Pulmonary embolism incidence among patient admitted under psychiatry department: a case-control study.

Background: Pulmonary embolism (PE) is a serious and potentially life-threatening condition that requires prompt diagnosis and treatment. Identifying risk factors and diagnostic markers can aid in the early detection and management of this condition. Methods: This case-control study examined 10,077 patients admitted to Shenzhen Kangning Hospital's psychiatry facility in 2020. Among these, 65 patients were diagnosed with PE, including 50 new cases. After survival sampling for controls and age-and-gender matching, the study included 41 new PE cases and 41 age-and-gender-matched controls. Data on demographics, comorbidities, and medication use were extracted from electronic records. Conditional logistic regression analyses were performed to determine the association between each predictor and PE risk. Additionally, the sensitivity and specificity of the d-dimer diagnostic tool were assessed. Results: In univariable conditional logistic regression, active alcoholism was associated with a higher PE risk (OR=3.675, 95% CI 1.02-13.14, P=0.046). A history of physical restraint (OR=4.33, 95% CI 1.24-15.21, P=0.022) and chemical restraint (OR 4.67, 95% CI 1.34-16.24, p=0.015) also increased PE risk, as did benzodiazepine use (OR=3.33, 95% CI 1.34-8.30, P=0.010). Conversely, psychotropic medication before admission was associated with a lower risk of PE (OR=0.07, 95% CI 0.01-0.59, P=0.013). Stepwise multivariable forward conditional regression identified two subsets of psychiatric patients at higher risk of PE: new psychiatric cases without medication at admission who were chemically restrained, and cases without medication at admission who were started on antipsychotics and benzodiazepines. The d-dimer diagnostic tool, with an optimal threshold of 570 ng/ml determined by the Youden index (J statistic of 0.6098), showed a sensitivity of 73.17% and specificity of 87.80% for detecting PE, with an AUC of 0.833 (95% CI: 0.735-0.906). Conclusion: Our findings suggest that a history of restraint, alcoholism, and the use of antipsychotics and benzodiazepines are important predictors of PE in psychiatric inpatients. Conversely, psychotropic medications at admission may be linked to a lower PE risk. The d-dimer diagnostic tool shows good value for screening PE in psychiatric inpatients. These predictors and diagnostic markers could help clinicians identify high-risk patients and implement appropriate prevention strategies.

Driving mechanism of groundwater quality and probabilistic health risk quantification in the central Yinchuan Plain.

The environmental changes from climatic, terrestrial and anthropogenic drivers can significantly influence the groundwater quality that may pose a threat to human health. However, the driving mechanism of groundwater quality and potential health risk still remains to be studied. In this paper, 165 groundwater samples were analyzed to evaluate the groundwater quality, driving mechanism, and probabilistic health risk in the central Yinchuan Plain by applying fuzzy comprehensive evaluation method (FCEM), redundance analysis (RDA) and Monte Carlo simulation. The results showed that hydrochemical evolution of groundwater were strongly influenced by water-rock interaction, evaporation and human activities. While 55.2% of groundwater samples reached the drinking water quality standard (Class I, II and III), 44.8% of samples exceeded the standard limits of Class III water quality (Class IV and V), indicating a high pollution level of groundwater. Mn, TDS, NH4+, NO3-, Fe, F-, NO2-, As were among major indicators that influence the groundwater quality due to the natural and anthropogenic processes. The RDA analysis revealed that climatic factors (PE: 10.9%, PRE: 1.1%), GE chemical properties (ORP: 20.7%, DO: 2.4%), hydrogeological factors (BD: 16.5%, K: 4.1%), and terrestrial factors (elevation: 1.2%; distanced: 5.6%, distancerl: 1.5%, NDVI: 1.2%) were identified as major driving factors influencing the groundwater quality in the study area. The HHRA suggested that TCR values of arsenic in infants, children and teens greatly exceeded the acceptable risk threshold of 1E-4, indicating a high cancer risk with a basic trend: infants > children > teens, while TCR values of adults were within the acceptable risk level. THI values of four age groups in the RME scenario were nearly ten times higher than those in the CTE scenario, displaying a great health effect on all age groups (HQ > 1). The present study provides novel insights into the driving mechanism of groundwater quality and potential health hazard in arid and semi-arid regions.

Advances in DNA methylation of imprinted genes and folic acid regulation of growth and development.

DNA methylation is closely related to folate levels and acts as a mechanism linking developmental disorders to chronic diseases. Folic acid supplementation can impact DNA methylation levels of imprinted genes crucial for neonatal development. Imprinted genes are vital for regulating embryonic and postnatal fetal growth. This review summarizes imprinted genes, DNA methylation, folic acid's influence on growth and development and their correlation. It aims to provide a comprehensive overview of research advancements on imprinted genes, DNA methylation and folic acid regulation concerning growth and development.

[Box: see text].

Two rhombic ice phases from aqueous salt solutions under graphene confinement.

Water exhibits rich ice phases depending upon its respective formation conditions, and in particular, the two-dimensional ice with nonhexagonal symmetry adsorbed on solids relates to the exceptional arrangement of water molecules. Despite extensive reporting of two-dimensional ice on various solid surfaces, the geometry and thermodynamics of ice formation from an aqueous salt solution are still unknown. In this Letter, we show the formation of single- and two-phase mixed two-dimensional rhombic ice from aqueous salt solutions with different concentrations under strong compressed confinement of graphene at ambient temperature by using classical molecular dynamics simulations and first-principles calculations. The two rhombic ice phases exhibit identical geometry and thermodynamic properties, but different projections of the oxygen atoms against solid surface symmetry, where they relate to the stable and metastable arrangements of water molecules confined between two graphene layers. A single-phase rhombic ice would grow from the confined saturated aqueous solutions since the previously stable rhombic molecular arrangement becomes an unstable high-energy state by introducing salt ions nearby. Our result reveals different rhombic ice phases growing from pure water and aqueous solutions, highlighting the deciding role of salt ions in the ice formation process due to their common presence in liquids.

Effects of copper on chemical kinetics and brown carbon formation in the aqueous ˙OH oxidation of phenolic compounds.

Many phenolic compounds (PhCs) in biomass burning and fossil fuel combustion emissions can partition into atmospheric aqueous phases (e.g., cloud/fog water and aqueous aerosols) and undergo reactions to form secondary organic aerosols (SOAs) and brown carbon (BrC). Redox-active transition metals, particularly Fe and Cu, are ubiquitous species in atmospheric aqueous phases known to participate in Fenton/Fenton-like chemistry as a source of aqueous ˙OH. However, even though the concentrations of water-soluble Cu are close to those of water-soluble Fe in atmospheric aqueous phases in some areas, unlike Fe, the effects that Cu have on SOA and BrC formation in atmospheric aqueous phases have scarcely been studied and remain poorly understood. We investigated the effects of Cu(II) on PhC reaction rates and BrC formation during the aqueous oxidation of four PhCs (guaiacol, catechol, syringol, and vanillin) by ˙OH generated from Fenton-like chemistry under different pH conditions. While the PhCs reacted when both H2O2 and Cu(II) were present in the absence (i.e., dark oxidation) and presence (i.e., photooxidation) of light, the reaction rates were at least one order of magnitude higher during photooxidation. Higher PhC reaction rates were measured at higher pH during both dark oxidation and photooxidation as a result of higher ˙OH concentrations produced by Fenton-like chemistry. Only water-soluble BrC was formed during dark oxidation and photooxidation when Cu(II) was present. Mass absorption coefficients (103 to 104 cm2 g-1) comparable to those of biomass burning BrC were measured during dark oxidation and photooxidation when Cu(II) was present. Light absorption was enhanced at higher pH during dark oxidation and photooxidation, which indicated that higher quantities and/or more absorbing BrC chromophores were formed at higher pH. The effects that Cu(II) had on the PhC reaction rates and the composition of SOAs and BrC formed depended on the PhC base structure (i.e., benzenediol vs. methoxyphenol). Overall, these results show how aqueous reactions involving Cu(II), H2O2, and PhCs can be an efficient source of daytime and nighttime water-soluble BrC and SOAs, which can have significant implications for how the atmospheric fates of PhCs are modeled for areas with substantial concentrations of water-soluble Cu in highly to moderately acidic cloud/fog water and aqueous aerosols.

Experimental Study on Aerodynamic Characteristics of Downwind Bionic Tower Wind Turbine.

The vibrissae of harbor seals exhibit a distinct three-dimensional structure compared to circular cylinders, resulting in a wave-shaped configuration that effectively reduces drag and suppresses vortex shedding in the wake. However, this unique cylinder design has not yet been applied to wind power technologies. Therefore, this study applies this concept to the design of downwind wind turbines and employs wind tunnel testing to compare the wake flow characteristics of a single-cylinder model while also investigating the output power and wake performance of the model wind turbine. Herein, we demonstrate that in the single-cylinder test, the bionic case shows reduced turbulence intensity in its wake compared to that observed with the circular cylinder case. The difference in the energy distribution in the frequency domain behind the cylinder was mainly manifested in the near-wake region. Moreover, our findings indicate that differences in power coefficient are predominantly noticeable with high tip speed ratios. Furthermore, as output power increases, this bionic cylindrical structure induces greater velocity deficit and higher turbulence intensity behind the rotor. These results provide valuable insights for optimizing aerodynamic designs of wind turbines towards achieving enhanced efficiency for converting wind energy.

An injectable hydrogel dressing for controlled release of hydrogen sulfide pleiotropically mediates the wound microenvironment.

The healing of scalded wounds faces many challenges such as chronic inflammation, oxidative stress, wound infection, and difficulties in vascular and nerve regeneration. Treating a single problem cannot effectively coordinate the complex regenerative microenvironment of scalded wounds, limiting the healing and functional recovery of the skin. Therefore, there is a need to develop a multi-effect treatment plan that can adaptively address the issues at each stage of wound healing. In this study, we propose a scheme for on-demand release of hydrogen sulfide (H2S) based on the concentration of reactive oxygen species (ROS) in the wound microenvironment. This is achieved by encapsulating peroxythiocarbamate (PTCM) in the ROS-responsive polymer poly(ethylene glycol)-poly(L-methionine) (PMet) to form nanoparticles, which are loaded into a thermosensitive injectable hydrogel, F127-poly(L-aspartic acid-N-hydroxysuccinimide) (F127-P(Asp-NHS)), to create a scald dressing. The H2S released by the hydrogel dressing on demand regulates the wound microenvironment by alleviating infection, reducing oxidative stress, and remodeling inflammation, thereby accelerating the healing of full-thickness scalded wounds. This hydrogel dressing for the adaptive release of H2S has great potential in addressing complex scalded wounds associated with infection and chronic inflammation.

Development of insomnia in patients with stroke: A systematic review and meta-analysis.

BACKGROUND AND AIM: Stroke is a serious threat to human life and health, and post-stroke insomnia is one of the common complications severely impairing patients' quality of life and delaying recovery. Early understanding of the relationship between stroke and post-stroke insomnia can provide clinical evidence for preventing and treating post-stroke insomnia. This study was to investigate the prevalence of insomnia in patients with stroke. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library databases were used to obtain the eligible studies until June 2023. The quality assessment was performed to extract valid data for meta-analysis. The prevalence rates were used a random-efect. I2 statistics were used to assess the heterogeneity of the studies. RESULTS: Twenty-six studies met the inclusion criteria for meta-analysis, with 1,193,659 participants, of which 497,124 were patients with stroke.The meta-analysis indicated that 150,181 patients with stroke developed insomnia during follow-up [46.98%, 95% confidence interval (CI): 36.91-57.18] and 1806 patients with ischemic stroke (IS) or transient ischemic attack (TIA) developed insomnia (47.21%, 95% CI: 34.26-60.36). Notably, 41.51% of patients with the prevalence of nonclassified stroke developed insomnia (95% CI: 28.86-54.75). The incidence of insomnia was significantly higher in patients with acute strokes than in patients with nonacute strokes (59.16% vs 44.07%, P < 0.0001).Similarly, the incidence of insomnia was significantly higher in the patients with stroke at a mean age of ≥65 than patients with stroke at a mean age of <65 years (47.18% vs 40.50%, P < 0.05). Fifteen studies reported the follow-up time. The incidence of insomnia was significantly higher in the follow-up for ≥3 years than follow-up for <3 years (58.06% vs 43.83%, P < 0.05). Twenty-one studies used the Insomnia Assessment Diagnostic Tool, and the rate of insomnia in patients with stroke was 49.31% (95% CI: 38.59-60.06). Five studies used self-reporting, that the rate of insomnia in patients with stroke was 37.58% (95% CI: 13.44-65.63). CONCLUSIONS: Stroke may be a predisposing factor for insomnia. Insomnia is more likely to occur in acute-phase stroke, and the prevalence of insomnia increases with patient age and follow-up time. Further, the rate of insomnia is higher in patients with stroke who use the Insomnia Assessment Diagnostic Tool.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Background: Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods: A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results: Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion: Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

The LiV3O8 Superlattice Cathode with Optimized Zinc Ion Insertion Chemistry for High Mass-Loading Aqueous Zinc-Ion Batteries.

Resolving the sluggish transport kinetics of divalent Zn2+ in the cathode lattice and improving mass-loading performance are crucial for advancing the zinc-ion batteries (AZIBs) application. Herein, PEO-LiV3O8 superlattice nanosheets (PEO-LVO) with expanded interlayer spacing (1.16 nm) are fabricated to provide a high-rate, stable lifetime, and large mass-loading cathode. The steady in-plane expansion without shrinkage after the first cycle, but reversible H+/Zn2+ co-insertion in PEO-LVO are demonstrated by operando synchrotron X-ray diffraction and ex situ characterizations. Moreover, the large capacity of PEO-LVO is traced back to the optimized Zn2+ insertion chemistry with increased Zn2+ storage ratio, which is facilitated by the interlayer PEO in lowering the Zn2+ diffusion barrier and increased number of active sites from additional interfaces, as anticipated by density functional theory. Due to the optimized ion insertion resulting in stalled interfacial byproducts and rapid kinetics, PEO-LVO achieves excellent high mass-loading performance (areal capacity up to 6.18 mAh cm-2 for freestanding electrode with 24 mg cm-2 mass-loading and 2.8 mAh cm-2 at 130 mA cm-2 for conventional electrode with 27 mg cm-2 mass-loading). As a proof-of-concept, the flexible all-solid-state fiber-shaped AZIBs with high mass-loading woven into a fabric can power an electronic watch, highlighting the application potential of PEO-LVO cathode.

The association between monocyte to high-density lipoprotein cholesterol ratio and chronic kidney disease in a Chinese adult population: a cross-sectional study.

BACKGROUND: Monocyte to high-density lipoprotein cholesterol ratio (MHR) was confirmed as a novel inflammatory marker and strongly associated with the risk of several diseases. This study aimed to investigate the relationship between MHR and chronic kidney disease (CKD) in a Chinese adult population. METHODS: In this cross-sectional study, 232,775 community-dwelling adults in Binhai who completed health checkups in 2021 were enrolled. Participants were categorized based on the MHR quartiles. Clinical characteristics of participants across different groups were compared using one-way ANOVA, Kruskal-Wallis h-test, and Chi-squared test as appropriate. Univariate and multivariable logistic regression analyses were taken to assess the relationship between MHR and the presence of CKD, as well as its association with low estimated glomerular filtration rate (eGFR) and proteinuria. Subgroup analyses were further executed to confirm the reliability of this relationship. RESULTS: A total of 21,014 (9.0%) individuals were diagnosed with CKD. Characteristic indicators including waist circumference, body mass index (BMI), blood pressure (BP), serum uric acid (SUA), triglyceride, and fasting blood glucose (FBG) showed a gradual increase with higher MHR quartiles, whereas parameters such as age, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and eGFR decreased (p < .001). In the multivariable logistic regression analysis, we observed independent associations between MHR (per 1 SD increase) and CKD, as well as low eGFR and proteinuria, with odds ratio (ORs) and 95% confidence intervals (95%CIs) of 1.206 (1.186-1.225), 1.289 (1.260-1.319), and 1.150 (1.129-1.171), respectively (p < .001). Similar conclusions were confirmed in subgroup analysis stratified by gender, age, BMI, central obesity, hypertension, and diabetes mellitus, after justification for confounding factors. CONCLUSION: Elevated MHR level was independently associated with the presence of CKD, suggesting that it might serve as a useful clinical tool for risk stratification, offering valuable insights to inform preventive and therapeutic approaches for clinicians in their routine medical practice.

A Comprehensive Survey on Deep Graph Representation Learning.

Graph representation learning aims to effectively encode high-dimensional sparse graph-structured data into low-dimensional dense vectors, which is a fundamental task that has been widely studied in a range of fields, including machine learning and data mining. Classic graph embedding methods follow the basic idea that the embedding vectors of interconnected nodes in the graph can still maintain a relatively close distance, thereby preserving the structural information between the nodes in the graph. However, this is sub-optimal due to: (i) traditional methods have limited model capacity which limits the learning performance; (ii) existing techniques typically rely on unsupervised learning strategies and fail to couple with the latest learning paradigms; (iii) representation learning and downstream tasks are dependent on each other which should be jointly enhanced. With the remarkable success of deep learning, deep graph representation learning has shown great potential and advantages over shallow (traditional) methods, there exist a large number of deep graph representation learning techniques have been proposed in the past decade, especially graph neural networks. In this survey, we conduct a comprehensive survey on current deep graph representation learning algorithms by proposing a new taxonomy of existing state-of-the-art literature. Specifically, we systematically summarize the essential components of graph representation learning and categorize existing approaches by the ways of graph neural network architectures and the most recent advanced learning paradigms. Moreover, this survey also provides the practical and promising applications of deep graph representation learning. Last but not least, we state new perspectives and suggest challenging directions which deserve further investigations in the future.

Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Structure-activity relationship and biofilm formation-related gene targets of oleanolic acid-type saponins from Pulsatilla chinensis against Candida albicans.

In the course of our investigations of antifungal natural products, the structure-activity relationship and antifungal activities of oleanolic acid-type saponins (1-28) from Pulsatilla chinensis against human and plant pathogenic fungi were elucidated. The analysis of structure-activity relationship of oleanolic acid-type saponins showed that the free carboxyl at C-28 was essential for their antifungal activities; the free hydroxyl group at the C-23 site of oleanolic acid-type saponins played a crucial role in their antifungal activities; the oligosaccharide chain at C-3 oleanolic acid-type saponins showed significant effects on antifungal efficacy and a disaccharide or trisaccharide moiety at position C-3 displayed optimal antifungal activity. The typical saponin pulchinenoside B3 (16, PB3) displayed satisfactory antifungal activity against human and plant pathogenic fungi, especially, C. albicans with an MIC value of 12.5 µg/mL. Furthermore, PB3 could inhibit the biofilm formation of C. albicans through downregulating the expression of the integrated network of biofilm formation-associated transcription factors (Bcr1 Efg1, Ndt80, Brg1, Rob1 and Tec1) and adhesion-related target genes (HWP1, ALS1, and ALS3). Meanwhile, we found that PB3 could effectively destroy the mature biofilm of C. albicans by the oxidative damage and inducing mitochondria-mediated apoptosis in cells.

Safety and effectiveness of laparoscopic renal biopsy: a single-center review and meta-analysis.

BACKGROUND: While renal biopsy remains the preferred diagnostic method for assessing proteinuria, hematuria, or renal failure, laparoscopic renal biopsy (LRB) can serve as an alternative for high-risk patients when percutaneous kidney biopsy (PKB) is not recommended. This study was aimed to evaluate the safety of LRB. METHODS: In study 1, Fourteen patients from January 2021 to January 2023 had a LRB taken for various indications, such as morbid obesity, abnormal kidney construction, uncontrolled hypertension, and coagulopathy. We also conducted a Meta-analysis of the success rate and complication rate of previous LRB in study 2. RESULTS: All the patients completed biopsies and adequate renal tissues were obtained. The success rate was 100%. The median number of glomeruli obtained was 22.5 (range:12.0, 45.0). The complication rate was 7.1% (urinary tract infection). There were no significant differences between levels of hemoglobin, serum creatinine, and urinary NAGL before and after surgery. In the meta-analysis, the success rate of operation, satisfactory rate of sample, and complication rate of surgery were 99.9%, 99.1%, and 2.6% respectively. CONCLUSION: LRB can achieve a good success rate and specimen retrieval and does not increase the risk of complications for high-risk patients. It can present as one of the alternative methods for patients with glomerular diseases.

Enrichment of phosphopeptides by arginine-functionalized magnetic chitosan nanoparticles.

One of the most crucial and prevalent post-translational modifications is the phosphorylation of proteins. The study and examination of protein phosphorylation hold immense importance in comprehending disease mechanisms and discovering novel biomarkers. However, the inherent low abundance, low ionization efficiency, and coexistence with non phosphopeptides seriously affect the direct analysis of phosphopeptides by mass spectrometry. In order to tackle these problems, it is necessary to carry out selective enrichment of phosphopeptides prior to conducting mass spectrometry analysis. Herein, magnetic chitosan nanoparticles were developed by incorporating arginine, and were then utilized for phosphopeptide enrichment. A tryptic digest of ß-casein was chosen as the standard substance. After enrichment, combined with matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), the detection limit of the method was 0.4 fmol. The synthesized magnetic material demonstrated great potential in the detection of phosphopeptides in complex samples, as proven by its successful application in detecting phosphopeptides in skim milk and human saliva samples.

Disrupting circadian control of autophagy induces podocyte injury and proteinuria.

The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.

GLP-1 receptor agonist attenuates tubular cell ferroptosis in diabetes via enhancing AMPK-fatty acid metabolism pathway through macropinocytosis.

Kidney tubules are mostly responsible for pathogenesis of diabetic kidney disease. Actively reabsorption of iron, high rate of lipid metabolism and exposure to concentrated redox-active compounds constructed the three main pillars of ferroptosis in tubular cells. However, limited evidence has indicated that ferroptosis is indispensable for diabetic tubular injury. Glucagon-like peptide-1 receptor agonist (GLP-1RA) processed strong benefits on kidney outcomes in people with diabetes. Moreover, GLP-1RA may have additive effects by improving dysmetabolism besides glucose control and weight loss. Therefore, the present study aimed at exploring the benefits of exendin-4, a high affinity GLP-1RA on kidney tubular dysregulation in diabetes and the possible mechanisms involved, with focus on ferroptosis and adenosine 5'-monophosphate-activated protein kinase (AMPK)-mitochondrial lipid metabolism pathway. Our data revealed that exendin-4 treatment markedly improved kidney structure and function by reducing iron overload, oxidative stress, and ACSL4-driven lipid peroxidation taken place in diabetic kidney tubules, along with reduced GPX4 expression and GSH content. AMPK signaling was identified as the downstream target of exendin-4, and enhancement of AMPK triggered the transmit of its downstream signal to activate fatty acid oxidation in mitochondria and suppress lipid synthesis and glycolysis, and ultimately alleviated toxic lipid accumulation and ferroptosis. Further study suggested that exendin-4 was taken up by tubular cells via macropinocytosis. The protective effect of exendin-4 on tubular ferroptosis was abolished by macropinocytosis blockade. Taken together, present work demonstrated the beneficial effects of GLP-1RA treatment on kidney tubular protection in diabetes by suppressing ferroptosis through enhancing AMPK-fatty acid metabolic signaling via macropinocytosis.

PPARα/δ dual agonist H11 alleviates diabetic kidney injury by improving the metabolic disorders of tubular epithelial cells.

Diabetic kidney disease (DKD) is responsible for nearly half of all end-stage kidney disease and kidney failure is a major driver of mortality among patients with diabetes. To date, few safe and effective drugs are available to reverse the decline of kidney function. Kidney tubules producing energy by fatty acid metabolism are pivotal in development and deterioration of DKD. Peroxisome proliferator-activated receptors (PPARs), comprising PPARα, PPARδ and PPARγ play a senior role in the pathogenesis of DKD for their functions in glycemic control and lipid metabolism; whereas systemic activation of PPARγ causes serious side-effects in clinical settings. Compound H11 was a potent PPARα and PPARδ (PPARα/δ) dual agonist with potent and well-balanced PPARα/δ agonistic activity and a high selectivity over PPARγ. In this study, the potential therapeutic effects of compound H11 were determined in a db/db mouse model of diabetes. Expressions of PPARα and PPARδ in nuclei of tubules were markedly reduced in diabetes. Transcriptional changes of tubular cells showed that H11 was an effective PPARα/δ dual agonist taking effects both in vivo and in vitro. Systemic administration of H11 showed glucose tolerance and lipid metabolic benefits in db/db mice. Moreover, H11 treatment exerted protective effects on diabetic kidney injury. In addition to fatty acid metabolism, H11 also regulated diabetes-induced metabolic alternations of branch chain amino acid degradation and glycolysis. The present study demonstrated a crucial role of H11 in regulation of energy homeostasis and metabolism in glucose-treated tubular cells. Overall, compound H11 holds therapeutic promise for DKD.

Associations of Intracranial Artery Length and Branch Number on Time-of-Flight MRA With Cognitive Impairment in Hypertensive Older Males.

BACKGROUND: Hypertension-induced impairment of the cerebral artery network contributes to cognitive impairment. Characterizing the structure and function of cerebral arteries may facilitate the understanding of hypertension-related pathological mechanisms and lead to the development of new indicators for cognitive impairment. PURPOSE: To investigate the associations between morphological features of the intracranial arteries distal to the circle of Willis on time-of-flight MRA (TOF-MRA) and cognitive performance in a hypertensive cohort. STUDY TYPE: Prospective observational study. POPULATION: 189 hypertensive older males (mean age 64.9 ± 7.2 years). FIELD STRENGTH/SEQUENCE: TOF-MRA sequence with a 3D spoiled gradient echo readout and arterial spin labeling perfusion imaging sequence with a 3D stack-of-spirals fast spin echo readout at 3T. ASSESSMENT: The intracranial arteries were segmented from TOF-MRA and the total length of distal arteries (TLoDA) and number of arterial branches (NoB) were calculated. The mean gray matter cerebral blood flow (GM-CBF) was extracted from arterial spin labeling perfusion imaging. The cognitive level was assessed with short-term and long-term delay-recall auditory verbal learning test (AVLT) scores, and with montreal cognitive assessment. STATISTICAL TESTS: Univariable and multivariable linear regression were used to analyze the associations between TLoDA, NoB, GM-CBF and the cognitive assessment scores, with P < 0.05 indicating significance. RESULTS: TLoDA (r = 0.314) and NoB (r = 0.346) were significantly correlated with GM-CBF. Multivariable linear regression analyses showed that TLoDA and NoB, but not GM-CBF (P = 0.272 and 0.141), were significantly associated with short-term and long-term delay-recall AVLT scores. These associations remained significant after adjusting for GM-CBF. DATA CONCLUSION: The TLoDA and NoB of distal intracranial arteries on TOF-MRA are significantly associated with cognitive impairment in hypertensive subjects. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.