Ultracompact high-efficiency polarising beam splitter based on silicon nanobrick arrays

Since the transmission of anisotropic nano-structures is sensitive to the polarisation of an incident beam, a novel polarising beam splitter (PBS) based on silicon nanobrick arrays is proposed. With careful design of such structures, an incident beam with polarisation direction aligned with the long axis of the nanobrick is almost totally reflected (~98.5%), whilst that along the short axis is nearly totally transmitted (~94.3%). More importantly, by simply changing the width of the nanobrick we can shift the peak response wavelength from 1460 nm to 1625 nm, covering S, C and L bands of the fiber telecommunications windows. The silicon nanobrick-based PBS can find applications in many fields which require ultracompactness, high efficiency, and compatibility with semiconductor industry technologies

Validation of the Alzheimer's disease-resemblance atrophy index in classifying and predicting progression in Alzheimer's disease

BACKGROUND: Automated tools for characterising dementia risk have the potential to aid in the diagnosis, prognosis, and treatment of Alzheimer’s disease (AD). Here, we examined a novel machine learning-based brain atrophy marker, the AD-resemblance atrophy index (AD-RAI), to assess its test-retest reliability and further validate its use in disease classification and prediction. METHODS: Age- and sex-matched 44 probable AD (Age: 69.13 ± 7.13; MMSE: 27–30) and 22 non-demented control (Age: 69.38 ± 7.21; MMSE: 27–30) participants were obtained from the Minimal Interval Resonance Imaging in Alzheimer’s Disease (MIRIAD) dataset. Serial T1-weighted images (n = 678) from up to nine time points over a 2-year period, including 179 pairs of back-to-back scans acquired on same participants on the same day and 40 pairs of scans acquired at 2-week intervals were included. All images were automatically processed with AccuBrain® to calculate the AD-RAI. Its same-day repeatability and 2-week reproducibility were first assessed. The discriminative performance of AD-RAI was evaluated using the receiver operating characteristic curve, where DeLong’s test was used to evaluate its performance against quantitative medial temporal lobe atrophy (QMTA) and hippocampal volume adjusted by intracranial volume (ICV)-proportions and ICV-residuals methods, respectively (HVR and HRV). Linear mixed-effects modelling was used to investigate longitudinal trajectories of AD-RAI and baseline AD-RAI prediction of cognitive decline. Finally, the longitudinal associations between AD-RAI and MMSE scores were assessed. RESULTS: AD-RAI had excellent same-day repeatability and excellent 2-week reproducibility. AD-RAI’s AUC (99.8%; 95%CI = [99.3%, 100%]) was equivalent to that of QMTA (96.8%; 95%CI = [92.9%, 100%]), and better than that of HVR (86.8%; 95%CI = [78.2%, 95.4%]) or HRV (90.3%; 95%CI = [83.0%, 97.6%]). While baseline AD-RAI was significantly higher in the AD group, it did not show detectable changes over 2 years. Baseline AD-RAI was negatively associated with MMSE scores and the rate of the change in MMSE scores over time. A negative longitudinal association was also found between AD-RAI values and the MMSE scores among AD patients CONCLUSIONS: The AD-RAI represents a potential biomarker that may support AD diagnosis and be used to predict the rate of future cognitive decline in AD patients

Effects of Low-Light Environments on the Growth and Physiological and Biochemical Parameters of <i>Indocalamus</i> and Seasonal Variations in Leaf Active Substance Contents

Indocalamus, characterized by its expansive leaves, low height, strong reproductive capacity, and abundant bioactive compounds, has extensive utility in the realms of food processing, the manufacturing of packaging materials, and the advancement of novel pharmaceuticals. Two light environments, CK (100% full light) and ST (50% full light), were established to explore the effects of low-light environments on the reproductive ability, morphological characteristics, photosynthetic properties, and leaf active substances of 14 Indocalamus species. The findings revealed that in comparison to the CK treatment, for 14 species of Indocalamus under the ST treatment, (1) the diameter, single leaf area, and leaf area index increased by 8.27%, 8.14%, and 17.88%, respectively; (2) the net photosynthetic rate decreased by 15.14%, and the total chlorophyll contents increased by 20.25%; and (3) the total flavonoid contents increased by 18.28% in autumn, the total polyphenol contents increased by 48.96% in spring, and the total polysaccharide contents increased by 31.44% and 30.81% in summer and winter, respectively. In summary, Indocalamus are adapted to survive in low-light environments; the growth and physiological indices differ significantly between the two light environments, and the low-light environment can effectively promote the growth and development of the leaves. Furthermore, the leaves are rich in flavonoids, polyphenols, polysaccharides, and active substances, which are affected by the light intensity and the season to varying degrees, and autumn and winter are the best times for harvesting the leaves. The leaves of I. hunanensis and I. lacunosus are richest in flavonoids and polyphenols, while the leaves of I. kunmingensis cv. fuminer are richest in polysaccharides. The main findings of this study demonstrate that Indocalamus has strong shade tolerance and tremendous leaf value, laying the foundation for broadening the application of their leaves and for their industrial development in understory composite planting systems

EPO promotes bone repair through enhanced cartilaginous callus formation and angiogenesis.

Erythropoietin (EPO)/erythropoietin receptor (EPOR) signaling is involved in the development and regeneration of several non-hematopoietic tissues including the skeleton. EPO is identified as a downstream target of the hypoxia inducible factor-α (HIF-α) pathway. It is shown that EPO exerts a positive role in bone repair, however, the underlying cellular and molecular mechanisms remain unclear. In the present study we show that EPO and EPOR are expressed in the proliferating, pre-hypertrophic and hypertrophic zone of the developing mouse growth plates as well as in the cartilaginous callus of the healing bone. The proliferation rate of chondrocytes is increased under EPO treatment, while this effect is decreased following siRNA mediated knockdown of EPOR in chondrocytes. EPO treatment increases biosynthesis of proteoglycan, accompanied by up-regulation of chondrogenic marker genes including SOX9, SOX5, SOX6, collagen type 2, and aggrecan. The effects are inhibited by knockdown of EPOR. Blockage of the endogenous EPO in chondrocytes also impaired the chondrogenic differentiation. In addition, EPO promotes metatarsal endothelial sprouting in vitro. This coincides with the in vivo data that local delivery of EPO increases vascularity at the mid-stage of bone healing (day 14). In a mouse femoral fracture model, EPO promotes cartilaginous callus formation at days 7 and 14, and enhances bone healing at day 28 indexed by improved X-ray score and micro-CT analysis of microstructure of new bone regenerates, which results in improved biomechanical properties. Our results indicate that EPO enhances chondrogenic and angiogenic responses during bone repair. EPO's function on chondrocyte proliferation and differentiation is at least partially mediated by its receptor EPOR. EPO may serve as a therapeutic agent to facilitate skeletal regeneration

Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1α in Chondrocytes and Promotes Articular Cartilage Repair.

Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1α) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1α may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1α expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1α in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1α mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2α1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes including Mmp2, Mmp9, Mmp13, Adamts4 and Adamts5 was downregulated following Icariin treatment for 14 days. In a differentiation assay using bone marrow mesenchymal stem cells (MSCs) carrying HIF-1α floxed allele, the promotive effect of Icariin on chondrogenic differentiation is largely decreased following Cre recombinase-mediated deletion of HIF-1α in MSCs as indicated by Alcian blue staining for proteoglycan synthesis. In an alginate hydrogel 3D culture system, Icariin increases Safranin O positive (SO+) cartilage area. This phenotype is accompanied by upregulation of HIF-1α, increased proliferating cell nuclear antigen positive (PCNA+) cell numbers, SOX9+ chondrogenic cell numbers, and Col2 expression in the newly formed cartilage. Coincide with the micromass culture, Icariin treatment upregulates mRNA levels of Sox9, Col2α1, aggrecan and Col10α1 in the 3D cultures. We then generated alginate hydrogel 3D complexes incorporated with Icariin. The 3D complexes were transplanted in a mouse osteochondral defect model. ICRS II histological scoring at 6 and 12 weeks post-transplantation shows that 3D complexes incorporated with Icariin significantly enhance articular cartilage repair with higher scores particularly in selected parameters including SO+ cartilage area, subchondral bone and overall assessment than that of the controls. The results suggest that Icariin may inhibit PHD activity likely through competition for cellular iron ions and therefore it may serve as an HIF-1α activator to promote articular cartilage repair through regulating chondrocyte proliferation, differentiation and integration with subchondral bone formation

Changes and significance of vascular endothelial injury markers in patients with diabetes mellitus and pulmonary thromboembolism

Abstract Background To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). Methods This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). Results Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P  676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. Conclusions Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE

EPO promotes the proliferation of primary chondrocytes.

<p>(A) Examination of mRNA expression of EPOR in chondrocytes by real-time PCR after siRNA mediated knockdown of EPOR. (B) Western blot analysis of EPOR expression in primary chondrocytes with or without siRNA mediated knockdown of EPOR. (C) BrdU incorporation assay in primary chondrocytes with or without siRNA mediated knockdown of EPOR after 48 hours of EPO exposure. Con, non-treatment control. *<i>P</i><0.05; **<i>P</i><0.01; <i>n</i> = 3.</p

EPO improves biomechanical properties during consolidation of bone healing.

<p>Biomechanical parameters including peak load (A), elastic modulus (B), bend strain at maximum (C), and bend strength at maximum (D) were calculated at day 28 post-surgery. Con, non-treatment control. *<i>P</i><0.05; **<i>P</i><0.01, <i>n</i> = 3.</p

EPO stimulates angiogenesis <i>in vitro</i> and <i>in vivo</i>.

<p>(A) Representative images of endothelial sprouting from metatarsal bones of E17.5 embryos which were treated with different conditions as indicated. The endothelial sprouting was visualized by immunostaining for CD31. VEGF was used as positive control. Con, non-treatment control. Magnification: 2.5×. (B) Quantitation of the endothelial sprouting area for each group. (C) Representative micro-CT 3D reconstruction of vasculature at the fracture site following EPO treatment. The specimens were harvested for micro-CT scanning at day 14 post-surgery. Con, non-treatment control. (D) Quantitation of vascular parameters including the total volume (TV), vessel volume (VV), vessel surface (VS), and vessel thickness (VTh) by micro-CT angiography analysis. ** <i>P</i><0.01, <i>n</i> = 5.</p