Search Results (47)

Background: CCAAT/enhancer-binding protein alpha–basic leucine zipper in-frame (CEBPA^bZIP-inf) mutations are associated with favorable outcomes in acute myeloid leukemia (AML). So far, there are limited data on integrating clinical and genomic features impacting the outcomes. Methods: Clinical and genomic data from consecutive patients with CEBPA^bZIP-inf were reviewed. A Cox proportional hazards regression was used to identify the variables associated with event-free survival (EFS), relapse-free survival (RFS) and survival. Results: 224 CEBPA^bZIP-inf patients were included in this study. In the 201 patients, except for the 19 receiving the transplant in the first complete remission with no events (the transplant cohort), multivariate analyses showed that IKZF1 mutations/deletions were significantly associated with poor EFS (p = 0.001) and RFS (p < 0.001); FLT3-ITD mutations, poor RFS (p = 0.048). In addition, increasing WBC count, lower hemoglobin concentration, non-intensive induction, and MRD positivity after first consolidation predicted poor outcomes. On the basis of the number of adverse prognostic covariates for RFS, the 201 patients were classified into low-, intermediate- or high-risk subgroups, and there were significant differences in the 3-year EFS, RFS and survival rates (all p < 0.001); however, except for survival in the low-risk group, these metrics were lower than those in the transplant cohort. Conclusions: We identified a potential high-risk population with adverse prognostic factors in CEBPA^bZIP-inf AML patients for which transplantation should be considered. Full article

Background/Objectives: The role of KDM6A gene mutations in acute myeloid leukemia (AML) remains poorly understood. This study aimed to evaluate the impact of KDM6A mutations on relapse risk, cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) in adult AML patients, with a particular focus on those with RUNX1::RUNX1T1 fusion. Methods: the retrospective analysis was conducted on 1970 adult AML patients treated at Peking University People’s Hospital. Of these, 1676 patients who achieved complete remission (CR) were included. Among them, 27 harbored KDM6A mutations. Propensity score matching (PSM) was used (1:10 ratio) to compare outcomes between patients with and without KDM6A mutations. Further analysis focused on 207 patients with RUNX1::RUNX1T1 fusion, among whom 13 had KDM6A mutations (PSM 1:5). Results: In the overall cohort, KDM6A variants (n = 27) had a higher 2-year CIR (45.7% vs. 28.6%, p = 0.04). Fine–Gray analysis showed KDM6A variants independently increased relapse risk (HR = 1.98 [1.08–3.63], p = 0.03). KDM6A mutations were associated with inferior 2-year RFS (36.3% vs. 60.9%, p = 0.044). Multivariable analysis confirmed KDM6A mutations as independent predictors of poor RFS (HR = 3.08 [1.56–6.08], p = 0.001). Among RUNX1::RUNX1T1 patients, KDM6A mutations significantly increased relapse risk (75.0% vs. 21.7%, p < 0.001), raised 2-year CIR (46.9% vs. 24.0%, p = 0.05), worsened 2-year RFS (31.3% vs. 71.9%, p < 0.001), and lowered 2-year OS (63.3% vs. 86.4%, p = 0.002). They were also independent predictors of CIR (HR = 2.46 [1.11–5.47], p = 0.03), RFS (HR = 5.1, [2.5–10.5], p < 0.001) and OS (HR = 12.9, [4.3–38.7], p < 0.001). Conclusions: KDM6A mutations are significantly associated with increased relapse risk and poor prognosis in AML, especially in patients with RUNX1::RUNX1T1 fusion, and may serve as a valuable prognostic biomarker. Full article

Background: Rice bacterial leaf blight, caused by the Gram-negative bacterium Xanthomonas oryzae pv. Oryzae (Xoo), significantly impacts rice production. To address this disease, research efforts have focused on discovering and utilizing novel disease-resistant genes and examining their functional mechanisms. Methods and Results: In this study, a variety of bacterial strains were utilized. CX28-3, AX-11, JC12-2, and X10 were isolated from the high-altitude japonica rice-growing region on the Yunnan Plateau. Additionally, PXO61, PXO86, PXO99, and PXO339, sourced from the International Rice Research Institute (IRRI), were included in the analysis. To evaluate the resistance characteristics of Haonuoyang, artificial leaf cutting and inoculation methods were applied. Results indicated that Haonuoyang exhibited broad-spectrum resistance. Additionally, to explore the genetic mechanisms of resistance, the TFAIII-type transcription factor OsZFPH was cloned from Haonuoyang using PCR amplification. The subcellular localization method identified the precise location of the OsZFPH gene within the cell. The expression of OsZFPH was induced by Xoo stress. The overexpression of OsZFPH resulted in increased activities of enzymes, including SOD, CAT, and POD, while silencing the gene led to reduced enzyme activities. Furthermore, the hormones SA (salicylic acid), JA (jasmonic acid), and GA (gibberellin) were shown to positively regulate the gene expression. Protein interactions with OsZFPH were verified through a yeast two-hybrid system and BiFC technology. Hap5, which aligned with the sequence of Haonuoyang, was found to belong to a haplotype consisting of Jingang 30, 40 resequenced rice varieties, 18 Oryza rufipogon, and 29 Oryza granulata. Conclusions: The findings of this study emphasize the vital role of OsZFPH in rice resistance to bacterial leaf blight. The identification of broad-spectrum resistance in Haonuoyang and the understanding of OsZFPH gene functions provide valuable insights for the future development of rice varieties with improved resistance to this destructive disease. Full article

A nuclear export signal (NES) is a cluster of hydrophobic amino acids that can maintain the dynamic shuttling of target proteins between the nucleus and cytoplasm. Bioinformatics analysis showed that the hydrophobic region of ⁹²PLLLHKFLLA in Bm65 is very likely to be an NES and may be involved in the production of infectious virions. In this study, we generated several mutations in ⁹²PLLLHKFLLA of Bm65, which were further used to generate recombinant viruses to study their roles in viral propagation. Subcellular analysis revealed that the ⁹²PLLLHKFLLA sequence was an NES involved in the dynamic transport of Bm65. Mutations in the hydrophobic region could block the formation and accumulation of Bm65 aggregates, resulting in a uniform distribution of Bm65 in BmN cells. The ribosomal protein L13 (RPL13) of silkworms was previously reported to interact with Bm65. Here, intracellular co-localization analysis showed that the interaction between Bm65 and RPL13 was regulated by the ⁹²PLLLHKFLLA of Bm65. In summary, the interaction between Bm65 and RPL13 is essential for the production and accumulation of Bm65 aggregates and may play an important role in the regulation of viral propagation. Full article

Solar ultraviolet radiation (UV) may cause DNA damage. We first report in this study that the large subunit ribosome protein RPL12, from Bomby mori (BmRPL12), participated in UV-induced DNA damage repair. BmRPL12 enhanced the resistance of Escherichia coli (E. coli) to UV radiation and facilitated faster repair of UV-induced DNA damage in silkworm cells. BmRPL12 mainly existed in the cytoplasm in the dimer forms, and the N-terminal nuclear export signal was crucial for the localization of BmRPL12. After UV radiation, BmRPL12 was unable to localize at the UV-induced DNA damage sites to participate in damage repair directly and might indirectly regulate UV-induced DNA damage repair. Our previous research found that BmNPV Bm65 was an important UV damage-induced endonuclease. Here, it was further found that in BmNPV-infected silkworm cells, BmRPL12 in monomeric forms interacted with the virus Bm65 protein only after UV radiation, and BmRPL12 specifically localized at the UV-induced DNA damage sites only in the presence of Bm65. We speculate that after viral infection in cells subjected to UV-induced DNA damage, viral protein Bm65 interacts with BmRPL12 and localizes BmRPL12 to sites of UV-damaged DNA. Full article

Purpose: This study aimed to investigate the efficacy and the clinical and molecular predictors of response and survival following venetoclax plus hypomethylating agents (VEN + HMAs) in adult relapsed/refractory acute myeloid leukemia (R/R AML) patients. Methods: We retrospectively analyzed 197 adult R/R AML patients who received the VEN + HMAs regimen. Molecular profiling was performed using targeted next-generation sequencing (NGS) of 139 genes to explore potential response and survival genetic predictors. Results: The median treatment cycle was 1 (1–4) cycle. The composite complete remission (CRc) rate, encompassing complete remission (CR) and CR with incomplete hematologic recovery (CRi), was 44.7%, while the overall response rate (ORR) reached 59.9%. With a median follow-up period of 14.0 months (range: 0.7–54.0 months), the 1-year and 2-year overall survival (OS) rates were 55.4% and 40.2%, respectively. Multivariate analyses revealed that mutations in NPM1 and SRSF2 were significantly associated with improved response rates. Conversely, prior exposure to HMA therapy, early relapse, and the presence of GATA2 mutations were linked to lower response rates. Regarding survival outcomes, the CBFB-MYH11 fusion gene, as well as mutations in NPM1 and IDH1/2, were found to be favorable prognostic factors for OS, whereas mutations in FLT3-ITD, TP53, DNMT3A, and GATA2 were associated with worse OS. Conclusions: The VEN + HMAs regimen demonstrated considerable efficacy in the treatment of R/R AML patients, with both response rates and overall survival being influenced by distinct genetic features. These findings provide valuable insights into optimizing personalized treatment strategies for this challenging patient population. Full article

Background: During the COVID-19 pandemic, we continuously monitored the epidemiology of influenza virus among pediatric patients from January 2021 to December 2023 in Hainan Island, China. Methods: In this study, we collected 54,974 nasopharyngeal swab samples for influenza A Virus (IAV) testing and 53,151 samples for influenza B Virus (IBV) testing from pediatric outpatients. Additionally, we also collected 19,687 nasopharyngeal swab samples from pediatric inpatients for IAV and IBV testing. Outpatient samples were screened for influenza viruses (IVs) infection by the colloidal gold method. Targeted Next-Generation Sequencing (tNGS) was used to detect influenza virus infections in inpatients. Influenza virus types were identified by analyzing the HA/NA partial regions. Results: The findings revealed a significant decrease in the infection rate of IBV over the specified period, while the infection rate of IAV exhibited a rising trend. Additionally, B/Victoria lineage was the dominant epidemic strain in 2021, while the epidemic strains in 2022 and 2023 underwent a dynamic transformation from A/H3N2 to A/H1N1. Phylogenetic analysis revealed close relationships among the circulating strains. Nonetheless, because the sample size is limited, additional research is required. Conclusions: Our findings suggest that the predominant types of influenza viruses in the pediatric population are undergoing dynamic changes, influenced by the implementation and relaxation of non-pharmaceutical intervention measures. These findings highlight the need for adaptive influenza vaccination and containment strategies, particularly in tropical regions like Hainan, where climate and public health policies significantly impact viral transmission patterns. The insights gained from this study could inform more effective public health strategies in similar regions to mitigate the impact of influenza outbreaks in the future. Full article

Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis. To investigate its structure and function, we employed phylogenetic analysis, subcellular localization, mutational analysis, and a dual-luciferase reporter system to characterize the nuclear localization signal (NLS) within NS2 and its effect on viral promoter activity. Additionally, co-immunoprecipitation and mass spectrometry were utilized to identify host proteins interacting with NS2. We identified a functional bipartite NLS in NS2, validated the combination pattern of key amino acids, and demonstrated its role in regulating viral promoter activity. Furthermore, we identified potential NLSs in NS2 homologs in other invertebrate ssDNA viruses based on sequence analysis. We also revealed interactions between NS2 and host nuclear transport proteins, suggesting that it plays a role in nuclear transport and viral replication. This research underscores the importance of NS2’s NLS in BmBDV’s life cycle and its potential conservation across invertebrate ssDNA viruses, providing insights into virus–host interactions and avenues for antiviral strategy development. Full article

In the era of widespread digital image sharing on social media platforms, deep-learning-based watermarking has shown great potential in copyright protection. To address the fundamental trade-off between the visual quality of the watermarked image and the robustness of watermark extraction, we explore the role of structural features and propose a novel edge-aware watermarking framework. Our primary innovation lies in the edge-aware secret hiding module (EASHM), which achieves adaptive watermark embedding by aligning watermarks with image structural features. To realize this, the EASHM leverages knowledge distillation from an edge detection teacher and employs a dual-task encoder that simultaneously performs edge detection and watermark embedding through maximal parameter sharing. The framework is further equipped with a social network noise simulator (SNNS) and a secret recovery module (SRM) to enhance robustness against common image noise attacks. Extensive experiments on three public datasets demonstrate that our framework achieves superior watermark imperceptibility, with PSNR and SSIM values exceeding 40.82 dB and 0.9867, respectively, while maintaining an over 99% decoding accuracy under various noise attacks, outperforming existing methods by significant margins. Full article

Heat shock proteins (Hsps), acting as molecular chaperones, play a pivotal role in plant responses to environmental stress. In this study, we found a total of 192 genes encoding Hsps, which are distributed across all 12 chromosomes, with higher concentrations on chromosomes 1, 2, 3, and 5. These Hsps can be divided into six subfamilies (sHsp, Hsp40, Hsp60, Hsp70, Hsp90, and Hsp100) based on molecular weight and homology. Expression pattern data indicated that these Hsp genes can be categorized into three groups: generally high expression in almost all tissues, high tissue-specific expression, and low expression in all tissues. Further analysis of 15 representative genes found that the expression of 14 Hsp genes was upregulated by high temperatures. Subcellular localization analysis revealed seven proteins localized to the endoplasmic reticulum, while others localized to the mitochondria, chloroplasts, and nucleus. We successfully obtained the knockout mutants of above 15 Hsps by the CRISPR/Cas9 gene editing system. Under natural high-temperature conditions, the mutants of eight Hsps showed reduced yield mainly due to the seed setting rate or grain weight. Moreover, the rice quality of most of these mutants also changed, including increased grain chalkiness, decreased amylose content, and elevated total protein content, and the expressions of starch metabolism-related genes in the endosperm of these mutants were disturbed compared to the wild type under natural high-temperature conditions. In conclusion, our study provided new insights into the HSP gene family and found that it plays an important role in the formation of rice quality and yield. Full article

The Cleavage Stimulation Factor (CstF) complex, consisting of three subunits, is essential for the 3′ end processing of precursor messenger RNA (pre-mRNA). In mammals, this complex includes CstF50, CstF64, and CstF77, named according to their molecular weights, and these proteins are conserved across many organisms. However, the functional roles of the three CstF genes (NlCstF50, NlCstF64, and NlCstF77) in Nilaparvata lugens, a major rice pest, have not been fully explored. This study identified and characterized the sequences of these genes, with proteins encoded by NlCstF50, NlCstF64, and NlCstF77 consisting of 439, 419, and 732 amino acids, respectively. These proteins are conserved among various insect species. Spatio-temporal expression analysis revealed that these genes are expressed at all developmental stages and in various tissues, with peak levels in eggs and testes. RNA interference (RNAi) targeting one or all three NlCstF genes resulted in a reduction in gene expression by 68% to 90% at 72 h post-injection, indicating that multi-gene dsRNA can achieve similar silencing outcomes as single-gene dsRNA. Knocking down one or all three NlCstF genes caused significant lethal phenotypes and molting disruptions. Mortality rates increased from 62.5% (dsNlCstF50) to 95.4% (dsNlCstF(50+64+77)). Additionally, silencing these genes reduced the number of eggs laid per female and hatch rates. These results highlight the critical role of NlCstF genes in the development and reproduction of N. lugens, suggesting their potential as targets for RNAi-based pest control strategies. Full article

Human parainfluenza viruses (HPIVs) are the leading causes of acute respiratory tract infections (ARTIs), particularly in children. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) significantly influenced the epidemiology of respiratory viruses. This study analyzed 19,339 respiratory specimens from pediatric patients with ARTIs to detect HPIVs using PCR or tNGS, focusing on the period from 2021 to 2023. HPIVs were identified in 1395 patients (7.21%, 1395/19,339), with annual detection rates of 6.86% (303/4419) in 2021, 6.38% (331/5188) in 2022, and 7.82% (761/9732) in 2023. Notably, both the total number of tests and HPIV-positive cases increased in 2023 compared to 2021 and 2022. Seasonal analysis revealed a shift in HPIV prevalence from winter and spring in 2021–2022 to spring and summer in 2023. Most HPIV-positive cases were in children aged 0–7 years, with fewer infections among those aged 7–18 years. Since June 2022, HPIV-3 has been the most prevalent serotype (59.55%, 524/880), whereas HPIV-2 had the lowest proportion (0.80%, 7/880). The proportions of HPIV-1 (24.89%, 219/880) and HPIV-4 (15.45%, 136/880) were similar. Additionally, the incidence of co-infections with other common respiratory pathogens has increased since 2021. This study highlights rising HPIV detection rates post-COVID-19 and underscores the need for continuous surveillance of HPIVs to inform public health strategies for future epidemic seasons. Full article

Phytohormones have the potential to enhance the nutrient removal efficiency of aquatic plants in wastewater treatment. Here, we investigated the impact of indoleacetic acid (IAA) on nitrogen removal by Hydrocotyle vulgaris Lam during the remediation process of eutrophic water. This investigation involved evaluating the biological indicators of H. vulgaris Lam, the nitrogen salt removal efficiency in eutrophic water, as well as analyzing the bacterial structure and function in both the rhizosphere and eutrophic water surrounding H. vulgaris Lam. The results indicated that surface-sprayed 50 mg/L IAA significantly stimulated the growth of H. vulgaris Lam, including parameters such as blade number, leaf area, petiole length, stem thickness, stem length, and root length of H. vulgaris Lam. Furthermore, exogenous application of IAA significantly accelerated the nitrogen removal of NH₄⁺−N, NO₃⁻−N and total nitrogen (TN) in eutrophic water by promoting the NH₄−N uptake of H. vulgaris Lam and NO₃⁻−N denitrification. These findings suggest a potential application for exogenous IAA to enhance the nitrogen removal of H. vulgaris Lam in eutrophication control. Full article

Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1H-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented. Full article

A pumping-while-tripping method is proposed to mitigate pressure swabs during tripping out in wells with a narrow mud density window and extended reach. In the proposed tripping-out process, the fluid circulation is started by using a special pump from a customized circulation line before tripping is initiated. During the tripping out, drilling fluid is circulated in the wellbore simultaneously while the drilling string is moving. A model to simulate the dynamic pressure changes in this process is developed based on the Navier–Stokes (N-S) equations and a damped free vibration system. The model was initially developed for Herschel–Bulkley (H-B) fluid; however, it can be applied to other fluid models by eliminating the non-existing terms. An analysis was conducted to investigate the effect of tripping velocity and circulation pumping rate on the pressure changes. The results show that pumping-while-tripping is effective in mitigating the pressure swab during tripping out, which is especially useful for extended-reach wells. It can also help to increase tripping out velocity and save tripping time for drilling operations. Full article