Formal estimation of wireless network services for signal strength and electromagnetic wave association in an International Green University.

The United Nations focuses on 17 urgent problems to call for action in all countries. Goal 7 of the 17 urgent problems is based on affordable and clean energy. Since 2017, National Taitung University (NTTU) has dedicated more time and effort to attain the wisdom, health, sustainability and aesthetics as an international green university. To accomplish this, we adhere and construct a safe radiofrequency and electromagnetic wave environment to achieve healthy and sustainable campus objectives. According to the UI GreenMetric World University Rankings, NTTU was ranked 74th in 2021, 67th in 2022 and 58th in 2023. In this study, we propose a formal estimation of wireless network services for classrooms or smart spaces to achieve the goal of safe radiofrequency and electromagnetic waves. Inside classrooms or smart spaces, better wireless signal strength and safer electromagnetic waves are achieved. Moreover, the proposed method can be used to determine the quantity of wireless access points for a given classroom or smart space to avoid unsafe electromagnetic waves and inappropriate energy consumption. The experimental results show that all benchmarks meet the wireless exposure limits of the WHO and physician safe technologies in the NTTU.

Expression feature and prognostic function of a novel immune checkpoint Siglec-15 in human colorectal cancer.

BACKGROUND: Sialic acid-bound immunoglobulin lectin 15 (Siglec-15) plays an important role in the development of cancer. However, the association between Siglec-15 expression and clinicopathological characteristics of colorectal cancer (CRC) has not been fully investigated. METHODS: In this present study, a number of bioinformatics analyses were performed to provide an overview and detailed characteristics of Siglec-15. Quantitative real-time polymerase chain reaction (qPCR), western blotting and immunohistochemistry analyses were conducted to characterize the expression of Siglec-15 in CRC. Kaplan-Meier survival and Cox regression analyses were performed to identify the prognostic parameters of CRC. RESULTS: The results of bioinformatics analyses revealed the expression characteristics and prognostic roles of Siglec-15 in CRC. The data of qCPR, western blotting, and IHC analyses demonstrated that the expression of Siglec-15 in CRC tissues was significantly higher than that in non-cancerous tissues. Moreover, the expression level of Siglec-15 in CRC was significantly associated with lymph node metastasis (p=0.001), TNM stage (p=0.001), and overall survival (p=0.026). COX multi-factor analysis indicated that Siglec-15 expression (p=0.023) and tumor differentiation (p=0.003) were independent prognostic factors for CRC. CONCLUSIONS: Collectively, the data suggested that Siglec-15 expression may serve as a novel prognostic factor and Siglec-15 might be identified as an ideal candidate for immunotherapy in CRC treatment.

The essential role of dual-energy x-ray absorptiometry in the prediction of subclinical cardiovascular disease.

Subclinical cardiovascular disease (Sub-CVD) is an early stage of cardiovascular disease and is often asymptomatic. Risk factors, including hypertension, diabetes, obesity, and lifestyle, significantly affect Sub-CVD. Progress in imaging technology has facilitated the timely identification of disease phenotypes and risk categorization. The critical function of dual-energy x-ray absorptiometry (DXA) in predicting Sub-CVD was the subject of this research. Initially used to evaluate bone mineral density, DXA has now evolved into an indispensable tool for assessing body composition, which is a pivotal determinant in estimating cardiovascular risk. DXA offers precise measurements of body fat, lean muscle mass, bone density, and abdominal aortic calcification, rendering it an essential tool for Sub-CVD evaluation. This study examined the efficacy of DXA in integrating various risk factors into a comprehensive assessment and how the application of machine learning could enhance the early discovery and control of cardiovascular risks. DXA exhibits distinct advantages and constraints compared to alternative imaging modalities such as ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography. This review advocates DXA incorporation into cardiovascular health assessments, emphasizing its crucial role in the early identification and management of Sub-CVD.

Model Predicting the Risk of Endometrial Hyperplasia Developing into Endometrial Cancer.

Background: This study retrospectively analyzed the medical records of 200 patients with endometrial hyperplasia to predict the risk of concurrent endometrial cancer. Methods: Patients were categorized into either the endometrial cancer group or the endometrial hyperplasia group based on post-hysterectomy pathology. The investigation compared general information, tumor indices, fertility history, preoperative endometrial sampling methods, comorbidities, and clinical symptoms between the groups to identify risk factors for endometrial hyperplasia complicating endometrial cancer. Results: (1) Of the 200 patients, 68 (34.0%) were diagnosed with concurrent endometrial cancer post-hysterectomy. Among these, 60 (88.24%) had endometrioid adenocarcinoma, while 8 (11.76%) had other types. Stage I was identified in 58 patients (85.29%) and Stage II in 10 patients (14.71%). High differentiation was observed in 57 cases (83.82%), moderate differentiation in 7 cases (10.29%), and poor differentiation in 4 cases (5.89%), indicating that most endometrial cancers complicated by hyperplasia were early-stage, well-differentiated endometrioid carcinomas; (2) Univariate analysis revealed statistically significant differences in age, menopausal status, length of menopause, and preoperative endometrial pathology of severe atypical hyperplasia between the groups; (3) Multivariate analysis indicated significant differences for age ≥ 53.5 years (OR: 4.307, 95% CI: 2.018-9.192, p < 0.05), menopausal status (OR: 5.250, 95% CI: 2.449-11.252, p < 0.05), and severe atypical endometrial hyperplasia (OR: 4.817, 95% CI: 1.260-18.419, p < 0.05); (4) Significant differences were observed among patients with endometrial hyperplasia when stratified by the presence of zero, one, two, or three high-risk factors. Conclusion: In conclusion, patients aged ≥ 53.5 years, those who are menopausal, and those with severe atypical endometrial hyperplasia preoperatively are at higher risk for endometrial cancer. The risk increases with the number of high-risk factors present in patients with atypical endometrial hyperplasia.

Melatonin Improves Oxidative Stress Injury in Retinopathy of Prematurity by Targeting miR-23a-3p/Nrf2.

PURPOSE: Melatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model. METHODS: Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, ß-actin, and Lamin B1. RESULTS: Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2. CONCLUSION: Our study showed that melatonin could ameliorate H2O2-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration.

Rapid prediction of the chemical composition of pet food using a benchtop and handheld near-infrared spectrometer.

Quality of pet foods can be affected by many factors such as raw materials, formulations, and processing techniques. The pet food manufacturers require fast analyses to control the nutritional quality of their products. Herein, near-infrared spectroscopy (NIR) was evaluated to quantify the chemical composition of pet food, and the performances of two NIR spectrometers were investigated and compared: a benchtop instrument (1000-2500 nm) and a low-cost handheld instrument (900-1700 nm). Seventy cat food and thirty-six dog samples were characterized using reference methods for crude protein, crude fat, crude fibre, crude ash, moisture, calcium (Ca), and phosphorus (P). Principal component regression (PCR) and partial least squares regression (PLSR) were used to establish the models that involved the cat food and mixed model. The characteristic wavelengths were selected using a competitive adaptive reweighted-sampling (CARS) algorithm. The Optimal models obtained from the benchtop instrument for crude protein, crude fat, and moisture were classified as "Good" or "Very good" (Residual prediction variation (RPD) > 3), for crude fibre were classified as "Poor" (RPD>2), and for crude ash, Ca and P (RPD<2) were classified as "Very poor". The Optimal calibrations obtained from the handheld instrument for crude protein, crude fat, and moisture were classified as "Good" or "Very good" (RPD>3), for crude fibre, crude ash, Ca, and P were classified as "Very poor" (RPD<2). Generally, the the performance of benchtop and handheld instrument was close, and the cat food model outperformed the mixed model. Results from the current study revealed the potential to monitor the chemical compositions in pet food on a large scale.

Electrochemical Na+/K+ Ion Exchange in Zeolitic Vanadium(IV) Borophosphate K1.33Na0.67[VO(B2O)(PO4)2(HPO4)]·1.63H2O as Cathode Material for Sodium-Ion Batteries.

Electrochemical ion exchange has recently been demonstrated to be a unique method for the preparation of novel cathode materials, which cannot be accessible by traditional direct synthesis routes. In this study, the vanadium borophosphate compound K1.33Na0.67[VO(B2O)(PO4)2(HPO4)]·1.63H2O (KNVBP) with zeolitic framework exhibits fast electrochemical Na+/K+ ion exchange when used as cathode material in sodium-ion batteries (SIBs). Ex situ structural analyses and electrochemical measurements confirm that most of the K+ ions in the parent KNVBP can be extracted and exchanged by Na+ ions after the first charge/discharge cycle. The in situ-generated Na-rich phase shows reversible electrochemical activity at approximately 3.9 V versus Na+/Na with a specific capacity of 52.9 mAh g-1, comparable to 96.2% of the theoretical capacity. Moreover, enhanced ionic diffusion kinetics can be achieved after the Na+/K+ exchange. This study provides a valuable insight into the electrochemical ion exchange in polyanion compounds toward application in metal-ion batteries.

Anion Substitution to Suppress the Voltage Hysteresis of Na3MnTi(PO4)3 as a Cathode Material for Sodium-Ion Batteries.

The Mn-based polyanion compound Na3MnTi(PO4)3 (NMTP) with a Na superionic conductor (NASICON) structure has attracted incremental attention as a potential cathode material for sodium-ion batteries. However, the occupation of Mn2+ on Na+ vacancies usually leads to severe voltage hysteresis, which in turn results in significant capacity loss, slow Na+ diffusion kinetics, and poor cycling stability. Herein, anion-substituted compounds Na3MnTi(PO4)3-x(SiO4)x (x = 0.1, 0.2, and 0.3) are synthesized. It reveals that the SiO44- substitution could induce partial oxidation of Mn2+ to Mn3+, and the latter has a lower occupancy preference on Na+ vacancies. By the proposed charge compensation strategy, the Mn2+ occupation on Na+ vacancies can be significantly suppressed. As a result, the voltage hysteresis is substantially inhibited, and greatly improved electrochemical performance is achieved. This study offers an alternative strategy to address the voltage hysteresis associated with NMTP and other Mn-based NASICON cathode materials.

A longitudinal evaluation of oxidative stress - mitochondrial dysfunction - ferroptosis genes in anthracycline-induced cardiotoxicity.

BACKGROUND: Antineoplastic medications, including doxorubicin, idarubicin, and epirubicin, have been found to adversely affect the heart due to oxidative stress - mitochondrial dysfunction - ferroptosis (ORMFs), which act as contributing attributes to anthracycline-induced cardiotoxicity. To better understand this phenomenon, the time-resolved measurements of ORMFS genes were analyzed in this study. METHODS: The effect of three anthracycline drugs on ORMFs genes was studied using a human 3D cardiac microtissue cell model. Transcriptome data was collected over 14 days at two doses (therapeutic and toxic). WGCNA identified key module-related genes, and functional enrichment analysis investigated the biological processes quantified by ssGSEA, such as immune cell infiltration and angiogenesis. Biopsies were collected from heart failure patients and control subjects. GSE59672 and GSE2965 were collected for validation. Molecular docking was used to identify anthracyclines's interaction with key genes. RESULTS: The ORMFs genes were screened in vivo or in vitro. Using WGCNA, six co-expressed gene modules were grouped, with MEblue emerging as the most significant module. Eight key genes intersecting the blue module with the dynamic response genes were obtained: CD36, CDH5, CHI3L1, HBA2, HSD11B1, OGN, RPL8, and VWF. Compared with control samples, all key genes except RPL8 were down-regulated in vitro ANT treatment settings, and their expression levels varied over time. According to functional analyses, the key module-related genes were engaged in angiogenesis and the immune system pathways. In all ANT-treated settings, ssGSEA demonstrated a significant down-regulation of angiogenesis score and immune cell activity, including Activated CD4 T cell, Immature B cell, Memory B cell, Natural killer cell, Type 1 T helper cell, and Type 2 T helper cell. Molecular docking revealed that RPL8 and CHI3L1 show significant binding affinity for anthracyclines. CONCLUSION: This study focuses on the dynamic characteristics of ORMFs genes in both human cardiac microtissues and cardiac biopsies from ANT-treated patients. It has been highlighted that ORMFs genes may contribute to immune infiltration and angiogenesis in cases of anthracycline-induced cardiotoxicity. A thorough understanding of these genes could potentially lead to improved diagnosis and treatment of the disease.

Integration of serum pharmacochemistry with network pharmacology to reveal the potential mechanism of Yangqing Chenfei formula for the treatment of silicosis.

OBJECTIVE: To explore the mechanisms of Yangqing Chenfei formula (, YCF) in the treatment of silicosis through a comprehensive strategy consisting of serum pharmacochemistry, network pharmacology analysis, and in vitro validation. METHODS: An ultrahigh-performance liquid chroma-tography-tandem mass spectrometry method was used to confirm the active components in YCF-medicated serum. Then, we obtained targets for active components and genes for silicosis from multiple databases. Furthermore, a protein-protein interaction network was constructed, and Kyoto Encyclopedia of Genes and Genomes pathway and biological process analyses were conducted to elucidate the mechanisms of YCF for the treatment of silicosis. Finally, we validated the important components and mechanisms in vitro. RESULTS: Altogether, 19 active components were identified from rat serum after YCF administration. We identified 724 targets for 19 components, which were mainly related to inflammation [phosphatidy linositol 3 kinase/protein kinase B, forkhead box O, hypoxia inducible factor, and T-cell receptor signaling pathway, nitric oxide biosynthetic process], fibrotic processes [vascular endothelial growth factor signaling pathway, extracellular signal regulated kinase (ERK) 1 and ERK2 cascade, smooth muscle cell proliferation], and apoptosis (negative regulation of apoptotic process). In addition, 218 genes for silicosis were identified and were mainly associated with the inflammatory response and immune process [cytokine?cytokine receptor interaction, tumor necrosis factor alpha (TNF-α), toll-like receptor, and nucleotide binding oligomerization domain-like receptor signaling pathway]. Taking an intersection of active component targets and silicosis genes, we obtained 61 common genes that were mainly related to the inflammatory response and apoptosis, such as the phosphatidylinositol-3-kinase/protein kinase B signaling pathway, mitogen activated protein kinases signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, biosynthesis of nitric oxide, and apoptotic process. In the herb-component-gene-pathway network, paeoniflorin, rutin and nobiletin targeted the most genes. In vitro, paeoniflorin, rutin and nobiletin decreased the mRNA levels of inflammatory factors [interleukin (IL)-6, TNF-α, and IL-1ß], suppressed p-AKT and cleaved caspase-3, and increased B cell lymphoma (Bcl)-2 protein expression in silica-induced macrophages in a concentration-dependent manner. CONCLUSION: YCF could significantly relieve the inflammatory response of silicosis via suppression of the AKT/Bcl-2/Caspase-3 pathway.

Sanhua Tang protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and experiments.

OBJECTIVE: To assess the effect and mechanism of Sanhua Tang (, SHT) in treating ischemic stroke (IS) through the "Kaitong Xuanfu" theory by using network pharmacology and animal experiments. METHODS: The active ingredients and targets of SHT and IS were screened by public databases such as Traditional Chinese Medicine systems pharmacology, GeneCards, and online mendelian inheritance in man. Visual network topographies were constructed using R, Cytoscape 3.6.0, AutoDockTools, a user-sponsored molecular visualization system on an open-source foundation, and other software to analyze the correlation between targets and active ingredients. The middle cerebral artery occlusion (MCAO) model was established by operation. Animals were divided into the Sham group, MCAO group (M group), aloe-emodin (AE) group (MCAO rats treated with aloe-emodin), SHT at low dosage (SL group) (MCAO rats treated with SL), SHT at medium dosage (SM group), and SHT at high dosage (SH group). 2,3,5-triphenyl tetrazolium chloride staining was used to detect the volume of cerebral infarction; Nissl staining was used to observe the morphology of neuronal cells; transmission electron microscopy was used to observe the integrity of the blood-brain barrier (BBB); enzyme-linked immunosorbent assay was used to detect the content of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α) in serum. Western blot was used to detect the expression of vascular endothelial growth factor A (VEGFA) protein in the cerebral ischemic penumbra. RESULTS: Using network pharmacology and molecular docking validation, four active ingredients (lignan, naringenin, aloe-rhodopsin, and ß-sitosterol), seven target proteins (protein kinase b 1, IL-6, TNF, VEGFA, TP53, jun proto-oncogene, and cysteinyl aspartate specific proteinase 3), and inflammatory signaling pathways were identified. Animal experiments showed that the SH and AE groups had fewer neurological deficits, reduced brain infarct volumes, decreased serum inflammatory factor levels, increased expression of VEGFA protein, and less structural damage to neurons and BBB. CONCLUSION: The present study found that the therapeutic mechanism of SHT against IS may be related to the inhibition of BBB inflammatory damage, which is also the mechanism of "Kaitong Xuanfu." The high-dose group of SHT was relatively effective in regulating inflammatory factors, improving BBB permeability, and protecting neuronal cells from damage.

A mediation approach in resting-state connectivity between the medial prefrontal cortex and anterior cingulate in mild cognitive impairment.

Mild cognitive impairment (MCI) is recognized as the prodromal phase of dementia, a condition that can be either maintained or reversed through timely medical interventions to prevent cognitive decline. Considerable studies using functional magnetic resonance imaging (fMRI) have indicated that altered activity in the medial prefrontal cortex (mPFC) serves as an indicator of various cognitive stages of aging. However, the impacts of intrinsic functional connectivity in the mPFC as a mediator on cognitive performance in individuals with and without MCI have not been fully understood. In this study, we recruited 42 MCI patients and 57 healthy controls, assessing their cognitive abilities and functional brain connectivity patterns through neuropsychological evaluations and resting-state fMRI, respectively. The MCI patients exhibited poorer performance on multiple neuropsychological tests compared to the healthy controls. At the neural level, functional connectivity between the mPFC and the anterior cingulate cortex (ACC) was significantly weaker in the MCI group and correlated with multiple neuropsychological test scores. The result of the mediation analysis further demonstrated that functional connectivity between the mPFC and ACC notably mediated the relationship between the MCI and semantic fluency performance. These findings suggest that altered mPFC-ACC connectivity may have a plausible causal influence on cognitive decline and provide implications for early identifications of neurodegenerative diseases and precise monitoring of disease progression.

A phase 1, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of SHR-1905, a long-acting anti-thymic stromal lymphopoietin antibody, in healthy subjects.

Introduction: Thymic stromal lymphopoietin (TSLP) is integral to inducing innate and T helper two cell inflammation that leads to clinical symptoms of asthma. SHR-1905 is a humanized immunoglobulin G1 kappa monoclonal antibody that inhibits TSLP bioactivity, developed for the treatment of severe uncontrolled asthma. This phase 1, randomized, double-blind, placebo-controlled single ascending dose study assessed the safety, tolerability, pharmacokinetics (PK), and immunogenicity of subcutaneous SHR-1905 in healthy subjects. Methods: Five dose cohorts were planned (50, 100, 200, 400, and 600 mg) and subjects were randomized (8:2) in each cohort to receive SHR-1905 or placebo with a follow-up period up to Day 253. Results: The majority of treatment-emergent adverse events (TEAEs) were mild and the incidence of TEAEs was comparable between the SHR-1905 and the placebo groups. The maximum serum concentration was reached 7.0-17.6 days after injection. The serum concentration of SHR-1905 increased with increasing dose level, and SHR-1905 exposure exhibited in a slightly greater-than-dose-proportional manner from 50 to 600 mg. SHR-1905 had a prolonged serum half-life around 80 days supporting every 6-month dosing. In SHR-1905 treated subjects, 15% tested positive for anti-drug antibodies post-dose with no apparent effect on corresponding PK profiles or safety. Conclusion: SHR-1905 demonstrated a good safety and tolerability profile with a long half-life in healthy subjects after a single administration in the dose range of 50-600 mg. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04800263.

Prediction of developmental toxic effects of fine particulate matter (PM2.5) water-soluble components via machine learning through observation of PM2.5 from diverse urban areas.

The global health implications of fine particulate matter (PM2.5) underscore the imperative need for research into its toxicity and chemical composition. In this study, zebrafish embryos exposed to the water-soluble components of PM2.5 from two cities (Harbin and Hangzhou) with differences in air quality, underwent microscopic examination to identify primary target organs. The Harbin PM2.5 induced dose-dependent organ malformation in zebrafish, indicating a higher level of toxicity than that of the Hangzhou sample. Harbin PM2.5 led to severe deformities such as pericardial edema and a high mortality rate, while the Hangzhou sample exhibited hepatotoxicity, causing delayed yolk sac absorption. The experimental determination of PM2.5 constituents was followed by the application of four algorithms for predictive toxicological assessment. The random forest algorithm correctly predicted each of the effect classes and showed the best performance, suggesting that zebrafish malformation rates were strongly correlated with water-soluble components of PM2.5. Feature selection identified the water-soluble ions F- and Cl- and metallic elements Al, K, Mn, and Be as potential key components affecting zebrafish development. This study provides new insights into the developmental toxicity of PM2.5 and offers a new approach for predicting and exploring the health effects of PM2.5.

Gelatin methacryloyl microneedle loaded with 3D-MSC-Exosomes for the protection of ischemia-reperfusion.

Exosomes (Exo) generated from mesenchymal stem cells (MSCs) have great therapeutic potential in ischemia-reperfusion treatment. For best therapeutic effect, high quality Exo product and effective delivery system are indispensable. In this study, we developed a new strategy for ischemia-reperfusion recovery by combining MSCs 3D (3D-MSC) culturing technology to generate Exo (3D-MSC-Exo) and microneedle for topical delivery. Firstly, primary MSCs from neonatal mice were isolated and 3D cultured with gelatin methacryloyl (GelMA) hydrogel to prepare 3D-MSC-Exo. The 3D-MSC showed better viability and 3D-MSC-Exo exhibited more effective effects of reducing neuroinflammation, inhibiting glial scarring, and promoting angiogenesis. Subsequently, the biocompatible GelMA was used to construct microneedles for 3D-Exo delivery (GelMA-MN@3D-Exo). The results demonstrated GelMA microneedles had excellent 3D-Exo loading capacity and enabled continuous 3D-Exo release to maintain effective therapeutic concentrations. Furthermore, the rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic effect of GelMA-MN@3D-Exo in ischemia-reperfusion in vivo. Animal experiments showed that the GelMA-MN@3D-Exo system could effectively reduce the local neuroinflammatory reaction, promote angiogenesis and minimize glial scar proliferation in ischemia-reperfusion. The underlying reasons for the stronger neuroprotective effect of 3D-Exo was further studied using mass spectrometry and transcriptome assays, verifying their effects on immune regulation and cell proliferation. Taken together, our findings demonstrated that GelMA-MN@3D-Exo microneedle can effectively attenuate ischemia-reperfusion cell damage in the MCAO model, which provides a promising therapeutic strategy for ischemia-reperfusion recovery.

Association between Life's Essential 8 and estimated pulse wave velocity among adults in the US: a cross-sectional study of NHANES 2011-2018.

Background: Arterial stiffness, typically evaluated via estimated pulse wave velocity (ePWV), is believed to have a significant association with cardiovascular diseases. The objective of this study was to investigate the correlation between Life's Essential 8 (LE8), a newly revised metric of cardiovascular health, and ePWV among adult population in the United States. Methods: This research employed a cross-sectional methodology, drawing upon data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2011 to 2018. To explore the relationship between LE8 and ePWV among adults in the US, both univariate and multivariate linear regression analyses were carried out. Additionally, the restricted cubic splines method was utilized to examine any non-linear correlation. Results: The study comprised 6,742 participants with an average age of 48.30 ± 0.35 years. Among these, 3,236 were males, representing a weighted percentage of 48%. The population's weighted average LE8 score was 68.68 ± 0.37, while the average ePWV was 8.18 ± 0.04. An entirely adjusted model revealed a negative correlation between ePWV and LE8 scores [in the moderate LE8 group, coefficient - 0.17, 95% CI -0.28 to -0.06, p = 0.004; in the high LE8 group, coefficient - 0.44, 95% CI -0.56 to -0.32, p < 0.0001]. This negative correlation was consistent with the findings in demographic subgroup analysis, with the effect size being more pronounced among adults under the age of 60, and individuals without hypertension, cardiovascular disease, or diabetes. Conclusion: Our study reveals a negative correlation between LE8 and ePWV in the adult population of the US, suggesting that LE8 could potentially serve as an indicative marker for evaluating the risk of vascular stiffness. This inverse relationship is markedly stronger in adults below 60 years and those without diagnosed vascular diseases. This implies that lifestyle upgrades and risk factor management could be especially advantageous in curbing arterial stiffness within these groups. These conclusions underscore the importance of primary prevention in mitigating the risk of vascular aging in a relatively healthy group, emphasizing the significance of early intervention and risk factor management in cardiovascular disease.

Marrow mesenchymal stem cell mediates diabetic nephropathy progression via modulation of Smad2/3/WTAP/m6A/ENO1 axis.

Diabetic nephropathy (DN) is one of the common microvascular complications in diabetic patients. Marrow mesenchymal stem cells (MSCs) have attracted attention in DN therapy but the underlying mechanism remains unclear. Here, we show that MSC administration alleviates high glucose (HG)-induced human kidney tubular epithelial cell (HK-2 cell) injury and ameliorates renal injury in DN mice. We identify that Smad2/3 is responsible for MSCs-regulated DN progression. The activity of Smad2/3 was predominantly upregulated in HG-induced HK-2 cell and DN mice and suppressed with MSC administration. Activation of Smad2/3 via transforming growth factor-ß1 (TGF-ß1) administration abrogates the protective effect of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Smad2/3 has been reported to interact with methyltransferase of N6-methyladenosine (m6A) complex and we found a methyltransferase, Wilms' tumor 1-associating protein (WTAP), is involved in MSCs-Smad2/3-regulated DN development. Moreover, WTAP overexpression abrogates the improvement of MSCs on HG-induced HK-2 cell injury and renal injury of DN mice. Subsequently, α-enolase (ENO1) is the downstream target of WTAP-mediated m6A modification and contributes to the MSCs-mediated regulation. Collectively, these findings reveal a molecular mechanism in DN progression and indicate that Smad2/3/WTAP/ENO1 may present a target for MSCs-mediated DN therapy.

The gut-brain-axis: A positive relationship between gut microbial dysbiosis and glioblastoma brain tumour.

The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while Firmicutes experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae in GBM patients, while levels of Veillonellaceae, Rikenellaceae, and Prevotellaceae were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of Parasutterella, Escherichia-Shigella, and Bacteroides, alongside significantly lower levels of Ruminococcus 2, Faecalibacterium, and Prevotella_9 in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in Bacteroides vulgatus and Escherichia coli in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.

BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in MI/R induced myocyte apoptosis.

BACKGROUND: Cardiomyocyte apoptosis plays a vital role in myocardial ischemia-reperfusion (MI/R) injury; however, the role of beclin1 (BECN1) remains unclear. This study aimed at revealing the function of BECN1 during cardiomyocyte apoptosis after MI/R injury. METHODS: In vivo, TTC and Evan's blue double staining was applied to verify the gross morphological alteration in both wild type (WT) mice and BECN1 transgene mice (BECN1-TG), and TUNEL staining and western blot were adopted to evaluate the cardiomyocyte apoptosis. In vitro, a hypoxia/reoxygenation (H/R) model was established in H9c2 cells to simulate MI/R injury. Proteomics analysis was preformed to verify if apoptosis occurs in the H/R cellular model. And apoptosis factors, RIPK1, Caspase-1, Caspase-3, and cleaved Caspase-3, were investigated using western bolting. In addition, the mRNA level were verified using RT-PCR. To further investigate the protein interactions small interfering RNA and lentiviral transfection were used. To continue investigate the protein interactions, immunofluorescence and coimmunoprecipitation were applied. RESULTS: Morphologically, BECN1 significantly attenuated the apoptosis from TTC-Evan's staining, TUNEL, and cardiac tissue western blot. After H/R, a RIPK1-induced complex (complex II) containing RIPK1, Caspase-8, and FADD was formed. Thereafter, cleaved Caspase-3 was activated, and myocyte apoptosis occurred. However, BECN1 decreased the expression of RIPK1, Caspase-8, and FADD. Nevertheless, BECN1 overexpression increased RIPK1 ubiquitination before apoptosis by inhibiting OTUD1. CONCLUSIONS: BECN1 regulates FADD/RIPK1/Caspase-8 complex formation via RIPK1 ubiquitination by downregulating OTUD1 in C-Caspase-3-induced myocyte apoptosis after MI/R injury. Therefore, BECN1 can function as a cardioprotective candidate.