes in the T-LBL and/or T-ALL datasets was analyzed using the R package limma, and 1/3 of the differentially expressed genes were found in both the T-ALL and T-LBL datasets. High expression of PI3K-Akt signal pathway genes and the USP34 gene was found in the T-LBL dataset. Conclusion Although T-ALL and T-LBL both originate from precursor T-cells and are considered different manifestations of the same disease and the outcome of T-LBL is favorable when using T-ALL-based chemotherapy, there are differences in the gene distribution between T-LBL and T-ALL. It seems that the PI3K-Akt signaling pathway and the USP34 gene play important roles in T-LBL, but medicines targeting the USP34 gene or the PI3K-Akt pathway may be invalid.

为了探明腐皮镰刀菌对紫花苜蓿种苗的致病性,本研究采用常规组织分离法从苜蓿根部分离纯化真菌,对分离得到的菌株进行形态学结合分子生物学的鉴定,并以菌饼放置种子的方法,分别以水琼脂培养基(water agar,WA)和马铃薯葡萄糖琼脂培养基(potato dextrose agar,PDA)对22个紫花苜蓿品种的种子进行试验,在14 d测定相对根长、相对苗长、相对根苗长度比、相对发芽率和病情指数,并通过隶属函数综合各个指标,对22个苜蓿品种的抗病性进行评价.结果表明:腐皮镰刀菌为导致苜蓿根腐病的病原真菌;在两种培养基质上,腐皮镰刀菌对22个苜蓿品种均有致病性,且在PDA培养基上的致病性强于WA培养基;参试的22个苜蓿品种之间抗病性有所差异,塔苜5S的抗病性最强,中苜1号、Bara310SC、乐寒F3和金皇后的抗病性较强,中兰2号、赛迪7、龙牧803和甘农3号的抗病性较弱,Paola的抗病性最弱.