Knockdown of LncRNA-HAGLR restrains the viability and motility of pancreatic cancer via miR-625-5p/TAF15 axis in vitro and in vivo.

Dysregulation of long non-coding RNAs (lncRNAs) has been strongly involved to the development of pancreatic cancer (PC). However, the potential mechanisms by which lncRNA regulate PC development still need to be further explored. We attempted to elucidate the functional role and regulatory mechanism of lncRNA HAGLR on PC progression in vitro and vivo. RT-qPCR, Western blot, RNA pull-down, luciferase reporter assay, RNA immunoprecipitation assay, CCK-8 assay, EdU assay, flow cytometry, transwell assay and xenograft tumor experiment were performed in this study. We found that the expressions of HAGLR and TAF15 were increased in PC tissues and cells. HAGLR silencing restrained the PC cell growth and invasion, but induced cell apoptosis. Moreover, HAGLR targeted miR-625-5p to modulate the expression of TAF15. HAGLR overexpression partially eliminated the suppressive effect of TAF15 depletion on PC cell growth and the stimulative effect on apoptosis. In vivo assays showed that HAGLR knockdown inhibited PC cell growth by regulating the TAF15 expression. These findings suggest HAGLR could facilitate PC cell malignant behaviors through regulating the TAF15 expression, demonstrating that HAGLR might be a valuable target for the PC treatment.

Brucea javanica Seed Oil Emulsion and Shengmai Injections Improve Peripheral Microcirculation in Treatment of Gastric Cancer.

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. ß-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS: YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. ß-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.

Relationship of the trajectory of the triglyceride-glucose index with heart failure: the Kailuan study.

BACKGROUND: A high triglyceride-glucose index (TyG) is associated with a higher risk of incident heart failure. However, the effects of longitudinal patterns of TyG index on the risk of heart failure remain to be characterized. Therefore, in the present study, we aimed to characterize the relationship between the trajectory of TyG index and the risk of heart failure. METHODS: We performed a prospective study of 56,149 participants in the Kailuan study who attended three consecutive surveys in 2006-2007, 2008-2009, and 2010-2011 and had no history of heart failure or cancer before the third wave survey (2010-2011). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2], and we used latent mixture modeling to characterize the trajectory of the TyG index over the period 2006-2010. Additionally, Cox proportional risk models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for incident heart failure for the various TyG index trajectory groups. RESULTS: From 2006 to 2010, four different TyG trajectories were identified: low-stable (n = 13,554; range, 7.98-8.07), moderate low-stable (n = 29,435; range, 8.60-8.65), moderate high-stable (n = 11,262; range, 9.31-9.30), and elevated-stable (n = 1,898; range, 10.04-10.25). A total of 1,312 new heart failure events occurred during a median follow-up period of 10.04 years. After adjustment for potential confounders, the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident heart failure for the elevated-stable, moderate high-stable, and moderate low-stable groups were 1.55 (1.15, 2.08), 1.32 (1.08, 1.60), and 1.17 (0.99, 1.37), respectively, compared to the low-stable group. CONCLUSIONS: Higher TyG index trajectories were associated with a higher risk of heart failure. This suggests that monitoring TyG index trajectory may help identify individuals at high risk for heart failure and highlights the importance of early control of blood glucose and lipids for the prevention of heart failure.

Association between the atherogenic index of plasma trajectory and risk of heart failure among hypertensive patients: a prospective cohort study.

BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular events. However, it remains unclear whether hypertensive patients with long-term high AIP levels are at greater risk of developing heart failure (HF). Therefore, the aim of this study was to investigate the association between AIP trajectory and the incidence of HF in hypertensive patients. METHODS: This prospective study included 22,201 hypertensive patients from the Kailuan Study who underwent three waves of surveys between 2006 and 2010. Participants were free of HF or cancer before or during 2010. The AIP was calculated as the logarithmic conversion ratio of triglycerides to high-density lipoprotein cholesterol. Latent mixed modeling was employed to identify different trajectory patterns for AIP during the exposure period (2006-2010). Cox proportional hazard models were then used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for incident HF among different trajectory groups. RESULTS: Four distinct trajectory patterns were identified through latent mixture modeling analysis: low-stable group (n = 3,373; range, -0.82 to -0.70), moderate-low stable group (n = 12,700; range, -0.12 to -0.09), moderate-high stable group (n = 5,313; range, 0.53 to 0.58), and elevated-increasing group (n = 815; range, 1.22 to 1.56). During a median follow-up period of 9.98 years, a total of 822 hypertensive participants experienced HF. After adjusting for potential confounding factors, compared with those in the low-stable group, the HR and corresponding CI for incident HF in the elevated-increasing group, moderate-high stable group, and moderate-low stable group were estimated to be 1.79 (1.21,2.66), 1.49 (1.17,1.91), and 1.27 (1.02,1.58), respectively. These findings remained consistent across subgroup analyses and sensitivity analyses. CONCLUSION: Prolonged elevation of AIP in hypertensive patients is significantly associated with an increased risk of HF. This finding suggests that regular monitoring of AIP could aid in identifying individuals at a heightened risk of HF within the hypertensive population.

Nonenzymatic Sequestering of Formaldehyde into the Antibiotic Methylene-Bridged Dimer Phaeochromycin F by Streptomyces sp. OUCMDZ-4982 as a Possible Multipronged Chemical Defense Mechanism.

Metabolites with high chemical reactivity serve important roles in chemical defenses of organisms. Formaldehyde, as a simple and highly reactive small molecule, can be produced by microorganisms, plants, and animals. Its toxicity is well known, but information about its other biological functions remains scarce. Here, we report that the natural product SEK34b produced by Streptomyces species can react nonenzymatically with formaldehyde in water to yield the methylene-bridged dimer phaeochromycin F. This process can eliminate the toxic substance formaldehyde produced by Staphylococcus aureus. Furthermore, there is a substantial inhibitory impact of phaeochromycin F on S. aureus. We hypothesize that these constitute an integrated system of defense and attack of Streptomyces species against competitors. Our study indicates that formaldehyde can react with vancomycin and tigecycline under mild conditions to generate the derivatives bearing an imidazolidin-4-one moiety, thereby reducing the antibacterial activity of these antibiotics. These data provide a possible chemical interaction mechanism of bacteria involving the nonenzymatic reactions of formaldehyde with highly reactive natural products.

Melatonin derivative 6a protects Caenorhabditis elegans from formaldehyde neurotoxicity via ADH5.

Formaldehyde (FA) is a carcinogen that is not only widespread in the environment, but is also produced endogenously by metabolic processes. In organisms, FA is converted to formic acid in a glutathione (GSH)-dependent manner by alcohol dehydrogenase 5 (ADH5). The abnormal accumulation of FA in the body can cause a variety of diseases, especially cognitive impairment leading to Alzheimer's disease (AD). In this study, melatonin derivative 6a (MD6a) markedly improved the survival and chemotactic performance of wild-type Caenorhabditis elegans exposed to high concentrations of FA. MD6a lowered FA levels in the nematodes by enhancing the release of covalently-bound GSH from S-hydroxymethyl-GSH in an adh-5-dependent manner. In addition, MD6a protected against mitochondrial dysfunction and cognitive impairment in beta-amyloid protein (Aß) transgenic nematodes by lowering endogenous FA levels and reducing Aß aggregation in an adh-5-dependent manner. Our findings suggest that MD6a detoxifies FA via ADH5 and protects against Aß toxicity by reducing endogenous FA levels in the C. elegans AD models. Thus, ADH5 might be a potential therapeutic target for FA toxicity and AD.

Neratinib stimulates senescence of mammary cancer cells by reducing the levels of SIRT1.

Neratinib, a typical small-molecule, pan-human tyrosine kinase inhibitor (TKI), has been licensed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the underlying pharmacological mechanism is still unknown. In the current study, we report a novel function of Neratinib by showing that its treatment stimulates senescence of the mammary cancer AU565 cells. Our results demonstrate that Neratinib induces mitochondrial injury by increasing mitochondrial reactive oxygen species (ROS) and reducing intracellular adenosine triphosphate (ATP). Also, we found that Neratinib induced DNA damage by increasing the levels of 8-Hydroxy-desoxyguanosine (8-OHdG) and γH2AX in AU565 cells. Additionally, Neratinib reduced the levels of telomerase activity after 7 and 14 days incubation. Importantly, the senescence-associated-ß-galactosidase (SA-ß-Gal) assay revealed that Neratinib stimulated senescence of AU565 cells. Neratinib decreased the gene levels of human telomerase reverse transcriptase (hTERT) but increased those of telomeric repeat-binding factor 2 (TERF2) in AU565 cells. Further study displayed that Neratinib upregulated the expression of K382 acetylation of p53 (ac-K382) and p21 but reduced the levels of sirtuin-1 (SIRT1). However, overexpression of SIRT1 abolished the effects of Neratinib in cellular senescence. These findings provide strong preclinical evidence of Neratinib's treatment of breast cancer.

Preoperative prediction of lymph node metastasis in colorectal cancer using 18F-FDG PET/CT peritumoral radiomics analysis.

BACKGROUND: Radiomics has been used in the diagnosis of tumor lymph node metastasis (LNM). However, to date, most studies have been based on intratumoral radiomics. Few studies have focused on the use of 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG PET/CT) peritumoral radiomics for the diagnosis of LNM in colorectal cancer (CRC). PURPOSE: Determining the value of radiomics features extracted from 18F-FDG PET/CT images of the peritumoral region in predicting LNM in patients with CRC. METHODS: The clinical data and preoperative 18F-FDG PET/CT images of 244 CRC patients were retrospectively analyzed. Intratumoral and peritumoral radiomics features were screened using the mutual information method, and least absolute shrinkage and selection operator regression. Based on the selected radiomics features, a radiomics score (Rad-score) was calculated, and independent risk factors obtained from univariate and multivariate logistic regression analyses were used to construct clinical and combined (Radiomics + Clinical) models. The performance of these models was evaluated using the DeLong test, while their clinical utility was assessed by decision curve analysis. Finally, a nomogram was constructed to visualize the predictive model. RESULTS: The most optimal set of features retained by the feature filtering process were all peritumoral radiomic features. Carcinoembryonic antigen levels, PET/CT-reported lymph node status and Rad-score were found to be independent risk factors for LNM. All three LNM risk assessment models exhibited good predictive performance, with the combined model showing the best classification results, with areas under the curve of 0.85 and 0.76 in the training and validation groups, respectively. The DeLong test revealed that the performance of the combined model was superior to that of the clinical and radiomics models in both the training and validation groups, although this difference was only statistically significant in the training group. DCA indicated that the combined model displayed better clinical utility. CONCLUSIONS: 18F-FDG PET/CT peritumoral radiomics is uniquely suited to predict the presence of LNM in patients with CRC. In particular, the predictive efficacy of LNM for precision therapy and individualized patient management can be improved by using a combination of clinical risk factors.

Casual associations between blood metabolites and colon cancer.

BACKGROUND: Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer. AIM: To investigate causal associations between blood metabolites and colon cancer. METHODS: The study utilized a two-sample Mendelian randomization (MR) analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer. The primary method of analysis used was the inverse variance weighted model. To further validate the results several sensitivity analyses were performed, including Cochran's Q test, MR-Egger intercept test, and MR robust adjusted profile score. These additional analyses were conducted to ensure the reliability and robustness of the findings. RESULTS: After rigorous selection for genetic variation, 486 blood metabolites were included in the MR analysis. We found Mannose [odds ratio (OR) = 2.09 (1.10-3.97), P = 0.024], N-acetylglycine [OR = 3.14 (1.78-5.53), P = 7.54 × 10-8], X-11593-O-methylascorbate [OR = 1.68 (1.04-2.72), P = 0.034], 1-arachidonoylglycerophosphocholine [OR = 4.23 (2.51-7.12), P = 6.35 × 10-8] and 1-arachidonoylglycerophosphoethanolamine 4 [OR = 3.99 (1.17-13.54), P = 0.027] were positively causally associated with colorectal cancer, and we also found a negative causal relationship between Tyrosine [OR = 0.08 (0.01-0.63), P = 0.014], Urate [OR = 0.25 (0.10-0.62), P = 0.003], N-acetylglycine [0.73 (0.54-0.98), P = 0.033], X-12092 [OR = 0.89 (0.81-0.99), P = 0.028], Succinylcarnitine [OR = 0.48 (0.27-0.84), P = 0.09] with colorectal cancer. A series of sensitivity analyses were performed to confirm the rigidity of the results. CONCLUSION: This study showed a causal relationship between 10 blood metabolites and colorectal cancer, of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors. The other five blood metabolites are protective factors.

Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway.

Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes.

BACKGROUND: Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis. AIM: To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM. METHODS: Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed. RESULTS: A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis. CONCLUSION: Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

Using tumor habitat-derived radiomic analysis during pretreatment 18F-FDG PET for predicting KRAS/NRAS/BRAF mutations in colorectal cancer.

BACKGROUND: To investigate the association between Kirsten rat sarcoma viral oncogene homolog (KRAS) / neuroblastoma rat sarcoma viral oncogene homolog (NRAS) /v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and the tumor habitat-derived radiomic features obtained during pretreatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in patients with colorectal cancer (CRC). METHODS: We retrospectively enrolled 62 patients with CRC who had undergone 18F-FDG PET/computed tomography from January 2017 to July 2022 before the initiation of therapy. The patients were randomly split into training and validation cohorts with a ratio of 6:4. The whole tumor region radiomic features, habitat-derived radiomic features, and metabolic parameters were extracted from 18F-FDG PET images. After reducing the feature dimension and selecting meaningful features, we constructed a hierarchical model of KRAS/NRAS/BRAF mutations by using the support vector machine. The convergence of the model was evaluated by using learning curve, and its performance was assessed based on the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis. The SHapley Additive exPlanation was used to interpret the contributions of various features to predictions of the model. RESULTS: The model constructed by using habitat-derived radiomic features had adequate predictive power with respect to KRAS/NRAS/BRAF mutations, with an AUC of 0.759 (95% CI: 0.585-0.909) on the training cohort and that of 0.701 (95% CI: 0.468-0.916) on the validation cohort. The model exhibited good convergence, suitable calibration, and clinical application value. The results of the SHapley Additive explanation showed that the peritumoral habitat and a high_metabolism habitat had the greatest impact on predictions of the model. No meaningful whole tumor region radiomic features or metabolic parameters were retained during feature selection. CONCLUSION: The habitat-derived radiomic features were found to be helpful in stratifying the status of KRAS/NRAS/BRAF in CRC patients. The approach proposed here has significant implications for adjuvant treatment decisions in patients with CRC, and needs to be further validated on a larger prospective cohort.

Comprehensive Analysis of circRNA, lncRNA, miRNA and mRNA Expression Profiles and Their Competing Endogenous RNA Networks in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Pursuing knowledge about circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles and their competing endogenous RNA (ceRNA) networks in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) was the focus of this research. Expression patterns of circRNAs, lncRNAs, miRNAs, and mRNAs were searched for in relation to HBV-related HCC using whole-transcriptome sequencing. The expression levels of chosen circRNA, lncRNA, miRNA, and mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential connections and roles of ceRNA were deduced via bioinformatics research. The sum of 284 circRNAs, 2,927 lncRNAs, 693 miRNAs, and 5566 mRNAs were discovered to be expressed at considerably different levels in HBV-related HCC tissue and adjacent normal tissue. And the most significantly up- and down-regulated circRNAs, lncRNAs, miRNAs, and mRNAs were verified in HBV-related HCC by qRT-PCR. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of HBV-related HCC were established, and the ceRNA regulatory networks revealed the gene expression mechanisms controlled by ncRNAs. Collectively, we revealed the contribution of various circRNA, lncRNA, miRNA, and mRNA expression profiles and identified their ceRNA regulatory networks in HBV-related HCC, providing a theoretical basis for further exploration.

Non-invasively Discriminating the Pathological Subtypes of Non-small Cell Lung Cancer with Pretreatment 18F-FDG PET/CT Using Deep Learning.

RATIONALE AND OBJECTIVES: To develop an end-to-end deep learning (DL) model for non-invasively predicting non-small cell lung cancer (NSCLC) pathological subtypes based on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images, and to explore the potential value of DL technology. MATERIALS AND METHODS: Preoperative 18F-FDG PET/CT images of 189 patients with NSCLC were retrospectively collected. The whole cohort was randomly divided into a training cohort, a validation cohort, and an internal/extended test cohort at the ratio of 6:2:2 after preprocessing the images. In the training and validation cohorts, seven DL models-Shufflenet, VGG16, Googlenet, Inception v3, Resnet50, Densenet201, and Mobilenet v2-were trained and optimized. The generalization ability and clinical utility of the optimal model were evaluated in the internal and extended test cohorts. Moreover, Spearman's correlation analysis was used to evaluate the correlation between DL features and traditional radiological features such as tumor size and maximum standardized uptake values (SUVmax). RESULTS: Some DL features were significantly correlated with SUVmax and tumor size (P < 0.05). The Mobilenet v2 model achieved the best performance during the model development and validation phases. In the internal test group (area under the receiver operating characteristic curve [AUC]: 0.744, area under the precision-recall curve [AP]: 0.759) and extended test group (AUC: 0.767, AP: 0.768), the Mobilenet v2 model showed good generalization ability and reproducibility. Meanwhile, the decision curve analysis revealed that patients can benefit from the decisions made based on the Mobilenet v2 model. CONCLUSION: DL models offer great potential for classifying NSCLC pathological subtypes. Specifically, the Mobilenet v2 model performs well at end-to-end non-invasive pathological subtype stratification of NSCLC.

Hybridization and divergent climatic preferences drive divergence of two allopatric Gentiana species on the Qinghai-Tibet Plateau.

BACKGROUND AND AIMS: Exploring how species diverge is vital for understanding the drivers of speciation. Factors such as geographical separation and ecological selection, hybridization, polyploidization and shifts in mating system are all major mechanisms of plant speciation, but their contributions to divergence are rarely well understood. Here we test these mechanisms in two plant species, Gentiana lhassica and G. hoae, with the goal of understanding recent allopatric species divergence on the Qinghai-Tibet Plateau (QTP). METHODS: We performed Bayesian clustering, phylogenetic analysis and estimates of hybridization using 561 302 nuclear genomic single nucleotide polymorphisms (SNPs). We performed redundancy analysis, and identified and annotated species-specific SNPs (ssSNPs) to explore the association between climatic preference and genetic divergence. We also estimated genome sizes using flow cytometry to test for overlooked polyploidy. KEY RESULTS: Genomic evidence confirms that G. lhassica and G. hoae are closely related but distinct species, while genome size estimates show divergence occurred without polyploidy. Gentiana hoae has significantly higher average FIS values than G. lhassica. Population clustering based on genomic SNPs shows no signature of recent hybridization, but each species is characterized by a distinct history of hybridization with congeners that has shaped genome-wide variation. Gentiana lhassica has captured the chloroplast and experienced introgression with a divergent gentian species, while G. hoae has experienced recurrent hybridization with related taxa. Species distribution modelling suggested range overlap in the Last Interglacial Period, while redundancy analysis showed that precipitation and temperature are the major climatic differences explaining the separation of the species. The species differ by 2993 ssSNPs, with genome annotation showing missense variants in genes involved in stress resistance. CONCLUSIONS: This study suggests that the distinctiveness of these species on the QTP is driven by a combination of hybridization, geographical isolation, mating system differences and evolution of divergent climatic preferences.

A functional nucleic acid-based fluorescence sensing platform based on DNA supersandwich nanowires and cation exchange reaction.

Accurate and sensitive analysis of p53 DNA is important for early diagnosis of cancer. In this work, a fluorescence sensing system based on DNA supersandwich nanowires and cation exchange (CX)-triggered multiplex signal amplification was constructed for the detection of p53 DNA. In the presence of p53 DNA, the DNA self-assembles to form a DNA supersandwich nanowire that generates long double-stranded DNA. Subsequently, the cation exchange (CX) reaction between ZnS and Ag+ was utilized to release free Zn2+. With the participation of Zn2+, DNAzyme catalyzes the hydrolysis of numerous catalytic molecular beacons, resulting in a greatly enhanced fluorescence signal due to the cycling of DNAzyme. The fluorescence values increased in proportion to the concentrations of p53 DNA in the range of 10 pM to 200 nM, and a detection limit (LOD) of 2.34 pM (S/N = 3) was obtained. This method provides an effective strategy for the quantitative detection of p53 DNA.

Efficacy and safety of pan retinal photocoagulation combined with intravitreal anti-VEGF agents for high-risk proliferative diabetic retinopathy: A systematic review and meta-analysis.

BACKGROUND: High-risk proliferative diabetic retinopathy (HR-PDR) is the advanced stage of diabetic retinopathy progression with poor prior treatment efficacy and high rates of blindness. This meta-analysis aims to compare the efficacy and safety of pan retinal photocoagulation (PRP) combined with intravitreal anti-vascular endothelial growth factor (aVEGF) (PRP + aVEGF) versus PRP monotherapy in HR-PDR patients. METHODS: A thorough search was performed through PubMed, Web of Science, EMBASE, and the Cochran Library from inception to December 18, 2022. Outcome measures included change in central macular thickness, best-corrected visual acuity, fluorescein angiography, incidence of undergoing vitrectomy, and adverse events during the follow-up period. RESULTS: Eight studies (6 randomized controlled trials and 2 retrospective studies) with 375 eyes were included in this meta-analysis. There were no obvious differences in the changes of best-corrected visual acuity and fluorescein angiography between the PRP + aVEGF and PRP monotherapy groups. However, PRP + aVEGF group had a significant reduction in the change of central macula thickness (standard mean deviations = -1.44, 95%CI = -2.55 to -0.32, P = .01) and the rate of undergoing vitrectomy (odds ratio = 0.20, 95%CI = 0.05-0.83, P = .01). Additionally, the risks of vitreous hemorrhage and other complications were not significantly different between the 2 groups. CONCLUSION SUBSECTIONS: Our meta-analysis indicated that PRP + aVEGF might have potential benefits in the treatment of HR-PDR patients. However, given several limitations of this study, more research is needed to confirm our findings.

Clinical application of Al18F-NOTA-FAPI PET/CT in diagnosis and TNM staging of pancreatic adenocarcinoma, compared to 18F-FDG.

PURPOSE: This study aimed to investigate the ability of Al18F-NOTA-FAPI PET/CT to diagnose pancreatic carcinoma and tumor-associated inflammation with the comparison of 18F-FDG PET/CT. METHODS: Prospective analysis of Al18F-NOTA-FAPI PET/CT and 18F-FDG PET/CT scans of 31 patients from 05/2021 to 05/2022 were analyzed. Al18F-NOTA-FAPI imaging was performed in patients who had Ce-CT and FDG PET/CT and the diagnosis was still unclear. Follow-up histopathology or radiographic examination confirmed the findings. Radiotracer uptake, diagnostic performance, and TNM (tumor-node-metastasis) classifications were compared. RESULTS: A total of 31 patients with pancreatic carcinoma (all were adenocarcinoma) underwent Al18F-NOTA-FAPI-04 PET/CT, including 20 male and 11 female patients, with a mean age of 58.2 ± 8.5 years. FAPI-04 PET/CT imaging showed a higher value of SUVmax-15min/30min/60min, SUVmean-15min/30min/60min, TBR1, and TBR2 in pancreatic carcinoma than FDG (all P < 0.01). The mean level of Al18F-NOTA FAPI-04 uptake values of the pancreatic ductal adenocarcinoma was higher than that of pancreatitis in both SUVmax-30min (P < 0.01), SUVmean-30min (P < 0.05), SUVmax-60min (P < 0.01), and SUVmean-60min (P < 0.01). The FAPI △SUVmax-1, △SUVmax-2, and △SUVmean-2 uptake values of pancreatic carcinoma were higher than tumor-associated inflammation (all P < 0.01). TNM staging of 16/31 patients changed after Al18F-NOTA FAPI-04 PET/CT examination with all upstaging changes. CONCLUSION: Al18F-NOTA-FAPI-04 PET/CT at 15 and 30 min also demonstrated an equivalent detection ability of pancreatic lesion to 18F-FDG PET/CT. Delayed-phase Al18F-NOTA-FAPI-04 PET/CT can help differentiate pancreatic carcinoma and tumor-associated inflammation. Al18F-NOTA FAPI-04 PET/CT also performed better than FDG PET/CT in TNM staging. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100051406. Registered 23 September 2021, https://www.chictr.org.cn/showproj.html?proj=133033.

Explore the anti-inflammation mechanism of safflower total flavonoids in the treatment of endometritis based on celluar transcriptomics.

OBJECTIVES: Safflower is a traditional Chinese medicine for the treatment of gynecological diseases and its flavonoids have potential anti-inflammatory effects. The purpose is to explore the possible effects of safflower total flavonoids (STF) on lipopolysaccharide (LPS)-induced inflammatory damage of Ishikawa cells. METHOD: In this study, LPS-induced endometrial carcinoma Ishikawa cells were used to establish an inflammatory injury model. The effective concentration of STF was screened by CCK-8 and enzyme-linked immunosorbent assay. The apoptosis of damaged Ishikawa cells was detected by flow cytometry. The contents of caspase11 and caspase 3 in Ishikawa cells were observed by fluorescence imaging. Western blot and RT-qPCR were used to detect the expression of related proteins and mRNA in damaged Ishikawa cells, and the possible mechanism of safflower flavonoids against LPS-induced endometrial carcinoma Ishikawa cells was analyzed by cell transcriptomics. KEY FINDINGS: The STF-reduced tumor necrosis factor α, interleukin-1ß, and interleukin-6 expression level; the expression level of the proteins ASK1, Caspase3, and Caspase11 was also significantly decreased, and the proteins ERα, p-PI3K, and p-AKT were significantly increased. The transcriptome results showed that the PI3K-Akt signal pathway may be the main signal pathway for the STF. CONCLUSION: The STF could regulate the PI3K/AKT signal pathway to treat the inflammatory injury of Ishikawa cells.