Predicting survival in patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis.

We investigated data from 180 consecutive patients with myelodysplastic/myeloproliferative neoplasms with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T) who were diagnosed according to the 2022 World Health Organization (WHO) classification of myeloid neoplasms to identify covariates associated with survival. At a median follow-up of 48 months (95% confidence interval [CI] 35-61 months), the median survival was 69 months (95% CI 59-79 months). Patients with bone marrow ring sideroblasts (RS) < 15% had shorter median overall survival (OS) than did those with bone marrow RS ≥ 15% (41 months [95% CI 32-50 months] versus 76 months [95% CI 59-93 months]; P < 0.001). According to the univariable analyses of OS, age ≥ 65 years (P < 0.001), hemoglobin concentration (Hb) < 80 g/L (P = 0.090), platelet count (PLT) ≥ 800 × 10E + 9/L (P = 0.087), bone marrow RS < 15% (P < 0.001), the Revised International Prognostic Scoring System (IPSS-R) cytogenetic category intermediate/poor/very poor (P = 0.005), SETBP1 mutation (P = 0.061) and SRSF2 mutation (P < 0.001) were associated with poor survival. Based on variables selected from univariable analyses, two separate survival prediction models, a clinical survival model, and a clinical-molecular survival model, were developed using multivariable analyses with the minimum value of the Akaike information criterion (AIC) to specifically predict outcomes in patients with MDS/MPN-SF3B1-T according to the 2022 WHO classification.

Analysis of clinical features of heart failure in children with cardiomyopathy and improved ejection fraction.

Background: The prognosis of children with heart failure varies considerably. After treatment, left ventricular ejection fraction (LVEF) can be improved in some children. The aim of this study was to analyze the clinical features of children with heart failure accompanied by cardiomyopathy and recovered ejection fraction [heart failure with recovered ejection fraction (HFrecEF)] and to identify the predictors of improved LVEF. Methods: Children diagnosed with heart failure in Beijing Anzhen Hospital Affiliated to Capital Medical University from 2018 to 2021 were retrospectively enrolled. According to the baseline and change of LVEF, the patients were divided into two groups: a reduced ejection fraction (HFrEF) group and an HFrecEF group. The t-test was used to evaluate the difference between the two groups. The predictive factors of ejection fraction improvement were analyzed with a logistic regression model. Results: A total of 72 children were included in this study, including 31 (43.1%) in the HFrEF group and 41 (56.9%) in the HFrecEF group. Compared with children in the HFrEF group, children in the HFrecEF group were younger and had faster resting heart rates, lower creatinine, lower suppression of tumorigenicity 2 (ST2) expression, a lower platelet-to-lymphocyte (PLT:LYM) ratio, and smaller left atrial diameter. After a mean follow-up of 35.87 months, 26 cases returned to normal ejection fraction. In the HFrEF group, sudden cardiac death occurred in two cases, and four cases received heart transplantation. Logistic analysis showed that virus infection [odds ratio (OR) =1.279; 95% confidence interval (CI): 0.374-4.379; P=0.007], low ST2 expression (cutoff value =1.89 ng/mL: OR =1.042; 95% CI: 1.007-1.082; P=0.032), and treatment with intravenous immunoglobulin (IVIG) (OR =5.077; 95% CI: 1.458-17.684; P=0.011) were predictors of improvement in LVEF in patients with heart failure after treatment. Conclusions: In some patients with HFrecEF, LVEF eventually returned to normal. The combination of viral infection, low ST2 expression, and the application of IVIG therapy were found to be independent predictors of LVEF improvement in patients with heart failure after treatment.

Combination therapy with venetoclax and azacitidine for the treatment of myelodysplastic syndromes with DDX41 mutations.

Myelodysplastic syndromes (MDS) patients with DEAD-box helicase 41 (DDX41) mutations have been reported to be treated effectively with lenalidomide; however, there are no randomized studies to prove it. Venetoclax and azacitidine are safe and effective in high-risk MDS/AML. In this study, we evaluated the efficacy of venetoclax and azacitidine combination therapy in eight consecutive MDS patients with DDX41 mutations at our centre from March 2021 to November 2023. We retrospectively analyzed the genetic features and clinical characteristics of these patients. Our findings suggest that MDS patients with DDX41 mutation may benefit from the therapy, for six subjects received this regimen as initial therapy and five of the six subjects achieved complete remission.

Validation and comparison of 5th edition World Health Organization classification (WHO 2022) and International Consensus Classification proposals for MDS-SFB31.

The criteria of myelodysplastic syndromes (MDS) with mutated SFB31 (MDS-SFB31) proposed by the 5th edition of the WHO classification (WHO 2022) and the International Consensus Classification (ICC) need validation. We analysed 125 consecutive MDS cases with SFB31 mutation or ring sideroblasts (RS) ≥15% without excess blasts. We found that SFB31-negative MDS with RS had significantly different clinical features and worse prognosis. According to WHO 2022, the detection of ≥15% RS may substitute for SF3B1 mutation and our analyses support this proposal for similar prognosis of two groups after excluding high-risk genetic features referred by WHO 2022. Patients with variant allele frequency (VAF) <10% SFB31 tend to have briefer survival, supporting the VAF 10% threshold of ICC. Patients with multilineage dysplasia (MLD) had significantly shorter OS than those with single lineage dysplasia. MLD is still a powerful morphological marker of worse outcome in WHO 2022 and ICC-defined MDS-SF3B1.

Rejuvenating classical brain electrophysiology source localization methods with spatial graph Fourier filters for source extents estimation.

EEG/MEG source imaging (ESI) aims to find the underlying brain sources to explain the observed EEG or MEG measurement. Multiple classical approaches have been proposed to solve the ESI problem based on different neurophysiological assumptions. To support clinical decision-making, it is important to estimate not only the exact location of the source signal but also the extended source activation regions. Existing methods may render over-diffuse or sparse solutions, which limit the source extent estimation accuracy. In this work, we leverage the graph structures defined in the 3D mesh of the brain and the spatial graph Fourier transform (GFT) to decompose the spatial graph structure into sub-spaces of low-, medium-, and high-frequency basis. We propose to use the low-frequency basis of spatial graph filters to approximate the extended areas of brain activation and embed the GFT into the classical ESI methods. We validated the classical source localization methods with the corresponding improved version using GFT in both synthetic data and real data. We found the proposed method can effectively reconstruct focal source patterns and significantly improve the performance compared to the classical algorithms.

Secreted salt and hydrodynamic factors combine to affect dynamic fluctuations of microplastics on mangrove leaves.

Mangrove leaves have been acknowledged as crucial sink for coastal microplastics (MPs). Whereas, the temporal dynamics of MPs intercepted by mangrove leaves have remained poorly understood. Here, we detected MPs intercepted by submerged and non-submerged mangrove leaves over time and the potential driving factors. Abundance and characteristics of MPs interception by mangrove leaves exhibited dynamic fluctuations, with the coefficient of variation (CV) of submerged mangrove leaves (CV = 0.604; 1.76 n/g to 15.45 n/g) being approximately twofold higher than non-submerged mangrove leaves (CV = 0.377; 0.74 n/g to 3.28 n/g). Partial least squares path model (PLS-PM) analysis further illustrated that MPs abundance on submerged mangrove leaves were negative correlated to hydrodynamic factors (i.e., current velocity and tidal range). Intriguingly, secreted salt as a significantly driver of MPs intercepted by mangrove leaves. Results of this work highlights that MPs intercepted by mangrove leaves is characterized by dynamic fluctuations and reveals the importance of hydrodynamic factors and secreted salt. Overall, this work identifies the pivotal buffering role played by mangrove leaves in intercepting MPs, which provides basic knowledge for better understanding of microplastic pollution status and control from mangrove plants.

Review of Anaka Dworakowska & Viraktamath, 1975 (Hemiptera, Cicadellidae, Typhlocybinae) with the descriptions of five new species from China.

The dikraneurine leafhopper genus Anaka is reviewed based on a comparative morphological study. Five new species, Anakaauriculasp. nov., Anakacruciatasp. nov., Anakacurvatasp. nov., Anakarosaceasp. nov., and Anakaspiralissp. nov. from China are described and illustrated in detail. Additionally, a key to known Anaka species is provided along with a checklist of all species and their distributions.

Relevance Analysis of TPM2 and Clinicopathological Characteristics in Breast Cancer.

Background: The function of tropomyosin 2 (TPM2) in breast cancer is still far understudied. In this study, we aim to explore the roles of TPM2 in breast cancer progression. Methods: This research included 155 breast cancer tissues. The expression of TPM2 was analyzed by immunohistochemical staining and grading. The mRNA expression of TPM2 in pan-cancer was analyzed with The Cancer Genome Atlas (TCGA) data plate form. The differential expression of TPM2 protein and the differential promoter methylation level of TPM2 between breast cancer tissues and normal breast tissues were analyzed by the UALCAN online database. The relationship between TPM2 and signaling pathways was interpreted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway enrichment analyses. The survival curve of TPM2 was analyzed across the Kaplan-Meier plotter online database. Furthermore, the relationship between TPM2 expression and infiltrating macrophages was validated through in vitro co-culture experiments. Results: TPM2 expression was significantly down-regulated in breast cancer samples. In addition, TPM2 expression was correlated with lymph node metastasis and high-grade histopathological morphology. The receiver operating characteristic (ROC) curve indicated that TPM2 expression could well distinguish between normal breast tissue and breast cancer tissue. TPM2 may have potential value in breast cancer diagnosis. Bioinformatics analysis illustrated that TPM2 was mainly involved in extracellular matrix organization, collagen fibril organization, cell junction assembly, focal adhesion, cAMP signaling pathway, estrogen signaling pathway, Wnt signaling pathway, and adaptive immune system. TPM2 expression was correlated with immune infiltrating cells and immune checkpoint molecules. Our in vitro co-culture experiments showed that the M2 macrophages could upregulate the expression of TPM2. Conclusion: TPM2 may play key roles in breast cancer occurrence and development, especially in cancer metastasis. TPM2 may be a potential biomarker for breast cancer diagnosis.

Insight into the role of niche concept in deciphering the ecological drivers of MPs-associated bacterial communities in mangrove forest.

Myriad inherent and variable environmental features are controlling the assembly and succession of bacterial communities colonizing on mangrove microplastics (MPs). However, the mechanisms governing mangrove MPs-associated bacterial responses to environmental changes still remain unknown. Here, we assessed the dissimilarities of MPs-associated bacterial composition, diversity and functionality as well as quantified the niche variations of each taxon on plastispheres along river-mangrove-ocean and mangrove landward-to-seaward gradients in the Beibu Gulf, China, respectively. The bacterial richness and diversity as well as the niche breadth on mangrove sedimentary MPs dramatically decreased from landward to seaward regions. Characterizing the niche variations linked the difference of ecological drivers of MPs-associated bacterial populations and functions between river-mangrove-ocean (microplastic properties) and mangrove landward-to-seaward plastispheres (sediment physicochemical properties) to the trade-offs between selective stress exerted by inherent plastic substrates and microbial competitive stress imposed by environmental conditions. Notably, Rhodococcus erythropolis was predicted to be the generalist species and closely associated to biogeochemical cycles of mangrove plastispheres. Our work provides a reliable pathway for tackling the hidden mechanisms of environmental factors driving MPs-associated microbe from perspectives of niches and highlights the spatial dynamic variations of mangrove MPs-associated bacteria.

Transformation of 6PPDQ during disinfection: Kinetics, products, and eco-toxicity assessment.

N-phenyl-N'-(1,3-dimethyl butyl)-p-phenylenediamine-quinone (6PPDQ) currently arouses broad concerns because of its acute lethality to coho salmon and rainbow trout at environmentally relevant concentrations and the wide occurrence in runoff-impacted water. Investigation on the fate and transformation of 6PPDQ in various treatment processes is necessary for its risk assessment and control. Here, we explored the transformation of 6PPDQ during disinfection with its precursor 6PPD as a reference, focusing on kinetics, products, and toxicity variation. 6PPDQ readily reacted with hypochlorite and chlorine dioxide with second-order rate constants of 2580 ± 143 M-1 s-1 and 614 ± 52 M-1 s-1 (pH 7.0 and 25 °C), which are slightly lower than the reactions of 6PPD. We tentatively identified thirteen transformation products for 6PPDQ and eight for 6PPD in reaction with the two disinfectants. It seems that the quinone ring of 6PPDQ and the p-phenylenediamine moiety of 6PPD are reactive sites. The transformation of these compounds probably proceeds through Cl-substitution, ring cleavage, hydroxylation, and amine oxidation and hydrolysis. Tests with zebrafish embryos revealed that the transformation products of 6PPDQ could have higher eco-toxicity than the parent compound, while the toxicity of the 6PPD products remained nearly unchanged. The increased toxicity of 6PPDQ during disinfection highlights the necessity to substantially reduce its content before the disinfection of runoff-impacted water.

VHL loss enables immune checkpoint blockade therapy by boosting type I interferon response.

Despite a moderate mutation burden, clear cell renal cell carcinoma (ccRCC) responds well to immune checkpoint blockade (ICB) therapy. Here we report that loss-of-function mutations in the von Hippel-Lindau (VHL) gene, the most frequent in ccRCC, underlies its responsiveness to ICB therapy. We demonstrate that genetic knockout of the VHL gene enhanced the efficacy of anti-PD-1 therapy in multiple murine tumor models in a T cell-dependent manner. Mechanistically, we discovered that upregulation of HIF1α and HIF2α induced by VHL gene loss decreased mitochondrial outer membrane potential and caused the cytoplasmic leakage of mitochondrial DNA (mtDNA), which triggered cGAS-STING activation and induced type I interferons. Our study thus provided novel mechanistic insights into the role of VHL gene loss in potentiating ccRCC immunotherapy.

Identification of the AP2/ERF transcription factor family of Eleutherococcus senticosus and its expression correlation with drought stress.

In this study, through analysis of the genome of Eleutherococcus senticosus (ES). 228 AP2/ERF genes were identified and classified into 5 groups AP2 (47 genes), ERF (108 genes), RAV (6 genes), DREB (64 genes), and soloist (3 genes). According to the AP2/ERF classification of Arabidopsis thaliana, the ES AP2/ERF proteins were subdivided into 15 groups. The gene structure and motifs of each group of AP2/ERF in ES were highly similar, which confirmed the conservation of AP2/ERF genes. The ES AP2/ERF genes were unevenly distributed on chromosomes, and a total of four pairs of tandem repeats, and 84 co-linear gene pairs were found, so the AP2/ERF genes expanded in a fragment replication manner, and dominated by pure selection during evolution. By analyzing the transcriptome data of ES under different drought stress conditions, 87 AP2/ERF genes with differential expression were obtained, of which 10 genes with highly significant differences were further analyzed and screened for qRT-PCR validation. To the best of our knowledge, this is the first report on the AP2/ERF gene of Eleutherococcus senticosus, and the bioinformatics analysis and experimental validation provided valuable information about them, which is of great significance for further research on the molecular mechanisms of ES in response to drought stress.

Correlation of Claudin18.2 expression with clinicopathological characteristics and prognosis in gastric cancer.

OBJECTIVES: Claudin18.2 (Cldn18.2) is a tight junction protein expressed in gastric epithelial cells and is an emerging target for gastric cancer (GC). This study aimed to analyze the correlation between Cldn18.2 and clinicopathological parameters in GC patients undergoing radical surgery. METHODS AND RESULTS: This study included 426 GC patients who underwent radical gastrectomy. The expression of Cldn18.2 was analyzed by immunohistochemical staining and grading. The statistical results indicated that the expression of Cldn18.2 was correlated with T stage, TNM stage, Lauren classification, and the expression level of Mucin-2 (MUC2), Mucin-5AC (MUC5AC), Mucin-6 (MUC6), human epidermal growth factor receptor 2 (HER2), P53 and trefoil factor 2 (TFF2). In addition, through data mining of the Cancer Genome Atlas (TCGA) database, it is suggested that Cldn18.2 expression level is significantly correlated with the expression level of MUC5AC, MUC6, and TFF2. Besides, Cldn18.2 is related to tumor immune infiltration, programmed cell death protein 1 (PD 1) pathway, cell cycle and Wnt signaling pathway. CONCLUSIONS: The expression of Cldn18.2 was closely related to gastric-type GC, so gastric-type GC patients may benefit more from targeted drugs targeting Cldn18.2. In GC cells, depletion of Cldn18.2 may influence cell cycle and immune response by affecting Wnt signaling pathway and PD 1 pathway.

Distinct microplastics abundance variation in root-associated sediments revealed the underestimation of mangrove microplastics pollution.

Mangrove sediment is acknowledged as the critical sink of microplastics (MPs). However, the potential effect of mangrove root systems on the MPs migration in sediment remains largely unknown. Here, our study characterized the spatial distribution of MPs trapped in root hair, rhizosphere, and non-rhizosphere zones, and analyzed their correlations with physicochemical properties of sediments. The significantly increased MPs abundances toward root systems shed light on the distinct effect on the migration of MPs exerted by mangrove root systems. Partial least squares path modeling (PLS-PM) analysis revealed that pore water content and pH influenced the abundances of different MP characteristics (shape, color, size, and type) and further promoted the accumulation of MPs toward the root systems. In different mangrove areas from landward to seaward, other sediment properties (median grain size, clay content, and salinity) also controlled MP distribution. Additionally, smaller-sized MPs (<1000 µm) were more easily transported to the root systems. Our study emphasizes the importance of considering root systems effect when investigating the mechanisms of MPs distribution and migration in mangrove sediments.

Mechanistic insight into the adverse outcome of tire wear and road particle leachate exposure in zebrafish (Danio rerio) larvae.

Tire wear particles (TWP) have become the major microplastic pollution in China. Road runoff containing TWP leachate can decrease the eye size and even induced mortality in the aquatic organisms. However, the toxic mechanism of TWP and road particles (RP) leachate on aquatic organisms is still unclear. In this study, the zebrafish embryos were exposed to TWP or RP leachate for 5 days at both environmental relevant and high concentrations. The adverse outcome pathways (AOPs) were screened from individual to molecular levels. The morphological and behavioral analysis demonstrated that the leachate exposure mainly impaired the eye development of zebrafish larvae and inhibited the larval swim behavior and phototactic response, which are the adverse outcomes. The phototransduction modulated by zebrafish retina was significantly down-regulated through transcriptomics and metabolomics analysis. The eye histopathological analysis showed that the decreased thickness of the retinal outer nuclear layer (ONL) and retinal pigmented epithelium (RPE) after leachate exposure were caused by the decreased photoreceptor cells. Moreover, the expression of NR2E3 and TPO genes showed concentration-dependent down-regulation after leachate exposure. The inhibition of photoreceptor cell proliferation was identified as the main reason for photoreceptor cell decrease in zebrafish larval eye. This study, for the first time, uncovered the underlying toxic mechanism of TWP and RP on zebrafish larval eyes.

Regional horizontal ecological compensation and ecosystem service value based on water resources pattern and insurance gain.

Ecological compensation plays an important role in maintaining ecosystem services and promoting regional green development. We built a regional horizontal ecological compensation model based on water resources pattern and insurance gain, and which was used to solve the problems of single compensation method and low compensation efficiency. Taking the Beijing-Tianjin-Hebei region as an example, we analyzed water footprint and water ecological carrying capacity from 2000 to 2019. The compensation subject and object and water footprint compensation amount were determined according to the input cost of ecological protection and allocation factor. Then, the insurance pricing model was introduced to determine ecological insurance premium rate. We calculated insurance compensation, ecological compensation standard and different types of ecosystem service value. Results showed that the whole region was at a state of water ecological deficit, with the agricultural water footprint accounting for 94.5%. From the perspective of the compensation subject and object, Beijing and Tianjin, as the compensation subject, needed to pay 0.402 billion yuan and 0.396 billion yuan (the amount of compensation) to Hebei Province each year. Hebei Province obtained a total of 0.228 billion yuan of ecological insurance with an insurance premium rate of 1.4%, and should receive an average annual ecological compensation standard of 0.81 billion yuan from Beijing and Tianjin. Hydrological regulation was the core ecosystem service in the region, with an average value of 187.974 billion yuan. It was of strategic significance to introduce ecological insurance mechanism to construct horizontal ecological compensation mechanism, improve ecosystem service function, and enhance the value of ecosystem services in the study area.

Role of mangrove forest in interception of microplastics (MPs): Challenges, progress, and prospects.

Mangroves receive microplastics (MPs) from terrestrial, marine and atmospheric sources, acting as a huge filter for environmental MPs between land and sea. Due to the high primary production and complex hydrodynamic conditions in mangroves, MPs are extensively intercepted in various ways while flowing through mangroves, leading to a long-standing but fiercely increasing MPs accumulation. However, current researches mainly focused on the occurrence, source and fate of MPs pollution in mangroves, ignoring the role of mangrove forests in the interception of MPs. Our study firstly demonstrates that mangrove ecosystems have significantly greater MPs interception capacity than their surrounding environments. Then, the current status of studies related to the interception of MPs in mangrove ecosystems is comprehensively reviewed, with the main focus on the interception process and mechanisms. At last, the most pressing shortcomings of current research are highlighted regarding the intercepted flux, interception mechanisms, retention time and ecological risks of MPs in mangrove ecosystems and the relevant future perspectives are provided. This review is expected to emphasize the critical role of mangrove forests in the interception of MPs and provide the foundational knowledge for evaluating the MPs interception effect of mangrove forests globally.

Potential key genes are expected to become biomarker for early diagnosis of colorectal cancer through bioinformatics analysis.

Colorectal cancer (CRC) is the leading cause of cancer-related deaths in the world. The aim of this study was to identify the potential key genes, and associated pathways for early-onset CRC through bioinformatics methods. We integrated the gene expression patterns of CRC from three RNAseq datasets (GSE8671, GSE20916, GSE39582) from GEO database to identify DEGs between CRC and normal samples. We established a gene co-expression network through WGCNA. Through the WGCNA calculation, the genes were divided into six modules. The WGCNA analysis screened 242 genes associated with pathological stage and colorectal adenocarcinoma, 31 of which had the ability to predict OS with an AUC >0.7. The GSE39582 dataset identified 2040 DEGs between the CRC and normal samples. The two were intersected to obtain two genes: NPM1 and PANK3. The two genes were used as a threshold to divide the samples into high group and low group for survival analysis. Survival analysis showed that increased expression of both genes was significantly associated with a poorer prognosis. These two genes (NPM1 and PANK3) could be possible marker genes for early diagnosis of CRC, providing ideas for other experimental studies in the future.