Identification of mitophagy-related genes and analysis of immune infiltration in the astrocytes based on machine learning in the pathogenesis of major depressive disorder.

BACKGROUNDS: Major depressive disorder (MDD) is a pervasive mental and mood disorder with complicated and heterogeneous etiology. Mitophagy, a selective autophagy of cells, specifically eliminates dysfunctional mitochondria. The mitochondria dysfunction in the astrocytes is regarded as a critical pathogenetic mechanism of MDD. However, studies on the mitophagy of astrocytes in MDD are scarce. To explore the impact of mitophagy on the astrocytes, we used bioinformatic methods to analyze the correlation between astrocyte-related genes and mitophagy-related genes in MDD. METHODS: The microarray dataset of MDD was downloaded from the Gene Expression Omnibus database and identified astrocyte- and mitophagy-related differentially expressed genes (AMRDEGs). We used three machine learning algorithms to identify hub AMRDEGs and constructed a diagnostic prediction model. Also, we analyzed transcription factor-gene and gene-microRNA interaction networks, and the immune infiltration in MDD and healthy controls. Besides, we performed consensus clustering analysis, immune infiltration analysis, and gene set variation analysis of MDD samples. RESULTS: The present research identified 3 hub AMRDEGs (GRN, NDUFAF4, and SNCA), and a good diagnostic model with potential clinical applications was constructed and validated. Besides, we identified 6 transcription factors and 14 microRNAs. The immune infiltration analysis showed that MDD was closely related to immune cells. Gene set variant analysis showed that MDD was related to immune and mitochondrial metabolism and inflammatory signaling pathways. CONCLUSIONS: We identified 3 hub AMRDEGs, new biomarkers for treating and diagnosing MDD and associated with immuno-inflammation. Our research provides new insights into the early diagnosis and treatment of MDD.

Comparative analysis of bile acid composition and metabolism in the liver of Bufo gargarizans aquatic larvae and terrestrial adults.

Bile acids are crucial for lipid metabolism and their composition and metabolism differ among species. However, there have been no data on the differences in the composition and metabolism of bile acids between aquatic larvae and terrestrial adults of amphibians. This study explored the differences in composition and metabolism of bile acid between Bufo gargarizans larvae and adults. The results demonstrated that adult liver had a lower total bile acid level and a higher conjugated/total bile acid ratio than larval liver. Meanwhile, histological analysis revealed that the larvae showed a larger cross-sectional area of bile canaliculi lumen compared with the adults. The transcriptomic analysis showed that B. gargarizans larvae synthesized bile acids through both the alternative and the 24-hydroxylase pathway, while adults only synthesized bile acids through the 24-hydroxylase pathway. Moreover, bile acid regulator-related genes FXR and RXRα were highly expressed in adult, whereas genes involved in bile acid synthesis (CYP27A1 and CYP46A1) were highly expressed in larvae. The present study will provide valuable insights into understanding metabolic disorders and exploring novel bile acid-based therapeutics.

Efficient photocatalytic in-situ Fenton degradation of 2,4-dichlorophenol via anthraquinone-modified carbon nitride for 2e- oxygen reduction.

Constructing a photocatalytic in-situ Fenton system (PISFs) is a promising strategy to address the need for continuous hydrogen peroxide (H2O2) addition and the low efficiency of H2O2 activation for hydroxyl radical generation in the traditional Fenton reaction. In this study, we constructed a photocatalytic in-situ Fenton system using anthraquinone-modified carbon nitride (AQ-C3N4) for efficient pollutant degradation. The resultant AQ-C3N4 not only enhanced the production of H2O2 but also increased the generation of hydroxyl radical (·OH). Experimental results demonstrated that, the apparent rate constant for the degradation of 2,4-Dichlorophenol (2,4-DCP) by AQ-C3N4-PISFs was 0.145 min-1, which is 2.74 times higher than that of C3N4 under visible light. Density functional theory (DFT) calculations indicate that AQ modification promotes electron-hole separation while increasing the adsorption energy of O2. Independent gradient model (IGM) analysis based on Hirshfeld Partition revealed that van der Waals interactions between AQ-C3N4 and 2,4-DCP promoted the degradation process. This work provides new ideas to overcome the problems of continuous addition of H2O2 and low utilization of ·OH that exist in conventional Fenton system.

Sappanone A enhances hepatocyte proliferation in lipopolysaccharide-induced acute liver injury in mice by promoting injured hepatocyte apoptosis and regulating macrophage polarization.

OBJECTIVES: Lipopolysaccharide (LPS), also known as endotoxin, is the main toxic component of the cell wall of gram negative bacteria, which is released after bacterial death and widely exists in the living environment. Human exposure to endotoxin may cause sepsis. The occurrence of septic liver injury is a prominent factor contributing to mortality in patients with sepsis. The purpose of this study is to explore the role of Sappanone A (SA), a homoisoflavonoid isolated from the heartwood of Caesalpinia sappan Linn., in LPS-induced acute liver injury (ALI). METHODS: An LPS-induced ALI mouse model was used to evaluate the effects of SA on septic ALI, and murine cells were treated with LPS to explore the mechanisms underlying SA-provided effects. RESULTS: Treating SA substantially improved LPS-induced ALI. We also performed in silico prediction and RNA-seq analysis to elucidate SA's potential mechanisms of action. The terms generated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of predicted target proteins of SA include inflammation, oxidative stress, and apoptosis; protein-protein interaction network (PPI) analysis indicated that fas binding protein 1 (Fbf1) has the strongest correlation with SA. Consistently, RNA-seq analysis displayed that SA administration regulates cell apoptosis and inflammatory responses, which was further confirmed by checking related markers in livers of mice and murine cells challenged with LPS. Of note, SA significantly decreased the expression of Fbf1 in mouse livers, and promoted apoptosis of injured hepatocytes and hepatocyte proliferation, which were substantially abolished by Fbf1 knockdown in AML12 cells. Besides, SA could increase M2 phenotype polarization but inhibit M1 macrophage polarization in LPS-induced ALI in mice. CONCLUSION: SA enhances hepatocyte proliferation and liver repair in LPS-induced ALI in mcie by promoting injured hepatocyte apoptosis through Fbf1 inhibition and regulating macrophage polarization.

Atrazine concentration detection based on NiAl-layer double hydroxides nanosheets synaptic transistor.

A transistor inspired by biological systems, which possesses synaptic and sensing capabilities, has demonstrated significant promise in the field of neuromorphic electronics and sensory systems resembling the human brain. Despite the remarkable advancements in emulating neuromorphic operations, the development of a synaptic FET with a bionic architecture, extended lifespan, minimal energy usage, and marker monitoring capability remains challenging. In this work, a synaptic transistor based on NiAl-layer double hydroxides nanosheets is reported. The synaptic transistor exhibits a significant ratio of on/off current (1.35×107) and possesses a high transconductance value (10.05 mS). The successful emulation included key synaptic characteristics, such as excitatory/inhibitory postsynaptic current, paired-pulse facilitation/depression, short-term plasticity spike amplitude-dependent plasticity, spike timing-dependent plasticity, as well as spike number-dependent plasticity. A consumption of 64.8 pJ per spike was achieved as a result of the efficient carrier transfer pathway facilitated by the nanosheets composed of double hydroxides. In addition, the FET's linear detection region (with a coefficient R2=0.811) encompassed atrazine concentrations ranging from 10 pg/mL to 0.1 µg/mL, thanks to its high surface area and significant transconductance. Therefore, this study presents a potential approach for achieving energy-efficient neuromorphic computing and high-performance synaptic devices.

Extracellular vesicles in the HCC microenvironment: Implications for therapy and biomarkers.

Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer and the third leading cause of cancer mortality globally. Despite surgical resection being the preferred approach for early-stage HCC, most patients are diagnosed at intermediate to advanced stages, limiting treatment options to chemotherapy and immunotherapy, which often yield poor outcomes. Extracellular vesicles (EVs), minute lipid-bilayered particles released by diverse cells under various physiological and pathological conditions, are crucial for mediating communication between cells. Mounting evidence indicates that EVs sourced from different cells can profoundly influence the HCC tumor microenvironment (TME), thereby affecting the progression of HCC. Given their immunogenicity and liver-targeting properties, these EVs not only hold promise for HCC treatment but also provide avenues for advancing early diagnostic methods and assessing prognosis. This review not only describes the function of EVs within the HCC tumor microenvironment but also analyzes their therapeutic advantages and explores their significance in various therapeutic approaches for HCC, including chemotherapy, immunotherapy, combination therapy, and their role as innovative drug delivery carriers. Furthermore, it highlights the potential of EVs as biomarkers for the diagnosis and prognosis of HCC.

Responsive Protection of Magnesium Alloys From Multicorrosive Media by Constructing Nanofluidic Channels in Self-Repairing Coatings.

Low-density magnesium (Mg) alloys are excellent engineering materials, and can significantly reduce energy consumption by replacing existing steel and aluminum materials. However, Mg species are susceptible to corrosion, especially in harsh environments (high-temperature or acidic), severely limiting the range of practical applications. Here, 2D covalent organic framework (COF) is synthesized with pore diameters ranging from 1.5 to 2.9 nm to obtain ultrafast nanofluidic channels. Loaded with silver (Ag+) ions, 2-mercaptobenzimidazole (2-MB) inhibitors are immobilized in the COF channels through the silver bridges. Based on the strong metal-complexing capability, Ag+ ions precipitated with various corrosive media (Cl-, Br-, I-, SO3 2-, S2-, S2O3 2- SO4 2-, CO3 2-, PO4 3-); meanwhile, the 2-MB inhibitors are rapidly released through the nanofluidic channels, forming a passivation film as a corrosion barrier to protect the Mg substrate. After integration with commercial polyethersulfone (PES), the COF-based coating exhibits high repairing capability achieving 100% damage restoration within 7 h, outperforming all existing coatings of Mg alloys. Notably, the coating shows almost complete protection of Mg alloys after being treated in respective 473 K, acidic (pH ≈4.0), and alkaline (pH ≈10.0) environments.

Treatment expectations of patients and clinicians: a cross-sectional study.

Importance: Understanding treatment expectations of patients and their clinicians is of great importance in improving personalized medical services and enhancing patient safety systems. Objective: To investigate treatment expectations of patients and their clinicians and compare differences between both, by using a pair of validated structured assessment tools covering three key aspects/dimensions of clinical interests. Design setting and participants: This single-center cross-sectional study was conducted at Peking Union Medical College Hospital in China. The study enrolled patients aged 16 years and older receiving inpatient care and their clinicians. Patient recruitment was conducted from March 2023 to November 2023. Assessments: In addition to demographic and clinical characteristics, this study employed two validated structured assessment tools to evaluate treatment expectations among patients and their clinicians: the Hospitalized Patients' Expectations for Treatment Scale-Patient version (HOPE-P) and its counterpart, the Hospitalized Patients' Expectations for Treatment Scale-Clinician version (HOPE-C). Results: A total of 233 patients (mean [SD] age, 52.3 [15.1] years; 108 [46.4%] female) along with their clinicians, who numbered 75 in total were enrolled in this study. The distribution of total scores for HOPE-P and HOPE-C displayed similar patterns, with most scores concentrated in the higher range (above 50% of the full score). The mean HOPE-P total score was higher than that of HOPE-C (mean [SD] score, 38.78 [4.86] vs 37.49 [4.32]; t = 3.12, P = 0.002). In Dimension 2, the HOPE-P score was higher than HOPE-C (23.67 [3.20] vs 21.72 [3.03]; t = 6.98, P < 0.001). However, in Dimensions 1 and 3, HOPE-P scored lower than HOPE-C (13.37 [2.44] vs 13.84 [1.73]; t = -2.384, P < 0.018; 1.74 [1.14] vs 1.94 [1.00]; t = -2.00, P = 0.047). Certain demographic and clinical characteristics led to variations in patients' treatment expectations, including marital status, monthly family income, and smoking history. Conclusions and relevance: This cross-sectional study revealed significant differences between patients' and doctors' treatment expectations. Notably, it highlighted the need for clinicians to focus on rationalizing patients' expectations concerning treatment outcomes. Trial Registration Chinese Clinical Trial Registry Identifier: ChiCTR2300075262.

Assessment of psychometric properties of the union physio-psycho-social assessment questionnaire (UPPSAQ-70) in a large sample of general hospital psychiatric outpatients.

OBJECTIVE: To evaluate the psychometric properties of the Union Physio-Psycho-Social Assessment Questionnaire (UPPSAQ-70) among general hospital psychiatric outpatients. METHODS: A total of 2000 participants responded to the survey. Factor analyses were used to test the construct validity of the scale. Convergent validity was evaluated by the correlation between UPPSAQ-70 and symptoms measured using the Chinese versions of Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Patient Health Questionnaire-15 (PHQ-15), Somatic Symptom Disorder - B Criteria Scale (SSD-12) and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The nine-factor model was supported (χ2 = 8816.395, df = 2309, χ2/df = 3.818, RMSEA = 0.053, CFI = 0.929). The UPPSAQ-70 showed significant correlation with the SAS (r = 0.396, P < .001), SDS (r = 0.451, P < .001), PHQ-15 (r = 0.381, P < .001), SSD-12 (r = 0.324, P < .001) and PSQI (r = 0.220, P < .001). UPPSAQ-70 and its subscales showed good internal consistency with Cronbach's alpha coefficients ranging from 0.79 to 0.96. CONCLUSIONS: The UPPSAQ-70 was a rating scale with good construct validity and reliability, which can measure overall health in the biological, psychological, and social domains for Chinese psychiatric outpatients, but its convergent validity still requires further empirical research.

Characterization of Surface Patterning on Polymer-Grafted Nanocubes Using Atomic Force Microscopy and Force Volume Mapping.

Atomic force microscopy (AFM), in particular force spectroscopy, is a powerful tool for understanding the supramolecular structures associated with polymers grafted to surfaces, especially in regimes of low polymer density where different morphological structures are expected. In this study, we utilize force volume mapping to characterize the nanoscale surfaces of Ag nanocubes (AgNCs) grafted with a monolayer of polyethylene glycol (PEG) chains. Spatially resolved force-distance curves taken for a single AgNC were used to map surface properties, such as adhesion energy and deformation. We confirm the presence of surface octopus micelles that are localized on the corners of the AgNC, using force curves to resolve structural differences between the micelle "bodies" and "legs". Furthermore, we observe unique features of this system including a polymer corona stemming from AgNC-substrate interactions and polymer bridging stemming from particle-particle interactions.

Extracellular vesicle-derived biomarkers in prostate cancer care: Opportunities and challenges.

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide, presenting a significant global public health challenge that necessitates early detection and personalized treatment. Recently, non-invasive liquid biopsy methods have emerged as promising tools to provide insights into the genetic landscape of PCa and monitor disease progression, aiding decision-making at all stages. Research efforts have concentrated on identifying liquid biopsy biomarkers to improve PCa diagnosis, prognosis, and treatment prediction. This article reviews recent research advances over the last five years utilizing extracellular vesicles (EVs) as a natural biomarker library for PCa, and discusses the clinical translation of EV biomarkers, including ongoing trials and key implementation challenges. The findings underscore the transformative role of liquid biopsy, particularly EV-based biomarkers, in revolutionizing PCa diagnosis, prediction, and treatment.

Effect of physical activity intervention on weight change in rural older Chinese: a cluster randomized controlled trial.

BACKGROUND: Current randomized trial evidence for the effects of physical activity intervention on weight change in adults was mainly from western countries, with little reliable evidence from low- and middle-income countries, such as China, where lifestyle factors and obesity patterns differ substantially from those in western countries. We examined the effects of physical activity intervention on weight change using cluster randomized trial data among Chinese older adults. METHODS: The cluster randomized controlled trial included an 8-week physical activity intervention period and was followed up to 24 months. Eight villages were randomly assigned to the intervention group (4 villages, n = 240) or the control group (4 villages, n = 268). The intervention group received physical activity intervention based on the socio-ecological model, while the control group did not. The intervention involved three levels: individual, interpersonal, and community levels, which aimed to promote leisure-time physical activity of participants. The primary outcome of the present study was the difference in percentage weight change at 24 months from baseline. We used Tanita BC-601 analyzer scales to measure weight and recorded it to the nearest 0.1 kg. RESULTS: Among the 508 participants, the mean age was 70.93 (SD, 5.69) years, and 55.5% were female. There were significant differences in percentage weight change between the intervention group and the control group with a mean change of -1.78% (95% CI, -2.67% to -0.90%; p < 0.001) in the total sample, -1.94% (95% CI, -3.14% to -0.73%; p = 0.002) in participants with overweight/obesity, and -1.45% (95% CI, -2.73% to -0.18%; p = 0.027) among participants with underweight/healthy weight in favor of the intervention group at 24 months. CONCLUSIONS: Physical activity intervention resulted in weight loss in rural older sample at 24 months. This suggested that physical activity interventions are feasible for weight loss among older adults, especially for those with overweight/obesity or aged under 80. TRIAL REGISTRATION: The study has been registered on the Chinese Clinical Trial Registry on April 20, 2021 (ChiCTR2100045653), https://www.chictr.org.cn/showproj.html?proj=123704 .

Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.

Confirming the efficacy and safety of CDK4/6 inhibitors in the first-line treatment of HR+ advanced breast cancer: a systematic review and meta-analysis.

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = -1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13-11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Preparation of starch-based green nanofiber mats for probiotic encapsulation by electrospinning.

In this study, starch-based nanofiber mats were successfully prepared from aqueous solution by electrospinning and used for probiotic encapsulation for the first time. The physicochemical properties of the octenylsuccinated (OS) starch/poly(vinyl alcohol) (PVA) blend solutions were systematically investigated. Through Fourier transform infrared spectroscopy and X-ray diffraction spectra analysis, it was found that miscibility and hydrogen bonding interactions exist between OS starch and PVA molecules. Thermogravimetric analysis and derivative thermogravimetric analysis revealed that the produced nanofibers possess satisfactory thermal stability. Scanning electron microscopy images and diameter distribution histograms showed that continuous and defect-free nanofibers were obtained and along with the increase in the weight ratio of OS starch, the average diameter gradually decreased. In addition, it was confirmed that the probiotics were successfully encapsulated in nanofiber mats. The survival rates of Lactobacillus plantarum AB-1 and Lactobacillus rhamnosus GG encapsulated in nanofibers were as high as 94.63% and 92.42%, respectively, significantly higher than those of traditional freeze-drying. Moreover, compared to free cells, probiotics encapsulated in nanofiber mats retained better viability after 21 days of storage at 4 and 25°C, and showed remarkably higher survival rates after exposure to simulated gastric and intestinal fluid. This study showed that the developed nanofibers can be a promising encapsulation system for the protection of probiotics.

Relationship between 1,5-anhydroglucitol and renal function assessed by dynamic renal scintigraphy in type 2 diabetes.

CONTEXT: The reliability of serum 1,5-anhydroglucitol (1,5-AG) in type 2 diabetic patients with renal insufficiency remains controversial. OBJECTIVE: To evaluate the relationship between renal function and serum 1,5-AG, and to assess the extent to which renal function influences 1,5-AG. METHODS: A total of 5337 participants with type 2 diabetes were enrolled. The measured glomerular filtration rate (mGFR) was assayed using 99mTc-DTPA dynamic renal scintigraphy. All subjects were stratified into five groups based on mGFR (≥ 120 [n = 507], 90-120 [n = 2015], 60-90 [n = 2178], 30-60 [n = 604], and < 30 mL/min/1.73 m2 [n = 33]). RESULTS: Overall, the serum 1,5-AG and mGFR levels were 3.3 (1.7-7.0) µg/mL and 88.6 ± 24.1 mL/min/1.73 m2, respectively. mGFR was found to be negatively correlated with 1,5-AG levels (r = -0.189, P < 0.001). Multiple linear regression revealed that mGFR was independently and negatively related to serum 1,5-AG after adjusting for covariates including HbA1c (P < 0.001). In subgroups with mGFR ≥ 30 mL/min/1.73 m2, the correlation coefficients between 1,5-AG and HbA1c, fasting plasma glucose, postprandial plasma glucose, and the differences between postprandial and fasting plasma glucose remained significant (range from -0.126 to -0.743, all P < 0.01). However, the link between 1,5-AG and traditional glycemic markers was attenuated in individuals with mGFR < 30 mL/min/1.73 m2. Sensitivity analysis after excluding anemic patients showed similar results regarding the relationship between serum 1,5-AG and HbA1c across the mGFR subgroups. CONCLUSIONS: Although we observed a weak inverse correlation (r = -0.189) between mGFR and serum 1,5-AG in type 2 diabetes, 1,5-AG remains a valid marker for assessing glucose control in subjects with mild or moderate renal dysfunction.

Revealing Changes in Celecoxib Nanostructured Lipid Carrier's Bioavailability Using Hyaluronic Acid as an Enhancer by HPLC-MS/MS.

Purpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions. Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats. Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug's half-life in vivo. Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug's in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib.