Synaptic adhesion molecule protocadherin-γC5 mediates ß-amyloid-induced neuronal hyperactivity and cognitive deficits in Alzheimer's disease.

Neuronal hyperactivity induced by ß-amyloid (Aß) is an early pathological feature in Alzheimer's disease (AD) and contributes to cognitive decline in AD progression. However, the underlying mechanisms are still unclear. Here, we revealed that Aß increased the expression level of synaptic adhesion molecule protocadherin-γC5 (Pcdh-γC5) in a Ca2+-dependent manner, associated with aberrant elevation of synapses in both Aß-treated neurons in vitro and the cortex of APP/PS1 mice in vivo. By using Pcdhgc5 gene knockout mice, we demonstrated the critical function of Pcdh-γC5 in regulating neuronal synapse formation, synaptic transmission, and cognition. To further investigate the role of Pcdh-γC5 in AD pathogenesis, the aberrantly enhanced expression of Pcdh-γC5 in the brain of APP/PS1 mice was knocked down by shRNA. Downregulation of Pcdh-γC5 efficiently rescued neuronal hyperactivity and impaired cognition in APP/PS1 mice. Our findings revealed the pathophysiological role of Pcdh-γC5 in mediating Aß-induced neuronal hyperactivity and cognitive deficits in AD and identified a novel mechanism underlying AD pathogenesis.

CUDC-907 exhibits potent antitumor effects against ovarian cancer through multiple in vivo and in vitro mechanisms.

PURPOSE: CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo. METHODS: Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo. RESULTS: Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest. CONCLUSION: Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.

Inokosterone activates the BMP2 to promote the osteogenic differentiation of bone marrow mesenchymal stem cells and improve bone loss in ovariectomized rats.

Evidence suggests that enhancing the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs) may be beneficial in the fight against osteoporosis (OP) effects. Inokosterone (IS) is a major active constituent of Achyranthis bidentatae radix (ABR), which stimulates osteogenic differentiation of mouse embryonic osteoblasts. This study aims to investigate effect of IS on OP using osteogenic differentiated BMSCs and ovariectomy (OVX)-induced OP rats. The BMSCs were treated with 50, 100, or 200 mg/L IS and OP rats were given 2 or 4 mg/kg of IS by gavage. Cell viability, the osteogenic differentiation marker protein expression level, and mineralization were observed. This study proved that IS improved cell viability, osteogenic differentiation, and cellular mineralization in BMSCs and raised expression levels of bone morphogenetic protein-2 (BMP2), Smad1, runt-related transcription factor 2 (RUNX2), collagen I, ALP, and OCN. By BMP2 knockdown/overexpression, this study also proved the BMP2 signaling pathway activation is a potential biological mechanism of IS to improve osteogenic differentiation and mineralization in osteogenic differentiated BMSCs. In OVX-induced OP rats, IS was observed to antagonize bone loss, improve osteogenic differentiation marker protein expression levels, and activate BMP-2, smad1, and RUNX2. These findings provide scientific support for further investigation of the biological mechanisms of IS in ameliorating OP.

Dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique.

Information encryption technique has broad applications in individual privacy, military confidentiality, and national security, but traditional electronic encryption approaches are increasingly unable to satisfy the demands of strong safety and large bandwidth of high-speed data transmission over network. Optical encryption technology could be more flexible and effective in parallel programming and multiple degree-of-freedom data transmitting application. Here, we show a dual-layer optical encryption fluorescent polymer waveguide chip based on optical pulse-code modulation technique. Fluorescent oligomers were doped into epoxy cross-linking SU-8 polymer as a gain medium. Through modifying both the external pumping wavelength and operating frequency of the pulse-code modulation, the sender could ensure the transmission of vital information is secure. If the plaintext transmission is eavesdropped, the external pumping light will be switched, and the receiver will get warning commands of ciphertext information in the standby network. This technique is suitable for high-integration and high-scalability optical information encryption communications.

Triple-layered optical interconnecting integrated waveguide chip based on epoxy cross-linking fluorinated polymer photonic platform.

In this study, a triple-layered optical interconnecting integrated waveguide chip was designed and fabricated using an epoxy cross-linking polymer photonic platform. Fluorinated photopolymers FSU-8 and AF-Z-PC EP were self-synthesized as waveguide cores and cladding materials, respectively. The triple-layered optical interconnecting waveguide device comprised 4 × 4 arrayed waveguide grating (AWG) -based wavelength-selective switching (WSS) arrays, 4 × 4 multi-mode interference (MMI) -cascaded channel-selective switching (CSS) arrays, and 3 × 3 direct-coupling (DC) interlayered switching arrays. The overall optical polymer waveguide module was fabricated by direct UV writing. For the multilayered WSS arrays, the wavelength-shifting sensitivity was ∼0.48 nm/°C. For the multilayered CSS arrays, the average switching time was ∼280 µs, and the maximum power consumption was <30 mW. For interlayered switching arrays, the extinction ratio approximated 15.2 dB. The transmission loss for the triple-layered optical waveguide chip was measured as 10.0-12.1 dB. The flexible multilayered photonic integrated circuits (PIC) can be used in high-density integrated optical interconnecting systems with a large-volume optical information transmission capacity.

Classification molecular subtypes of hepatocellular carcinoma based on PRMT-related genes.

Background: Recent studies highlighted the functional role of protein arginine methyltransferases (PRMTs) catalyzing the methylation of protein arginine in malignant progression of various tumors. Stratification the subtypes of hepatocellular carcinoma (HCC) is fundamental for exploring effective treatment strategies. Here, we aim to conduct a comprehensive analysis of PRMTs with bioinformatic tools to identify novel biomarkers for HCC subtypes classification and prognosis prediction, which may be potential ideal targets for therapeutic intervention. Methods: The expression profiling of PRMTs in HCC tissues was evaluated based on the data of TCGA-LIHC cohort, and further validated in HCC TMA cohort and HCC cell lines. HCC was systematically classified based on PRMT family related genes. Subsequently, the differentially expressed genes (DEGs) between molecular subtypes were identified, and prognostic risk model were constructed using least absolute shrinkage and selection operator (LASSO) and Cox regression analysis to evaluate the prognosis, gene mutation, clinical features, immunophenotype, immunotherapeutic effect and antineoplastic drug sensitivity of HCC. Results: PRMTs expression was markedly altered both in HCC tissues and HCC cell lines. Three molecular subtypes with distinct immunophenotype were generated. 11 PRMT-related genes were enrolled to establish prognostic model, which presented with high accuracy in predicting the prognosis of two risk groups in the training, validation, and immunotherapy cohort, respectively. Additionally, the two risk groups showed significant difference in immunotherapeutic efficacy. Further, the sensitivity of 72 anticancer drugs was identified using prognostic risk model. Conclusion: In summary, our findings stratified HCC into three subtypes based on the PRMT-related genes. The prognostic model established in this work provide novel insights into the exploration of related therapeutic approaches in treating HCC.

Comparative transcriptome analysis reveals the immune response of turbot (Scophthalmus maximus) induced by inactivated bivalent vaccine.

Vibrio species are important pathogens that affect a wide range of farmed fish. Vaccination is regarded as the most efficacious strategy for fighting bacterial infections. However, the underlying mechanisms remain to be elucidated. In the present study, a comparative transcriptome analysis was performed on the spleens from turbot (Scophthalmus maximus) induced by an inactivated bivalent vaccine (Vibrio anguillarum and Vibrio harveyi, IVVah1) at 4 week and 1 day post further challenge. Strong immune responses were induced by the bivalent vaccine, besides differentially expressed genes (DEGs) associated with adaptive immunity, more innate immunity-related DEGs were detected. At the late stage of vaccination, immune-related molecules associated with pattern recognition receptors, inflammatory factors, complement and coagulation cascade-related components, and antigen processing and presentation were significantly regulated, and some of them were even further up-regulated after the bacterial challenge, indicating the cooperation of multiple immune processes during the vaccine immunization process. In addition to the terms or pathways associated with the immune response, enrichment analysis revealed multiple significantly enriched terms/pathways associated with the response to stimulus/stress, homeostasis, metabolism, and biosynthesis, suggesting that a defensive status was established by the bivalent vaccine. This study furnishes new insights into the internal mechanism of immunity upon a combined vaccine administrating in turbot and lays a foundation for developing highly immunogenic vaccines in teleost.

Design of Monolithic 2D Optical Phased Arrays Heterogeneously Integrated with On-Chip Laser Arrays Based on SOI Photonic Platform.

In this work, heterogeneous integration of both two-dimensional (2D) optical phased arrays (OPAs) and on-chip laser arrays based on a silicon photonic platform is proposed. The tunable multi-quantum-well (MQW) laser arrays, active switching/shifting arrays, and grating antenna arrays are used in the OPA module to realize 2D spatial beam scanning. The 2D OPA chip is composed of four main parts: (1) tunable MQW laser array emitting light signals in the range of 1480-1600 nm wavelengths; (2) electro-optic (EO) switch array for selecting the desired signal light from the on-chip laser array; (3) EO phase-shifter array for holding a fixed phase difference for the uniform amplitude of specific optical signal; and (4) Bragg waveguide grating antenna array for controlling beamforming. By optimizing the overall performances of the 2D OPA chip, a large steering range of 88.4° × 18° is realized by tuning both the phase and the wavelength for each antenna. In contrast to the traditional thermo-optic LIDAR chip with an external light source, the overall footprint of the 2D OPA chip can be limited to 8 mm × 3 mm, and the modulation rate can be 2.5 ps. The ultra-compact 2D OPA assembling with on-chip tunable laser arrays using hybrid integration could result in the application of a high-density, high-speed, and high-precision lidar system in the future.

Description of Abyssalbus ytuae gen. nov., sp. nov., a novel member of the family Flavobacteriaceae isolated from the sediment of the Mariana Trench.

In this study, we describe a Gram-stain-negative, rod-shaped, non-motile and aerobic bacterium, named strain MT3330T, which was isolated from the deep-sea sediment of the Mariana Trench. Growth of MT3330T occurred at 15-40 °C (optimum, 25-30 °C), pH 5.0-10.0 (optimum, 7.0-8.0) and with 0-8.0 % (w/v) NaCl (optimum, 0-2.0 %). The results of phylogenetic analysis based on 16S rRNA gene sequence indicated that MT3330T represented a member of the family Flavobacteriaceae and was most closely related to Zhouia spongiae HN-Y44T (92.3 % sequence similarity). The results of genomic analysis indicated that MT3330T contains a circular chromosome of 4 365 036 bp with a DNA G+C content of 35.2 %. The predominant respiratory quinone of MT3330T was MK-6. The polar lipids of MT3330T included phosphatidylethanolamine, three unidentified amino lipids and four unidentified lipids. The major fatty acids of MT3330T included C15 : 0, iso-C15 : 1G, iso-C15 : 0 3-OH, and iso-C17 : 0 3-OH. On the basis of the results of the phylogenetic, physiological, biochemical and morphological analyses, it is suggested that strain MT3330T represents a novel genus and a novel species of the family Flavobacteriaceae, and the name Abyssalbus ytuae gen. nov., sp. nov. is proposed. The type strain is MT3330T (=MCCC 1K06012T=KCTC 82823T).

Rotation alignment of a camera-IMU system using a single affine correspondence.

We propose an accurate and easy-to-implement method on rotation alignment of a camera-inertial measurement unit (IMU) system using only a single affine correspondence in the minimal case. The known initial rotation angles between the camera and IMU are utilized; thus, the alignment model can be formulated as a polynomial equation system based on homography constraints by expressing the rotation matrix in a first-order approximation. By solving the equation system, we can recover the rotation alignment parameters. Furthermore, more accurate alignment results can be achieved with the joint optimization of multiple stereo image pairs. The proposed method does not require additional auxiliary equipment or a camera's particular motion. The experimental results on synthetic data and two real-world data sets demonstrate that our method is efficient and precise for the camera-IMU system's rotation alignment.

Self-calibration of cameras using affine correspondences and known relative rotation angle.

This paper proposes a flexible method for camera self-calibration using affine correspondences and known relative rotation angle, which applies to the case that camera and inertial measurement unit (IMU) are tightly fixed. An affine correspondence provides two more constraints for the self-calibration problem than a traditional point correspondence, and the relative rotation angle can be derived from the IMU. Therefore, calibrating intrinsic camera parameters needs fewer correspondences, which can reduce the iterations and improve the algorithm's robustness in the random sample consensus framework. The proposed method does not require rotational alignment between the camera and the IMU. This advantage makes our method more convenient and flexible. The experimental results of both synthetic data and publicly available real datasets demonstrate that our method is effective and accurate for camera self-calibration.

Long non-coding RNA DANCR regulates proliferation and apoptosis of chondrocytes in osteoarthritis via miR-216a-5p-JAK2-STAT3 axis.

Osteoarthritis (OA) is one of the most common chronic joint disease. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in a variety of diseases including OA. However, the underlying mechanism of lncRNA differentiation antagonizing non-protein coding RNA (DANCR) in OA has not been well elucidated. The expression of DANCR in cartilage tissues from OA patients was detected using quantitative real-time PCR. After cell transfection, the effects of DANCR inhibition on the proliferation, apoptosis and inflammatory factors of OA chondrocytes were detected using Cell Counting Kit-8 assay and flow cytometry assay. Novel target of DANCR was then identified through bioinformatics analysis and confirmed by luciferase reporter assay and RNA immunoprecipitation assay. The expression of DANCR was significantly increased in OA patients. Function assays demonstrated that DANCR suppression inhibited the proliferation, inflammation, and promoted apoptosis of chondrocytes cells. Additionally, DANCR regulated survival of OA chondrocytes through acting as a competitive endogenous RNA for miR-216a-5p. Furthermore, JAK2 was a direct target of miR-216a-5p, and DANCR regulated the JAK2/STAT3 signal pathway through miR-216a-5p in OA chondrocytes. In the present study, we concluded that DANCR promoted the proliferation, inflammation, and reduced cell apoptosis in OA chondrocytes through regulating miR-216a-5p/JAK2/STAT3 signaling pathway, indicating DANCR might be a useful biomarker and potential therapeutic target for OA treatment.

Long non-protein coding RNA DANCR functions as a competing endogenous RNA to regulate osteoarthritis progression via miR-577/SphK2 axis.

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). This study aimed to explore the role of differentiation antagonizing non-protein coding RNA (DANCR) in OA and identify the potential molecular mechanisms. The expression of DANCR in cartilage samples from patients with OA was detected using quantitative reverse transcription-polymerase chain reaction. The effects of DANCR on the viability of OA chondrocytes and apoptosis were explored using cell counting kit 8 assay and flow cytometry assay, respectively. Additionally, the interaction among DANCR, miR-577, and SphK2 was explored using dual-luciferase reporter and RIP assays. The present study found that DANCR was significantly upregulated in patients with OA. Functional assays demonstrated that DANCR inhibition suppressed the proliferation of OA chondrocytes and induced cell apoptosis. The study also showed that DANCR acted as a competitive endogenous RNA to sponge miR-577, which targeted the mRNA of SphK2 to regulate the survival of OA chondrocytes. In conclusion, the study revealed that lncRNA DANCR might promote the proliferation of OA chondrocytes and reduce apoptosis through the miR-577/SphK2 axis. Thus, lncRNA DANCR might be considered as a potential therapeutic target for OA treatment.

Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells.

miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-ß pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.

Fold-ray videometrics method for the deformation measurement of nonintervisible large structures.

An optical measurement method, the fold-ray videometrics method, that is applicable to the deformation measurement of large structures is proposed. Through an illustration of ship deformation, the principle of fold-ray videometrics and the composition of the deformation measurement system are introduced. The fold-ray videometrics method is able to transfer or relay three-dimensional geometric information with a fold-ray optical path and thus is capable of real-time measurement of three-dimensional positions, attitudes, and deformations between nonintervisible objects and those of intervisible objects with a very large angle of view. The proposed method therefore has the potential to be applied in deformation measurement of large structures.

Two improved algorithms with which to obtain contoured windows for fringe patterns generated by electronic speckle-pattern interferometry.

Fringe patterns generated by electronic speckle-pattern interferometry are full of high-spatial-frequency and high-contrast speckle noise. Filtering with contoured windows has proved to be an efficient approach to filtering out speckle noise while retaining the fringe patterns. Furthermore, with contoured windows the contoured correlation fringe pattern method can be used to derive smooth, normalized, consistent fringes. Contoured windows previously were determined by fringe orientation only, and this process generated accumulated errors. We propose two new algorithms with which to obtain the contoured windows according to the fringe intensity slope and the distance ratio to neighboring skeletons. These new techniques can determine contoured windows more precisely.

Extraction of phase field from a single contoured correlation fringe pattern of ESPI.

Speckle fringe patterns of ESPI are full of high-level speckle noise and normally are processed by phase shifting methods that require multi speckle fringe patterns. We propose a novel method to generate a speckle-noise-free fringe pattern from a single speckle fringe pattern and to extract the phase field from the new pattern. With the new method, the correlation between two speckle patterns is performed only within contour windows instead of rectangular windows and this contoured correlation results in a smooth, normalized fringe pattern without speckle noise. The new ESPI fringe patterns are speckle-noise-free and of comparable quality to that of moiré and hologram, which is unimaginable with traditional ESPI methods. In addition to the smoothness, the resultant fringe pattern is normalized automatically so that the full phase field can be extracted from this single fringe pattern by the single-image phase-shifting method.

Single-phase-step method with contoured correlation fringe patterns for ESPI.

Speckle fringe patterns of electronic speckle pattern interferometry (ESPI) are full of high-level speckle noise and are mainly processed by phase-shifting methods that normally require three speckle fringe patterns or more. The author proposes a novel method, the contoured correlation-fringe-pattern (CCFP) method, by which speckle-noise-free fringe patterns can be generated for ESPI. The application of this novel method is extended to the phase-shifting or phase-stepping for ESPI after its improvement. It generates speckle-noise-free phase fringes and remains valid for single phase-step condition, thus eliminates the two main disadvantages of the phase-shifting (stepping) methods of ESPI.

Spin filtering with curve windows for interferometric fringe patterns.

Filtering off noise from fringe patterns is important for the processing and analysis of interferometric fringe patterns. Spin filters proposed by the author have been proven to be effective in filtering off noise without blurring and distortion to fringe patterns with small fringe curvature. But spin filters still have problems processing fringe patterns with large fringe curvature. We develop a new spin filtering with curve windows that is suitable for all kinds of fringe pattern regardless of fringe curvature. The experimental results show that the new spin filtering provides optimal results in filtering off noise without distortion of the fringe features, regardless of fringe curvature.