Mitochondrial Metabolic Reprogramming by CD36 Signaling Drives Macrophage Inflammatory Responses.

RATIONALE: A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE: To investigate mechanisms linking dyslipidemia, oxidative stress, and macrophage activation through modulation of immunometabolism and to explore therapeutic potential targeting specific metabolic pathways. METHODS AND RESULTS: Using a combination of biochemical, immunologic, and ex vivo cell metabolic studies, we report that CD36 mediates a mitochondrial metabolic switch from oxidative phosphorylation to superoxide production in response to its ligand, oxidized LDL (low-density lipoprotein). Mitochondrial-specific inhibition of superoxide inhibited oxidized LDL-induced NF-κB (nuclear factor-κB) activation and inflammatory cytokine generation. RNA sequencing, flow cytometry, 3H-labeled palmitic acid uptake, lipidomic analysis, confocal and electron microscopy imaging, and functional energetics revealed that oxidized LDL upregulated effectors of long-chain fatty acid uptake and mitochondrial import, while downregulating fatty acid oxidation and inhibiting ATP5A (ATP synthase F1 subunit alpha)-an electron transport chain component. The combined effect is long-chain fatty acid accumulation, alteration of mitochondrial structure and function, repurposing of the electron transport chain to superoxide production, and NF-κB activation. Apoe null mice challenged with high-fat diet showed similar metabolic changes in circulating Ly6C+ monocytes and peritoneal macrophages, along with increased CD36 expression. Moreover, mitochondrial reactive oxygen species were positively correlated with CD36 expression in aortic lesional macrophages. CONCLUSIONS: These findings reveal that oxidized LDL/CD36 signaling in macrophages links dysregulated fatty acid metabolism to oxidative stress from the mitochondria, which drives chronic inflammation. Thus, targeting to CD36 and its downstream effectors may serve as potential new strategies against chronic inflammatory diseases such as atherosclerosis.

Comparison of fast track protocol and standard care in patients undergoing elective open colorectal resection: a meta-analysis update.

OBJECTIVE: We conducted a systematic review of randomized controlled trials assessing the clinical results of fast track protocol (FTP) and standard care (SC) in patients undergoing elective open colorectal resection using meta-analysis. METHOD: A literature search for electronic databases and references for eligible studies was conducted through Medline, Embase and Cochrane library between 1966 and 2013. RESULT: A total of 9 randomized controlled trials (n=947 patients) were included. From the pooled results, we obtained: FTP showed significantly better results compared to SC in terms of postoperative complications, total hospital stay as well as time for flatus, defecation, and soft diet. However, no difference in the incidence of readmission was observed. Postoperative rate of death within 4 weeks did not differ significantly between two groups. CONCLUSION: The current evidence of this meta-analysis suggested that fast track protocol after colorectal surgery pathways might be able to reduce postoperative complication rates, length of hospital stay as well as time for gut function recovery without affecting readmission rate or mortality compared to standard care.

Comparison of high tibial osteotomy and unicompartmental knee arthroplasty in the treatment of unicompartmental osteoarthritis: a meta-analysis.

We conducted a systematic review of comparative clinical trials assessing the results of high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) in patients with strictly unilateral osteoarthritis of the knee. A literature search was conducted through Medline, Embase and Cochrane library. A total of 11 comparative studies were included. Pooled results showed: UKA showed significantly better results compared to HTO in terms of function results, however, no difference in specific knee score was observed; HTO got slightly better results of the range of motion; a trend towards an increased velocity was found in UKA without significant difference. Postoperative rate of revision and complications did not differ significantly between two groups. With the correct patient selection, both HTO and UKA show effective and reliable results.

Na/K-ATPase suppresses LPS-induced pro-inflammatory signaling through Lyn.

Na/K-ATPase (NKA), besides its ion transporter function, is a signal transducer by regulating Src family kinases (SFK). The signaling NKA contributes to oxidized LDL-induced macrophage foam cell formation and interacts with TLR4. However, its role in lipopolysaccharides (LPS)-induced signaling and glycolytic switch in macrophages remains unclear. Using peritoneal macrophages from NKA α1 haploinsufficient mice (NKA α1+/-), we found that NKA α1 haploinsufficiency led to enhanced LPS-stimulated NF-κB pathway, ROS signaling, and pro-inflammatory cytokines. Intraperitoneal injection of LPS resulted in more severe lung inflammation and injury with lower survival rate in NKA α1+/- mice. Additionally, LPS induced a higher extent of the metabolic switch from oxidative phosphorylation to glycolysis. Mechanistically, NKA α1 interacted with TLR4 and Lyn. The presence of NKA α1 in this complex attenuated Lyn activation by LPS, which subsequently restricted the downstream ROS and NF-κB signaling. In conclusion, we demonstrated that NKA α1 suppresses LPS-induced macrophage pro-inflammatory signaling through Lyn.

Direct observation of the transfer of orbital angular momentum to metal particles from a focused circularly polarized Gaussian beam.

It is well known that a circularly polarized Gaussian beam carries spin angular momentum, but not orbital angular momentum. This paper demonstrates that focusing a beam carrying spin angular momentum can induce an orbital angular momentum which we used to drive the orbital motion of a micron-sized metal particle that is trapped off the beam axis. The direction of the orbital motion is controlled by the handedness of the circular polarization. The orbiting dynamics of the trapped particle, which acted as an optical micro-detector, were quantitatively measured and found to be in excellent agreement with the theoretical predictions.

Optofluidic generation of Laguerre-Gaussian beams.

Laguerre-Gaussian (LG) beams have been extensively studied due to their unique structure, characterized by a phase singularity at the center of the beam. Common methods for generating such beams include the use of diffractive optical elements and spatial light modulators, which although offering excellent versatility, suffers from several drawbacks, including in many cases a low power damage threshold as well as complexity and expense. This paper presents a simple, low cost method for the generation of high-fidelity LG beams using rapid prototyping techniques. Our approach is based on a fluidic-hologram concept, whereby the properties of the LG beam can be finely controlled by varying the refractive-index of the fluid that flows through the hologram. This simple approach, while optimized here for LG beam generation, is also expected to find applications in the production of tunable fluidic optical trains.

Compartmentalization of chemically separated components into droplets.

Not merely a drop in the ocean: The integration of capillary electrophoresis (CE) with droplet generation driven by electroosmotic flow enabled the compartimentalization of molecular components separated by CE in a series of droplets (see picture; the green bars represent the separated analytes). The droplet-confined bands can be docked and studied on a chip.

Optical gradient flow focusing.

This paper describes a new method for carrying out flow cytometry, which employs optical gradient forces to guide and focus particles in the fluid flow. An elliptically shaped Gaussian beam was focused at the center of a microchannel to exert radiation pressure on suspended nanoparticles that are passing through the channel, such that these particles are guided to the center of the channel for efficient detection and sorting. To verify the efficiency of this optical-gradient-flow-focusing method, we present numerical simulations of the trajectories of the nanoparticles in both electroosmotic flow (EOF) and pressure-driven flow (PDF).

Accurate sizing of nanoparticles using confocal correlation spectroscopy.

The ability to accurately size low concentrations of nanoscale particles in small volumes is useful for a broad range of disciplines. Here, we characterize confocal correlation spectroscopy (CCS), which is capable of measuring the sizes of both fluorescent and nonfluorescent particles, such as quantum dots, gold colloids, latex spheres, and fluorescent beads. We accurately measured particles ranging in diameter from 11 to 300 nm, a size range that had been difficult to probe, owing to a phenomenon coined biased diffusion that causes diffusion times, or particle size, to deviate as a function of laser power. At low powers, artifacts mimicking biased diffusion are caused by saturation of the detector, which is especially problematic when probing highly fluorescent or highly scattering nanoparticles. However, at higher powers (>1 mW), autocorrelation curves in both resonant and nonresonant conditions show a structure indicative of an increased contribution from longer correlation times coupled with a decrease in shorter correlation times. We propose that this change in the autocorrelation curve is due to the partial trapping of the particles as they transit the probe volume. Furthermore, we found only a slight difference in the effect of biased diffusion when comparing resonant and nonresonant conditions. Simulations suggest the depth of trapping potential necessary for biased diffusion is > 1 k(B)T. Overcoming artifacts from detector saturation and biased diffusion, CCS is particularly advantageous due to its ability to size particles in the small volumes characteristic of microfluidic channels and aqueous microdroplets. We believe the method will find increasing use in a wide range of applications in measuring nanoparticles and macromolecular systems.

Comparison of Venous Thromboembolism after Total Artificial Joint Replacement between Musculoskeletal Tumors and Osteoarthritis of the Knee by a Single Surgeon.

The purpose of this study was to compare and evaluate the event of VTE (Venous Thromboembolism Event) after total artificial joint replacement between two groups diagnosed with either musculoskeletal tumors or osteoarthritis (OA) of the knee. From 2004 to 2014, a total of 1,402 patients (308 in tumor group, 1,094 in OA group) were involved in this study. The rate of asymptomatic DVT (Deep vein thrombosis) was significantly higher in tumor group when compared with OA group. Though both the incidence of symptomatic DVT and PE (Pulmonary embolism) were slightly higher in tumor group, no significant difference was detected. Tumor patients suffered an almost equal risk of VTE compared with OA patients except a higher rate of asymptomatic DVT after total artificial joint replacement. For patients with tumor, no significant association was observed between any potential risk factor and DVT.

Outcome of hemiarthroplasty and total hip replacement for active elderly patients with displaced femoral neck fractures: a meta-analysis of 8 randomized clinical trials.

BACKGROUND: Displaced fracture of the femoral neck has been a common clinical problem, especially in aged patients. However, the optimal treatment choice remains controversial. The purpose of this study is to conduct a systematic review of randomized clinical trials assessing the results of hemiarthroplasty and total hip replacement in patients undergoing either alternative using meta-analysis. METHODS: A literature search for randomized clinical trials was conducted through Medline, Embase and Cochrane library between 1969 and 2013 with no restrictions. Additional relevant articles were referred as source of information by way of manual searches on major orthopedic journals. Upon the search, two authors independently evaluated study quality and relevant data was extracted. RESULTS: A total of 8 studies with 983 patients were included in this meta-analysis. After pooling the available data, a significant dominance of Harris hip score was found for total hip replacement compared with hemiarthroplasty (SMD: -7.11, 95%:-10.70,-3.53) one year postoperatively and the advantage kept over (SMD: -6.91, 95%:-12.98, -0.85) two years after surgery. A trend toward a higher dislocation rate was found in total hip replacement group (RR: 0.46, 95%: 0.21, 1.02), of which the difference was considered insignificant. The risk of revision in group hemiarthroplasty appeared to be more than two folds higher than that after total hip replacement (RR: 4.14, 95%CI: 2.09, 8.19). CONCLUSION: Even though there is a higher rate of dislocation after total hip replacement, this disadvantage could be accounted for, on the basis of a better functional score and the lower revision rate. However, from the results, it stands to reason that total hip replacement should be strongly suggested in elderly active patients with femoral neck fracture.

Quantitative force mapping of an optical vortex trap.

This paper describes the quantitative force mapping of micron-sized particles held in an optical vortex trap. We present a simple and efficient model, which accounts for the diffraction of the strongly localized optical field of the tightly focused laser beam, the spherical aberration introduced by the dielectric glass-to-water interface, employs the multidipole approximation for force calculations, and is able to reproduce, with quantitative agreement, the experimentally measured force map.

Spin-to-orbital angular momentum conversion in a strongly focused optical beam.

As a fundamental property of light, the angular momentum of photons has been of great interest. Here, we demonstrate that optical spin-to-orbital angular momentum conversion can occur in a homogeneous and isotropic medium. This Letter presents both theoretical and experimental studies of this conversion in a tightly focused beam and shows that the orbital rotation speeds of trapped particles are altered because of this conversion as predicted by theory.

Vortex-trap-induced fusion of femtoliter-volume aqueous droplets.

This paper describes the use of an optical vortex trap for the transport and fusion of single femtoliter-volume aqueous droplets. Individual droplets were generated by emulsifying water in acetophenone with SPAN 80 surfactant. We demonstrate the ability of optical vortex traps to position trapped droplets precisely while excluding surrounding aqueous droplets from entering the trap, thereby preventing unwanted cross contamination by other nearby droplets. Additionally, the limitation of optical vortex traps for inducing droplet fusion is illustrated, and a remedy is provided through modulation of the spatial intensity profile of the optical vortex beam. Spatial modulation was achieved by translating the computer-generated hologram (CGH) with respect to the input Gaussian beam, thereby shifting the location of the embedded phase singularity (dark core) within the optical vortex beam. We present both simulated and experimentally measured intensity profiles of the vortex beam caused by translation of the CGH. We further describe the use of this technique to achieve controlled and facile fusion of two aqueous droplets.

Using polarization-shaped optical vortex traps for single-cell nanosurgery.

Single-cell nanosurgery and the ability to manipulate nanometer-sized subcellular structures with optical tweezers has widespread applications in biology but so far has been limited by difficulties in maintaining the functionality of the transported subcellular organelles. This difficulty arises because of the propensity of optical tweezers to photodamage the trapped object. To address this issue, this paper describes the use of a polarization-shaped optical vortex trap, which exerts less photodamage on the trapped particle than conventional optical tweezers, for carrying out single-cell nanosurgical procedures. This method is also anticipated to find broad use in the trapping of any nanoparticles that are adversely affected by high-intensity laser light.

Creation of a three-dimensional optical chain for controllable particle delivery.

We propose a design for producing a conveyable quasi-periodic optical chain that can stably trap and deliver multiple individual particles in three dimensions at different planes near the focus. A diffractive optical element (DOE) is designed to spatially modulate the phase of an incoming radially polarized beam. For a tighly focused beam, a three-dimensional (3D) optical chain can be formed because of the difference in the Gouy phase shift from two concentric regions of the DOE. A desired number of particles can be stably tweezed one by one with individual 3D volumes in this trapping structure. By controlling the phase modulation of the incident beam, one can manipulate the interference pattern to accelerate and transport trapped particles along the optical axis in a prescribed way.

Vector iterative algorithm for the design of diffractive optical elements applied to uniform illumination.

A vector angular-spectrum iterative algorithm for the design of diffractive optical elements to produce uniform illumination is described. In the algorithm, the variation of beam polarization is related to a unit wave vector and a random mixture of intensity is used for super-Gaussian beam shaping [corrected]. The simulated results show that approximately 95.3% of the incident energy has converged into the desired region. The greatest profile error and the mean-square error of intensity fitted to the corresponding parameters of the 100th-power super-Gaussian function are approximately 8 x 10(-4) and 3.5 x 10(-3), respectively.