Using high-diffraction-efficiency holographic optical elements in a full-color augmented reality display system.

Holographic optical elements (HOEs) play an important role in augmented reality (AR) systems. However, the fabrication of full-color HOEs is difficult and the diffraction efficiency is low. In this paper, we use the time-scheduled iterative exposure method to fabricate full-color HOEs with high diffraction efficiency. Through this method, a full-color HOE with an average diffraction efficiency of 73.4% was implemented in a single photopolymer, the highest rate yet reported. In addition, the AR system is simulated by the geometric optics method combining k-vector circle and ray tracing and structured by combining laser micro-drop and high diffraction efficiency HOEs. A good color blending effect was achieved in a full-color AR system by using the reconstruction wavelength consistent with the recording light. It can present clear holographic images in a full-color AR display system.

Runx2 overexpression promotes bone repair of osteonecrosis of the femoral head (ONFH).

BACKGROUND: Runt-related transcription factor-2 (Runx2) has been considered an inducer to improve bone repair ability of mesenchymal stem cells (MSCs). METHODS AND RESULTS: Twenty-four rabbits were used to establish Osteonecrosis of the femoral head (ONFH) and randomly devided into four groups: Adenovirus Runx2 (Ad-Runx2) group, Runx2-siRNA group, MSCs group and Model group. At 1 week after model establishment, the Ad-Runx2 group was treated with 5 × 107 MSCs transfected through Ad-Runx2, the Runx2-siRNA group was treated with 5 × 107 MSCs transfected through Runx2-siRNA, the MSCs group was injected with 5 × 107 untreated MSCs, and the Model group was treated with saline. The injection was administered at 1 week and 3 weeks after model establishment. The expression of bone morphogenetic protein 2 (BMP-2), Runx2 and Osterix from the femoral head was detected at 3 and 6 weeks after MSCs being injected, and Masson Trichrome Staining, Gross Morphology, X-ray and CT images observation were used to evaluate the repair effect of ONFH. The data revealed that the expression of BMP-2, Runx2 and Osterix in the Runx2-siRNA group was reduced at 3 weeks compared with the MSCs group, and then the expression further reduced at 6 weeks, but was still higher than the Model group besides Osterix; The expression of these three genes in the Ad-Runx2 group was higher than in the MSCs group. Masson Trichrome Staining, Gross Morphology and X-ray and CT images observation revealed that necrotic femoral head of the MSCs group was more regular and smooth than the Runx2-siRNA group, which has a collapsed and irregular femoral head. In the Ad-Runx2 group, necrotic femoral head was basically completely repaired and covered by rich cartilage and bone tissue. CONCLUSIONS: Overexpression of Runx2 can improve osteoblastic phenotype maintenance of MSCs and promote necrotic bone repair of ONFH.

Direct or Indirect Action Mechanisms of Naringin in Maintaining Bone Homeostasis.

Disruption of bone homeostasis is the pathological basis of bone diseases. Multiple cells work together to maintain homeostasis and bone health. As a natural flavonoid compound, Naringin (NG) can positively affect the maintenance of bone homeostasis by acting on different types of cells. In this review, we discuss the direct and indirect osteoprotective effects of NG as well as the underlying mechanisms, and we provide a critical perspective on its clinical translation.

Apocarotenoids from Equisetum debile Roxb. ex Vaucher regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway.

Sixteen undescribed apocarotenoids (1-16), along with 22 known analogues, were isolated from the aerial parts of Equisetum debile. Their structures, including absolute configurations, were elucidated by NMR, HRESIMS, X-ray diffraction analysis, the modified Mosher's method and the quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Compounds 1-9, 11-12 are the first example of C16-apocarotenoids appeared in nature. The plausible biosynthetic pathway of 1-16 was proposed. Moreover, the isolates were evaluated for their lipid-lowering activity, and the results showed that 13, 14, 15, 22, 31, 32 and 33 could remarkably decrease the levels of both TC and TG in FFA induced HepG2 cells at 20 µM. The oil red staining assay further demonstrated the lipid-lowering effects of 13, 14 and 15. The western blot results indicated that compounds 13, 14 and 15 could regulate the lipid metabolism via the activation of the AMPK/ACC/SREBP-1c signaling pathway. A preliminary structure-activity relationship (SAR) study of the isolates indicated that the apocarotenoids with 6/5 ring system displayed more potent lipid-lowering effects.

All-fiber bidirectional mode-locked laser to generate cylindrical vector beam asynchronous noise-like pulses.

We proposed and demonstrated a bidirectional mode-locked fiber laser to generate cylindrical vector beam (CVB) asynchronous pulses based on a graded index multimode fiber. A homemade fused taper two-mode fiber optical coupler (TMF-OC) is employed as a mode converter. The central wavelength for clockwise (CW) pulses can be tuned from 1030.32 nm to 1041.04 nm due to the filtering effect based on multimode interference, that of counterclockwise (CCW) pulses is from 1030.81 nm to 1039.28 nm. When the central wavelengths are 1033.22 nm and 1032.71 nm for CW direction and CCW direction respectively, CVB asynchronous noise-like pulses with a repetition rate difference of ∼436.9 Hz can be obtained. The purity of CVB in CW direction and CCW direction is 95.7% and 93.4% respectively. This bidirectional mode-locked fiber laser with CVB output can be better applied to laser gyroscopes, asynchronous sampling, and dual-comb technique, and impel the interdisciplinary studies in the future.

High-power cylindrical vector beam fiber laser based on an all-polarization-maintaining structure.

We propose and demonstrate an all-polarization-maintaining (PM) high-power cylindrical vector beam (CVB) fiber laser based on the principle of mode superposition. The non-degenerated LPy 11a is generated from the oscillator with the maximum power of 11.9W, whose slope efficiency is 24.4%. Then the stable single TE01 vector beam is achieved by the superposition of LPy 11a and LPx 11b in an all-PM architecture, its output power is 3.1W and mode purity of 91.2%. Due to the all-PM architecture, our configuration is free of adjusting polarization controller (PC) and reliable during long-term operation. This laser could be used as a high-power CVBs source for a wide range of applications towards scientific research and industrial field.

Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity.

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and comparison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 µM. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

Jatrophane Diterpenoids from Euphorbia peplus as Multidrug Resistance Modulators with Inhibitory Effects on the ATR-Chk-1 Pathway.

Twelve undescribed jatrophane diterpenoids, euphpepluones A-L (1-12), together with seven known analogues (13-19), were isolated from the whole plant of Euphorbia peplus, and their structures were elucidated by spectroscopic studies. The absolute configurations of 1 and 4 were assigned by X-ray crystallographic analysis. All isolates were investigated for their inhibitory effects against the ATR-Chk1 pathway using a Western blotting assay. As a result, 1, 2, 5, 8, 10, and 16 were found to suppress the camptothecin (CPT)-induced phosphorylation of Chk1, indicating that these compounds inhibit the activation of the ATR-Chk1 pathway. A preliminary structure-activity relationship (SAR) study of the isolates was conducted. When compound 10 and CPT were combined, apoptosis was induced in A549 cells with PARP cleavage, while there was no apoptotic effect by treatment with CPT or 10 alone. The data obtained indicate that 10 potentiates the chemotherapeutic sensitivity of A549 cells to CPT.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα.

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.

Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Traumatic osteonecrosis of the femoral head (ONFH) is a condition leading to the collapse of the femoral head, and the primary treatment is a total hip replacement, which has a poor prognosis. The current study was conducted with the aim of investigating the role of exosomes from bone marrow-derived mesenchymal stem cells (BM-MSCs) carrying microRNA-224-3p (miR-224-3p) in traumatic ONFH. Initially, a microarray analysis was performed to screen the differentially expressed genes and miRs associated with traumatic ONFH. Patients with traumatic and nontraumatic ONFH were enrolled, and HUVECs were obtained. The BM-MSCs-derived exosomes were purified and characterized, after which HUVECs were cocultured with exosomes. The functional role of miR-224-3p in traumatic ONFH was determined using ectopic expression, depletion, and reporter assay experiments. Endothelial cell proliferation, migration, invasion abilities, and angiogenesis were evaluated. Based on microarray analysis, miR-224-3p was found to be down-regulated, whereas focal adhesion kinase family interacting protein of 200 kDa (FIP200) was up-regulated in ONFH. Traumatic ONFH exosomes resulted in the up-regulation of FIP200 and down-regulation of miR-224-3p. FIP200 was confirmed to be a target gene of miR-224-3p. Exosomes were internalized by vascular endothelial cells. The down-regulation of exosomal miR-224-3p was observed to promote endothelial cell proliferation, migration, invasion abilities, angiogenesis, and FIP200 expression. In addition, FIP200 overexpression promoted angiogenesis. In summary, the results highly indicated that lower miR-224-3p levels in exosomes derived from BM-MSCs promote angiogenesis of traumatic ONFH by up-regulating FIP200. The present study provides a potential strategy for the treatment of traumatic ONFH.-Xu, H.-J., Liao, W., Liu, X.-Z., Hu, J., Zou, W.-Z., Ning, Y., Yang, Y., Li, Z.-H. Down-regulation of exosomal microRNA-224-3p derived from bone marrow-derived mesenchymal stem cells potentiates angiogenesis in traumatic osteonecrosis of the femoral head.

Chemical Constituents from Endophytic Fungus Annulohypoxylon cf. stygium in Leaves of Anoectochilus roxburghii.

The chemical investigation on endophytic fungus Annulohypoxylon cf. stygium in leaves of Anoectochilus roxburghii (Wall.) Lindl. has been performed. Sixteen compounds were isolated and their structures were identified as (-)-notoamide A, (-)-notoamide B, (+)-versicolamide B, notoamide C, notoamide D, stephacidin A, sterigmatocystin, dihydrosterigmatocystin, secosterigmatocystin, versiconol, averufanin, kipukasin D, kipukasin E, diorcinal, palmarumycin CP2 and (-)-(3R)-mellein methyl ether, respectively, by spectroscopic analysis and comparison with literature data. All the compounds were isolated from Annulohypoxylon genus for the first time. Sterigmatocystin and palmarumycin CP2 showed selective cytotoxic activities against HepG2, HeLa, MCF-7 and HT-29.

BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head.

Mesenchymal stem cells (MSCs) with multipotential differentiation capacity can differentiate into bone cells under specific conditions and can be used to treat osteonecrosis (ON) of the femoral head (ONFH) through cell transplantation. The current study aims to explore the role of bone marrow (BM) MSCs (BMSCs)-derived exosomes carrying microRNA-122-5p (miR-122-5p) in ONFH rabbit models.First, rabbit models with ONFH were established. ONFH-related miRNAs were screened using the Gene Expression Omnibus (GEO) database. A gain-of-function study was performed to investigate the effect of miR-122-5p on osteoblasts and BMSCs and effects of exosomes carrying miR-122-5p on ONFH. Co-culture experiments for osteoblasts and BMSCs were performed to examine the role of exosomal miR-122-5p in osteoblast proliferation and osteogenesis. The target relationship between miR-122-5p and Sprouty2 (SPRY2) was tested.MiR-122, significantly decreased in ONFH in the GSE89587 expression profile, was screened. MiR-122-5p negatively regulated SPRY2 and elevated the activity of receptor tyrosine kinase (RTK), thereby promoting the proliferation and differentiation of osteoblasts. In vivo experiments indicated that bone mineral density (BMD), trabecular bone volume (TBV), and mean trabecular plate thickness (MTPT) of femoral head were increased after over-expressing miR-122-5p in exosomes. Significant healing of necrotic femoral head was also observed.Exosomes carrying over-expressed miR-122-5p attenuated ONFH development by down-regulating SPRY2 via the RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Findings in the present study may provide miR-122-5p as a novel biomarker for ONFH treatment.

Association of KIR Genotypes and Haplotypes in HBeAg-positive Chronic Hepatitis B Patients Treated with Entecavir.

BACKGROUND: A large proportion of patients with chronic hepatitis B (CHB) in China do not respond to entecavir (ETV) treatment. It remains unclear whether the Killer immunoglobulin-like receptor (KIR) genotypes and haplotypes were associated with the advantage of seroconversion in phepatitis B e-Antigen (HBeAg) positive CHB patients treated with ETV. METHODS: Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to analyze KIR genes in a Chinese Han population of 198 ETV-treated HBeAg-positive CHB patients and 200 healthy controls. Of the 198 patients, 59 were complete response group (CRG) and 139 were null or partial response group (NPRG) to the treatment with ETV. RESULTS: The frequencies of KIR genotype M, and haplotype 8 were significantly higher(P = 0.017, OR = 2.497，95%CI = 5.39-1.16 and P = 0.034, OR = 1.905，95%CI = 3.48-1.04, respectively), while the frequencies of genotype AH and haplotype 5 were significantly lower (P = 0.039, OR = 0.504, 95%CI = 0.97-0.26 and P = 0.031, OR = 0.601, 95%CI = 0.96-0.38, respectively) in HBeAg-positive CHB patient group than those in healthy group. Of note, the frequencies of KIR genotype AF and haplotype 1 were significantly higher (P = 0.022, OR = 2.860, 95%CI = 7.24-1.13 and P = 0.001, OR = 3.261, 95%CI = 6.47-1.64, respectively), while the frequencies of genotype AH and haplotype 5 were significantly lower (P = 0.038, OR = 0.338, 95%CI = 0.98-0.12 and P = 0.004, OR = 0.354, 95%CI = 0.73-0.17, respectively) in NPRG than those in CRG. CONCLUSIONS: The patients with KIR genotype AF and haplotype 1 might be negative, while genotype AH and haplotype 5 might be of advantage to the therapy with ETV, which are useful for improving novel personalized precise therapy strategy in HBeAg-positive CHB patients.

Score risk model for predicting severe fever with thrombocytopenia syndrome mortality.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality in East Aisa, especially in China. To predict the prognosis of SFTS precisely is important in clinical practice. METHODS: From May 2013 to November 2015, 233 suspected SFTS patients were tested for SFTS virus using RT-PCR. Cox regression model was utilized to comfirm independent risk factors for mortality. A risk score model for mortality was constructed based on regression coefficient of risk factors. Log-rank test was used to evaluate the significance of this model. RESULTS: One hundred seventy-four patients were confirmed with SFTS, of which 40 patients died (23%). Baseline age, serum aspartate aminotransferase (AST) and serum creatinine (sCr) level were independent risk factors of mortality. The area under ROC curve (AUCs) of these parameters for predicting death were 0.771, 0.797 and 0.764, respectively. And hazard ratio (HR) were 1.128, 1.002 and 1.013, respectively. The cutoff value of the risk model was 10. AUC of the model for predicting mortality was 0.892, with sensitivity and specificity of 82.5 and 86.6%, respectively. Log-rank test indicated strong statistical significance (×2 = 88.35, p < 0.001). CONCLUSIONS: This risk score model may be helpful to predicting the prognosis of SFTS patients.

Aptamer Technology and Its Applications in Bone Diseases.

Aptamers are single-stranded nucleic acids (DNA, short RNA, or other artificial molecules) produced by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technology, which can be tightly and specifically combined with desired targets. As a comparable alternative to antibodies, aptamers have many advantages over traditional antibodies such as a strong chemical stability and rapid bulk production. In addition, aptamers can bind targets in various ways, and are not limited like the antigen-antibody combination. Studies have shown that aptamers have tremendous potential to diagnose and treat clinical diseases. However, only a few aptamer-based drugs have been used because of limitations of the aptamers and SELEX technology. To promote the development and applications of aptamers, we present a review of the methods optimizing the SELEX technology and modifying aptamers to boost the selection success rate and improve aptamer characteristics. In addition, we review the application of aptamers to treat bone diseases.

A natural product targets BRD4 to inhibit phase separation and gene transcription.

The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.

Advances in the Treatment of Partial-Thickness Cartilage Defect.

Partial-thickness cartilage defects (PTCDs) of the articular surface is the most common problem in cartilage degeneration, and also one of the main pathogenesis of osteoarthritis (OA). Due to the lack of a clear diagnosis, the symptoms are often more severe when full-thickness cartilage defect (FTCDs) is present. In contrast to FTCDs and osteochondral defects (OCDs), PTCDs does not injure the subchondral bone, there is no blood supply and bone marrow exudation, and the nearby microenvironment is unsuitable for stem cells adhesion, which completely loses the ability of self-repair. Some clinical studies have shown that partial-thickness cartilage defects is as harmful as full-thickness cartilage defects. Due to the poor effect of conservative treatment, the destructive surgical treatment is not suitable for the treatment of partial-thickness cartilage defects, and the current tissue engineering strategies are not effective, so it is urgent to develop novel strategies or treatment methods to repair PTCDs. In recent years, with the interdisciplinary development of bioscience, mechanics, material science and engineering, many discoveries have been made in the repair of PTCDs. This article reviews the current status and research progress in the treatment of PTCDs from the aspects of diagnosis and modeling of PTCDs, drug therapy, tissue transplantation repair technology and tissue engineering ("bottom-up").

Bisabolane-type sesquiterpenes from Vernonia amygdalina: Absolute configuration and anti-inflammatory activity.

The phytochemical assessment of Vernonia amygdalina resulted in the isolation and identification of seven undescribed bisabolane-type sesquiterpenes designated amygdanoids A-G and one known analogue. This is the first report of this type of sesquiterpene from V. amygdalina. Their structures, including the absolute configurations, were elucidated by comprehensive analysis with HRESIMS, 1D and 2D NMR, quantum chemical calculations of NMR and electronic circular dichroism (ECD), modified Mosher's method, and the in situ dimolybdenum CD method. The anti-inflammatory activity of the isolates was evaluated. All the isolated compounds clearly inhibited the production of NO and the expression of the iNOS protein. Secretion of the COX-2 protein was constrained by amygdanoids A-F. Further investigation suggested that amygdanoids E exhibited anti-inflammatory activity by suppressing the expression of iNOS and COX-2 as well as the PI3K/AKT/NF-κB signaling pathway.

Inhibitory effects of phenolic glycosides from Trollius chinensis Bunge on α-glucosidase: inhibition kinetics and mechanisms.

Two undescribed phenolic glycosides, trochinenols B and C (1 and2), together with four known analogues (3-6), were isolated from the functional tea Trollius chinensis Bunge and their α-glucosidase inhibitory kinetics and mechanisms were investigated. It was found that 1 inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 25.96 µM, while 3 showed a notable inhibitory effect against α-glucosidase in an uncompetitive manner with an IC50 value of 3.14 µM. Analysis of synchronous fluorescence and circular dichroism spectroscopy indicated that the binding of 1 to α-glucosidase led to the rearrangement and conformational alteration of the α-glucosidase enzyme. Furthermore, molecular docking indicated that 1 had a high affinity close to the active site pocket of α-glucosidase and indirectly inhibited the catalytic activity of the enzyme. However, 3 was bound to the entrance part of the active center of α-glucosidase and could hinder the release of the substrate as well as the catalytic reaction product, eventually suppressing the catalytic activity of α-glucosidase.