Development of a Multiparticulate Metal-Organic Framework/Textile Fiber Swatch.

The versatility of metal-organic frameworks (MOFs) has led to groundbreaking applications in a wide variety of fields, especially in the areas of energy, environment, and sustainability. For example, MOFs can be designed for high uptake of toxic gases and pollutants, such as CO2, NH3, and SO2, but designing a single MOF that shows tangible uptake for all of these gases is challenging due to the differences in the chemical and physical properties of these molecules. To this end, integrating multiple MOFs onto textile fibers and crafting various structures have emerged as pivotal developments, enhancing framework durability and usability. MOF composites prepared on readily available textile fibers offer the flexibility essential for critical applications, including heterogeneous catalysis, chemical sensing, toxic gas adsorption, and drug delivery, while preserving the unique characteristics of MOFs. This study introduces a scalable and adaptable method for seamlessly embedding multiple high-performing MOFs onto a single textile fiber using a dip-coating method. We explored the uptake capacity of these multi-MOF composites for CO2, NH3, and SO2 and observed a performance similar to that of traditional powdered materials. Along with harmful gas adsorption, we also have evaluated the permeation and reactivity of these MOF/textile composites toward chemical warfare agents (CWAs) like GD (soman), HD (mustard gas), and VX. In combination, these results demonstrate a fundamental advancement toward establishing a consistent strategy for the hydrolysis of nerve agents in real-world scenarios. This approach can substantially increase the protection toward CWAs and enhance the effectiveness of protective equipment such as fabrics for protective garments. This dip-coating method for the integration of multiple MOFs on a single textile fiber unlocks a wealth of possibilities and paves the way for future innovations in the deployment of MOF-based composites.

Highly Sensitive, Degradable, and Rapid Self-Healing Hydrogel Sensor with Semi-Interpenetrating Network for Recognition of Micro-Expressions.

Flexible conductive hydrogels have revolutionized the lives and are widely applied in health monitoring and wearable electronics as a new generation of sensing materials. However, the inherent low mechanical strength, sensitivity, and lack of rapid self-healing capacity results in their short life, poor detection accuracy, and environmental pollution. Inspired by the molecular structure of bone and its chemical characteristics, a novel fully physically cross-linked conductive hydrogel is fabricated by the introduction of nanohydroxyapatite (HAp) as the dynamic junction points. In detail, the dynamically cross-linked network, including multiple physical interactions, provides it with rapid self-healing ability and excellent mechanical properties (elongation at break (>1200%), tensile strength (174kPa), and resilience (92.61%)). Besides, the ions (Cl-, Li+, Ca2+) that move freely within the system impart outstanding electrical conductivity (2.46 ± 0.15 S m-1), high sensitivity (gauge factor, GF>8), good antifreeze (-40.2 °C), and humidity properties. The assembled sensor can be employed to sensitively detect various large human motions and subtle changes in behavior (facial expressions, speech recognition). Meanwhile, the hydrogel sensor can also degrade in phosphate-buffered saline solution without causing any environmental pollution. Therefore, the designed hydrogels may become a promising candidate material in the future potential applications for smart wearable sensors and electronic skin.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Liver organoids: updates on generation strategies and biomedical applications.

The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.

Elucidating the role of S100A10 in CD8+ T cell exhaustion and HCC immune escape via the cPLA2 and 5-LOX axis.

Hepatocellular carcinoma (HCC) is a common malignant tumor with a complex immune evasion mechanism posing a challenge to treatment. The role of the S100A10 gene in various cancers has garnered significant attention. This study aims to elucidate the impact of S100A10 on CD8+ T cell exhaustion via the cPLA2 and 5-LOX axis, thereby elucidating its role in immune evasion in HCC. By analyzing the HCC-related data from the GEO and TCGA databases, we identified differentially expressed genes associated with lipid metabolism and developed a prognostic risk model. Subsequently, through RNA-seq and PPI analyses, we determined vital lipid metabolism genes and downstream factors S100A10, ACOT7, and SMS, which were significantly correlated with CD8+ T cell infiltration. Given the most significant expression differences, we selected S100A10 for further investigation. Both in vitro and in vivo experiments were conducted, including co-culture experiments of CD8+ T cells with MHCC97-L cells, Co-IP experiments, and validation in an HCC mouse model. S100A10 was significantly overexpressed in HCC tissues and potentially regulates CD8+ T cell exhaustion and lipid metabolism reprogramming through the cPLA2 and 5-LOX axis. Silencing S100A10 could inhibit CD8+ T cell exhaustion, further suppressing immune evasion in HCC. S100A10 may activate the cPLA2 and 5-LOX axis, initiating lipid metabolism reprogramming and upregulating LTB4 levels, thus promoting CD8+ T cell exhaustion in HCC tissues, facilitating immune evasion by HCC cells, ultimately impacting the growth and migration of HCC cells. This research highlights the critical role of S100A10 via the cPLA2 and 5-LOX axis in immune evasion in HCC, providing new theoretical foundations and potential targets for diagnosing and treating HCC.

Study on the Migration Patterns of Oxygen Elements during the Refining Process of Ti-48Al Scrap under Electromagnetic Levitation.

This study investigated the migration patterns of oxygen in the deoxidation process of Ti-48Al alloy scrap using electromagnetic levitation (EML) technology. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were employed to analyze the oxygen distribution patterns and migration path during EML. The refining process resulted in three types of oxygen migration: (1) escape from the lattice and evaporation in the form of AlO, Al2O; (2) formation of metal oxides and remaining in the alloy melt; (3) attachment to the quartz tube wall in the form of metal oxides such as Al2O3 and Cr2O3. The oxygen content of the scrap was dropped with a deoxidation ratio of 62%. It indicated that EML can greatly promote the migration and removal of oxygen elements in Ti-Al alloy scrap.

Classification of anatomy and treatment approaches for aneurysms originating from the proximal of the A1 segment of the anterior cerebral artery in clinical settings.

Objective: To explore the spatial relationship between A1 segment proximal anterior cerebral artery aneurysms and their main trunks, classify them anatomically and develop targeted treatment strategies. Methods: This single-center retrospective analysis involved 39 patients diagnosed with aneurysms originating from the proximal of A1 segment of the anterior cerebral artery (2014-2023). Classify the patient's aneurysm into 5 types based on the location of the neck involving the carrier artery and the spatial relationship and projection direction of the aneurysm body with the carrier artery, and outcomes from treatment methods were compared. Results: Among 39 aneurysms, 18 cases underwent endovascular intervention treatment, including 6 cases of stent assisted embolization, 1 case of flow-diverter embolization, 5 cases of balloon assisted embolization, and 6 cases of simple coiling. At discharged, the mRS score of all endovascularly treated patients was 0, and the GOS score was 5 at 6 months after discharge. At discharge, the mRS score of microsurgical clipping treated patients was 0 for 15 cases, 3 for 1 case, 4 for 1 case and 5 for 2 cases. Six months after discharge, the GOS score was 5 for 16 cases, 4 for 2 cases, 3 for 2 cases, and 1 for 1 case. GOS outcomes at 6 months were better for endovascularly treated patients (p = 0.047). Conclusion: Results showed better outcomes for the endovascular treatment group compared to microsurgical clipping at 6 months after surgery. The anatomical classification of aneurysms in this region may be of help to develop effective treatment strategies.

Relationship between enteral nutrition timing and 28-day mortality in critically ill stroke patients in the MIMIC-IV database.

Background: The ideal timing for commencing enteral nutrition (EN) in critically ill stroke patients in the intensive care unit (ICU) remains a subject of debate, with ongoing controversy regarding the impact of early EN (EEN) initiation. In this study, we investigated the association between the timing of EN initiation and 28-day mortality using data from the MIMIC-IV database. Methods: This study employed a retrospective cohort design using the MIMIC-IV database to identify stroke patients who received EN during their hospital stay. The main focus of this investigation was to examine 28-day mortality among these patients following hospital admission. Various demographic, clinical, laboratory, and intervention variables were considered as covariates. The Cox regression analysis was employed to assess the correlation between the timing of EN initiation and 28-day mortality, and restricted cubic splines (RCS) analysis was used to test for non-linear correlation. Patients were then stratified into two cohorts depending on the timing of EN initiation: within 2 days (n = 564) and beyond 2 days (n = 433). A multivariate Cox regression analysis was used to investigate the difference in 28-day mortality between the groups. Results: A total of 997 participants were included in this study, with 318 (31.9%) dying within 28 days. We observed that the timing of EN initiation correlated with 28-day mortality, but this correlation was not significant after adjusting for covariates (crude HR: 0.94, 95% CI: 0.88-1, p = 0.044; adjusted HR: 0.96, 95% CI: 0.9-1.02, p = 0.178). The RCS analysis showed that the correlation was not non-linear. Notably, in the multivariate regression models, early EN initiation was associated with a higher mortality rate compared to late EN initiation [odds ratio (OR) = 1.34, 95% CI: 1.06-1.67, p = 0.012]. After adjusting for various confounding factors in the multivariate Cox regression models, we identified that patients in the early EN group had a 28% higher risk of mortality than those in the reference group (OR = 1.27, 95% CI: 1-1.61, p = 0.048). These associations remained consistent across various patient characteristics, as revealed through stratified analyses. Conclusions: Early commencement of EN in critically ill stroke patients may be linked to a higher risk of 28-day mortality, highlighting the need for further investigation and a more nuanced consideration of the optimal timing for commencing EN in this patient population.

Risk Factors for Perioperative Hypothermia in Pregnant Women undergoing Cesarean Section: A Systematic Review and Meta-Analysis.

AIM: Hypothermia is one of the common complications of cesarean section, which has a serious impact on intraoperative surgical safety and postoperative recovery of pregnant women. Mitigation of the risk factors of hypothermia in pregnant women undergoing cesarean section may reduce the probability of its occurrence and improve the perioperative comfort of pregnant women. Therefore, this study systematically evaluates the influencing factors of hypothermia in patients undergoing cesarean section, aiming to provide references for the prevention of hypothermia in pregnant women undergoing cesarean section. METHODS: A systematic search was conducted across various databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Biomedical Literature databases to gather observational studies on the factors affecting hypothermia in pregnant women undergoing cesarean section. The search deadline was January 30, 2024. Two researchers independently screened literature, extracted data, evaluated quality, and crosschecked the outcomes. Meta analysis was conducted using RevMan 5.3 and Stata17.0. RESULTS: Twelve studies were included in this review, all of which were case-control studies conducted from 2014 to 2022, encompassing a total of 5561 pregnant women. The quality of the studies included was average or above. The meta-analysis results showed that body mass index (mean difference (MD) = -1.47; 95% confidence interval (CI) [-2.84, -0.11]; p = 0.03), operating room temperature (odds ratio (OR) = 2.08; 95% CI [1.56, 2.76]; p < 0.00001), anesthesia method (OR = 1.84; 95% CI [1.40, 2.42]; p < 0.0001), fluid loss (MD = 160.09; 95% CI [77.31, 242.87]; p = 0.0002), flushing volume (MD = 66.43; 95% CI [8.46, 124.40]; p = 0.02), and hypothyroidism (OR = 2.29; 95% CI [1.61, 3.27]; p < 0.00001) were risk factors for perioperative hypothermia in pregnant women undergoing cesarean section (p < 0.05). CONCLUSIONS: The occurrence of hypothermia in pregnant women during the perioperative period is influenced by factors such as low body mass index, spinal anesthesia, low operating room temperature, intraoperative fluid loss, large flushing volume, and hypothyroidism.

Effect of supraglottic jet oxygenation and ventilation on hypoxemia in patients undergoing endoscopic surgery with sedation: A meta-analysis of randomized controlled trials.

BACKGROUND: Nasal cannulas and face masks are common oxygenation tools used in conventional oxygen therapy for patients undergoing endoscopic surgery with sedation. However, as a novel supraglottic ventilation technique, the application of supraglottic jet oxygenation and ventilation (SJOV) in endoscopic surgery has not been well established. METHOD: We searched six electronic databases from inception to January 16, 2024, to assess the oxygenation/ventilation efficacy and side effects of the of SJOV in endoscopic surgery. The primary outcome was the incidence of hypoxemia. The secondary outcomes were the incidence of respiratory depression and adverse effects (nasal bleeding, sore throat, and dry mouth). RESULTS: Nine trials involving 2017 patients were included. The results demonstrated that the incidence of hypoxemia was lower in the SJOV group compared with the conventional oxygen therapy (COT) group [9 trails; 2017 patients; risk ratio (RR) = 0.18; 95% confidence interval (CI), (0.11-0.28)]. Subgroup analyses showed that SJOV reduced the incidence of hypoxemia in the high-risk group but had no effect on the low-risk group. The incidence of respiratory depression is lower in SJOV than in COT, but has increased side effects such as dry mouth. There was no statistically significant difference in nose bleeding or sore throat between the two groups. CONCLUSION: Compared with the COT, the SJOV decreased the incidence of hypoxemia in high-risk patients during endoscopic surgery with sedation. There was an increased risk of dry mouth, but not of nose bleeding or sore throat, during endoscopic surgery under sedation.

Development and validation of a nomogram for cerebral hemorrhage in patients with carotid stenosis undergoing stenting: a multicenter retrospective study.

BACKGROUND: Hyperperfusion-induced cerebral hemorrhage (HICH) is a rare but severe complication in patients with carotid stenosis undergoing stent placement for which predictive models are lacking. Our objective was to develop a nomogram to predict such risk. METHODS: We included a total of 1226 patients with carotid stenosis who underwent stenting between June 2015 and December 2022 from three medical centers, divided into a development cohort of 883 patients and a validation cohort of 343 patients. The model used LASSO regression for feature optimization and multivariable logistic regression to develop the predictive model. Model accuracy was assessed via the receiver operating characteristic curve, with further evaluation of calibration and clinical utility through calibration curves and decision curve analysis (DCA). The model underwent internal validation using bootstrapping and external validation with the validation cohort. RESULTS: Older age (OR 1.07, p=0.005), higher degrees of carotid stenosis (OR 1.07, p=0.006), poor collateral circulation (OR 6.26, p<0.001), elevated preoperative triglyceride levels (OR 1.27, p=0.041) and neutrophil counts (OR 1.36, p<0.001) were identified as independent risk factors for HICH during hospitalization. The nomogram constructed based on these predictive factors demonstrated an area under the curve (AUC) of 0.817. The AUCs for internal and external validation were 0.809 and 0.783, respectively. Calibration curves indicated good model fit, and DCA confirmed substantial clinical net benefit in both cohorts. CONCLUSION: We developed and validated a nomogram to predict HICH in patients with carotid stenosis post-stenting, facilitating early identification and preventive intervention in high-risk individuals.

Numerical Simulation of Electromagnetic-Thermal-Fluid Coupling for the Deformation Behavior of Titanium-Aluminum Alloy under Electromagnetic Levitation.

Electromagnetic levitation (EML) is a good method for high-temperature processing of reactive materials such as titanium-aluminum (Ti-Al) alloys. In this study, the oscillation and deformation processes of Ti-48Al-2Cr alloy specimens at different high-frequency currents during the EML process were simulated using the Finite Element Method and Arbitrary Lagrangian-Eulerian (ALE) methods. The data of oscillation, stabilization time, deformation, and distribution of electromagnetic-thermal-fluid fields were finally obtained. The accuracy of the simulation results was verified by EML experiments. The results show the following: the strength and distribution of the induced magnetic field inside the molten droplet are determined by the high-frequency current; under the coupling effect of the electromagnetic field, thermal field, and fluid field, the temperature rise of electromagnetic heating is rapid, and accompanied by strong stirring, resulting in a uniform distribution of the internal temperature and a small temperature difference. Under the joint action of gravity and Lorentz force, the molten droplets are first within a damped oscillation and then tend to stabilize with time, and finally maintain the "near rhombus" shape.

[Astragaloside IV reduces renal injury in mice with IgA nephropathy by inhibiting TIM-1 signaling pathway and increasing Th1/Th2 cell ratio].

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.

Changes in productivity partitioning induced by precipitation extremes increase inaccuracy of grassland carbon estimation.

The fraction of net primary productivity (NPP) allocated to belowground organs (fBNPP) in grasslands is a critical parameter in global carbon cycle models; moreover, understanding the effect of precipitation changes on this parameter is vital to accurately estimating carbon sequestration in grassland ecosystems. However, how fBNPP responds to temporal precipitation changes along a gradient from extreme drought to extreme wetness, remains unclear, mainly due to the lack of long-term data of belowground net primary productivity (BNPP) and the fact that most precipitation experiments did not have a gradient from extreme drought to extreme wetness. Here, by conducting both a precipitation gradient experiment (100-500 mm) and a long-term observational study (34 years) in the Inner Mongolia grassland, we showed that fBNPP decreased linearly along the precipitation gradient from extreme drought to extreme wetness due to stronger responses in aboveground NPP to drought and wet conditions than those of BNPP. Our further meta-analysis in grasslands worldwide also indicated that fBNPP increased when precipitation decreased, and the vice versa. Such a consistent pattern of fBNPP response suggests that plants increase the belowground allocation with decreasing precipitation, while increase the aboveground allocation with increasing precipitation. Thus, the linearly decreasing response pattern in fBNPP should be incorporated into models that forecast carbon sequestration in grassland ecosystems; failure to do so will lead to underestimation of the carbon stock in drought years and overestimation of the carbon stock in wet years in grasslands.

Are community oncology practices with or without clinical research programs different? A comparison of patient and practice characteristics.

BACKGROUND: Expanding access to clinical trials in community settings is a potential approach to addressing disparities in accrual of historically underrepresented populations. However, little is known about the characteristics of practices that do not participate in research. We investigated differences in patient and practice characteristics of US community oncology practices with high vs low engagement in clinical research. METHODS: We included patients from a real-world, nationwide electronic health record-derived, de-identified database who received active treatment for cancer at community oncology practices between November 1, 2017, and October 31, 2022. We assessed patient and practice characteristics and their associations with high vs low research engagement using descriptive analyses and logistic regression models. RESULTS: Of the 178 practices, 70 (39.3%) events had high research engagement, treated 57.8% of the overall 568 540 patient cohort, and enrolled 3.25% of their patients on cancer treatment trials during the 5-year observation period (vs 0.27% enrollment among low engagement practices). Practices with low vs high research engagement treated higher proportions of the following patient groups: ages 75 years and older (24.2% vs 21.8%), non-Latinx Black (12.6% vs 10.3%) or Latinx (11.6% vs 6.1%), were within the lowest socioeconomic status quintile (21.9% vs16.5%), and were uninsured or had no documented insurance (22.2% vs 13.6%). CONCLUSIONS: Patient groups historically underrepresented in oncology clinical trials are more likely to be treated at community practices with limited or no access to trials. These results suggest that investments to expand the clinical research footprint among practices with low research engagement could help address persistent inequities in trial representation.

Evaluation of PVC and PTFE filters for direct-on-filter crystalline silica quantification by FTIR.

Direct-on-Filter (DoF) analysis of respirable crystalline silica (RCS) by Fourier Transform Infrared (FTIR) spectroscopy is a useful tool for assessing exposure risks. With the RCS exposure limits becoming lower, it is important to characterize and reduce measurement uncertainties. This study systematically evaluated two filter types (i.e., polyvinyl chloride [PVC] and polytetrafluoroethylene [PTFE]) for RCS measurements by DoF FTIR spectroscopy, including the filter-to-filter and day-to-day variability of blank filter FTIR reference spectra, particle deposition patterns, filtration efficiencies, and pressure drops. For PVC filters sampled at a flow rate of 2.5 L/min for 8 h, the RCS limit of detection (LOD) was 7.4 µg/m3 when a designated laboratory reference filter was used to correct the absorption by the filter media. When the spectrum of the pre-sample filter (blank filter before dust sampling) was used for correction, the LOD could be up to 5.9 µg/m3. The PVC absorption increased linearly with reference filter mass, providing a means to correct the absorption differences between the pre-sample and reference filters. For PTFE, the LODs were 12 and 1.2 µg/m3 when a designated laboratory blank or the pre-sample filter spectrum was used for blank correction, respectively, indicating that using the pre-sample blank spectrum will reduce RCS quantification uncertainty. Both filter types exhibited a consistent radially symmetric deposition pattern when particles were collected using 3-piece cassettes, indicating that RCS can be quantified from a single measurement at the filter center. The most penetrating aerodynamic diameters were around 0.1 µm with filtration efficiencies ≥ 98.8% across the measured particle size range with low-pressure drops (0.2-0.3 kPa) at a flow rate of 2.5 L/min. This study concludes that either the PVC or the PTFE filters are suitable for RCS analysis by DoF FTIR, but proper methods are needed to account for the variability of blank absorption among different filters.

FOSL2-mediated transcription of ISG20 induces M2 polarization of macrophages and enhances tumorigenic ability of glioblastoma cells.

BACKGROUND: Interferon stimulated exonuclease gene 20 (ISG20) has been reported to be correlated with macrophage infiltration in glioblastoma (GBM) in previous bioinformatics-based studies. This study explores the exact effect of ISG20 on macrophage polarization in GBM. METHODS: ISG20 expression in GBM tissues and cells was determined by RT-qPCR and/or immunohistochemistry. GBM cells were co-cultured with M0 macrophages (PMA-stimulated THP-1 cells) in vitro, followed by flow cytometry and ELISA to analyze the M2 polarization of macrophages. Fluorescence-contained GBM cells were intracranially injected into nude mice along with M0 macrophages to generate orthotopic xenograft tumor models. Upstream regulator of ISG20 was predicted using bioinformatics. Loss- or gain-of-function assays of Fos like 2 (FOSL2) and ISG20 were performed in GBM cells. DNA methylation level of FOSL2 was analyzed by bisulfite sequencing analysis. RESULTS: ISG20 was found highly expressed in GBM tissues and cells. ISG20 silencing in GBM cells decreased CD206 and CD163 levels in the co-cultured macrophages and reduced secretion of IL-10 and TGF-ß. It also enhanced survival of nude mice bearing xenograft tumors, blocked tumor growth, and suppressed M2 polarization of macrophages in vivo. FOSL2, highly expressed in GBM, bound to the ISG20 promoter to activate its transcription. FOSL2 silencing similarly blocked M2 polarization of macrophages, which was negated by ISG20 overexpression. The high FOSL2 expression in GBM was attributed to DNA hypomethylation. CONCLUSION: This study demonstrates that FOSL2 is highly expressed in GBM due to DNA hypomethylation. It activates transcription of ISG20, thus promoting M2 polarization of macrophages and GBM development.

Systemic Anticancer Therapy and Overall Survival in Patients With Very Advanced Solid Tumors.

Importance: Two prominent organizations, the American Society of Clinical Oncology and the National Quality Forum (NQF), have developed a cancer quality metric aimed at reducing systemic anticancer therapy administration at the end of life. This metric, NQF 0210 (patients receiving chemotherapy in the last 14 days of life), has been critiqued for focusing only on care for decedents and not including the broader population of patients who may benefit from treatment. Objective: To evaluate whether the overall population of patients with metastatic cancer receiving care at practices with higher rates of oncologic therapy for very advanced disease experience longer survival. Design, Setting, and Participants: This nationwide population-based cohort study used Flatiron Health, a deidentified electronic health record database of patients diagnosed with metastatic or advanced disease, to identify adult patients (aged ≥18 years) with 1 of 6 common cancers (breast cancer, colorectal cancer, non-small cell lung cancer [NSCLC], pancreatic cancer, renal cell carcinoma, and urothelial cancer) treated at health care practices from 2015 to 2019. Practices were stratified into quintiles based on retrospectively measured rates of NQF 0210, and overall survival was compared by disease type among all patients treated in each practice quintile from time of metastatic diagnosis using multivariable Cox proportional hazard models with a Bonferroni correction for multiple comparisons. Data were analyzed from July 2021 to July 2023. Exposure: Practice-level NQF 0210 quintiles. Main Outcome and Measure: Overall survival. Results: Of 78 446 patients (mean [SD] age, 67.3 [11.1] years; 52.2% female) across 144 practices, the most common cancer types were NSCLC (34 201 patients [43.6%]) and colorectal cancer (15 804 patients [20.1%]). Practice-level NQF 0210 rates varied from 10.9% (quintile 1) to 32.3% (quintile 5) for NSCLC and 6.8% (quintile 1) to 28.4% (quintile 5) for colorectal cancer. No statistically significant differences in survival were observed between patients treated at the highest and the lowest NQF 0210 quintiles. Compared with patients seen at practices in the lowest NQF 0210 quintiles, the hazard ratio for death among patients seen at the highest quintiles varied from 0.74 (95% CI, 0.55-0.99) for those with renal cell carcinoma to 1.41 (95% CI, 0.98-2.02) for those with urothelial cancer. These differences were not statistically significant after applying the Bonferroni-adjusted critical P = .008. Conclusions and Relevance: In this cohort study, patients with metastatic or advanced cancer treated at practices with higher NQF 0210 rates did not have improved survival. Future efforts should focus on helping oncologists identify when additional therapy is futile, developing goals of care communication skills, and aligning payment incentives with improved end-of-life care.

Comparison of the therapeutic effects of febuxostat combined with a low-purine diet and allopurinol combined with a low-purine diet on the improvement of gout patients.

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.

Role of Na/K-ATPase α1 caveolin-binding motif in adipogenesis.

Deficiencies in mice and in humans have brought to the fore the importance of the caveolar network in key aspects of adipocyte biology. The conserved N-terminal caveolin-binding motif (CBM) of the ubiquitous Na/K-ATPase (NKA) α1 isoform, which allows NKA/caveolin-1 (Cav1) interaction, influences NKA signaling and caveolar distribution. It has been shown to be critical for animal development and ontogenesis, as well as lineage-specific differentiation of human induced pluripotent stem cells (hiPSCs). However, its role in postnatal adipogenesis has not been fully examined. Using a genetic approach to alter CBM in hiPSC-derived adipocytes (iAdi-mCBM) and in mice (mCBM), we investigated the regulatory function of NKA CBM signaling in adipogenesis. Seahorse XF cell metabolism analyses revealed impaired glycolysis and decreased ATP synthesis-coupled respiration in iAdi-mCBM. These metabolic dysfunctions were accompanied by evidence of extensive remodeling of the extracellular matrix (ECM), including increased collagen staining, overexpression of ECM marker genes, and heightened TGF-ß signaling uncovered by RNAseq analysis. Rescue of mCBM by lentiviral delivery of WT NKA α1 or treatment of mCBM hiPSCs with the TGF-ß inhibitor SB431542 normalized ECM, suggesting that NKA CBM signaling integrity is required for adequate control of TGF-ß signaling and ECM stiffness during adipogenesis. The physiological impact was revealed in mCBM male mice with reduced fat mass accompanied by histological and transcriptional evidence of elevated adipose fibrosis and decreased adipocyte size. Based on these findings, we propose that the genetic alteration of the NKA/Cav1 regulatory path uncovered in human iAdi leads to lipodystrophy in mice.NEW & NOTEWORTHY A Na/K-ATPase α1 caveolin-binding motif regulates adipogenesis. Mutation of this binding motif in the mouse leads to reduced fat with increased extracellular matrix production and inflammation. RNA-seq analysis and pharmacological interventions in human iPSC-derived adipocytes revealed that TGF-ß signal, rather than Na/K-ATPase-mediated ion transport, is a key mediator of NKA regulation of adipogenesis.