Digital protractor as an intraoperative guide to cup anteversion in total hip arthroplasty.

INTRODUCTION: To explore if digital protractor could guide the anteversion of acetabular cup during primary THA and make it consistent with preoperative. METHODS: We retrospectively reviewed 172 cases of primary THA with direct anterior approach (DAA) over 2 years. The anteversion of acetabular cup were measured from computed tomography (CT) scan preoperative and de-identified plain radiographs postoperative by two blinded investigators who were not involved in the surgery. The effect of the digital protractor on the anteversion was determined using regression analysis. RESULTS: The mean anteversion for the THAs in digital protractor group was 15.5°and 21.4°in control group (P < 0.01). The mean anteversion bias for the THAs in digital protractor group was 1.59° and 6.63° in control group (P < 0.01).Regression analysis identified a 10.7% difference in anteversion due to the use of digital protractor (P < 0.01), and THAs performed without digital protractor were six times more likely to result in anteversion of > 25°. The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.94. CONCLUSION: The digital protractor is a practical tool in the DAA for THA to determine the anteversion of the acetabular prosthesis.

Angelica sinensis polysaccharide improves mitochondrial metabolism of osteoarthritis chondrocytes through PPARγ/SOD2/ROS pathways.

Osteoarthritis (OA) is a common degenerative joint disease, which is characterized by wear of articular cartilage and narrow joint space, resulting in joint movement disorder. At present, accurate molecular mechanisms and effective interventions are still being explored. Here, we propose that angelica sinensis polysaccharide (ASP) alleviates OA progression by activating peroxisome proliferator-activated receptor gamma (PPARγ). Therapeutic effect of ASP improving mitochondrial metabolism of OA chondrocytes was evaluated in vitro and in vivo, respectively. During cell experiments, the concentration and time response of tert butyl hydroperoxide (TBHP) and ASP were determined by cell viability. Apoptosis was detected by flow cytometry. Mitochondrial metabolism was detected by reactive oxygen species (ROS), mitochondrial membrane potential (MMP), release of cytochrome C, adenosine triphosphate (ATP) production, and superoxide dismutase 2 (SOD2) activity. Expressions of Aggrecan, collagen type II (Col2a1), PPARγ, and SOD2 were detected by qRT-PCR and western blot. In animal experiments, we detected cell apoptosis and target protein expression separately through terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining and immunohistochemistry. Pretreatment of ASP significantly activated PPARγ and SOD2 in rat chondrocytes incubated with TBHP, cleared ROS, improved mitochondrial metabolism, increased chondrocytes viability, and alleviated chondrocytes apoptosis. In vivo, the administration of ASP could effectively ameliorate cartilage degeneration in OA rats, promote extracellular matrix synthesis, and decelerate the progress of OA. Our research identifies the role of ASP in mitochondrial metabolism of OA chondrocytes through PPARγ/SOD2/ROS pathways, which provides a new idea for the treatment of OA.

Preclinical pharmacology and toxicology evaluation of an anti-CD52 monoclonal antibody produced by perfusion fermentation process.

Anti-cluster of differentiation 52 (CD52) monoclonal antibody (mAb) has been employed in the treatment of chronic lymphoblastic leukemia and multiple sclerosis. Previously we developed a perfusion process to produce the biosimilar mAb named "Mab-TH." A series of quality assessments was conducted in the fields of structural identification, purity analysis, and activity measurement. After these quality researches, this report laid emphasis on preclinical pharmacology and toxicology evaluation. Mab-TH was characterized in biological, pharmacological, and toxicological properties in comparison with the original drug, alemtuzumab. Binding activity and immune-dependent toxicity as in vitro activity were evaluated. Severe immunodeficient mice transplanted with a human leukemia cell line were also used as an in vivo pharmacological model and a 4-week repeated dosing study in cynomolgus monkeys was conducted to evaluate the safety differences. Our results demonstrated that Mab-TH, the anti-CD52 antibody generated by a perfusion process, had high similarity in in vitro and in vivo activities compared with alemtuzumab in relevant preclinical models. The results supported it as a biosimilar candidate for clinical evaluation.

LncRNA LUADT1 regulates miR-34a/SIRT1 to participate in chondrocyte apoptosis.

It is known that miR-34a can promote the apoptosis of chondrocytes, which directly contribute to osteoarthritis (OA). Through bioinformatics analysis, we found that long noncoding RNA LUADT1 may interact with miR-34a. We, therefore, further investigate the interactions between them in osteoarthritis. We found that LUADT1 was downregulated, while miR-34a was upregulated in OA synovial fluid. Correlation analysis revealed no significant correlation between them. Overexpression experiment also revealed no significant effects of LUADT1 and miR-34a on the expression of each other. However, the dual-luciferase assay showed that LUADT1 and miR-34a can directly interact with each other. Moreover, LUADT1 overexpression led to the upregulation of SIRT1, which is a downstream target of miR-34a. Cell apoptosis showed that LUADT1 and SIRT1 overexpression led to decreased, while miR-34a led to increased apoptotic rates of chondrocytes. Therefore, LUADT1 regulates miR-34a/SIRT1 to participate in chondrocyte apoptosis.

Effects of Hesperidin on H2O2-Treated Chondrocytes and Cartilage in a Rat Osteoarthritis Model.

BACKGROUND The purpose of this research was to investigate the effects of hesperidin on hydrogen peroxide (H2O2)-induced chondrocytes injury and cartilage degeneration in a rat model of osteoarthritis (OA). MATERIAL AND METHODS Chondrocytes were isolated from rat knee joints and treated with hesperidin alone or combined with H2O2. Then, Cell Counting Kit-8 (CCK-8) assay was used to assess cell viability. Activity of reactive oxygen species (ROS) and levels of malondialdehyde (MDA) were estimated. Cell apoptosis was assessed by flow cytometry assay. In addition, gene expression levels were measured for caspase 3, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), collagen type II (Col2a1), aggrecan, (sex-determining region Y)-box 9 (SOX9), matrix metalloproteinase (MMP)-13, and inducible nitric oxide synthase (iNOS) through quantitative real-time polymerase chain reaction (qPCR). To examine the effects on cartilage destruction in vivo, hesperidin or vehicle control were orally administrated in a surgically-induced osteoarthritis (OA) model. RESULTS The results indicated that hesperidin pretreatment of chondrocytes reduce H2O2-induced cytotoxicity and apoptosis. Hesperidin pretreatment decreased the formation of MDA and intracellular ROS, including chondrocyte apoptosis. Hesperidin also reversed the activity of H2O2 on inhibiting the Col2a1, aggrecan, and SOX9 gene expression and increasing the gene expression of caspase 3, IL-1ß, TNFα, iNOS, and MMP13. In addition, hesperidin administration markedly attenuated cartilage destruction and reduced IL-1ß and TNF-α levels in a surgically-induced OA model. CONCLUSIONS Our study suggests that hesperidin can prevent H2O2-induced chondrocytes injury through its antioxidant effects in vitro and reduce cartilage damage in a rat model of OA.

Medical Applications of Collagen and Hyaluronan in Regenerative Medicine.

In order to develop and commercialize for the regenerative medicinal products, smart biomaterials with biocompatibility must be needed. In this chapter, we introduce collagen and hyaluronic acid (HA) as extracellular matrix as well as deal with the molecular mechanism as microenvironment, mechanistic effects, and gene expression. Application of collagen and HA have been reviewed in the area of orthopedics, orthopedics, ophthalmology, dermatology and plastic surgery. Finally, the ongoing and commercial products of collagen and HA for regenerative medicine have been introduced.

Plasmonic Sensing Characteristics of Gold Nanorods with Large Aspect Ratios.

Plasmonic gold nanorods play important roles in nowadays state-of-the-art plasmonic sensing techniques. Most of the previous studies and applications focused on gold nanorods with relatively small aspect ratios, where the plasmon wavelengths are smaller than 900 nm. Gold nanorods with large aspect ratios are predicted to exhibit high refractive-index sensitivity (Langmir 2008, 24, 5233⁻5237), which therefore should be promising for the development of high-performance plasmonic chemical- and bio-sensors. In this study, we developed gold nanorods with aspect ratios over 7.9, which exhibit plasmon resonances around 1064 nm. The refractive index (RI) sensitivity of these nanorods have been evaluated by varying their dielectric environment, whereby a sensitivity as high as 473 nm/RIU (refractive index unit) can be obtained. Furthermore, we have demonstrated the large-aspect-ratio nanorods as efficient substrate for surface enhanced Raman spectroscopy (SERS), where an enhancement factor (EF) as high as 9.47 × 108 was measured using 4-methylbenzenethiol (4-MBT) as probe molecule. Finally, a type of flexible SERS substrate is developed by conjugating the gold nanorods with the polystyrene (PS) polymer. The results obtained in our study can benefit the development of plasmonic sensing techniques utilized in the near-infrared spectral region.

Room-Temperature Strong Light-Matter Interaction with Active Control in Single Plasmonic Nanorod Coupled with Two-Dimensional Atomic Crystals.

Strong light-matter coupling manifested by Rabi splitting has attracted tremendous attention due to its fundamental importance in cavity quantum-electrodynamics research and great potentials in quantum information applications. A prerequisite for practical applications of the strong coupling in future optoelectronic devices is an all-solid-state system exhibiting room-temperature Rabi splitting with active control. Here we realized such a system in heterostructure consisted of monolayer WS2 and an individual plasmonic gold nanorod. By taking advantages of the small mode volume of the nanorod and large transition dipole moment of the WS2 exciton, giant Rabi splitting energies of 91-133 meV can be achieved at ambient conditions, which only involve a small number of excitons. The strong light-matter coupling can be dynamically tuned either by electrostatic gating or temperature scanning. These findings can pave the way toward active nanophotonic devices operating at room temperature.

Different fermentation processes produced variants of an anti-CD52 monoclonal antibody that have divergent in vitro and in vivo characteristics.

The anti-CD52 antibody has already been approved for the treatment of patients with resistant chronic lymphocytic leukemia, relapsing-remitting multiple sclerosis, and has demonstrable efficacy against stem cell transplantation rejection. A CHO cell line expressing a humanized anti-CD52 monoclonal antibody (mAb-TH) was cultivated in both fed-batch and perfusion modes, and then purified. The critical quality attributes of these mAb variants were characterized and the pharmacokinetics (PK) properties were investigated. Results showed that the perfusion culture achieved higher productivity, whereas the fed-batch culture produced more aggregates and acid components. Additionally, the perfusion culture produced similar fucose, more galactose and a higher proportion of sialic acid on the anti-CD52 mAb compared to the fed-batch culture. Furthermore, the perfusion process produced anti-CD52 mAb had higher complement-dependent cytotoxicity (CDC) efficacy than that produced by the fed-batch culture, a result probably linked to its higher galactose content. However, antibody produced by fed-batch and perfusion cultures showed similar PK profiles in vivo. In conclusion, perfusion is a more efficient method than fed-batch process in the production of functional anti-CD52 monoclonal antibody. Product quality variants of anti-CD52 mAb were found in different cell culture processes, which demonstrated different physiochemical and biological activities, but comparable PK properties. Whether these observations apply to all mAbs await further investigation.

Experimental Demonstration of the Effectiveness of Electromagnetically Induced Transparency for Enhancing Cross-Phase Modulation in the Short-Pulse Regime.

We present an experiment using a sample of laser-cooled Rb atoms to show that cross-phase modulation schemes continue to benefit from electromagnetically induced transparency (EIT) even as the transparency window is made narrower than the signal bandwidth (i.e., for signal pulses much shorter than the response time of the EIT system). Addressing concerns that narrow EIT windows might not prove useful for such applications, we show that while the peak phase shift saturates in this regime, it does not drop, and the time-integrated effect continues to scale inversely with EIT window width. This integrated phase shift is an important figure of merit for tasks such as the detection of single-photon-induced cross-phase shifts. Only when the window width approaches the system's dephasing rate γ does the peak phase shift begin to decrease, leading to an integrated phase shift that peaks when the window width is equal to 4γ.

Observing the onset of effective mass.

The response of a particle in a periodic potential to an applied force is commonly described by an effective mass, which accounts for the detailed interaction between the particle and the surrounding potential. Using a Bose-Einstein condensate of (87)Rb atoms initially in the ground band of an optical lattice, we experimentally show that the initial response of a particle to an applied force is in fact characterized by the bare mass. Subsequently, the particle response undergoes rapid oscillations and only over time scales that are long compared to those of the interband dynamics is the effective mass observed to be an appropriate description. Our results elucidate the role of the effective mass on short time scales, which is relevant for example in the interaction of few-cycle laser pulses with dielectric and semiconductor materials.

E26 transformation-specific-1 (ETS1) and WDFY family member 4 (WDFY4) polymorphisms in Chinese patients with rheumatoid arthritis.

E26 transformation-specific-1 (ETS1) and WDFY family member 4 (WDFY4) are closely related with systemic lupus erythematosus. We hypothesized that ETS1 and WDFY4 polymorphisms may contribute to rheumatoid arthritis (RA) susceptibility. We studied ETS1 rs1128334 G/A and WDFY4 rs7097397 A/G gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. When the WDFY4 rs7097397 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly increased risk for RA. In the dominant model, when the WDFY4 rs7097397 AA homozygote genotype was used as the reference group, the AG/GG genotypes were associated with a significant increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the WDFY4 rs7097397 AG genotype was evident among female patients, younger patients, C-reactive protein (CRP) negative patients and both anti-cyclic citrullinated peptide antibody (ACPA) positive patients and negative patients compared with the WDFY4 rs7097397 AA genotype. These findings suggested that WDFY4 rs7097397 A/G may be associated with the risk of RA, especially among younger, female patients, CRP-negative patients and both ACPA positive and negative patients. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. To confirm these findings, validation by a larger study from a more diverse ethnic population is needed.

[Driving Factors Analysis for Spatial-Temporal Distribution of Organic Pollutants in the Yangtze River Delta Based on the Optimal-scale Geographical Detector].

Site contamination has caused serious harm to human health and the ecological environment, so understanding its spatial and temporal distribution patterns is the basis for contamination assessment and site remediation. For this reason, this study analyzed the spatial-temporal distribution patterns of organic pollutants and their driving factors in the Yangtze River Delta based on site sampling data using the optimal-scale geographical detector. The analysis results showed that:① There was a significant scale effect in the spatial distribution of organic pollutants in the Yangtze River Delta, and its optimal geographic detection scale grid was 8 000 meters. ② The main control factor of the spatial distribution of pollutants in the Yangtze River Delta originated mostly from the biological field, followed by the chemical field. ③ At the depth of 0-20 cm of soil, the explanatory power of sucrase content, urease content, microbial nitrogen amount, total nitrogen content, and cation exchange amount were stronger for the spatial distribution of organic pollutants. At the soil depth of 20-40 cm, the factors with stronger explanatory power on the spatial distribution of organic pollutants were soil moisture, population, and total nitrogen content. With the deepening of soil depth, the explanatory power of the factors of the hydrodynamic field increased. ④ Population, total nitrogen content, and polyphenol oxidase content had stronger explanatory power for the spatial distribution of organic pollutants in the spring. The spatial distribution of organic pollutants was more complex in autumn, and the factors showed stronger enhanced-nonlinear and enhanced-bi phenomena.

PPARγ regulates osteoarthritis chondrocytes apoptosis through caspase-3 dependent mitochondrial pathway.

Osteoarthritis (OA) is the most prevalent form of arthritis, characterized by a complex pathogenesis. One of the key factors contributing to its development is the apoptosis of chondrocytes triggered by oxidative stress. Involvement of peroxisome proliferator-activated receptor gamma (PPARγ) has been reported in the regulation of oxidative stress. However, there remains unclear mechanisms that through which PPARγ influences the pathogenesis of OA. The present study aims to delve into the role of PPARγ in chondrocytes apoptosis induced by oxidative stress in the context of OA. Primary human chondrocytes, both relatively normal and OA, were isolated and cultured for the following study. Various assessments were performed, including measurements of cell proliferation, viability and cytotoxicity. Additionally, we examined cell apoptosis, levels of reactive oxygen species (ROS), nitric oxide (NO), mitochondrial membrane potential (MMP) and cytochrome C release. We also evaluated the expression of related genes and proteins, such as collagen type II (Col2a1), aggrecan, inducible nitric oxide synthase (iNOS), caspase-9, caspase-3 and PPARγ. Compared with relatively normal cartilage, the expression of PPARγ in OA cartilage was down-regulated. The proliferation of OA chondrocytes decreased, accompanied by an increase in the apoptosis rate. Down-regulation of PPARγ expression in OA chondrocytes coincided with an up-regulation of iNOS expression, leading to increased secretion of NO, endogenous ROS production, and decrease of MMP levels. Furthermore, we observed the release of cytochrome C, elevated caspase-9 and caspase-3 activities, and reduction of the components of extracellular matrix (ECM) Col2a1 and aggrecan. Accordingly, utilization of GW1929 (PPARγ Agonists) or Z-DEVD-FMK (caspase-3 inhibitor) can protect chondrocytes from mitochondrial-related apoptosis and alleviate the progression of OA. During the progression of OA, excessive oxidative stress in chondrocytes leads to apoptosis and ECM degradation. Activation of PPARγ can postpone OA by down-regulating caspase-3-dependent mitochondrial apoptosis pathway.

Coherent control of population transfer between vibrational states in an optical lattice via two-path quantum interference.

We demonstrate coherent control of population transfer between vibrational states in an optical lattice by using interference between a one-phonon transition at 2ω and a two-phonon transition at ω. The ω and 2ω transitions are driven by phase- and amplitude-modulation of the lattice laser beams, respectively. By varying the relative phase of these two pathways, we control the branching ratio between transitions to the first excited state and those to the higher states. Our best result shows a branching ratio of 17±2, which is the highest among coherent control experiments using analogous schemes. Such quantum control techniques may find broad application in suppressing leakage errors in a variety of quantum information architectures.

IRAK1 rs3027898 C/A polymorphism is associated with risk of rheumatoid arthritis.

IRAK1 and miR-499 play an important role in the etiology of rheumatoid arthritis. Few studies to date have focused on the influence of the IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C polymorphisms in the susceptibility of the Chinese population to rheumatoid arthritis. We hypothesized that these polymorphisms may contribute to rheumatoid arthritis susceptibility. We studied IRAK1 rs3027898 C/A and hsa-mir-499 rs3746444 T/C gene polymorphisms in 214 rheumatoid arthritis cases and 478 controls in a Chinese population. Genotyping was performed by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the IRAK1 rs3027898 CC homozygote genotype was used as the reference group, the AA genotype was associated with significantly increased risk of rheumatoid arthritis (odds ratio (OR) = 1.91, 95 % confidence interval (CI) = 1.12-3.26, p = 0.017). A significantly increased risk of RA associated with the IRAK1 rs3027898 AA genotype was more evident among females, younger patients, CRP negative patients and both anti-CCP positive and negative patients compared with the IRAK1 rs3027898 CC/CA genotypes. The hsa-mir-499 rs3746444 T/C single nucleotide polymorphism (SNP) was not significantly associated with the risk for rheumatoid arthritis. Our findings suggest that the functional SNP IRAK1 rs3027898 C/A variant allele is associated with the development of rheumatoid arthritis. However, the hsa-mir-499 rs3746444 T/C polymorphism may not be associated with susceptibility to rheumatoid arthritis.

Influence of BLK polymorphisms on the risk of rheumatoid arthritis.

B cell lymphocyte kinase (BLK) encodes a member of the Src kinase family and thus may influence the proliferation and differentiation of cells. A single nucleotide polymorphism (SNP) located in the first intron of BLK has shown that the risk C allele of rs2248932 is associated with lower levels of messenger RNA expression of BLK. We hypothesized that this polymorphism may contribute to rheumatoid arthritis (RA) susceptibility. We studied BLK rs2248932 T/C gene polymorphisms in 329 patients with RA and 697 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). When the BLK rs2248932 TT homozygote genotype was used as the reference group, the CC genotype was associated with a significantly increased risk of RA. In the recessive model, when the BLK rs2248932 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased susceptibility to RA. In stratification analyses, a significantly increased risk for RA associated with the BLK rs2248932 CC genotype was evident among younger patients, CRP-negative patients and anti-CCP-positive patients compared with the BLK rs2248932 TT/TC genotype. The risk was also significantly evident among RF-positive patients, patients with lower ESR levels, patients with lower or higher DAS28 score and patients with a lower functional class. These findings suggested that the functional SNP BLK rs2248932 T/C variant allele was associated with RA development. However, our results were obtained from a moderate-sized sample, and therefore this is a preliminary conclusion. Validation in a larger study from a more diverse ethnic population is needed to confirm these findings.

Microbially-Induced Calcium Carbonate Precipitation Test on Yellow Sandstone Based on LF-NMR Monitoring.

The microbially-induced calcium carbonate precipitation (MICP) technique has shown great robustness in dealing with soil and groundwater contamination problems. A typical result of the implementation of MICP technique is a change in the pore structure. In this study, the effects of MICP on the pore structure of yellow sandstone from the Zigong area, Sichuan, China under different conditions, (e.g., temperature, pH, and calcium ion concentration) are investigated using LF-NMR resonance. The pore network of yellow sandstone is accurately measured using the peak area of the T2 spectral signal. The distribution of calcium carbonate in the pores of the yellow sandstone is characterized by the magnitude of the T2 signal variation. The results show that the precipitation of calcium carbonate caused by MICP tends to be deposited in relatively large pores. However, the calcium carbonate precipitates in the smaller pores at a higher temperature. A higher pH considerably enhances the precipitation, and the alkaline environment tends to cause the precipitation of the calcium carbonate in the large pores. Although the amount of produced calcium carbonate continuously increases as the MCIP process continues, which is expected, the production efficiency decreases steadily.

Characterization and pre-clinical assessment of a proposed biosimilar to its originator Omalizumab.

Omalizumab is an anti-IgE monoclonal antibody (mAb) approved for the treatment of moderate-to-severe asthma. Herein, we report physicochemical, biological, pharmacological, and toxicological characteristics of an Omalizumab biosimilar mAb named KA. We show that KA and its originator present only minimum differences. Their charge heterogeneity and primary, secondary structures are similar. The two molecules are comparable regarding in vitro activity, including molecular binding and cell-based inhibition. Pharmacological and toxicological properties were assessed using a mouse model of allergy and cynomolgus monkeys, and we determined that the efficacy, safety, and pharmacokinetic characteristics of KA are comparable to its originator. Our data, which demonstrated that KA has similar activity to the Omalizumab reference product in relevant preclinical models, calls for a clinical evaluation of its bio-similarity.

Visualization of Flow-Induced Strain Using Structural Color in Channel-Free Polydimethylsiloxane Devices.

Measuring flow of gases is of fundamental importance yet is typically done with complex equipment. There is, therefore, a longstanding need for a simple and inexpensive means of flow measurement. Here, gas flow is measured using an extremely simple device that consists of an Ar plasma-treated polydimethylsiloxane (PDMS) slab adhered on a glass substrate with a tight seal. This device does not even have a channel, instead, gas can flow between the PDMS and the glass by deforming the PDMS wall, in other words, by making an interstice as a temporary path for the flow. The formation of the temporary path results in a compressive bending stress at the inner wall of the path, which leads to the formation of well-ordered wrinkles, and hence, the emergence of structural color that changes the optical transmittance of the device. Although it is very simple, this setup works sufficiently well to measure arbitrary gases and analyzes their flow rates, densities, and viscosities based on the change in color. It is also demonstrated that this technique is applicable to the flow-induced display of a pattern such as a logo for advanced applications.