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Gene fusions are thought to be driver mutations in multiple cancers and are an important factor for poor patient prognosis. Most of them appear in specific cancers, thus satisfactory strategies can be developed for the precise treatment of these types of cancer. Currently, there are few targeted drugs to treat gynecologic tumors, and patients with gynecologic cancer often have a poor prognosis because of tumor progression or recurrence. With the application of massively parallel sequencing, a large number of fusion genes have been discovered in gynecologic tumors, and some fusions have been confirmed to be involved in the biological process of tumor progression. To this end, the present article reviews the current research status of all confirmed fusion genes in gynecologic tumors, including their rearrangement mechanism and frequency in ovarian cancer, endometrial cancer, endometrial stromal sarcoma, and other types of uterine tumors. We also describe the mechanisms by which fusion genes are generated and their oncogenic mechanism. Finally, we discuss the prospect of fusion genes as therapeutic targets in gynecologic tumors.

Endogenous retroviruses (ERVs) are remnants of retroviral infections that have become stably integrated into host germline genomes. Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing. Particular emphasis is placed on the cross-talk between ERVs and exogenous retroviruses (XRVs), demonstrating how receptor competition, recombination, and immune evasion contribute to virus-host co-evolution. We explore ERVs as molecular markers for phylogenetic reconstruction, with case studies such as Koala retrovirus (KoRV) and HERV-K illustrating regional transmission dynamics and co-opted immune functions. Additionally, we discuss the functional domestication of ERVs into regulatory elements, non-coding RNAs, and envelope-derived fusion proteins that influence gene expression, antiviral defense, and placental development.

Phytoremediation technology, as an eco-friendly and cost-effective approach, is widely used to restore soil contaminated by heavy metal(loid)s. However, the adaptability and absorption capacity of plants to multiple elements are the crucial factors affecting the application of phytoremediation in mining areas. In this study, dominant native plant species and their paired soils were collected near a lead-zinc mine in Inner Mongolia, to assess the ecological risk of heavy metal(loid)s and phytoremediation potential. The results showed that Cd and As were the dominant soil pollutants, with levels of 90.91% and 100%, respectively, exceeding the risk intervention values for soil contamination of agricultural land. The rates of Pb, Cu, and Zn exceeding the risk screening values were 69.70%, 60.61%, and 96.97%, respectively. Extremely high ecological risk of heavy metal(loid)s was observed in this area. The ability of native plants accumulating heavy metals varied among species. The bioconcentration factor (BCF) varied from 0.14 to 2.59 for Cd, 0.02 to 0.45 for As, 0.06 to 0.76 for Pb, 0.05 to 2.69 for Cr, 0.15 to 1.00 for Cu, and 0.22 to 4.10 for Zn. Chinese Cinquefoil Herb ( Potentilla chinensis Ser.) showed the potential to accumulate multiple toxic elements based on the biomass, shoot content, translocation factor (TF), BCF, and metal extraction rate (MER), while, other species showed the potential to accumulate single toxic element: goosefoot ( Chenopodium album L.), Lespedeza daurica (Laxm.) Schindl. and peashrubs ( Caragana korshinskii Kom.), Herba Artemisiae Scopariae ( Artemisia capillaris Thunb.), alfalfa ( Medicago sativa L.), and Moldavian Dragonhead ( Dracocephalum moldavica L.) for Cd, As, Cr, Cu, and Zn, respectively. Furthermore, wild leek ( Allium ramosum L.), cogongrass ( Imperata cylindrica (L.) Beauv.), fringed sagebrush ( Artemisia frigida Willd.), and field bindweed ( Convolvulus arvensis L.) were selected for phytostabilization of specific elements, considering the heavy metal contents in the roots and low TF values. This study provides a reference for selecting appropriate species for the remediation of heavy metal-contaminated soils in certain mining areas.

ObjectiveA close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls.DesignWe first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing.ResultsA significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae.ConclusionsThis study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

Mucosal-associated invariant T (MAIT) cells, a novel population of innate-like lymphocytes, have been involved in various inflammatory and autoimmune diseases. However, their role in the development of nonalcoholic fatty liver disease (NAFLD) remains unclear. In this study, we investigated the alterations of phenotype and immunological function of MAIT cells in NAFLD. Analysis of PBMCs in 60 patients with NAFLD and 48 healthy controls (HC) revealed that circulating MAIT cell frequency decreased in NAFLD, especially in the patients with higher serum levels of γ-glutamyl transferase or total triglyceride. Functional alterations of circulating MAIT cells were also detected in NAFLD patients, such as the increased production of IL-4 whereas the decreased production of IFN-γ and TNF-α. Furthermore, elevated expression of CXCR6 was observed in circulating MAIT cells of patients. Meanwhile, we found an increased number of MAIT cells in the livers of NAFLD, and the number was even greater in patients with higher NAFLD activity score. Moreover, activated MAIT cells induced monocytes/macrophages differentiation into M2 phenotype . Additionally, MAIT cells were enriched and displayed Th2 type cytokines profile in livers of wild type mice fed with methionine and choline deficient diet (MCD). Notably, mice deficient of MAIT cells exhibited more severe hepatic steatosis and inflammation upon MCD, accompanied with more CD11c proinflammatory macrophages (M1) and less CD206 anti-inflammatory macrophages (M2) in livers. Our results indicate that MAIT cells protect against inflammation in NAFLD through producing regulatory cytokines and inducing anti-inflammatory macrophage polarization, which may provide novel therapeutic strategies for NAFLD.

T‐cell lymphoma (TCL) poses a significant challenge in clinical oncology, characterized by its aggressive behavior and resistance to conventional therapies. Despite considerable research efforts, the prognosis for TCL patients remains poor, primarily due to the lack of effective therapeutic strategies that can inhibit tumor progression and metastasis. In this study, we identified CaMKII‐α as a potential therapeutic target for TCL. To explore its role in TCL pathogenesis, we investigated its effects on TCL cell lines. Protein expression levels within the PI3K‐AKT signaling pathway were assessed using western blot analysis. Through siRNA‐mediated gene silencing, we downregulated CaMKII‐α expression and monitored TCL cell proliferation. Furthermore, we identified Evans Blue (IC50 = 197.1 nM) as a selective small‐molecule inhibitor of CaMKII‐α through high‐throughput screening (HTS). Evans Blue demonstrated significant tumor‐suppressive effects, potentially inhibiting TCL cell proliferation via regulation of the PI3K‐AKT signaling pathway. Notably, the antitumor effect of Evans Blue was comparable to that observed with genetic CaMKII‐α ablation, highlighting its potential as a novel therapeutic strategy for the treatment of TCL.

Graph neural networks (GNNs) are powerful tools for data mining on graph-structured data in various domains, such as social science, finance, and biology. However, most existing GNNs operate in Euclidean space and may fail to preserve the intrinsic network properties, such as self-similarity and hierarchy, that characterize many real-world graphs. Hyperbolic graph neural networks (HGNNs) address this limitation by embedding graphs into hyperbolic space, which can better capture the hierarchical structures of networks. However, HGNNs often involve complex computations in hyperbolic space or its tangent space during training, which may hinder their efficiency. In this paper, we propose hyperbolic attention graph neural networks (HA-GNN), which can leverage both network structure and node features for graph representation learning in an efficient way. Specifically, we design a structural properties attention mechanism that measures the structural connection between nodes based on their hyperbolic embeddings. We also design a node features attention mechanism that quantifies the feature similarity between nodes. We then combine these two attentions to obtain a hyperbolic attention that weights the relevance between all connected nodes. We conduct extensive experiments on five real-world networks and demonstrate that our model consistently and significantly outperforms other state-of-the-art methods. For example, on the Cora network, our model achieves an accuracy of 83.1 (± 0.4) on node classification tasks, which is 1.6% higher than the best baseline method in Euclidean space.

Based on the analysis of the water ice sampling system design at the lunar permanent shadow region(PSR), a rapid sampling channel construction method based on kinetic energy penetration was proposed, and an engineering prototype of the penetrator system based on the conversion of chemical energy and kinetic energy was developed, which can solve the problem that the subsurface lunar water ice is too difficult to sample quickly due to its significantly enhanced mechanical properties. Based on the mechanical properties boundary of lunar soil water ice, the performance of the engineering prototype was tested and verified. The test results show that the penetrating system developed in this paper can achieve rapid penetration into the lunar soil with uniaxial compressive strength of about 30MPa without consuming power consumption; the penetrating depth can reach 234mm, and the penetrating time is less than 1s. The penetrating system can rapidly construct sampling channels, which can effectively solve the problem of the high-hardness water ice samples located at the subsurface layer of the lunar soil that can be efficiently exposed faced by in-situ water ice sampling in the permanent shadow region.

Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that has a high mortality rate. Previous studies have indicated that recombinant RABV expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing antibodies than parental RABV in mice following intramuscular immunization. To investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal or intracranial administration in mice, the permeability of the blood-brain barrier (BBB), the infiltration of CD3 T cells, and innate immune response-related effector molecules in the CNS were examined. It was observed that infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal infection. More CD3 T cells infiltrated into the central nervous system (CNS) in mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain. Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response-related effector molecules, compared with the parental HEP-Flury strain, within the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger immune responses in mice brains, which is more beneficial for virus clearance. These results may also partly illustrate the role of IL6 in RABV infection.

Multiple genome-wide association studies of primary biliary cirrhosis (PBC) in both European and Japanese ancestries have shown significant associations of many genetic loci contributing to the susceptibility to PBC. Major differences in susceptibility loci between these two population groups were observed. In this study, we examined whether the most significant loci observed in either European and/or Japanese cohorts are associated with PBC in a Han Chinese population. In 1070 PBC patients and 1198 controls, we observed highly significant associations at CD80 (rs2293370, P  = 2.67 × 10 −8 ) and TNFSF15 (rs4979462, P  = 3.86 × 10 −8 ) and significant associations at 17q12-21 (rs9303277), PDGFB (rs715505), NF-κB1 (rs7665090), IL12RB2 (rs11209050), and STAT4 (rs7574865; all corrected P values <0.01). However, no association was observed for POU2AF1 (rs4938534), IL12A (rs485499 and rs2366408), IL7R (rs6897932), CXCR5 (rs715412), SOCS1 (rs725613), and TNFRSF1A (rs1800693). STAT4 (rs7574865) was strongly associated after additional control samples were analyzed. Our study is the first large-scale genetic analysis in a Han Chinese PBC cohort. These results do not only reflect that Han Chinese PBC patients share common genetic susceptibility genes with both their Japanese and European counterparts but also suggest a distinctly different genetic susceptibility profile.