ABSTRACT
The present study aims to investigate the role of interferon regulatory factor 4 (IRF4) in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. In this study, IRF4 is upregulated in periodontitis periodontal ligament tissues, as compared to healthy periodontal ligament tissues. IRF4 knockdown increases cell proliferation, decreases levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-8, enhances osteogenic activity, and increases the expression of RUNX family transcription factor 2, Collagen I, and Osteocalcin in PDLSCs. The opposite results are observed in IRF4 overexpressed PDLSCs. Additionally, GSEA shows that IRF4 activates the interleukin-18 (IL-18) signaling pathway. The expressions of IL-18, B-cell translocation gene 2, interleukin-1beta, and caspase-3 are decreased by IRF4 knockdown, while increased by IRF4 overexpression. IL-18 overexpression eliminates the promoting effect of IRF4 knockdown on osteogenic differentiation of PDLSCs. In conclusion, IRF4 suppresses osteogenic differentiation of PDLSCs by activating the IL-18 signaling pathway.
ABSTRACT
BACKGROUND: The clinical treatment of long bone defets in the extremities caused by trauma, infection, tumours, and nonunion has been a challenge for orthopaedic surgeons. Bone transport techniques have become the only way to treat such bone defects. However, inevitable difficulties and complications related to bone transport techniques have been reported in many studies. AIM: The purpose of this study was to investigate the risk factors for complications and the effectiveness of the Ilizarov bone transport technique in the treatment of tibial bone defects. METHODS: The study was conducted in 199 patients who underwent treatment with the Ilizarov bone transport technique at our institution from May 2012 to September 2019. Patient demographic data, complications and clinical outcomes after a minimum of 2 years of follow-up were collected and retrospectively analysed. Additionally, a risk factor analysis was performed for the top three major complications. The clinical outcomes were evaluated using the Association for the Study and Application of the Method of Ilizarov (ASAMI) criteria at the last clinical follow-up. RESULTS: A total of 199 patients underwent follow-up for 12-40 months, with an average of 23.5 months, and all achieved bone healing. A total of 310 complications occurred, with an average of 1.04 minor complications and 0.48 major complications per patient. The top three complications were pin tract infection in 48 cases (61.3%), axial deviation in 86 cases (43.2%), and delayed union in 50 cases (25.13%). Multivariate analysis showed that the bone defect length (P = 0.02, OR = 5.489), the number of previous surgeries (P = 0.003, OR = 2.204), and the external fixation index (P = 0.01, OR = 1.202) were significantly correlated with pin tract infection. Bone defects of the middle 1/3 (P < 0.001, OR = 23.769), the bone defect length (P < 0.001, OR = 2.776), and the external fixation index (P < 0.001, OR = 1.154) were significantly correlated with axial deviation. The bone defect length (P = 0.003, OR = 1.242), soft tissue defects (P = 0.013, OR = 0.312) and bone defects of the distal 1/3 (P = 0.023, OR = 4.257) were significantly correlated with delayed healing. The ASAMI bone score at the last follow-up showed a rate of excellent and good bone results of 95.48% and a rate of excellent functional results of 87.94%. CONCLUSION: The Ilizarov bone transfer technique is an effective method for treating tibial bone defects, and shortening the treatment period can reduce the incidence of complications. Older patients and those with longer bone defects, a higher external fixation index, more previous operations, and defects of the middle and distal 1/3 had a higher incidence of complications.
Subject(s)
Ilizarov Technique , Tibial Fractures , Humans , Retrospective Studies , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Tibia/diagnostic imaging , Tibia/surgery , Tibia/pathology , Ilizarov Technique/adverse effects , Wound Healing , Treatment Outcome , External FixatorsABSTRACT
Antibacterial hydrogel wound dressings have attracted considerable attention in recent years. However, bacterial infections can occur at any point during the wound-healing process. There is a demand for hydrogels that possess on-demand antibacterial and excellent wound repair properties. Herein, we report a near-infrared (NIR)-light-responsive indocyanine green (ICG)-loaded polydopamine (PDA)-mediated graphene oxide (PGO) and amorphous calcium phosphate (CaP)-incorporated poly(vinyl alcohol) (PVA) hydrogel using a mussel-inspired approach. PGO was reduced by PDA, which endowed the hydrogel with electroactivity and provided abundant sites for loading ICG. Amorphous CaP was formed in situ in the PVA hydrogel to enhance its mechanical properties and biocompatibility. Taking advantage of the high photothermal and photodynamic efficiency of ICG-PGO, the ICG-PGO-CaP-PVA hydrogel exhibited fascinating on-demand antibacterial activity through NIR light irradiation. Moreover, the thermally induced gel-sol conversion of PVA accelerated the release of Ca ions and allowed the hydrogel to adapt to irregular wounds. Meanwhile, PGO endows the hydrogel with conductivity and cell affinity, which facilitate endogenous electrical signal transfer to control cell behavior. In vitro and in vivo studies demonstrated that the ICG-PGO-CaP-PVA hydrogel exhibited a strong tissue repair activity under NIR light irradiation. This mussel-inspired strategy offers a novel way to design hydrogel dressings for wound healing.
Subject(s)
Hydrogels , Indoles , Hydrogels/pharmacology , Indoles/pharmacology , Indocyanine Green , Anti-Bacterial Agents/pharmacologyABSTRACT
The study explored the methods of determining the diameter of clear optic of intraocular lenses by analyzing the design principles and influencing factors of clear optic. Measure and compare the clear optic diameters of intraocular lenses from -10.0 D to 36.0 D respectively. The measurement results of the two methods have good consistency and can be used in the measurement of clear optic. But considering the accuracy and convenience of actual measurement, profile projector measurement principle is more suitable for conventional mass production testing. The Schlieren technique method can provide more useful information in product development and feature description stage, and can be used as an auxiliary verification method for clear optic diameter measurement.
Subject(s)
Lenses, Intraocular , Eye , Optics and Photonics , Prosthesis DesignABSTRACT
As a kind of class II medical device, medical optical radiation protective eyewears should meet the requirements of safety and effectiveness. In this study, the evaluation system of medical optical radiation protective eyewears is established. Combined with the medical device registration unit division guidelines, the classification method of medical optical radiation protective eyewears is given. Medical optical radiation protective eyewears are not only assembled spectacles, but also have special optical radiation protection performance. The performance evaluation method of medical optical radiation protective eyewears and the evaluation method of shelf life for medical optical radiation protective eyewears are given.
Subject(s)
Radiation ProtectionABSTRACT
Ovarian cancer is a common cancer affecting women with high morbidity and mortality globally. Circular RNAs (circRNAs) have been found play vital roles in multifarious cancers, including OC. This study aims to explore the biological role and underlying mechanism of circ_0072995 in OC progression. Circ_0072995 was upregulated in OC tissues and cells in a stable structure. Functional experiments indicated that circ_0072995 knockdown suppressed cell proliferation, migration, invasion and accelerated cell apoptosis of OC cells. Mechanistically, miR-122-5p was a direct target of circ_0072995, and its knockdown reversed the effects of circ_0072995 silence on inhibition of OC cell progression. Meanwhile, SLC1A5 was a downstream target gene of miR-122-5p, and miR-122-5p overexpression inhibited the progression of OC cells by targeting SLC1A5. Moreover, circ_0072995 positively regulated SLC1A5 expression via sponging miR-122-5p. Circ_0072995 could play oncogenic role in tumorigenesis and malignant development of OC by regulating miR-122-5p/SLC1A5 axis, providing a novel approach for OC treatment.
Subject(s)
Amino Acid Transport System ASC/genetics , MicroRNAs , Minor Histocompatibility Antigens/genetics , Ovarian Neoplasms , RNA, Circular/genetics , Cell Line, Tumor , Female , Humans , MicroRNAs/genetics , Oncogenes , Ovarian Neoplasms/geneticsABSTRACT
The Huntington's disease (HD) is still a devastating neurological disease without a specific cure. In this report, the peripheral blood mononuclear cells (PBMCs) from two members of a HD family from Southwestern China were reprogrammed into hiPSC lines by an episomal and non-integrating Sendai virus delivery method. The induced HD-hiPSC lines, SPPHi001-A and SPPHi002-A, were expanded and validated for their stem cell-like pluripotency, normal karyotyping, and capability of in vitro differentiation into three germ-layers. These newly generated HD hiPSC lines from Chinese HD patients enable us to further elucidate the mechanism of HD and discover its specific treatment.
ABSTRACT
Wireless fingerprinting localization (FL) systems identify locations by building radio fingerprint maps, aiming to provide satisfactory location solutions for the complex environment. However, the radio map is easy to change, and the cost of building a new one is high. One research focus is to transfer knowledge from the old radio maps to a new one. Feature-based transfer learning methods help by mapping the source fingerprint and the target fingerprint to a common hidden domain, then minimize the maximum mean difference (MMD) distance between the empirical distributions in the latent domain. In this paper, the optimal transport (OT)-based transfer learning is adopted to directly map the fingerprint from the source domain to the target domain by minimizing the Wasserstein distance so that the data distribution of the two domains can be better matched and the positioning performance in the target domain is improved. Two channel-models are used to simulate the transfer scenarios, and the public measured data test further verifies that the transfer learning based on OT has better accuracy and performance when the radio map changes in FL, indicating the importance of the method in this field.
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The article is to study the objective evaluation method of the imaging quality of aspheric intraocular lens with different design concepts by establishing the model eye which is close to the actual corneal spherical aberration characteristics. Combined with the research data of corneal spherical aberration, the simulated cornea corresponding to Zernike c(4,0) coefficient 0.00 µm, 0.10 µm, 0.20 µm and 0.28 µm was established respectively. The optical quality of the measured simulated corneal lenses basically reached the theoretical design effect, and the deviation between the MTF value and the theoretical design value was equivalent to the MTF test repeatability. The establishment of model eye for artificial lens provides a research tool for the evaluation of aspheric intraocular lens imaging quality.
Subject(s)
Lens Implantation, Intraocular , Lenses, Intraocular , Cornea , Lenses, Intraocular/standards , Quality Control , Vision, OcularABSTRACT
Although antiviral drugs are available for the treatment of influenza infection, it is an urgent requirement to develop new antiviral drugs regarding the emergence of drug-resistant viruses. The nucleoprotein (NP) is conserved among all influenza A viruses (IAVs) and has no cellular equivalent. Therefore, NP is an ideal target for the development of new IAV inhibitors. In this study, we identified a novel anti-influenza compound, ZBMD-1, from a library of 20,000 compounds using cell-based influenza A infection assays. We found that ZBMD-1 inhibited the replication of H1N1 and H3N2 influenza A virus strains in vitro, with an IC50 ranging from 0.41-1.14 µM. Furthermore, ZBMD-1 inhibited the polymerase activity and specifically impaired the nuclear export of NP. Further investigation indicated that ZBMD-1 binds to the nuclear export signal 3 (NES3) domain and the dimer interface of the NP pocket. ZBMD-1 also protected mice that were challenged with lethal doses of A/PR/8/1934 (H1N1) virus, effectively relieving lung histopathology changes, as well as strongly inhibiting the expression of pro-inflammatory cytokines/chemokines, without inducing toxicity effects in mice. These results suggest that ZBMD-1 is a promising anti-influenza compound which can be further investigated as a useful strategy against IAVs in the future.
Subject(s)
Active Transport, Cell Nucleus/drug effects , Antiviral Agents/pharmacology , Influenza A virus/drug effects , RNA-Binding Proteins/antagonists & inhibitors , Viral Core Proteins/antagonists & inhibitors , Virus Replication/drug effects , Animals , Humans , Influenza A Virus, H1N1 Subtype/drug effects , Influenza A Virus, H1N1 Subtype/metabolism , Influenza A Virus, H3N2 Subtype/drug effects , Influenza A Virus, H3N2 Subtype/metabolism , Influenza A virus/metabolism , Inhibitory Concentration 50 , Male , Mice, Inbred BALB C , Nucleocapsid Proteins , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/virology , RNA-Binding Proteins/metabolism , Small Molecule Libraries/pharmacology , Viral Core Proteins/metabolismABSTRACT
Three series of substituted pyrimidines were designed and synthesized. All target compounds were screened for kinase inhibitory activities against PI3Kα, and most IC50 values were found within the nanomolar range. Compounds 5d and 5p displayed comparable activities relative to the positive control 5a. 5p also showed a significant isozyme selectivity (PI3Kß/α). Furthermore, the cytotoxicities of these pyrimidines against human cancer cell lines were evaluated and the in vivo anticancer effect of 5d was also tested.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Design , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Phosphatidylinositol 3-Kinase/metabolism , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity RelationshipABSTRACT
BACKGROUND: Abundant evidence from epidemiological and clinical studies has proven that diabetes mellitus (DM) is correlated with an increased incidence of dementia and Alzheimer's disease (AD). Insulin resistance is considered to play an important role in the associations between DM and dementia. However, whether insulin sensitizer drugs are effective in preventing dementia still remains unclear. METHODS: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies that reported about the associations between insulin sensitizers and the incidence of dementia. The included studies were reviewed, and a meta-analysis was performed using STATA to determine the combined relative risk (RR) for the incidence of dementia when using insulin sensitizers. Subgroup analysis and meta regression were also conducted. RESULTS: In total, nine comparisons out of six studies were qualified for inclusion, and data from 544,093 participants were evaluated. The results of the meta-analysis revealed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015) for the incidence of dementia when using insulin sensitizers. The incidence rate of dementia was reduced with either metformin (RR 0.79, 95% CI 0.62-1.01, p = 0.064) or thiazolidinediones (RR 0.75, 95% CI 0.56-1.00, p = 0.050), both with a marginal trend toward significance. CONCLUSIONS: The results indicate that insulin sensitizer drugs might provide protection against incident dementia. Controlled studies with large samples should be conducted to further confirm these conclusions and provide information for clinical strategies.
Subject(s)
Dementia , Hypoglycemic Agents/pharmacology , Insulin Resistance/physiology , Metformin/pharmacology , Aged , Dementia/epidemiology , Dementia/prevention & control , Humans , Risk Factors , Thiazolidinediones/pharmacologyABSTRACT
There are numerous biologically active substances with novel structures and unique physiological functions in marine organisms. These substances are important sources of new lead compounds. Pelorol is a natural product isolated from marine organisms that possesses a novel structure with high bioactivity. In this paper, the synthesis of pelorol has been completed, and the synthesis of some intermediates has been optimized and scaled up. Five pelorol analogs have also been prepared. Preliminary biological activity testing demonstrated that compounds 5 and 6 might be potential lead compounds for cancer therapy.
Subject(s)
Biological Products/chemistry , Biological Products/pharmacology , Phosphoinositide-3 Kinase Inhibitors , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacology , Aquatic Organisms/chemistry , HeLa Cells , Humans , K562 Cells , MCF-7 Cells , U937 CellsABSTRACT
BACKGROUND: This study aimed to study the dynamic changes of B cell lymphoma/leukaemia 2 (Bcl-2), caspase-3 and heat shock response protein 70 (Hsp70) in blood serum following acute middle cerebral artery occlusion (MCAO) in rats. METHODS: Occlusion of the cerebral artery was accomplished via the intraluminal filament, followed by the TTC staining evaluation and neurological deficit score. Meanwhile, the blood serum was extracted at 0.5, 2, 3, 6, 12 and 24 hours and 3 and 7 days after surgery. The serum expression levels of caspase-3, Bcl-2 and Hsp70 were determined using ELISA kits according to the manufacturer's protocols. Expression correlations between Bcl-2 and Hsp70, Bcl-2 and caspase-3 were analysed using correl function. A rats model was successfully established. RESULTS: The expression of all three indexes, including Bcl-2, caspase-3 and Hsp70, was significantly increased after surgery (p < 0.05) and peaked at 12, 24 and 24 hours, respectively. Up to 7 days after MCAO, the expression levels of these proteins recovered to the control levels. There were positive correlations between the expressions of Bcl-2 and Hsp70, Bcl-2 and caspase-3 (p < 0.05). CONCLUSIONS: The altered expressions of these proteins in the blood serum may result in many symptoms in acute ischaemic stroke individuals.
Subject(s)
Caspase 3/biosynthesis , HSP70 Heat-Shock Proteins/biosynthesis , Infarction, Middle Cerebral Artery/blood , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Animals , Apoptosis/physiology , Brain Ischemia/blood , Brain Ischemia/metabolism , Caspase 3/blood , Disease Models, Animal , Female , HSP70 Heat-Shock Proteins/blood , Infarction, Middle Cerebral Artery/pathology , Male , Proto-Oncogene Proteins c-bcl-2/blood , Random Allocation , Rats , Stroke/blood , Stroke/pathologyABSTRACT
We present a simple and fast regularized frequency-stabilizing method for single open- or closed-fringe interferogram demodulation. The proposed method recovers the phase maps of interferograms by establishing a cost function, according to prior knowledge. Because only the phase field to be estimated is employed in the cost function, the optimization process is fast. Moreover, the recovered phase is continuous, and no further phase unwrapping is necessary. Computer simulation and experimental results have demonstrated both the rapidity and the efficiency of the method.
ABSTRACT
The two-dimensional regularized phase-tracking (RPT) technique is one of the most powerful approaches to demodulate a single interferogram with either open or closed fringes. However, it often fails in the cases of complex interferograms and needs well-defined scanning strategies. An improved algorithm based on the RPT is presented in this paper. We use a paraboloid phase model to approximate the phase function and modify the cost functional to search the smoothest phase solutions in the function space C(2). With these modifications, the phase tracker preserves the robustness of the RPT while at the same time it is no more sensitive to stationary points and is capable of demodulating complex interferograms with arbitrary scanning schemes. Moreover, the phase reconstructed by the proposed algorithm is normally more accurate than that of the RPT both for noiseless and noisy interferograms under the same conditions. Computer simulations and experimental results are both presented.
ABSTRACT
Nonnull test is often adopted for aspheric testing. But due to its violation of null condition, the testing rays will follow different paths from the reference and aberrations from the interferometer will not cancel out, leading to widely difference between the obtained surface figure and that of the real, which is called the Retrace-error accordingly. In this paper, retrace error of nonnull aspheric testing is analyzed in detail with conclusions that retrace error has much to do with the aperture, F number and surface shape error of the aspheric under test. Correcting methods are proposed according to the manner of the retrace errors. Both computer simulation and experimental results show that the proposed methods can correct the retrace error effectively. The analysis and proposed correction methods bring much to the application of nonnull aspheric testing.