Search

The rapid and efficient design strategy represents a highly intriguing research domain within the realm of metasurfaces. It necessitates minimizing the data load in coding metasurface design, facilitating the development of a precise approach to designing metasurfaces with specific characteristics. In this paper, we proposed a restrictive design strategy of metasurface for coding phase distributions based on the Fibonacci sequences, which is efficient to optimize designated radar cross section (RCS) reduction according to application requirements. Through the given restrictive strategy, the encoding range of the metasurfaces is reduced from the entire metasurfaces to the initial phase units in the corners, greatly reducing the total amount of data in the optimization database. In order to verify the availability of the strategy, RCS reduction metasurfaces with variable phase sequences in microwave region are analyzed. For broadband and wide-angle RCS reduction, the optimized Fibonacci discrete phase gradient (FDPG) metasurface is obtained by adjusting the phase sequences. Both the simulation and measured results show that the optimized FDPG metasurfaces by the proposed designing strategy have the RCS reduction of −10 dB in the frequency ranges of 6 GHz to 18 GHz under wide incidence angles from 0° to 30°. The simulated and measured results are good consistent over the whole frequency ranges and angle regions. This method combines mathematical sequences with physics organically, making it an important field in metasurfaces research and it is expected to play an important role in future studies.

A broadband radar cross-section (RCS) reduction employed by the vortex metasurface is proposed. The underlying physics is associated with the Pancharatnam-Berry geometrical phases involved in spin-to-orbital angular momentum conversion. The proposed metasurface generates spin-controlled vortex waves with different topological charges. The vortex singularity implements specular extremely low RCS reduction. The prototypes are fabricated and measured to verify the wideband performance of the RCS reduction. The simulated results illustrate that −10 dB broadband RCS reduction from 9 GHz to 22.5 GHz and the RCS reduction has peak values −37.2 dB, −40.8 dB, and −42.5 dB at 9.8 GHz, 13.1 GHz, and 20.8 GHz, respectively. The measurement results illustrate that −10 dB RCS reduction over 9.1–18 GHz is realized, and the RCS reduction peak −53 dB at 10.1 GHz. The measured electric field intensities and phase distribution of the vortex metasurface also be displayed. Due to the limitation of experimental conditions, no test was done in the range greater than 18 GHz. Far-field results achieve good agreement between simulations and experiments, and the near-field measurements are a subtle difference in the experimental results. This work reveals the potential advantages of vortex waves in the fields of multifunctional electromagnetic stealth, beamforming for communication systems, etc.

Abstract The intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate (EP) and annulus fibrosus (AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol (2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

Different types of mesenchymal progenitors participate in ectopic bone formation. Here, the authors show Col2+ lineage cells adopt a lymphatic endothelium cell fate, which regulates local inflammatory microenvironment after trauma, thus influencing heterotopic ossification (HO) development via a FGFR3-BMPR1a pathway.

Abstract Developing an economical, durable, and efficient electrode that performs well at high current densities and is capable of satisfying large‐scale electrochemical hydrogen production is highly demanded. A self‐supported electrocatalytic “Pt‐like” WC porous electrode with open finger‐like holes is produced through industrial processes, and a tightly bonded nitrogen‐doped WC/W (WC‐N/W) heterostructure is formed in situ on the WC grains. The obtained WC‐N/W electrode manifests excellent durability and stability under multi‐step current density in the range of 30–1000 mA cm−2 for more than 220 h in both acidic and alkaline media. Although WC is three orders of magnitude cheaper than Pt, the produced electrode demonstrates comparable hydrogen evolution reaction performance to the Pt electrode at high current density. Density functional theory calculations attribute its superior performance to the electrode structure and the modulated electronic structure at the WC‐N/W interface.

Congenital scoliosis is a complex genetic disorder characterized by vertebral malformation. Here, the authors demonstrate that loss of dstyk leads to scoliosis in zebrafish due to dysregulated biogenesis of notochord vacuoles and that DSTYK is required for lysosome biogenesis through mTORC1 regulation.

Purpose: Postoperative anemia has been a threat to total hip arthroplasty patients. We introduced a novel medullary cavity hemostasis (MCH) technique and combined it with tranexamic acid (TXA) to prevent postoperative anemia in elder patients. This trial was conducted to evaluate the effectiveness and safety of this technique. Methods: In this retrospective consecutive study, each group has 88 patients who were all over 70 years old. In the control group, patients were given TXA. In the experimental group, the MCH technique and same TXA application were used. Results: The average of total blood loss, drainage volume, and hidden blood loss were significantly less in the experimental group. The postoperative hemoglobin (Hb) level was significantly higher in the experimental group (100.6 g/dL) than it is in the control group (81.4 g/dL). None of the patient has shown signs of prosthesis subsidence, periprosthetical osteolysis, or stem loosening during follow-ups in the average follow-up time of 3 years. Conclusion: We discovered that application of TXA alone is not sufficient to prevent postoperative moderate anemia in patients over 70 years old. Combination of TXA and MCH is an effective and safe way to alleviate the severity of postoperative anemia.

Influenza virus infection is a major health care concern associated with significant morbidity and mortality worldwide, and cause annual seasonal epidemics and pandemics at irregular intervals. Recent research has highlighted that viral components can be found on the extracellular vesicles (EVs) released from infected cells, implying a functional relevance of EVs with influenza virus dissemination. Therefore, exploring the role of EVs in influenza virus infection has been attracting significant attention. In this review, we will briefly introduce the biogenesis of EVs, and focus on the role of EVs in influenza virus infection, and then discuss the EVs-based influenza vaccines and the limitations of EVs studies, to further enrich and boost the development of preventative and therapeutic strategies to combat influenza virus.

Background/Aims: We have demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent BMPs in regulating osteoblast differentiation of mesenchymal stem cells (MSCs) although the molecular mechanism underlying BMP9-induced osteogenesis remains to be fully elucidated. It is known that epigenetic regulations play an important role in regulating the stem cell potency and lineage commitment. Here, we investigate if the inhibition of histone deacetylases (Hdacs) affects BMP9-induced osteogenic differentiation of MSCs. Methods: Using the Hdac inhibitor trichostatin A (TSA), we assess that TSA enhances BMP9-mediated osteogenic markers and matrix mineralization in MSCs, and bone formation in mouse embryonic limb explants. Results: We find that the endogenous expression of most of the 11 Hdacs is readily detectable in MSCs. BMP9 is shown to induce most Hdacs in MSCs. We demonstrate that TSA potentiates BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs, as well as late osteogenic markers osteopontin (OPN) and osteocalcin (OCN) and matrix mineralization. Fetal limb explant culture studies reveal that TSA potentiates BMP9-induced endochondral bone formation, possibly by expanding hypertrophic chondrocyte zone of growth plate. Conclusion: Our findings strongly suggest histone deacetylases may play an important role in fine-tuning BMP9-mediated osteogenic signaling through a negative feedback network in MSCs. Thus, Hdac inhibitors may be used as novel therapeutics for bone fracture healing.

Cartilage tissue engineering holds great promise for treating cartilaginous pathologies including degenerative disorders and traumatic injuries. Effective cartilage regeneration requires an optimal combination of biomaterial scaffolds, chondrogenic seed cells, and biofactors. Obtaining sufficient chondrocytes remains a major challenge due to the limited proliferative capability of primary chondrocytes. Here we investigate if reversibly immortalized mouse articular chondrocytes (iMACs) acquire long-term proliferative capability while retaining the chondrogenic phenotype. Primary mouse articular chondrocytes (MACs) can be efficiently immortalized with a retroviral vector-expressing SV40 large T antigen flanked with Cre/loxP sites. iMACs exhibit long-term proliferation in culture, although the immortalization phenotype can be reversed by Cre recombinase. iMACs express the chondrocyte markers Col2a1 and aggrecan and produce chondroid matrix in micromass culture. iMACs form subcutaneous cartilaginous masses in athymic mice. Histologic analysis and chondroid matrix staining demonstrate that iMACs can survive, proliferate, and produce chondroid matrix. The chondrogenic growth factor BMP2 promotes iMACs to produce more mature chondroid matrix resembling mature articular cartilage. Taken together, our results demonstrate that iMACs acquire long-term proliferative capability without losing the intrinsic chondrogenic features of MACs. Thus, iMACs provide a valuable cellular platform to optimize biomaterial scaffolds for cartilage regeneration, to identify biofactors that promote the proliferation and differentiation of chondrogenic progenitors, and to elucidate the molecular mechanisms underlying chondrogenesis.

Three-dimensional organoids have been recently established from various tissue-specific progenitors (such as intestinal stem cells), induced pluripotent stem cells, or embryonic stem cells. These cultured self-sustaining stem cell-based organoids may become valuable systems to study the roles of tissue-specific stem cells in tissue genesis and disease development. It is thus conceivable that effective genetic manipulations in such organoids may allow us to reconstruct disease processes and/or develop novel therapeutics. Recombinant adenoviruses are one of the most commonly used viral vectors for in vitro and in vivo gene deliveries. In this study, we investigate if adenoviruses can be used to effectively deliver transgenes into the cultured "mini-gut" organoids derived from intestinal stem cells. Using adenoviral vectors that express fluorescent proteins, we demonstrate that adenoviruses can effectively deliver transgenes into the cultured 3-D "mini-gut" organoids. The transgene expression can last at least 10 days in the cultured organoids. As a proof-of-principle experiment, we demonstrate that adenovirus-mediated noggin expression effectively support the survival and self-renewal of mini-gut organoids, while adenovirus-mediated expression of BMP4 inhibits the self-sustainability and proliferation of the organoids. Thus, our results strongly suggest that adenovirus vectors can be explored as effective gene delivery vehicles to introduce genetic manipulations in 3-D organoids.

Mesenchymal stem cells (MSCs) are multipotent progenitors, which can undergo self-renewal and give rise to multi-lineages. A great deal of attentions have been paid to their potential use in regenerative medicine as potential therapeutic genes can be introduced into MSCs. Genetic manipulations in MSCs requires effective gene deliveries. Recombinant adenoviruses are widely used gene transfer vectors. We have found that although MSCs can be infected in vitro by adenoviruses, high virus titers are needed to achieve high efficiency. Here, we investigate if the commonly-used cationic polymer Polybrene can potentiate adenovirus-mediated transgene delivery into MSCs, such as C2C12 cells and iMEFs. Using the AdRFP adenovirus, we find that AdRFP transduction efficiency is significantly increased by Polybrene in a dose-dependent fashion peaking at 8 μg/ml in C2C12 and iMEFs cells. Quantitative luciferase assay reveals that Polybrene significantly enhances AdFLuc-mediated luciferase activity in C2C12 and iMEFs at as low as 4 μg/ml and 2 μg/ml, respectively. FACS analysis indicates that Polybrene (at 4 μg/ml) increases the percentage of RFP-positive cells by approximately 430 folds in AdRFP-transduced iMEFs, suggesting Polybrene may increase adenovirus infection efficiency. Furthermore, Polybrene can enhance AdBMP9-induced osteogenic differentiation of MSCs as early osteogenic marker alkaline phosphatase activity can be increased more than 73 folds by Polybrene (4 μg/ml) in AdBMP9-transduced iMEFs. No cytotoxicity was observed in C2C12 and iMEFs at Polybrene up to 40 μg/ml, which is about 10-fold higher than the effective concentration required to enhance adenovirus transduction in MSCs. Taken together, our results demonstrate that Polybrene should be routinely used as a safe, effective and inexpensive augmenting agent for adenovirus-mediated gene transfer in MSCs, as well as other types of mammalian cells.

Mouse embryonic fibroblasts (MEFs) are mesenchymal stem cell (MSC)-like multipotent progenitor cells and can undergo self-renewal and differentiate into to multiple lineages, including bone, cartilage and adipose. Primary MEFs have limited life span in culture, which thus hampers MEFs' basic research and translational applications. To overcome this challenge, we investigate if piggyBac transposon-mediated expression of SV40 T antigen can effectively immortalize mouse MEFs and that the immortalized MEFs can maintain long-term cell proliferation without compromising their multipotency. Using the piggyBac vector MPH86 which expresses SV40 T antigen flanked with flippase (FLP) recognition target (FRT) sites, we demonstrate that mouse embryonic fibroblasts (MEFs) can be efficiently immortalized. The immortalized MEFs (piMEFs) exhibit an enhanced proliferative activity and maintain long-term cell proliferation, which can be reversed by FLP recombinase. The piMEFs express most MEF markers and retain multipotency as they can differentiate into osteogenic, chondrogenic and adipogenic lineages upon BMP9 stimulation in vitro. Stem cell implantation studies indicate that piMEFs can form bone, cartilage and adipose tissues upon BMP9 stimulation, whereas FLP-mediated removal of SV40 T antigen diminishes the ability of piMEFs to differentiate into these lineages, possibly due to the reduced expansion of progenitor populations. Our results demonstrate that piggyBac transposon-mediated expression of SV40 T can effectively immortalize MEFs and that the reversibly immortalized piMEFs not only maintain long-term cell proliferation but also retain their multipotency. Thus, the high transposition efficiency and the potential footprint-free natures may render piggyBac transposition an effective and safe strategy to immortalize progenitor cells isolated from limited tissue supplies, which is essential for basic and translational studies.

Objectives The role of Paeoniflorin on hepatic fibrosis and the specific mechanisms has not yet been elucidated. Therefore, we explored whether Paeoniflorin exerted protective effects on carbon tetrachloride (CCl4)-induced hepatic fibrosis and the underlying mechanisms. Methods A model of hepatic fibrosis was induced by intraperitoneally injecting with CCl4 (10% 5 µl/g) twice a week for 7 weeks. To explore the effects of Paeoniflorin, mice were treated with Paeoniflorin (100 mg/kg) by gavage once a day at 1 week after modeling until they were sacrificed. Key findings Paeoniflorin remarkably improved liver function and histopathological changes of hepatic tissues in CCl4-induced liver injury. Besides, the serum MAO enzyme activity and hydroxyproline contents were notably decreased following the intervention of Paeoniflorin. The decreased expression of Vimentin, a-SMA, Col1a and Desmin manifested the inhibition of the hepatic stellate cells (HSCs) activation. Interestingly, Paeoniflorin intervention significantly upregulated the expression of heme oxygenase-1, and attenuated the inflammatory cytokines production as well as the CCl4-induced oxidative stress imbalance. Conclusions Paeoniflorin could effectively alleviate CCl4-induced hepatic fibrosis by upregulation of heme oxygenase-1, and it might be a new effective option for the comprehensive treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Although nonsurgical methods and many surgical techniques have been developed for repairing a ruptured Achilles tendon, there is no consensus on its best treatment. In this article, a novel minimally invasive technique called the Panda Rope Bridge Technique (PRBT) is described. Methods: Patients with acute Achilles tendon rupture were operated on in the prone position. The PRBT began with making the proximal bridge anchor (Krackow sutures in the myotendinous junction), the distal bridge anchor (two suture anchors in the calcaneus bone) and the ropes (threads of the suture anchors) stretched between the anchor sites. Then a small incision was made to debride and reattach the stumps of ruptured tendon. After the surgery, no cast or splint fixation was applied. All patients performed enhanced recovery after surgery (ERAS), which included immediate ankle mobilisation from day 1, full weight-bearing walking from day 5 to 7, and gradually taking part in athletic exercises from 8 weeks postoperatively. Results: PBRT was performed in II patients with acute Achilles tendon rupture between June 2012 and June 2015. No wound infection, fistula, skin necrosis, sural nerve damage, deep venous thrombosis or tendon re-rupture was found. One year after the surgery, all patients reported 100 [American Orthopedic Foot & Ankle Society] AOFAS ankle-hindfoot score points and the mean [Achilles Tendon Total Rupture Score] ATRS was 96.6. Conclusion: The PRBT is a simple, effective and minimally invasive technique, with no need for immobilization of the ankle, making possible immediate and aggressive postoperative rehabilitation. [ABSTRACT FROM AUTHOR]

Tumorigenesis is a multistep process involving various cell growth-associated factors. Accumulated evidence indicates that the disordered regulation of microRNAs (miRNAs) contributes to tumorigenesis. However, the detailed mechanism underlying the involvement of miRNAs in oncogenesis remains to be fully elucidated. In the present study, the repressed expression of microRNA (miR)-494 was identified in 18 patients with osteosarcoma (OS) and OS cell lines, compared with corresponding controls. To determine whether deregulated miR-494 exerts tumor-suppressive effects in the development of OS, the effects of miR-494 on cell proliferation and metastasis were evaluated. It was found that the restoration of miR-494 in MG-63 and U2OS cells led to inhibited cell proliferation and attenuated migratory propensity in vitro, determined through analysis using MTT, colony formation and Transwell assays. In addition, overexpression of miR-494 markedly suppressed the tumor volume and weight in vivo. In accordance, the ectopic expression of miR-494 induced cell cycle arrest at the G1/S phase in OS cells. Bioinformatics analysis and luciferase reporter assays were performed to investigate the potential regulatory role of miR-494, the results of which indicated that miR-494 directly targeted cyclin-dependent kinase 6 (CDK6). Of note, the data obtained through reverse transcription-quantitative polymerase chain reaction and western blot analyses suggested that the elevated expression of miR-494 resulted in reduced mRNA and protein expression levels of CDK6. Taken together, these findings indicated that the miR-494/CDK6 axis has a significant tumor-suppressive effect on OS, and maybe a diagnostic and therapeutic target for the treatment of OS. [ABSTRACT FROM AUTHOR]

Apert syndrome is caused mainly by gain-of-function mutations of fibroblast growth factor receptor 2. We have generated a mouse model ( Fgfr2 +/P253R) mimicking human Apert syndrome resulting from fibroblast growth factor receptor 2 Pro253Arg mutation using the knock-in approach. This mouse model in general has the characteristic skull morphology similar to that in humans with Apert syndrome. To characterize the detailed changes of form in the overall skull and its major anatomic structures, euclidean distance matrix analysis was used to quantitatively compare the form and growth difference between the skulls of mutants and their wild-type controls. There were substantial morphological differences between the skulls of mutants and their controls at 4 and 8 weeks of age ( P < 0.01). The mutants showed shortened skull dimensions along the rostrocaudal axis, especially in their face. The width of the frontal bone and the distance between the two orbits were broadened mediolaterally. The neurocrania were significantly increased along the dorsoventral axis and slightly increased along the mediolateral axis, and also had anteriorly displayed opisthion along the rostrocaudal axis. Compared with wild-type, the mutant mandible had an anteriorly displaced coronoid process and mandibular condyle along the rostrocaudal axis. We further found that there was catch-up growth in the nasal bone, maxilla, zygomatic bone and some regions of the mandible of the mutant skulls during the 4–8-week interval. The above-mentioned findings further validate the Fgfr2 +/P253R mouse strain as a good model for human Apert syndrome. The changes in form characterized in this study will help to elucidate the mechanisms through which the Pro253Arg mutation in fibroblast growth factor receptor 2 affects craniofacial development and causes Apert syndrome. [ABSTRACT FROM AUTHOR]

The facile preparation of ZnO possessing high visible luminescence intensity remains challenging due to an unclear luminescence mechanism. Here, two basic approaches are proposed to enhance the luminescent intensity based on the theoretical analysis over surface defects. Based on the deduction, we introduce a methodology for obtaining hybrid tetrapod-like zinc oxide (T-ZnO), decorated by carbon nanomarterials on T-ZnO surfaces through the catalytic chemical vapor deposition approach. The intensity of the T-ZnO green emission can be modulated by topography and the proportion of carbon. Under proper experiment conditions, the carbon decorating leads to dramatically enhanced luminescence intensity of T-ZnO from 400 to 700 nm compared with no carbon decorated, which elevates this approach to a simple and effective method for the betterment of fluorescent materials in practical applications. [ABSTRACT FROM AUTHOR]