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Among the various kinds of spin defects in hexagonal boron nitride (hBN), the negatively charged boron vacancy (V B - ) spin defect that can be site-specifically generated is undoubtedly a potential candidate for quantum sensing, but its low quantum efficiency restricts its practical applications. Here, we demonstrate a robust enhancement structure called reflective dielectric cavity (RDC) with advantages including easy on-chip integration, convenient processing, low cost and suitable broad-spectrum enhancement for V B - defects. In the experiment, we used a metal reflective layer under the hBN flakes, filled with a transition dielectric layer in the middle, and adjusted the thickness of the dielectric layer to achieve the best coupling between RDC and spin defects in hBN. A remarkable 11-fold enhancement in the fluorescence intensity of V B - spin defects in hBN flakes can be achieved. By designing the metal layer into a waveguide structure, high-contrast optically detected magnetic resonance (ODMR) signal (∼21%) can be obtained. The oxide layer of the RDC can be used as the integrated material to implement secondary processing of micro-nano photonic devices, which means that it can be combined with other enhancement structures to achieve stronger enhancement. This work has guiding significance for realizing the on-chip integration of spin defects in two-dimensional materials.

Hexagonal boron nitride (hBN) is a remarkable two-dimensional (2D) material that hosts solid-state spins and has great potential to be used in quantum information applications, including quantum networks. However, in this application, both the optical and spin properties are crucial for single spins but have not yet been discovered simultaneously for hBN spins. Here, we realize an efficient method for arraying and isolating the single defects of hBN and use this method to discover a new spin defect with a high probability of 85%. This single defect exhibits outstanding optical properties and an optically controllable spin, as indicated by the observed significant Rabi oscillation and Hahn echo experiments at room temperature. First principles calculations indicate that complexes of carbon and oxygen dopants may be the origin of the single spin defects. This provides a possibility for further addressing spins that can be optically controlled., (© 2023. The Author(s).)

Ice on aircraft wing changes the aircraft aerodynamic shape, and has negative effects on flight dynamic characteristics, seriously threatening flight safety. Plasma ice shape regulation is a new de-icing method. Plasma actuator produces an apparent thermal effect, which is designed to dissolve the continuous ice into intermittent ice pieces. How to achieve the optimal regulation ice shape to improve the flight dynamics characteristics under icing conditions is a technical problem restricting the application of this method. A simulation ice shape based on previous ice tunnel experiments and a scale model of swept wing were established. The aerodynamic parameters of no ice, full ice, and two regulation ice schemes were obtained based on wind tunnel. Six degrees of freedom flight dynamics model was established, and flight simulation had been carried out. As the analysis of trim characteristics, dynamic stability, and maneuverability, flight dynamics characteristics were better improved when the ratio of ice width to the mean aerodynamic chord was 0.15. The evaluation method of plasma ice shape regulation schemes was proposed. The proposed method, which can compare and optimize the arrangement of plasma actuators, realized the optimal regulation ice shape on the premise of balancing flight safety and energy consumption., (© 2022. The Author(s).)

Ethnopharmacological Relevance: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment., Aim of the Study: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model., Materials and Methods: The main compounds in CBP extract were analyzed by UPLC, 1 H-NMR and 13 C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H 2 O 2 -treated SRA01/04 lens epithelial cells., Results: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H 2 O 2 -induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins., Conclusion: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Retinitis pigmentosa (RP) is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes blindness. However, the pathogenesis of RP is still unclear, making it difficult to establish satisfying treatments. Evidence have been found to support the theory that vascular dysfunction is associated with the progression of RP. Optical coherence tomography angiography (OCTA) is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature non-invasively. Advances in OCTA have opened a window for in-depth understanding of RP pathogenesis. Here, we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP, which includes four stages and two important key factors, vascular dysfunction and microglia activation. Further, we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the hypothesis. The final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis., (International Journal of Ophthalmology Press.)

SF3B1 mutations occur in many cancers, and the highly conserved His662 residue is one of the hotspot mutation sites. To address effects on splicing and development, we constructed strains carrying point mutations at the corresponding residue His698 in Drosophila using the CRISPR-Cas9 technique. Two mutations, H698D and H698R, were selected due to their frequent presence in patients and notable opposite charges. Both the sf3b1-H698D and-H698R mutant flies exhibit developmental defects, including less egg-laying, decreased hatching rates, delayed morphogenesis and shorter lifespans. Interestingly, the H698D mutant has decreased resistance to fungal infection, while the H698R mutant shows impaired climbing ability. Consistent with these phenotypes, further analysis of RNA-seq data finds altered expression of immune response genes and changed alternative splicing of muscle and neural-related genes in the two mutants, respectively. Expression of Mef2-RB, an isoform of Mef2 gene that was downregulated due to splicing changes caused by H698R, partly rescues the climbing defects of the sf3b1-H698R mutant. Lariat sequencing reveals that the two sf3b1-H698 mutations cause aberrant selection of multiple intronic branch sites, with the H698R mutant using far upstream branch sites in the changed alternative splicing events. This study provides in vivo evidence from Drosophila that elucidates how these SF3B1 hotspot mutations alter splicing and their consequences in development and in the immune system., Competing Interests: The authors have declared that no competing interests exist.

Background: Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology., Methods: Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets., Results: 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes., Conclusion: AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Qi Jin et al.)

Background: The addition of bevacizumab to neoadjuvant chemotherapy improves the pathological complete response rate of human epidermal growth factor 2 (HER2)-negative breast cancer patients. However, the characteristics of adverse events associated with the use of bevacizumab should receive more attention from clinicians. Objective: This meta-analysis aimed to detect the adverse events of adding bevacizumab to neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in HER2-negative breast cancer patients. Methods: PubMed, Cochrane Library, Web of Science, and EMBASE databases were systematically accessed to find eligible studies from January 1, 2000, to October 20, 2019. Reference lists were searched for additional studies. Pooled risk ratios for adverse events of bevacizumab were meta-analyzed. Results: Overall, 6 of 829 initially identified studies met the inclusion criteria, with 4681 patients randomized (2321 in the bevacizumab plus neoadjuvant chemotherapy group and 2360 in the neoadjuvant chemotherapy group). The incidence of grade ≥3 hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia significantly increased in patients treated with bevacizumab plus neoadjuvant chemotherapy. However, adding bevacizumab to neoadjuvant chemotherapy was not associated with increasing the incidences of grade ≥3 proteinuria, dyspnea, heart failure, peripheral neurotoxicity, thrombosis, thrombocytopenia, fatigue, leucopenia, vomiting, nausea, and diarrhea. Conclusion and Relevance: Adding bevacizumab to neoadjuvant chemotherapy to treat HER2-negative breast cancer patients increased adverse events. However, most adverse events are clinically manageable. Patients, therefore, need to be monitored carefully for hypertension, left-ventricular dysfunction, mucositis, febrile neutropenia, infection, pain, hand-foot syndrome, hemorrhage, and neutropenia when treated with bevacizumab and neoadjuvant chemotherapy simultaneously.

Artemisinin, also named qinghaosu , is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant ( Artemisia annua ), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives (artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasite-related infections. Recently, this long-considered anti-malarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future., (International Journal of Ophthalmology Press.)

Artemisinin, also called qinghaosu, is originally derived from the sweet wormwood plant (Artemisia annua), which is used in traditional Chinese medicine. Artemisinin and its derivatives (artemisinins) have been widely used for many years as anti-malarial agents, with few adverse side effects. Interestingly, evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria, including cancers, inflammatory diseases, and autoimmune disorders. Neurodegeneration is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions, whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders, including Alzheimer's disease. Recently discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation, inflammation, and amyloid beta protein (Aβ). In this review, we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities, suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders., Competing Interests: None

Calcium activated Chloride Channel A4 (CLCA4), as a tumor suppressor, was reported to contribute to the progression of several malignant tumors, yet little is known about the significance of CLCA4 in invasion and prognosis of hepatocellular carcinoma (HCC). CLCA4 expression was negatively correlated with tumor size, vascular invasion and TNM stage. Kaplan-Meier analysis showed that CLCA4 was an independent predictor for overall survival (OS) and time to recurrence (TTR). In addition, CLCA4 status could act as prognostic predictor in different risk of subgroups. Moreover, combination of CLCA4 and serum AFP could be a potential predictor for survival in HCC patients. Furthermore, CLCA4 may inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling. Knockdown of CLCA4 significantly increased the migration and invasion of HCC cells and changed the expression pattern of EMT markers and PI3K/AKT phosphorylation. An opposite expression pattern of EMT markers and PI3K/AKT phosphorylation was observed in CLCA4-transfected cells. Additionally, immunohistochemistry and RT-PCR results further confirmed this correlation. Taken together, CLCA4 contributes to migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favourable prognosis of HCC. CLCA4/AFP expression may help to distinguish different risks of HCC patients after hepatectomy.

Purpose: To investigate the occurrence of postoperative malocclusion of patients with temporomandibular joint disc repositioning and the necessity of postoperative orthodontic treatment., Methods: One hundred and eight patients who received temporomandibular joint disc repositioning from 2010.10 to 2015.10 were selected in this study. The patients' occlusion was recorded preoperatively and postoperatively. All patients received functional appliance or orthodontic treatment after surgery. The occlusion and the relative position of the articular disc and condyle were evaluated at regular follow-up., Results: Postoperative malocclusion occurred in all patients. The use of functional appliance for 3-6 months may decrease the proportion of malocclusion. After orthodontic treatment, all patients had a complete recovery of malocclusion and remained good articular disc and condyle relationship during long term follow-up., Conclusions: Postoperatively malocclusion may occur after temporomandibular joint disc repositioning, and the use of functional appliance and orthodontic treatment are strongly recommended to retain good articular disc and condyle relationship.

Purpose: The purpose of this study was to introduce a minimally invasive bone splitting technique which is suitable for cases with missing anterior teeth and obvious depression of alveolar bone in labial side, and to evaluate its clinical results., Methods: Minimally invasive bone splitting technique was used in 8 healthy adults with bone defects in the aesthetic zone. The labial alveolar bone incisions were confined around the bone defects which were smaller than traditional incisions. The other procedures were the same as conventional bone splitting technique. Cone-beam CT (CBCT) for missing anterior teeth was taken before surgery, after the surgery and 6 months after surgery and alveolar bone height and width were recorded with landmark identification designed by ourselves in this study. The data were analyzed with SPSS 21.0 software package for paired t test., Results: Paired t test indicated that after surgery and six months after surgery, the labial bone defect was significant improved (P<0.05), but the height of the alveolar ridge bone didn't increase significantly (P>0.05) while the width of the alveolar ridge bone significant improved (P>0.05)., Conclusions: This minimally invasive technique can achieve good clinical results for not only intact labial alveolar ridge bones but also good bone grafts, which is beneficial to implantation and prosthetic aesthetics. The long-term outcome needs to be observed.

Globins are globular proteins for either transport or storage of oxygen which are critical for cellular metabolism. Four globins have been identified in rodent and human brains. Among them, neuroglobin, cytoglobin and hemoglobin chains are constitutively expressed in normal brain, while myoglobin is only expressed in some neurological disorders. Studies on the molecular structure, expression and functional features of these brain globins indicated that they may play crucial roles in maintenance of neural cell survival and activity, including neurons and astrocytes. Their regulation in neurological disorders may help thoroughly understand initiation and progression of ischemia, Alzheimer's disease and glioma, etc . Elucidation of the brain globin functions might remarkably improve medical strategies that sustain neurological homeostasis and treat neurological diseases. Here the expression pattern and functions of brain globins and their involvement in neurological disorders are reviewed., Competing Interests: The authors declare no conflicts of interest.

Objective: This study was aimed to confirm whether I62V and Y402H polymorphisms of complement factor H (CFH) were risk factors for age-related macular degeneration (AMD)., Method: 109 AMD patients and 165 AMD-free controls were enrolled in the study. The I62V and Y402H polymorphisms were analyzed by polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by the X2 test to assess the relationship of I62V and Y402H polymorphisms with AMD risk. Analysis of haplotype and stratification by age and smoking status was conducted as well., Results: AA genotype and A allele of I62V polymorphism was significantly associated with increased risk for AMD (OR=3.75, 95% CI=1.70-8.30; OR=1.64, 95% CI=1.14-2.36). For Y402H polymorphism, CT genotype showed strong effects on the occurrence of AMD (OR=2.10, 95% CI=1.04-4.27). Moreover, C allele was also a risk factor for AMD (OR=1.95, 95% CI=1.02-3.72). The haplotypes analysis suggested that the risk for AT haplotype carriers was high, compared with GT haplotype (OR=3.91, 95% CI=2.58-5.94). In addition, we found that smoking status could affect the genotype distribution of Y402H polymorphism (P<0.05)., Conclusions: Our results revealed that CFH polymorphisms I62V and Y402H might be associated with the susceptibility to AMD in Chinese population.

Aims: Intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) had been documented to improve functional outcome after ischemic stroke. However, the timing and appropriate cell number of transplantation to achieve better outcome after an episode of stroke remain further to be optimized., Methods: To determine the optimal conditions, we transplanted different concentrations of BMSCs at different time points in a rat model of ischemic stroke. Infarction volume and neurological behavioral tests were performed after ischemia., Results: We found that transplantation of BMSCs at 3 and 24 h, but not 7 days after focal ischemia, significantly reduced the lesion volume and improved motor deficits. We also found that transplanted cells at 1 × 10(6) to 10(7) , but not at 1 × 10(4) to 10(5) , significantly improved functional outcome after stroke. In addition to inhibiting macrophages/microglia activation in the ischemic brain, BMSC transplantation profoundly reduced infiltration of gamma delta T (γδT) cells, which are detrimental to the ischemic brain, and significantly increased regulatory T cells (Tregs), along with altered Treg-associated cytokines in the ischemic brain., Conclusions: Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation., (© 2014 John Wiley & Sons Ltd.)

This study assesses the effect of low intensity pulsed ultrasound (LIPUS) on new bone formation during mandibular distraction osteogenesis (DO) in rabbits. 24 rabbits underwent DO on the right side of the mandible. 12 rabbits received a daily 20-min LIPUS (1.5 MHz, 30 mW/cm2) treatment on the first day of the distraction until they were killed at week 0 (immediately after the distraction), week 2 and week 4 after the distraction. Four rabbits were killed at each time point. The other 12 rabbits followed the same protocol without the ultrasound treatment. A plain radiography, a micro-CT scan, a microhardness test and a histological examination were used to evaluate new bone formation in the distraction gap. At week 0 and week 2 after the distraction, the treatment groups showed higher radiopacity and microhardness (p<0.05), and more bone formation was detected by the histological examination. At week 4 after the distraction, there was no statistical difference between the two groups. In this study, LIPUS accelerated new bone formation during the distraction period and 2 weeks after the distraction, which implies that the effective time for using LIPUS is in the early stage of DO., (Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Grb2 (growth-factor receptor-bound protein-2) is a signaling adaptor that interacts with numerous receptors and intracellular signaling molecules. However, its role in B-cell development and function remains unknown. Here we show that ablation of Grb2 in B cells results in enhanced B-cell receptor signaling; however, mutant B cells do not form germinal centers in the spleen after antigen stimulation. Furthermore, mutant mice exhibit defects in splenic architecture resembling that observed in B-cell-specific lymphotoxin-β-deficient mice, including disruption of marginal zone and follicular dendritic cell networks. We find that grb2(-/-) B cells are defective in lymphotoxin-β expression. Although lymphotoxin can be up-regulated by chemokine CXCL13 and CD40 ligand stimulation in wild-type B cells, elevation of lymphotoxin expression in grb2(-/-) B cells is only induced by anti-CD40 but not by CXCL13. Our results thus define Grb2 as a nonredundant regulator that controls lymphoid follicle organization and germinal center reaction. Loss of Grb2 has no effect on B-cell chemotaxis to CXCL13, indicating that Grb2 executes this function by connecting the CXCR5 signaling pathway to lymphotoxin expression but not to chemotaxis.

Background: CC chemokine receptor 3 (CCR3), expressed on some inflammatory cells, is a member of the chemokine receptor family. Its ligand is eotaxin/CCL11. In this research, we studied the expression and function of CCR3 induced by interleukin-2 (IL-2) and interleukin-4 (IL-4) on human germinal centre (GC) B cells., Methods: Cells isolated from human tonsils were stimulated with IL-2 or/and IL-4 followed by bonding with eotaxin/CCL11. Flow cytometry was used to detect expression of CCR3 on GC B cells and apoptosis of GC B cells. Real time quantitative reverse transcription polymerase chain reaction and Northern blot assays were used to analyse the CCR3 mRNA expressed in the GC B cells. Chemotaxis and adhesion assays were used to determine the effect of eotaxin/CCL11 ligand bonded to CCR3 on GC B cells., Results: There was no CCR3 expression on human freshly isolated GC B cells. The combination IL-2 and IL-4 could upregulate CCR3 mRNA and protein expression on GC B cells. Eotaxin could not induce GC B cell chemotaxis and adhesion but triggered apoptosis of GC B cells., Conclusion: IL-2 and IL-4 together induced expression of CCR3 on GC B cells, and the receptor acted as a death receptor.

Aim: To study the pharmcokinetics of fluconazole (FCZ) in the aqueous humors and tears of New Zealand white rabbits following topically applied in-situ-forming gels of 0.5% FCZ (ISG-FCZ) and 0.5% FCZ eye drops to rabbit eyes., Methods: The rabbit tears and aqueous humors were obtained and quantified at different times after topically applying single dose of ISG-FCZ and FCZ eye drops to the rabbit eyes. The drug levels were assayed by megabore capillary gas-liquid chromatography with nitrogen-selective detector. The pharmacokinetic parameters were calculated with nonlinear least square method with computer., Results: FCZ concentrations in rabbit tears within 180 min after applying ISG-FCZ were found to be significantly higher compared with those of FCZ eye drops. The FCZ levels in the aqueous at 10, 30, 60, 90 and 120 min after applying ISG-FCZ are significantly higher compared with FCZ eye drops. The time for arriving peak concentration (Tmax) and the area under concentration (AUC)-time curve as well as the half-life (T1/2) of FCZ in rabbit aqueous humors were markedly higher after application of ISG-FCZ. The peak levels in the aqueous humors showed no difference between the two groups., Conclusion: The ISG-FCZ, which upon exposure to physiological conditions will shift the gel phase, can significantly extend FCZ release and increase the precorneal residence time of the drug, thus enhance ocular bioavailability compared with FCZ eye drops.