Loss of GCN5L1 exacerbates damage in alcoholic liver disease through ferroptosis activation.

BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD. RESULTS: Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol-induced ferroptosis. GCN5L1-modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure. CONCLUSION: Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol-induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol-induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.

Compilation of a self-management assessment scale for postoperative patients with aortic dissection.

Objective: The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods: The initial version of the "postoperative self-management assessment scale for patients with aortic dissection" was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the "postoperative self-management assessment scale for patients with aortic dissection." A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results: The formal version of the scale had 6 dimensions and 35 entries. The Cronbach's α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test-retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker-Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2/df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion: We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

FeSe2 and Its Composites for Pollutants Removal: Synthesis, Mechanisms, and Application Potential.

In recent years, the research of FeSe2 and its composites in environmental remediation has been gradually carried out. And the FeSe2 materials show great catalytic performance in photocatalysis, electrocatalysis, and Fenton-like reactions for pollutants removal. Therefore, the studies and applications of FeSe2 materials are reviewed in this work, including the common synthesis methods, the role of Fe and Se species as well as the catalyst structure, and the potential for practical environmental applications. Hereinto, it is worth noting in particular that the lower-valent Se (Se2- ), unsaturated Se (Se- ), and Se vacancies (VSe ) can play different roles in promoting pollutants removal. In addition, the FeSe2 material also demonstrates high stability, reusability, and adaptability over a wider pH range as well as universality to different pollutants. In view of the overall great properties and performance of FeSe2 materials compared with other typical Fe-based materials, it deserves and needs further research. And finally, this paper presents some challenges and perspectives in future development, looking forward to providing helpful guidance for the subsequent research of FeSe2 and its composites for environmental application.

A new generation of structural biologists in China.

We have asked young scientists who spoke at our recent Cell Symposium "Structural biology from the nanoscale to cellular mesoscale" in Huangshan, China to tell us more about themselves and their exciting research in this collection of Voices.

Dataset on the tested and simulated response of thick cold-formed circular hollow sections under cyclic loading.

This article describes a dataset used to calibrate a finite element model of a thick circular hollow section (CHS) with varying d/t (diameter to thickness) ratio under cyclic loading which may be used as a computational model validation benchmark by researchers working on similar problems in structural and mechanical engineering. The test data consists of seven cold-formed S335J2H steel CHS tube specimens tested to buckling failure in low-cycle fatigue under a three-point bending arrangement, instrumented with discrete strain gauges, displacement transducers and string potentiometers together with continuous surface deformation fields obtained by two pairs of digital image correlation (DIC) cameras. 'Half-cycle' material data from the uniaxial tensile testing of dog-bone coupons is also provided. Comparisons between measured and simulated entities such as midspan forces, moments, displacements and mean curvatures can be obtained with MATLAB processing scripts. Complete ABAQUS model input files are also provided to aid in benchmarking.

Utilizing physician modified fenestration on the castor branched stent technique for reconstruction of an isolated left vertebral artery on the aortic arch.

The study aimed to provide physician modified fenestration (PMF) on a single-branched stent for the aortic arch (Castor) to protect the isolated left vertebral artery (ILVA) during thoracic endovascular aortic repair (TEVAR). Patients who underwent TEVAR involving ILVA reconstruction through PMF performing on the Castor branched stent were included in a retrospective, multi-centre study from June 2018 to December 2022. In these patients, all proximal landing zones of "Castor" were positioned in Ishimaru zone 2a. A total of twenty-five patients met the inclusion criteria and the achievement rate showed 25/25 (100%) success in them. The twenty-five patients had a median follow-up length of 28.5 ± 14.6 months. One patient (4.0%) suffered from postoperative ischemic stroke before discharge. One patient (4.0%) died from a hemodialysis-related brain hemorrhage before discharge on the 29th day after the procedure. One patient died of advanced liver cancer in the 33th month after discharge. Aortic rupture, stroke or spinal cord injury did not occur throughout the follow-up period after discharge. Two patients (8.0%) experienced endoleak at the fenestration, however, resulting in only one's necessity for reintervention. Notably, the procedure effectively maintained ILVAs patency for all patients during follow up. According to our preliminary findings, performing a TEVAR under local anaesthesia using PMF on a Castor branched stent for ILVA preservation appeared practical, secure, and effective.

Investigating the correlation of delirium after cardiac surgery with memories and posttraumatic stress disorder consequences of intensive care unit: A prospective cohort study.

OBJECTIVES: To explore the differences in post-intensive care unit memory and posttraumatic stress disorder symptoms between patients with and without delirium, and assess the correlations between the two. DESIGN: Prospective cohort observation study. SETTING: A cardiac intensive care unit of a tertiary hospital in China. We enrolled 318 consecutive patients after cardiac surgery between December 2017 and March 2019. MAIN OUTCOME MEASURES: Delirium was assessed using the Confusion Assessment Method for the ICU from intensive care unit admission to discharge. Intensive care unit memory was assessed using the ICU-Memory Tool through face-to-face interviews one week after discharge. Posttraumatic stress disorder was measured telephonically using the Impact of Events Scale-revised questionnaire at three months post-discharge. RESULTS: Eighty patients each in the delirium and non-delirium groups were enrolled for follow-up interviews. Patients with delirium had vaguer memories of pre-intensive care unit admission and of their stay, and recollected more memories of feelings (vs. without delirium). Posttraumatic stress disorder was diagnosed in 14 patients with and in seven without delirium, with non-significant differences between groups. Delirium did not influence post-intensive care unit factual, feeling, and delusional memories, nor posttraumatic stress disorder and hyperarousal, intrusion, and avoidance. The memories of feelings were positively correlated with the last three (r = 0.285, r = 0.390 and r = 0.373, respectively). CONCLUSION: Patients with delirium had vague intensive care unit memories. Memories of feelings were positively correlated with symptoms of hyperarousal, intrusion, and avoidance. Delirium did not influence factual, feeling, or delusional memories nor posttraumatic stress disorder incidence and symptoms. IMPLICATIONS FOR CLINICAL PRACTICE: Interventions are needed to reduce the impact of vague memory in patients with post-intensive care unit delirium. Memories of feelings should be focused on because of their correlation with hyperarousal, intrusion, and avoidance. Delirium prevention and early recognition measures are suggested.

circNINL facilitates aerobic glycolysis, proliferation, invasion, and migration in lung cancer by sponging miR-3918 to mediate FGFR1 expression.

Previously characterized as an oncogenic player in breast cancer, the function of circular RNA NINL (circNINL) in lung cancer (LC) remained elusive. This study aimed to delineate the biological role of circNINL in LC and to unveil its potential molecular mechanisms. We discovered elevated expression levels of circNINL and Fibroblast Growth Factor Receptor 1 (FGFR1) concomitant with diminished expression of microRNA-3918 (miR-3918) in LC specimens. Knockdown of circNINL led to a marked decrease in cell proliferation, migration, invasion, and aerobic glycolysis, alongside an upsurge in apoptosis in LC cells. Either downregulation of miR-3918 or overexpression of FGFR1 mitigated the suppressive impact of circNINL knockdown on LC pathogenesis. Mechanistic studies validated that circNINL served as a competitive endogenous RNA for miR-3918, thus influencing FGFR1 expression. Further, in vivo experiments using nude mouse xenograft models underscored that silencing circNINL substantially curtailed tumor growth in LC. Collectively, these findings illuminate that circNINL exacerbates LC malignancy via the miR-3918/FGFR1 axis, a process integrally linked with the activation of aerobic glycolysis.

Three new species of Cortinarius section Delibuti (Cortinariaceae, Agaricales) from China.

Three new species of CortinariussectionDelibuti, namely C.fibrillososalor, C.pseudosalor, and C.subtropicus are described as new to science based on morphological and phylogenetic evidences. Cortinariuspseudosalor is extremely morphologically similar to C.salor, but it differs from the latter by smaller coarsely verrucose basidiospores. Cortinariusfibrillososalor can be easily differentiated by its fibrillose pileus. The pileus of C.subtropicus becomes brown without lilac tint at maturity comparing with other members of section Delibuti. A combined dataset of ITS and LSU sequences was used for phylogenetic analysis. The phylogenetic reconstruction of section Delibuti revealed that these three new species clustered and formed independent lineages with full support respectively. A key to the three new species and related species of section Delibuti is provided in this work.

Long-term NO2 exposure and mortality: A comprehensive meta-analysis.

In response to the World Health Organization's (WHO) revised annual mean nitrogen dioxide (NO2) standard from 40 µg/m3 to 10 µg/m3, reflecting the growing evidence linking long-term exposure to ambient NO2 and excess mortality, we conducted a comprehensive meta-analysis incorporating 11 new studies published since the WHO analysis. Our investigation involved a systematic search of three major databases (PubMed, Web of Science, and Scopus) for articles published until July 1, 2022. We employed random effects models to calculate summarized risk ratios (RR) along with 95% confidence intervals (CIs) for overall and subgroup analyses. Sensitivity analyses were conducted to assess result robustness, and publication bias was evaluated using funnel plots and Egger's linear regression. Out of 2799 identified articles, 56 were included in our meta-analysis. The findings indicate a heightened risk of all-cause, cardiovascular, and respiratory mortality associated with long-term exposure to ambient NO2, with pooled RR values of 1.03 (95% CI: 1.02, 1.05), 1.07 (95% CI: 1.04, 1.10), and 1.03 (95% CI: 1.02, 1.05) per 10 µg/m3 increase, respectively. Substantial heterogeneity (I2 = 84%-96%) among studies was observed. Subgroup analysis revealed significantly elevated RR values in Asia and Oceania (p-value <0.05). The aggregated values for all-cause and cardiovascular mortality were slightly larger than those reported in previous studies. Our study emphasizes the imperative to develop more patient cohorts and conduct age-refined analyses to explore the impact of existing chronic diseases on these associations. Further, additional cohorts in Asia and Oceania are essential to fortify evidence in these regions. Lastly, we recommend using fused multi-source data with higher spatiotemporal resolution for individual exposure representation to minimize heterogeneity among studies in future research.

Transfer Learning in Large-scale Gaussian Graphical Models with False Discovery Rate Control.

Transfer learning for high-dimensional Gaussian graphical models (GGMs) is studied. The target GGM is estimated by incorporating the data from similar and related auxiliary studies, where the similarity between the target graph and each auxiliary graph is characterized by the sparsity of a divergence matrix. An estimation algorithm, Trans-CLIME, is proposed and shown to attain a faster convergence rate than the minimax rate in the single-task setting. Furthermore, we introduce a universal debiasing method that can be coupled with a range of initial graph estimators and can be analytically computed in one step. A debiased Trans-CLIME estimator is then constructed and is shown to be element-wise asymptotically normal. This fact is used to construct a multiple testing procedure for edge detection with false discovery rate control. The proposed estimation and multiple testing procedures demonstrate superior numerical performance in simulations and are applied to infer the gene networks in a target brain tissue by leveraging the gene expressions from multiple other brain tissues. A significant decrease in prediction errors and a significant increase in power for link detection are observed.

Development of Emulsion Gels Stabilized by Chitosan and Octenyl Succinic Anhydride-Modified ß-Cyclodextrin Complexes for ß-Carotene Digestion and 3D Printing.

ß-cyclodextrin (ß-CD)-based emulsion gels encapsulated with nutrition for three-dimensional (3D) printing are promising, while obstacles such as low bioaccessibility of bioactive compounds and the molding process in food manufacturing hinder their application. This study intended to develop stable composite emulsion gels using the complexes of chitosan (CS) and octenyl succinic anhydride (OSA)-modified ß-CD (OCD) to conquer these challenges. The esterification of OSA generated more negatively charged OCD and ester groups, which aided in the combination of OCD and CS through enhanced electrostatic and hydrogen bonding interactions. The addition of CS improved the emulsification properties of the complexes and acted as a bridge link in the aqueous phase, thereby increasing the gel strength of the composite emulsion gels. Moreover, the encapsulation of ß-carotene destabilized the strength of the emulsion gels by lowering the interfacial tension. The emulsion gel stabilized by OCD3/CS-0.75% at an initial pH not only successfully encapsulated ß-carotene and presented the highest bioaccessibility of 41.88 ± 0.87% in the in vitro digestion but also showed excellent 3D printability. These results provided a promising strategy to enhance the viscoelasticity of ß-CD-based emulsion gels and accelerate their application in bioactive compound delivery systems and 3D food printing.

Analysis of serum calcium change trajectories and prognostic factors in patients with acute type A aortic dissection.

OBJECTIVES: This study aimed to analyze the correlation between serum calcium changes and short-term prognosis of patients with acute type A aortic dissection. METHODS: Patients who underwent acute type A aortic dissection surgery at Fujian Heart Medical Center between June 2019 and June 2021 were retrospectively analyzed. RESULTS: A total of 383 patients were enrolled. According to the changing track of serum calcium in patients after acute type A aortic dissection, three potential category tracks were determined: high-level (n = 85), medium-level (n = 259), and continuous low-level groups (n = 39). Using the medium-level group as the control, regression analysis showed that poor prognosis risk was increased in the group with continuous low serum calcium (odds ratio = 2.454, P < 0.05) and in the group with continuous low serum calcium > 48 h (odds ratio = 3.595, P < 0.05). Age (odds ratio = 1.063, P < 0.001), body mass index (odds ratio = 1.138, P < 0.05), hypertension (odds ratio = 3.697, P < 0.05), and the highest lactic acid within 72 h after surgery(odds ratio = 1.093, P < 0.05) were independent risk factors for poor prognosis after aortic dissection. CONCLUSION: Continuous low serum calcium was an independent predictor of poor prognosis in patients with acute type A aortic dissection.

Preoperative Nutritional Status of Infants with Non-Restricted Ventricular Septal Defect and Its Influence on Postoperative Recovery.

PURPOSE: This study described the preoperative nutritional status of infants with nonrestricted ventricular septal defects (VSDs) and evaluated its effect on postoperative recovery. METHODS: We retrospectively collected data from infants with nonrestricted VSD who received surgical treatment in our hospital from January 2020 to December 2021 and analyzed their preoperative nutritional status and postoperative recovery. RESULTS: Fifty (53.8%) patients were underweight (weight for age Z score (WAZ) ≤-1), and 31 (33.3%) patients were malnourished (WAZ ≤-2). The mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery of patients with WAZ ≤-2 were significantly longer than those of patients with WAZ >-2 (p < 0.05). The results of linear correlation analysis showed that age, WAZ and prealbumin were negatively correlated with mechanical ventilation time, duration of intensive care unit stay and hospital stay time after surgery, respectively. Multiple linear regression analysis showed that mechanical ventilation time = 7.080 - 0.668 WAZ - 0.013 prealbumin - 0.618 age (R2: 0.729, F: 79.773, p: 0.001); duration of intensive care unit admission = 11.775 - 1.385 WAZ - 0.018 prealbumin - 0.102 age (R2: 0.714, F: 74.072, p: 0.001); and hospital stay time = 17.663 - 1.673 WAZ - 0.017 prealbumin - 1.07 age (R2: 0.711, F: 72.842, p: 0.001). CONCLUSION: The incidence of malnutrition in infants with nonrestricted VSD was very high, and malnutrition had a significant adverse effect on postoperative recovery. Malnutrition significantly prolonged mechanical ventilation time, duration of intensive care unit stay and hospital stay after surgery.

Anti-Inflammatory Phomalones from the Deep-Sea-Derived Fungus Trichobotrys effuse FS522.

Four new phomalones A-D (1-4), together with five known analogues (5-9) were isolated from the deep-sea-derived fungus Trichobotrys effuse FS522. Their structures of the new compounds established by analysis of their NMR and HR-ESI-MS spectroscopic data, and the absolute configurations of 2 was determined by electronic circular dichroism (ECD) calculations. compounds 4, 6 and 8 substantially inhibited the production of nitric oxide (NO) with IC50 values of 4.64, 13.90, and 34.07 µM.

Simultaneous infection with Fusarium proliferatum and Prototheca wickerhamii localized at different body sites.

2012 Elsevier Ltd. All rights reserved. Subcutaneous infections caused by two unusual fungi are rare. Here we report an elderly woman with long-term glucocorticoid use who was infected with Fusarium proliferatum on the right dorsum of the hand presenting with a verrucous plaque and Prototheca wickerhamii on the left dorsum of the hand presenting with geographic ulcers with erythematous plaques. The diagnosis was made through histopathological examination of skin samples and fungal culture, with identification through molecular examination. She was successfully treated with voriconazole.

Comprehensive regulatory networks for tomato organ development based on the genome and RNAome of MicroTom tomato.

MicroTom has a short growth cycle and high transformation efficiency, and is a prospective model plant for studying organ development, metabolism, and plant-microbe interactions. Here, with a newly assembled reference genome for this tomato cultivar and abundant RNA-seq data derived from tissues of different organs/developmental stages/treatments, we constructed multiple gene co-expression networks, which will provide valuable clues for the identification of important genes involved in diverse regulatory pathways during plant growth, e.g. arbuscular mycorrhizal symbiosis and fruit development. Additionally, non-coding RNAs, including miRNAs, lncRNAs, and circRNAs were also identified, together with their potential targets. Interacting networks between different types of non-coding RNAs (miRNA-lncRNA), and non-coding RNAs and genes (miRNA-mRNA and lncRNA-mRNA) were constructed as well. Our results and data will provide valuable information for the study of organ differentiation and development of this important fruit. Lastly, we established a database (http://eplant.njau.edu.cn/microTomBase/) with genomic and transcriptomic data, as well as details of gene co-expression and interacting networks on MicroTom, and this database should be of great value to those who want to adopt MicroTom as a model plant for research.

The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study.

The efficacy and safety of nilotinib in pediatric patients with imatinib/dasatinib resistant/intolerant (R/I) or newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP) was demonstrated in the phase 2, open-label DIALOG study. In this final analysis, long-term efficacy and safety are presented for patients who completed 66 cycles (of 28 days) of treatment with nilotinib (230 mg/m2 twice daily) or discontinued early. Overall, 59 patients were enrolled and 58 were treated (R/I, n = 33; ND, n = 25; median time on treatment: 60.5 and 51.9 months, respectively). In the R/I cohort, the cumulative major molecular response (MMR; BCR::ABL1 international scale [IS] ≤ 0.1%) rate was 60.6%, and no patients had a confirmed loss of MMR. Among ND patients, the best overall MMR rate was 76.0%; 3 patients had a confirmed loss of MMR. The cumulative molecular response MR4 (BCR::ABL1IS ≤ 0.01%) and MR4.5 (BCR::ABL1IS ≤ 0.0032%) rates by 66 cycles were 27.3% and 12.1% in the R/I cohort, and 56.0% and 44.0% in the ND cohort, respectively. The safety profile of nilotinib was consistent with those of earlier reports. No on-treatment deaths occurred. These long-term (up to ∼5 years) data support the efficacy and safety of nilotinib in pediatric patients with Ph+ CML-CP. This trial was registered at www.clinicaltrials.gov.uk as #NCT01844765.