Selective correlations between aliphatic 13C nuclei in protein solid-state NMR.

Solid-state nuclear magnetic resonance (NMR) is a potent tool for studying the structures and dynamics of insoluble proteins. It starts with signal assignment through multi-dimensional correlation experiments, where the aliphatic 13Cα-13Cß correlation is indispensable for identifying specific residues. However, developing efficient methods for achieving this correlation is a challenge in solid-state NMR. We present a simple band-selective zero-quantum (ZQ) recoupling method, named POST-C4161 (PC4), which enhances 13Cα-13Cß correlations under moderate magic-angle spinning (MAS) conditions. PC4 requires minimal 13C radio-frequency (RF) field and proton decoupling, exhibits high stability against RF variations, and achieves superior efficiency. Comparative tests on various samples, including the formyl-Met-Leu-Phe (fMLF) tripeptide, microcrystalline ß1 immunoglobulin binding domain of protein G (GB1), and membrane protein of mechanosensitive channel of large conductance from Methanosarcina acetivorans (MaMscL), demonstrate that PC4 selectively enhances 13Cα-13Cß correlations by up to 50 % while suppressing unwanted correlations, as compared to the popular dipolar-assisted rotational resonance (DARR). It has addressed the long-standing need for selective 13C-13C correlation methods. We anticipate that this simple but efficient PC4 method will have immediate applications in structural biology by solid-state NMR.

Exploring the economic toxicity experiences and coping styles of patients with colorectal cancer fistula in Jiangsu province, China: a qualitative study.

OBJECTIVES: In recent years, economic toxicity has significantly affected the physical and mental health as well as the quality of life of patients with colorectal cancer. However, this issue has not garnered adequate attention from healthcare professionals. This study aims to investigate the experiences of economic toxicity and coping strategies among patients with colorectal cancer fistula. The findings are intended to inform the development of suitable and effective intervention programmes to address economic toxicity within this patient population. DESIGN: A descriptive phenomenological approach was employed in this qualitative research, using a semistructured method for data collection and analysis of interview data. Traditional content analysis methods were applied, encompassing coding, categorisation and theme distillation. Data analysis continued until thematic saturation was achieved, with no new themes emerging. SETTING: Nanjing Medical University Lianyungang Clinical Medical College. PARTICIPANTS: A total of 21 patients with colorectal cancer fistula were selected as interview subjects through purposive sampling. The selection took place from May 2022 to May 2023, involving patients during their stay at a tertiary hospital in Lianyungang city, Jiangsu province, China. RESULTS: In total, three pieces and eight subthemes were distilled: subjective feelings (worries about treatment costs, concerns about uncertainty about the future, worries about daily life), coping styles (coping alone, unwillingness to help, prepurchased insurance, dealing with illness, giving up treatment, inability to afford costs) and needs and aspirations (need for health policies, need for social support). CONCLUSIONS: Patients with colorectal cancer fistulae experience economic toxicity, leading to significant impairment in both physical and mental health. Despite employing various coping strategies, healthcare professionals must prioritise addressing the economic toxicity issue in patients. Implementing rational and effective interventions can greatly assist patients in effectively managing economic toxicity.

An efficient method for detecting membrane protein oligomerization and complex using 05SAR-PAGE.

Oligomerization is an important feature of proteins, which gives a defined quaternary structure to complete the biological functions. Although frequently observed in membrane proteins, characterizing the oligomerization state remains complicated and time-consuming. In this study, 0.05% (w/v) sarkosyl-polyacrylamide gel electrophoresis (05SAR-PAGE) was used to identify the oligomer states of the membrane proteins CpxA, EnvZ, and Ma-Mscl with high sensitivity. Furthermore, two-dimensional electrophoresis (05SAR/sodium dodecyl sulfate-PAGE) combined with western blotting and liquid chromatography-tandem mass spectrometry was successfully applied to study the complex of CpxA/OmpA in cell lysate. The results indicated that 05SAR-PAGE is an efficient, economical, and practical gel method that can be widely used for the identification of membrane protein oligomerization and the analysis of weak protein interactions.

Association of sudomotor dysfunction with risk of diabetic retinopathy in patients with type 2 diabetes.

PURPOSE: Sudomotor dysfunction is considered as one of the earliest manifestations of diabetic peripheral neuropathy. We aimed to investigate the association between sudomotor dysfunction non-invasively detected by the SUDOSCAN device and diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: A total of 2010 patients admitted to a tertiary hospital located in Shanghai were included from March 2020 to September 2023. Sudomotor function was assessed by the SUDOSCAN device, and sudomotor dysfunction was defined as feet electrochemical skin conductance (FESC) <60 µs. Fundus radiography was used for DR assessment, which was graded according to the severity, specifically: (1) non-DR; (2) mild nonproliferative DR (NPDR); (3) moderate NPDR/vision-threatening DR (VTDR). RESULTS: Among the enrolled 2010 patients, 525 patients had sudomotor dysfunction; 648 were diagnosed with DR, which was equivalent to 32.2% of all patients. Patients with sudomotor dysfunction had a significantly higher prevalence of DR, compared to those with normal sudomotor function (40.8% vs. 29.2%, P < 0.05). After controlling for confounding factors including HbA1c, sudomotor dysfunction was significantly associated with any DR (odd ratio [OR] = 1.57, 95% CI 1.26-1.96). When FESC was considered as a continuous variable, the multivariable-adjusted OR of DR was 1.29 (95% CI 1.17-1.42) for per 1-SD decrease in FESC. Furthermore, multinomial logistic regression revealed significant associations between sudomotor dysfunction and all stages of DR (mild NPDR: OR = 1.40, 95% CI 1.11-1.78; moderate NPDR/VTDR: OR = 2.35, 95% CI 1.60-3.46). CONCLUSIONS: Sudomotor dysfunction was significantly associated with DR in patients with type 2 diabetes.

Membrane Protein Structures in Native Cellular Membranes Revealed by Solid-State NMR Spectroscopy.

The structural characterization of membrane proteins within the cellular membrane environment is critical for understanding the molecular mechanism in their native functional context. However, conducting residue site-specific structural analysis of membrane proteins in native membranes by solid-state NMR faces challenges due to poor spectral sensitivity and serious interference from background protein signals. In this study, we present a new protocol that combines various strategies for cellular membrane sample preparations, enabling us to reveal the secondary structure of the mechanosensitive channel of large conductance from Methanosarcina acetivorans (MaMscL) in Escherichia coli inner membranes. Our findings demonstrate the feasibility of achieving complete resonance assignments and the potential for determining the 3D structures of membrane proteins within cellular membranes. We find that the use of the BL21(DE3) strain in this protocol is crucial for effectively suppressing background protein labeling without compromising the sensitivity of the target protein. Furthermore, our data reveal that the structures of different proteins exhibit varying degrees of sensitivity to the membrane environment. These results underscore the significance of studying membrane proteins within their native cellular membranes when performing structural characterizations. Overall, this study opens up a new avenue for achieving the atomic-resolution structural characterization of membrane proteins within their native cellular membranes, providing valuable insights into the nativeness of membrane proteins.

Solid-state NMR structure determination of a membrane protein in E. coli cellular inner membrane.

Structure determination of membrane proteins in native cellular membranes is critical to precisely reveal their structures in physiological conditions. However, it remains challenging for solid-state nuclear magnetic resonance (ssNMR) due to the low sensitivity and high complexity of ssNMR spectra of cellular membranes. Here, we present the structure determination of aquaporin Z (AqpZ) by ssNMR in Escherichia coli inner membranes. To enhance the signal sensitivity of AqpZ, we optimized protein overexpression and removed outer membrane components. To suppress the interference of background proteins, we used a "dual-media" expression approach and antibiotic treatment. Using 1017 distance restraints obtained from two-dimensional 13C-13C spectra based on the complete chemical shift assignments, the 1.7-Å ssNMR structure of AqpZ is determined in E. coli inner membranes. This cellular ssNMR structure determination paves the way for analyzing the atomic structural details for membrane proteins in native cellular membranes.

Stochastic simulations of self-organized elastogenesis in the developing lung.

In the normal lung, the dominant cable is an elastic "line element" composed of elastin fibers bound to a protein scaffold. The cable line element maintains alveolar geometry by balancing surface forces within the alveolus and changes in lung volume with exercise. Recent work in the postnatal rat lung has suggested that the process of cable development is self-organized in the extracellular matrix. Early in postnatal development, a blanket of tropoelastin (TE) spheres appear in the primitive lung. Within 7 to 10 days, the TE spheres are incorporated into a distributed protein scaffold creating the mature cable line element. To study the process of extracellular assembly, we used cellular automata (CA) simulations. CA simulations demonstrated that the intermediate step of tropoelastin self-aggregation into TE spheres enhanced the efficiency of cable formation more than 5-fold. Similarly, the rate of tropoelastin production had a direct impact on the efficiency of scaffold binding. The binding affinity of the tropoelastin to the protein scaffold, potentially reflecting heritable traits, also had a significant impact on cable development. In contrast, the spatial distribution of TE monomer production, increased Brownian motion and variations in scaffold geometry did not significantly impact simulations of cable development. We conclude that CA simulations are useful in exploring the impact of concentration, geometry, and movement on the fundamental process of elastogenesis.

Hypoxia-Induced FUS-circTBC1D14 Stress Granules Promote Autophagy in TNBC.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is suggested to be associated with hypoxia. This study is the first to identify a novel circular RNA (circRNA), circTBC1D14, whose expression is significantly upregulated in TNBC. The authors confirm that high circTBC1D14 expression is associated with a poor prognosis in patients with breast cancer. circTBC1D14-associated mass spectrometry and RNA-binding protein-related bioinformatics strategies indicate that FUS can interact with circTBC1D14, which can bind to the downstream flanking sequence of circTBC1D14 to induce cyclization. FUS is an essential biomarker associated with stress granules (SGs), and the authors find that hypoxic conditions can induce FUS-circTBC1D14-associated SG formation in the cytoplasm after modification by protein PRMT1. Subsequently, circTBC1D14 increases the stability of PRMT1 by inhibiting its K48-regulated polyubiquitination, leading to the upregulation of PRMT1 expression. In addition, FUS-circTBC1D14 SGs can initiate a cascade of SG-linked proteins to recognize and control the elimination of SGs by recruiting LAMP1 and enhancing lysosome-associated autophagy flux, thus contributing to the maintenance of cellular homeostasis and promoting tumor progression in TNBC. Overall, these findings reveal that circTBC1D14 is a potential prognostic indicator that can serve as a therapeutic target for TNBC treatment.

Hypoxia-induced GPCPD1 depalmitoylation triggers mitophagy via regulating PRKN-mediated ubiquitination of VDAC1.

Mitophagy, which selectively eliminates the dysfunctional and excess mitochondria by autophagy, is crucial for cellular homeostasis under stresses such as hypoxia. Dysregulation of mitophagy has been increasingly linked to many disorders including neurodegenerative disease and cancer. Triple-negative breast cancer (TNBC), a highly aggressive breast cancer subtype, is reported to be characterized by hypoxia. However, the role of mitophagy in hypoxic TNBC as well as the underlying molecular mechanism is largely unexplored. Here, we identified GPCPD1 (glycerophosphocholine phosphodiesterase 1), a key enzyme in choline metabolism, as an essential mediator in hypoxia-induced mitophagy. Under the hypoxic condition, we found that GPCPD1 was depalmitoylated by LYPLA1, which facilitated the relocating of GPCPD1 to the outer mitochondrial membrane (OMM). Mitochondria-localized GPCPD1 could bind to VDAC1, the substrate for PRKN/PARKIN-dependent ubiquitination, thus interfering with the oligomerization of VDAC1. The increased monomer of VDAC1 provided more anchor sites to recruit PRKN-mediated polyubiquitination, which consequently triggered mitophagy. In addition, we found that GPCPD1-mediated mitophagy exerted a promotive effect on tumor growth and metastasis in TNBC both in vitro and in vivo. We further determined that GPCPD1 could serve as an independent prognostic indicator in TNBC. In conclusion, our study provides important insights into a mechanistic understanding of hypoxia-induced mitophagy and elucidates that GPCPD1 could act as a potential target for the future development of novel therapy for TNBC patients.Abbreviations: ACTB: actin beta; 5-aza: 5-azacytidine; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; ChIP: chromatin immunoprecipitation; co-IP: co-immunoprecipitation; CQ: chloroquine; CsA: cyclosporine; DOX: doxorubicin; FIS1: fission, mitochondrial 1; FUNDC1: FUN14 domain containing 1; GPCPD1: glycerophosphocholine phosphodiesterase 1; HAM: hydroxylamine; HIF1A: hypoxia inducible factor 1 subunit alpha; HRE: hypoxia response element; IF: immunofluorescence; LB: lysis buffer; LC3B/MAP1LC3B: microtubule associated protein 1 light chain 3 beta; LC-MS: liquid chromatography-mass spectrometry; LYPLA1: lysophospholipase 1; LYPLA2: lysophospholipase 2; MDA231: MDA-MB-231; MDA468: MDA-MB-468; MFN1: mitofusin 1; MFN2: mitofusin 2; MKI67: marker of proliferation Ki-67; OCR: oxygen consumption rate; OMM: outer mitochondrial membrane; OS: overall survival; PalmB: palmostatin B; PBS: phosphate-buffered saline; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; SDS: sodium dodecyl sulfate; TOMM20: translocase of outer mitochondrial membrane 20; TNBC: triple-negative breast cancer; VBIT-4: VDAC inhibitor; VDAC1: voltage dependent anion channel 1; WT: wild type.

Association of Dietary and Supplement Intake of Antioxidants with Risk of Dementia: A Meta-Analysis of Cohort Studies.

BACKGROUND: Dementia is a neuropsychiatric disorder with cognitive decline due to multiple factors. With the arrival of the aging population, the incidence of dementia has gradually increased. There is still no effective treatment for dementia, and therefore, the prevention of dementia has become crucial. Oxidative stress is considered to be one of the pathogenesis of dementia; therefore, antioxidant therapy and prevention of dementia have been gradually proposed. OBJECTIVE: Our meta-analysis aimed to investigate the association of antioxidants with risk of dementia. METHODS: We searched PubMed, Embase, and Web of Science databases for articles on antioxidants associated with dementia risk, and those containing cohort studies with high-dose versus low-dose controls were included in our meta-analysis. The resulting risk ratios (RR) and hazard ratios (HR) and 95% confidence intervals were statistically analyzed using Stata12.0 free software. RESULTS: A total of 17 articles were included in this meta-analysis. Of 98,264 participants, 7,425 had dementia after 3-23 years of follow-up. The results of the meta-analysis showed a trend towards a lower incidence of dementia with high intake of antioxidants (RR = 0.84, 95% CI 0.77-1.19 I2 = 54.6%), but this was not statistically significant. High antioxidant intake significantly reduced the incidence of Alzheimer 's disease (RR = 0.85, 95% CI 0.79-0.92 I2 = 45.5%), and we additionally carried out subgroup analyses by nutrient type, diet or supplement, region, and study quality score. CONCLUSION: Dietary intake of antioxidants or supplements reduces both the risk of dementia and the risk of Alzheimer's disease.

Identifying the drivers of changes in embodied food-energy-water in the Bohai mega-urban region, China: A perspective of final demands.

Food-energy-water (FEW) systems in the Bohai mega-urban region (MUR) have experienced astonishing changes in recent decades; however, the dynamics of these changes are not fully understood. This study combined an ecological multiscale input-output model and a structural decomposition analysis (SDA) to explore the variation in embodied FEW consumption and its drivers. The results showed that, although almost all sectoral embodied FEW intensities decreased, embodied FEW demands increased by approximately 9.9×108 tons, 4.61×107 TJ and 1.1×1011 m3 over 10-year period. The embodied FEW flow diagrams show that local consumption and trade were strengthened. Urban household consumption, fixed capital formation and exports were the main components affecting the embodied FEW use increases. An SDA revealed that the consumption level effect (∆c) was the dominant contributor that promoted the increase in the Bohai MUR's embodied FEW consumption. The scale effect (∆p) also had a positive effect on the embodied FEW consumption increases. The technological effect (∆e) was the primary contributor to offset the embodied FEW consumption increase. The economic efficiency effect (∆L) and structural effect (∆sd) also contributed to offsetting the total embodied FEW consumption increase. The effect of the change in domestic and foreign imports (∆D and ∆F) impacted the increase in embodied FEW mainly through the change in the embodied FEW intensities and trade volumes. This study identified the changes in FEW systems and highlighted future coping strategies.

The co-effect of copper and lipid vesicles on Aß aggregation.

Both metal ions and lipid membranes have a wide distribution in amyloid plaques and play significant roles in AD pathogenesis. Although influences of different metal ions or lipid vesicles on the aggregation of Aß peptides have been extensively studied, their combined effects are less understood. In this study, we reported a unique effect of copper ion on Aß aggregation in the presence of lipid vesicles, different from other divalent metal ions. Cu2+ in a super stoichiometric amount leads to the rapid formation of ß-sheet rich structure, containing abundant low molecular weight (LMW) oligomers. We demonstrated that oligomerization of Aß40 induced by Cu2+ binding was an essential prerequisite for the rapid conformation transition. Overall, the finding provided a new view on the complex triple system of Aß, copper ion and lipid vesicles, which might help understanding of Aß pathologies.

Relationship between time in range and corneal nerve fiber loss in asymptomatic patients with type 2 diabetes.

BACKGROUND: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM). METHODS: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm 2 . RESULTS: Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P   <  0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P  = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients. CONCLUSIONS: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

Association of vitamin E intake in diet and supplements with risk of dementia: A meta-analysis.

Background: Dementia is a chronic progressive neurodegenerative disease that can lead to disability and death in humans, but there is still no effective prevention and treatment. Due to the neuroprotective effects of vitamin E, a large number of researchers have explored whether vitamin E can reduce the risk of dementia. Some researchers believe that vitamin E can reduce the risk of dementia, while others hold the opposite conclusion. We therefore performed a meta-analysis to clarify the relationship between them. Methods: We searched PubMed, Embase, and Web of Science databases for articles on the connection of dietary and supplementation vitamin E with dementia risk from inception through April 2022 using the main keywords "dementia," "Alzheimer's disease," "vitamin E," and "tocopherol," and used a random-utility model for pooled effect sizes. Odds ratios (OR) and 95% confidence intervals were derived using lower and higher doses as contrasts. Obtained data were shown and assessed using Stata12.0 free software. Results: We included 15 articles in sum. Among them, there were nine articles containing AD. By comparing the highest intake with the lowest intake, Combined ORs for high intake were as follows: dementia (OR = 0.79, 95% CI 0.70-0.88 I 2 = 35.0%), Alzheimer's disease (OR = 0.78, 95% CI 0.64-0.94 I 2 = 36.9%). Subgroup analyses were also performed by study type, diet and supplementation, and NOS score. Conclusions: High vitamin E intake from diet and supplements significantly reduces the risk of dementia and Alzheimer's disease.

Serum IL-17A concentration and a IL17RA single nucleotide polymorphism contribute to the risk of autoimmune type 1 diabetes.

AIMS: Interleukin (IL)-17 is associated with autoimmunity. This study aimed to affirm the role of IL-17A, IL-17F and single nucleotide polymorphisms (SNPs) in genes related to them and their receptors in autoimmune type 1 diabetes (T1D) for Chinese population. METHODS: In this study, 130 patients with autoimmune T1D and 140 non-T1D controls were included for analysis. Clinical and biochemical data were collected, and serum levels of IL-17A, IL-17F, IL-6, and high-sensitivity C reactive protein were measured using ELISA. The SNPs rs2275913, rs8193036, rs3819025, rs763780, rs879577, rs4819554, and rs708567 were genotyped using the SNaPshot assay. RESULTS: IL-17A levels were higher in patients with autoimmune T1D than in controls (median [IQR] 28.83[37.38] vs. 16.68[8.10], p < 0.001) and high IL-17A was a risk factor for autoimmune T1D (odds ratio (OR), 1.013; 95% CI, 1.003-1.023; p = 0.013) after adjusting for confounding factors. Linear regression analysis revealed that log10 IL-17A levels were independently associated with fasting C-peptide, IL-6, body mass index, and IL-17F. However, no independent association was found between IL-17F and autoimmune T1D. The GG genotype of SNP rs4819554 in the interleukin 17 receptor A (IL17RA) gene was associated with a decreased risk of autoimmune T1D (OR, 0.458; 95% CI, 0.246-0.852; p = 0.014) after adjusting for other confounders. The IL17RA rs4819554 GG genotype was negatively correlated with serum glutamic acid decarboxylase antibody appearance (p < 0.05). CONCLUSIONS: Increased serum IL-17A, but not IL-17F, is a risk factor for autoimmune T1D. The GG genotype of IL17RA rs4819554 might decrease the risk for autoimmune T1D.

3D Printing of Stretchable, Adhesive and Conductive Ti3C2Tx-Polyacrylic Acid Hydrogels.

Stretchable, adhesive, and conductive hydrogels have been regarded as ideal interfacial materials for seamless and biocompatible integration with the human body. However, existing hydrogels can rarely achieve good mechanical, electrical, and adhesive properties simultaneously, as well as limited patterning/manufacturing techniques posing severe challenges to bioelectronic research and their practical applications. Herein, we develop a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel by a simple pre-crosslinking method followed by successive direct ink writing 3D printing. Pre-polymerization of acrylic acid can be initiated by mechanical mixing with Ti3C2Tx nanosheet suspension, leading to the formation of viscous 3D printable ink. Secondary free radical polymerization of the ink patterns via 3D printing can achieve a stretchable, adhesive, and conductive Ti3C2Tx-polyacrylic acid hydrogel. The as-formed hydrogel exhibits remarkable stretchability (~622%), high electrical conductivity (5.13 S m-1), and good adhesion strength on varying substrates. We further demonstrate the capability of facilely printing such hydrogels into complex geometries like mesh and rhombus patterns with high resolution and robust integration.

Improvement of average magnetic field measurement based on magnetic-field-sensitive Ramsey fringes.

Accurate magnetic field measurement is the key to evaluating the second-order Zeeman effect. The conventional method is to deduce the magnetic field by determining the center frequency of the magnetic-field-sensitive Ramsey fringes. In this Letter, we present a more rigorous theory for this method and demonstrate that the current peak-searching method has a non-negligible sub-Hz or even larger deviation. We introduce an improved method that considers more parameters and a strict formula that can correct the deviation and suppress it to below 0.1 Hz. Corresponding experiments on the 85Rb atomic fountain demonstrate that this improved method is expected to enhance the precision of magnetic field measurement and improve the atomic fountain clock.

Dynamics properties of membrane proteins in native cell membranes revealed by solid-state NMR spectroscopy.

Cell membranes provide an environment that is essential to the functions of membrane proteins. Cell membranes are mainly composed of proteins and highly diverse phospholipids. The influence of diverse lipid compositions of native cell membranes on the dynamics of the embedded membrane proteins has not been examined. Here we employ solid-state NMR to investigate the dynamics of E. coli Aquaporin Z (AqpZ) in its native inner cell membranes, and reveal the influence of diverse lipid compositions on the dynamics of AqpZ by comparing it in native cell membranes to that in POPC/POPG bilayers. We demonstrate that the dynamic rigidity of AqpZ generally conserves in both native cell membranes and POPC/POPG bilayers, due to its tightly packed tetrameric structure. In the gel and the liquid crystal phases of lipids, our experimental results show that AqpZ is more dynamic in native cell membranes than that in POPC/POPG bilayers. In addition, we observe that phase transitions of lipids in native membranes are less sensitive to temperature variations compared with that in POPC/POPG bilayers, which results in that the dynamics of AqpZ is less affected by the phase transitions of lipids in native cell membranes than that in POPC/POPG bilayers. This study provides new insights into the dynamics of membrane proteins in native cell membranes.

Urine Uric Acid Excretion Levels are Positively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Patients without Chronic Kidney Disease.

PURPOSE: We aimed to investigate whether urine uric acid excretion (UUAE) levels are associated with obesity and abdominal obesity in patients with type 2 diabetes (T2D). METHODS: There were 2785 type 2 diabetic patients in this cross-sectional study. Obesity was defined as BMI ≥ 25 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥90 cm for men and WC ≥ 80 cm for women based on World Health Organization (WHO) recommendations for Asians. Chronic kidney disease (CKD) was defined as the estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and/or urinary albumin excretion (UAE) ≥300 mg/24h. 24-h UUAE was determined enzymatically using a single 24-hour urine collection. All the subjects were stratified into quartiles based on UUAE levels. Both obesity and abdominal obesity were compared among the UUAE quartile groups, respectively. Furthermore, the associations of UUAE with obesity and abdominal obesity were analyzed in both CKD and non-CKD patients, respectively. RESULTS: There was an obvious increased trend in both obesity prevalence (36.2%, 41.5%, 46.3%, and 63.4%, respectively, p < 0.001 for trend) and abdominal obesity prevalence (58.1%, 61.2%, 64.7%, and 75.8%, respectively, p < 0.001 for trend) in patients with T2D across the UUAE quartiles after controlling for age, sex and diabetes duration. Multiple logistic regression analyses revealed independent associations between UUAE quartiles and obesity (p < 0.001) and abdominal obesity (p < 0.001) in all patients. However, UUAE was significantly associated with obesity and abdominal obesity only in the T2D patients without CKD (p < 0.001 in model 1, model 2, model 3 and model 4, respectively). CONCLUSION: Increased UUAE levels were significantly associated with the presence of obesity, especially abdominal obesity in T2D patients without CKD.