A novel halloysite nanotubes-based hybrid monolith for in-tube solid-phase microextraction of polar cationic pesticides.

The accurate determination of polar cationic pesticides in food poses a challenge due to their high polarity and trace levels in complex matrices. This study hypothesized that the use of halloysite nanotubes (HNTs) can significantly enhance the extraction efficiency and sensitivity of these analytes because of their rich hydroxyl groups and cation exchange sites. Therefore, we chemically incorporated HNTs with organic polymer monoliths for in-tube solid-phase microextraction (SPME). This novel hybrid monolith extended service life, improved adsorption capacity, and exhibited excellent extraction performance for polar cationic pesticides. Based on these advancements, a robust and sensitive in-tube SPME-HILIC-MS/MS method was constructed to determine trace levels of polar cationic pesticides in complex food matrices. The method achieved limits of detection of 1.9, 2.1, and 0.1 µg/kg for maleic hydrazide, amitrole, and cyromazine, respectively. The spiked recoveries in five food samples ranged from 80.2 to 100.8%, with relative standard deviations below 10.7%.

Acidic Electrolyzed Water Maintains the Storage Quality of Postharvest Wampee Fruit by Activating the Disease Resistance.

Harvested wampee fruit is susceptible to disease, resulting in postharvest losses. Acidic electrolyzed water (AEW), a safe and innovative sterilization technology, plays a role in enhancing disease resistance in harvested produce. In this study, the efficacy of AEW in delaying wampee disease development was assessed, along with its association with disease resistance metabolism. Wampee fruit was treated with AEW (pH 2.5) at different available chlorine concentrations (ACCs) (20, 40, 60, and 80 mg/L) and subsequently stored at 25 °C for 8 days. Results revealed that 40 mg/L ACC in AEW (pH 2.5) was most effective in improving the postharvest quality of wampee fruit. Compared with control wampee fruit, those treated with 40 mg/L ACC in AEW exhibited lower incidence of fruit disease, higher pericarp lignin content, and higher activities of pericarp disease resistance enzymes (DREs), such as cinnamate-4-hydroxylase, phenylalanine ammonia-lyase, chitinase, ß-1,3-glucanase, polyphenol oxidase, 4-coumarate CoA ligase, and cinnamyl alcohol dehydrogenase. These results suggested that AEW elevated DRE activities, promoted lignin accumulation, and ultimately enhanced disease resistance, suppressed disease development, and improved storage quality in harvested wampee fruit. Consequently, AEW emerged as a safe technology to mitigate the disease development and enhance the storage quality of harvested wampee fruit.

A Two-Decade Bibliometric Analysis of Laser in Ophthalmology: From Past to Present.

Background: Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends. Methods: We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. Results: From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies. Conclusion: This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.

Personalized prediction of diabetic foot ulcer recurrence in elderly individuals using machine learning paradigms.

BACKGROUND: This study utilizes machine learning to analyze the recurrence risk of diabetic foot ulcers (DFUs) in elderly diabetic patients, aiming to enhance prevention and intervention efforts. OBJECTIVE: The goal is to construct accurate predictive models for assessing the recurrence risk of DFUs based on high-risk factors, such as age, blood sugar control, alcohol consumption, and smoking, in elderly diabetic patients. METHODS: Data from 138 elderly diabetic patients were collected, and after data cleaning, outlier screening, and feature integration, machine learning models were constructed. Support Vector Machine (SVM) was employed, achieving an accuracy rate of 93%. RESULTS: Experimental results demonstrate the effectiveness of SVM in predicting the recurrence risk of DFUs in elderly diabetic patients, providing clinicians with a more accurate tool for assessment. CONCLUSIONS: The study highlights the significance of machine learning in managing foot ulcers in elderly diabetic patients, particularly in predicting recurrence risk. This approach facilitates timely intervention, reducing the likelihood of patient recurrence, and introduces computer-assisted medical strategies in elderly diabetes management.

Autonomous Feedback-Driven Engineered DNAzyme-Coated Trojan Horse-like Nanocapsules for On-Demand CRISPR/Cas9 Delivery.

Manipulating the expression of cellular genes through efficient CRISPR/Cas9 delivery is rapidly evolving into a desirable tumor therapeutics. The exposure of CRISPR/Cas9 to a complex external environment poses challenges for conventional delivery carriers in achieving responsive and accurate release. Here, we report a Trojan horse-like nanocapsule for the on-demand delivery of CRISPR/Cas9 in a microRNA-responsive manner, enabling precise tumor therapy. The nanocapsule comprises a nanoassembled, engineered DNAzyme shell encasing a Cas9/sgRNA complex core. The DNAzyme, functioning as a catalytic unit, undergoes a conformational change in the presence of tumor-associated microRNA, followed by activating a positive feedback-driven autonomous catabolic cycle of the nanocapsule shell. This catabolic cycle is accomplished through chain reactions of DNAzyme "cleavage-hybridization-cleavage", which ensures sensitivity in microRNA recognition and effective release of Cas9/sgRNA. Utilizing this Trojan horse-like nanocapsule, as low as 1.7 pM microRNA-21 can trigger the on-demand release of Cas9/sgRNA, enabling the specific editing of the protumorigenic microRNA coding gene. The resulting upregulation of tumor suppressor genes induces apoptosis in tumor cells, leading to significant inhibition of tumor growth by up to 75.94%. The Trojan horse-like nanocapsule, with superior programmability and biocompatibility, is anticipated to serve as a promising carrier for tailoring responsive gene editing systems, achieving enhanced antitumor specificity and efficacy.

Gastrointestinal syndrome encountered during a train voyage to high altitudes: A 14-day survey of 69 passengers in China.

BACKGROUND: The diagnosis and evaluation of the severity of acute mountain sickness (AMS) continue to be problematic due to a lack of consensus on the inclusion of symptoms in a scoring system. Recent investigations highlight the significance of gastrointestinal symptoms in identifying this condition. However, the specific gastrointestinal symptoms associated with AMS have not been thoroughly elucidated in previous studies, and the underlying risk factors remain inadequately comprehended. METHODS: This study aimed to investigate the characteristics, trends, and risk factors related to gastrointestinal symptoms encountered during train travel to high altitude. A total of 69 passengers, specifically all with medical backgrounds, were surveyed 6 times over a period of 14 days. RESULTS: The daily incidence of abdominal discomfort was higher than non-gastrointestinal symptoms within 14 days. Gastrointestinal symptoms demonstrated a greater prevalence, longer duration, and increased risk compared to non-gastrointestinal symptoms, such as headaches. The symptoms of abdominal distension and bowel sound hyperaction were found to be prevalent and persistent among patients diagnosed with AMS, exhibiting a high incidence rate. Gender, age, body mass index (BMI), smoking habits, and alcohol consumption were identified as risk factors associated with the occurrence and duration of gastrointestinal symptoms. CONCLUSION: This study suggests that gastrointestinal symptoms are more common and persistent when traveling to the plateau by train. These symptoms should be taken into consideration in the further diagnosis and prevention of AMS. Therefore, this study provides a significant theoretical foundation for the prevention and treatment of AMS.

Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach.

Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.

Anti-cancer agent piperlongumine is an inhibitor of transient receptor potential melastatin 7 channel in oral squamous cell carcinoma.

OBJECTIVES: To elucidate the association between the anticancer activities of piperlongumine (PL) and its potential target, transient receptor potential melastatin 7 channel (TRPM7), in oral squamous cell carcinoma (OSCC). METHODS: The expression levels and electrical characteristics of TRPM7 as well as cell viability in response to various PL treatments were investigated in the OSCC cell line Cal27. RESULTS: PL treatment resulted in a concentration- and time-dependent reduction in TRPM7 mRNA and protein expression in Cal27 cells. Furthermore, PL treatment inhibited TRPM7-like rectifying currents in Cal27 cells; however, this inhibition was less effective than that of the TRPM7 antagonist waixenicin A. Rapid perfusion and washout experiments revealed an immediate inhibitory effect of PL on TRPM7-like currents. The antagonistic effect of PL occurred within 1 min and was not completely reversed following washout. Notably, the extracellular Ca2+ concentration still influenced PL-induced changes in the TRPM7-like current, indicating that PL can directly but gently antagonize the TRPM7 channel. Functional changes in TRPM7 correlated with the observed antiproliferative and cytotoxic effects of PL in Cal27 cells. CONCLUSIONS: These findings suggest that PL exhibits potent inhibitory effects on TRPM7 and exerts its anti-cancer effects by downregulating TRPM7 expression and antagonizing channel currents.

Advance Care Planning Affects End-of-Life Treatment Preferences Among Patients With Heart Failure: A Randomized Controlled Trial.

This study explored the effects of advance care planning interventions on end-of-life treatment decisions among patients with heart failure. The study design was a randomized controlled trial. An intervention involving a motivational video, a cartoon version educational brochure, and a guided discussion was implemented. A total of 82 hospitalized patients with heart failure were recruited. Half of the participants received the intervention, and the other half received routine care. The Life Support Preferences Questionnaire was the primary measurement instrument. Before the advance care planning intervention, a significant difference between the experimental and control groups was observed in the cardiopulmonary resuscitation score but not the total, antibiotics, surgery, and artificial nutrition and hydration scores. In the experimental group but not in the control group, significant differences were observed between pretest and posttest total, antibiotics, cardiopulmonary resuscitation, surgery, and artificial nutrition and hydration scores. Significant differences in mean score changes were observed in total and each treatment score between the experimental and control groups. The advance care planning intervention led participants to select fewer medical treatments. This intervention may be suitable for societies where people are unfamiliar with advance care planning and may feel uncomfortable discussing death.

Advances in Research on Marine-Derived Lipid-Lowering Active Substances and Their Molecular Mechanisms.

Hyperlipidemia (HLP) is a metabolic disorder caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing year by year. In addition, lipid-lowering drugs currently in clinical use have shown significant improvement in blood lipid levels, but are accompanied by certain side effects. However, bioactive marine substances have been shown to possess a variety of physiological activities such as hypoglycemic, antioxidant, antithrombotic and effects on blood pressure. Therefore, the hypolipidemic efficacy of marine bioactive substances with complex and diverse structures has also attracted attention. This paper focuses on the therapeutic role of marine-derived polysaccharides, unsaturated fatty acids, and bioactive peptides in HLP, and briefly discusses the main mechanisms by which these substances exert their hypolipidemic activity in vivo.

Resveratrol inhibits TGF-ß1-induced fibrotic effects in human pterygium fibroblasts.

BACKGROUND: Resveratrol is a polyphenolic phytoalexin which has the properties of anti-oxidant, anti-inflammatory and anti-fibrotic effects. The aim of this study was to investigate the anti-fibrotic effects of resveratrol in primary human pterygium fibroblasts (HPFs) and elucidate the underlying mechanisms. METHOD: Profibrotic activation was induced by transforming growth factor-beta1 (TGF-ß1). The expression of profibrotic markers, including type 1 collagen (COL1), α-smooth muscle actin (α-SMA), and fibronectin, were detected by western blot and quantitative real-time-PCR after treatment with various concentrations of resveratrol in HPFs to investigate the anti-fibrotic effects. Relative signaling pathways downstream of TGF-ß1 were detected by Western blot to assess the underlying mechanism. Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry to evaluate proliferation and drug-induced cytotoxicity. Cell migration and contractile phenotype were detected through wound healing assay and collagen gel contraction assay. RESULTS: The expression of α-SMA, FN and COL1 induced by TGF-ß1 were suppressed by treatment with resveratrol in dose-dependent manner. The Smad3, mitogen-activated protein kinase (p38 MAPK) and phosphatidylinositol-3-kinase (PI3K) / protein kinase B (AKT) pathways were activated by TGF-ß1, while resveratrol attenuated those pathways. Resveratrol also inhibited cellular proliferation, migration and contractile phenotype, and induced apoptosis in HPFs. CONCLUSIONS: Resveratrol inhibit TGF-ß1-induced myofibroblast activation and extra cellular matrix synthesis in HPFs, at least partly, by regulating the TGF-ß/Smad3, p38 MAPK and PI3K/AKT pathways.

Epigenetics research in eye diseases: a bibliometric analysis from 2000 to 2023.

CLINICAL RELEVANCE: A bibliometric analysis is a quantitative study that utilises methods such as citation analysis to evaluate research performance. A bibliometric analysis could provide a valuable reference for ophthalmic researchers to understand the trends in epigenetics research. BACKGROUND: The number of studies on epigenetics in eye diseases has exceeded 5,000, but the progress and scope of epigenetic research on eye diseases remain unclear. The study aimed to bibliometrically analyse epigenetic research conducted in eye diseases. METHODS: Studies concerning epigenetic research on eye diseases from 2000-2023 were searched using the Web of Science Core Collection. Following this, the included studies were analysed for citations, journals, keywords, authors, and countries, using the Bibliometrix package in R Studio. RESULTS: In total, 3758 studies were included in the analysis, including 3099 original articles, 599 reviews, 11 editorials, and 49 early access articles. Investigative Ophthalmology & Visual Science was the most published journal with 185 articles, and Proceedings of the National Academy of Sciences of the United States of America was the most cited journal, with 8727 citations. The journal with the highest h-index was Oncogene (h-index = 38).Renu A Kowluru from the Kresge Eye Institute, Wayne State University, Detroit, USA, had the most citations with 1,690 and the highest h-index (h-index = 23). China and the USA were the countries with the highest number of publications (1739) and total citations (40533), respectively. Furthermore, from 2000-2023, the top five frequent research topics were diabetic retinopathy, 522; microribonucleic acid, 469; retinoblastoma, 370; apoptosis, 268; and epigenetics, 206. CONCLUSIONS: The results of this bibliometric study provide the current status and trends of epigenetic research in eye diseases and will help researchers identify areas of current interest in the field, which should help highlight new research directions.

Integrated spatial transcriptomics and lipidomics of precursor lesions of pancreatic cancer identifies enrichment of long chain sulfatide biosynthesis as an early metabolic alteration.

Background: The development of diverse spatial profiling technologies has provided an unprecedented insight into molecular mechanisms driving cancer pathogenesis. Here, we conducted the first integrated cross-species assessment of spatial transcriptomics and spatial metabolomics alterations associated with progression of intraductal papillary mucinous neoplasms (IPMN), bona fide cystic precursors of pancreatic ductal adenocarcinoma (PDAC). Methods: Matrix Assisted Laster Desorption/Ionization (MALDI) mass spectrometry (MS)-based spatial imaging and Visium spatial transcriptomics (ST) (10X Genomics) was performed on human resected IPMN tissues (N= 23) as well as pancreata from a mutant Kras;Gnas mouse model of IPMN. Findings were further compared with lipidomic analyses of cystic fluid from 89 patients with histologically confirmed IPMNs, as well as single-cell and bulk transcriptomic data of PDAC and normal tissues. Results: MALDI-MS analyses of IPMN tissues revealed long-chain hydroxylated sulfatides, particularly the C24:0(OH) and C24:1(OH) species, to be selectively enriched in the IPMN and PDAC neoplastic epithelium. Integrated ST analyses confirmed that the cognate transcripts engaged in sulfatide biosynthesis, including UGT8, Gal3St1 , and FA2H , were co-localized with areas of sulfatide enrichment. Lipidomic analyses of cystic fluid identified several sulfatide species, including the C24:0(OH) and C24:1(OH) species, to be significantly elevated in patients with IPMN/PDAC compared to those with low-grade IPMN. Targeting of sulfatide metabolism via the selective galactosylceramide synthase inhibitor, UGT8-IN-1, resulted in ceramide-induced lethal mitophagy and subsequent cancer cell death in vitro , and attenuated tumor growth of mutant Kras;Gnas allografts. Transcript levels of UGT8 and FA2H were also selectively enriched in PDAC transcriptomic datasets compared to non-cancerous areas, and elevated tumoral UGT8 was prognostic for poor overall survival. Conclusion: Enhanced sulfatide metabolism is an early metabolic alteration in cystic pre-cancerous lesions of the pancreas that persists through invasive neoplasia. Targeting sulfatide biosynthesis might represent an actionable vulnerability for cancer interception.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke.

BACKGROUND AND PURPOSE: The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). METHODS: We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. RESULTS: IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237-0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. CONCLUSIONS: Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Comprehensive analyses of membrane lipids and phenolics metabolisms reveal the developments of chilling injury and browning in Chinese olives during cold storage.

The impacts of chilling injury (CI) temperature (2 °C) and non-CI temperature (8 °C) on the CI development, browning occurrence, and its underlying mechanism in Chinese olives were investigated. The results showed that, 2 °C induced higher levels of CI index, browning degree, chromaticity a* and b* values, but lower values of h°, chlorophyll and carotenoid contents in Chinese olives as compared to 8 °C. Furthermore, 2 °C raised cell membrane permeability, increased the activities of phospholipase D, lipase and lipoxygenase, accelerated the hydrolyses of phosphatidylcholine and phosphatidylinositol to phosphatidic acid, and promoted the conversions of unsaturated fatty acids to saturated fatty acids in Chinese olives. Moreover, 2 °C-stored Chinese olives showed higher activities of peroxidase and polyphenol oxidase, but lower contents of tanin, flavonoid and phenolics. These findings demonstrated that the CI and browning developments in Chinese olives were closely associated with the metabolisms of membrane lipid and phenolics.

[Research advance on the role of pro-inflammatory cytokines in sepsis].

Sepsis, a series of pathophysiological abnormalities caused by infection, is also one of the most important factors of death and disability in infected patients all over the world, so it has always been the focus of the medical community. Cytokines are small molecule proteins secreted by cells with biological activity, involved in the immune and inflammatory regulation of sepsis. Many studies using cytokine targeting to treat sepsis have achieved beneficial effects, and the level of cytokines is also believed to be related to the development, severity of sepsis, so they are reliable biomarkers of sepsis. Among them, pro-inflammatory cytokines such as interferon-ß (IFN-ß) and interleukins (IL-1ß, IL-3, IL-6, and IL-7) are the focus of the discussion in this review. IFN-ß and IL-1ß are double-sided in the treatment of sepsis, namely early low-dose treatment can reduce sepsis by restoring the function of immune cells and play a protective effect, but they are also related to severe inflammatory response of sepsis and can aggravate the mortality of sepsis patients. IL-3 and IL-6 focus more on enhancing inflammatory factors and play a damage role. IL-7 mainly participates in immune regulation, promoting lymphocyte activation and protecting sepsis.

Slightly acidic electrolyzed water treatment improves the quality and storage properties of carambola fruit.

This study aimed to explore the impacts of slightly acidic electrolyzed water (SAEW) treatment on the physiology, quality, and storage properties of postharvest carambola. The carambolas were immersed in SAEW with a pH value of 6.0, ORP of 1340 mV and ACC of 80 mg/L. Results demonstrated that SAEW could significantly reduce the respiration rate, inhibit the increase in cell membrane permeability, and delay apparent color change. Relatively higher contents of bioactive compounds and nutritional components, such as flavonoids, polyphenols, reducing sugars, sucrose, vitamin C, total soluble sugar, and total soluble solid, as well as higher titratable acidity were maintained in SAEW-treated carambola. In addition, SAEW-treated carambola exhibited a higher commercial acceptability rate and a higher firmness, but lower weight loss and peel browning index than control fruits. Our results indicated that SAEW treatment achieved high fruit quality and nutritional values, potentially contributing to improve storage properties of harvested carambola.

c-MYC-Driven Polyamine Metabolism in Ovarian Cancer: From Pathogenesis to Early Detection and Therapy.

c-MYC and its paralogues MYCN and MYCL are among the most frequently amplified and/or overexpressed oncoproteins in ovarian cancer. c-MYC plays a key role in promoting ovarian cancer initiation and progression. The polyamine pathway is a bona fide target of c-MYC signaling, and polyamine metabolism is strongly intertwined with ovarian malignancy. Targeting of the polyamine pathway via small molecule inhibitors has garnered considerable attention as a therapeutic strategy for ovarian cancer. Herein, we discuss the involvement of c-MYC signaling and that of its paralogues in promoting ovarian cancer tumorigenesis. We highlight the potential of targeting c-MYC-driven polyamine metabolism for the treatment of ovarian cancers and the utility of polyamine signatures in biofluids for early detection applications.

Kynureninase Upregulation Is a Prominent Feature of NFR2-Activated Cancers and Is Associated with Tumor Immunosuppression and Poor Prognosis.

The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is frequently activated in various cancer types. Aberrant activation of NRF2 in cancer is attributed to gain-of-function mutations in the NRF2-encoding gene NFE2L2 or a loss of function of its suppressor, Kelch-like ECH-associated protein 1 (KEAP1). NRF2 activation exerts pro-tumoral effects in part by altering cancer cell metabolism. Previously, we reported a novel mechanism of NRF2 tumoral immune suppression through the selective upregulation of the tryptophan-metabolizing enzyme kynureninase (KYNU) in lung adenocarcinoma. In the current study, we explored the relevance of NRF2-mediated KYNU upregulation across multiple cancer types. Specifically, using a gene expression dataset for 9801 tumors representing 32 cancer types from The Cancer Genome Atlas (TCGA), we demonstrated that elevated KYNU parallels increased gene-based signatures of NRF2-activation and that elevated tumoral KYNU mRNA expression is strongly associated with an immunosuppressive tumor microenvironment, marked by high expression of gene-based signatures of Tregs as well as the immune checkpoint blockade-related genes CD274 (PDL-1), PDCD1 (PD-1), and CTLA4, regardless of the cancer type. Cox proportional hazard models further revealed that increased tumoral KYNU gene expression was prognostic for poor overall survival in several cancer types, including thymoma, acute myeloid leukemia, low-grade glioma, kidney renal papillary cell carcinoma, stomach adenocarcinoma, and pancreatic ductal adenocarcinoma (PDAC). Using PDAC as a model system, we confirmed that siRNA-mediated knockdown of NRF2 reduced KYNU mRNA expression, whereas activation of NFE2L2 (the coding gene for NRF2) through either small-molecule agonists or siRNA-mediated knockdown of KEAP1 upregulated KYNU in PDAC cells. Metabolomic analyses of the conditioned medium from PDAC cell lines revealed elevated levels of KYNU-derived anthranilate, confirming that KYNU was enzymatically functional. Collectively, our study highlights the activation of the NRF2-KYNU axis as a multi-cancer phenomenon and supports the relevance of tumoral KYNU as a marker of tumor immunosuppression and as a prognostic marker for poor overall survival.

DNP and ATP regulate the breakdown occurrence in the pulp of Phomopsis longanae Chi-infected longan fruit through modulating the metabolism of membrane lipid.

This study aimed to illustrate how DNP and ATP affected the pulp breakdown occurrence in P. longanae-infected longan and their relationship with the membrane lipid metabolism. Compared with P. longanae-inoculated samples, the pulp of DNP-treated P. longanae-infected longan exhibited higher cellular membrane permeability, breakdown index, activities of PI-PLC, PLD, PC-PLC, LOX, and lipase, and values of SFAs, PA, and DAG, while lower levels of PI, PC, USFAs, IUFA and U/S. However, the opposite findings were observed in ATP-treated P. longanae-infected longan. The data manifested that DNP-increased the pulp breakdown occurrence in P. longanae-inoculated samples was due to the elevated MLDEs activities that reduced the contents of phospholipids (PI, PC) and USFAs, disrupting the cell membrane structures. Nevertheless, ATP decreased the pulp breakdown occurrence in P. longanae-inoculated samples, which was ascribed to the reduced MLDEs activities that raised phospholipids (PI, PC) and USFAs contents, thus maintaining the cell membrane structures.