Search Results (95)

Central nervous system (CNS) tumor with BCL6 corepressor gene BCOR/BCORL1 fusion is an extremely rare tumor entity, with fewer than 40 cases reported. These tumors are distinct from the WHO 2021-defined CNS tumor with BCOR internal tandem duplication. Even rarer are CNS tumors that match to the methylation class of CNS tumors with BCOR/BCORL1 fusion, but lack fusions and instead harbor truncating small nucleotide variants in BCOR. To our knowledge, only two other cases of this scenario have been previously reported. Due to their scarcity and morphological features that mimic oligodendrogliomas and ependymomas, the diagnosis of CNS tumor with BCOR/BCORL1 fusion can be challenging, and misdiagnoses are not uncommon. Histologic findings of Olig2 positivity with focal to absent GFAP warrant further evaluation for this tumor entity. Moreover, no standard of care therapy exists for these tumors, making treatment selection difficult. We present a case of a 37-year-old woman with a midline CNS tumor with BCOR/BCORL1 fusion, harboring a pathogenic BCOR c.626del (p.S209Cfs*7) (Exon 4) variant, who was successfully treated with definitive radiation therapy and adjuvant temozolomide. Notably, EMA showed focal strong dot-like perinuclear immunoreactivity, which has not been previously reported in these tumors. This case adds to the limited but growing body of evidence supporting the use of radiation and temozolomide in treating tumors matching the methylation class of CNS tumors with BCOR/BCORL1 fusion without a detectable fusion. Full article

Ginseng peptides, as bioactive components of ginseng, have attracted increasing attention. In this study, a 14-amino acid ginseng peptide was selected and heterologously expressed in Saccharomyces cerevisiae using a multicopy tandem fusion strategy, named 7RS14α. The secondary structure of the recombinant ginseng tetradecapeptide (7RS14α) was analyzed, and a high-glucose model was established in mouse adipocytes to evaluate its biological activity. Transcriptomic profiling was further performed to elucidate its potential mechanisms. Results demonstrated that 7RS14α significantly enhanced glucose uptake in high-glucose model cells, likely by modulating lipid metabolism pathways and insulin signaling cascades, thereby influencing energy homeostasis in adipocytes. Full article

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of uterine mesenchyme, accounting for 15–20% of uterine sarcomas. It is classified into low-grade (LG-ESS) and high-grade (HG-ESS) subtypes, each defined by distinct histopathological and molecular features. LG-ESS exhibits slow progression, resembling proliferative-phase endometrial stroma, with genetic alterations like JAZF1-SUZ12 fusions. HG-ESS is more aggressive, characterized by high mitotic activity, necrosis, and genetic markers such as BCOR internal tandem duplication, often leading to advanced-stage diagnosis. Surgical resection is the cornerstone for managing early-stage ESS. A total hysterectomy with bilateral salpingo-oophorectomy (BSO) is recommended to prevent recurrence. Fertility-preserving approaches may be considered in LG-ESS but are associated with high recurrence rates. Lymphadenectomy is not routinely performed, given its limited prognostic value. HG-ESS, due to its aggressiveness, often requires additional treatment, including chemotherapy. Adjuvant therapy varies by subtype. LG-ESS responds well to hormonal treatments such as aromatase inhibitors and progestins, while tamoxifen is contraindicated. HG-ESS, lacking hormonal receptor expression, is managed with chemotherapy, often incorporating doxorubicin-based regimens. Radiotherapy may improve local control in select cases but shows limited impact on overall survival. Advanced-stage ESS treatment focuses on complete cytoreduction, supplemented by systemic therapies. Hormonal therapy remains the standard for advanced LG-ESS, whereas HG-ESS relies on chemotherapy. Prognosis depends on the subtype and stage. LG-ESS has favorable outcomes, with five-year survival exceeding 90% in early stages, but recurrent disease remains common. HG-ESS is associated with poorer survival due to its aggressive nature. Advances in molecular profiling offer promising avenues for personalized therapies, integrating genomic insights with targeted treatments to improve outcomes in this rare malignancy. Full article

Rice (Oryza sativa) is one of the key staple crops, providing food for nearly half of the world’s population. The past twenty years have seen significant advances in understanding Oryza species through genome sequencing efforts. However, the stability of Oryza genomes during their divergence has not been well characterized. Here, by performing gene collinearity and comparative genomics analysis, we selected ten Oryza species and three other Poaceae species to check their genome stability, with Leersia perrieri as the reference. Intra- and intergenomic analysis showed a ~30% difference in homologous block numbers and a 35.7% difference in collinear gene numbers per block, indicating that Oryza genomes have undergone extensive DNA permutations. Notably, we found that Oryza chromosomes with smaller ordinal numbers have often preserved larger percentages of genes, while those with bigger numbers have undergone more gene losses. This unique observation may be explained by elevated gene losses incurred by illegitimate or homoeologous recombination between homoeologous chromosomes produced by the grass-common tetraploidization (GCT) ~100 million years ago (Mya), e.g., Chro. 11 and 12. However, the lowered gene loss rates in Chro. 1–3 could be explained by earlier restriction of illegitimate recombination after the GCT due to there often being (larger) neo-chromosomes produced by the fusion of ancestral chromosomes. The enriched NBS-LRR (nucleotide-binding site and leucine-rich repeat) genes in chromosomes 11 and 12 are another explanation for the above observation. Further evidence was obtained from other Poaceae plants. Moreover, we revealed around twice as many differences in tandem genes and their densities among Oryza plants, further showing their divergent levels of genome stability. The present efforts may contribute to the understanding of the stability of the Oryza genome and its formation, evolution, and functional innovation. Full article

Underwater observation and operation for divers and underwater robots still largely depend on optic methods, such as cameras videos, etc. However, due to the poor quality of images captured in murky waters, underwater operations in such areas are greatly hindered. In order to solve the issue of degraded images, this paper proposes a multi-module combination method (UMMC) for underwater image enhancement. This is a new solution for processing a single image. Specifically, the process consists of five modules. With five separate modules working in tandem, UMMC provides the flexibility to address key challenges such as color distortion, haze, and low contrast. The UMMC framework starts with a color deviation detection module that intelligently separates images with and without color deviation, followed by a color and white balance correction module to restore accurate color. Effective defogging is then performed using a rank-one prior matrix-based approach, while a reference curve transformation adaptively enhances the contrast. Finally, the fusion module combines the visibility and contrast functions with reference to two weights to produce clear and natural results. A large number of experimental results demonstrate the effectiveness of the method proposed in this paper, which shows good performance compared to existing algorithms, both on real and synthetic data. Full article

Previously, we reported on the peptide–HLA-I fusion protein EpCAM-ReTARG^TPR, which allows us to redirect the cytotoxic activity of pre-existing anti-CMV CD8^pos T cell immunity to selectively eliminate EpCAM^pos cancer cells. EpCAM-ReTARG^TPR consists of the CMV pp65-derived peptide TPRVTGGGAM (TPR) fused in tandem with a soluble HLA-B*07:02/β2-microglobulin (β2M) molecule and an EpCAM-directed Fab antibody fragment. To further enhance its anticancer activity, we equipped EpCAM-ReTARG^TPR with the immune-potentiating cytokine muteins IL2^(H16A,F42A) and IFNα^R149A, respectively. Both cytokines are engineered to have attenuated affinity for their respective cytokine receptors. Compared to EpCAM-ReTARG^TPR, in vitro treatment of EpCAM^pos carcinoma cell lines with EpCAM-ReTARG^TPRvIL2 for 24 h increased the cytotoxic activity of PBMCs containing low levels of TPR-specific CD8^pos T cells by ~15%, whereas EpCAM-ReTARG^TPRIFNα^R149A induced an increase of ~50%. Moreover, treatment for 120 h with EpCAM-ReTARG^TPRIFNα^R149A inhibited the proliferative capacity of the cancer cell lines OvCAR3 and PC3M by ~91% without compromising the viability of the TPR-specific CD8^pos T cells and increased their capacity for IFNγ secretion. Importantly, EpCAM-ReTARG^TPRIFNα^R149A potently induced the elimination of primary EpCAM^pos refractory carcinoma cells from a Merkel cell carcinoma (MCC) patient. Taken together, the armoring of the carcinoma-directed peptide–HLA-I fusion protein EpCAM-ReTARG^TPR with IFNα^R149A potently enhanced the efficacy of pre-existing anti-CMV CD8^pos T cell immunity to selectively eliminate EpCAM^pos cancer cells. Full article

It was found that the serine protease inhibitors BmSPI38 and BmSPI39 in silkworm can strongly inhibit the activity of porcine pancreatic elastase, which has potential applicational value in the drug research and development of lung diseases, inflammatory diseases, and skin aging caused by the excessive release of elastase. Previous studies have shown that homotypic multimers obtained by tandem expression can significantly enhance the antifungal activity and structural homogeneity of BmSPI38 and BmSPI39, while the effect of the tandem expression of these two inhibitors, with different combinations, on the total activity and expression levels of multimers remains unclear. The aim of this study is to explore whether it is possible to obtain the combination of BmSPI38 and BmSPI39 with strong total expression activity by protein engineering. In this study, 40 tandem multimer expression vectors with different combinatorial forms of BmSPI38 and BmSPI39 were constructed by the isocaudomer method, and recombinant proteins were obtained by the prokaryotic expression system. The target proteins were separated by SDS-PAGE to analyze the expression levels of multimer proteins with different combinatorial forms. The total activity of the recombinant expression products with different tandem forms was investigated using the in-gel activity staining technique of protease inhibitors. The SDS-PAGE results show that the expression levels of tandem multimers containing the BmSPI39 module at the carboxyl terminus were generally higher in the Escherichia coli supernatant than that of the tandem multimers containing the BmSPI38 module at the carboxyl terminus. The activity staining results indicate that compared with BmSPI38 and BmSPI39 homotypic multimers, the total activity of some recombinant expression products with different tandem forms was stronger. Furthermore, the total activity level was relatively higher when the carboxyl terminus of the multimer was a BmSPI39 module, such as the tandem dimers SPIAB and SPIaB and the tandem trimers SPIabB, SPIaaB, and SPIbaB. In this study, the expression of tandem fusion proteins with different combinations of the silkworm protease inhibitors BmSPI38 and BmSPI39 in E. coli was successfully achieved. It was confirmed that the tandem of different combinatorial forms, based on protein engineering, was an effective way to enhance the total activity of the fusion proteins of BmSPI38 and BmSPI39 and to improve their expression levels. Additionally, a number of multimer proteins with strong total activity and high exogenous expression levels were also screened, for example, SPIbaA, SPIbbA, SPIbbB, SPIabB, SPIaaB, and SPIbaB. This study not only lays the foundation for the exogenous production and development of BmSPI38 and BmSPI39 but also provides a reference for the construction of tandem and multimerization exploration of other protease inhibitors. Full article

Background/Objectives: Arachnids are a megadiverse arthropod group. The present study investigated the chromosomes of pedipalpid tetrapulmonates (orders Amblypygi, Thelyphonida, Schizomida) and two arachnid orders of uncertain phylogenetic placement, Ricinulei and Solifugae, to reconstruct their karyotype evolution. Except for amblypygids, the cytogenetics of these arachnid orders was almost unknown prior to the present study. Methods: Chromosomes were investigated using methods of standard (Giemsa-stained preparations, banding techniques) and molecular cytogenetics (fluorescence in situ hybridization, comparative genomic hybridization). Results and Conclusions: New data for 38 species, combined with previously published data, suggest that ancestral arachnids possessed low to moderate 2n (22–40), monocentric chromosomes, one nucleolus organizer region (NOR), low levels of heterochromatin and recombinations, and no or homomorphic sex chromosomes. Karyotypes of Pedipalpi and Solifugae diversified via centric fusions, pericentric inversions, and changes in the pattern of NORs and, in solifuges, also through tandem fusions. Some solifuges display an enormous amount of constitutive heterochromatin and high NOR number. It is hypothesized that the common ancestor of amblypygids, thelyphonids, and spiders exhibited a homomorphic XY system, and that telomeric heterochromatin and NORs were involved in the evolution of amblypygid sex chromosomes. The new findings support the Cephalosomata clade (acariforms, palpigrades, and solifuges). Hypotheses concerning the origin of acariform holocentric chromosomes are presented. Unlike current phylogenetic hypotheses, the results suggest a sister relationship between Schizomida and a clade comprising other tetrapulmonates as well as a polyploidization in the common ancestor of the clade comprising Araneae, Amblypygi, and Thelyphonida. Full article

Background and Objectives: In previous studies, we reported that the assessment of the cumulative thermal dose in the crystalline lens, conducted through computational modeling utilizing a supercomputer and the biothermal transport equation, exhibited a significant association with the incidence of nuclear cataracts. In this study, we have investigated the types of proteins that expressed underlying 35.0 °C (normal-temp) and 37.5 °C (warming-temp) by using the shotgun liquid chromatography (LC) with tandem mass spectrometry (MS/MS)-based global proteomic approach. Materials and Methods: We have discussed the changes in protein expression in warmed iHLEC-NY2 cells using Gene Ontology analysis and a label-free semiquantitative method based on spectral counting. Results: In iHLEC-NY2, 615 proteins were detected, including 307 (49.9%) present in both lenses cultured at normal-temp and warming-temp, 130 (21.1%) unique to the lens cultured at normal-temp, and 178 (29.0%) unique to the lens cultured at warming-temp. Furthermore, LC–MS/MS analysis showed that warming decreased the expression of actin, alpha cardiac muscle 1, actin-related protein 2, putative tubulin-like protein alpha-4B, ubiquitin carboxyl-terminal hydrolase 17-like protein 1, ubiquitin-ribosomal protein eL40 fusion protein, ribosome biogenesis protein BMS1 homolog, histone H2B type 1-M, and histone H2A.J. in iHLEC-NY2. Conclusions: The decreases in the specific protein levels of actin, tubulin, ubiquitin, ribosomes, and histones may be related to cataract development under warming conditions. This investigation could provide a critical framework for understanding the correlation between temperature dynamics and the development of nuclear cataracts. Full article

KMT2A partial tandem duplication (PTD) involves intragenic KMT2A duplications and has been associated with poorer prognosis. In this study, we evaluated KMT2A PTD in 1277 patients with hematological malignancies using optical genome mapping (OGM). KMT2A PTD was detected in 35 patients with acute myeloid leukemia (AML) (7%), 5 patients with myelodysplastic syndrome (MDS) (2.2%), and 5 patients with chronic myelomonocytic leukemia (CMML) (7.1%). The PTDs varied in size, region, and copy number. An Archer RNA fusion assay confirmed KMT2A PTD in all 25 patients tested: 15 spanning exons 2 to 8 and 10 spanning exons 2 to 10. Most patients exhibited a normal (n = 21) or non-complex (n = 20) karyotype. The most common chromosomal abnormalities included loss of 20q or 7q and trisomy 11/gain of 11q. All patients had gene mutations, with FLT3 ITD and DNMT3A prevalent in AML and DNMT3A and RUNX1 common in MDS and CMML. Among patients who received treatment and had at least one follow-up bone marrow evaluation, 82% of those with de novo AML achieved complete remission after initial induction chemotherapy, whereas 90% of patients with secondary or refractory/relapsed AML showed refractory or partial responses. All but one patient with MDS and CMML were refractory to therapy. We conclude that OGM is an effective tool for detecting KMT2A PTD. Neoplasms with KMT2A PTD frequently harbor gene mutations and display normal or non-complex karyotypes. Patients with KMT2A PTD are generally refractory to conventional therapy, except for de novo AML. Full article

Background: KMT2A rearrangements are major genetic entities in the classification of acute myeloid leukemias (AMLs), but their diverse and frequently cryptic nature makes their detection and characterization challenging. Karyotypic anomalies at the KMT2A locus and/or abnormal KMT2A Fluorescence in situ hybridization (FISH) results strongly indicate a KMT2A fusion, but the identification of the translocation partner gene often requires further investigation. KMT2A partial tandem duplications (PTDs), on the other hand, are undetectable by standard cytogenetics methods. Methods: We herein report the optical genome mapping (OGM) analysis of 38 AML samples: 12 cryptic/hard-to-characterize KMT2A fusions, 20 KMT2A-PTDs and 6 cases with no KMT2A anomaly. Results: In all the fusion cases, the rearrangement between 5’KMT2A and the 3’partner gene was identified as a translocation t(v;11q23.3)(v;118479068), and the analysis of co-occurring variants elucidated the formation of the rearrangement. The KMT2A variants detected in the KMT2A-PTD cases were surprisingly diverse. Combined with RNAseq data, OGM analysis identified 9 distinct in-frame KMT2A-PTD variants among the 20 cases analyzed. Conclusions: With the clinical development of menin inhibitors for the treatment of patients with KMT2A-rearranged acute leukemias, the characterization of these rearrangements is of utmost importance. Our results suggest that OGM is a promising tool for accurate genetic diagnosis in this context. Full article

Plant viruses and virus-like particles (VLPs) are safe for mammals and can be used as a carrier/platform for the presentation of foreign antigens in vaccine development. The aim of this study was to use the coat protein (CP) of Physalis mottle virus (PhMV) as a carrier to display the extracellular domain of the transmembrane protein M2 of influenza A virus (M2e). M2e is a highly conserved antigen, but to induce an effective immune response it must be linked to an adjuvant or carrier VLP. Four tandem copies of M2e were either fused to the N-terminus of the full-length PhMV CP or replaced the 43 N-terminal amino acids of the PhMV CP. Only the first fusion protein was successfully expressed in Escherichia coli, where it self-assembled into spherical VLPs of about 30 nm in size. The particles were efficiently recognized by anti-M2e antibodies, indicating that the M2e peptides were exposed on the surface. Subcutaneous immunization of mice with VLPs carrying four copies of M2e induced high levels of M2e-specific IgG antibodies in serum and protected animals from a lethal influenza A virus challenge. Therefore, PhMV particles carrying M2e peptides may become useful research tools for the development of recombinant influenza vaccines. Full article

Although great progress has been made in transgenic technology, increasing the expression level and thus promising the expected phenotypes of exogenous genes in transgenic plants is still a crucial task for genetic transformation and crop engineering. Here, we conducted a comparative study of the enhancing efficiency of three putative translational enhancers, including Ω (natural leader from a plant virus), OsADH 5′ (natural leader from a plant gene), and ARC (active ribosomal RNA complementary), using the transient gene expression systems of Nicotiana benthamiana and Chirita pumila. We demonstrate that three tandem repeats of ARC (3 × ARC) are more efficient than other enhancers in expression. The enhancing efficiency of 6 × ARC is further increased, up to 130 times the expression level without the insertion of enhancers. We further evaluated the enhancing efficiency of 6 × ARC under agrobacterium-mediated transformation systems. In C. pumila, 6 × ARC significantly amplifies the phenotypic effect of CpCYC1 and CpCYC2 in repressing stamen development and yellow pigmentation. In Arabidopsis thaliana, 6 × ARC and the AtAP1 promoter work together to promote the accumulation of anthocyanin pigments in vegetative and reproductive organs. Most significantly, the fusion of 6 × ARC in a CpCYC1/2 transgenic system in C. pumila fully reveals that these genes have the complete function of repressing the yellow spots, displaying an advantage in manifesting the function of exogenous genes. This study highlights the application potential of the enhancer 6 × ARC in gene function research in plants. Full article

Accurately predicting the remaining useful life (RUL) of lithium-ion batteries (LIBs) not only prevents battery system failure but also promotes the sustainable development of the energy storage industry and solves the pressing problems of industrial and energy crises. Because of the capacity regeneration phenomenon and random interference during the operation of lithium-ion batteries, the prediction precision and generalization performance of a single model can be poor. This article proposes a novel RUL prediction based on data pre-processing methods and the CNN-LSTM-ASAN framework. The model is based on a fusion technique for optimizing the tandem fusion of the Convolutional Neural Network (CNN) and the Long Short-Term Memory Network (LSTM). Firstly, the improved adaptive noise fully integrates empirical mode decomposition (ICEEMDAN) and the Pearson correlation coefficient (PCC), which are used to estimate the global deterioration tendency component and the local capacity restoration component, to reconstruct the dataset and eliminate the noise. Then, the Adaptive Sparse Attention Network (ASAN) is added in the model construction stage to improve the training efficiency of the model. The reconstructed degraded data are features extracted by the CNN-LSTM-ASAN model. Finally, the proposed method is validated against models such as DCLA, using the NASA public datasets, the CALCE public datasets, and the self-use datasets. And the results show that the root mean square error (RMSE) of the model is below 1.5%. Full article

KMT2A (alias: mixed-lineage leukemia [MLL]) gene mapping on chromosome 11q23 encodes the lysine-specific histone N-methyltransferase 2A and promotes transcription by inducing an open chromatin conformation. Numerous genomic breakpoints within the KMT2A gene have been reported in young children and adults with hematologic disorders and are present in up to 10% of acute leukemias. These rearrangements describe distinct features and worse prognosis depending on the fusion partner, characterized by chemotherapy resistance and high rates of relapse, with a progression-free survival of 30–40% and overall survival below 25%. Less intensive regimens are used in pediatric patients, while new combination therapies and targeted immunotherapeutic agents are being explored in adults. Beneficial therapeutic effects, and even cure, can be reached with hematopoietic stem cell transplantation, mainly in young children with dismal molecular lesions; however, delayed related toxicities represent a concern. Herein, we summarize the translocation partner genes and partial tandem duplications of the KMT2A gene, their molecular impact, clinical aspects, and novel targeted therapies. Full article