Airborne pollen exposure and risk of hospital admission for allergic rhinitis in Beijing: A time-stratified case-crossover study.

BACKGROUND: Airborne pollen is a crucial risk factor in allergic rhinitis (AR). The severity of AR symptoms can vary based on pollen type and concentration. This study aimed to estimate the association between exposure to different pollen types and AR risk. METHODS: We obtained data from patients admitted to the Beijing Tongren Hospital for AR, and data on pollen concentration, meteorological factors, and fine particulate matter (PM2.5) from 13 districts in Beijing from 2016 to 2019. We used a time-stratified case-crossover study design and calculated odds ratios (ORs) related to the risk of AR associated with a 10 grain/1000 mm2 increase in total pollen concentrations for specific pollen types. A stratified analysis was conducted to assess whether the associations were varied by age and sex. RESULTS: The OR of AR associated with a 10 grain/1000 mm2 increase in the 7-day average pollen concentration was 1.014 (95% CI: 1.014, 1.015), 1.076 (95% CI: 1.070, 1.082), 1.024 (95% CI: 1.023, 1.025), 1.042 (95% CI: 1.039, 1.045), 1.142 (95% CI: 1.137, 1.147), 1.092 (95% CI: 1.088, 1.097), 1.046 (95% CI: 1.035, 1.058), and 1.026 (95% CI: 1.024, 1.028) for total pollen, Ulmus, Cupressaceae, Populus, Fraxinus, Pinus, Betula, and Artemisia, respectively. Both tree pollen (Ulmus, Cupressaceae, Populus, Fraxinus, Betula, and Pinus) and weed pollen (Artemisia, Chenopodium, and Humulus) were correlated with an increased risk of AR. These associations remained consistent across distinct subgroups defined by both age and sex. CONCLUSION: Exposure to pollen from trees and weeds might be associated with an increased risk of AR. This research provides valuable scientific support for both clinical practitioners and patients with AR regarding the hazards of pollen exposure.

Tripterygium drug-loaded liposome alleviates renal function by promoting vascularization and inhibiting fibrosis.

Introduction: Tripterygium species have been traditionally used in Chinese medicine for treating various conditions. The aim of the study was to construct a drug-modified renal infarction targeting liposome (rTor-LIP) containing Tripterygium in order to improve the therapeutic effect on renal injury. Methods: rTor-LIP was prepared using the extruder method containing Tripterygium solution. The preparation was characterized by transmission electron microscopy, Marvin laser particle size analyzer, and Western blotting. In vitro experiments were conducted to verify the biocompatibility of rTor-LIP, and in vivo experiments were conducted to verify the therapeutic effect of rTor- LIP on renal injury. Results and discussion: The surface of rTor-LIP was regular and oval. In vitro results showed that after co-incubation with rTor-LIP, endothelial cells did not show significant apoptosis, and there were no significant abnormalities in the mitochondrial metabolism. The in vivo results showed that the morphology of endothelial cells in the rTor-LIP group was uniform and the cytoplasmic striations were clear, but the local striations had disappeared. Thus, rTor-LIP nano-targeted liposomes can effectively target hypoxic kidney tissue, providing a new idea for the treatment of renal infarction.

Elevated serum uric acid to creatinine ratio is associated with adverse pregnancy outcomes: a prospective birth cohort study.

Purpose: This study evaluated the association between maternal serum uric acid-to-creatinine ratio (SUA/SCr) in the first trimester and adverse maternal and neonatal outcomes. Methods: A prospective birth cohort study was conducted between 2018 and 2021. Logistic regression models and restricted cubic splines were utilized to estimate the associations between the SUA/SCr ratio and feto-maternal pregnancy outcomes. Women were stratified according to maternal age and pre-pregnancy body mass index. Results: This study included 33,030 pregnant women with live singleton pregnancies. The overall prevalence of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), cesarean delivery, preterm birth, large-for-gestational age (LGA), small-for-gestational age, and low Apgar scores were 15.18%, 7.96%, 37.62%, 4.93%, 9.39%, 4.79% and 0.28%, respectively. The highest quartile of SUA/SCr was associated with the highest risk of GDM (odds ratio [OR] 2.14, 95% CI 1.93-2.36), PIH (OR 1.79, 95% CI 1.58-2.04), cesarean delivery (OR 1.24, 95% CI 1.16-1.33), and preterm birth (OR 1.30, 95% CI 1.12-1.51). The associations between SUA/SCr with adverse pregnancy outcomes showed linear relationships except for GDM (P < 0.001 for all, P < 0.001 for non-linearity). Subgroup analyses revealed that the associations between the SUA/SCr ratio and the risks of PIH and LGA were significantly stronger in younger pregnant women (P = 0.033 and 0.035, respectively). Conclusion: Maternal SUA/SCr levels were associated positively with the risk of adverse pregnancy outcomes. Timely monitoring of SUA and SCr levels during early pregnancy may help reduce the risk of adverse pregnancy outcomes and provide a basis for interventions.

Exploration of effective biomarkers for venous thrombosis embolism in Behçet's disease based on comprehensive bioinformatics analysis.

Behçet's disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein-protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723-0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

A comparative DFT study of HCHO decomposition on different terminations of the Co3O4(110) surface.

Density functional theory calculations have been performed to compare the HCHO decomposition on Co3O4(110)-A and (110)-B terminations. The results showed that the energy barriers of the two C-H bond cleavages of HCHO on the (110)-A termination were lower than those on the (110)-B termination, suggesting that the (110)-A termination had stronger HCHO decomposition ability than the (110)-B termination. Electronic structures revealed that the stronger HCHO decomposition ability of the (110)-A termination might be ascribed to the strong covalent bond between HCHO and the (110)-A termination, as well as the higher d-band center of Co3+ ions on the (110)-A termination. Furthermore, we proposed that the preparation of Co3O4 under oxygen-rich growth conditions was beneficial to HCHO decomposition because the (110)-A termination was more stable under oxygen-rich conditions.

Circadian clock disruption stimulates bone loss via regulatory T cell-Mediated regulation of IL-10 expression.

Circadian rhythms play a crucial role in regulating various physiological processes, including specific immune functions that enhance the body's ability to anticipate and respond to threats effectively. However, research on the impact of circadian rhythms on osteoimmunology remains limited. Our study uncovered that circadian disruption leads to bone mass loss by reducing the population of Treg cells in the bone marrow. Furthermore, we observed a significant decrease in serum IL-10 cytokine levels in jet lagged mice. In our current investigation, we explored the anti-osteoclastogenic effects of IL-10 and found that IL-10 inhibits RANKL-induced osteoclastogenesis in a dose-dependent manner. Our findings suggest that the diminished anti-osteoclastogenic properties of Tregs under circadian disruption are mediated by IL-10 cytokine production. Moreover, our discoveries propose that administration of IL-10 or butyrate could potentially reverse bone mass loss in individuals experiencing jet lag.

Stress hyperglycemia ratio and the clinical outcome of patients with heart failure: a meta-analysis.

Background: Stress hyperglycemia ratio (SHR) is a newly suggested measure of stress-induced hyperglycemia that combines both short-term and long-term glycemic conditions. The study aimed to explore the association between SHR and the incidence of adverse clinical events with heart failure (HF) through a meta-analysis. Methods: Cohort studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and CNKI. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Results: Ten studies involving 15250 patients with HF were included. Pooled results showed that compared to patients with lower SHR at baseline, those with a higher SHR were associated with an increased risk of all-cause mortality during follow-up (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.17 to 2.21, p = 0.003; I2 = 82%). Further meta-regression analysis suggests that different in the cutoff of SHR significantly modify the results (coefficient = 1.22, p = 0.02), and the subgroup analysis suggested a more remarkable association between SHR and all-cause mortality in studies with cutoff of SHR ≥ 1.05 than those with cutoff of SHR < 1.05 (RR: 2.29 versus 1.08, p for subgroup difference < 0.001). Subsequent meta-analyses also showed that a high SHR at baseline was related to the incidence of cardiovascular death (RR: 2.19, 95% CI: 1.55 to 3.09, p < 0.001; I2 = 0%), HF-rehospitalization (RR: 1.83, 95% CI: 1.44 to 2.33, p < 0.001; I2 = 0%), and major adverse cardiovascular events (RR: 1.54, 95% CI: 1.15 to 2.06, p = 0.004; I2 = 74%) during follow-up. Conclusion: A high SHR at baseline is associated with a poor clinical prognosis of patients with HF. Systematic review registration: https://inplasy.com, identifier INPLASY202430080.

Additive manufacturing of degradable metallic scaffolds for material-structure-driven diabetic maxillofacial bone regeneration.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn-Mg-Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Lower psoas mass indicates worse prognosis in percutaneous vertebroplasty-treated osteoporotic vertebral compression fracture.

The correlation between lower psoas mass and the prognosis of osteoporotic vertebral compression fractures (OVCF) is still unclear. This study aims to investigate the impact of lower psoas mass on the prognosis of patients undergoing percutaneous vertebroplasty (PVP). One hundred and sixty-three elderly patients who underwent single-segment PVP from January 2018 to December 2021 were included. The psoas to L4 vertebral index (PLVI) via MRI were measured to assess psoas mass. Patients were divided into high PLVI (> 0.79) and low PLVI (≤ 0.79) groups based on the median PLVI in the cohort. The basic information (age, gender, body mass index (BMI) and bone mineral density (BMD)), surgical intervention-related elements (duration of operation, latency to ambulation, period of hospital stay, and surgical site), postoperative clinical outcomes (Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, Japanese Orthopaedic Association (JOA) scores), and incidence of secondary fractures) were compared. Patients showed no statistically significant differences in terms of age, gender, surgical sute, BMI, BMD and preoperative VAS, ODI, JOA scores (P > 0.05) between the two groups. However, there were significant differences in terms of latency to ambulation, period of hospital stay (P < 0.05). VAS, ODI, and JOA scores at 1, 6, and 12 months after surgery showed that the high PLVI group had significantly better outcomes than the low PLVI group (P < 0.05). Additionally, the low PLVI group had a significantly higher incidence of recurrent fracture (P < 0.05). Lower psoas mass can reduce the clinical effect of PVP in patients with osteoporotic vertebral compression fractures, and is a risk factor for recurrent vertebral fracture.

Complete mitogenome and phylogenetic analysis of Hyalinocerus flavoscutatus Cai and Shen 1998 (Hemiptera: Eurymelinae: Idiocerini).

This study presents the initial sequencing and characterization of the complete mitochondrial genome (mitogenome) of Hyalinocerus flavoscutatus, making the first comprehensive exploration of the mitogenome in the Hyalinocerus. Utilizing next-generation sequencing techniques, we identified a circular DNA molecule spanning 15,307 bp. The mitogenome comprises 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a primary non-coding region. Maximum likelihood phylogenetic evaluation, based on 13 protein-coding genes and two ribosomal RNA genes, robustly supports H. flavoscutatus as the basal group within Idiocerini. This research unveils valuable insights into the mitogenome of H. flavoscutatus and enhances our understanding of phylogenetic placement within the broader context of related tribes.

The mediating effect of personal mastery and perceived social support between emotional intelligence and social alienation among patients receiving peritoneal dialysis.

Aim: This study aims to assess the extent of social alienation in patients undergoing peritoneal dialysis and examine how personal mastery and perceived social support mediate the association between emotional intelligence and social alienation in this patient population. Methods: This study adopts a cross-sectional survey design. A total of 192 patients were recruited from a tertiary hospital located in Henan Province, China, using a convenience sampling method. We have developed a structural equation model to investigate the mediating influence of personal mastery and perceived social support on the emotional intelligence and social alienation of patients undergoing Peritoneal dialysis. Results: Peritoneal patients exhibited an social alienation score of 42.01 ± 3.15. Elevated EI levels (coefficient = -0.616, p < 0.001) were significantly correlated with reduced social alienation. The mediation model demonstrated that personal mastery and perceived social support fully mediated the impact of emotional intelligence on social alienation. Conclusion: The social alienation of peritoneal dialysis patients is serious, and healthcare professionals should pay attention to patients' social alienation, improve patients' emotional intelligence through relevant interventions, increase personal mastery and perceived social support, and finally reduce social alienation.

Antitumor Therapy through Photothermal Performance Synergized with Catalytic Activity Based on the Boron Cluster Supramolecular Frameworks.

Chemodynamic therapy (CDT) has received widespread attention as a tumor optical treatment strategy in the field of malignant tumor therapy. Nonmetallic multifunctional nanomaterials as CDT agents, due to their low toxicity, long-lasting effects, and safety characteristics, have promising applications in the integrated diagnosis and treatment of cancer. Here, we modified the supramolecular framework of boron clusters, coupled with a variety of dyes to develop a series of metal-free agent compounds, and demonstrated that these nonmetallic compounds have excellent CDT activities through experiments. Subsequently, the best performing Methylene Blue/[closo-B12H12]2- (MB@B12H12) was used as an example. Through theoretical calculations, electron paramagnetic resonance spectroscopy, and 808 nm light irradiation, we confirmed that MB@B12H12 exhibited photothermal performance and CDT activity further. More importantly, we applied MB@B12H12 to melanoma cells and subcutaneous tumor, demonstrating its effective suppression of melanoma growth in vitro and in vivo through the synergistic effects of photothermal performance and CDT activity. This study emphasizes the generalizability of the coupling of dyes to [closo-B12H12]2- with important clinical translational potential for CDT reagents. Among them, MB@B12H12 may have a brighter future, paving the way for the rapid development of metal-free CDT reagents.

Reciprocal regulation between RACGAP1 and AR contributes to endocrine therapy resistance in prostate cancer.

BACKGROUND: Endocrine resistance driven by sustained activation of androgen receptor (AR) signaling pathway in advanced prostate cancer (PCa) is fatal. Characterization of mechanisms underlying aberrant AR pathway activation to search for potential therapeutic strategy is particularly important. Rac GTPase-activating protein 1 (RACGAP1) is one of the specific GTPase-activating proteins. As a novel tumor proto-oncogene, overexpression of RACGAP1 was related to the occurrence of various tumors. METHODS: Bioinformatics methods were used to analyze the relationship of expression level between RACGAP1 and AR as well as AR pathway activation. qRT-PCR and western blotting assays were performed to assess the expression of AR/AR-V7 and RACGAP1 in PCa cells. Immunoprecipitation and immunofluorescence experiments were conducted to detect the interaction and co-localization between RACGAP1 and AR/AR-V7. Gain- and loss-of-function analyses were conducted to investigate the biological roles of RACGAP1 in PCa cells, using MTS and colony formation assays. In vivo experiments were conducted to evaluate the effect of RACGAP1 inhibition on the tumor growth. RESULTS: RACGAP1 was a gene activated by AR, which was markedly upregulated in PCa patients with CRPC and enzalutamide resistance. AR transcriptionally activated RACGAP1 expression by binding to its promoter region. Reciprocally, nuclear RACGAP1 bound to the N-terminal domain (NTD) of both AR and AR-V7, blocking their interaction with the E3 ubiquitin ligase MDM2. Consequently, this prevented the degradation of AR/AR-V7 in a ubiquitin-proteasome-dependent pathway. Notably, the positive feedback loop between RACGAP1 and AR/AR-V7 contributed to endocrine therapy resistance of CRPC. Combination of enzalutamide and in vivo cholesterol-conjugated RIG-I siRNA drugs targeting RACGAP1 induced potent inhibition of xenograft tumor growth of PCa. CONCLUSION: In summary, our results reveal that reciprocal regulation between RACGAP1 and AR/AR-V7 contributes to the endocrine resistance in PCa. These findings highlight the therapeutic potential of combined RACGAP1 inhibition and enzalutamide in treatment of advanced PCa.

Chemical composition-induced evolution of the structure, domain and electrical properties of Sm-doped (1 - x)Pb(Ni1/3Nb2/3)O3-xPbTiO3.

As the two typical basic binary solid solutions of the relaxor-PbTiO3 family, Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) has been widely investigated, whereas Pb(Ni1/3Nb2/3)O3-PbTiO3 (PNN-PT) has not. Here, 1.5 mol% Sm-doped (1 - x)Pb(Ni1/3Nb2/3)O3-xPbTiO3, (1 - x)PNN-xPT:0.015Sm with x = 0.33-0.39, ceramics have been prepared and the chemical composition-induced evolution of crystal structure, domain, and electrical properties investigated systematically. With increasing PT content, evolution of the rhombohedral-tetragonal structure was observed. A rhombohedral-tetragonal morphotropic phase boundary occurred around x = 0.36-0.37, which showed a peak piezoelectric property with piezoelectric constant d33 = 531 pC N-1 and planar electromechanical coupling factor kp = 0.37 at room temperature. At the same time, the x = 0.36 composition showed improved ferroelectric behavior with remanent polarization Pr = 13.4 µC cm-2 and coercive field Ec = 3.2 kV cm-1. Interestingly, different from its PMN-PT counterpart, there is no temperature-driven phase transition between room temperature and the Curie temperature for (1 - x)PNN-xPT:0.015Sm. These parameters indicated that the PNN-PT system is worthy of more attention and is a promising platform for further development of high-performance piezo/ferroelectric materials.

Serum Metabolomics Reveals Metabolomic Profile and Potential Biomarkers in Asthma.

PURPOSE: Asthma is a highly heterogeneous disease. Metabolomics plays a pivotal role in the pathogenesis and development of asthma. The main aims of our study were to explore the underlying mechanism of asthma and to identify novel biomarkers through metabolomics approach. METHODS: Serum samples from 102 asthmatic patients and 18 healthy controls were collected and analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) system. Multivariate analysis and weighted gene co-expression network analysis (WGCNA) were performed to explore asthma-associated metabolomics profile and metabolites. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Subsequently, 2 selected serum hub metabolites, myristoleic acid and dodecanoylcarnitine, were replicated in a validation cohort using ultra-high performance LC-MS/MS system (UHPLC-MS/MS). RESULTS: Distinct metabolomics profile of asthma was revealed by multivariate analysis. Then, 116 overlapped asthma-associated metabolites between multivariate analysis and WGCNA, including 12 hub metabolites, were identified. Clinical features-associated hub metabolites were also identified by WGCNA. Among 116 asthma-associated metabolites, Sphingolipid metabolism and valine, leucine and isoleucine biosynthesis were revealed by KEGG analysis. Furthermore, serum myristoleic acid and dodecanoylcarnitine were significantly higher in asthmatic patients than in healthy controls in validation cohort. Additionally, serum myristoleic acid and dodecanoylcarnitine demonstrated high sensitivities and specificities in predicting asthma. CONCLUSIONS: Collectively, asthmatic patients showed a unique serum metabolome. Sphingolipid metabolism and valine, leucine and isoleucine biosynthesis were involved in the pathogenesis of asthma. Furthermore, our results suggest the promising values of serum myristoleic acid and dodecanoylcarnitine for asthma diagnosis in adults.

A novel strategy for ratiometric determination of o-phenylenediamine via in-situ fluorogenic reaction and generation of metal nanoparticles.

Herein, a novel ratiometric strategy for ultra-sensitive detection of o-phenylenediamine (OPD) was proposed based on combinatorial reactions of in-situ fluorogenic reaction and in-situ formation of red fluorescent dithiothreitol-copper nanoparticles (DTT-CuNPs). Here, Cu2+ is used both as an oxidant and as a precursor. Dehydroascorbic acid (DHAA) is formed via redox reaction of AA and Cu2+. Then, DHAA reacts with OPD to yield blue fluorescent quinoxaline (OXD) with emission peak at 434 nm through in-situ fluorogenic reaction. Red emitting DTT-CuNPs with emission peak at 666 nm is instantly generated due to the coordination reaction between DTT and the residual Cu2+ which is not consumed by AA. The fluorescence intensity (FI) of OXD at 434 nm is closely relied on the concentration of OPD, which can be used as a response signal for OPD detection. Meanwhile, FI of DTT-CuNPs at 666 nm has no significant change, which can be used as a reference signal for OPD detection. Thus, the ratio (F434/F666) of the Cu2+/AA/DTT sensing system is successfully employed to quantify OPD, exhibiting a wide linear range from 0.2 µM to 60 µM, with LOD of 0.09 µM.

LTR retrotransposon-derived LncRNA LINC01446 promotes hepatocellular carcinoma progression and angiogenesis by regulating the SRPK2/SRSF1/VEGF axis.

The causal link between long terminal repeat (LTR) retrotransposon-derived lncRNAs and hepatocellular carcinoma (HCC) remains elusive and whether these cancer-exclusive lncRNAs contribute to the effectiveness of current HCC therapies is yet to explore. Here, we investigated the activation of LTR retrotransposon-derived lncRNAs in a broad range of liver diseases. We found that LTR retrotransposon-derived lncRNAs are mainly activated in HCC and is correlated with the proliferation status of HCC. Furthermore, we discovered that an LTR retrotransposon-derived lncRNA, LINC01446, exhibits specific expression in HCC. HCC patients with higher LINC01446 expression had shorter overall survival times. In vitro and in vivo assays showed that LINC01446 promoted HCC growth and angiogenesis. Mechanistically, LINC01446 bound to serine/arginine protein kinase 2 (SRPK2) and activated its downstream target, serine/arginine splicing factor 1 (SRSF1). Furthermore, activation of the SRPK2-SRSF1 axis increased the splicing and expression of VEGF isoform A165 (VEGFA165). Notably, inhibiting LINC01446 expression dramatically impaired tumor growth in vivo and resulted in better therapeutic outcomes when combined with antiangiogenic agents. In addition, we found that the transcription factor MESI2 bound to the cryptic MLT2B3 LTR promoter and drove LINC01446 transcription in HCC cells. Taken together, our findings demonstrate that LTR retrotransposon-derived LINC01446 promotes the progression of HCC by activating the SRPK2/SRSF1/VEGFA165 axis and highlight targeting LINC01446 as a potential therapeutic strategy for HCC patients.

Tuber transcriptome analysis reveals a novel WRKY transcription factor StWRKY70 potentially involved in potato pigmentation.

Tuber flesh pigmentation, conferred by the presence of secondary metabolite anthocyanins, is one of many key agronomic traits for potato tubers. Although several genes of potato anthocyanin biosynthesis have been reported, transcription factors (TFs) contributing to tuber flesh pigmentation are still not fully understood. In this study, transcriptomic profiling of diploid potato accessions with or without tuber flesh pigmentation was conducted and genes of the anthocyanin biosynthesis pathway were found significantly enriched within the 1435 differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and connectivity analysis pinpointed a subset of 173 genes closely related to the key biosynthetic gene StDFR. Of the eight transcription factors in the subset, group III WRKY StWRKY70, was chosen for showing high connectivity to StDFR and ten other anthocyanin biosynthetic genes and homology to known WRKYs of anthocyanin pathway. The transient activation assay showed StWRKY70 predominantly stimulated the expression of StDFR and StANS as well as the accumulation of anthocyanins by enhancing the function of the MYB transcription factor StAN1. Furthermore, the interaction between StWRKY70 and StAN1 was verified by Y2H and BiFC. Our analysis discovered a new transcriptional activator StWRKY70 which potentially involved in tuber flesh pigmentation, thus may lay the foundation for deciphering how the WRKY-MYB-bHLH-WD40 (WRKY-MBW) complex regulate the accumulation of anthocyanins and provide new strategies to breed for more nutritious potato varieties with enhanced tuber flesh anthocyanins.