ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target

BackgroundAcute Respiratory Distress Syndrome (ARDS) is a common condition in the intensive care unit (ICU) with a high mortality rate, yet the diagnosis rate remains low. Recent studies have increasingly highlighted the role of aging in the occurrence and progression of ARDS. This study is committed to investigating the pathogenic mechanisms of cellular and genetic changes in elderly ARDS patients, providing theoretical support for the precise treatment of ARDS.MethodsGene expression profiles for control and ARDS samples were obtained from the Gene Expression Omnibus (GEO) database, while aging-related genes (ARGs) were sourced from the Human Aging Genomic Resources (HAGR) database. Differentially expressed genes (DEGs) were subjected to functional enrichment analysis to understand their roles in ARDS and aging. The Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning pinpointed key modules and marker genes, with ROC curves illustrating their significance. The expression of four ARDS-ARDEGs was validated in lung samples from aged mice with ARDS using qRT-PCR. Gene set enrichment analysis (GSEA) investigated the signaling pathways and immune cell infiltration associated with TYMS expression. Single-nucleus RNA sequencing (snRNA-Seq) explored gene-level differences among cells to investigate intercellular communication during ARDS onset and progression.ResultsARDEGs are involved in cellular responses to DNA damage stimuli, inflammatory reactions, and cellular senescence pathways. The MEmagenta module exhibited a significant correlation with elderly ARDS patients. The LASSO, RRF, and XGBoost algorithms were employed to screen for signature genes, including CKAP2, P2RY14, RBP2, and TYMS. Further validation emphasized the potential role of TYMS in the onset and progression of ARDS. Immune cell infiltration indicated differential proportion and correlations with TYMS expression. SnRNA-Seq and cell-cell communication analysis revealed that TYMS is highly expressed in endothelial cells, and the SEMA3 signaling pathway primarily mediates cell communication between endothelial cells and other cells.ConclusionEndothelial cell damage associated with aging could contribute to ARDS progression by triggering inflammation. TYMS emerges as a promising diagnostic biomarker and potential therapeutic target for ARDS

Performance of deep learning algorithms to distinguish high-grade glioma from low-grade glioma: A systematic review and meta-analysis

Summary: This study aims to evaluate deep learning (DL) performance in differentiating low- and high-grade glioma. Search online database for studies continuously published from 1st January 2015 until 16th August 2022. The random-effects model was used for synthesis, based on pooled sensitivity (SE), specificity (SP), and area under the curve (AUC). Heterogeneity was estimated using the Higgins inconsistency index (I2). 33 were ultimately included in the meta-analysis. The overall pooled SE and SP were 94% and 93%, with an AUC of 0.98. There was great heterogeneity in this field. Our evidence-based study shows DL achieves high accuracy in glioma grading. Subgroup analysis reveals several limitations in this field: 1) Diagnostic trials require standard method for data merging for AI; 2) small sample size; 3) poor-quality image preprocessing; 4) not standard algorithm development; 5) not standard data report; 6) different definition of HGG and LGG; and 7) poor extrapolation

The longitudinal and regional analysis of bleomycin-induced pulmonary fibrosis in mice by microcomputed tomography

Introduction: Microcomputed tomography (micro-CT) is powerful for assessment of the progression of lung fibrosis in animal model, but current whole lung analysis (WLA) methods are time-consuming. Here, a longitudinal and regional analysis (LRA) method was developed to assess fibrosis easily and quickly by micro-CT. Method: Firstly, we investigated the distribution pattern of lesions in BLM-induced pulmonary fibrosis mice. Then, the VOIs for LRA were selected based on the anatomical locations and we compared the robustness, accuracy, repeatability, analysis time of LRA to WLA. Additionally, LRA was applied to assess different stages of pulmonary fibrosis, and was validated with conventional endpoint measurements (such as lung hydroxyproline and histopathology). Results: The lesions of fibrosis in 66 bleomycin (BLM)-induced pulmonary fibrosis mice were mostly in the middle and upper parts of lungs. By applying LRA, the percentages of high-density voxels in selected volumes of interest (VOIs) were well correlated with that in WLA both at Day 7 and Day 21 after bleomycin induction (R2 = 0.8784 and 0.8464, respectively). The relative standard deviation (RSD) of the percentage of high-density voxels in the VOIs was lower than that of WLA (P < 0.05). The cost time of LRA was shorter than that of WLA (P < 0.05) and the accuracy of LRA was further confirmed by the histological analysis and biochemical quantification of hydroxyproline. Conclusion: LRA is probably an easier and more time-saving method to assess fibrosis formation and evaluate treatment efficacy

Structure Evolution of Iron (Hydr)oxides under Nanoconfinement and Its Implication for Water Treatment

In the development of nanoenabled technologies for large-scale water treatment, immobilizing nanosized functional materials into the confined space of suitable substrates is one of the most effective strategies. However, the intrinsic effects of nanoconfinement on the decontamination performance of nanomaterials, particularly in terms of structural modulation, are rarely unveiled. Herein, we investigate the structure evolution and decontamination performance of iron (hydr)­oxide nanoparticles, a widely used material for water treatment, when confined in track-etched (TE) membranes with channel sizes varying from 200 to 20 nm. Nanoconfinement drives phase transformation from ferrihydrite to goethite, rather than to hematite occurring in bulk systems, and the increase in the nanoconfinement degree from 200 to 20 nm leads to a significant drop in the fraction of the goethite phase within the aged products (from 41% to 0%). The nanoconfinement configuration is believed to greatly slow down the phase transformation kinetics, thereby preserving the specific adsorption of ferrihydrite toward As­(V) even after 20-day aging at 343 K. This study unravels the structure evolution of confined iron hydroxide nanoparticles and provides new insights into the temporospatial effects of nanoconfinement on improving the water decontamination performance

A Novel Virtual Network Embedding Algorithm with Load Balancing in Elastic Optical Networks

This paper proposes a novel load balancing algorithm for virtual network embedding problem in elastic optical networks. Simulation results show the algorithm achieves a better tradeoff between balancing spectrum resource load and reducing spectrum usage. ? 2014 OSA.EI

Discovery of novel benzohydroxamate-based histone deacetylase 6 (HDAC6) inhibitors with the ability to potentiate anti-PD-L1 immunotherapy in melanoma

AbstractIn this study, a novel series of histone deacetylases 6 (HDAC6) inhibitors containing polycyclic aromatic rings were discovered and evaluated for their pharmacological activities. The most potent compound 10c exhibited high HDAC6 inhibitory activity (IC50 = 261 nM) and excellent HDAC6 selectivity (SI = 109 for HDAC6 over HDAC3). 10c also showed decent antiproliferative activity in vitro with IC50 of 7.37–21.84 μM against four cancer cell lines, comparable to that of tubastatin A (average IC50 = 6.10 μM). Further mechanism studies revealed that 10c efficiently induced apoptosis and S-phase arrest in B16-F10 cells. In addition, 10c markedly increased the expression of acetylated-α-tubulin both in vitro and in vivo, without affecting the levels of acetylated-H3 (marker of HDAC1 inhibition). Furthermore, 10c (80 mg/kg) exhibited moderate antitumor efficacy in a melanoma tumour model with a tumour growth inhibition (TGI) of 32.9%, comparable to that (TGI = 31.3%) of tubastatin A. Importantly, the combination of 10c with NP19 (a small molecule PD-L1 inhibitor discovered by us before) decreased tumour burden substantially (TGI% = 60.1%) as compared to monotherapy groups. Moreover, the combination of 10c with NP19 enhanced the anti-tumour immune response, mediated by a decrease of PD-L1 expression levels and increased infiltration of anti-tumour CD8+ T cells in tumour tissues. Collectively, 10c represents a novel HDAC6 inhibitor deserving further investigation as a potential anti-cancer agent

Correction to: Temporal patterns of influenza A subtypes and B lineages across age in a subtropical city, during pre-pandemic, pandemic, and post-pandemic seasons

Following publication of the original article [1], the author reported an error in the title

Distribution and diversity of twelve <i>Curcuma</i> species in China

<p>Genus <i>Curcuma</i> a wild species presents an important source of valuable characters for improving the cultivated <i>Curcuma</i> varieties. Based on the collected germplasms, herbariums, field surveys and other literatures, the ecogeographical diversity of Genus <i>Curcuma</i> and its potential distributions under the present and future climate are analysed by DIVA-GIS. The results indicate Genus <i>Curcuma</i> is distributed over 17 provinces in China, and particularly abundant in Guangxi and Guangdong provinces. The simulated current distributions are close to the actual distribution regions. In the future climate, the suitable areas for four <i>Curcuma</i> species will be extended, while for other three species the regions will be significantly decreased, and thus these valuable resources need protecting.</p