Association between Human Urotensin II and Essential Hypertension—A 1:1 Matched Case-Control Study

Objective

We aimed to evaluate the controversial association between human urotensin II and essential hypertension in untreated hypertensive cases and normotensive controls.

Methods

197 newly diagnosed hypertensive patients and 197 age- and sex-matched normotensive controls were studied. Plasma urotensin II, nitric oxide metabolites, and other traditional biomarkers were examined.

Results

Hypertensive patients had higher urotensin II [median (interquartile rang): 9.32 (7.86–11.52) ng/mL vs 8.52 (7.07–10.41) ng/mL] and lower nitric oxide metabolites [19.19 (2.55–38.48) µmol/L vs 23.83 (11.97–43.40) µmol/L] than normotensive controls. Urotensin II was positively correlated with systolic blood pressure (r = 0.169, P<0.001) and diastolic blood pressure (r = 0.113, P = 0.024) while negatively correlated with nitric oxide metabolites (r = −0.112, P = 0.027). In multivariate regression analysis, subjects in the highest quartile of urotensin II were more likely to have hypertension than those in the lowest quartile (OR, 2.58; 95% CI, 1.21–5.49). Sub-group analyses in 106 pairs of cases and controls with either both normal or both abnormal nitric oxide metabolites levels showed that the association between urotensin II levels and hypertension persisted (P value for trend = 0.039).

Conclusion

Human urotensin II is markedly associated with essential hypertension, and the association is independent of nitric oxide metabolites. Our results indicated that urotensin II might be an independent risk factor for essential hypertension.     

Nitrotyrosine Level Was Associated with Mortality in Patients with Acute Kidney Injury

Background

To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma nitrotyrosine levels and 90-day mortality in patients with AKI.

Methodology/Principal Findings

158 patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and 15 age and gender-matched healthy subjects served as control. Plasma 3-nitrotyrosine was analyzed in relation to 90-day all cause mortality of patients with AKI. The patients with AKI were followed up for 90 days and grouped according to median plasma 3-nitrotyrosine concentrations. Highest 3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The 90-day survival curves of patients with high 3-NT/Tyr showed significant differences compared with the curves of individuals with low 3-NT/Tyr (p = 0.001 by log rank test). Multivariate analysis (Cox regression) revealed that 3-NT/Tyr (p = 0.025) was independently associated with mortality after adjustment for age, gender, sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) II score.

Conclusions/Significance

There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content. 3-NT/Tyr level was associated with mortality of AKI patients independent of the severity of illness.     

Bis(heptalene) “submarine” metal dimer sandwich compounds (C12H10)2M2 (M = Ti, V, Cr, Mn, Fe, Co, Ni)

The bis(heptalene)dimetal complexes (C₁₂H₁₀)₂M₂ of the first row transition metals from Ti to Ni are predicted by density functional theory to exhibit “submarine” sandwich structures with a pair of metal atoms sandwiched between the two heptalene rings. For the early transition metal derivatives (C₁₂H₁₀)₂M₂ (M = V, Cr) there are two types of such structures. In one structural type the metals are sandwiched between two heptahapto heptalene rings with metal-metal distances (3.5–3.8 Å) too long for direct metal-metal bonding. The other type of (C₁₂H₁₀)₂M₂ (M = V, Cr, Mn) structure has a pair of bonded metal atoms sandwiched between a fully bonded heptalene ligand and a heptalene ligand bonded to the metals only through an eight-carbon heptafulvene subunit, leaving an uncomplexed cis-1,3-diene unit. The formal metal-metal bond orders in these latter structures are 3, 2, and 1 for M = V, Cr, and Mn with predicted bond lengths of 2.5, 2.7, and 2.8 Å, respectively. For (C₁₂H₁₀)₂Fe₂ a singlet structure with each iron atom sandwiched between a hexahapto and a tetrahapto heptalene ring is energetically preferred over an alternate structure with ferrocene-like iron atoms sandwiched between two pentahapto heptalene rings. Partial bonding of each heptalene ring to the metal atoms occurs in the late transition metal derivatives (C₁₂H₁₀)₂M₂ (M = Co, Ni). This leads to an unsymmetrical structure for the cobalt derivative and a structure for the nickel derivative with each nickel atom sandwiched between a trihapto ligand and a tetrahapto ligand.

The dynamic motion of a M (M = Ca, Yb) atom inside the C74 (D 3h) cage: a relativistic DFT study

The interaction between M (M?=?Ca, Yb) atom and C₇₄ (D _3h) has been investigated by all electron relativistic density function theory. With the aid of the representative patch of C₇₄ (D _3h), we studied the interaction between C₇₄ (D _3h) and M (M?=?Ca, Yb) atom and obtained the interaction potential. Optimized structures show that there are three equivalent stable isomers and there is one transition state between every two stable isomers. According to the minimum energy pathway, the possible movement trajectory of M (M?=?Ca, Yb) atom in the C₇₄ (D _3h) cage is explored. The calculated energy barrier for Yb atoms moving from the stable isomer to the transition state is 10.4 kcal mol^?1 and the energy barrier for Ca atoms is 6.1 kcal mol^?1. The calculated NMR spectra of M@C₇₄ (M?=?Ca, Yb) are in good agreement with the experimental data. There are nine lines in the spectra: one 1/6 intensity signal, four half intensity signals and four full intensity signals.     

One‐Step Fabrication of Ultrathin Porous Nickel Hydroxide‐Manganese Dioxide Hybrid Nanosheets for Supercapacitor Electrodes with Excellent Capacitive Performance

A facile one‐step hydrothermal co‐deposition method for growth of ultrathin Ni(OH)₂‐MnO₂ hybrid nanosheet arrays on three dimensional (3D) macroporous nickel foam is presented. Due to the highly hydrophilic and ultrathin nature of hybrid nanosheets, as well as the synergetic effects of Ni(OH)₂ and MnO₂, the as‐fabricated Ni(OH)₂‐MnO₂ hybrid electrode exhibits an ultrahigh specific capacitance of 2628 F g^?1. Moreover, the asymmetric supercapacitor with the as‐obtained Ni(OH)₂‐MnO₂ hybrid film as the positive electrode and the reduced graphene oxide as the negative electrode has a high energy density (186 Wh kg^?1 at 778 W kg^?1), based on the total mass of active materials.     

Sandwich‐Type Microporous Carbon Nanosheets for Enhanced Supercapacitor Performance

Sandwich‐type microporous hybrid carbon nanosheets (MHCN) consisting of graphene and microporous carbon layers are fabricated using graphene oxides as shape‐directing agent and the in‐situ formed poly(benzoxazine‐co‐resol) as carbon precursor. The reaction and condensation can be readily completed within 45 min. The obtained MHCN has a high density of accessible micropores that reside in the porous carbon with controlled thickness (e.g., 17 nm), a high surface area of 1293 m² g^?1 and a narrow pore size distribution of ca. 0.8 nm. These features allow an easy access, a rapid diffusion and a high loading of charged ions, which outperform the diffusion rate in bulk carbon and are highly efficient for an increased double‐layer capacitance. Meanwhile, the uniform graphene percolating in the interconnected MHCN forms the bulk conductive networks and their electrical conductivity can be up to 120 S m^?1 at the graphene percolation threshold of 2.0 wt.%. The best‐practice two‐electrode test demonstrates that the MHCN show a gravimetric capacitance of high up to 103 F g^?1 and a good energy density of ca. 22.4 Wh kg^?1 at a high current density of 5 A g^?1. These advanced properties ensure the MHCN a great promise as an electrode material for supercapacitors.     

Systematic research on the pretreatment of peptides for quantitative proteomics using a C18 microcolumn

Reversed phase microcolumns have been widely used for peptide pretreatment to desalt and remove interferences before tandem LC–MS in proteomics studies. However, few studies have characterized the effects of experimental parameters as well as column characteristics on the composition of identified peptides. In this study, several parameters including the concentration of ACN in washing buffer, the microcolumn's purification effect, the peptide recovery rate, and the dynamic‐binding capacity were characterized in detail, based upon stable isotope labeling by amino acids in a cell culture quantitative approach. The results showed that peptide losses can be reduced with low ACN concentration in washing buffers resulting in a recovery rate of approximately 82%. Furthermore, the effects of ACN concentration and loading amount on the properties of identified peptides were also evaluated. We found that the dynamic‐binding capacity of the column was approximately 26 μg. With increased loading amounts, more hydrophilic peptides were replaced by hydrophobic peptides.     

Distinct and Atypical Intrinsic and Extrinsic Cell Death Pathways between Photoreceptor Cell Types upon Specific Ablation of Ranbp2 in Cone Photoreceptors

Non-autonomous cell-death is a cardinal feature of the disintegration of neural networks in neurodegenerative diseases, but the molecular bases of this process are poorly understood. The neural retina comprises a mosaic of rod and cone photoreceptors. Cone and rod photoreceptors degenerate upon rod-specific expression of heterogeneous mutations in functionally distinct genes, whereas cone-specific mutations are thought to cause only cone demise. Here we show that conditional ablation in cone photoreceptors of Ran-binding protein-2 (Ranbp2), a cell context-dependent pleiotropic protein linked to neuroprotection, familial necrotic encephalopathies, acute transverse myelitis and tumor-suppression, promotes early electrophysiological deficits, subcellular erosive destruction and non-apoptotic death of cones, whereas rod photoreceptors undergo cone-dependent non-autonomous apoptosis. Cone-specific Ranbp2 ablation causes the temporal activation of a cone-intrinsic molecular cascade highlighted by the early activation of metalloproteinase 11/stromelysin-3 and up-regulation of Crx and CoREST, followed by the down-modulation of cone-specific phototransduction genes, transient up-regulation of regulatory/survival genes and activation of caspase-7 without apoptosis. Conversely, PARP1⁺-apoptotic rods develop upon sequential activation of caspase-9 and caspase-3 and loss of membrane permeability. Rod photoreceptor demise ceases upon cone degeneration. These findings reveal novel roles of Ranbp2 in the modulation of intrinsic and extrinsic cell death mechanisms and pathways. They also unveil a novel spatiotemporal paradigm of progression of neurodegeneration upon cell-specific genetic damage whereby a cone to rod non-autonomous death pathway with intrinsically distinct cell-type death manifestations is triggered by cell-specific loss of Ranbp2. Finally, this study casts new light onto cell-death mechanisms that may be shared by human dystrophies with distinct retinal spatial signatures as well as with other etiologically distinct neurodegenerative disorders.     

The Wilms Tumor Gene,Wt1, Is Critical for Mouse Spermatogenesis via Regulation of Sertoli Cell Polarity and Is Associated with Non-Obstructive Azoospermia in Humans

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1^flox and Cre-ER^TM mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood–testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.