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Leymus chinensis (Trin.) Tzvel., a vital native forage grass in northern China for ecological restoration and livestock production, faces severe yield losses and grassland degradation due to rust (Puccinia spp.) infection. Current control strategies, reliant on chemical interventions, are limited by evolving resistance risks and environmental concerns, while rust-resistant breeding remains hindered by insufficient molecular insights. To address this, we systematically evaluated rust resistance in 24 L. chinensis germplasms from diverse geographic origins, identifying six highly resistant (HR) and five extremely susceptible (ES) genotypes. Integrating transcriptomics and metabolomics, we dissected molecular responses to Puccinia infection, focusing on contrasting HR (Lc71) and ES (Lc5) germplasms at 48 h post-inoculation. Transcriptomic analysis revealed 1012 differentially expressed genes (DEGs: 247 upregulated, 765 downregulated), with enrichment in cell wall biosynthesis and photosynthesis pathways but suppression of flavonoid synthesis. Metabolomic profiling identified 287 differentially accumulated metabolites (DAMs: 133 upregulated, 188 downregulated), showing significant downregulation of pterocarpans and flavonoids in HR germplasms, alongside upregulated cutin synthesis-related metabolites. Multi-omics integration uncovered 79 co-enriched pathways, pinpointing critical regulatory networks: (1) In the nucleotide metabolism pathway, genes Lc5Ns011910, Lc1Xm057211, and Lc4Xm043884 exhibited negative cor-relations with metabolites Deoxycytidine and Cytosine. (2) In flavonoid biosynthesis, Lc2Xm054924, Lc4Xm044161, novel.8850, Lc2Ns006303, and Lc7Ns021884 were linked to naringenin and naringenin-7-O-glucoside accumulation. These candidate genes likely orchestrate rust resistance mechanisms in L. chinensis. Our findings advance the molecular understanding of rust resistance and provide actionable targets for breeding resilient germplasms.

In the testes, spermatogonial stem cells (SSCs) maintain normal spermatogenesis through the dual potential of self-renewal and differentiation, which is essential for male fertility. Myotubularin-associated protein 7 (MTMR7), as a vital member of MTMR family with phosphatase activity, is involved in a variety of membrane transport processes through regulating the levels of phosphoinositides (PIPs). Our earlier research demonstrated that MTMR7 controls the cell cycle and maintains homeostasis in mouse SSCs by inhibiting PI3K/AKT signaling. However, its role in human SSCs has not been reported. This study found that knocking down MTMR7 increased the proliferation and migration of human SSCs, whereas MTMR7 overexpression inhibited these processes. Through mass spectrometry and immunoprecipitation, we identified filamin B (FLNB) as an interacting protein of MTMR7, and MTMR7 is required for FLNB ubiquitination and subsequent degradation. Further validation using immunofluorescence confirmed the involvement of the downstream β-catenin signaling. Altogether, this study is the first to demonstrate that MTMR7 regulates β-catenin expression and inhibits human SSCs proliferation and migration by mediating the ubiquitination and degradation of FLNB. These findings may offer new therapeutic strategies and target gene loci for treating male infertility caused by SSCs dysfunction.

In the testes, spermatogonial stem cells (SSCs) maintain normal spermatogenesis through the dual potential of self-renewal and differentiation, which is essential for male fertility. Myotubularin-associated protein 7 (MTMR7), as a vital member of MTMR family with phosphatase activity, is involved in a variety of membrane transport processes through regulating the levels of phosphoinositides (PIPs). Our earlier research demonstrated that MTMR7 controls the cell cycle and maintains homeostasis in mouse SSCs by inhibiting PI3K/AKT signaling. However, its role in human SSCs has not been reported. This study found that knocking down MTMR7 increased the proliferation and migration of human SSCs, whereas MTMR7 overexpression inhibited these processes. Through mass spectrometry and immunoprecipitation, we identified filamin B (FLNB) as an interacting protein of MTMR7, and MTMR7 is required for FLNB ubiquitination and subsequent degradation. Further validation using immunofluorescence confirmed the involvement of the downstream β-catenin signaling. Altogether, this study is the first to demonstrate that MTMR7 regulates β-catenin expression and inhibits human SSCs proliferation and migration by mediating the ubiquitination and degradation of FLNB. These findings may offer new therapeutic strategies and target gene loci for treating male infertility caused by SSCs dysfunction.

With the rapid development of autonomous driving technology, traffic sign recognition (TSR) has emerged as a foundational component of mobile driving systems. Although significant progress has been made in current research, existing techniques still face challenges in recognizing traffic signs under complex weather conditions. This model employs an attention-based dynamic sequence fusion feature pyramid, which enhances recognition accuracy for small-target traffic sign instances in adverse weather, as opposed to traditional feature pyramid networks. Additionally, the model integrates a dynamic snake convolution operator along with Wise-IoU, enabling it to capture fine small-scale feature information while mitigating the impact of low-quality instances. Furthermore, the model introduces a novel data augmentation library, Albumentations, to simulate real-world complex weather scenarios, and utilizes a new performance evaluation metric, TIDE, to more effectively assess model performance in such conditions. We demonstrate the effectiveness of our model on the TT-100 K dataset, the GTSDB dataset, and the BDD 100 K dataset, achieving improvements in mAP of 9%, 1.5%, and 2.6%, respectively. Compared to the baseline model, Cls and Loc metrics decreased by approximately 3 and 1.2.The experiments indicate that our model exhibits excellent generalization ability and robustness, successfully performing small target detection under complex weather conditions in the realm of traffic sign recognition.

Background Human spermatogonial stem cells (SSCs) exhibit a remarkable capacity for proliferation, crucial for sustaining spermatogenesis throughout life. While the Cullin-RING E3 ubiquitin ligase 2 (CRL2) complex is known to regulate various cellular functions, its precise role in human SSCs has not been fully elucidated. This study aimed to investigate a novel variant of the CRL2 complex, termed CRL2 LRRC41 , and its role in SSC function. Methods We utilized molecular biology techniques, including gene knockdown and functional assays, to assess the effects of CRL2 LRRC41 on the proliferative and migratory abilities of human spermatogonial stem cell-like cell (SSCLC) line. Additionally, we employed proteomics and biochemical approaches to identify potential substrates of CRL2 LRRC41 . We specifically focused on ATP-dependent RNA helicase DDX5, a known regulator of spermatogenesis, to explore its interaction with CRL2 LRRC41 and the downstream molecular mechanisms involved. Results Our findings revealed that the disruption or dysfunction of CRL2 LRRC41 led to reduced proliferative and migratory abilities in human SSCLCs. Through our investigation, we identified DDX5 as a ubiquitination substrate of CRL2 LRRC41 . Notably, the ubiquitination of DDX5 fosters its interaction with the RNA-binding protein ELAVL1, without directing DDX5 towards degradation via the ubiquitin–proteasome system (UPS). This interaction enhances the stability of the downstream transcript, Noggin (NOG), thereby supporting human SSCLC proliferation and migration. Conclusions This study provides the first identification of the CRL2 LRRC41 complex in human SSCLCs and elucidates the molecular mechanisms by which CRL2 LRRC41 facilitates SSCLC function via ubiquitination-mediated protein interactions. These findings offer novel insights into the molecular underpinnings of male infertility.

The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively ( P  > 0.05). These values were significantly different at 1 and 5 years postoperatively ( P  < 0.05), and the Waveflex group showed better ROM values than those of the PLIF group ( P  < 0.05). PI values were not significantly different between the groups, but PT showed a significant improvement in the Waveflex group 5 years postoperatively ( P  < 0.05). The Waveflex semi-rigid dynamic fixation system can effectively reduce the probability of intervertebral disc degeneration in upper adjacent segments. Simultaneously, patients in the Waveflex group showed postoperative improvements in LL, spinal sagittal imbalance, and quality of life.

Ovarian cancer (OC) is one of the most prevalent and lethal malignancies affecting the female reproductive system, due to its tendency for metastasis and recurrence. This study identified the overexpression of LINC01320 (or long intergenic nonprotein coding RNA 1320) in tissues of ovarian cancer through the analysis of patient samples and online datasets. In vitro and in vivo experiments demonstrate that silencing of LINC01320 expression led to inhibition of proliferation and metastasis of OC cells. RNA pull-down followed by liquid chromatography tandem mass spectrometry (RNA pull-down-LC-MS/MS) revealed that LINC01320 interacted with purine-rich element binding protein B (PURB), a transcriptional repressor. Furthermore, the RNA-seq analysis identified damage-specific DNA binding protein 2 (DDB2) as a major common target of LINC01320 and PURB. Mechanistically, LINC01320 could recruit PURB to the promoter region of DDB2 to repress DDB2 transcription; thus, promoting the expression of NEDD4L and impeding the TGF-β/SMAD signaling pathway, and ultimately facilitating the progression of OC. Finally, rescue experiments confirmed the involvement of the DDB2/NEDD4L/TGF-β axis in LINC01320-mediated OC progression. In conclusion, this study unveils for the first time the pivotal function of the LINC01320/PURB/DDB2/NEDD4L/TGF-β axis and explores its prospective clinical implications in OC.

Cancer-induced bone pain (CIBP) is one of the most common and feared symptoms in patients with advanced tumors. The X-C motif chemokine ligand 12 (CXCL12) and the CXCR4 receptor have been associated with glial cell activation in bone cancer pain. Moreover, mitogen-activated protein kinases (MAPKs), as downstream CXCL12/CXCR4 signals, and c-Jun, as activator protein AP-1 components, contribute to the development of various types of pain. However, the specific CIBP mechanisms remain unknown. Esketamine is a non-selective N-methyl-d-aspartic acid receptor (NMDA) inhibitor commonly used as an analgesic in the clinic, but its analgesic mechanism in bone cancer pain remains unclear. We used a tumor cell implantation (TCI) model and explored that CXCL12/CXCR4, p-MAPKs, and p-c-Jun were stably up-regulated in the spinal cord. Immunofluorescence images showed activated microglia in the spinal cord on day 14 after TCI and co-expression of CXCL12/CXCR4, p-MAPKs (p-JNK, p-ERK, p-p38 MAPK), and p-c-Jun in microglia. Intrathecal injection of the CXCR4 inhibitor AMD3100 reduced JNK and c-Jun phosphorylations, and intrathecal injection of the JNK inhibitor SP600125 and esketamine also alleviated TCI-induced pain and reduced the expression of p-JNK and p-c-Jun in microglia. Overall, our data suggest that the CXCL12/CXCR4-JNK-c-Jun signaling pathway of microglia in the spinal cord mediates neuronal sensitization and pain hypersensitivity in cancer-induced bone pain and that esketamine exerts its analgesic effect by inhibiting the JNK-c-Jun pathway.

Background. The pathogenesis of ankylosing spondylitis (AS) is still not clear, and immune-related genes have not been systematically explored in AS. The purpose of this paper was to identify the potential early biomarkers most related to immunity in AS and develop a predictive disease risk model with bioinformatic methods and the Gene Expression Omnibus database (GEO) to improve diagnostic and therapeutic efficiency. Methods. To identify differentially expressed genes and create a gene coexpression network between AS and healthy samples, we downloaded the AS-related datasets GSE25101 and GSE73754 from the GEO database and employed weighted gene coexpression network analysis (WGCNA). We used the GSVA, GSEABase, limma, ggpubr, and reshape2 packages to score immune data and investigated the links between immune cells and immunological functions by using single-sample gene set enrichment analysis (ssGSEA). The value of the core gene set and constructed model for early AS diagnosis was investigated by using receiver operating characteristic (ROC) curve analysis. Results. Biological function and immune score analyses identified central genes related to immunity, key immune cells, key related pathways, gene modules, and the coexpression network in AS. Granulysin (GNLY), Granulysin (GZMK), CX3CR1, IL2RB, dysferlin (DYSF), and S100A12 may participate in AS development through NK cells, CD8+ T cells, Th1 cells, and other immune cells and represent potential biomarkers for the early diagnosis of AS occurrence and progression. Furthermore, the T cell coinhibitory pathway may be involved in AS pathogenesis. Conclusion. The AS disease risk model constructed based on immune-related genes can guide clinical diagnosis and treatment and may help in the development of personalized immunotherapy.

The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database to perform bioinformatic analyses. The results showed that ten hub genes may predict RIF with high specificity and sensitivity (area under the curve = 1.000). Protein–protein interaction analysis revealed close interactions between the hub genes and the endometrial receptivity array. The real-time quantitative polymerase chain reaction further validated three potential biomarkers (RAB32, TRIB2, and FAM155B). Functional enrichment analyses indicated that immune pathways were significantly downregulated and lipid metabolism pathways were significantly upregulated in RIF compared with the controls. Significant negative correlations were observed between fatty acid biosynthesis and the immune pathways. Immune cell infiltration, including those in CD56dim natural killer, dendritic, Th1, Th2, and regulatory T cells, as well as macrophages, was significantly reduced in RIF compared with the controls used herein. This study may provide a novel perspective on the diagnosis and treatment of RIF.