IMPORTANCE Although the benefit of reducing blood pressure for primary and secondary prevention of stroke has been established, the effect of antihypertensive treatment in patients with acute ischemic stroke is uncertain.OBJECTIVE To evaluate whether immediate blood pressure reduction in patients with acute ischemic stroke would reduce death and major disability at 14 days or hospital discharge. DESIGN, SETTING, AND PARTICIPANTS The China Antihypertensive Trial in Acute IschemicStroke, a single-blind, blinded end-points randomized clinical trial, conducted among 4071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure. Patients were recruited from 26 hospitals across China between August 2009 and May 2013.INTERVENTIONS Patients (n = 2038) were randomly assigned to receive antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours after randomization, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization) or to discontinue all antihypertensive medications (control) during hospitalization (n = 2033). MAIN OUTCOMES AND MEASURESPrimary outcome was a combination of death and major disability (modified Rankin Scale score Ն3) at 14 days or hospital discharge.RESULTS Mean systolic blood pressure was reduced from 166.7 mm Hg to 144.7 mm Hg (−12.7%) within 24 hours in the antihypertensive treatment group and from 165.6 mm Hg to 152.9 mm Hg (−7.2%) in the control group within 24 hours after randomization (difference, −5.5% [95% CI, −4.9 to −6.1%]; absolute difference, −9.1 mm Hg [95% CI, −10.2 to −8.1]; P < .001). Mean systolic blood pressure was 137.3 mm Hg in the antihypertensive treatment group and 146.5 mm Hg in the control group at day 7 after randomization (difference, −9.3 mm Hg [95% CI, −10.1 to −8.4]; P < .001). The primary outcome did not differ between treatment groups (683 events [antihypertensive treatment] vs 681 events [control]; odds ratio, 1.00 [95% CI, 0.88 to 1.14]; P = .98) at 14 days or hospital discharge. The secondary composite outcome of death and major disability at 3-month posttreatment follow-up did not differ between treatment groups (500 events [antihypertensive treatment] vs 502 events [control]; odds ratio, 0.99 [95% CI, 0.86 to 1.15]; P = .93).CONCLUSION AND RELEVANCE Among patients with acute ischemic stroke, blood pressure reduction with antihypertensive medications, compared with the absence of hypertensive medication, did not reduce the likelihood of death and major disability at 14 days or hospital discharge.

Nanoengineered multifunctional capsules with tailored structures and properties are of particular interest due to their multifunctions and potential applications as new colloidal structures in diverse fields. Among the available fabrication methods, the layer-by-layer (LbL) assembly of multilayer films onto colloidal particles followed by selective template removal has attracted extensive attention due to its advantages of precise control over the size, shape, composition, wall thickness and functions of the obtained capsules. The past decade has witnessed a rapid increase of research concerning the new fabrication strategies, functionalization and applications of this kind of capsules, particularly in the biomedical fields such as drug delivery, biosensors and bioreactors. In this critical review, the very recent progress of the multilayer capsules is summarized. First, the advances in assembly of capsules by the LbL technique are introduced with focus on tailoring the properties of hydrogen-bonded multilayer capsules by cross-linking, and fabrication of capsules based on covalent bonding and bio-specific interactions. Then the fabrication strategies which can speed up capsule fabrication are reviewed. In the following sections, the multi-compartmental capsules and the capsules that can transform their shape under stimulus are presented. Finally, the biomedical applications of multilayer capsules with particular emphasis on drug carriers, biosensors and bioreactors are described (306 references).

Peptide self-assemblies with multiple nanostructures have great potentials in functional biomaterials, and yet the tedious and costly covalent peptide modification and the lack of facile controllability on self-assembly morphology retard the peptide-related exploration. Here we report a simple approach to fabricate a supramolecular peptide that shows programmable self-assembly with multiple morphologies and application in photodynamic therapy. Pillar[5]arene-based host−guest recognition is used to construct a supramolecular peptide, which simplify the peptide modification and promote the controllability of the self-assembly behavior. Due to the ERGDS sequences on the exterior surfaces and hydrophobic cores of self-assemblies, the nanoparticles formed from the supramolecular peptide are suitable vehicles to encapsulate a photosensitizer for photodynamic therapy. In vitro and in vivo studies demonstrate that the inherent targeting capability and supramolecular strategy greatly boost its photodynamic therapeutic efficiency. This supramolecular peptide holds promising potentials in precise cancer therapy and perspectives for the peptide modification.

The stability of hollow microcapsules against environmental alterations such as pH, osmotic pressure, and temperature is a critical issue for practical applications. It is demonstrated here that multilayer capsules assembled from poly(allylamine hydrochloride) (PAH) and sodium poly(styrene sulfonate) (PSS) can be considerably stabilized by cross-linking of only the PAH component with glutaraldehyde (GA). Formation of a Schiff base between the aldehyde and the amine groups was evidenced by UV−vis spectroscopy. After cross-linking by 2% GA for 2 h, an apparently thicker capsule wall was obtained with higher folds, and no alteration of the macroscopic topology of the capsules was observed after incubation in 0.1 M NaOH for 24 h. The cross-linking significantly improved the mechanical strength of the capsules to resist osmotic pressure induced invagination. Consequently, both the critical pressure and the elasticity modulus (680 MPa) of the capsule wall were doubled compared with that of the control. The cross-linking also greatly lowered the permeability of the capsule wall, as evidenced by confocal laser scanning microscopy and fluorescence recovery after photobleaching. Quantitative analysis revealed that the permeation coefficient for dextran (Mw ∼ 250 kD) was reduced by a factor of 3 after cross-linking.

Multilayer microcapsules showing unique charge-controlled permeability have been successfully fabricated by employing poly(styrene sulfonate) (PSS)-doped CaCO3 particles as templates. Encapsulation of the PSS molecules is thus achieved after core removal. Scanning force microscopy (SFM), UV-vis, Raman spectroscopy, and zeta-potential confirm the existence of the PSS molecules in the CaCO3 particles and the resultant microcapsules, which are initially incorporated during the core fabrication process. A part of these additionally introduced PSS molecules interacts with PAH molecules residing on the inner surface of the multilayer wall to form a stable complex, while the other part is intertwined in the capsule wall or in a free state. Capsules with this structure possess many special features, such as highly sensitive permeability tuned by probe charge and environmentally controlled gating. They can completely reject negatively charged probes, but attract positively charged species to form a higher concentration in the capsule interior, as evidenced by confocal microscopy. For example, the capsules completely exclude dextran labeled with fluorescein isothiocyanate (FITC-dextran), but are permeable for dextran labeled with tetramethylrhodamine isothiocyanate (TRITC-dextran) having similar molecular mass (from 4 to 70 kDa), although there are only few charged dyes in a dextran chain. By reversing the charge of the probes through pH change, or by suppressing charge repulsion through salt addition, the permeation can be readily switched for proteins such as albumin or small dyes such as fluorescein sodium salt.