Tolerogenic dendritic cells alleviate collagen-induced arthritis by forming microchimerism and affecting the expression of immune checkpoint molecules.

Tolerogenic dendritic cells (tolDCs) have the potential to treat rheumatoid arthritis (RA) by inducing immune tolerance. However, the mechanism of intervention needs further study. Here, we investigated whether tolDCs formed microchimerism and their effect on the expression of immune checkpoint molecules after infusion of tolDCs into rats with collagen-induced arthritis (CIA). TolDCs derived from male SD rats were labeled with fluorescence and infused into female CIA rats. The fluorescence signals as well as the sex-determining region of Y-chromosome (SRY) gene revealed that tolDCs formed microchimerism in the mesenteric lymph nodes and ankle joints. We further explored the effect of tolDCs on the expression of immune checkpoint molecules in mesenteric lymph nodes and ankle joints. For stimulatory immune checkpoint molecules, the expressions of CD86 and CD40 decreased in mesenteric lymph nodes, and the expressions of CD40, CD40L, CD28, CD80, and CD86 also decreased in rat ankle joints. In contrast, the inhibitory immune checkpoint molecule PDL1 increased in mesenteric lymph nodes, and PD1, PDL1, and CTLA4 increased in ankle joints. In conclusion, our results suggested that intervention of tolDCs in CIA is associated with the formation of microchimerism and the effect on immune checkpoints.

Simultaneous sensing of strain and temperature based on the inline-MZI embedded point-shaped taper structure with low crosstalk.

An embedded spherical dot taper structure (EDT) based on the MZI principle is proposed in this paper, which is mainly fabricated by using two special arc discharges in the preparation process. The proposed structure involves two specialized arc discharge techniques. First, an oversaturated discharge fusion process creates a micro-arc spherical area on the fiber end face to form the first link type. Second, an unsaturated discharge-pulling taper fusion joint creates a local micro-extrusion operation on this micro-arc fiber end face to form the second link. The thermal stress from instantaneous discharge causes a reverse spherical expansion zone to form in the end face structure, similar to the micromachining of long-period fiber gratings that use local CO2 laser etching to create modulated zones. The study involves a mathematical and theoretical analysis of how geometric parameters in the spherical modulation zone impact the structure's characteristic spectrum. The research demonstrates the potential for this structure to function as a light-intensity modulated strain sensor device through both theoretical and experimental means. As per the experimental findings, the optimized structure displays a high level of strain sensing sensitivity at 0.03 dB/µÎµ and temperature sensing sensitivity of 73 pm/°C (20°C-75°C) and 169 pm/°C (75°C-120°C). Additionally, it possesses excellent cross-sensitivity at only ∼0.0015 µÎµ/°C. Therefore, this sensor presents a favorable option for strain and temperature synchronization sensing and monitoring components, and exhibits notable application prospects in precision engineering, which encompasses mechanical manufacturing, the power and electrical industry, healthcare domain, and certain specialized areas of small-scale precision engineering.

Brasilterpenes A-E, Bergamotane Sesquiterpenoid Derivatives with Hypoglycemic Activity from the Deep Sea-Derived Fungus Paraconiothyrium brasiliense HDN15-135.

Five bergamotane sesquiterpenoid derivatives, brasilterpenes A-E (1-5), bearing an unreported spiral 6/4/5 tricyclic ring system, were isolated from the deep sea-derived ascomycete fungus Paraconiothyrium brasiliense HDN15-135. Their structures, including absolute configurations, were established by extensive spectroscopic methods complemented by single-crystal X-ray diffraction analyses, electronic circular dichroism (ECD), and density-functional theory (DFT) calculations of nuclear magnetic resonance (NMR) data including DP4+ analysis. The hypoglycemic activity of these compounds was assessed using a diabetic zebrafish model. Brasilterpenes A (1) and C (3) significantly reduced free blood glucose in hyperglycemic zebrafish in vivo by improving insulin sensitivity and suppressing gluconeogenesis. Moreover, the hypoglycemic activity of compound 3 was comparable to the positive control, anti-diabetes drug rosiglitazone. These results suggested brasilterpene C (3) had promising anti-diabetes potential.

Unusual Tetrahydropyridoindole-Containing Tetrapeptides with Human Nicotinic Acetylcholine Receptors Targeting Activity Discovered from Antarctica-Derived Psychrophilic Pseudogymnoascus sp. HDN17-933.

Chemical investigation of the psychrophilic fungus Pseudogymnoascus sp. HDN17-933 derived from Antarctica led to the discovery of six new tetrapeptides psegymamides A-F (1-6), whose planar structures were elucidated by extensive NMR and MS spectrometric analyses. Structurally, psegymamides D-F (4-6) possess unique backbones bearing a tetrahydropyridoindoles unit, which make them the first examples discovered in naturally occurring peptides. The absolute configurations of structures were unambiguously determined using solid-phase total synthesis assisted by Marfey's method, and all compounds were evaluated for their inhibition of human (h) nicotinic acetylcholine receptor subtypes. Compound 2 showed significant inhibitory activity. A preliminary structure-activity relationship investigation revealed that the tryptophan residue and the C-terminal with methoxy group were important to the inhibitory activity. Further, the high binding affinity of compound 2 to hα4ß2 was explained by molecular docking studies.

Regulation of fast and slow light characteristics of the add-drop ring-resonator employing an assisted ring.

We demonstrate theoretically and experimentally that the fast and slow light characteristics of the add-drop ring-resonator (ADRR) can be regulated by introducing an assisted ring. This novel geometry is named ring-assisted add-drop ring-resonator (RA-ADRR). When the assisted ring is under-coupled, the fast and slow light characteristics of through and drop ports of the RA-ADRR will be reversed, which is different from the coupled resonator induced transparency (CRIT) studied previously. With the decrease of loss, the dispersion peak (dip) of the two ports will grow up towards the opposite directions and finally the inversion occurs. Meanwhile, we find that by increasing the circumference of the assisted ring, the dispersion of the two ports could be improved proportionally. The experimental results show that the maximum group delays of the through and drop ports are 115 ns and -485 ns, respectively. This novel phenomenon could greatly enhance the sensitivity of slow light interferometers and also has potential applications in optical communication, network, filtering and switching.

Circ_101064 regulates the proliferation, invasion and migration of glioma cells through miR-154-5p/ PIWIL1 axis.

This study aimed to investigate the effects of Circ_101064 on glioma cell proliferation, invasion, migration and explore the underlying mechanisms. The expression levels of Circ_101064 in glioma/para-carcinoma tissues and glioma cells were analyzed using RT-qPCR. Moreover, U251 and U87 cells were transfected with si-Circ_101064 or miR-154-5p mimics. Cell proliferation rate was determined by CCK-8 assay; the invasion and migration activities were examined using Transwell assay; the expression levels of PIWIL1 were evaluated by RT-qPCR and western blotting. The expression level of Circ_101064 was significantly upregulated in glioma tissues compared with control, and was closely associated with tumor grading and diameter. Furthermore, increased Circ_101064 expression was detected in human glioma cell lines. In addition, knockdown of Circ_101064 remarkably suppressed cell proliferation, invasion and migration in glioma cells in vitro. Moreover, microRNA-154-5p (miR-154-5p) could be a target of Circ_101064. Additionally, PIWIL1 is a putative downstream molecule of miR-154-5p, and its expression was downregulated by knockdown of Circ_101064. The effects on cell growth and metastasis caused by si-Circ_101064 were notably enhanced by miR-154-5p mimics. However, the influences of miR-154-5p-suppressed proliferation, migration and invasion of glioma cells could be abolished by overexpressed PIWIL1. In summary, our findings provided novel insight into the regulatory functions of Circ_101064 during tumor development in glioma. More importantly, Circ_101064/miR-154-5p/PIWIL1 axis could be a promising therapeutic target for the treatment of this disease.

Autler-Townes splitting and induced transparency windows in a multimode microfiber knot.

In this Letter, Autler-Townes splitting and induced transparency windows are observed in a multimode microfiber knot. The microfiber knot is fabricated using tapered single-mode fiber, with the knot position located at the transition area of the tapered fiber. The spectrum, in analogy to Autler-Townes splitting, derives from the mode splitting of two high-order excited modes, which is theoretically explained by the multimode transfer matrix method. Moreover, without adding resonators, two induced transparency windows are realized with the tunable coupling coefficients and phase difference of excited knot modes. The tunable, easily fabricated, compact, and robust microfiber knot has potential applications in optical sensing, filters, slow light, and optical switching.

Novel 3,4-dihydroquinolin-2(1H)-one derivatives as dual inhibitor targeting AKR1B1/ROS for treatment of diabetic complications: Design, synthesis and biological evaluation.

AKR1B1 (Aldose reductase) has been used as therapeutic intervention target for treatment of diabetic complications over 50 years, and more recently for inflammation and cancer. However, most developed small molecule inhibitors have the defect of low bioactivity. To address this limitation, novel series of 3,4-dihydroquinolin-2(1H)-one derivatives as dual inhibitor targeting AKR1B1/ROS (Reactive Oxygen Species) were designed and synthesized. Most of these derivatives were found to be potent and selective against AKR1B1, and compound 8a was the most active with an IC50 value of 0.035 µM. Moreover, some prepared derivatives showed strong anti-ROS activity, and among them the phenolic 3,5-dihydroxyl compound 8b was proved to be the most potent, even comparable to that of the well-known antioxidant Trolox at a concentration of 100 µM. Thus the results suggested a success in the construction of potent dual inhibitor for the therapeutic intervention target of AKR1B1/ROS.

Overexpression of TRIM26 suppresses the proliferation, metastasis, and glycolysis in papillary thyroid carcinoma cells.

Papillary thyroid carcinoma (PTC) is the common subtype of thyroid cancer, which is a common endocrine malignancy. Tripartite motif 26 (TRIM26) has been found to act as a tumor suppressor in several cancers. However, the functional roles of TRIM26 in PTC remain unknown. In this study, we examined the TRIM26 expression in PTC and evaluated the effects of TRIM26 on proliferation, metastasis, and glycolysis in PTC cells. The results proved that TRIM26 was significantly downregulated in PTC tissues and cell lines. TRIM26 overexpression inhibited cell proliferation, migration, and invasion in PTC cells. TRIM26 overexpression also suppressed the epithelial-to-mesenchymal transition process. Besides, overexpression of TRIM26 caused significant decrease in glucose uptake and lactate production in PTC cells. Further investigations revealed that TRIM26 overexpression inhibited the activation of PI3K/Akt pathway. Treatment with an activator (740Y-P) of the PI3K/AKT pathway reversed the antitumor effects of TRIM26 on PTC cells. These findings provided evidence that TRIM26 acted as a tumor suppressor in PTC.

High-temperature sensor based on suspended-core microstructured optical fiber.

We propose a high-temperature sensor based on a suspended-core microstructured optical fiber (SCMF). The sensor is constructed by fusion splicing a piece of SCMF between two sections of multimode fibers (MMFs) which act as light beam couplers. The multimode interference is formed by the air cladding modes and the silica core modes in the SCMF. Fast Fourier transform is adapted to filtering the raw transmission spectra of the MMF-SCMF-MMF structure. The wavelength shift of the dominant spatial frequency is monitored as the temperature varies from 50 °C to 800 °C. The sensitivities of 31.6 pm/°C and 51.6 pm/°C in the temperature range of 50 °C-450 °C and 450 °C-800 °C are respectively achieved. Taking advantage of the compact size, good stability and repeatability, easy fabrication, and low cost, this proposed high-temperature sensor has an applicable value.

Magnetic-field tuning whispering gallery mode based on hollow microbubble resonator with Terfenol-D-fixed.

We propose a method of magnetic-field tuning whispering gallery modes (WGMs) based on a hollow microbubble resonator (HMBR) with Terfenol-D-fixed. WGMs are excited by the evanescent field from a tapered fiber coupling with an HMBR. Both ends of the HMBR are fixed with Terfenol-D and vary with different lengths of the Terfenol-D. The length of the Terfenol-D varies with the external magnetic field for the high magnetostriction coefficient of Terfenol-D. The magnetic field sensitivity of 0.081 pm/mT in the magnetic field range of 0.14 mT-21.8 mT is achieved. The $Q$Q-factor of the HMBR can be regulated up to ${2.07} \times {{10}^4}$2.07×104 with physical stretching HMBR. This work provides a novel tuning whispering gallery mode scheme and a broad application prospect in the fields of optical measurement and precise optical clocks in the future.

Temperature-insensitive fiber optic Fabry-Perot interferometer based on special air cavity for transverse load and strain measurements.

We experimentally demonstrate transverse load and strain sensing based on a fiber optic Fabry-Perot interferometer (FPI) with special air cavity, which was created by fusion splicing single mode fiber (SMF), hollow core fiber (HCF) and several electrical arc discharges. The cavity height of this structure is higher than the cladding diameter of SMF so that it can sense transverse load with high sensitivity. The transverse load sensitivity of this air cavity FPI sensor is 1.31 nm∕N and about 5 times more sensitive compared to the current fiber tip interferometer (0.2526 nm∕N). Meanwhile, this sensor also can measure strain and the strain sensitivity of 3.29 pm∕µÎµ is achieved. In addition, the low temperature sensitivity (1.08 pm/°C) of the sensor can reduce the temperature-induced measurement error. This novel air cavity FPI can be developed and used as high-sensitivity transverse load and strain sensor with temperature-insensitive.

High expression of BAG3 predicts a poor prognosis in human medulloblastoma.

Bcl2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock protein (Hsp) 70, regulates various physiological and pathological processes. However, its role in human medulloblastoma has not been clarified. First of all, the expression of BAG3 was examined in formalin-fixed, paraffin-embedded specimens by immunohistochemical staining. And then, the prognostic role of BAG3 was analyzed in 51 medulloblastoma samples. Finally, the roles of BAG3 in the proliferation, migration, and invasion of Daoy medulloblastoma cell were investigated using a specific short hairpin RNA (shRNA). The expression of BAG3 in medulloblastoma tissues was higher than nontumorous samples. Furthermore, BAG3 overexpression significantly correlated with poor prognosis of patients with medulloblastoma. The overall survival and tumor-free survival in patients with BAG3 low expression were higher than high expression. Univariate and multivariate analysis showed that BAG3 overexpression was an independent prognostic marker for medulloblastoma. After the BAG3 knockdown, the Daoy cells exhibited decreased the ability to proliferate and form neurosphere. The preliminary mechanism study showed that overexpression of BAG3 might facilitate the cell cycle transition from G1 to S phase by modulating the cyclin-dependent kinase 2 (CDK2) and cyclin E expression. Additionally, we found that BAG3 might enhance the medulloblastoma cell migratory and invasive ability. In summary, BAG3 overexpression may regulate the survival and invasive properties of medulloblastoma and may serve as a potential therapy target for medulloblastoma.

Electromagnetically induced-transparency-like spectrum in an add/drop interferometer.

We propose a single-ring-resonator-based add/drop interferometer and theoretically investigate the transmission characteristics. Due to coherent interference of two resonant pathways, an electromagnetically induced-transparency (EIT)-like spectrum is produced and the line shapes of the transmission spectra are tunable by controlling the coupling coefficients between the waveguide and ring resonator. We observe the EIT-like behavior in a fiber system which agrees well with the theoretical analysis. The proposed configuration has potential applications in tunable delay lines.

Reconfigurable dual-channel dropping filters based on a self-coupled resonator Sagnac interferometer.

We report a reconfigurable dual-mode resonator-based dual-channel dropping filter. The dual dropping channels are generated within a free spectral range (FSR) via the interference between the electromagnetically induced transparency (EIT)-like and electromagnetically induced absorption (EIA)-like resonances despite only one resonator used. The reconfiguration of the dual channels enabling the truly on/off switching mechanism is realized, and the output modes resembling the add/drop/neutral states are provided. The compact, reliable, flexible, versatile, and extendable filter has profound implications for wavelength division multiplexing (WDM) applications in optical interconnection networks.

Dexmedetomidine inhibits the migration, invasion, and glycolysis of glioblastoma cells by lactylation of c-myc.

BACKGROUND: Glioblastoma (GBM) is a brain tumor with poor prognosis. Dexmedetomidine (Dex) regulates the biological behaviors of tumor cells to accelerate or decelerate cancer progression. OBJECTIVE: We investigated the effects of Dex on the migration, invasion, and glycolysis in GBM. METHODS: The concentration of Dex was determined using the cell counting kit-8 assay. The impacts of Dex on biological behaviors of GBM cells were assessed using Transwell assay, XF96 extracellular flux analysis, and western blot. The expression of c-Myc was examined using reverse transcription-quantitative polymerase chain reaction. The lactylation or stability of c-Myc was measured by western blot after immunoprecipitation or cycloheximide treatment. RESULTS: We found that Dex (200 nM) inhibited GBM cell viability, migration, invasion, and glycolysis. C-Myc was highly expressed in GBM cells and was decreased by Dex treatment. Moreover, Dex suppressed lactylated c-Myc levels via suppressing glycolysis, thereby reducing the protein stability of c-Myc. Sodium lactate treatment abrogated the effects of Dex on the biological behaviors of GBM cells. CONCLUSION: Dex suppressed the migration, invasion, and glycolysis of GBM cells via inhibiting lactylation of c-Myc and suppressing the c-Myc stability, suggesting that Dex may be a novel therapeutic drug for GBM treatment.

A temperature compensated fiber probe for highly sensitive detection in virus gene biosensing.

This research presents an innovative reflective fiber optic probe structure, mutinously designed to detect H7N9 avian influenza virus gene precisely. This innovative structure skillfully combines multimode fiber (MMF) with a thin-diameter seven-core photonic crystal fiber (SCF-PCF), forming a semi-open Fabry-Pérot (FPI) cavity. This structure has demonstrated exceptional sensitivity in light intensity-refractive index (RI) response through rigorous theoretical and experimental validation. The development of a quasi-distributed parallel sensor array, which provides temperature compensation during measurements, has achieved a remarkable RI response sensitivity of up to 532.7 dB/RIU. The probe-type fiber optic sensitive unit, expertly functionalized with streptavidin, offers high specificity in detecting H7N9 avian influenza virus gene, with an impressively low detection limit of 10-2 pM. The development of this biosensor marks a significant development in biological detection, offering a practical engineering solution for achieving high sensitivity and specificity in light-intensity-modulated biosensing. Its potential for wide-ranging applications in various fields is now well-established.

Hyaluronic acid modified indocyanine green nanoparticles: a novel targeted strategy for NIR-II fluorescence lymphatic imaging.

The lymphatic system, alongside blood circulation, is crucial for maintaining bodily equilibrium and immune surveillance. Despite its importance, lymphatic imaging techniques lag behind those for blood circulation. Fluorescence imaging, particularly in the near-infrared-II (NIR-II) region, offers promising capabilities with centimeter-scale tissue penetration and micron-scale spatial resolution, sparking interest in visualizing the lymphatic system. Although indocyanine green (ICG) has been approved by the Food and Drug Administration (FDA) for use as a near-infrared-I (NIR-I) region fluorescent dye, its limitations include shallow penetration depth and low signal-to-noise ratio. Research suggests that ICG's fluorescence emission tail in the second near-infrared window holds potential for high-quality NIR-II imaging. However, challenges like short circulation half-life and concentration-dependent aggregation hinder its wider application. Here we developed HA@ICG nanoparticles (NPs), a superior ICG-based NIR-II fluorescent probe with excellent biocompatibility, prolonging in vivo imaging, and enhancing photostability compared to ICG alone. Leveraging LYVE-1, a prominent lymphatic endothelial cell receptor that binds specifically to hyaluronic acid (HA), our nanoprobes exhibit exceptional performance in targeting lymphatic system imaging. Moreover, our findings demonstrate the capability of HA@ICG NPs for capillary imaging, offering a means to assess local microcirculatory blood supply. These compelling results underscore the promising potential of HA@ICG NPs for achieving high-resolution bioimaging of nanomedicines in the NIR-II window.

A fully automatic MRI-guided decision support system for lumbar disc herniation using machine learning.

Background: Normalized decision support system for lumbar disc herniation (LDH) will improve reproducibility compared with subjective clinical diagnosis and treatment. Magnetic resonance imaging (MRI) plays an essential role in the evaluation of LDH. This study aimed to develop an MRI-based decision support system for LDH, which evaluates lumbar discs in a reproducible, consistent, and reliable manner. Methods: The research team proposed a system based on machine learning that was trained and tested by a large, manually labeled data set comprising 217 patients' MRI scans (3255 lumbar discs). The system analyzes the radiological features of identified discs to diagnose herniation and classifies discs by Pfirrmann grade and MSU classification. Based on the assessment, the system provides clinical advice. Results: Eventually, the accuracy of the diagnosis process reached 95.83%. An 83.5% agreement was observed between the system's prediction and the ground-truth in the Pfirrmann grade. In the case of MSU classification, 95.0% precision was achieved. With the assistance of this system, the accuracy, interpretation efficiency and interrater agreement among surgeons were improved substantially. Conclusion: This system showed considerable accuracy and efficiency, and therefore could serve as an objective reference for the diagnosis and treatment procedure in clinical practice.

The lifetime of the triplet excited state and modulation characteristics of all-optical switching in phenoxy-phthalocyanines liquid.

We present our experimental results on the measurements of excited state dynamics in 2, 9, 16, 23-phenoxy-phthalocyanine (Pc1) and 2, 9, 16, 23-phenoxy-phthalocyanine-zinc (Pc2) using the pump-probe experiment. The results show that the lifetime of the first triplet excited state of the Pc2 longer than Pc1. The lifetimes of the triplet excited state for Pc2 and Pc1 are 12.8 µs and 10.1 µs at the same intensity, respectively. Moreover, analysis of modulation characteristics of all-optical switching (A-OS) shows that the stronger the light intensity of the pump light is, the smaller the normalized transmittance is, and the lower the A-OS response time is. The consequences of such short lifetimes are also discussed in view of the strong A-OS properties of these molecules.