Hsa_circ_0022383 promote non-small cell lung cancer tumorigenesis through regulating the miR-495-3p/KPNA2 axis.

Hsa_circ_0022383 (circ_0022383) is a newly discovered circRNA. Its functions and relevant molecular mechanisms in tumorigenesis have not been reported. Here we aimed to explore how circ_0022383 regulates the tumorigenesis of non-small-cell lung cancer (NSCLC). We found thatcirc_0022383 expression was dramatically elevated in NSCLC tissues and cell lines. Upregulation of circ_0022383 was associated with poor prognosis in NSCLC patients. Silencing of circ_0022383 repressed cell proliferation and migration in vitro and inhibited oncogenesis and tumor metastasis in vivo. Moreover, our results discovered that circ_0022383 was mainly located in the cytoplasm of NSCLC cells. Mechanistically, circ_0022383 sponged miR-495-3p to modulate KPNA2 expression, thereby regulating NSCLC tumorigenesis and progression. In conclusion, our study demonstrates that circ_0022383 facilitates NSCLC tumorigenesis by regulating the miR-495-3p/KPNA2 axis, providing new insights into NSCLC development.

Circ_ATAD3B inhibits cell proliferation of breast cancer via mediating the miR-570-3p/MX2 axis.

It has been discovered that some circular RNAs can serve as excellent therapeutic targets for breast cancer (BC). However, the biological role that circ ATAD3B plays in BC is not yet completely understood. As a result, the purpose of this work was to evaluate the function of circ_ATAD3B in the development of BC. Three different GEO datasets were used to compile the expression profiles of circRNAs related to BC (GSE101124, GSE165884, and GSE182471). CCK-8 and the production of clones, in addition to RT-PCR and western blot assays, were utilized in this study to evaluate the regulation of these three biological molecules in the process of BC carcinogenesis.circ_ATAD3B was the only potential BC-related circRNA that was significantly reduced in BC tumor tissues, and it functioned as a miR-570-3p sponge to suppress cell survival and proliferation, as stated by the aforementioned two algorithms. The expression of MX2 was boosted when circ_ATAD3B was used to sponge miR-570-3p. The inhibitory effect that circ_ATAD3B has on the malignant phenotype of BC cells was overcome by the expression of miR-570-3p through up-regulation and MX2 through down-regulation. The tumor suppressor circ_ATAD3B prevents cancer progression by regulating the miR-570-3p/MX2 pathway. Circ_ATAD3B may be a candidate for targeted therapy of breast cancer.

Deep learning for efficiently imaging through the localized speckle field of a multimode fiber.

Due to the occurrence of redundant speckle, multimode fiber (MMF) imaging is extremely challenging. Our work studies the relationship between the effective feature distribution of the speckle field and the local spatial position and area, and proves that the information distribution of the speckle is highly redundant. The effective feature refers to the phase and amplitude information of the optical field carrying the image point information and the co-exciting very redundant information due to mode dispersion, interference, coupling, and entrained noise through transmission. The neural network Swin-Unet can well learn the association information between global and local features, greatly simplifies the fitting of the MMF end-to-end global mapping relationship, and achieves high-fidelity reconstruction from the local speckle field to the global image. This work will contribute to the realization of MMF real-time large-field endoscopic imaging.

Deep learning image transmission through a multimode fiber based on a small training dataset.

An improved deep neural network incorporating attention mechanism and DSSIM loss function (AM_U_Net) is used to recover input images with speckles transmitted through a multimode fiber (MMF). The network is trained on a relatively small dataset and demonstrates an optimal reconstruction ability and generalization ability. Furthermore, a bimodal fusion method is developed based on S polarization and P polarization speckles, greatly improving the recognition accuracy. These findings prove that AM_U_Net has remarkable capabilities for information recovery and transfer learning and good tolerance and robustness under different MMF transmission conditions, indicating its significant application potential in medical imaging and secure communication.

Resonance prediction and inverse design of multi-core selective couplers based on neural networks.

Resonance analysis and structural optimization of multi-channel selective fiber couplers currently rely on numerical simulation and manual trial and error, which is very repetitive and time consuming. To realize fast and accurate resonance analysis and calculation, we start with dual-core structures and establish forward classification and regression neural networks to classify and predict different resonance properties, including resonance types, operating wavelength, coupling coefficient, coupling length, 3 dB bandwidth, and conversion efficiency. The pre-trained forward neural networks for dual-core fibers can also realize accurate and fast prediction for multi-core fibers if the mode energy exchange occurs only between one surrounding core and the central core. For the inverse design, a tandem neural network has been constructed by cascading the pre-trained forward neural network and the inverse network to solve the non-uniqueness problem and provide an approach to search for appropriate and desired multi-core structures. The proposed forward and inverse neural networks are efficient and accurate, which provides great convenience for resonance analysis and structural optimization of multi-channel fiber structures and devices.

Diagnosis of Alzheimer's disease by feature weighted-LSTM: a preliminary study of temporal features in brain resting-state fMRI.

The long short-term memory network (LSTM) is widely used in time series data processing as a temporal recursive network. The resting-state functional magnetic resonance data shows that not only are there temporal variations in the resting state, but there are also interactions between brain regions. To integrate the temporal and spatial characteristics of brain regions, this paper proposes a model called feature weighted-LSTM (FW-LSTM). The feature weight is defined by spatial characteristics calculating the frequency of connectivity of each brain region and further integrated into the LSTM. Thus, it can comprehensively model both temporal and spatial changes in rs-fMRI brain regions. The FW-LSTM model on the Alzheimer's disease neuroimaging initiative (ADNI) dataset is used to extract the time-varying characteristics of 90 brain regions for Alzheimer's disease (AD) classification. The model performances are 77.80%, 76.41%, and 78.81% in accuracy, sensitivity, and specificity. It outperformed the one-dimensional convolutional neural networks (1D-CNN) model and LSTM model, which only used temporal features of brain regions.

Mechanism and characteristics of a tunable dispersion-compensating dual-ring microstructure fiber for different orbital angular momentum modes.

A tunable dual-ring microstructure fiber that can support stable transmission for different orbital angular momentum (OAM) states and possess ultrahigh dispersion coefficients and low confinement losses is proposed and theoretically investigated. The proposed fiber is composed of two high-refractive-index rings and a double-cladding structure. Owing to the central air core and outer cladding, the dual-ring structure can support stable transmission for the OAM states. The mode fields of different OAM states in the inner ring can spread to the outer ring under certain conditions, which leads to high absolute values of dispersion around the coupling wavelengths. By tuning the refractive indices of the dual rings, the proposed fiber can achieve dispersion control for different OAM modes. Moreover, the specially designed two-layer air holes in the inner cladding can affect the mode-coupling coefficients, which are characterized by the effective mode areas and the overlap integral of the electric fields between the resonant ring modes. Therefore, the dispersion curves and operating wavelengths of the OAM modes can be modulated by regulating the physical parameters (the radius of the two-layer air holes or the infiltrated functional materials) of the inner cladding. We built a theoretical model and analyzed the modulation method and mechanism of the dispersion curves based on the coupled mode theory. The theoretical results indicate that the proposed fiber is flexible and has potential dispersion-compensating applications in fiber OAM systems.

Intensity-interrogated magnetic sensor based on S-tapered and multimode fiber integrated with ferrofluids.

In this study, a high-sensitivity intensity-interrogated fiber sensor integrated with ferrofluids is proposed for the measurement of a weak magnetic field (MF) with resolved temperature cross-sensitivity. The MF sensor is fabricated simply by an offset tapering single-mode fiber concatenated with a multimode fiber (MMF), which is then encapsulated into a capillary tube filled with ferrofluids. In the presence of MMF, stronger mode coupling could be achieved over the S-tapered fiber region. Its spectral response to variations in the applied MF intensity and ambient temperature have been investigated in detail. The proposed sensor shows a high MF sensitivity up to -0.1130dB/Oe for the measurement range of 40 to 120 Oe, which, to our best knowledge, is higher than other previously reported MF sensors. And moreover, the measurement errors caused by temperature cross-sensitivity have been corrected by using a sensing matrix for the temperature range of 25°C to 35°C. Our proposed MF sensor possesses the advantages of high sensitivity, low cost, and applicability for applications in weak MF measurements.

Orbital angular momentum generation in a dual-ring fiber based on the phase-shifted coupling mechanism and the interference of supermodes.

Based on the phased-shifted interference between supermodes, a novel method that can directly convert LP01 mode to orbital angular momentum (OAM) mode in a dual-ring microstructure optical fiber is proposed. In this fiber, the resonance between even and odd HE11 modes in inner ring and higher order mode in outer ring will form two pairs of supermodes, and the intensities and phases of the complete superposition mode fields for the involved supermodes created by the resonance at different wavelengths and propagating lengths are investigated and exhibited in this paper. We demonstrate that OAM mode can be generated from π/2-phase-shifted linear combinations of supermodes, and the phase difference of the even and odd higher order eigenmodes can accumulate to π/2 during the coupling process, which is defined as "phase-shifted" conversion. We build a complete theoretical model and systematically analyze the phase-shifted coupling mechanism, and the design principle and optimization method of this fiber are also illustrated in detail. The proposed microstructure fiber is compact, and the OAM mode conversion method is simple and flexible, which could provide a new approach to generate OAM states.

MiR-145-5p suppresses the proliferation, migration and invasion of gastric cancer epithelial cells via the ANGPT2/NOD_LIKE_RECEPTOR axis.

OBJECTIVE: This study aimed to investigate the relationship among miR-145-5p, ANGPT2 and the NOD_LIKE_RECEPTOR pathway, thereby revealing the molecular mechanism of these three factors underlying the proliferation, migration and invasion of gastric cancer (GC) epithelial cells. METHODS: qRT-PCR was carried out to detect the expression of miR-145-5p and ANGPT2 mRNA. Western blot was performed to test the protein levels of ANGPT2 as well as NOD1, NOD2 and NF-κB in the NOD_LIKE_RECEPTOR pathway. The targeting relationship between miR-145-5p and ANGPT2 was verified via a dual-luciferase reporter gene assay. The proliferation, migration and invasion of GC cells were detected through MTT and Transwell assays, respectively. RESULTS: The expression of miR-145-5p was significantly down-regulated in GC cells, while that of ANGPT2 was notably up-regulated. MiR-145-5p directly bound with the 3'-UTR of ANGPT2 mRNA, thereby targeting ANGPT2 after transcription. Overexpression of miR-145-5p inhibited the proliferation, migration and invasion of GC cells by suppressing ANGPT2. Moreover, low expression of ANGPT2 affected the protein levels of NOD1, NOD2 and NF-κB in the NOD_LIKE_RECEPTOR pathway, thus weakening the abilities of cell proliferation, migration and invasion. CONCLUSIONS: MiR-145-5p plays an important role in GC epithelial cells, and it can affect cell proliferation, migration and invasion of GC cells by targeting ANGPT2 and regulating the NOD_LIKE_RECEPTOR pathway. Overall, our study further elucidates the molecular mechanism underlying the malignant progression of GC.

A toll-like receptor 9 agonist sensitizes mice to mitochondrial dysfunction-induced hepatic apoptosis via the Fas/FasL pathway.

Early hepatocyte death occurs in most liver injury cases and triggers liver inflammation, which in combination with other risk factors leads to the development of liver disease. However, the pathogenesis of early phase hepatocyte death remains poorly understood. Here, C57BL/6J mice were treated with the hepatotoxic drug flucloxacillin (FLUX) and the toll-like receptor 9 agonist CpG oligodeoxynucleotide (ODN) to reproduce the early phase of drug-induced hepatotoxicity and investigate its pathogenesis. C57BL/6J mice were treated with FLUX (100 mg/kg, gavage) alone or in combination with ODN (40 µg/mouse, intraperitoneally). Plasma alanine aminotransferase (ALT) level was measured as a marker of hepatotoxicity. FLUX or ODN alone was insufficient to induce ALT elevation, whereas combination treatment with FLUX and ODN increased ALT levels 24 h after FLUX treatment and upregulated Fas ligand in natural killer T (NKT) cells and Fas in hepatocytes. FLUX induced mitochondrial permeability transition (MPT), and pretreatment with ODN sensitized mitochondria to FLUX-induced MPT. The increase in ALT levels induced by ODN and FLUX co-treatment was suppressed in Fas ligand (gld/gld)-deficient mice and in mice deficient in a component of MPT pore opening (cyclophilin D-knockout mice). These results suggested that ODN activated the Fas/Fas ligand-mediated pathway in NKT cells and hepatocytes, which may predispose to FLUX-induced mitochondrial dysfunction and lead to early phase hepatocyte apoptosis. Taken together, these findings elucidate a potentially novel mechanism underlying drug-induced early phase hepatocyte death related to the Fas/Fas ligand death receptor pathway and mitochondrial dysfunction.

Application of Bone Turnover Markers PICP and ß-CTx in the Diagnosis and Treatment of Breast Cancer with Bone Metastases.

BACKGROUND: This study is to investigate the application of the bone turnover markers type I procollagen carboxyterminal propeptide (PICP) and ß-isomerized forms of type I collagen breakdown products (ß-CTx) in the diagnosis and treatment of breast cancer with bone metastases. METHODS: A total of 162 breast cancer patients were included in this study. There were 70 cases with bone metastasis (BM group) and 92 cases without bone metastasis (non-bone metastasis, NBM group). The levels of the bone turnover markers PICP and ß-CTx were measured using Electro-Chemiluminescence Immunoassay to compare the difference between BM and NBM group, before and after treatments in the NBM group, and to analyse the relationship with therapeutic effects. RESULTS: The BM group had higher PICP and ß-CTx levels than the NBM group and also higher in the non-luminal type group than the luminal type group, the differences were all statistically significant. However, no statistically significant differences were found among the pN0, pN1, pN2, and pN3 subgroups of the NBM group. Among the 70 cases of BM patient after 3 months of treatment, there were 48 cases that showed clinical benefits, with significantly reduced PICP and ß-CTx levels (p = 0.02, p = 0.00, respectively), but 22 cases showed disease progression with elevated PICP and ß-CTx levels (p = 0.01, p = 0.04, respectively). CONCLUSIONS: The bone turnover markers PICP and ß-CTx have crucial value in the diagnosis and treatment efficacy evaluation for women of breast cancer with bone metastases.

Evaluation of immune-mediated idiosyncratic drug toxicity using chimeric HLA transgenic mice.

Immune-mediated idiosyncratic drug toxicity (IDT) is a rare adverse drug reaction, potentially resulting in death. Although genome-wide association studies suggest that the occurrence of immune-mediated IDT is strongly associated with specific human leukocyte antigen (HLA) allotypes, these associations have not yet been prospectively demonstrated. In this study, we focused on HLA-B*57:01 and abacavir (ABC)-induced immune-mediated IDT, and constructed transgenic mice carrying chimeric HLA-B*57:01 (B*57:01-Tg) to determine if this in vivo model may be useful for evaluating immune-mediated IDT. Local lymph node assay (LLNA) results demonstrated that percentages of BrdU+, IL-2+, and IFN-γ+ in CD8+ T cells of ABC (50 mg/kg/day)-applied B*57:01-Tg mice were significantly higher than those in littermates (LMs), resulting in the infiltration of inflammatory cells into the ear. These immune responses were not observed in B*57:03-Tg mice (negative control). Furthermore, oral administration of 1% (v/v) ABC significantly increased the percentage of CD44highCD62Llow CD8+ memory T cells in lymph nodes and spleen derived from B*57:01-Tg mice, but not in those from B*57:03-Tg mice and LMs. These results suggest that B*57:01-Tg mice potentially enable the reproduction and evaluation of HLA-B*57:01 and ABC-induced immune-mediated IDT.

[Design, synthesis and evaluation of a novel MEK protein inhibitors].

This study was conducted to design and synthetize highly efficient, specific, non-resistant small MEK inhibitors. Based on active small molecules which have been reported, we studied the action mode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designed novel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumor activities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT method in vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. The compounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity, and the compounds 2, 9 showed cell selectivity in killing tumor.

Highly sensitive twist sensor employing Sagnac interferometer based on PM-elliptical core fibers.

A highly sensitive optical fiber twist sensor has been proposed by employing a Sagnac interferometer based on polarization-maintaining elliptical core fibers (PM-ECFs). The twist effects have been theoretically analyzed and experimentally demonstrated. Based on the photoelastic effect, the resonance wavelength linearly shifts with the increment of twist and the wavelength shift is also dependent on the torsion direction. The maximum torsion sensitivities reach 18.60nm/(rad/m) for clockwise (CW) torsion direction and 15.83nm/(rad/m) for anticlockwise (ACW) torsion direction, respectively. To eliminate the temperature cross-sensitivity effect, a sensor matrix for simultaneous measurement of twist and temperature has also been obtained. Moreover, theoretical and experimental investigations indicate that by optimizing the refractive index difference between the core and cladding, core ellipticity and cladding diameter, the twist sensitivity could be further improved.

Magnetically controllable wavelength-division-multiplexing fiber coupler.

In this paper, a magnetically controllable wavelength-division-multiplexing (WDM) fiber coupler has been proposed and experimentally demonstrated. A theoretical model has been established to analyze the influences of the weak as well as strong couplings to the wavelength tunability of this coupler. Experimental results show that the operation wavelength tunability of the proposed WDM coupler could be fulfilled for an applied magnetic field intensity range of 0 Oe to 500 Oe, and particularly it possesses high operation performances within the magnetic field intensity ranging from 25 Oe to 125 Oe when additional transmission loss and isolation are both considered. Within this range, the two selected channels show the wavelength tunability of 0.05 nm/Oe and 0.0744 nm/Oe, respectively, and the isolation between the two branches is higher than 24.089 dB. Owing to its high isolation, good splitting ratio stability, and high wavelength tunability, the proposed controllable WDM coupler is anticipated to find potential applications in such fields as fiber laser, fiber sensing and fiber-optic communications. Moreover, the fiber coupler integrated with the magnetic fluid would be valuable for the design of magnetically controllable mode-division-multiplexing devices.

Low-temperature cross-talk magnetic-field sensor based on tapered all-solid waveguide-array fiber and magnetic fluids.

A compact fiber-optic magnetic-field sensor based on tapered all-solid waveguide-array fiber (WAF) and magnetic fluid (MF) has been proposed and experimentally demonstrated. The tapered all-solid WAF is fabricated by using a fusion splicer, and the sensor is formed by immersing the tapered all-solid WAF into the MF. The transmission spectra have been measured and analyzed under different magnetic-field intensities. Experimental results show that the acquired magnetic-field sensitivity is 44.57 pm/Oe for a linear magnetic-field intensity range from 50 to 200 Oe. All-solid WAF has very similar thermal expansion coefficient for high- and low-refractive-index glasses, so mode profile is not affected by thermal drifts. Also, magnetically induced refractive-index changes into the ferrofluid are of the order of ∼5×10(-2), while the corresponding thermally induced refractive-index changes into the ferrofluid are expected to be lower. The temperature response has also been detected, and the temperature-induced wavelength shift perturbation is less than 0.3 nm from temperature of 26.9°C-44°C. The proposed magnetic-field sensor has such advantages as low temperature sensitivity, simple structure, and ease of fabrication. It also indicates that the magnetic-field sensor based on tapered all-solid WAF and MF is helpful to reduce temperature cross-sensitivity for the measurement of magnetic field.

Serum ferritin levels are associated with carotid atherosclerosis in Chinese postmenopausal women: the Shanghai Changfeng Study.

Postmenopausal women are at increased risk of CVD: the increased serum ferritin level may be involved in the pathogenesis. The aim of the present study is to investigate the relationship of ferritin and carotid atherosclerosis in postmenopausal women. A total of 1178 postmenopausal women (mean age, 60·8 years) were enrolled from the Changfeng Study. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral CIMT (carotid intima-media thickness) were measured using ultrasonography, and the presence of carotid plaques was assessed. Serum ferritin was measured using electrochemiluminescence immunoassay. The results showed that serum ferritin was 181·9 (sd 65·8) ng/ml in the postmenopausal women. Multivariate, linear, stepwise regression analysis demonstrated that age (standardised ß = 0·233, P< 0·001), alanine transaminase (standardised ß = 0·194, P< 0·001), log homeostasis model assessment index for insulin resistance (standardised ß = 0·181, P< 0·001), TAG (standardised ß = 0·083, P= 0·003), Hb (standardised ß = 0·080, P= 0·004) and PPG (2-h glucose levels following a 75-g oral glucose challenge) (standardised ß = 0·079, P= 0·004) were independently associated with serum ferritin. Compared with the ferritin level of subjects in the first quartile, that in the fourth quartile had greater CIMT, and higher prevalence of carotid plaque. After adjusting for conventional CVD risk factors, Hb, leucocytes, log urine albumin:creatinine ratio and liver function, the ferritin level of postmenopausal women in the fourth quartile had a 1·587-fold increased risk of carotid plaques relative to those in the lowest quartile. In conclusion, these results suggest that serum ferritin is independently and positively associated with carotid atherosclerosis in postmenopausal women and that ferritin may be implicated in atherosclerosis.

Photonic crystal fiber modal interferometer based on thin-core-fiber mode exciter.

A thin-core-fiber excited photonic crystal fiber modal interferometer has been proposed and experimentally demonstrated. By employing a thin-core fiber as the mode exciter, both of the core and cladding modes propagate in the photonic crystal fiber and interfere with each other. The experimental results show that the transmission dips corresponding to different-order modes have various strain responses with opposite shift directions. The strain sensitivity could be improved to 58.57 pm/µÎµ for the applied strain from 0 to 491 µÎµ by utilizing the wavelength interval between the dips with opposite shift directions. Moreover, due to the pure silica property of the employed photonic crystal fiber, the proposed fiber modal interferometer exhibits a low-temperature sensitivity of about 0.56 pm/°C within a temperature range from 26.4°C (room temperature) to 70°C. Additionally, the proposed fiber modal interferometer has several advantages, such as good stability, compact structure, and simple fabrication. Therefore, it is more applicable for strain measurement with reducing temperature cross-sensitivity.

Liquid-filled photonic-crystal-fiber-based multimodal interferometer for simultaneous measurement of temperature and force.

In this paper, a multimodal interferometer based on the liquid-filled photonic crystal fiber (PCF) has been proposed and experimentally demonstrated for simultaneous measurement of temperature and force. Experimental results show that different spectral minima have distinctive sensitivities to the temperature and force. The proposed interferometer shows the temperature sensitivities of -9.214 nm/°C, -24.757 nm/°C, and -12.543/°C and the force sensitivities of 0 nm/N, 4.978 nm/N, and 0 nm/N, respectively, for the three selected spectral minima. The sensing matrices are thus established and simultaneous measurement of temperature and force has been experimentally demonstrated. The proposed liquid-filled PCF-based multimodal interferometer would find potential applications in multiple-parameter sensing owing to its high sensitivity, compactness, ease of fabrication, and low cost.