•Acrolein induced pyroptosis and suppressed migration in HUVECs.•Acrolein-induced pyroptosis was dependent on the activation of NLRP3 inflammsome.•Acrolein-suppressed cell migration was involved in ...NLRP3 inflammsome and pyroptosis.•ROS-dependent autophagy signal pathway was the main way.•Collapse of ΔΨm was autophagy dependent and damaged mitochondrion accentuated NLRP3 inflammsome and pyroptosis.
Acrolein is a common environmental pollutant that has been linked to cardiovascular diseases, such as atherosclerosis (AS). Increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms haven’t been completely elucidated. In human umbilical vein endothelial cells (HUVECs), we observed that acrolein treatment induced cell reactive oxygen species (ROS) generation, autophagy, pyroptosis and reduced cell migration. In addition, exposure to acrolein resulted in NLRP3 inflammasome activation as evidenced by cleavage of caspase-1 and downstream mature interleukin (IL)-1β and IL-18 secretion. Knockdown of NLRP3 by small interfering RNA remarkably suppressed acrolein-induced pyroptosis and increased cell migration. Moreover, the scavenging ROS relieved the autophagy, NLRP3 inflammasome activation and pyroptosis. Furthermore, the role of autophagy in the acrolein-medicated pyroptosis and cell migration was investigated. In our study, 3-methyladenine (3-MA), an autophagy inhibitor, aggravated NLRP3 inflammasome activation, pyroptosis and decreased cell migration, rapamycin (Rapa), an autophagy inducer, alleviated aforementioned phenomenon under acrolein stress. Besides, we found damaged mitochondrion accentuated NLRP3 inflammasome and pyroptosis in acrolein-treated cells. In conclusion, it is possible that acrolein induced cell pyroptosis and suppressed cell migration via ROS-dependent autophagy. What’s more, NLRP3 inflammasome activation plays a key role in this process.
Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan ...domestic mammals compared to reciprocal lowlanders. Furthermore, m
A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
Precise identification and spatial analysis of land salinity in China’s Yellow River Delta are essential for the rational utilization and sustainable development of land resources. However, the ...accurate retrieval model construction for monitoring land salinity remains challenging. This study constructed a land salinity retrieval framework using a harmonized UAV and Landsat-9 multi-spectral dataset. The Kenli district of the Yellow River Delta was selected as the case study area, and a land salinity monitoring index (LSMI) was proposed based on field survey data and UAV multi-spectral image and applied to the reflectance-corrected Landsat-9 OLI image. The land salinity distribution patterns were then mapped and spatially analyzed using Moran’s I and Getis-Ord GI* analysis. The results demonstrated the following: (1) The LSMI-based method can accurately retrieve land salinity content with a validation determination coefficient (R2), root mean square error (RMSE), and residual predictive deviation (RPD) of 0.75, 1.89, and 2.11, respectively. (2) Land salinization affected 93.12% of the cultivated land in the study area, and the severely saline soil grade (with a salinity content of 6–8 g/kg) covered 38.41% of the total cultivated land area and was widely distributed throughout the study area. (3) Saline land exhibited a positive spatial autocorrelation with a value of 0.311 at the p = 0.000 level; high–high cluster types occurred mainly in the Kendong and Huanghekou towns (80%), while low–low cluster types were mainly located in the Dongji, Haojia, Kenli, and Shengtuo towns (88.46%). The spatial characteristics of various salinity grades exhibit significant variations, and conducting separate spatial analyses is recommended for future studies.
Varieties of raisins are diverse, and different varieties have different nutritional properties and commercial value. In this paper, we propose a method to identify different varieties of raisins by ...combining near-infrared (NIR) spectroscopy and machine learning algorithms. The direct averaging of the spectra taken for each sample may reduce the experimental data and affect the extraction of spectral features, thus limiting the classification results, due to the different substances of grape skins and flesh. Therefore, this experiment proposes a method to fuse the spectral features of pulp and peel. In this experiment, principal component analysis (PCA) was used to extract baseline corrected features, and linear models of k-nearest neighbor (KNN) and linear discriminant analysis (LDA) and nonlinear models of back propagation (BP), support vector machine with genetic algorithm (GA-SVM), grid search-support vector machine (GS-SVM) and particle swarm optimization with support vector machine (PSO- SVM) coupling were used to classify. This paper compared the results of four experiments using only skin spectrum, only flesh spectrum, average spectrum of skin and flesh, and their spectral feature fusion. The experimental results showed that the accuracy and Macro-F1 score after spectral feature fusion were higher than the other three experiments, and GS-SVM had the highest accuracy and Macro-F1 score of 94.44%. The results showed that feature fusion can improve the performance of both linear and nonlinear models. This may provide a new strategy for acquiring spectral data and improving model performance in the future. The code is available at
Non-small cell lung cancer (NSCLC) is the most common type of human lung cancers, which has diverse pathological features. Although many signaling pathways and therapeutic targets have been defined ...to play important roles in NSCLC, limiting efficacies have been achieved.
Bioinformatics methods were used to identify differential long non-coding RNA expression in NSCLC. Real-time RT-PCR experiments were used to examine the expression pattern of lncRNA PKMYT1AR, miR-485-5p. Both in vitro and in vivo functional assays were performed to investigate the functional role of PKMYT1AR/miR-485-5p/PKMYT1 axis on regulating cell proliferation, migration and tumor growth. Dual luciferase reporter assay, fluorescent in situ hybridization (FISH), immunoblot, co-immunoprecipitation experiments were used to verify the molecular mechanism.
Here, we identify a human-specific long non-coding RNA (lncRNA, ENST00000595422), termed PKMYT1AR (PKMYT1 associated lncRNA), that is induced in NSCLC by Yin Yang 1 (YY1) factor, especially in cancerous cell lines (H358, H1975, H1299, H1650, A549 and SPC-A1) compared to that in normal human bronchial epithelium cell line (BEAS-2B). We show that PKMYT1AR high expression correlates with worse clinical outcome, and knockdown of PKMYT1AR inhibits tumor cell proliferation, migration and xenograft tumor formation abilities. Bioinformatic analysis and a luciferase assay demonstrate that PKMYT1AR directly interacts with miR-485-5p to attenuate the inhibitory role on its downstream oncogenic factor PKMYT1 (the protein kinase, membrane-associated tyrosine/threonine 1) in NSCLC. Furthermore, we uncover that miR-485-5p is downregulated in both cancerous cell lines and peripheral blood serum isolated from NSCLC patients compared to reciprocal control groups. Consistently, forced expression of miR-485-5p inhibits the proliferation and migration abilities of tumor cells. Moreover, we provide evidence showing that PKMYT1AR targeting antisense oligonucleotide (ASO) dramatically inhibit tumor growth in vivo. Mechanistic study shows that PKMYT1AR/ miR-485-5p /PKMYT1 axis promotes cancer stem cells (CSCs) maintenance in NSCLC via inhibiting β-TrCP1 mediated ubiquitin degradation of β-catenin proteins, which in turn causes enhanced tumorigenesis.
Our findings reveal the critical role of PKMYT1AR/miR-485-5p /PKMYT1 axis during NSCLC progression, which could be used as novel therapeutic targets in the future.
Brainstem gliomas are molecularly heterogeneous diseases, many of which are difficult to safely surgically resect and have limited treatment options due to their eloquent location. These constraints ...pose challenges to biopsy, which limits the use of routine molecular profiling and identification of personalized therapies. Here, we explored the potential of sequencing of circulating tumor DNA (ctDNA) isolated from the cerebrospinal fluid (CSF) of brainstem glioma patients as a less invasive approach for tumor molecular profiling. CSF was obtained from patients either intraoperatively (91.2%, 52/57), from ventricular-peritoneal shunt (3.5%, 2/57), or by lumbar puncture (5.3%, 3/57), all prior to surgical manipulation of the tumor. Deep sequencing of glioma-associated genes was performed on CSF-derived ctDNA and, where available, matched blood and tumor DNA from 57 patients, including nine medullary and 23 diffuse intrinsic pontine gliomas (DIPG). At least one tumor-specific mutation was detected in over 82.5% of CSF ctDNA samples (47/57). In cases with primary tumors harboring at least one mutation, alterations were identified in the CSF ctDNA of 97.3% of cases (36/37). In over 83% (31/37) of cases, all primary tumor alterations were detected in the CSF, and in 91.9% (34/37) of cases, at least half of the alterations were identified. Among ten patients found to have primary tumors negative for mutations, 30% (3/10) had detectable somatic alterations in the CSF. Finally, mutation detection using plasma ctDNA was less sensitive than sequencing the CSF ctDNA (38% vs. 100%, respectively). Our study indicates that deep sequencing of CSF ctDNA is a reliable technique for detecting tumor-specific alterations in brainstem tumors. This approach may offer an alternative approach to stereotactic biopsy for molecular profiling of brainstem tumors.
Background and aimsSTAT3 gene mutation causes autosomal dominant hyper- IgE syndrome (AD-HIES)is a rare primary immunodeficiency disease. We described the clinical and molecular features of 20 ...AD-HIES patients in Mainland China.MethodsWe diagnosed patients with AD-HIES on the basis of NIH score of ≥40 points, described the clinical features, sequenced the STAT3 gene of 20 patients, and quantified Th17 cells in peripheral blood of 19 patients by flow cytometry.ResultsAmong the 20 patients (14 males and 6 females), the onset age ranged from 1 days to 6 months, and the diagnostic age ranged from 1 to 12 years. All patients (100%) had characteristic manifestation of HIES with the range of NIH scores 41–77 points, including recurrent eczema and pneumonia, particularly high serum IgE levels and eosinophilia. Characteristic facial features (100%), bone abnormalities, recurrent skin abscesses (85%), lung abscesses (60%), recurrent oral thrush (55%) were also present in the studied patients. STAT3 hot mutations V637M or R382W/Q were identified in 12 patients (60%), two novel heterozygous missense mutations (T620S and R609G) were identifiedin 2 patients respectively, and other mutations (C712G, S636F, Q469H, Y705H, V432M, c.1139+5G>T) were identified in other 6 patients. The percentage of Th17 cells in CD4+ T cells (CD3+CD8IL-17A+/CD3+CD8 cells) of 19 patients with STAT3 mutation was significantly decreased or deficient as compared with healthy controls.ConclusionsChildren with repeated Staphylococcus aureus pneumonia, cold skin abscess, fungal infection, eczema, increased serum IgE level and eosinophil, should be alert to AD-HIES. Detection of Th17 cell by flow cytometry assist clinical diagnosis when the NIH score ≥40 points. Further STAT3 gene analysis can confirmed the diagnosis.Early diagnosis and active prevention of infection can significantly improve the quality of life of patients.
Ligament injuries are common in sports and other rigorous activities. It is a great challenge to achieve ligament regeneration after an injury due the avascular structure and low self-renewal ...capability. Herein, we developed vascular endothelial growth factor (VEGF)-binding aligned electrospun poly(caprolactone)/gelatin (PCL/Gel) scaffolds by incorporating prominin-1-binding peptide (BP) sequence and exploited them for patellar ligament regeneration. The adsorption of BP onto scaffolds was discerned by various techniques, such as Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscope. The accumulation of VEGF onto scaffolds correlated with the concentration of the peptide in vitro. BP-anchored PCL/Gel scaffolds (BP@PCL/Gel) promoted the tubular formation of human umbilical vein endothelial cells (HUVECs) and wound healing in vitro. Besides, BP containing scaffolds exhibited higher content of CD31+ cells than that of the control scaffolds at 1 week after implantation in vivo. Moreover, BP containing scaffolds improved biomechanical properties and facilitated the regeneration of matured collagen in patellar ligament 4 weeks after implantation in mice. Overall, this strategy of peptide-mediated orchestration of VEGF provides an enticing platform for the ligament regeneration, which may also have broad implications for tissue repair applications.
Ligament injuries are central to sports and other rigorous activities. Given to the avascular nature and poor self-healing capability of injured ligament tissues, it is a burgeoning challenge to fabricate tissue-engineered scaffolds for ligament reconstruction. Vascular endothelial growth factor (VEGF) is pivotal to the neo-vessel formation. However, the high molecular weight of VEGF as well as its short half-life in vitro and in vivo limits its therapeutic potential. To circumvent these limitations, herein, we functionalized aligned electrospun polycaprolactone/gelatin (PCL/Gel)-based scaffolds with VEGF-binding peptide (BP) and assessed their biocompatibility and performance in vitro and in vivo. BP-modified scaffolds accumulated VEGF, improved tube formation of HUVECs, and induced wound healing in vitro, which may have broad implications for regenerative medicine and tissue engineering.
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Background Serum lipoprotein(a) Lp(a) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the general population, its association with ASCVD incidence in Chinese ...maintenance hemodialysis (MHD) patients remains unclear. We aimed to evaluate the relationship between Lp(a) levels and ASCVD incidence among MHD patients in Beijing, China. Methods This retrospective, observational cohort study included MHD patients at Beijing Tongren Hospital from January 1, 2013 to December 1, 2020, and followed until December 1,2023. The primary outcome was ASCVD occurrence. Kaplan-Meier survival analysis was used to evaluate ASCVD-free survival in MHD patients, with stratification based on Lp(a) levels. Cox regression analyses were conducted to assess the association between Lp(a) levels and the occurrence of ASCVD. Results A total of 265 patients were enrolled in the study. The median follow-up period were 71 months.78 (29.4%) participants experienced ASCVD events, and 118 (47%) patients died, with 58 (49.1%) deaths attributed to ASCVD. Spearman rank correlation analyses revealed positive correlations between serum Lp(a) levels and LDL-c levels, and negative correlations with hemoglobin, triglyceride, serum iron, serum creatinine, and albumin levels. Multivariate Cox regression analysis showed that Lp(a) levels greater than or equal to 30 mg/L, increased age, decreased serum albumin levels, and a history of diabetes mellitus were significantly associated with ASCVD incidence. Conclusions This study demonstrated an independent and positive association between serum Lp(a) levels and the risk of ASCVD in MHD patients, suggesting that serum Lp(a) could potentially serve as a clinical biomarker for estimating ASCVD risk in this population. Keywords: Lipoprotein (a), Atherosclerotic cardiovascular disease, Cardiovascular disease, End-stage renal disease, Maintenance hemodialysis
Terpenes are important components of plant aromas, and terpene synthases (TPSs) are the key enzymes driving terpene diversification. In this study, we characterized the volatile terpenes in five ...different Chrysanthemum nankingense tissues. In addition, genome-wide identification and expression analysis of TPS genes was conducted utilizing an improved chromosome-scale genome assembly and tissue-specific transcriptomes. The biochemical functions of three representative TPSs were also investigated. We identified tissue-specific volatile organic compound (VOC) and volatile terpene profiles. The improved Chrysanthemum nankingense genome assembly was high-quality, including a larger assembled size (3.26 Gb) and a better contig N50 length (3.18 Mb) compared to the old version. A total of 140 CnTPS genes were identified, with the majority representing the TPS-a and TPS-b subfamilies. The chromosomal distribution of these TPS genes was uneven, and 26 genes were included in biosynthetic gene clusters. Closely-related Chrysanthemum taxa were also found to contain diverse TPS genes, and the expression profiles of most CnTPSs were tissue-specific. The three investigated CnTPS enzymes exhibited versatile activities, suggesting multifunctionality. We systematically characterized the structure and diversity of TPS genes across the Chrysanthemum nankingense genome, as well as the potential biochemical functions of representative genes. Our results provide a basis for future studies of terpene biosynthesis in chrysanthemums, as well as for the breeding of improved chrysanthemum varieties.
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