HOE-642 improves the protection of hypothermia on neuronal mitochondria after cardiac arrest in rats.

HOE-642 has been shown to provide significant protection in a variety of models of cerebral and myocardial ischemia/reperfusion injury. In this study, we examined the impact of HOE-642, a selective Na+/H+ exchanger 1 inhibitor, with or without hypothermia on neuronal and neuronal mitochondrial function during resuscitation. Cardiac arrest was induced by 8 min of asphyxia in rats. Five groups were included in this study: sham; normothermia (N); HOE-642 (HOE, 1 mg/kg); hypothermia (Hypo, 33±0.5°C); and HOE-642 plus hypothermia (HOE+Hypo). Survival and neurological deficit scores (NDS) were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, mitochondrial complex I-IV activity, and ultrastructural changes of the hippocampal mitochondria were evaluated. Survival in the HOE+Hypo group (85.7%) was higher than in the N group (42.9%) and HOE group (31.8%), P<0.05. NDS in the Hypo and HOE+Hypo groups were lower than in the N and HOE groups, P<0.05. ΔΨm in the HOE group (2.7±0.9) were higher than in the N (1.3±0.3) and Hypo (1.4±0.4) groups, P<0.05. Mitochondrial swelling in the N group was severe than in the HOE and Hypo groups, P<0.05. The production of ROS in the HOE and HOE+Hypo groups were lower than in the N group, P<0.05. Complex I-IV activity in the HOE+Hypo group was higher than in the other groups. The ultrastructure of mitochondria in the N group was severely damaged. The mitochondria maintained structural integrity in the HOE, Hypo and HOE+Hypo groups. HOE-642 plus hypothermia during resuscitation was beneficial than HOE-642 or hypothermia alone.

Chiral Nematic Liquid Crystal Behavior of Core-Shell Hybrid Rods Consisting of Chiral Cellulose Nanocrystals Dressed with Non-chiral Conformal Polymeric Skins.

The current work investigates how the nanoscale conformal coating layers of non-chiral polymeric materials can influence the chiral nematic liquid crystal (CLC) behaviors of the rodlike cellulose nanocrystals (CNCs), the bio-derived nanomaterials that have attracted significant attention. For this, we developed strategies to coat the CNC rods on the single-particle level with a homogeneous bioinspired polydopamine (PDA) layer, leading to well-defined core-shell CNC@PDA rods with various PDA coating thicknesses and excellent colloidal stability. Comprehensive investigation revealed that the CNC@PDA hybrid nanorods in concentrated suspensions form well-defined nematic liquid crystal phases with clear phase separation behavior that depend on the rod concentrations and ionic strengths, typical of charged rods. Most intriguingly, the nematic LC phases formed by the CNC@PDA rods with the PDA coating thickness achieved herein are indeed the perfect CLC phases, which form following the classic pathway of nucleation and coalesce of chiral tactoids and have colorful chiral fingerprints standing out from the dark suspensions. The pitches of the CLC phase increase sharply with increasing PDA coating thicknesses and are significantly larger than those of the pristine CNCs. Such observations can be attributed to the blurring effects of the PDA coating on the intrinsic surface chiral features of CNC of whatever origins that drive the formation of the CLC phases, resulting in weakening chiral interactions between CNC@PDA rods. Besides benefiting the understanding of the long-sought origin of the CLC phases of the pristine CNC, the current work demonstrates the possibility of controlling the CLC phase behaviors of CNC by tuning the thickness of the coating materials and also serves as the first example of directly transferring the unique chirality of CNC to other non-chiral materials.

Exploration of the optimal dose of HOE-642 for the protection of neuronal mitochondrial function after cardiac arrest in rats.

INTRODUCTION: It has been demonstrated HOE-642 ameliorates ischemic contracture, prevents post-resuscitation diastolic dysfunction, and favors the earlier return of contractile function. This study is the first report to explore the optimal dose of HOE-642 in protecting the neuronal mitochondrial function after cardiac arrest. METHODS: Cardiac arrest was induced by 8 min asphyxia in rats. There were Sham (S), Normothermic (NORM), and Hypothermic (HYPO) groups. The NORM or HYPO groups consist of four subgroups: NORM/HYPO + HOE-642 0, 1, 3, and 5 mg/kg. Survival and NDS were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, and mitochondrial complex IIV activity of the hippocampus were detected. RESULTS: Survival in the HYPO + 1 mg group was the best and significantly higher than in the NORM + 0 mg and NORM + 1 mg groups. NDS in the HYPO + 0 mg, HYPO + 1 mg, and HYPO + 3 mg groups was significantly lower than in the NORM + 0 mg group. ΔΨm in the NORM + 1 mg (n = 5) group was significantly higher than in the NORM + 0 mg (n = 8), NORM + 3 mg (n = 5), and NORM + 5 mg (n = 5) groups. The ROS production in the NORM + 1 mg and NORM + 3 mg groups were significantly lower than in the NORM + 0 mg and NORM + 5 mg groups. Complex I and III activities in the HYPO + 1 mg (n = 5) group were significantly higher than in the HYPO + 3 mg (n = 5), and HYPO + 5 mg (n = 5) groups. Complex II and IV activities in the NORM + 3 mg and HYPO + 3 mg groups were significantly higher than in the NORM + 0 mg, NORM + 1 mg, and HYPO + 0 mg (n = 4)groups. CONCLUSIONS: HOE-642 1 or 3 mg/kg showed benefits compared to HOE-642 5 mg/kg used when initiating resuscitation. When combined with hypothermia after cardiac arrest, HOE-642 1 or 3 mg/kg improved survival and neurological function compared with hypothermia or HOE-642 alone, however, HOE-642 5 mg/kg plus hypothermia did not.

A prospective, randomized, double-blind, placebo-controlled trial of acute postoperative pain treatment using opioid analgesics with intravenous ibuprofen after radical cervical cancer surgery.

This study assessed the efficacy and tolerability of intravenous ibuprofen in the improvement of post-operative pain control and the reduction of opioid usage. Patients were randomly divided into placebo, ibuprofen 400 mg and ibuprofen 800 mg groups. All patients received patient-controlled intravenous morphine analgesia after surgery. The first dose of study drugs was administered intravenously 30 min before the end of surgery and then every 6 hours, for a total of 8 doses after surgery. The primary endpoint of this study was the mean amount of morphine used during the first 24 hours after surgery. Morphine use was reduced significantly in the ibuprofen 800 mg group compared with the placebo group (P = 0.04). Tramadol use was reduced significantly in the ibuprofen 400 mg and ibuprofen 800 mg groups compared with the placebo group (P < 0.01). The area under the curve of visual analog scale pain ratings was not different between groups. Safety assessments and side effects were not different between the three groups. Intravenous ibuprofen 800 mg was associated with a significant reduction in morphine requirements, and it was generally well tolerated for postoperative pain management in patients undergoing radical cervical cancer surgery.

A tuning method based on the coupled mode frequencies in biperiodic coupled-cavity linear accelerator.

A coupled-cavity linac (CCL) is widely used around the world in many fields. The radio frequency design is always a fundamental and crucial problem in CCL. In biperiodic structures, especially side-coupled structures, entirely different structures between accelerating cavities (ACs) and coupled cavities (CCs) will cause different frequency drops (δf) with the introduction of coupling slots. In order to achieve precise and consistent frequencies in each cell, the rule of individual cavity frequency drops should be figured out. A model of lumped resonant circuits is chosen to provide accurate prediction for normal mode frequencies. Through solving equivalent circuit equations, a parameter called frequency gap difference (ΔF g ) is proposed, whose value is directly proportional to the frequency difference (df) between AC and CC and the ratio is one-to-one when AC frequency ( f a ) is close to CC frequency ( f c ). Based on the property of ΔF g , a simplified method on how to design and tune a triplet CCL is proposed; instead of tuning each individual cell, the new method only requires measuring the frequencies of the coupled normal modes, which considerably simplifies the tuning process and reduces the turn-around time. The particular design flow and tuning method have been successfully applied in the Nanjing University CCL Project. In addition, through comparing cavities with and without coupling slots, the value of frequency drops with different coupling coefficients is revealed and analyzed.

Self-Etching of Metal-Organic Framework Templates during Polydopamine Coating: Nonspherical Polydopamine Capsules and Potential Intracellular Trafficking of Metal Ions.

Traditionally, containers made from steel or other metals are not good for making tea, probably due to the fact that polyphenol components in tea can chelate with metal ions. A similar reason might stand behind the observations as reported herein. During the coating of well-defined metal-organic framework (MOF) crystalline particles with polydopamine (PDA) via pH-induced self-polymerization of dopamine, we found that MOF templates automatically etch off during the coating, giving rise to nonspherical PDA capsules that inherit the morphologies of the templates. Such self-etching of MOF templates is ascribed to the chelation of the metal nodes of the MOFs by the catechol moieties in the PDA layer. In addition, the self-etching of the zeolitic imidazolate framework-8 (ZIF-8) with a truncated cubic shape probably follows a crystalline facet-dependent fashion, resulting in intermediate yolk-shell structures with ZIF-8 cargos of various shapes inside a highly biocompatible PDA shell. Incubation of such intermediate hybrid particles with the cancerous HeLa cell line leads to pronounced cytotoxicity, which is tentatively connected with the cellular internalization of the ZIF@PDA nanoparticles because of the cell affinity of the PDA layer. Subsequently, the continuous release of Zn2+ by the self-etching of the encapsulated ZIF-8 inside the cell increases intracellular Zn2+ to a harmful level. Therefore, intracellular delivery of metal ions is probably realized, which might offer a novel way for cancer therapy.

Ellipsoidal Colloids with a Controlled Surface Roughness via Bioinspired Surface Engineering: Building Blocks for Liquid Marbles and Superhydrophobic Surfaces.

Understanding the important role of the surface roughness of nano/colloidal particles and harnessing them for practical applications need novel strategies to control the particles' surface topology. Although there are many examples of spherical particles with a specific surface roughness, nonspherical ones with similar surface features are rare. The current work reports a one-step, straightforward, and bioinspired surface engineering strategy to prepare ellipsoidal particles with a controlled surface roughness. By manipulating the unique chemistry inherent to the oxidation-induced self-polymerization of dopamine into polydopamine (PDA), PDA coating of polymeric ellipsoids leads to a library of hybrid ellipsoidal particles (PS@PDA) with a surface that decorates with nanoscale PDA protrusions of various densities and sizes. Together with the advantages originated from the anisotropy of ellipsoids and rich chemistry of PDA, such a surface feature endows these particles with some unique properties. Evaporative drying of fluorinated PS@PDA particles produces a homogeneous coating with superhydrophobicity that arises from the two-scale hierarchal structure of microscale interparticle packing and nanoscale roughness of the constituent ellipsoids. Instead of water repelling that occurs for most of the lotus leaf-like superhydrophobic surfaces, such coating exhibits strong water adhesion that is observed with certain species of rose pedals. In addition, the as-prepared hybrid ellipsoids are very efficient in preparing liquid marble-isolated droplets covered with solid particles. Such liquid marbles can be placed onto many surfaces and might be useful for the controllable transport and manipulation of small volumes of liquids.

Prehospital therapeutic hypothermia after out-of-hospital cardiac arrest: a systematic review and meta-analysis.

BACKGROUND: The effectiveness and safety of the infusion of ice-cold fluids for prehospital hypothermia in cardiac arrest victims are unclear. This study assessed its effects in adult victims of out-of-hospital cardiac arrest. METHODS: An online search of PubMed and Cochrane Library databases was performed. Cooling methods were limited to ice-cold fluid perfusion. Randomized controlled trials were included in this review. The main outcomes were body temperature at hospital arrival, survival to hospital discharge, neurological recovery, incidence of pulmonary edema, and the rate of rearrest. RESULTS: Among 1155 citations, 5 studies were included in this meta-analysis. The pooled analysis of these studies revealed no differences in survival to hospital discharge, favorable neurological outcomes, and incidence of pulmonary edema between the treatment group and control group. There were significant differences in body temperature at hospital arrival (I2 = 0.0%, χ2 = 2.58, MD = -0.760, 95% confidence interval = -0.938 to -0.581, P < .001) and the rate of rearrest (I2 = 0.0%, χ2 = 0.69, 95% confidence interval = 1.109 to 1.479, P = .031). CONCLUSIONS: Prehospital therapeutic hypothermia induced by intravenous infusion of ice-cold fluids in patients with out-of-hospital cardiac arrest decreased body temperature at hospital arrival but did not improve survival to hospital discharge and favorable neurological outcomes. Ice-cold fluid infusion did not increase the incidence of pulmonary edema but increased the incidence of rearrests.