Fluid shear stress regulates the survival of circulating tumor cells via nuclear expansion.

Distant metastasis mainly occurs through hematogenous dissemination, where suspended circulating tumor cells (CTCs) experience a considerable level of fluid shear stress. We recently reported that shear flow induced substantial apoptosis of CTCs, although a small subpopulation could still persist. However, how suspended tumor cells survive in shear flow remains poorly understood. This study finds that fluid shear stress eliminates the majority of suspended CTCs and increases nuclear size, whereas it has no effect on the viability of adherent tumor cells and decreases their nuclear size. Shear flow promotes histone acetylation in suspended tumor cells, the inhibition of which using one drug suppresses shear-induced nuclear expansion, suggesting that shear stress might increase nuclear size through histone acetylation. Suppressing histone acetylation-mediated nuclear expansion enhances shear-induced apoptosis of CTCs. These findings suggest that suspended tumor cells respond to shear stress through histone acetylation-mediated nuclear expansion, which protects CTCs from shear-induced destruction. Our study elucidates a unique mechanism underlying the mechanotransduction of suspended CTCs to shear flow, which might hold therapeutic promise for CTC eradication.

Redox Promoted Rapid and Deep Reconstruction of Defect-Rich Nickel Precatalysts for Efficient Water Oxidation.

Understanding the reconstruction mechanism to rationally design cost-effective electrocatalysts for oxygen evolution reaction (OER) is still challenging. Herein, a defect-rich NiMoO4 precatalyst is used to explore its OER activity and reconstruction mechanism. In situ generated oxygen vacancies, distorted lattices, and edge dislocations expedite the deep reconstruction of NiMoO4 to form polycrystalline Ni (oxy)hydroxides for alkaline oxygen evolution. It only needs ≈230 and ≈285 mV to reach 10 and 100 mA cm-2, respectively. The reconstruction boosted by the redox of Ni is confirmed experimentally by sectionalized cyclic voltammetry activations at different specified potential ranges combined with ex situ characterization techniques. Subsequently, the reconstruction route is presented based on the acid-base electronic theory. Accordingly, the dominant contribution of the adsorbate evolution mechanism to reconstruction during oxygen evolution is revealed. This work develops a novel route to synthesize defect-rich materials and provides new tactics to investigate the reconstruction.

Lipid Identification of Biomarkers in Esophageal Squamous Cell Carcinoma by Lipidomic Analysis.

Lipids participate in many important biological functions through energy storage, membrane structure stabilization, signal transduction, and molecular recognition. Previous studies have shown that patients with esophageal squamous cell carcinoma (ESCC) have abnormal lipid metabolism. However, studies characterizing lipid metabolism in ESCC patients through lipidomics are limited. Plasma lipid profiles of 65 ESCC patients and 42 healthy controls (HC) were characterized by lipidomics-based ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Single-factor and multi-factor statistical analysis were used to screen the differences in blood lipids between groups, and combined with component ratio analysis and receiver operating characteristic (ROC) curve diagnostic efficiency assessment, to reveal the potential mechanisms and biomarkers of ESCC. There were significant differences in lipid profiles between the ESCC and HC groups. Thirty-six differential lipids (11 up-regulated and 25 down-regulated) were selected based on the criteria of p < .05 and fold change > 1.3 or < 0.77. Glycerophospholipids were the major differential lipids, suggesting that these lipid metabolic pathways exhibit a significant imbalance that may contribute to the development of esophageal squamous cell carcinoma. Among them, the seven candidate biomarkers for esophageal squamous cell carcinoma with the highest diagnostic value are three phosphatidylserine (PS), three fatty acids (FA) and one phosphatidylcholine (PC).

Smartphone-Aided Fluorescence Detection of Cardiac Biomarker Myoglobin by a Ratiometric Fluorescent AuNCs-QDs Nanohybrids Probe with High Sensitivity.

Simple and sensitive detection of cardiac biomarkers is of great significance for early diagnosis and prevention of acute myocardial infarction (AMI). Here, a ratiometric fluorescent nanohybrids probe (AuNCs-QDs) was synthesized through the coupling of bovine serum albumin-functionalized gold nanoclusters (AuNCs) with CdSe/ZnS quantum dots (QDs) to realize simple and sensitive detection of cardiac biomarker myoglobin (Mb). The AuNCs-QDs probe shows pink fluorescence under UV light, with two emission peaks at 468 nm and 630 nm belonging to QDs and AuNCs, respectively. Importantly, the presence of Mb caused fluorescence quenching of the blue-emitting QDs, thereby inhibiting the fluorescence resonance energy transfer (FRET) process between QDs and AuNCs, and reducing the fluorescence intensity ratio (F468/F630) of AuNCs-QDs probe effectively. As the concentration of Mb increases, the ratiometric fluorescent probe also exhibits a visible fluorescence color change. The detection limit was as low as 4.99 µg/mL, and the response of the probe to Mb showed a good linear relationship up to 0.52 mg/mL. Moreover, the probe has excellent specificity for Mb. Besides, the AuNCs-QDs has been applied to detect Mb of urine samples. More importantly, we also developed an AuNCs-QDs probe modified smartphone-aided paper-based strip for on-site monitoring of Mb. As far as we know, this is the first report of a smartphone-aided paper-based strip for on-site quick monitoring of Mb, which provides a useful approach for AMI biomarker monitoring and may can be extended to other medical diagnostics.

U-shaped relationship between non-high-density lipoprotein cholesterol and cognitive impairment in Chinese middle-aged and elderly: a cross-sectional study.

BACKGROUND: The relationship between blood lipids and cognitive function has long been a subject of interest, and the association between serum non-high-density lipoprotein cholesterol (non-HDL-C) levels and cognitive impairment remains contentious. METHODS: We utilized data from the 2011 CHARLS national baseline survey, which after screening, included a final sample of 10,982 participants. Cognitive function was assessed using tests of episodic memory and cognitive intactness. We used multiple logistic regression models to estimate the relationship between non-HDL-C and cognitive impairment. Subsequently, utilizing regression analysis results from fully adjusted models, we explored the nonlinear relationship between non-HDL-C as well as cognitive impairment using smooth curve fitting and sought potential inflection points through saturation threshold effect analysis. RESULTS: The results showed that each unit increase in non-HDL-C levels was associated with a 5.5% reduction in the odds of cognitive impairment (OR = 0.945, 95% CI: 0.897-0.996; p < 0.05). When non-HDL-C was used as a categorical variable, the results showed that or each unit increase in non-HDL-C levels, the odds of cognitive impairment were reduced by 14.2%, 20.9%, and 24% in the Q2, Q3, and Q4 groups, respectively, compared with Q1. In addition, in the fully adjusted model, analysis of the potential nonlinear relationship by smoothed curve fitting and saturation threshold effects revealed a U-shaped relationship between non-HDL-C and the risk of cognitive impairment, with an inflection point of 4.83. Before the inflection point, each unit increase in non-HDL-C levels was associated with a 12.3% decrease in the odds of cognitive impairment. After the tipping point, each unit increase in non-HDL-C levels was associated with an 18.8% increase in the odds of cognitive impairment (All p < 0.05). CONCLUSION: There exists a U-shaped relationship between non-HDL-C and the risk of cognitive impairment in Chinese middle-aged and elderly individuals, with statistical significance on both sides of the turning points. This suggests that both lower and higher levels of serum non-high-density lipoprotein cholesterol increase the risk of cognitive impairment in middle-aged and elderly individuals.

Matrix stiffness, endothelial dysfunction and atherosclerosis.

Atherosclerosis (AS) is the leading cause of the human cardiovascular diseases (CVDs). Endothelial dysfunction promotes the monocytes infiltration and inflammation that participate fundamentally in atherogenesis. Endothelial cells (EC) have been recognized as mechanosensitive cells and have different responses to distinct mechanical stimuli. Emerging evidence shows matrix stiffness-mediated EC dysfunction plays a vital role in vascular disease, but the underlying mechanisms are not yet completely understood. This article aims to summarize the effect of matrix stiffness on the pro-atherosclerotic characteristics of EC including morphology, rigidity, biological behavior and function as well as the related mechanical signal. The review also discusses and compares the contribution of matrix stiffness-mediated phagocytosis of macrophages and EC to AS progression. These advances in our understanding of the relationship between matrix stiffness and EC dysfunction open the avenues to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.

RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy.

In recent years, the fabrication of nano-drug delivery systems for targeted treatment of thrombus has become a research hotspot. In this study, we intend to construct a biomimetic nanomedicine for targeted thrombus treatment. The poly lactic-co-glycolic acid (PLGA) was selected as the nanocarrier material. Then, urokinase and perfluoro-n-pentane (PFP) were co-loaded into PLGA by the double emulsification solvent evaporation method to prepare phase change nanoparticles PPUNPs. Subsequently, the RGD peptide-modified red blood cell membrane (RBCM) was coated on the surface of PPUNPs to prepare a biomimetic nano-drug carrier (RGD-RBCM@PPUNPs). The as-prepared RGD-RBCM@PPUNPs possessed a "core-shell" structure, have good dispersibility, and inherited the membrane protein composition of RBCs. Under ultrasound stimulation, the loaded urokinase could be rapidly released. In vitro cell experiments showed that RGD-RBCM@PPUNPs had good hemocompatibility and cytocompatibility. Due to the coated RGD-RBC membrane, RGD-RBCM@PPUNPs could effectively inhibit the uptake of macrophages. In addition, RGD-RBCM@PPUNPs showed better thrombolytic function in vitro. Overall, the results suggested that this biomimetic nanomedicine provided a promising therapeutic strategy for the targeted therapy of thrombosis.

A Unique Chemo-photodynamic Antitumor Approach to Suppress Hypoxia via Ultrathin Graphitic Carbon Nitride Nanosheets Supported a Platinum(IV) Prodrug.

Tumor hypoxia severely restrains the efficiency of irreversible O2-consumption photodynamic therapy. The deep hypoxia induced by photodynamic therapy can promote the level of hypoxia inducible factor 1α that participates in many tumor processes and eventually lead to poor therapeutic outcomes. Herein, a chemo-photodynamic antitumor strategy based on ultrathin graphitic carbon nitride nanosheets loaded with a hypoxia-targeting platinum(IV) prodrug is reported. Under low-intensity visible light irradiation, such integrated nanosheets effectively generate reactive oxygen species together with DNA binding platinum species to achieve enhanced antiproliferation efficacy by downregulating HIF-1α under hypoxic conditions.

A gemcitabine-based conjugate with enhanced antitumor efficacy by suppressing HIF-1α expression under hypoxia.

Hypoxia is one of the unique features of tumor physiology. Hypoxia inducible factor (HIF-1α), as a major transcription factor in response to hypoxia, has been considered as a promising tumor-specific target for anticancer therapy. The formation of a hypoxic microenvironment in tumors can decrease the curative effect of cytotoxic chemotherapeutic drugs. To promote the antitumor efficacy of chemotherapy by suppressing hypoxia, we designed and prepared a novel gemcitabine-based drug conjugate (GEM-5) containing a HIF-1α inhibitor (YC-1). As expected, GEM-5 showed excellent antiproliferative activity (IC50 = 0.03 µΜ under hypoxia) and remarkably induced the apoptosis of A2780 cells in vitro. Additionally, western blot analysis demonstrated that GEM-5 significantly down-regulated the expression of HIF-1α and up-regulated the expression of tumor suppressor p53. More importantly, GEM-5 effectively inhibited tumor growth in the A2780 xenograft mouse model and significantly ameliorated tumor hypoxia in vivo. This novel, simple, and effective strategy for overcoming tumor hypoxia and enhancing the antitumor effect of chemotherapeutic drugs has great potential in cancer therapy.

Design, synthesis and biological evaluation of cinnamamide-quinazoline derivatives as potential EGFR inhibitors to reverse T790M mutation.

Gatekeeper T790M mutation in EGFR is the most common factor for acquired resistance. Acrylamide-bearing 4-anilinoquinazoline scaffold are powerful irreversible inhibitors for overcoming resistance. In this work, three series of EGFR inhibitors derived from incorporation of cinnamamide into the quinazoline scaffold were designed and synthesized to reverse resistance resulting from insurgence of T790M mutation. SAR studies revealed that methoxy and acetoxy substitutions on the cinnamic phenyl ring were found to elevate the activity. In particular, compound 7g emerged as the most potent derivative against mutant-type H1975 cells, which exhibited comparable activity to osimertinib (0.95 µM) towards H1975 cells with an IC50 value of 1.22 µM. Kinase inhibition studies indicated that 7g showed excellent inhibitory effect on EGFRT790M enzyme, which was 11 times more effective than gefitinib. Besides, selectivity index of 7g toward the EGFRT790M mutant over the EGFRWT is 2.72, hinting its effect of reducing off-target. Mechanism study indicated that 7g induced apoptosis of H1975 cells and arrest the cell cycle at G2/M phase in a dose-dependent manner. Moreover, 7g could significantly inhibit the expression of p-EGFR and its downstream p-AKT and p-ERK in H1975 cells. Molecular docking was also performed to gain insights into the ligand-binding interactions of 7g inside EGFRWT and EGFRT790M binding sites.

Exploring the Hydrolytic Behavior of the Platinum(IV) Complexes with Axial Acetato Ligands.

Platinum(IV) complexes are generally thought to be kinetically inert, and are expected to be stable enough to resist premature aquation before entering the cancer cells. Nevertheless, in this work, complex 2 with axial acetato ligands can hydrolyze relatively quickly under biologically relevant conditions with a half-life of 91.7 min, resulting in the loss of the equatorial chlorido ligand. Further study indicated that the fast hydrolysis of complex 2 may be attributed to the strong σ-donor ability of N-isopropyl-1R,2R-diaminocyclohexane, and an increasing σ-donor ability of the amine group can promote the hydrolysis rate of the corresponding platinum(IV) complex. The experiment results were proven by the corresponding DFT calculation. Our study can help to re-evaluate the aqueous properties of the platinum(IV) complexes with axial acetate, which may be less inert to hydrolysis than expected under biologically relevant conditions.

Design, synthesis and biological evaluation of benzylisoquinoline derivatives as multifunctional agents against Alzheimer's disease.

A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced ß-amyloid (Aß) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being 1000-fold and 3-fold more potent than its precursor benzylisoquinoline (10) and the positive control galanthamine, respectively. In addition, 9k was a moderately potent inhibitor for h-ChEs. Compared with precursor benzylisoquinoline (36.0% at 20µÐœ), 9k (78.4% at 20µÐœ) could further inhibit Aß aggregation. Moreover, 9k showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Therefore, compound 9k might be a promising lead compound for AD treatment.

Magnetic multilayer hydrogel oral microrobots for digestive tract treatment.

Oral administration is a convenient drug delivery method in our daily lives. However, it remains a challenge to achieve precise target delivery and ensure the efficacy of medications in extreme environments within the digestive system with complex environments. This paper proposes an oral multilayer magnetic hydrogel microrobot for targeted delivery and on-demand release driven by a gradient magnetic field. The inner hydrogel shells enclose designated drugs and magnetic microparticles. The outer hydrogel shells enclose the inner hydrogel shells, magnetic microparticles, and pH neutralizers. The drug release procedure is remotely implemented layer-by-layer. When the required gradient magnetic field is applied, the outer hydrogel shells are destroyed to release their inclusions. The enclosed pH neutralizers scour the surrounding environment to avoid damaging drugs by the pH environment. Subsequently, the inner hydrogel shells are destroyed to release the drugs. A set of experiments are conducted to demonstrate the wirelessly controllable target delivery and release in a Petri dish and biological tissues. The results demonstrated attractive advantages of the reported microrobot in microcargo delivery with almost no loss, remote controllable release, and drug protection by the pH neutralizers. It is a promising approach to advance next-generation precision oral therapies in the digestive system.

Nano-scale and micron-scale plastics amplify the bioaccumulation of benzophenone-3 and ciprofloxacin, as well as their co-exposure effect on disturbing the antioxidant defense system in mussels, Perna viridis.

Plastics ranging from nano-scale to micron-scale are frequently ingested by many marine animals. These particles exhibit biotoxicity and additionally perform as vectors that convey and amass adsorbed chemicals within organisms. Meanwhile, the frequency of detection of the benzophenone-3 and ciprofloxacin can be adsorbed on plastic particles, then accumulated in bivalves, causing biotoxicity. To understand their unknown accumulative kinetics in vivo affected by different plastic sizes and toxic effect from co-exposure, several scenarios were set up in which the mode organism were exposed to 0.6 mg/L of polystyrene carrying benzophenone-3 and ciprofloxacin in three sizes (300 nm, 38 µm, and 0.6 mm). The live Asian green mussels were chosen as mode organism for exposure experiments, in which they were exposed to environments with plastics of different sizes laden with benzophenone-3 and ciprofloxacin, then depurated for 7 days. The bioaccumulation and depuration kinetics of benzophenone-3 and ciprofloxacin were measured using HPLC-MS/MS after one week of exposure and depuration. Meanwhile, their toxic effect were investigated by measuring the changes in six biomarkers (condition index, reactive oxygen species, catalase, glutathione, lipid peroxidation, cytochrome P450 and DNA damage). The bioconcentration factors in mussels under different exposure conditions were 41.48-111.75 for benzophenone-3 and 6.45 to 12.35 for ciprofloxacin. The results suggested that microplastics and nanoplastics can act as carriers to increase bioaccumulation and toxicity of adsorbates in mussels in a size-dependent manner. Overproduction of reactive oxygen species caused by microplastics and nanoplastics led to increased DNA damage, lipid peroxidation, and changes in antioxidant enzymes and non-enzymatic antioxidants during exposure. Marked disruption of antioxidant defenses and genotoxic effects in mussels during depuration indicated impaired recovery. Compared to micron-scale plastic with sizes over a hundred micrometers that had little effect on bivalve bioaccumulation and toxicity, nano-scale plastic greatly enhanced the biotoxicity effect.

Association between waist circumference and lung function in American middle-aged and older adults: findings from NHANES 2007-2012.

PURPOSE: There is a major epidemic of obesity, and many obese patients suffer from respiratory symptoms and disease. However, limited research explores the associations between abdominal obesity and lung function indices, yielding mixed results. This study aims to analyze the association between waist circumference (WC), an easily measurable marker of abdominal obesity, and lung function parameters in middle-aged and older adults using the National Health and Nutrition Examination Survey (NHANES). METHODS: This study utilized data obtained from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, with a total sample size of 6089 individuals. A weighted multiple regression analysis was conducted to assess the relationship between WC and three pulmonary function parameters. Additionally, a weighted generalized additive model and smooth curve fitting were applied to capture any potential nonlinear relationship within this association. RESULTS: After considering all confounding variables, it was observed that for each unit increase in WC, in males, Forced Vital Capacity (FVC) increased by 23.687 ml, Forced Expiratory Volume in one second (FEV1) increased by 12.029 ml, and the FEV1/FVC ratio decreased by 0.140%. In females, an increase in waist circumference by one unit resulted in an FVC increase of 6.583 ml and an FEV1 increase of 4.453 ml. In the overall population, each unit increase in waist circumference led to a FVC increase of 12.014 ml, an FEV1 increase of 6.557 ml, and a decrease in the FEV1/FVC ratio by 0.076%. By constructing a smooth curve, we identified a positive correlation between waist circumference and FVC and FEV1. Conversely, there was a negative correlation between waist circumference and the FEV1/FVC ratio. CONCLUSIONS: Our findings indicate that in the fully adjusted model, waist circumference, independent of BMI, positively correlates with FVC and FEV1 while exhibiting a negative correlation with FEV1/FVC among middle-aged and older adults in the United States. These results underscore the importance of considering abdominal obesity as a potential factor influencing lung function in American middle-aged and older adults.

Non-linear associations of atherogenic index of plasma with prediabetes and type 2 diabetes mellitus among Chinese adults aged 45 years and above: a cross-sectional study from CHARLS.

Background: Dyslipidemia is strongly associated with the development of prediabetes and type 2 diabetes mellitus (T2DM). The atherogenic index of plasma (AIP), as a comprehensive index for assessing lipid metabolism, has received extensive attention from researchers in recent years. However, there are relatively few studies exploring the relationships between AIP and the risk of prediabetes and T2DM in the Chinese population. This study focuses on exploring the relationships of AIP with the risk of prediabetes and T2DM in the Chinese population. Methods: We conducted an analysis of the public data from the China Health and Retirement Longitudinal Study (CHARLS), involving a total of 12,060 participants aged 45 years and above in China. The study explored the relationships of AIP with prediabetes and T2DM risk through multivariate logistic regression, subgroup analysis, smooth curve fitting, and threshold effect analysis. Results: After adjusting for potential confounding factors, we observed positive associations between AIP and the risk of prediabetes [odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.49-2.06] and T2DM (OR = 2.91, 95% CI: 2.38-3.57). Participants with higher AIP levels demonstrated a significantly elevated risk of prediabetes (OR = 1.52, 95% CI: 1.33-1.74) and T2DM (OR = 2.28, 95% CI: 1.92-2.71) compared to those with lower AIP levels. AIP showed consistent correlations with prediabetes and T2DM risk in different subgroups. The results showed the non-linear relationships between AIP and risk of prediabetes and T2DM, with inflection points at 0.29 and -0.04, respectively. When AIP > 0.29, there was a positive association between AIP and the risk of prediabetes (OR = 2.24, 95% CI: 1.67-3.00, p < 0.0001). Similarly, when AIP > -0.04, AIP was positively associated with the risk of T2DM (OR = 3.33, 95% CI: 2.67-4.16, p < 0.0001). Conclusions: This study demonstrated non-linear positive associations of AIP with the risk of prediabetes and T2DM among participants ≥ 45 years of age in China.

Association of Dietary Inflammatory Index with CKD progression and estimated glomerular filtration rate in the American CKD population: A cross-sectional study.

PURPOSE: The number of CKD patients is on the rise worldwide, and diet has become an essential aspect influencing the treatment and prognosis of CKD. However, limited research has explored the association of the Dietary Inflammatory Index (DII) with CKD progression and the essential kidney function indicator, eGFR, in CKD patients. This study aimed to analyze the association between DII and CKD progression and eGFR in the US CKD population using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study utilized data obtained from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018, with a total sample size of 2,488 individuals. Study used multiple imputation, based on 5 replications and a chained equation approach method in the R MI procedure, to account for missing data. Weighted multiple logistic regression was used to analyze the relationship between DII and the risk of higher CKD stage and a weighted multiple regression analysis was used to assess the relationship between DII and eGFR. Weighted Generalized Additive Models and smoothed curve fitting were applied to detect potential non-linear relationships in this association. RESULTS: In all three models, it was found that DII was positively associated with the risk of higher CKD stage (P < 0.0001), and an increase in DII was associated with a decrease in eGFR (P < 0.0001). The trend across quartiles of DII remained statistically significant, revealing a gradual elevation in higher CKD stage risk and reduction in eGFR levels for the second, third, and fourth quartiles compared to the lowest quartile (P for trend < 0.0001). Upon adjusting for age, gender, race, education level, poverty income ratio (PIR), marital status, body mass index (BMI), metabolic equivalent (MET) score, drinking, smoking, history of hypertension, history of diabetes, cotinine, systolic blood pressure, diastolic blood pressure, total triglycerides, and total cholesterol, we found a positive correlation between DII and the risk of higher CKD stage (OR = 1.26, 95% CI: 1.14-1.40). Further investigation revealed that an increase in DII was associated with a decrease in eGFR (ß = -1.29, 95% CI: -1.75, -0.83). Smooth curves illustrated a non-linear positive correlation between DII and CKD risk, while a non-linear negative correlation was observed between DII and eGFR. CONCLUSIONS: Our study results indicate that an increase in DII is associated with an increased risk of higher CKD stage and a decrease in eGFR in all three models. In the fully adjusted model, the risk of higher CKD stage increased by 26% and the eGFR decreased by 1.29 ml/min/1.73 m2 for each unit increase in DII. This finding suggests that in patients with CKD in the US, improved diet and lower DII values may help slow the decline in eGFR and delay the progression of CKD.

Triglyceride-Glucose Index and Its Correlates: Associations with Serum Creatinine and Estimated Glomerular Filtration Rate in a Cross-Sectional Study from CHARLS 2011-2015.

Background: Chronic kidney disease (CKD) has emerged as a significant global public health challenge, and the estimated glomerular filtration rate (eGFR) is widely used due to its convenience, low cost, and broad clinical applicability. Concurrently, insulin resistance (IR) serves as a crucial marker of metabolic disturbance, and alternative indicators have garnered increasing attention in CKD research in recent years. Objective: This study aims to investigate the relationship between IR-related indices (TyG index, TyG-BMI index, and TyG-WC index) and serum creatinine levels, as well as the eGFR, with the intention of uncovering their potential roles in the assessment of renal function. Methods: We analyzed nationally representative cross-sectional data from a cohort of individuals aged 45 and above in China, comprising 11,608 participants. Participants were categorized into different groups based on quartiles of the TyG index, and multiple factors, including gender, age, lifestyle, and co-morbidities, were adjusted for using linear regression models. Results: By linear regression, TyG, TyG-BMI, and TyG-WC indices were significantly positively correlated with serum creatinine and significantly negatively correlated with eGFR. Results showed similar trends when TyG, TyG-BMI, and TyG-WC indices were used as categorical variables. In the fully adjusted model, the highest quartile of serum creatinine was higher than the first quartile for TyG, TyG-BMI, and TyG-WC indices, with ß values of 2.673, 3.67, and 1.937 mg/dL, respectively; the highest quartile of eGFR was lower than the first quartile, with ß values of -2.4, -2.955, and -1.823 mL/min/1.73 m2. P values were statistically significant. Conclusions: This study indicates a consistent correlation between the TyG index and its related indices with serum creatinine levels and eGFR among the middle aged and elderly population in China. These findings suggest the potential utility of these indices in early screening and management of the risk of chronic kidney disease.

Recent advances of mechanosensitive genes in vascular endothelial cells for the formation and treatment of atherosclerosis.

Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide. Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells, and it plays an important role in gene regulation of pro-inflammatory, pro-thrombotic, pro-oxidative stress, and cell permeability. Many important endothelial cell mechanosensitive genes have been discovered, including KLK10, CCN gene family, NRP2, YAP, TAZ, HIF-1α, NF-κB, FOS, JUN, TFEB, KLF2/KLF4, NRF2, and ID1. Some of them have been intensively studied, whereas the relevant regulatory mechanism of other genes remains unclear. Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease. Thus, this article reviews the mechanosensitive genes affecting vascular endothelial cells, including classical pathways and some newly screened genes, and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights for anti-atherosclerosis.