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Background The research about the influence of triglyceride-glucose index on early prognosis in stroke is lacking. Aims In this study, we evaluated the association between triglyceride-glucose index and early neurological deterioration in patients with single subcortical infarctions. Methods Consecutive patients with single subcortical infarctions within 72 h of symptom onset between 2011 and 2015. Early neurological deterioration was defined as an increase of ≥2 in the total NIHSS score or ≥1 in the motor NIHSS score. The triglyceride-glucose index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. Results A total of 305 patients with single subcortical infarctions were evaluated. In multivariable analysis, the triglyceride-glucose index (adjusted odds ratio [aOR] = 2.94, 95% confidence interval [CI] = 1.58–5.45) and age (aOR = 1.05, 95% CI = 1.01–1.09) were associated with early neurological deterioration. In subgroup analysis according to the type of single subcortical infarctions, only patients with proximal single subcortical infarctions showed a significant association between the triglyceride-glucose index and early neurological deterioration (aOR = 2.92, 95% CI = 1.35–6.29). On the other hand, there was no statistical significance in patients with distal single subcortical infarctions. Patients with untreated diabetes also showed the close association between the triglyceride-glucose index and early neurological deterioration (aOR = 3.94, 95% CI = 1.47–10.52). Conclusions The triglyceride-glucose index was associated with early neurological deterioration in single subcortical infarctions. This association differed depending on the location of lesion and the presence of untreated diabetes.

Adherens junctions (AJs) create spatially, chemically and mechanically discrete microdomains at cellular interfaces. Here, using a mechanogenetic platform that generates artificial AJs with controlled protein localization, clustering and mechanical loading, we find that AJs also organize proteolytic hotspots for γ-secretase with a spatially regulated substrate selectivity that is critical in the processing of Notch and other transmembrane proteins. Membrane microdomains outside of AJs exclusively organize Notch ligand-receptor engagement (LRE microdomains) to initiate receptor activation. Conversely, membrane microdomains within AJs exclusively serve to coordinate regulated intramembrane proteolysis (RIP microdomains). They do so by concentrating γ-secretase and primed receptors while excluding full-length Notch. AJs induce these functionally distinct microdomains by means of lipid-dependent γ-secretase recruitment and size-dependent protein segregation. By excluding full-length Notch from RIP microdomains, AJs prevent inappropriate enzyme-substrate interactions and suppress spurious Notch activation. Ligand-induced ectodomain shedding eliminates size-dependent segregation, releasing Notch to translocate into AJs for processing by γ-secretase. This mechanism directs radial differentiation of ventricular zone-neural progenitor cells in vivo and more broadly regulates the proteolysis of other large cell-surface receptors such as amyloid precursor protein. These findings suggest an unprecedented role of AJs in creating size-selective spatial switches that choreograph γ-secretase processing of multiple transmembrane proteins regulating development, homeostasis and disease.

Congenital myasthenic syndrome (CMS) is an important diagnosis to consider in an adult with both fixed and fatigable weakness.

Aberrant cleavage of Notch by γ-secretase is implicated in numerous diseases, but how cleavage is regulated in space and time is unclear. Here, we report that cadherin-based adherens junctions (cadAJs) are sites of high cell-surface γ-secretase activity, as well as sites of constrained physical space that excludes γ-secretase substrates having large extracellular domains (ECDs) like Notch. ECD shedding initiates drastic spatial relocalization of Notch to cadAJs, allowing enzyme-substrate interactions and downstream signaling. Spatial mutations by adjusting the ECD size or the physical constraint alter signaling. Dysregulation of this spatial switch promotes precocious differentiation of ventricular zone neural progenitor cells in vivo. We show the generality of this spatial switch for amyloid precursor protein proteolysis. Thus, cadAJs create spatially distinct biochemical compartments regulating cleavage events involving γ-secretase and preventing aberrant activation of receptors.

We describe 2 patients presenting with multiplex mononeuritis, associated with skin manifestation, secondary to minocycline-induced vasculitis. One of the cases is associated neither with lupus nor polyarteritis nodosa. An extensive laboratory workup ruled out any possible underlying immunologic disorder. Electrodiagnostic studies were conducted to show axonal neuropathy in patchy and multifocal distribution consistent with multiplex mononeuritis. This diagnosis was confirmed with nerve biopsy. Withdrawing from the offending medication, minocycline, improved the patients' clinical condition and the quantitative serological measures.

This letter demonstrates a method for fabricating single-crystal Si nanolines, with rectangular cross sections and nearly atomically flat sidewalls. The high quality of these nanolines leads to superb mechanical properties, with the strain to fracture measured by nanoindentation tests exceeding 8.5% for lines of 74 nm width. A large displacement burst before fracture was observed, which is attributed to a buckling mechanism. Numerical simulations show that the critical load for buckling depends on the friction at the contact surface.

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (50 mg/kg) administration to control male Sprague–Dawely rats and mutant Nagase analbuminemic rats (NARs). In NARs, the expression and mRNA level of CYP1A2 increased, and oltipraz was mainly metabolized via CYP1A1/2, 2B1/2, 2C11, 201, and 3A1/2 in male rats. Hence, it may be expected that the CL of oltipraz would be significantly faster in NARs. This was proven by the following results. After intravenous administration, the CL of oltipraz was significantly faster in NARs (125% increase) than controls due to significantly greater free fractions (unbound to plasma proteins) of oltipraz (197% increase) and significantly faster CL int for the disappearance of oltipraz (11.4% increase) in NARs, since oltipraz is an intermediate hepatic extraction ratio drug in rats. The V ss was significantly larger in NARs (109% increase) and this could be due to significant increase in free fractions of oltipraz in NARs. After oral administration, the AUC of oltipraz was also significantly smaller in NARs (61.9% decrease). This could also be due to significant increase in free fractions of oltipraz and significantly faster CL int in NARs. However, this was not due to decrease in absorption in NARs.

A nanoindentation system was employed to characterize mechanical properties of silicon nanolines (SiNLs), which were fabricated by an anisotropic wet etching (AWE) process. The SiNLs had the linewidth ranging from 24 nm to 90 nm, having smooth and vertical sidewalls and the aspect ratio (height/linewidth) from 7 to 18. During indentation, a buckling instability was observed at a critical load, followed by a displacement burst without a load increase, men a full recovery of displacement upon unloading. This phenomenon was explained by two bucking modes. It was also found that the difference in friction at the contact between the indenter and SiNLs directly affected buckling response of these nanolines. The friction coefficient was estimated to be in a range of 0.02 to 0.05. For experiments with large indentation displacements, irrecoverable indentation displacements were observed due to fracture of Si nanolines, with the strain to failure estimated to be from 3.8% to 9.7%. These observations indicated that the buckling behavior of SiNLs depended on the combined effects of load, line geometry, and the friction at contact. This study demonstrated a valuable approach to fabrication of well‐defined Si nanoline structures and the application of the nanoindentation method for investigation of their mechanical properties at the nanoscale.

Atomic force microscope-(AFM-) based indentation tests were performed to examine mechanical properties of parallel single-crystal silicon nanolines (SiNLs) of sub-100-nm line width, fabricated by a process combining electron-beam lithography and anisotropic wet etching. The SiNLs have straight and nearly atomically flat sidewalls, and the cross section is almost perfectly rectangular with uniform width and height along the longitudinal direction. The measured load-displacement curves from the indentation tests show an instability with large displacement bursts at a critical load ranging from 480 μNto 700 μN. This phenomenon is attributed to a transition of the buckling mode of the SiNLs under indentation. Using a set of finite element models with postbuckling analyses, we analyze the indentation-induced buckling modes and investigate the effects of tip location, contact friction, and substrate deformation on the critical load of mode transition. The results demonstrate a unique approach for the study of nanomaterials and patterned nanostructures via a combination of experiments and modeling.

Swell-induced surface instability has been observed experimentally in rubbers and gels. Here we present a theoretical model that predicts the critical condition along with a characteristic wavelength for swell-induced surface instability in substrate-confined hydrogel layers. The effect of surface tension is found to be critical in suppressing short-wavelength modes of instability, while the substrate confinement suppresses long-wavelength modes. Together, an intermediate wavelength is selected at a critical swelling ratio for the onset of surface instability. Both the critical swelling ratio and the characteristic wavelength depend on the initial thickness of the hydrogel layer as well as other material properties of the hydrogel. It is found that the hydrogel layer becomes increasingly stable as the initial layer thickness decreases. A critical thickness is predicted, below which the hydrogel layer swells homogeneously and remains stable at the equilibrium state.

High-quality single-crystal silicon nanolines (SiNLs) with a 24 nm linewidth and a height/width aspect ratio of 15 were fabricated. The mechanical properties of the SiNLs were characterized by nanoindentation tests with an atomic force microscope. The indentation load-displacement curves showed an instability with large displacement bursts at a critical load ranging from 9 to 30 μN. This phenomenon was attributed to a transition of the buckling mode of the SiNLs under indentation, which occurred preceding the final fracture of the nanolines. The mechanics of SiNLs under indentation was analyzed by finite element simulations, which revealed two different buckling modes depending on the contact friction at the nanoscale.