Growth-inhibiting effects of the unconventional plant APYRASE 7 of Arabidopsis thaliana influences the LRX/RALF/FER growth regulatory module.

Plant cell growth involves coordination of numerous processes and signaling cascades among the different cellular compartments to concomitantly enlarge the protoplast and the surrounding cell wall. The cell wall integrity-sensing process involves the extracellular LRX (LRR-Extensin) proteins that bind RALF (Rapid ALkalinization Factor) peptide hormones and, in vegetative tissues, interact with the transmembrane receptor kinase FERONIA (FER). This LRX/RALF/FER signaling module influences cell wall composition and regulates cell growth. The numerous proteins involved in or influenced by this module are beginning to be characterized. In a genetic screen, mutations in Apyrase 7 (APY7) were identified to suppress growth defects observed in lrx1 and fer mutants. APY7 encodes a Golgi-localized NTP-diphosphohydrolase, but opposed to other apyrases of Arabidopsis, APY7 revealed to be a negative regulator of cell growth. APY7 modulates the growth-inhibiting effect of RALF1, influences the cell wall architecture and -composition, and alters the pH of the extracellular matrix, all of which affect cell growth. Together, this study reveals a function of APY7 in cell wall formation and cell growth that is connected to growth processes influenced by the LRX/RALF/FER signaling module.

Comparative genomic analysis reveals expansion of the DnaJ gene family in Lagerstroemia indica and its members response to salt stress.

DnaJs/Hsp40s/JPDs are obligate co-chaperones of heat shock proteins (Hsp70), performing crucial biological functions within organisms. A comparative genome analysis of four genomes (Vitis vinifera, Eucalyptus grandis, Lagerstroemia indica, and Punica granatum) revealed that the DnaJ gene family in L. indica has undergone expansion, although not to the extent observed in P. granatum. Inter-genome collinearity analysis of four plants indicates that members belonging to Class A and B are more conserved during evolution. In L. indica, the expanded members primarily belong to Class-C. Tissue expression patterns and the biochemical characterization of LiDnaJs further suggested that DnaJs may be involved in numerous biological processes in L. indica. Transcriptome and qPCR analyses of salt stressed leaves identified at least ten LiDnaJs that responded to salt stress. In summary, we have elucidated the expansion mechanism of the LiDnaJs, which is attributed to a recent whole-genome triplication. This research laid the foundation for functional analysis of LiDnaJs and provides gene resources for breeding salt-tolerant varieties of L. indica.

Neonatal Exposure to Polystyrene Nanoplastics Impairs Microglia-Mediated Synaptic Pruning and Causes Social Behavioral Defects in Adulthood.

The increasing prevalence and persistence of nanoplastics (NPs) have become critical environmental concerns. These particles have the potential to enter the food chain and accumulate in living organisms, which exerts their adverse effects on human health. The release of nanoparticles from feeding bottles raises concerns about potential health issues, especially for newborns exposed to NPs at the neonatal stage. In this study, we examined the impacts of neonatal exposure to polystyrene nanoplastics (PS-NPs) on neurodevelopment. Our study demonstrates that exposure to PS-NPs in newborn mice impairs microglial autophagic function and energy metabolism, leading to the disruption of microglia-mediated synaptic pruning during early neurodevelopment. These mice subsequently develop social behavioral defects in adulthood, suggesting the long-lasting effects of neonatal PS-NP exposure on brain development and behavior. Together, these data provide insights into the mechanism by which PS-NPs affect early neurodevelopment, thus emphasizing the crucial need to address plastic pollution globally.

Physical activity diminished adverse associations of obesity with lipid metabolism in the population of rural regions of China.

The interactive effects of obesity and physical inactivity on lipid metabolism and prevalent dyslipidemia are scarcely reported in rural regions. 39029 subjects were obtained from the Henan Rural Cohort, and their metabolic equivalents (METs) of physical activity (PA) were computed. Independent associations of the obesity indices and PA with either lipid indices or prevalent dyslipidemia were analyzed by generalized linear models, and additive effects of obesity and PA on prevalent dyslipidemia were further quantified. Each obesity index was positively associated with total cholesterol, triglyceride, low-density lipoprotein or prevalent dyslipidemia but negatively associated with high-density lipoprotein, whereas the opposite association of PA with either each lipid index or prevalent dyslipidemia was observed. Joint association of PA and each obesity index with each lipid index and prevalent dyslipidemia was observed. Furthermore, the association of each obesity index in association with each lipid index was attenuated by increased PA levels.

XGBLC: an improved survival prediction model based on XGBoost.

MOTIVATION: Survival analysis using gene expression profiles plays a crucial role in the interpretation of clinical research and assessment of disease therapy programs. Several prediction models have been developed to explore the relationship between patients' covariates and survival. However, the high-dimensional genomic features limit the prediction performance of the survival model. Thus, an accurate and reliable prediction model is necessary for survival analysis using high-dimensional genomic data. RESULTS: In this study, we proposed an improved survival prediction model based on XGBoost framework called XGBLC, which used Lasso-Cox to enhance the ability to analyze high-dimensional genomic data. The novel first- and second-order gradient statistics of Lasso-Cox were defined to construct the loss function of XGBLC. We extensively tested our XGBLC algorithm on both simulated and real-world datasets, and estimated the performance of models with 5-fold cross-validation. Based on 20 cancer datasets from The Cancer Genome Atlas (TCGA), XGBLC outperforms five state-of-the-art survival methods in terms of C-index, Brier score and AUC. The results show that XGBLC still keeps good accuracy and robustness by comparing the performance on the simulated datasets with different scales. The developed prediction model would be beneficial for physicians to understand the effects of patient's genomic characteristics on survival and make personalized treatment decisions. AVAILABILITY AND IMPLEMENTATION: The implementation of XGBLC algorithm based on R language is available at: https://github.com/lab319/XGBLC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Association of serum NOD-like receptor protein 3 levels with impaired fat tolerance and hypertriglyceridemia.

The NOD-like receptor protein 3 (NLRP3) inflammasome plays a key role in lipid metabolism. We used an oral fat tolerance test (OFTT) to detect whether serum NLRP3 levels differed in people with different fat tolerances and evaluate whether NLRP3 was associated with impaired fat tolerance (IFT) and hypertriglyceridemia (HTG). We performed the OFTT using 176 volunteers. The groups were divided according to fasting and postprandial triglyceride (TG) levels: 1) normal fat tolerance (NFT) group (TG at 0 h <1.7 mmol/L and TG at any time point <2.5 mmol/L); 2) IFT group (TG at 0 h <1.7 mmol/L and TG at any time point >2.5 mmol/L); and 3) HTG group (TG at 0 h ≥1.7 mmol/L). With decreased lipid tolerance, the TG and NLRP3 levels increased gradually before a high-fat meal and at any time point after 0 h. NLRP3 levels reached a peak 2 h after meal consumption in all three groups. After adjustment for confounding indicators, logistic regression analysis revealed that fasting serum NLRP3 levels were positively associated with both IFT and HTG (for IFT, odds ratio [OR]: 1.079 [1.037-1.123], p < 0.001; for HTG, OR: 1.085 [1.049-1.123], p < 0.001). According to the receiver operating characteristic curve, fasting serum NLRP3 levels were an effective biomarker for IFT and HTG diagnosis. These results indicate that the fasting serum NLRP3 is an independent risk factor for IFT and HTG, and is a valuable indicator for the early diagnosis of IFT and HTG.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Aging biomarkers: Potential mediators of association between long-term ozone exposure and risk of atherosclerosis.

BACKGROUND: Long-term exposure to ambient ozone links to aging biomarkers and increased risk for atherosclerotic cardiovascular diseases (ASCVD). However, the roles of aging biomarkers in the association of long-term exposure to ambient ozone with ASCVD are unclear. METHODS: A total of 5298 participants completed the questionnaire and physical examination and provided biological specimens. Aging biomarkers (telomere length [TL] and mitochondrial copy number [mtDNA-CN]) were measured by using a real-time polymerase chain reaction method. The concentration of ambient ozone was assessed using a random forest model. Associations of ambient ozone or aging biomarkers with 10-year ASCVD risk were analyzed using logistic regression models. The roles of aging biomarkers in the association of ambient ozone exposure with 10-year ASCVD risk were explored by mediation analysis. RESULTS: The adjusted odds ratios and 95% confidence interval of high 10-year ASCVD risk were 1.16 (1.08, 1.25), 0.71 (0.60, 0.85), and 0.78 (0.64, 0.96) in association with each 1-unit increment in ambient ozone (1 µg/m3 ) concentration, relative TL, and mtDNA-CN, respectively. The mediated proportion of the association between ambient ozone exposure and high 10-year ASCVD risk by TL or mtDNA-CN was 21.13% or 7.75%, respectively. The total proportion of association between ambient ozone exposure and high 10-year ASCVD risk mediated by TL plus mtDNA-CN was 21.02%. CONCLUSIONS: Long-term exposure to ambient ozone was associated with increased 10-year ASCVD risk, and the association was partially mediated by aging biomarkers (shortened TL and decreased mtDNA-CN). This study indicated that ambient ozone pollution-related ASCVD risk might be partially explained by the telomere-mitochondrial axis of aging.

Neuronal activity-induced SUMOylation of Akt1 by PIAS3 is required for long-term potentiation of synaptic transmission.

Neuronal activity regulates spatial distribution of the SUMOylation system in cytosolic and dendritic sites, which has been implicated in learning, memory, and underlying synaptic structural and functional remodeling in the hippocampus. However, the functional target proteins for activated small ubiquitin-like modifiers (SUMOs) and downstream molecular consequences behind long-term potentiation (LTP) of synaptic plasticity remain to be elucidated. In this study, we showed that N-methyl-D-aspartate receptor-mediated neuronal activity induced the covalent modification of cytosolic Akt1 by small ubiquitin-like modifier 1 (SUMO1) in rat cortical and hippocampal CA1 neurons. Protein inhibitor of activated STAT3 (PIAS3) was involved in the activity-induced Akt1 SUMO1-ylation, and K64 and K276 residues were major SUMOylated sites. Importantly, Akt1 SUMOylation at K64 and K276 enhanced its enzymatic activity and facilitated T308 phosphorylation. Furthermore, the N-terminal SAP domain of PIAS3 bound Akt1 directly. The disruption of Akt1-PIAS3 interaction by Tat-SAP, a synthetic Tat-fused cell-permeable peptide containing PIAS3 SAP domain, inhibited neuronal activity-induced Akt1 SUMOylation and impaired LTP expression and late phase LTP maintenance in the hippocampus. Correlatedly, Tat-SAP not only blocked the LTP-related extracellular signal-regulated kinase (ERK)1/2-Elk-1-brain-derived neurotrophic factor (BDNF)/Arc signaling, but also disrupted mammalian target of rapamycin (mTOR)-eIF4E-binding protein 1 (4E-BP1) pathway. These findings reveal an activity-induced Akt1 SUMOylation by PIAS3 that contributes to ERK1/2-BDNF/Arc and mTOR-4E-BP1 cascades, and in turn, long-lasting excitatory synaptic responses.

Increased Levels of VCAM-1 in Sera and VLA-4 Expression on Neutrophils in Dermatomyositis with Interstitial Lung Disease.

Vascular cell adhesion molecule-1 (VCAM-1) and its ligand very late antigen (VLA-4) play important roles in many autoimmune diseases. Our study aimed to investigate the serum level of VCAM-1 and VLA-4 expression on peripheral blood neutrophil surface in patients with dermatomyositis (DM), especially focusing on patients with interstitial lung disease (ILD). Blood specimens of 42 patients with DM and 42 healthy controls matched for age and gender were recruited. Total serum VCAM-1 level was measured using commercial enzyme-linked immunosorbent assay (ELISA) and the percentages of VLA-4 expression on neutrophils were analyzed by flow cytometry. We divided patients into subgroups according to whether they had ILD and whether they exhibited diffuse alveolar damage (DAD) via high-resolution computed tomography (HRCT). sVCAM-1 was increased in classical DM (cDM) and clinical amyopathic dermatomyositis (CADM) compared with healthy controls (both p < .01). DM-ILD had higher sVCAM-1 levels than the none-ILD group (p < .01). sVCAM-1 was also significantly increased in the DAD group compared to the none-DAD group (p < .01). The percentages of VLA-4 expression on neutrophils in cDM and CADM patients were significantly elevated than that in healthy controls (both p < .01). The percentage of VLA-4 expression on neutrophils in DM patients with ILD was higher than none-ILD group (p < .01). In the patients with ILD, DAD group had a higher percentage of VLA-4 expression on neutrophils than none-DAD group (p < .01). Our findings indicated that serum VCAM-1 levels combined with VLA-4 expression on neutrophils might be useful for detecting the severity of lung disease in patients with DM.

Pterostilbene, a Resveratrol Derivative, Improves Ectopic Lipid Deposition in the Kidneys of Mice Induced by a High-Fat Diet.

BACKGROUND: Diabetic kidney disease is a major cause of global end-stage renal diseases. Ectopic lipid deposition in the renal tissues of diabetic kidney disease is one major factor leading to renal fibrosis and chronic kidney disease. Pterostilbene has been reported to display lipid-lowing activity and participate in many kidney diseases. However, the influence of pterostilbene on the ectopic lipid deposition is unclear. We intend to explore the influence of pterostilbene on the ectopic lipid deposition in the kidneys of mice induced by high fat. METHODS: A high-fat diet-induced diabetic mouse model was established to detect the alleviative effect of pterostilbene on the ectopic lipid deposition in the kidneys of diabetic mice. A biochemical analysis was performed to examine the levels of urine albumin, urine creatinine, serum creatinine, and blood urea nitrogen in mice after pterostilbene treatment. Histological analysis was conducted to detect the degree of renal injury and fibrosis. Oil red O staining and immunohistochemical staining were carried out to evaluate lipid droplets and the expression of adipose differentiation-related protein in renal tissues of the mice treated by pterostilbene. The protein levels were assessed by Western blotting. RESULTS: Pterostilbene inhibits the expression of the TGF-ß1 and p-smad3 and suppresses the protein levels of SREBP-1 and FAS, and it ultimately reduces the ectopic lipid deposition, alleviates the renal tubular damage and renal fibrosis in the kidneys of diabetic mice induced by high fat, and improves kidney function. CONCLUSION: Pterostilbene alleviates renal fibrosis and ectopic lipid deposition in the kidneys of diabetic mice induced by high-fat diet by inhibiting the TGF-ß1/smad3 signaling.

Physical activity attenuates the association between household air pollution and health-related quality of life in Chinese rural population: the Henan Rural Cohort Study.

BACKGROUND AND PURPOSE: Limited research focused on the association between household air pollution (HAP) and health-related quality of life (HRQoL). This study aimed to investigate the association of HAP with HRQoL and the effect modification of physical activity. METHOD: A total of 16,761 eligible participants were derived from the Henan Rural Cohort Study. Based on structured questionnaires, HAP was assessed by fuel type, cooking duration and kitchen ventilation; HRQoL was measured with utility index and VAS score from the European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L); physical activity was assessed by the International Physical Activity Questionnaire. Generalized linear models and tobit regression models were utilized to explore the relationship of HAP with HRQoL. Further sensitivity analyses were conducted using structural equation models. RESULTS: Compared with those who cooked with clean fuels, short-duration, or good kitchen ventilation, participants who cooked with solid fuels, long-duration, and poor ventilation had lower utility index and VAS score (All P < 0.001). The decrease in utility index for solid fuel users vs. clean fuel users were 0.06 [95%confidence interval (CI) 003, 0.08], 0.03 (95%CI 0.01, 0.04) and 0.02 (95%CI 0.01, 0.04) in low, moderate and high physical activity group, respectively, which decreased with physical activity levels (Pfor interaction < 0.05). Similar results were observed in associations of kitchen ventilation with utility index and VAS score. CONCLUSION: HAP negatively associated with HRQoL in rural population, and potential intervention aimed at maintaining adequate physical activity. TRAIL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Effect modification of kitchen ventilation on the associations of solid fuel use and long-duration cooking with the increased prevalence of depressive and anxiety symptoms: The Henan Rural Cohort Study.

Although solid fuel use for cooking is linked to an increased risk for depression, there is limited evidence on the effects of cooking duration and kitchen ventilation on these associations in rural areas. Among 29 903 participants from the Henan Rural Cohort, the independent and combined associations of cooking fuel type, cooking duration, and kitchen ventilation with depressive and anxiety symptoms were examined by logistic regression models and restricted cubic spline. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of solid fuel use for depressive and anxiety symptoms were 1.237 (1.041, 1.469) and 1.384 (1.153, 1.662), respectively. Increased cooking duration was associated with an increased prevalence of depressive symptoms (aOR: 1.098, 95% CI: 1.033, 1.166) and anxiety symptoms (aOR: 1.074, 95% CI: 1.009, 1.144). Solid fuel use and long-duration cooking associated with increased prevalence of depressive and anxiety symptoms were only observed in individuals without kitchen ventilation. Kitchen ventilation may attenuate the positive associations of solid fuel use and long-duration cooking with the prevalence of depressive and anxiety symptoms, which suggested popularizing clean fuel and promoting kitchen ventilation may be effective strategies to improve mental health related to household air pollution sourced from solid fuel use and long-duration cooking.

Association of household air pollution with glucose homeostasis markers in Chinese rural women: Effect modification of socioeconomic status.

BACKGROUND: Socioeconomic status (SES) was a crucial influencing factor of household air pollution (HAP). However, few studies have explored the potential effect modification of SES on the associations of HAP with type 2 diabetes mellitus (T2DM) and glucose homeostasis. METHODS: A total of 20900 participants were obtained from the Henan Rural Cohort. HAP reflected by cooking fuel type and cooking duration was assessed via questionnaire. SES was evaluated by two dimensions: educational level and average monthly income. Associations of cooking fuel type, cooking duration with T2DM and glucose homeostasis indices (insulin, fasting plasma glucose (FPG), and HOMA-ß) were assessed by the generalized linear model. Analyses were also conducted in different SES groups to explore the potential effect modification. RESULTS: Significant negative association of cooking fuel type and cooking duration with T2DM, FPG, and HOMA-ß was not observed. However, cooking with solid fuel and long-duration cooking were associated with decreased insulin level in women, and the adjusted coefficients were - 0.35 (95% confidence interval (95% CI): - 0.53, - 0.17) and - 0.36 (95% CI: -0.50, -0.21), respectively. Results from stratified analyses showed that these associations were more prominent in women with low average monthly income, with corresponding coefficient of - 0.57 (95% CI: -0.77, -0.37) for cooking with solid fuel and - 0.34 (95% CI: -0.52, -0.16) for long-duration cooking. Among women with low average monthly income, the largest decreased insulin level was observed in those who cooked with solid fuel, long-duration and poor kitchen ventilation, while the negative association of cooking fuel type and cooking duration with insulin level was slightly alleviated in the good kitchen ventilation group. CONCLUSIONS: Low average monthly income aggravated the negative association of HAP and insulin level among rural women, while improving kitchen ventilation may be a practical intervention. TRAIL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July, 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375.

On-Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Ladder Phenylenes Synthesized on Au(111) Surface via Selective [2+2] Cycloaddition.

Ladder phenylenes (LPs) composed of alternating fused benzene and cyclobutadiene rings have been synthesized in solution with a maximum length no longer than five units. Longer polymeric LPs have not been obtained so far because of their poor stability and insolubility. Here, we report the synthesis of linear LP chains on the Au(111) surface via dehalogenative [2+2] cycloaddition, in which the steric hindrance of the methyl groups in the 1,2,4,5-tetrabromo-3,6-dimethylbenzene precursor improves the chemoselectivity as well as the orientation orderliness. By combining scanning tunneling microscopy and noncontact atomic force microscopy, we determined the atomic structure and the electronic properties of the LP chains on the metallic substrate and NaCl/Au(111). The tunneling spectroscopy measurements revealed the charged state of chains on the NaCl layer, and this finding is supported by density functional theory calculations, which predict an indirect bandgap and antiferromagnetism in the polymeric LP chains.

A correlation study of the relationships between nonalcoholic fatty liver disease and serum triglyceride concentration after an oral fat tolerance test.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. Triglyceride (TG) accumulation is central to NAFLD development. People now spend most of their day in the postprandial state, and the measurement of postprandial blood lipid concentration can make up for the lack of simple detection of fasting blood lipids. Postprandial triglyceride (PTG) is commonly used as a surrogate for postprandial blood lipid concentrations, and many studies have shown that PTG is a risk factor for NAFLD. The aim of the present study was to investigate the relationship between PTG concentration during oral fat tolerance testing (OFTT) and NAFLD. METHODS: A total of 472 Chinese adults, aged 25 to 65 years, were enrolled in the study. All the participants underwent OFTT. The serum concentrations of TG and other lipids were measured, and their relationships with NAFLD were analyzed. RESULTS: Of the 472 participants, 155 were diagnosed with NAFLD. The fasting and postprandial TG concentrations of the participants with NAFLD were higher than those of healthy participants (P < 0.05). The TG concentrations of the healthy participants peaked 4 h postprandially, whereas those of the participants with NAFLD peaked 6 h postprandially and reached higher peak values. Postprandial TG concentration was significantly associated with a higher risk of NAFLD. CONCLUSIONS: High PTG is positively related to a higher risk of NAFLD, and the PTG concentrations of patients with NAFLD are higher than in healthy individuals, with a delayed peak. Therefore, 4-h PTG may represent a potential marker of NAFLD. TRIAL REGISTRATION: ChiCTR1800019514 .

Cyclin G2 regulates canonical Wnt signalling via interaction with Dapper1 to attenuate tubulointerstitial fibrosis in diabetic nephropathy.

Cyclin G2 (CCNG2) is an atypical cyclin that inhibits cell cycle progression and is often dysregulated in human cancers. Cyclin G2 in the occurrence and development of diabetic nephropathy (DN), one of the most severe diabetic complications, has not been fully identified. In this study, we investigated the function and regulatory mechanism of cyclin G2 in DN. In vivo studies revealed that a deficiency of cyclin G2 significantly increased albuminuria and promoted tubulointerstitial fibrosis in established DN. Cyclin G2 regulated the expression of fibrosis-related proteins via the canonical Wnt signalling pathway in renal tubular epithelial cells. Moreover, the binding of cyclin G2 to Dapper1 (Dpr1/DACT1), a protein involved in Wnt signalling, decreased the phosphorylation of Dpr1 at Ser762 by casein kinase 1 (CK1) and suppressed the Wnt signalling pathway. These findings reveal that cyclin G2 can protect against renal injury and fibrosis associated with DN and, thus, is a new target for the prevention and treatment of diabetic complications.

pH-Responsive aggregates transition from spherical micelles to WLMs induced by hydrotropes based on the dynamic imine bond.

In recent years, the use of dynamic chemical bonds to construct stimulus-responsive micelle systems has received increasing attention. However, current reports focus on the construction of dynamic covalent bond surfactants using dynamic chemical bonds, and the method of applying dynamic covalent bonds to hydrotropes has not been reported yet. In this study, a novel pH-responsive worm-like micelle system was constructed by mixing cetyltrimethylammonium bromide (CTAB), 4-hydroxybenzaldehyde (HB) and p-toluidine (MB) at the molar ratio of 60 mM : 40 mM : 40 mM. The formation mechanism of the dynamic covalent bond hydrotropes and the rheological behavior of the micelles were investigated via rheology, 1H-NMR spectroscopy and Cryo-TEM. The results show that as the pH increases, the viscosity of the solution first decreases and then increases rapidly. The microscopic aggregates in the solution transition from spherical micelles to worm-like micelles (WLMs), and the solution changes from a water-like fluid without viscosity to a gel system that can withstand its own weight. The transformation of the aggregates and their rheology can be attributed to the formation of MB-HB-, which is a type of hydrotrope with dynamic covalent bonds. Moreover, the transition from spherical micelles to worm-like micelles in this system is reversible.

Effects of sodium chloride on rheological behaviour of the gemini-like surfactants.

The gemini-like surfactants have been constructed by compounding N-erucamidopropyl-N,N-dimethylamine (UC22AMPM) and o-phthalic acid (o-PA), m-phthalic acid (m-PA), or p-phthalic acid (p-PA), and are denoted as o-EAPA, m-EAPA, and p-EAPA, respectively. It is well known that inorganic salts have significant effects on surfactant aggregates, and herein the effects of sodium chloride (NaCl) on gemini-like surfactants is explored by rheological and dynamic light scattering measurements, and cryo-TEM. It is found that the viscoelasticity of the EAPA systems first increases and then decreases with an increase of the NaCl concentration. And the optimal NaCl concentrations for these three systems are in the order of o-EAPA < m-EAPA < p-EAPA due to different spacer distances between the two carboxyl groups in the phthalic acid. Similar trends in the N,N-dimethyl oleoaminde-propylamine (DOAPA) and o-PA, m-PA, or p-PA systems were also observed. The results show that an appropriate NaCl concentration will promote gemini-like surfactants to form wormlike micelles (WLMs). Upon further increasing the NaCl concentration, the WLMs transform into vesicles. Excessive NaCl concentration will cause the surfactant systems to reach their cloud point and make the surfactants precipitate out. The mechanism of the effects of NaCl is that Cl- reduces the electrostatic repulsion between the headgroups of the surfactants. This work is helpful in understanding the effects of inorganic salts on the surfactants and this study is useful for exploring the practical applications of gemini-like surfactants.