The roles of lncRNA AP001469.3 in clinical implications, immune landscape and carcinogenesis of colorectal cancer.

Background: Previously, long non-coding RNA (lncRNA) gene AP001469.3 was reported to participate in the construction of an immune-related lncRNA signature, which showed promising clinical predictive value in colorectal cancer (CRC) patients. However, the clinical and immunological significance and biological function of AP001469.3 in CRC remain unclear. In this study, we aim to explore the roles of AP001469.3 in CRC progression, thereby opening an avenue for CRC treatment. Methods: Our study collected data from The Cancer Genome Atlas (TCGA) database and investigated the role of AP001469.3 in CRC through bioinformatics analysis. Cell-type Identification By Estimating Relative Subsets Of known RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) methods evaluated the immune infiltration. The biological functions of AP001469.3 in CRC were validated by in vitro experiments. Gene set enrichment analysis (GSEA) was used to estimate the enrichment of functional pathways and gene signatures. Results: In this work, high expression of AP001469.3 was found in CRC and was positively associated with tumor-node-metastasis (TNM) stage in CRC. AP001469.3 expression had a strong relationship with microsatellite instability (MSI) in colon adenocarcinoma (COAD). Additionally, AP001469.3 expression was associated with StromalScore, ImmuneScore, ESTIMATEScore, immune cell infiltration (ICI) levels and immune checkpoint (ICP) genes expression in CRC. Subsequent results showed that immunotherapy could be more effective in CRC patients with low-AP001469.3 expression using the immunophenoscore (IPS). We confirmed that the transcript of AP001469.3 gene ENST00000430259 was highly expressed in CRC tissues and cell lines. In vitro experiments indicated that ENST00000430259 knockdown reduced the proliferation, migration and invasion of CRC cells. Finally, our GSEA results showed that the majority of the differentially enriched signaling pathways between the high- and low-AP001469.3 expression groups were immune-related. Conclusions: Taken together, our study demonstrates that lncRNA gene AP001469.3 is associated with immunological characteristics in CRC and promotes malignant progression of CRC. Moreover, AP001469.3 can be potentially used as an immunotherapeutic indicator and a therapeutic target for CRC patients.

Insights into carbon-neutral treatment of rural wastewater by constructed wetlands: A review of current development and future direction.

In recent years, with the global rise in awareness regarding carbon neutrality, the treatment of wastewater in rural areas is increasingly oriented towards energy conservation, emission reduction, low-carbon output, and resource utilization. This paper provides an analysis of the advantages and disadvantages of the current low-carbon treatment process of low-carbon treatment for rural wastewater. Constructed wetlands (CWs) are increasingly being considered as a viable option for treating wastewater in rural regions. In pursuit of carbon neutrality, advanced carbon-neutral bioprocesses are regarded as the prospective trajectory for achieving carbon-neutral treatment of rural wastewater. The incorporation of CWs with emerging biotechnologies such as sulfur-based autotrophic denitrification (SAD), pyrite-based autotrophic denitrification (PAD), and anaerobic ammonia oxidation (anammox) enables efficient removal of nitrogen and phosphorus from rural wastewater. The advancement of CWs towards improved removal of organic and inorganic pollutants, sustainability, minimal energy consumption, and low carbon emissions is widely recognized as a viable low-carbon approach for achieving carbon-neutral treatment of rural wastewater. This study offers novel perspectives on the sustainable development of wastewater treatment in rural areas within the framework of achieving carbon neutrality in the future.

Therapeutic effect of iridoid and xanthone glycosides components extracted from Swertia Mussotti on calculous cholecystitis and its clinical complications by targeting COX2.

Swertia Mussotti is used as febrifuge, analgesic and to treat calculous cholecystitis, however, the underling mechanism remains unclear. This study investigates the therapeutic effect of the active fraction named iridoid and xanthone glycoside (IXG) extracted from S. mussotii on six animal models related to calculous cholecystitis and its complications, and to explore its potential target proteins. Four main compounds including swertiamarin (STR), sweroside (SRS), gentiopicroside (GPS) and mangiferin (MGR) were identified from the IXG by UHPLC-TOF-MS. The in vivo experiments results confirmed that IXG significantly decreased the level of total bilirubin (TBIL), direct bilirubin (DBIL) and cyclooxygenase-2 (COX2) in calculous cholecystitis. IXG treatment dramatically reduced the number of twists and the time of clicking foot in 2nd phase induced by glacial acetic acid and formalin, however, no effect was showed on central pain established by hot plate test. IXG also significantly decreased the anal temperature induced by yeast and 2,4-dinitrophenol. These results indicated that IXG alleviate calculous cholecystitis and its clinical symptom. In addition, IXG suppressed the expression of Prostaglandin E2 (PGE2) in vitro. Mechanistically, COX2 was identified as the direct target of IXG in RAW264.7 cells, and downregulated the protein levels of COX2. The results confirmed that IXG ameliorates calculous cholecystitis and its clinical symptom (pain and fever) by suppressing the production of PGE2 through targeting COX2.

Comparative transcriptome analysis of Cyperus esculentus and C. rotundus with contrasting oil contents in tubers defines genes and regulatory networks involved in oil accumulation.

Plant vegetative organs present great potential for lipid storage, with tubers of Cyperus esculentus as a unique example. To investigate the genome and transcriptomic features of C. esculentus and related species, we sequenced and assembled the C. esculentus genome at the contig level. Through a comparative study of high-quality transcriptomes across 36 tissues from high-oil and intermediate-oil C. esculentus and low-oil Cyperus rotundus, we identified potential genes and regulatory networks related to tuber oil accumulation. First, we identified tuber-specific genes in two C. esculentus cultivars. Second, genes involved in fatty acid (FA) biosynthesis, triacylglycerol synthesis, and TAG packaging presented increased activity in the later stages of tuber development. Notably, tubers with high oil contents presented higher levels of these genes than those with intermediate oil contents did, whereas tubers with low oil contents presented minimal gene expression. Notably, a large fragment of the FA biosynthesis rate-limiting enzyme-encoding gene BCCP1 was missing from the C. rotundus transcript, which might be responsible for blocking FA biosynthesis in its tubers. WGCNA pinpointed a gene module linked to tuber oil accumulation, with a coexpression network involving the transcription factors WRI1, MYB4, and bHLH68. The ethylene-related genes in this module suggest a role for ethylene signaling in oil accumulation, which is supported by the finding that ethylene (ETH) treatment increases the oil content in C. esculentus tubers. This study identified potential genes and networks associated with tuber oil accumulation in C. esculentus, highlighting the role of specific genes, transcription factors, and ethylene signaling in this process.

Redox-Driven Formation of Mn(III) in Ice.

Redox-driven reactions involving Mn(II) species adsorbed at Mn(IV) oxide surfaces can release Mn(III) in the form of dissolved Mn(III)-ligand species in natural waters. Using pyrophosphate (PP) as a model ligand, we show that freezing accelerates and enhances Mn(III) formation in the form of Mn(III)-PP complexes. This freeze-promoted reaction is explained by the concentration of Mn(IV) oxides and solutes (Mn(II), Na+, and Cl-) into the minute fractions of liquid water locked between ice (micro)crystals - the Liquid Intergrain Boundary (LIB). Time-resolved freezing experiments at -20 °C showed that Mn(III) yields were greatest at low salt (NaCl) content. In contrast, high salt content promoted Mn(III) formation through chloride complexation, although yields became lower as the cryosalt mineral hydrohalite (NaCl·2H2O) dehydrated the LIB by drawing water into its structure. Consecutive freeze-thaw cycles also showed that dissolved Mn(III) concentrations increased within the very first few minutes of each freezing event. Because each thaw event released unreacted PP previously locked in ice, each sequential freeze-thaw cycle increased Mn(III) yields, until ∼80% of the Mn was converted to Mn(III). This was achieved after only seven cycles. Finally, temperature-resolved freezing experiments down to -50 °C showed that the LIB produced the greatest quantities of Mn(III) at -10 °C, where the volumes were greater. Reactivity was however sustained in ice formed below the eutectic (-21.3 °C), down to -50 °C. We suspect that this sustained reactivity was driven by persistent forms of supercooled water, such as Mn(IV) oxide-bound thin water films. By demonstrating the freeze-driven production of Mn(III) by comproportionation of dissolved Mn(II) and Mn(IV) oxide, this study highlights the potentially important roles these reactions could play in the production of pools of Mn(III) in natural water and sediments of mid- and high-latitudes environments exposed to freeze-thaw episodes.

The mGluR5-mediated Arc activation protects against experimental traumatic brain injury in rats.

INTRODUCTION: Traumatic brain injury (TBI) is a complex pathophysiological process, and increasing attention has been paid to the important role of post-synaptic density (PSD) proteins, such as glutamate receptors. Our previous study showed that a PSD protein Arc/Arg3.1 (Arc) regulates endoplasmic reticulum (ER) stress and neuronal necroptosis in traumatic injury in vitro. AIM: In this study, we investigated the expression, regulation and biological function of Arc in both in vivo and in vitro experimental TBI models. RESULTS: Traumatic neuronal injury (TNI) induced a temporal upregulation of Arc in cortical neurons, while TBI resulted in sustained increase in Arc expression up to 24 h in rats. The increased expression of Arc was mediated by the activity of metabotropic glutamate receptor 5 (mGluR5), but not dependent on the intracellular calcium (Ca2+) release. By using inhibitors and antagonists, we found that TNI regulates Arc expression via Gq protein and protein turnover. In addition, overexpression of Arc protects against TBI-induced neuronal injury and motor dysfunction both in vivo and in vitro, whereas the long-term cognitive function was not altered. To determine the role of Arc in mGluR5-induced protection, lentivirus-mediated short hairpin RNA (shRNA) transfection was performed to knockdown Arc expression. The mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG)-induced protection against TBI was partially prevented by Arc knockdown. Furthermore, the CHPG-induced attenuation of Ca2+ influx after TNI was dependent on Arc activation and followed regulation of AMPAR subunits. The results of Co-IP and Ca2+ imaging showed that the Arc-Homer1 interaction contributes to the CHPG-induced regulation of intracellular Ca2+ release. CONCLUSION: In summary, the present data indicate that the mGluR5-mediated Arc activation is a protective mechanism that attenuates neurotoxicity following TBI through the regulation of intracellular Ca2+ hemostasis. The AMPAR-associated Ca2+ influx and ER Ca2+ release induced by Homer1-IP3R pathway might be involved in this protection.

MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications.

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21.

Association between the triglyceride-glucose index and serum soluble Klotho in middle-aged and older adults from NHANES 2007-2016.

Klotho, an anti-aging protein, is believed to participate in metabolic diseases and play a potential protective role by regulating insulin sensitivity. This study aimed to explore the relationship between the triglyceride-glucose (TyG) index (a simple marker of insulin resistance) and serum soluble Klotho (S-Klotho) levels. The cross-sectional study comprised 5237 adults aged 40-79 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2007-2016. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The serum levels of S-Klotho were measured by enzyme-linked immunosorbent assay. The association between the TyG index and S-Klotho levels was investigated by multiple linear regression models, smoothed curve fitting, segmented linear regression models, subgroup analyses, and interaction tests. The TyG index was inversely associated with serum S-Klotho level after full adjustment (ß = - 45.11, 95% CI (- 79.53, - 10.69), P = 0.011). Furthermore, we also found a non-linear correlation and saturation phenomenon between the TyG index and serum S-Klotho levels, with a turning point of 9.56. In addition, a significant interaction effect of sex was found between the two (P for interaction < 0.001), with a more pronounced association observed in females. Further studies are required to explore the mechanisms and verify the correlation.

Intelligent skin-removal photoacoustic computed tomography for human based on deep learning.

Photoacoustic computed tomography (PACT) has centimeter-level imaging ability and can be used to detect the human body. However, strong photoacoustic signals from skin cover deep tissue information, hindering the frontal display and analysis of photoacoustic images of deep regions of interest. Therefore, we propose a 2.5 D deep learning model based on feature pyramid structure and single-type skin annotation to extract the skin region, and design a mask generation algorithm to remove skin automatically. PACT imaging experiments on the human periphery blood vessel verified the correctness our proposed skin-removal method. Compared with previous studies, our method exhibits high robustness to the uneven illumination, irregular skin boundary, and reconstruction artifacts in the images, and the reconstruction errors of PACT images decreased by 20% ~ 90% with a 1.65 dB improvement in the signal-to-noise ratio at the same time. This study may provide a promising way for high-definition PACT imaging of deep tissues.

Constructing the Electron-Rich Microenvironment of an All-Polymer-Based S-Scheme Homostructure for Accelerating Uranium Capture from Nuclear Wastewater.

Large quantities of uranium-containing radioactive wastewater are typically generated during nuclear fuel cycle processes. Despite significant efforts, efficient capture of migratable hexavalent uranium U(VI) is still a huge challenge due to its acidity, radioactivity, coexisting organics, and high impurity cation abundance in wastewater. Herein, we have fabricated all-polymer-based 0D/2D C4N/C6N7 homostructure hybrids with an S-scheme electronic configuration by coordinating the band engineering of semiconductors to enrich uranium species from the complex wastewater environment. The sample can capture over 97% of U(VI) in the actual concentration of nuclear industrial reprocessing wastewater; also, the U(VI) enrichment ratio still exceeds 95% when the irradiation dose (including α, ß, and γ) is up to 100 kGy. Density functional theory and X-ray absorption spectroscopy demonstrate that the aggregation of charge carriers on the surface of the sample regulates the electron-rich microenvironment, thus accelerating the reduction conversion of single electron reaction uranium disproportionation. It is expected that this work can provide more insight into other functional materials, thereby promoting uranium removal advancements in nuclear wastewater.

Construction and Evaluation of BAL-PTX Co-Loaded Lipid Nanosystem for Promoting the Anti-Lung Cancer Efficacy of Paclitaxel and Reducing the Toxicity of Chemotherapeutic Drugs.

Purpose: The present study aimed to develop a lipid nanoplatform, denoted as "BAL-PTX-LN", co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs. Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining. Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 µg/mL vs 31.722 µg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration. Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder.

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

IQAGPT: computed tomography image quality assessment with vision-language and ChatGPT models.

Large language models (LLMs), such as ChatGPT, have demonstrated impressive capabilities in various tasks and attracted increasing interest as a natural language interface across many domains. Recently, large vision-language models (VLMs) that learn rich vision-language correlation from image-text pairs, like BLIP-2 and GPT-4, have been intensively investigated. However, despite these developments, the application of LLMs and VLMs in image quality assessment (IQA), particularly in medical imaging, remains unexplored. This is valuable for objective performance evaluation and potential supplement or even replacement of radiologists' opinions. To this end, this study introduces IQAGPT, an innovative computed tomography (CT) IQA system that integrates image-quality captioning VLM with ChatGPT to generate quality scores and textual reports. First, a CT-IQA dataset comprising 1,000 CT slices with diverse quality levels is professionally annotated and compiled for training and evaluation. To better leverage the capabilities of LLMs, the annotated quality scores are converted into semantically rich text descriptions using a prompt template. Second, the image-quality captioning VLM is fine-tuned on the CT-IQA dataset to generate quality descriptions. The captioning model fuses image and text features through cross-modal attention. Third, based on the quality descriptions, users verbally request ChatGPT to rate image-quality scores or produce radiological quality reports. Results demonstrate the feasibility of assessing image quality using LLMs. The proposed IQAGPT outperformed GPT-4 and CLIP-IQA, as well as multitask classification and regression models that solely rely on images.

Prolonged vs shorter awake prone positioning for COVID-19 patients with acute respiratory failure: a multicenter, randomised controlled trial.

PURPOSE: Awake prone positioning has been reported to reduce endotracheal intubation in patients with coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF). However, it is still unclear whether using the awake prone positioning for longer periods can further improve outcomes. METHODS: In this randomized, open-label clinical trial conducted at 12 hospitals in China, non-intubated patients with COVID-19-related AHRF were randomly assigned to prolonged awake prone positioning (target > 12 h daily for 7 days) or standard care with a shorter period of awake prone positioning. The primary outcome was endotracheal intubation within 28 days after randomization. The key secondary outcomes included mortality and adverse events. RESULTS: In total, 409 patients were enrolled and randomly assigned to prolonged awake prone positioning (n = 205) or standard care (n = 204). In the first 7 days after randomization, the median duration of prone positioning was 12 h/d (interquartile range [IQR] 12-14 h/d) in the prolonged awake prone positioning group vs. 5 h/d (IQR 2-8 h/d) in the standard care group. In the intention-to-treat analysis, intubation occurred in 35 (17%) patients assigned to prolonged awake prone positioning and in 56 (27%) patients assigned to standard care (relative risk 0.62 [95% confidence interval (CI) 0.42-0.9]). The hazard ratio (HR) for intubation was 0.56 (0.37-0.86), and for mortality was 0.63 (0.42-0.96) for prolonged awake prone positioning versus standard care, within 28 days. The incidence of pre-specified adverse events was low and similar in both groups. CONCLUSION: Prolonged awake prone positioning of patients with COVID-19-related AHRF reduces the intubation rate without significant harm. These results support prolonged awake prone positioning of patients with COVID-19-related AHRF.

Capecitabine mitigates cardiac allograft rejection via inhibition of TYMS-Mediated Th1 differentiation in mice.

OBJECTIVES: Previous studies elucidated that capecitabine (CAP) works as an anti-tumor agent with putative immunosuppressive effects. However, the intricate mechanisms underpinning these effects remain to be elucidated. In this study, we aimed to unravel the molecular pathways by which CAP exerts its immunosuppressive effects to reduce allograft rejection. METHODS: Hearts were transplanted from male BALB/c donors to male C57BL/6 recipients and treated with CAP for seven days. The rejection of these heart transplants was assessed using a range of techniques, including H&E staining, immunohistochemistry, RNA sequencing, LS-MS/MS, and flow cytometry. In vitro, naïve CD4+ T cells were isolated and cultured under Th1 condition medium with varying treatments, flow cytometry, LS-MS/MS were employed to delineate the role of thymidine synthase (TYMS) during Th1 differentiation. RESULTS: CAP treatment significantly mitigated acute allograft rejection and enhanced graft survival by reducing graft damage, T cell infiltration, and levels of circulating pro-inflammatory cytokines. Additionally, it curtailed CD4+ T cell proliferation and the presence of Th1 cells in the spleen. RNA-seq showed that TYMS, the target of CAP, was robustly increased post-transplantation in splenocytes. In vitro, TYMS and its metabolic product dTMP were differentially expressed in Th0 and Th1, and were required after activation of CD4+ T cell and Th1 differentiation. TYMS-specific inhibitor, raltitrexed, and the metabolite of capecitabine, 5-fluorouracil, could inhibit the proliferation and differentiation of Th1. Finally, the combined use of CAP and the commonly used immunosuppressant rapamycin can induce long-term survival of allograft. CONCLUSION: CAP undergoes metabolism conversion to interfere pyrimidine metabolism, which targets TYMS-mediated differentiation of Th1, thereby playing a significant role in mitigating acute cardiac allograft rejection in murine models.

ALOX5 contributes to glioma progression by promoting 5-HETE-mediated immunosuppressive M2 polarization and PD-L1 expression of glioma-associated microglia/macrophages.

BACKGROUND: Oxylipin metabolism plays an essential role in glioma progression and immune modulation in the tumor microenvironment. Lipid metabolic reprogramming has been linked to macrophage remodeling, while the understanding of oxylipins and their catalyzed enzymes lipoxygenases in the regulation of glioma-associated microglia/macrophages (GAMs) remains largely unexplored. METHODS: To explore the pathophysiological relevance of oxylipin in human glioma, we performed Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) analysis in human glioma and non-tumor brain tissues. To comprehensively investigate the role of arachidonate lipoxygenase 5 (ALOX5) in glioma, we performed in vivo bioluminescent imaging, immunofluorescence staining and flow cytometry analysis on tumors from orthotopic glioma-bearing mice. We developed an ALOX5-targeted nanobody, and tested its anti-glioma efficacy of combination therapy with α-programmed cell death protein-1 (PD-1). RESULTS: In this study, we found that ALOX5 and its oxylipin 5-hydroxyeicosatetraenoic acid (5-HETE) are upregulated in glioma, accumulating programmed death-ligand 1 (PD-L1)+ M2-GAMs and orchestrating an immunosuppressive tumor microenvironment. Mechanistically, 5-HETE derived from ALOX5-overexpressing glioma cells, promotes GAMs migration, PD-L1 expression, and M2 polarization by facilitating nuclear translocation of nuclear factor erythroid 2-related factor 2. Additionally, a nanobody targeting ALOX5 is developed that markedly suppresses 5-HETE efflux from glioma cells, attenuates M2 polarization of GAMs, and consequently ameliorates glioma progression. Furthermore, the combination therapy of the ALOX5-targeted nanobody plus α-PD-1 exhibits superior anti-glioma efficacy. CONCLUSIONS: Our findings reveal a pivotal role of the ALOX5/5-HETE axis in regulating GAMs and highlight the ALOX5-targeted nanobody as a potential therapeutic agent, which could potentiate immune checkpoint therapy for glioma.

Machine learning-based prognostic model for in-hospital mortality of aortic dissection: Insights from an intensive care medicine perspective.

Objective: Aortic dissection (AD) is a severe emergency with high morbidity and mortality, necessitating strict monitoring and management. This retrospective study aimed to identify prognostic factors and establish predictive models for in-hospital mortality among AD patients in the intensive care unit (ICU). Methods: We retrieved ICU admission records of AD patients from the Medical Information Mart for Intensive Care (MIMIC)-IV critical care data set and the eICU Collaborative Research Database. Functional data analysis was further applied to estimate continuous vital sign processes, and variables associated with in-hospital mortality were identified through univariate analyses. Subsequently, we employed multivariable logistic regression and machine learning techniques, including simple decision tree, random forest (RF), and eXtreme Gradient Boosting (XGBoost) to develop prognostic models for in-hospital mortality. Results: Given 643 ICU admissions from MIMIC-IV and 501 admissions from eICU, 29 and 28 prognostic factors were identified from each database through univariate analyses, respectively. For prognostic model construction, 507 MIMIC-IV admissions were divided into 406 (80%) for training and 101 (20%) for internal validation, and 87 eICU admissions were included as an external validation group. Of the four models tested, the RF consistently exhibited the best performance among different variable subsets, boasting area under the receiver operating characteristic curves of 0.870 and 0.850. The models highlighted the mean 24-h fluid intake as the most potent prognostic factor. Conclusions: The current prognostic models effectively forecasted in-hospital mortality among AD patients, and they pinpointed noteworthy prognostic factors, including initial blood pressure upon ICU admission and mean 24-h fluid intake.

Is catheterization via distal transradial access feasible in children? From vessel diameter perspective.

Background: Distal radial artery (DRA) access is an infrequent alternative access for pediatric catheterization. The feasibility of using the DRA for arterial catheterization in children depends on the vessel's size. Objectives: This study aims to provide a reference for pediatric catheterization via DRA access by evaluating the diameter of the DRA in the anatomic snuffbox (AS). Methods: We conducted a retrospective review of clinical and vascular ultrasound data of 412 children (ages 3-12) who were scheduled for arterial blood gas analysis via the DRA due to serious respiratory diseases between June 2023 and October 2023. Results: The corrected DRA diameter in the AS was 1.97 ± 0.37 mm overall, with no significant difference between males (1.98 ± 0.38 mm) and females (1.95 ± 0.35 mm) (p = 0.457). The anteroposterior, transverse, and corrected DRA diameters increased significantly with age (p < 0.05). The DRA diameter was significantly smaller than the proximal radial artery (PRA) diameter (1.97 ± 0.37 mm vs. 2.05 ± 0.33 mm, p < 0.001) but larger than the ulnar artery (UA) diameter (1.97 ± 0.37 mm vs. 1.88 ± 0.33 mm, p < 0.001). The proportions of patients with a DRA diameter greater than 2.0 mm and 1.5 mm were 38.83% and 86.89%, respectively. The proportions of patients with DRA diameters >2.0 mm and >1.5 mm increased significantly with age (p < 0.01). The percentages of individuals with a DRA/PRA ratio ≥1.0 were 55.10% overall, 52.12% in males, and 58.60% in females. DRA diameter showed significant correlations with age (r = 0.275, p < 0.01), height (r = 0.319, p < 0.01), weight (r = 0.319, p < 0.01), BMI (r = 0.241, p < 0.01), wrist circumference (r = 0.354, p < 0.01), PRA diameter (r = 0.521, p < 0.01), and UA diameter (r = 0.272, p < 0.01). Conclusion: The DRA diameter in children increases with age and size, making cardiac catheterization is theoretically feasible. Preoperative evaluation of the vessel diameter and intraoperative ultrasound-guided intervention are recommended for paediatric catheterization via the DRA access.

Synthesis of nicotinimidamides via a tandem CuAAC/ring-cleavage /cyclization/oxidation four-component reaction and their cytotoxicity.

Nicotinamide and its derivatives, recognized as crucial drug intermediates, have been a focal point of extensive chemical modifications and rigorous pharmacological studies. Herein, a series of novel nicotinamide derivatives, nicotinimidamides, were synthesized via a tandem CuAAC/ring-cleavage/cyclization/oxidation four-component reaction procedure from O-acetyl oximes, terminal ynones, sulfonyl azides, and NH4OAc. This strategy is significantly more efficient than previously reported, and the cytotoxicity of the nicotinimidamides is also tested. This project not only exhibits a sustainable and eco-friendly domino methodology for the creation of nicotinimidamides but also presents a promising candidate for liver cancer treatment.

Brush-Like Polymeric Gels Enabled Photonic Crystals toward Ultrasensitive Cosolvent Chromism.

Responsive photonic crystals (RPCs) exhibit dynamic chromism upon trigger by various solvents, showing potential applications in qualitative identification and quantitative analysis of multicomponent solvents. However, distinguishing similar solvents, especially traces of cosolvents, remains challenging due to the limited sensitivity of RPCs. To address this, we herein introduce brush-like polymeric gels inside photonic crystals, forming a brush-like polymeric photonic gel (BPPG) that can trace tiny component changes. In this BPPG system, the acrylate backbones and PEG side-chains stretch incrementally due to the cosolvency of ethanol-water mixtures, resulting in highly sensitive chromatic responses within ethanol-rich concentrations. With water content varying slightly from 0 to 1 vol%, the reflection wavelength of BPPG can sharply redshift over 30 nm, leading to very noticeable changes in structural color. This enhanced sensitivity makes BPPG suitable for real-time, in-situ purity monitoring of absolute ethanol during storage, transportation, and other applications.