Development of a novel six DNA damage response-related prognostic signature in osteosarcoma.

DNA damage response (DDR) plays a vital role in the development of cancer. Nevertheless, in osteosarcoma, the potential of DDR-related genes (DDRGs) remains unclear. Thus, the current research is intended to investigate the mechanisms of DDRGs in the development of osteosarcoma and to explore potential DDR-related biomarkers in forecasting the prognosis of osteosarcoma patients. The osteosarcoma genomic data from TCGA, GEO and cBioPortal databases were utilized for screening and identification of differentially expressed DDRGs (DEDDRGs). Consensus clustering analysis was performed to identify different subtypes of osteosarcoma based on the expressions of DDRGs. Key DEDRRGs were identified by overlapping DEDRRGs between different subtypes and DEDRRGs between tumor and control samples. Univariate, as well as LASSO regressions, were further applied to obtain robust prognostic signatures. GSVA and ssGSEA analysis were implemented to explore the underlying mechanisms of prognostic DDRG signature in regulating osteosarcoma. In addition, the drug sensitivity of patients in low- and high-risk groups was evaluated using pRRophetic algorithm. A total of 43 key DEDRRGs were identified. Followed by univariate Cox along with LASSO regression analyses, CDK6, CSF1R, EGFR, ERBB4, GATA3 and SOCS1 were identified as prognostic signatures in osteosarcoma. Cox regressions revealed that the risk score was an independent prognostic factor in osteosarcoma.  DDR may affect osteosarcoma via regulating immune microenvironment along with influencing cell proliferation, migration, adhesion and apoptosis. The chemotherapeutic response between patients in low- and high-risk groups was much different. The role of DDRGs in osteosarcoma and identified six DDR-linked biomarkers for forecasting the prognosis of osteosarcoma patients. Our outcomes enhanced the understanding of DDR-related molecular mechanisms involved in osteosarcoma and provided potential therapeutic targets for osteosarcoma patients.

Association of Different Types of Osteoarthritis with Different Immune-Related Subtypes and Hub Genes.

Background: Osteoarthritis (OA) is a diverse disorder that most frequently affects elderly people and makes them disabled. Many investigations have shown that the etiology of OA depends on cartilage wear, but immunology also plays a significant role. Thus, the goal of this study was to define the immune-related etiology of OA. Methods: Data from the "Gene Expression Omnibus (GEO)" database were used to find differentially expressed genes (DEGs), and the "Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm" was employed to calculate the quantity of distinct immune cells. We analyzed the results to identify patient subgroups and compare major active pathways. Results: The macrophage cell population accounts for the greatest percentage of infiltrating immune cells in OA. One hundred and twenty-two common intersection genes were identified, with the network analysis of protein-protein interactions revealing ten hub genes related to OA, including CXCL8, JUN, ATF3, DUSP1, PTGS2, IL6, MMP9, FOS, NFKBIA, and MYC. The random forest model showed that memory-activated CD4 T cells are strongly correlated with other immune cell types, while neutrophils have the weakest correlation with other immune cell types. Violin plots showed that OA patients had a significantly larger quantity of plasma cells and resting mast cells, with a significantly smaller quantity of resting memory CD4 T cells and activated mast cells than healthy controls. Conclusions: Two immune-related subgroups of OA were identified by semi-supervised clustering analysis of microarray data, and core genes were also determined by network analysis. A group of the immune infiltrating cells was selected by random forest analysis suggesting they are related to the pathogenesis of OA.

Biomimetic Nanovesicle with Mitochondria-Synthesized Sonosensitizer and Mitophagy Inhibition for Cancer Sono-Immunotherapy.

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.

Gut microbiome and osteoporosis: a review.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated. Cite this article: Bone Joint Res 2020;9(8):524-530.

Percutaneous Endoscopic Lumbar Discectomy: Indications and Complications.

BACKGROUND: Percutaneous endoscopic lumbar discectomy (PELD) often refers to percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID). As a minimally invasive spinal procedure, PELD has gained increasing recognition for its small incision, quick recovery, short hospital stay, and equivalent clinical outcome compared to open surgery. In order to obtain satisfactory clinical efficacy, adequate consideration should be given regarding the indication of PELD. On the other hand, complications related to PELD will also significantly affect the safety and outcome of surgery. OBJECTIVE: Our objective was to conduct a literature review of the indications and complications of PELD and to provide our experience in patient selection and solutions to complications related to PELD. STUDY DESIGN: The study is a literature review focused on the indications and complications of PELD. SETTING: The study is a literature review on the indications and complications of PELD. METHODS: A comprehensive review of available literature on PELD was performed. Particular focus was given to the development of indications and prevention of complications. The literature was searched in PubMed database, and key words were set as "percutaneous endoscopic lumbar discectomy", "percutaneous endoscopic transforaminal discectomy", "percutaneous endoscopic interlaminar discectomy", "PELD", "PETD", "PEID", "YESS" and "TESSYS". RESULTS: PELD is an effective and safe treatment for lumbar disc herniation, lumbar spinal stenosis, recurrent lumbar disc herniation, and other lumbar diseases. Complications related to PELD include dural tear, nerve root injury, recurrence, and so on. LIMITATIONS: Some results drawn in this review are based on retrospective study or small sample size. Studies of larger sample size and more multicenter, randomized controlled trials should be conducted to evaluate the clinical efficacy and safety of PELD. CONCLUSIONS: PELD is a promising surgical technique for lumbar diseases. Proper patient selection, excellent surgical skills, and rich experience are required for satisfactory outcomes. KEY WORDS: Complications, indications, minimally invasive spine surgery, PELD.

Percutaneous vertebral augmentation in special Genant IV osteoporotic vertebral compression fractures.

BACKGROUND: Percutaneous vertebral augmentation is widely used for treating osteoporotic vertebral compression fractures (OVCFs). Bony encroachment in the spinal canal can be detected in some severe cases, increasing the difficulty of operation and risks of perioperative complications. PURPOSE: A special type of OVCF has been introduced, and the clinical efficacy of vertebral augmentation has been evaluated in treating this special OVCF. MATERIALS AND METHODS: The medical history of patients with OVCF treated with vertebral augmentation was reviewed. The vertebral body height and local kyphotic angle were measured and calculated on the lateral plain radiographs. The visual analogue scale and Oswestry Disability Index were assessed preoperatively, two days after operation, and at final follow-up periods. Complications such as cement leakage and recurrent vertebral fractures were also recorded and followed up. RESULTS: Twenty-nine patients with special Genant IV OVCF accepted vertebral augmentation, and 28 of them were followed up. The mean follow-up duration was 21.9 months, ranging from 17 to 34 months. The lateral plain radiographs revealed significant restoration of vertebral body height and local kyphotic angle. Both visual analogue scale and Oswestry Disability Index scores showed improvement 2 days after surgery and at final follow-up. Four patients experienced asymptomatic cement leakage, and 6 patients suffered OVCF recurrence in other segments. CONCLUSION: Despite a great challenge, vertebral augmentation can be considered as a safe and effective option for treating special the Genant IV OVCF, showing significant restoration of vertebral body height, local kyphotic angle, and daily life function. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Vertebral augmentation has been proven a safe and effect surgery method for special Genant IV OVCF. While surgery complications related to the commercially available filling material - polymethyl methacrylate (PMMA) is common and inevitable. Hence, this article is aimed to provide practical surgical techniques and suggestions to the modification of PMMA and fabrication of newly developed bone cements.

Loss/gain-induced ultrathin antireflection coatings.

Tradional antireflection coatings composed of dielectric layers usually require the thickness to be larger than quarter wavelength. Here, we demonstrate that materials with permittivity or permeability dominated by imaginary parts, i.e. lossy or gain media, can realize non-resonant antireflection coatings in deep sub-wavelength scale. Interestingly, while the reflected waves are eliminated as in traditional dielectric antireflection coatings, the transmitted waves can be enhanced or reduced, depending on whether gain or lossy media are applied, respectively. We provide a unified theory for the design of such ultrathin antireflection coatings, showing that under different polarizations and incident angles, different types of ultrathin coatings should be applied. Especially, under transverse magnetic polarization, the requirement shows a switch between gain and lossy media at Brewster angle. As a proof of principle, by using conductive films as a special type of lossy antireflection coatings, we experimentally demonstrate the suppression of Fabry-Pérot resonances in a broad frequency range for microwaves. This valuable functionality can be applied to remove undesired resonant effects, such as the frequency-dependent side lobes induced by resonances in dielectric coverings of antennas. Our work provides a guide for the design of ultrathin antireflection coatings as well as their applications in broadband reflectionless devices.

Fano resonances from gradient-index metamaterials.

Fano resonances - resonant scattering features with a characteristic asymmetric profile - have generated much interest, due to their extensive and valuable applications in chemical or biological sensors, new types of optical switches, lasers and nonlinear optics. They have been observed in a wide variety of resonant optical systems, including photonic crystals, metamaterials, metallic gratings and nanostructures. In this work, a waveguide structure is designed by employing gradient-index metamaterials, supporting strong Fano resonances with extremely sharp spectra. As the changes in the transmission spectrum originate from the interaction of guided modes from different channels, instead of resonance structures or metamolecules, the Fano resonances can be observed for both transverse electric and transverse magnetic polarizations. These findings are verified by fine agreement with analytical calculations and experimental results at microwave, as well as simulated results at near infrared frequencies.

A broadband polarization-insensitive cloak based on mode conversion.

In this work, we demonstrate an one-dimensional cloak consisting of parallel-plated waveguide with two slabs of gradient index metamaterials attached to its metallic walls. In it objects are hidden without limitation of polarizations, and good performance is observed for a broadband of frequencies. The experiments at microwave frequencies are carried out, supporting the theoretical results very well. The essential principle behind the proposed cloaking device is based on mode conversion, which provides a new strategy to manipulate wave propagation.

Transformation optics with Fabry-Pérot resonances.

Transformation optics is a powerful tool to design various novel devices, such as invisibility cloak. Fantastic effects from this technique are usually accompanied with singular mappings, resulting in challenging implementations and narrow bands of working frequencies. Here in this article, Fabry-Pérot resonances in materials of extreme anisotropy are used to design various transformation optical devices that are not only easy to realize but also work well for a set of resonant frequencies (multiple frequencies). As an example, a prototype of a cylindrical concentrator is fabricated for microwaves.

An equivalent realization of coherent perfect absorption under single beam illumination.

We have experimentally and numerically demonstrated that the coherent perfect absorption (CPA) can equivalently be accomplished under single beam illumination. Instead of using the counter-propagating coherent dual beams, we introduce a perfect magnetic conductor (PMC) surface as a mirror boundary to the CPA configuration. Such a PMC surface can practically be embodied, utilizing high impedance surfaces, i.e., mushroom structures. By covering them with an ultrathin conductive film of sheet resistance 377 Ω, the perfect (100%) microwave absorption is achieved when the film is illuminated by a single beam from one side. Employing the PMC boundary reduces the coherence requirement in the original CPA setup, though the present implementation is limited to the single frequency or narrow band operation. Our work proposes an equivalent way to realize the CPA under the single beam illumination, and might have applications in engineering absorbent materials.