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关键词： Dectin-1   curdlan   erythroid progenitors and precursors   scRNASeq  

摘要： Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment, yet many patients fail to respond, underscoring the need to better understand mechanisms of resistance. One emerging mechanism involves the recruitment of erythroid progenitors and precursors, known as CD71+ erythroid cells (CECs to the tumor microenvironment. Using murine models of triple-negative breast cancer (TNBC we investigated the therapeutic effects of curdlan, a beta-glucan. We found that TNBC was associated with extramedullary erythropoiesis and expansion of CECs. Unexpectedly, curdlan worsened tumor progression by further increasing CEC abundance. Immunophenotypic analysis revealed a marked expansion of Galectin-3 (Gal-3)+ CECs in both spleen and tumor. Mechanistically, our findings suggest that curdlan-Dectin-1ligation induces Gal-3 shedding from CD11b+cells, enabling its deposition onto CECs. Notably, we discovered that Gal-3 is co-expressed and colocalized with PD-L1 and Dectin-1 on CECs. Importantly, PD-L1 blockade substantially reduced immunosuppressive Gal-3+PD-L1+ CECs, suppressed extramedullary erythropoiesis, and induced pronounced tumor regression. Re-analysis of publicly available scRNAseq datasets further confirmed the abundance of Gal-3+ CECs in human bone marrow. Collectively, these findings identify Gal-3+PD-L1+ CECs as key drivers of an immunosuppressive tumor microenvironment and reveal a previously unrecognized axis through which PD-L1 blockade exerts therapeutic benefit in breast cancer.

关键词： Bifurcations   Khater method   strange attractors   return maps   phaseportraits  

摘要： Soliton solutions and chaotic analysis in integrable equations have become a hot topic in recent years. This work presents the qualitative dynamics and analytical solutions of (4+1)-D Boiti-Leon-Manna-Pempinelli (BLMP) model. Utlizing dynamical system approach, the mathematical analysis is performed. The given model is transformed into system of nonlinear ordinary differential equations (ODEs) via the Galilean transform. We study the bifurcations, quasi-periodic and chaotic dynamics, return maps, power spectrum, and strange attractors of the proposed model. Moreover, the soliton solutions are obtained with applications of the Khater method and the modified extended Tanh-function method (METM). The obtained results are illustrated in detail through 2D and 3D graphical representations.

关键词： Nephronophthisis   NPHP1   renal cyst   spatiotemporal dynamic   pathological anatomy  

摘要： Nephronophthisis (NPH a rare but serious ciliopathy, is the predominant genetic cause of end-stage kidney disease (ESKD) in children and adolescents. Renal tubular dilatation and cyst formation are key pathological features of NPH. The mechanisms underlying renal cystogenesis remain poorly understood. This study employed sex-balanced Nphp1 deletion gene knockout (Nphp1 KO) mice at 8, 12, and 24 weeks of age to investigate the spatiotemporal dynamics of renal tubules and cyst development, aiming to identify the origins of renal cysts. Quantitative evaluation of cyst progression revealed a significant increase in cyst number from 8 to 12 weeks of age, but no substantial change from 12 to 24 weeks. Additionally, cyst size remained stable throughout the study period. Serial section tracing and segment-specific tubular marker analysis confirmed that these cysts originated from the distal convoluted tubule (DCT which displayed segmental dilation while preserving anatomical connections with adjacent, morphologically normal DCT. 3D reconstruction revealed that renal cysts appeared either as a single or in a bead-like arrangement. We demonstrated that human renal cyst epithelial cells from patients with NPH1 also originate primarily from the DCT. This study provides critical experimental evidence of the histopathological features of renal cysts in NPH1, advancing our understanding of the pathogenesis of NPHP-associated tubular dilation and cystogenesis.

关键词： Aquaporin-1   uremic peripheral neuropathy   peripheral nervous system   neuroinflammation   Schwann cells  

摘要： Background and objectives Aquaporin-1 (AQP1) is a well-characterized transmembrane water channel widely expressed in the peripheral nervous system (PNS where it contributes to water balance and regulation of the local neural microenvironment. Beyond its classical role in water transport, AQP1 has been implicated in edema formation, Schwann cell activity, nociceptive signaling, and inflammatory responses. However, these findings derive largely from experimental settings and vary in consistency across different models. Direct evidence supporting a role for AQP1 in uremic peripheral neuropathy (UPN) is currently lacking. This review re-examines the relevance of AQP1 in the PNS by integrating structural, cellular, and functional evidence, and evaluating how far current observations can be extended to the UPN context.Methods We synthesized available literature on AQP1 in peripheral nerve biology, with particular attention to non-uremic models including nerve injury, hypoxia, osmotic stress, and inflammation. The applicability of these mechanistic clues to the complex metabolic, toxic, and inflammatory environment of uremia was critically assessed.Discussion Alterations in AQP1 expression or function may plausibly contribute to peripheral nerve dysfunction under uremic conditions, potentially involving disrupted water homeostasis, Schwann cell instability, and altered neuroimmune interactions. However, these assumptions remain speculative. Existing models do not fully reproduce the uremic milieu, and no direct experimental validation in UPN is currently available.Conclusion Current knowledge on AQP1 in UPN remains fragmented, necessitating a clearer distinction between established findings and hypothesis-driven interpretations. Further studies in uremia-specific animal models and clinical cohorts will be essential to clarify the pathophysiological and therapeutic significance of AQP1 in this condition.

关键词： Allergen immunotherapy   allergic   PLGA   mites   rhinitis  

摘要： Subcutaneous immunotherapy has several limitations, including the long dose escalation period, frequent injections and risk of adverse reactions. Crude extracts used for immunotherapy can contain unrecognized immunostimulatory components or induce neosensitization. Therefore, in this study, we aimed to develop a new efficient method to induce allergen-specific immune tolerance using Dermatophagoides pteronyssinus (Der p) 1-containing nanoparticles. We developed two different types of allergen-containing poly(lactic-co-glycolic PLGA] nanoparticle vaccines: Der p 1-encapsulated and Der p 1-conjugated vaccines. House dust mite (HDM)-sensitized mice were administered positive control (PC PLGA (vehicle control encapsulated vaccine (EV and conjugated vaccine (CV) via intravenous injections one week after sensitization. Subcutaneous immunotherapy group received three subcutaneous HDM extract injections at two-day intervals. After challenge, we compared the rhinitis symptoms, immunoglobulin (Ig) levels, and histopathology of the nasal mucosa and analyzed splenocyte cultures for cytokine production and regulatory T cell activation. EV and CV groups exhibited improved nasal symptoms and lower ear swelling and inflammation in the nasopharyngeal lavage and nasal tissues than PC group. Serum HDM-specific IgG1 levels were higher in EV and CV groups than in PC group. No changes were observed in the total and HDM-specific IgE levels in EV group. EV group exhibited lower interleukin-4, -5, -13, and -17 levels and higher interleukin-10 and interferon-gamma levels than PC group. The two vaccinated groups exhibited significantly higher regulatory T cell activation than PC group. Overall, intravenously administered Der p 1-containing nanoparticles alleviated the allergic responses and induced tolerance in a murine allergic rhinitis model.

关键词： Diabetic kidney disease   hypoxia inducible factor-1 alpha   cathepsin S   epithelial-to-mesenchymal transition   bioinformatics analysis  

摘要： Tubulointerstitial fibrosis (TIF) plays an important role in the deterioration of diabetic kidney disease (DKD). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells (TECs) leads to TIF in the progression of DKD. Hypoxia-inducible factor-1 alpha (HIF-1 alpha;HIF1A) has been elucidated to promote EMT and TIF through inducing transforming growth factor-beta 1 (TGF-beta 1) pathway. In this study, we aimed to explore the mediation effect of key genes in HIF-1 alpha-induced EMT and TIF in DKD. Tubulointerstitial gene expression profiling data from DKD patients and healthy controls (HCs) were acquired from the GEO database, R packages were used for bioinformatics analysis, and the db/db mice and proximal TEC line (HK-2) were used to validate the bioinformatic findings. Consequently, we focused on cathepsin S (CTSS). Functional enrichment indicated that HIF1A and CTSS were jointly involved in inflammatory activation, extracellular matrix deposition, and cellular interaction. In vitro and in vivo experiments validated that in DKD models, HIF-1 alpha could upregulate Cathepsin S to promote partial EMT-associated phenotypic shift and fibrotic remodeling in TECs, thereby deteriorating diabetic kidney injury. Conclusively, CTSS may serve as a downstream effector of HIF-1 alpha participating in the regulation of partial EMT-associated phenotypic shift and fibrotic remodeling of TECs in diabetic kidney disease models.

关键词： Xijiaqi Formula   chronic heart failure   myocardial fibrosis   extracellular matrix remodeling   TGF-beta 1  

摘要： ContextChronic heart failure (CHF) is the common concern following myocardial infarction. Xijiaqi Formula (XJQ) effectively treats CHF clinically while the underlying mechanism remains unclarified.ObjectiveThis study was designed to investigate the effect and mechanism of XJQ on CHF in rats following MI.Materials and methodsUHPLC-Q-TOF-MS/MS was utilized to analyze the constituents of XJQ. Post-MI CHF was induced in rats by permanent ligation of the left anterior descending coronary artery. Cardiac function was assessed by echocardiogram and hemodynamic. Myocardial morphology, fibrosis, and ultrastructure were evaluated through HE staining, Masson staining, and transmission electron microscopy, respectively. Myocardial transcriptomics were employed to identify genes that may be altered in response to XJQ treatment. Consistently, XJQ inhibited TGF-beta 1-induced myofibroblast activation in vitro.ResultsXJQ significantly improved cardiac function and structure, mitigating fibrosis, edema, and mitochondrial damage, while reducing key biomarkers (BNP, NT-proBNP, cTnT, Ang II). Transcriptomic analysis indicated that the differentially expressed genes influenced by XJQ were predominantly associated with extracellular matrix (ECM) remodeling. Notably, XJQ inhibited the upregulation of ECM proteins, including Adamts2, Fbln1, Itgbl1, and Ltbp3 mRNAs, as well as the proteins TGF-beta 1, P-Smad2/3, and MMP2. Additionally, in vitro experiments revealed that XJQ significantly suppressed the activation of myofibroblasts induced by TGF-beta 1.ConclusionsXJQ significantly attenuated the progression from MI to CHF by inhibiting fibroblast activation mediated by TGF-beta 1/Smads signaling. The molecular mechanisms underlying this effect appear to be intricately linked to its regulation of ECM remodeling proteins, specifically Adamts2, Itgbl1, Fbln1, and Ltbp3.

关键词： Diabetes   islet   non-coding RNA   apoptosis   extracellular vesicles  

摘要： Small non-coding RNAs, such as microRNAs and tRNA-derived fragments, are key regulators of cellular processes, but the functions of small intronic RNAs (sinRNAs a recently identified RNA class, remain largely unknown. Here, we report that two sinRNAs, sinR-D and sinR-T, are upregulated in pancreatic beta-cells of NOD mice, a well-established model of type 1 diabetes. Using in vivo RNA-tagging, we demonstrate that these sinRNAs are packaged into extracellular vesicles released by infiltrating CD4+ T lymphocytes and subsequently delivered to beta-cells during the early stages of autoimmune attack. Functional analyses revealed that overexpression of sinR-T has little effect on beta-cell viability, whereas sinR-D markedly increases beta-cell apoptosis. This finding suggests that the transfer of sinR-D contributes to beta-cell destruction and the onset of type 1 diabetes. Furthermore, pull-down experiments with biotinylated sinRNAs identified Ago2, a core component of the RNA-induced silencing complex (RISC as a binding partner of sinR-D, indicating mechanistic parallels with microRNA-mediated regulation. Collectively, our data uncover a novel role for sinRNAs as extracellularly transferred regulators of beta-cell fate, expanding the repertoire of small RNAs implicated in the initiation of type 1 diabetes.

关键词： Fowl adenovirus   whole genome   coinfection   pathogenicity   differential transcriptomics  

摘要： Fowl adenoviruses (FAdVs) are widely distributed in poultry populations around the world, and many diseases are associated with FAdV infection in chickens. This study documented the first characterization of coinfection with fowl adenovirus serotypes 1 and 4 (FAdV-1 and -4) associated with hydropericardium hepatitis syndrome (HHS) in Chinese layer flocks, revealing a novel viral cooperation mechanism. Two novel strains (CH/SX/201805-1 and -4) were identified and isolated, with whole-genome sequencing showing CH/SX/201805-1 clustering with FAdV-1 (99.7% identity to FAdV-A-61/11z whereas CH/SX/201805-4 displayed characteristic ORF19/27/29 deletions mirroring emergent Chinese FAdV-4 variants. Experimental coinfection in SPF chickens resulted in 87.5% mortality, which was 16.7% greater than that resulting from infection alone, with exacerbated pathology. In vitro coinfection experiments demonstrated concurrent viral replication within same LMH cells, a previously unreported phenomenon, where FAdV-1 increased FAdV-4 replication efficiency 21-fold (p < 0.001). Transcriptomic profiling revealed heat shock protein A2 (HSPA2) as the most differentially expressed gene, which was upregulated 2.8-fold during coinfection compared with infection with FAdV-4 alone. Functional validation through HSPA2 knockdown reduced FAdV-4 replication, establishing that FAdV-1 potentiates FAdV-4 through HSPA2-mediated host modulation. These findings provide the first evidence of HSPA2-dependent interserotype synergy in FAdV and can be used to develop a cellular model for FAdV coinfection studies. These insights redefine the understanding of FAdV pathogenesis and create new avenues for targeted intervention strategies against emerging FAdV coinfections.

关键词： Crop mapping   remote sensing   artificial intelligence   agriculture  

摘要： Accurate crop classification is essential for global food security under climate uncertainty. This systematic review, following PRISMA 2020 guidelines, analyzes 111 peer-reviewed studies (2015-2025) on Sentinel-based crop mapping using artificial intelligence. Our meta-analysis reveals a clear methodological evolution: traditional machine learning achieved similar to 85% accuracy, deep learning pushed performance to 87-95%, while hybrid CNN-Transformer architectures attain 95-98% an 11-13% improvement over baselines. Multi-sensor fusion of Sentinel-1 SAR and Sentinel-2 optical data consistently yields 5-8% accuracy gains, particularly valuable in cloud-prone tropical regions. However, research concentrates on temperate systems in Asia and Europe, leaving Sub-Saharan Africa and South America critically understudied. We demonstrate that contextual factors dataset size, crop complexity, and validation protocols influence accuracies as substantially as algorithm choice, demanding standardized benchmarks. Future priorities include transfer learning and foundation models to address data scarcity, expanding coverage to tropical smallholder systems, and adopting uncertainty quantification for scalable global crop monitoring.