Accelerated Fibrosis Progression of Diabetic Nephropathy From High Uric Acid's Activation of the ROS/NLRP3/SHP2 Pathway in Renal Tubular Epithelial Cells Under High Glucose Conditions.

Context: Elevated uric-acid levels in the blood are closely associated with hypertension, metabolic syndrome, diabetic nephropathy, cardiovascular diseases, and chronic kidney disease (CKD). A high-glucose diet promotes the accumulation of uric acid. Fibrosis commonly occurs in patients with late-stage type 1 or 2 diabetes and can lead to organ dysfunction. Objective: The study intended to investigate whether high uric acid under high glucose conditions can promote the fibrotic progression of diabetic nephropathy by activating the reactive oxygen species (ROS)/ "nod-like receptor (NLR) family pyrin domain containing 3" (NLRP3)/ "Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2" (SHP2) pathway, which can promote epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells. Design: The research team conducted an animal study. Setting: The study took place at the Affiliated Hospital of Hebei University in Baoding, Hebei Province, China. Animals: The animals were 14 healthy, male, C57BL/6J mice. Outcome Measures: The research team: (1) using Masson's trichrome staining, examined the fibrosis of renal, tubular epithelial cells in the streptozotocin (STZ) modeling and the STZ modeling + uric-acid groups; (2) used Western Blot analysis to detect the protein expression of NLRP3, "nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase 2" (NOX2), NOX4, alpha-smooth muscle actin (α-SMA), fibronectin 1 (FN-1), collagen-I, and mothers against decapentaplegic homolog 2/3 (SMAD2/3); (3) conducted in-vitro experiments by dividing transformed C3H mouse kidney-1 (TCMK-1) cells into different groups: STZ modeling group, STZ modeling + high-glucose group, STZ modeling + high-glucose + advanced glycation end (AGE) product group, STZ modeling+ high-glucose + AGE + uric-acid group, STZ modeling+ high glucose + SHP2 small interfering RNA (SiRNA) group, STZ modeling + high glucose + SHP2 SiRNA + AGE group, and STZ modeling+ high-glucose + SHP2 SiRNA + AGE + uric-acid group for Western Blot experiments; and (4) performed immunofluorescence, CCK-8, and transwell experiments on the seven groups of TCMK-1 cells with different treatments. Results: The STZ modeling + uric acid group's levels of fibrosis was significantly higher than that of the STZ modeling group (P < .01). Additionally, the STZ modeling + uric acid groups' expression of α-SMA, FN-1, collagen-I, P-SMAD2, P-SMAD3, NLRP3, and reactive oxygen species (ROS), EMT, and SMAD-related proteins were significantly higher than those of the STZ modeling group (P < .01). The protein expression of SHP2, P-SMAD2, α-SMA, and FN-1 for the STZ modeling + high glucose + SHP2 SiRNA, the STZ modeling + high glucose + SHP2 SiRNA + AGE, and the STZ modeling + high glucose + SHP2 SiRNA + AGE + uric acid groups were significantly lower than those of the STZ modeling + high glucose, STZ modeling + high glucose + AGE, and the STZ modeling + high glucose + AGE + uric acid groups, respectively. Immunofluorescence indicated that the STZ modeling+ high glucose + AGE + uric acid group had the highest relative fluorescence intensity, while the three groups treated with SHP2 SiRNA showed the least expression. The cell counting kit-8 (CCK-8) assay showed that STZ modeling group had less cell proliferation, STZ modeling + high sugar group had less cell proliferation than STZ modeling + high sugar +AGE group, STZ modeling + high sugar +AGE+ uric acid group had the highest cell proliferation, STZ modeling + high sugar +SHP2 SiRNA group and STZ modeling + high sugar +SHP2 SiRNA+AGE group and STZ modeling + high sugar +SHP2 SiRNA+AGE+ uric acid group showed the least number of cell proliferation. The results of the transwell cell migration assay were consistent with the CCK-8 assay. Conclusions: In a high-glucose environment, high uric acid can promote the fibrotic progression of diabetic nephropathy by activating the ROS/NLRP3/SHP2 pathway, leading to mesenchymal transition between renal tubular epithelial cells.

Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

Photonic implementation of the input and reservoir layers for a reservoir computing system based on a single VCSEL with two Mach-Zehnder modulators.

Hardware implementation of reservoir computing (RC), which could reduce the power consumption of machine learning and significantly enhance data processing speed, holds the potential to develop the next generation of machine learning hardware devices and chips. Due to the existing solution only implementing reservoir layers, the information processing speed of photonics RC system are limited. In this paper, a photonic implementation of a VMM-RC system based on single Vertical Cavity Surface Emitting Laser (VCSEL) with two Mach Zehnder modulators (MZMs) has been proposed. Unlike previous work, both the input and reservoir layers are realized in the optical domain. Additionally, the impact of various mask signals, such as Two-level mask, Six-level mask, and chaos mask signal, employed in system, has been investigated. The system's performance improves with the use of more complex mask(t). The minimum Normalized mean square error (NMSE) can reach 0.0020 (0.0456) for Santa-Fe chaotic time series prediction in simulation (experiment), while the minimum Word Error Rate (WER) can 0.0677 for handwritten digits recognition numerically. The VMM-RC proposed is instrumental in advancing the development of photonic RC by overcoming the long-standing limitations of photonic RC systems in reservoir implementation. Linear matrix computing units (the input layer) and nonlinear computing units (the reservoir layer) are simultaneously implemented in the optical domain, significantly enhancing the information processing speed of photonic RC systems.

Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis.

BACKGROUND: Ferroptosis is a distinct iron-dependent non-apoptotic type of programmed cell death that is implicated in the pathophysiology of rheumatoid arthritis (RA). Although asiatic acid (AA) is documented to have significant anti-inflammatory effects in various diseases, it is not known whether it can regulate RA via ferroptosis. METHODS: The effects of AA on rheumatoid arthritis fibroid-like synoviocytes (RA-FLS) were assessed in vitro, and a rat model of type II collagen-induced arthritis (CIA) was established to evaluate the effectiveness of AA treatment in vivo. RESULTS: AA significantly reduced both viability and colony formation in cultured RA-FLS, while increasing the levels of reactive oxygen species (ROS), ferrous iron (Fe2+), malondialdehyde (MDA), and lactate dehydrogenase (LDH), as well as the expression of COX2. Furthermore, AA induced ferroptosis in RA-FLS by promoting Fe2+ accumulation through downregulation of the expression of Keap1 and FTH1 and upregulation of Nrf2 and HMOX1. In vivo, AA treatment was found to reduce toe swelling and the arthritis score in CIA rats, as well as relieve inflammation and ankle damage and significantly upregulate the expression of Nrf2 and HMOX1 in the synovial fluid. CONCLUSION: Treatment with AA significantly reduced the viability of RA-FLS and triggered ferroptosis by promoting accumulation of Fe2+via the Nrf2-HMOX1 pathway, and was effective in relieving inflammation in CIA model rats. These findings suggest that the use of AA may be a promising strategy for the clinical treatment of RA.

S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation.

BACKGROUND: Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. METHODS: We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. RESULTS: We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. CONCLUSIONS: S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

Human dopaminergic system in the exercise-cognition link.

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research.

Metal-Organic Framework Nanomaterials as a Medicine for Catalytic Tumor Therapy: Recent Advances.

Nanomaterials, with unique physical, chemical, and biocompatible properties, have attracted significant attention as an emerging active platform in cancer diagnosis and treatment. Amongst them, metal-organic framework (MOF) nanostructures are particularly promising as a nanomedicine due to their exceptional surface functionalities, adsorption properties, and organo-inorganic hybrid characteristics. Furthermore, when bioactive substances are integrated into the structure of MOFs, these materials can be used as anti-tumor agents with superior performance compared to traditional nanomaterials. In this review, we highlight the most recent advances in MOFs-based materials for tumor therapy, including their application in cancer treatment and the underlying mechanisms.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Eco-climate drivers shape virome diversity in a globally invasive tick species.

Spillovers of viruses into human occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China, encompassing diverse ecological conditions. Generalized additive modelling revealed that climate factors exerted a stronger influence on the virome of H. longicornis compared to other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and anti-viral immunity. We investigated the mechanistic understanding of how climate changes drive the tick virome using causality inference and emphasized its significance for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to an increased diversity of tick virome, particularly the evenness of vertebrate associated viruses. This finding may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections indicate that the diversity of H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019-2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.

COVID-19 was associated with the complications after allogeneic hematopoietic stem cell transplantation.

We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

Influence of Nickel on Microstructure and Mechanical Properties in Medium-Carbon Spring Steel.

The effects of adding nickel on the phase transition temperature, microstructure, and mechanical properties of medium-carbon spring steel have been investigated. The results show that adding nickel reduces the martensite start (Ms) temperature, improves hardenability, and refines the sub-microstructure of the martensite, thereby improving yield stress. The yield strength of martensitic steel increases by approximately 100 MPa due to a synergistic combination of grain refinement strengthening and dislocation strengthening, with an increase in the nickel content from 0 wt.% to 1 wt.%. The cryogenic impact toughness of martensitic steel also improved with a higher nickel content due to packet and block refinement and an increase in the proportion of high-angle grain boundaries (HAGBs).

CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice.

Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.

Using network pharmacology to discover potential drugs for hypertrophic scars.

BACKGROUND: Hypertrophic scar is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation, and existing drugs cannot achieve satisfactory therapeutic effects. OBJECTIVES: This study aimed to explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for hypertrophic scars. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, transforming growth factor ß (TGF-ß) signaling pathway, and other biological pathways. Integrin ß1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib, and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and pro-fibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA (siRNA) can also inhibit mouse scar hyperplasia. CONCLUSIONS: ITGB1 and TGF-ß signaling pathways are important for hypertrophic scar formation. Crizotinib could serve as a potential drug for hypertrophic scars.

The origin of exceptionally large ductility in molybdenum alloys dispersed with irregular-shaped La2O3 nano-particles.

Molybdenum and its alloys are known for their superior strength among body-centered cubic materials. However, their widespread application is hindered by a significant decrease in ductility at lower temperatures. In this study, we demonstrate the achievement of exceptional ductility in a Mo alloy containing rare-earth La2O3 nanoparticles through rotary-swaging, a rarity in Mo-based materials. Our analysis reveals that the large ductility originates from substantial variations in the electronic density of states, a characteristic intrinsic to rare-earth elements. This characteristic can accelerate the generation of oxygen vacancies, facilitating the amorphization of the oxide-matrix interface. This process promotes vacancy absorption and modification of dislocation configurations. Furthermore, by inducing irregular shapes in the La2O3 nanoparticles through rotary-swaging, incoming dislocations interact with them, creating multiple dislocation sources near the interface. These dislocation sources act as potent initiators at even reduced temperatures, fostering diverse dislocation types and intricate networks, ultimately enhancing dislocation plasticity.

Optimization and mechanisms of proteolytic enzyme immobilization onto large-pore mesoporous silica nanoparticles: Enhanced tumor penetration.

Immobilization of proteolytic enzymes onto nanocarriers is effective to improve drug diffusion in tumors through degrading the dense extracellular matrix (ECM). Herein, immobilization and release behaviors of hyaluronidase, bromelain, and collagenase (Coll) on mesoporous silica nanoparticles (MSNs) were explored. A series of cationic MSNs (CMSNs) with large and adjustable pore sizes were synthesized, and investigated together with two anionic MSNs of different pore sizes. CMSNs4.0 exhibited the highest enzyme loading capacity for hyaluronidase and bromelain, and CMSNs4.5 was the best for Coll. High electrostatic interaction, matched pore size, and large pore volume and surface area favor the immobilization. Changes of the enzyme conformations and surface charges with pH, existence of a space around the immobilized enzymes, and the depth of the pore structures, affect the release ratio and tunability. The optimal CMSNs-enzyme complexes exhibited deep and homogeneous penetration into pancreatic tumors, a tumor model with the densest ECM, with CMSNs4.5-Coll as the best. Upon loading with doxorubicin (DOX), the CMSNs-enzyme complexes induced high anti-tumor efficiencies. Conceivably, the DOX/CMSNs4.5-NH2-Coll nanodrug exhibited the most effective tumor therapy, with a tumor growth inhibition ratio of 86.1 %. The study provides excellent nanocarrier-enzyme complexes, and offers instructive theories for enhanced tumor penetration and therapy.

Development and validation of a risk prediction model for mild cognitive impairment in elderly patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of mild cognitive impairment (MCI) is steadily increasing among elderly people with type 2 diabetes (T2DM). This study aimed to create and validate a predictive model based on a nomogram. METHODS: This cross-sectional study collected sociodemographic characteristics, T2DM-related factors, depression, and levels of social support from 530 older adults with T2DM. We used LASSO regression and multifactorial logistic regression to determine the predictors of the model. The performance of the nomogram was evaluated using calibration curves, receiver operating characteristics (ROC), and decision curve analysis (DCA). RESULTS: The nomogram comprised age, smoking, physical activity, social support, depression, living alone, and glycosylated hemoglobin. The AUC for the training and validation sets were 0.914 and 0.859. The DCA showed good clinical applicability. CONCLUSIONS: This predictive nomogram has satisfactory accuracy and discrimination. Therefore, the nomogram can be intuitively and easily used to detect MCI in elderly adults with T2DM.

Bombyx mori RPL13 participates in UV-induced DNA damage repair of B. mori nucleopolyhedrovirus through interaction with Bm65.

Ribosomal protein L13 (RPL13) is highly conserved in evolution. At present, the properties and functions of RPL13 have not been characterised in insects. In this study, Bombyx mori RPL13 (BmRPL13) was first found to be specifically recruited to the sites of ultraviolet (UV)-induced DNA damage and contributed to UV damage repair. Escherichia coli expressing BmRPL13 showed better resistance to UV radiation. After knocking down the expression of BmRPL13 in BmN cells, the repair speed of UV-damaged DNA slowed down. The further results showed that BmRPL13 interacted with B. mori nucleopolyhedrovirus (BmNPV) ORF65 (Bm65) protein to locate at the UV-induced DNA damage sites of BmNPV and helped repair UV-damaged viral DNA.

Alleviation of hepatic insulin resistance and steatosis with NMN via improving endoplasmic reticulum-Mitochondria miscommunication in the liver of HFD mice.

The interaction between endoplasmic reticulum (ER) and mitochondria has been shown to play a key role in hepatic steatosis during chronic obesity. ß-nicotinamide mononucleotide (NMN) has been reported to regulate obesity, however, its molecular mechanism at the subcellular level remains unclear. Here, NMN improved liver steatosis and insulin resistance in chronic high-fat diet (HFD) mice. RNA-seq showed that compared with the liver of HFD mice, NMN intervention enhanced fat digestion and absorption and stimulated the cholesterol metabolism signaling pathways, while impaired insulin resistance and the fatty acid biosynthesis signaling pathways. Mechanistically, NMN ameliorated mitochondrial dysfunction and ER oxidative stress in the liver of HFD mice by increasing hepatic nicotinamide adenine dinucleotide (NAD+) (P < 0.01) levels. This effect increased the contact sites (mitochondria-associated membranes [MAMs]) between ER and mitochondria, thereby promoting intracellular ATP (P < 0.05) production and mitigating lipid metabolic disturbances in the liver of HFD mice. Taken together, this study provided a theoretical basis for restoring metabolic dynamic equilibrium in the liver of HFD mice by increasing MAMs via the nutritional strategy of NMN supplementation.

High Urine Albumin-to-Creatinine Ratio is Associated with Increased Arterial Stiffness in Diabetes: A Chinese Cross-Sectional Study.

Purpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes. Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out. Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p<0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176-0.276, p<0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19-1.33, p<0.001), and 1.16 (1.08-1.25, p<0.001) respectively in diabetic patients before and after adjusting for potential confounders. Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

1. The mean baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group.2. The sex-specific hierarchical analysis revealed that baPWV levels and the incidence of high baPWV were significantly elevated with increased UACR.3. Curvilinear relationships between log2-transformed UACR and the risk of high baPWV.4. Positive association between UACR and high baPWV in patients with diabetes.