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Highlights The large-scale, high-strength, super-tough, and multifunctional nacre-like heterocyclic aramid (HA)/MXene@polypyrrole (PPy) (HMP) nanocomposite papers were fabricated using the in-situ assembly of PPy onto the HA/MXene hydrogel template. The "brick-and-mortar" layered structure and abundant hydrogen-bonding interactions among MXene, PPy, and HA respond cooperatively to external stress and effectively increase the mechanical properties of HMP nanocomposite papers. The templating effect from HA/MXene was utilized to guide the assembly of conducting polymers, leading to high electrical conductivity and outstanding electromagnetic interference shielding performance.

Background: Pulmonary hypertension (PH) represents a progressive condition characterized by the remodeling of pulmonary arteries, ultimately culminating in right heart failure and increased mortality rates. Substantial evidence has elucidated the pivotal role of perivascular inflammatory factors and immune dysregulation in the pathogenesis of PH. Chemokines, a class of small secreted proteins, exert precise control over immune cell recruitment and functionality, particularly with respect to their migration to sites of inflammation. Consequently, chemokines emerge as critical drivers facilitating immune cell infiltration into the pulmonary tissue during inflammatory responses. This review comprehensively examines the significant contributions of CC chemokines in the maintenance of immune cell homeostasis and their pivotal role in regulating inflammatory responses. The central focus of this discussion is directed towards elucidating the precise immunoregulatory actions of CC chemokines concerning various immune cell types, including neutrophils, monocytes, macrophages, lymphocytes, dendritic cells, mast cells, eosinophils, and basophils, particularly in the context of pH processes. Furthermore, this paper delves into an exploration of the underlying pathogenic mechanisms that underpin the development of PH. Specifically, it investigates processes such as cellular pyroptosis, examines the intricate crosstalk between bone morphogenetic protein receptor type 2 (BMPR2) mutations and the immune response, and sheds light on key signaling pathways involved in the inflammatory response. These aspects are deemed critical in enhancing our understanding of the complex pathophysiology of PH. Moreover, this review provides a comprehensive synthesis of findings from experimental investigations targeting immune cells and CC chemokines. Aim of review: In summary, the inquiry into the inflammatory responses mediated by CC chemokines and their corresponding receptors, and their potential in modulating immune reactions, holds promise as a prospective avenue for addressing PH. The potential inhibition of CC chemokines and their receptors stands as a viable strategy to attenuate the inflammatory cascade and ameliorate the pathological manifestations of PH. Nonetheless, it is essential to acknowledge the current state of clinical trials and the ensuing progress, which regrettably appears to be less than encouraging. Substantial hurdles exist in the successful translation of research findings into clinical applications. The intention is that such emphasis could potentially foster the advancement of potent therapeutic agents presently in the process of clinical evaluation. This, in turn, may further bolster the potential for effective management of PH.

Hyperspectral image (HSI) classification is a challenging task in remote sensing applications, aiming to determine the category of each pixel by utilizing rich spectral and spatial information in HSI. Convolutional neural networks (CNNs) have been effective in processing HSI data by extracting local features, but they are deficient in capturing global contextual information. Recently, transformer has become proficient in attending to global information due to their self-attention mechanisms, yet they may fall short in capturing multiscale features of HSI. To address these limitations, a global–local multigranularity transformer (GLMGT) network is proposed for HSI classification. The GLMGT combines CNN with the transformer to comprehensively capture multigranularity spectral and spatial features across global and local scales. Specifically, we introduce a multigranularity spatial feature extraction block to extensively extract spatial information at different granularities, including multiscale local spatial features and global spatial features. In addition, we introduce a multigranularity spectral feature extraction block to fully leverage spectral information across different granularities. The validity of the proposed method is demonstrated through experimental validation using seven publicly available datasets, which include two Chinese satellite hyperspectral datasets (ZY1-02D Huanghekou and GF-5 Yancheng) and one UAV-based hyperspectral dataset.

Diabetic nephropathy (DN) is a common and serious complication of diabetes, contributing significantly to patient mortality. Complication of DN (CDN) ranks as the second leading cause of end-stage renal disease globally. To address this, understanding the genetic regulation underlying DN is crucial for personalized treatment strategies. In this study, we identified genes and lncRNAs associated with diabetes and diabetic nephropathy constructing a DN-related lncRNA–mRNA network (DNLMN). This network, characterized by scale-free biomolecular properties, generated through the study of topological properties, elucidates key regulatory interactions. Enrichment analysis of important network modules revealed critical biological processes and pathways involved in DN pathogenesis. In the second step, we investigated the differential expression and co-expression of hub nodes in diseased and normal individuals, identifying lncRNA-mRNA relationships implicated in disease regulation. Finally, we gathered DN-related single nucleotide polymorphisms (SNPs) and lncRNAs from the LincSNP 3.0 database. The DNLMN encompasses SNP-associated lncRNAs, and transcription factors (TFs) linked to differentially expressed lncRNAs between diseased and normal samples. These results underscore the significance of biomolecular networks in disease progression and highlighting the role of biomolecular variability contributes to personalized disease phenotyping and treatment.

ABSTRACT Purpose Upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) share histomorphological and therapeutic features but distinct epidemiologic and clinicopathologic characteristics. We examined alterations of chromatin regulatory genes in molecular subtypes, clonal relatedness, and T‐cell receptor (TCR) diversity in UTUC and UCB. Materials and Methods Targeted next‐generation sequencing or whole‐exome DNA sequencing and TCR sequencing were conducted with 34 UTUC and 49 UCB specimens from 63 patients. Tumors were subtyped based on the expression of CK5 and GATA3. Results of tissue microarray of 78 muscle‐invasive bladder cancer (MIBC) samples were used as prognostic factors of different subtypes of MIBC. Results Chromatin regulatory genes were frequently mutated in both UTUC and UCB. Rapid relapse and progression of non‐MIBC are correlated with alterations of KMT2C and EP300. Frequency of alterations in chromatin regulatory genes is higher in UTUC patients with SBS22 and SBS2 signatures and lower in UCB patients with SBS2 and SBS6 signatures. GATA3 and CK5 double‐positive patients with higher frequencies of SMARCA4, ARID1A, and EP300 mutations have better prognoses than patients with basal subtypes. Although UTUC and UCB in the same patient can be either clonally related or developed independently, mutated genes in chromatin pathway were enriched in the related clones. Compared to UTUC, UCB had more deleterious mutations in DNA damage repair (DDR) genes, higher levels of tumor mutation burden (TMB) and copy number variations (CNVs), as well as higher TCR clonality and lower TCR diversity. Conclusions Since genetic alterations of the chromatin pathway genes are important in both UTUC and UCB, they could serve as potential biomarkers for predicting disease progression and therapeutic targets. Differences in mutation frequencies of DDR pathway, TMB, CNV, and TCR might be the contributing factors for the distinct responses to immune checkpoint inhibitor (ICI) between UTUC and UCB.

Pulmonary hypertension (PH) is a progressive cardiopulmonary disease characterized by elevated pulmonary artery pressure and vascular remodeling, resulting in poor prognosis and increased mortality rates. Chemokine-like factor 1 (CKLF1) plays a significant role in inducing inflammation and cell proliferation, both of which are critical processes in the pathogenesis of various diseases. Dihydromyricetin (DMY) has garnered attention for its potent anti-inflammatory properties. This study evaluated the protective effects of DMY against PH, demonstrating that DMY treatment can mitigate pyroptosis in pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) in vivo via the CKLF1/CCR5 axis. Results indicated significant improvements in hemodynamics, inflammatory responses, fibrosis, vascular remodeling, and right ventricular hypertrophy in PH rats following DMY treatment. Furthermore, the interaction between CKLF1 and CCR5 was investigated in CKLF1-/- rats after PH induction. DMY was found to downregulate CKLF1 expression and the inflammatory response in the lungs, with its therapeutic efficacy diminished following CKLF1 knockdown. This study underscores the therapeutic potential of DMY in the management of PH and lays a foundation for future research and clinical applications.

Background: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. Methods: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. Results: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. Conclusion: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).

Abstract Background Hypertrophy ligamentum flavum is a prevalent chronic spinal condition that affects middle‐aged and older adults. However, the molecular pathways behind this disease are not well comprehended. Objective The objective of this work is to implement bioinformatics techniques in order to identify crucial biological markers and immune infiltration that are linked to hypertrophy ligamentum flavum. Further, the study aims to experimentally confirm the molecular mechanisms that underlie the hypertrophy ligamentum flavum. Methods The corresponding gene expression profiles (GSE113212) were selected from a comprehensive gene expression database. The gene dataset for hypertrophy ligamentum flavum was acquired from GeneCards. A network of interactions between proteins was created, and an analysis of functional enrichment was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases. An study of hub genes was performed to evaluate the infiltration of immune cells in patient samples compared to tissues from the control group. Finally, samples of the ligamentum flavum were taken with the purpose of validating the expression of important genes in a clinical setting. Results Overall, 27 hub genes that were differently expressed were found through molecular biology. The hub genes were found to be enriched in immune response, chemokine‐mediated signaling pathways, inflammation, ossification, and fibrosis processes, as demonstrated by GO and KEGG studies. The main signaling pathways involved include the TNF signaling pathway, cytokine–cytokine receptor interaction, and TGF‐β signaling pathway. An examination of immunocell infiltration showed notable disparities in B cells (naïve and memory) and activated T cells (CD4 memory) between patients with hypertrophic ligamentum flavum and the control group of healthy individuals. The in vitro validation revealed markedly elevated levels of ossification and fibrosis‐related components in the hypertrophy ligamentum flavum group, as compared to the normal group. Conclusion The TGF‐β signaling pathway, TNF signaling pathway, and related hub genes play crucial roles in the progression of ligamentum flavum hypertrophic. Our study may guide future research on fibrosis of the ligamentum flavum.

Abstract Background Pancreatic cancer stem cells are crucial for tumorigenesis and cancer metastasis. Presently, long non-coding RNAs were found to be associated with Pancreatic Ductal Adenocarcinoma stemness characteristics but the underlying mechanism is largely known. Here, we aim to explore the function of LINC00909 in regulating pancreatic cancer stemness and cancer metastasis. Methods The expression level and clinical characteristics of LINC00909 were verified in 80-paired normal pancreas and Pancreatic Ductal Adenocarcinoma tissues from Guangdong Provincial People’s Hospital cohort by in situ hybridization. RNA sequencing of PANC-1 cells with empty vector or vector encoding LINC00909 was experimented for subsequent bioinformatics analysis. The effect of LINC00909 in cancer stemness and metastasis was examined by in vitro and in vivo experiments. The interaction between LINC00909 with SMAD4 and the pluripotency factors were studied. Results LINC00909 was generally upregulated in pancreatic cancer tissues and was associated with inferior clinicopathologic features and outcome. Over-expression of LINC00909 enhanced the expression of pluripotency factors and cancer stem cells phenotype, while knock-down of LINC00909 decreased the expression of pluripotency factors and cancer stem cells phenotype. Moreover, LINC00909 inversely regulated SMAD4 expression, knock-down of SMAD4 rescued the effect of LINC00909-deletion inhibition on pluripotency factors and cancer stem cells phenotype. These indicated the effect of LINC00909 on pluripotency factors and CSC phenotype was dependent on SMAD4 and MAPK/JNK signaling pathway, another downstream pathway of SMAD4 was also activated by LINC00909. Specifically, LINC00909 was localized in the cytoplasm in pancreatic cancer cells and decreased the stability the SMAD4 mRNA. Finally, we found over-expression of LINC00909 not only accelerated tumor growth in subcutaneous mice models, but also facilitated tumorigenicity and spleen metastasis in orthotopic mice models. Conclusion We demonstrate LINC00909 inhibits SMAD4 expression at the post-transcriptional level, which up-regulates the expression of pluripotency factors and activates the MAPK/JNK signaling pathway, leading to enrichment of cancer stem cells and cancer metastasis in pancreatic cancer.

In the context of hepatocellular carcinoma (HCC) treatment, this study introduces a biomimetic “bomb” approach to target HCC by utilizing macrophages (MAs) as ultrasound-responsive carriers. This advanced biomimetic drug delivery system (MAs-DOX/PFP/Ms, MAs-DPM) encapsulates doxorubicin (DOX) and perfluoropentane (PFP) and is designed to precisely target HCC. MAs-DPM exhibits excellent drug loading capacity and biocompatibility, can effectively release DOX and enhance ultrasound imaging capabilities under ultrasound irradiation (UI). Experiments confirmed that MA maintained its biological activity and vitality during co-incubation and phagocytosis with DOX-loaded DPM, and microscopy confirmed that MA effectively engulfed DPM without changing cell morphology or function. Transwell experiments demonstrated that this bionic “bomb” (MAs-DPMs) not only retained the tumor targeting ability of macrophages, but also successfully delivered therapeutic drugs to tumor cells. Compared with samples without UI treatment, UI significantly increased the release of DOX from MAs-DPM, enhanced the drug release rate and inhibited the growth of HCC cells. Live/Dead staining experiments further intuitively revealed the precise “biobomb” effect of MAs-DPM under UI, effectively proving its ability to inhibit HCC cell proliferation. In vivo studies demonstrated that MAs-DPM was able to proficiently localize tumor sites within 24 h. Furthermore, the ultrasound-mediated phase transition of PFP enhanced the imaging efficacy, confirming the feasibility of macrophage-mimicking biological bombs for real-time in vivo ultrasound tracking. In the tumor-bearing nude mouse model, UI-treated MAs-DPMs remarkably delayed tumor growth and prolonged survival time compared with other groups. Subsequent histological and serum index evaluation further confirmed the in vivo safety of MAs-DPMs, and UI-treatment did not induce significant histological or pathological changes or statistical differences in vital organ or serum markers. These experiment results highlight the great potential of MAs-DPM as a strategic approach for the diagnosis and treatment of HCC.

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It is a chronic condition characterized by intricate pathogenesis and uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification on PH. PH is not only a pulmonary vascular disease, but also a systemic disease. The findings emphasize that the onset of PH is not exclusively confined to the pulmonary vasculature, consequently necessitating treatment approaches that extend beyond targeting pulmonary blood vessels. Hence, the research on the pathological mechanism of PH is not limited to target organs such as pulmonary vessels, but also focuses on exploring other fields (such as estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification).

【Objective】Endophytic bacteria exert an important role in plant growth and development. The study aims to analyze the community structure and diversity of endophytic bacteria in pulp of different litchi varieties, and screen and utilize the potential endophytic bacteria resources, which would provide references for further research on the interaction between litchi and endophytic bacteria.【Method】The pulp tissues of 6 different litchi varieties were used as materials. MiSeq high-throughput sequencing technology was used to compare and analyze the community composition and dominant flora of endophytic bacteria at phylum, family, genus and species classification levels in pulp tissues after the V3~V4 region of 16S rDNA was amplified by PCR. The diversity of endophytic bacteria was evaluated combined with Alpha diversity analysis.【Result】A total of 2 139 086 sequences of endophytic bacteria 16S rDNA were obtained in the V3~V4 region of 6 litchi varieties, and the average length of amplified sequences was 376 bp. There was no significant difference in the abundance and diversity of endophytic bacteria in different litchi varieties. At the phylum classification level, Proteobacteria was the main dominant bacterial group in litchi pulp tissue, followed by Actinomyces. At the levels of family, genus and species classification, the endophytic bacterial community structure of different litchi varieties was similar, but the bacterial abundance proportion was different. Differential bacterial community analysis showed that the Pseudomonas, Pectobacterium, Ochrobactrum and Dickeya were significantly enriched in the high-quality varieties of 'Edanli', 'Nuomici' and 'Guanyinlv'. In addition, Bradyrhizobium and Snodgrassella were only enriched in the 'Edanli'. The clustering analysis of relative abundance of bacteria showed that 'Guanyinlv', 'Nuomici' and 'Edanli', had higher similarity. Alpha diversity analysis showed that there were differences in the abundance and diversity of endophytic flora in pulps of 6 litchi varieties, but the differences were not significant.【Conclusion】In this study, the community structure of endophytic bacteria in the pulp of six different litchi varieties was analyzed, and some unique microbial genera were enriched in the high-quality litchi varieties. The results could provide a theoretical basis and important references for the development and utilization of endophytic bacteria to improve litchi quality.

Abstract Airway epithelial transcriptome analysis of asthma patients with different severity was used to disentangle the immune infiltration mechanisms affecting asthma exacerbation, which may be advantageous to asthma treatment. Here we introduce various bioinformatics methods and develop two models: an OVA/CFA-induced neutrophil asthma mouse model and an LPS-induced human bronchial epithelial cell damage model. Our objective is to investigate the molecular mechanisms, potential targets, and therapeutic strategies associated with asthma severity. Multiple bioinformatics methods identify meaningful differences in the degree of neutrophil infiltration in asthma patients with different severity. Then, PTPRC, TLR2, MMP9, FCGR3B, TYROBP, CXCR1, S100A12, FPR1, CCR1 and CXCR2 are identified as the hub genes. Furthermore, the mRNA expression of 10 hub genes is determined in vivo and in vitro models. Reperixin is identified as a pivotal drug targeting CXCR1, CXCR2 and MMP9. We further test the potential efficiency of Reperixin in 16HBE cells, and conclude that Reperixin can attenuate LPS-induced cellular damage and inhibit the expression of them. In this study, we successfully identify and validate several neutrophilic signatures and targets associated with asthma severity. Notably, Reperixin displays the ability to target CXCR1, CXCR2, and MMP9, suggesting its potential therapeutic value for managing deteriorating asthma.

BackgroundAccurate detection of the histological grade of pancreatic neuroendocrine tumors (PNETs) is important for patients’ prognoses and treatment. Here, we investigated the performance of radiological image-based artificial intelligence (AI) models in predicting histological grades using meta-analysis.MethodA systematic literature search was performed for studies published before September 2023. Study characteristics and diagnostic measures were extracted. Estimates were pooled using random-effects meta-analysis. Evaluation of risk of bias was performed by the QUADAS-2 tool.ResultsA total of 26 studies were included, 20 of which met the meta-analysis criteria. We found that the AI-based models had high area under the curve (AUC) values and showed moderate predictive value. The pooled distinguishing abilities between different grades of PNETs were 0.89 [0.84-0.90]. By performing subgroup analysis, we found that the radiomics feature-only models had a predictive value of 0.90 [0.87-0.92] with I2 = 89.91%, while the pooled AUC value of the combined group was 0.81 [0.77-0.84] with I2 = 41.54%. The validation group had a pooled AUC of 0.84 [0.81-0.87] without heterogenicity, whereas the validation-free group had high heterogenicity (I2 = 91.65%, P=0.000). The machine learning group had a pooled AUC of 0.83 [0.80-0.86] with I2 = 82.28%.ConclusionAI can be considered as a potential tool to detect histological PNETs grades. Sample diversity, lack of external validation, imaging modalities, inconsistent radiomics feature extraction across platforms, different modeling algorithms and software choices were sources of heterogeneity. Standardized imaging, transparent statistical methodologies for feature selection and model development are still needed in the future to achieve the transformation of radiomics results into clinical applications.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022341852.

Abstract Background The incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes. Methods We conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis. Results One hundred twenty‐one of 172 patients died during follow‐up, with a median follow‐up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride‐glucose index (TyG), triglyceride‐glucose index‐body mass index (TyG‐BMI), and triglyceride/high‐density lipoprotein cholesterol ratio (TG/HDL‐c). The ROC curve indicated that TyG, TyG‐BMI, and TG/HDL‐c had prognostic efficacy for PC with diabetes. We next optimized TyG‐BMI and obtained a new parameter, namely glucose‐lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG‐BMI, TyG/HDL‐c, BMI, TG, total cholesterol (TC), TC/HDL‐c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG‐BMI. Conclusions IR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with an extremely poor prognosis. Cancer stem cells (CSCs) are considered to be responsible for the poor survival, recurrence and therapy resistance of PDAC. Ferroptosis plays a crucial role in the sustain and survival of CSCs. Here, we employed a rigorous evaluation of multiple datasets to identify a novel stemness-based and ferroptosis-related genes (SFRGs) signature to access the potential prognostic application. This work we retrieved RNA-sequencing and clinical annotation data from the TCGA, ICGC, GTEx and GEO database, and acquired 26 stem cell gene sets and 259 ferroptosis genes from StemChecker database and FerrDb database, respectively. Based on consensus clustering and ssGSEA analysis, we identified two expression patterns of CSCs traits (C1 and C2). Then, WGCNA analysis was implemented to screen out hub module genes correlated with stemness. Furthermore, differential expression analysis, Pearson correlation analysis, and the Least absolute shrinkage and selection operator (LASSO) and Cox regression were performed to identify the SFRGs and to construct model. In addition, the differences in prognosis, tumor microenvironment (TME) components and therapy responses were evaluated between two risk groups. Finally, we verified the most influential marker ARNTL2 experimentally by western blot, qRT-PCR, sphere formation assay, mitoscreen assay, intracellular iron concentration determination and MDA determination assays. In conclusion, we developed a stemness-based and ferroptosis-related prognostic model, which could help predict overall survival for PDAC patients. Targeting ferroptosis may be a promising therapeutic strategy to inhibit PDAC progression by suppressing CSCs.

Starting from the idea of constructing the standard incidence rate, we take the effective contact times of individuals in the population per unit time as a contact function, $ T(\cdot) $, which depends on the population size. Considering the influence of disease on the contact function, the influence intensity factor of the disease affected by the infected person is integrated into the nonlinear incidence rate. We propose an epidemic model with a class of disease-related contact functions. Then, we analyze the well-posedness of the solutions of the model. By using the next generation matrix method, we get the basic reproduction number $ \mathcal{R}_0 $. We find that the existence and stability of the equilibria are not only related to $ \mathcal{R}_0 $, but also to the intensity of the disease affected for the infected person, $ \eta $, and the contact function, $ T(\cdot) $. We obtain some stability results under different assumptions about the contact function. Finally, we use MATLAB to simulate the system for several different contact functions. The numerical simulation results agree with our qualitative study. At the same time, we also prove that the system may have a Hopf bifurcation when the contact function $ T(\cdot) $ satisfies some corresponding conditions.

Abstract The main issue limiting the performance of the solar evaporators is that water-thermal management is difficult to coordinate. Herein, we achieve integrated water-thermal management by designing hierarchical MXene-reduced graphene oxide sponges with anisotropic thermal conductivity and axial-directional water conveyance channels. The reduced graphene oxide acts as the sponge framework and carbon source for in situ synthesis of MXenes on the surface. The axial-oriented framework supports the structure and provides fast water transmission channels to the air-water interface. Meanwhile, the MXene nanosheets are vertically aligned on the framework surface, making the radial thermal conductivity of the sponges much greater than the axial one, which suppresses heat loss in the axial direction. The material exhibits an evaporation rate of 2.35 kg m−2 h−1 under one sunlight and maintains 85 % energy efficiency under weak sunlight (0.5-sun). Furthermore, the sponge shows a long working life with 96 % evaporation rate retention after a 30-day-sustained operation.