The binding of PKCε and MEG2 to STAT3 regulates IL-6-mediated microglial hyperalgesia during inflammatory pain.

Studies have suggested that microglial IL-6 modulates inflammatory pain; however, the exact mechanism of action remains unclear. We therefore hypothesized that PKCε and MEG2 competitively bind to STAT3 and contribute to IL-6-mediated microglial hyperalgesia during inflammatory pain. Freund's complete adjuvant (FCA) and lipopolysaccharide (LPS) were used to induce hyperalgesia model mice and microglial inflammation. Mechanical allodynia was evaluated using von Frey tests in vivo. The interaction among PKCε, MEG2, and STAT3 was determined using ELISA and immunoprecipitation assay in vitro. The PKCε, MEG2, t-STAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, GLUT3, and TREM2 were assessed by Western blot. IL-6 promoter activity and IL-6 concentration were examined using dual luciferase assays and ELISA. Overexpression of PKCε and MEG2 promoted and attenuated inflammatory pain, accompanied by an increase and decrease in IL-6 expression, respectively. PKCε displayed a stronger binding ability to STAT3 when competing with MEG2. STAT3Ser727 phosphorylation increased STAT3 interaction with both PKCε and MEG2. Moreover, LPS increased PKCε, MEG2, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and GLUT3 levels and decreased TREM2 during microglia inflammation. IL-6 promoter activity was enhanced or inhibited by PKCε or MEG2 in the presence of STAT3 and LPS stimulation, respectively. In microglia, overexpression of PKCε and/or MEG2 resulted in the elevation of tSTAT3, pSTAT3Tyr705, pSTAT3Ser727, IL-6, and TREM2, and the reduction of GLUT3. PKCε is more potent than MEG2 when competitively binding to STAT3, displaying dual modulatory effects of IL-6 production, thus regulating the GLUT3 and TREM2 in microglia during inflammatory pain sensation.

TT-type resonator-based differential photoacoustic spectroscopy for trace gas detection.

A novel TT-type resonator was proposed for the first time, to our knowledge, to realize differential photoacoustic (PA) detection for trace gas measurement. The special design of the TT-type resonator allows us to install the microphone at the resonant center of the acoustic field to maximize the use of the absorption-induced PA signal. To meet the requirement of low gas consumption and easy integration, the TT-type resonator-based PA cell was fabricated as a fiber-coupled module with an inner volume of only 1.1 ml. For validation, the TT-type PA cell was integrated to a photoacoustic spectroscopy (PAS) system for acetylene detection. As a result, a linearity of 0.99999 was achieved in a concentration range from 0 to 5000 ppm with a noise equivalent sensitivity of 101 ppb. The proposed TT-type resonator contributes a new style of PA cell structure to the field of PAS gas detection, combining the advantages of easy integration, low gas consumption, differential detection, and photoacoustic enhancement together.

Optical system design of a femi-class ultra-high-resolution spectrometer based on the quaternary dispersion of a middle echelon grating.

In order to meet the needs of the femi-ultra-high spectral resolution test, an optical system of the femi-ultra-high spectral resolution spectrometer in the spectral range of 190-800 nm is designed based on the quaternary dispersion of the middle echelon grating under the condition that the volume and weight of the spectrometer do not increase sharply. After the optimization design, the spectral resolution can reach 51.149 fm in the full field of view of 0.5 mm; at the wavelength of 191 nm, the spectral resolution in the whole spectral range is better than 150 fm, and the maximum distortion of the system is 0.2288%, which can provide a feasible reference for the subsequent design of the spectrometer optical system to realize the simultaneous detection of a wide band and high spectral resolution.

An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action. METHODS: A cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed. RESULTS: CLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor. CONCLUSIONS: To our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE.

Deep ultraviolet high-resolution microscopic hyperspectral imager and its biological tissue detection.

Ultraviolet (UV) hyperspectral imaging technology is commonly used in the field of atmospheric remote sensing. In recent years, some in-laboratory research has been carried out for substance detection and identification. In this paper, UV hyperspectral imaging technology is introduced into microscopy to better utilize the obvious absorption characteristics of components, such as proteins and nucleic acids in biological tissues in the ultraviolet band. A deep UV microscopic hyperspectral imager based on the Offner structure with F # 2.5, low spectral keystone and smile is designed and developed. A 0.68 numerical aperture microscope objective is designed. The spectral range of the system is from 200 nm to 430 nm; the spectral resolution is better than 0.5 nm; and the spatial resolution is better than 1.3 µm. The K562 cells can be distinguished by transmission spectrum of nucleus. The UV microscopic hyperspectral image of the unstained mouse liver slices showed similar results to the microscopic image after hematoxylin and eosin staining, which could help to simplify the pathological examination process. Both results show a great performance in spatial and spectral detecting capabilities of our instrument, which has the potential for biomedical research and diagnosis.

Dexamethasone inhibits IL-8 via glycolysis and mitochondria-related pathway to regulate inflammatory pain.

BACKGROUND: Dexamethasone (Dexa) has been recently found to exert an analgesic effect, whose action is closely related to IL-8. However, whether dexamethasone induces antinociception via glycolysis and mitochondria-related pathways is still unclear. METHODS: Right hind paw inflammatory pain in mice was induced by intraplantar injection of Freund's Complete Adjuvant (FCA). Von Frey test was then used to measure the paw withdrawal threshold. The detection of glycolysis and mitochondrial pathway-related proteins and IL-8 were determined by Western blot and ELISA. The potential interaction between Dexa and fructose-1,6-bisphosphate (FBP, a PKM2 activator) was examined by simulation predictions using molecular docking. RESULTS: Intrathecal administration of Dexa (20 µg/20 µL) had an obvious analgesic effect in FCA-treated mice, which was counteracted by the glycolysis inhibitor 2-deoxyglucose (2-DG, 5 mg/20 µL) or the mitochondria-related pathway inhibitor oligomycin complex (Oligo, 5 µg/20 µL). In the glycolysis pathway, Dexa decreased GLUT3 and had no impact on HIF-1α expression during FCA-induced inflammation. Additionally, Dexa further increased the PKM2 level, accompanied by the formation of hydrogen bonds between Dexa and the PKM2 activator fructose-1,6-bisphosphate (FBP). In the mitochondrial pathway, Dexa downregulated the expression of Mfn2 protein but not the PGC-1α and SIRT-1 levels in the spinal cord. Moreover, both 2-DG and Oligo decreased Mfn2 expression. Finally, IL-8 level was reduced by the single or combined administration of Dexa, 2-DG, and Oligo. CONCLUSION: Dexa attenuated IL-8 expression via glycolysis and mitochondrial pathway-related proteins, thus mediating the analgesic effect during inflammatory pain.

Ultra-Stable Temperature Controller-Based Laser Wavelength Locking for Improvement in WMS Methane Detection.

In the wavelength modulation spectroscopy (WMS) gas detection system, the laser diode is usually stabilized at a constant temperature and driven by current injection. So, a high-precision temperature controller is indispensable in every WMS system. To eliminate wavelength drift influence and improve detection sensitivity and response speed, laser wavelength sometimes needs to be locked at the gas absorption center. In this study, we develop a temperature controller to an ultra-high stability level of 0.0005 °C, based on which a new laser wavelength locking strategy is proposed to successfully lock the laser wavelength at a CH4 absorption center of 1653.72 nm with a fluctuation of fewer than 19.7 MHz. For 500 ppm CH4 sample detection, the 1σ SNR is increased from 71.2 dB to 80.5 dB and the peak-to-peak uncertainty is improved from 1.95 ppm down to 0.17 ppm with the help of a locked laser wavelength. In addition, the wavelength-locked WMS also has the absolute advantage of fast response over a conventional wavelength-scanned WMS system.

Wideband, high spectral resolution UV convex grating imaging spectrometer based on an Offner structure.

Ultraviolet is an effective electromagnetic spectrum in material detection, which has wide application prospects in aerospace and environmental monitoring. A conventional imaging spectrometer has a narrow UV band and low spectral resolution. To solve this problem, a convex grating imaging spectrometer based on an Offner structure with F#2.5 and a 13 mm long slit was designed and developed. The working wavelength ranges from 200 to 433 nm, and the spectral resolution is greater than 0.5 nm. A hyperspectral data cube with both high spatial and spectral resolutions of external scenes can be obtained by the push-broom imaging mode. Fine Fraunhofer lines can be distinguished in the spectrum. The ultraviolet hyperspectral imager can be used for marine oil spills, trace gas monitoring, and other applications that require high signal-to-noise ratios, wide bands, and high spectral resolutions.

Detection and analysis of microplastics in offshore sediment by microscopic differential Raman spectroscopy.

In view of the problems of low pre-screening efficiency, a weak Raman signal, and strong fluorescence interference in the detection of microplastics by traditional Raman spectroscopy, a set of rapid detection system and research methods for microplastics, including fluorescence imaging technology, differential Raman spectroscopy technology, and confocal microscopic Raman technology, are constructed in this paper. A 784/785 nm dual-wavelength laser was used as the excitation light source in the rapid detection system for microplastics. The sediment in the coastal waters of Qingdao Shilaoren was taken as the research object. Polycarbonate and high-density polyethylene with a particle size of 40 µm in the samples were accurately detected and analyzed. The research method for microplastics proposed in this study breaks through relevant key technologies, which we believe will help promote the development of microplastic monitoring technology in the global marine environment and provide strong technical support for the healthy development of the global marine ecological environment.

Underwater hyperspectral imaging system with dual-scanning mode.

As a kind of underwater detecting technology, hyperspectral imaging technology has been well applied in many areas. But the systems usually have a large volume, and it is hard to mount them on different platforms because the external scanning mechanisms are needed for scanning imaging. To overcome these disadvantages, an underwater hyperspectral imaging system that achieves scanning imaging through moving the objective lens is designed. The design of the optical system and internal scanning and focusing structure were completed. According to the design result, the system is assembled and tested. The imaging quality of the whole system is good, and the obtained spectrum of different targets can be distinguished. The system has a good underwater detection capability, which can provide a new feasible technical scheme for underwater detection.

Phosphorylation at Ser 727 Increases STAT3 Interaction with PKCε Regulating Neuron-Glia Crosstalk via IL-6-Mediated Hyperalgesia In Vivo and In Vitro.

METHODS: A rat hyperalgesia model was induced using an intraplantar injection of Freund's complete adjuvant (FCA) or an intrathecal injection of IL-6. Mechanical allodynia was evaluated using von Frey filament tests after intrathecal injections of T-5224 (c-Fos/AP-1 inhibitor), minocycline (Mino, a specific microglia inhibitor), L-2-aminoadipic acid (LAA, an astroglial toxin), PKCε inhibitor peptide, APTSTAT3-9R (STAT3 inhibitor), or anti-IL-6 antibody. The c-Fos, GFAP, Iba-1, PKCε, STAT3, pSTAT3Tyr705 and pSTAT3Ser727, and IL-6 expression at the spinal cord level was assessed by Western blot analysis. The interactive effects of PKCε and STAT3 were determined using immunofluorescence staining and immunoprecipitation in vivo and in vitro. Interleukin-6 promoter activity was examined using luciferase assays. RESULTS: T-5224, Mino, and LAA attenuated FCA- or IL-6-mediated inflammatory pain, with a decrease in c-Fos, GFAP, Iba-1, PKCε, and IL-6 expression. PKCε inhibitor peptide and APTSTAT3-9R reversed FCA-induced nociceptive behavior, while decreasing pSTAT3Ser727, IL-6, c-Fos, GFAP, and Iba-1 expression and PKCε and STAT3 coexpression. Interleukin-6 promoter activity increased in the presence of PKCε and STAT3. The interaction with PKCε increased on phosphorylating STAT3 at Ser727 but not at Tyr705. CONCLUSION: STAT3 phosphorylation at Ser 727 and the interaction with PKCε contribute to hyperalgesia via the IL-6-mediated signaling pathway, thus regulating neuron-glia crosstalk during inflammatory pain.

Compact, UAV-mounted hyperspectral imaging system with automatic geometric distortion rectification.

A highly compact hyperspectral imager with an automatic geometric rectification function is developed in this study, which can be mounted on a UAV for ultra-wide range hyperspectral imaging. For better application, the system can provide visible light image transmission and hyperspectral imaging in the real-time mode. A specific design is proposed to allow the visible light camera and hyperspectral camera to share the same telescope optical path, making the system have a high integration level with a total mass of 1.9 kilograms. Thanks to the sharing-optical-path design, the field of view (FOV), frame rate, and spatial resolution are modified the same between the visible light camera and hyperspectral camera. As a result, the geometric rectification is easily performed, and repeated rectifications are eliminated to improve the imaging efficiency. A FOV of 40 degrees in the frame direction and 26 degrees in the flight direction are realized with a focal length of 13mm, providing a large spectral range from 400 nm to 1000 nm and an excellent spectral resolution of 2.5 nm. An automatic geometric rectification workflow is presented and verified in experiments, which can improve the geometric rectification of hyperspectral images in the presence of low-quality UAV navigation data through the incorporation of frame images. Experimental results show that the relative accuracy of geometric rectification is less than 2 pixels when applying the algorithm to our system dataset.

Design of a confocal micro-Raman spectroscopy system and research on microplastics detection.

Traditional micro-Raman spectroscopy technology has the disadvantages of a weak signal and low signal-to-noise ratio. To fix these issues, a cost-effective and rigorous design method is proposed in this paper, whereby a confocal micro-Raman spectroscopy system is designed and built, and a low-cost reflector and high-pass filter are introduced into the Raman signal-receiving module. The Raman light incident is fully perpendicular to the coupling lens by adjusting the reflection angle of the mirror, making the focus of the coupling lens highly conjugate with the focus of the microscope objective, to enhance the intensity of the Raman signal and improve the signal-to-noise ratio. In order to better apply this technology to the detection and study of microplastics in offshore sediments, a reflective illumination light path is used to avoid the visual interference caused by the capillary structure and opacity of the glass cellulose filter membrane. The detection and analysis of the microplastics on the glass cellulose filter membrane have been carried out by the confocal micro-Raman system designed, which is low cost and capable of obtaining good detection results and meeting the requirements of microplastics detection. The system designed in this paper is expected to be applied to the research and development of Raman detection equipment for microplastics in marine sediments, which is beneficial to promote the development of marine microplastic monitoring technology in the world.

Fluorescence hyperspectral imaging system for analysis and visualization of oil sample composition and thickness.

In this paper, a compact fluorescence hyperspectral imaging system based on a prism-grating-prism (PGP) structure is designed. Its spectrometer spectral range is 400-1000 nm with a spectral resolution of 2.5 nm, and its weight is less than 1.7 kg. The PGP imaging spectrometer combines the technical advantages of prism and grating, by not only using six lenses for imaging and collimation to realize the dual telecentres of object and image but also having a "straight cylinder" structure, which makes the installation and adjustment simple, compact, and stable. By the push-broom method, we obtained the three-dimensional cubic data of different oil products. By normalization processing, minimum noise separation transformation processing, visualization processing, and support vector machine classification processing of different oil fluorescence hyperspectral data, we demonstrate that the fluorescence hyperspectral imaging system can identify different kinds of oil and recognize the oil film thickness. The fluorescence hyperspectral imaging system can be used in oil spill detection, resource exploration, natural disaster monitoring, environmental pollution assessment, and many other fields.

Underwater hyperspectral imaging system using a prism-grating-prism structure.

An underwater hyperspectral imager (UHI) detection system is designed and developed, and a push-broom scan imaging mode was used. The telescope system adopts an image-side telecentric design with 22 mm focal length and 11∘×11∘ field of view. A prism-grating-prism structure was used as the spectral unit of spectrometer system to reduce spectral line bending. The UHI system reaches 5 nm spectral resolution in spectral range from 400 nm to 800 nm, and its modulation transfer function is greater than 0.62 at characteristic frequency in spectral range. An underwater hyperspectral detection experiment was carried out with an electric turntable, and the UHI system is of good imaging quality and spectral resolution, being able to distinguish various underwater targets.

Underwater High-Precision 3D Reconstruction System Based on Rotating Scanning.

This paper presents an underwater high-precision line laser three-dimensional (3D) scanning (LLS) system with rotary scanning mode, which is composed of a low illumination underwater camera and a green line laser projector. The underwater 3D data acquisition can be realized in the range of field of view of 50° (vertical) × 360° (horizontal). We compensate the refraction of the 3D reconstruction system to reduce the angle error caused by the refraction of light on different media surfaces and reduce the impact of refraction on the image quality. In order to verify the reconstruction effect of the 3D reconstruction system and the effectiveness of the refraction compensation algorithm, we conducted error experiments on a standard sphere. The results show that the system's underwater reconstruction error is less than 0.6 mm within the working distance of 140 mm~2500 mm, which meets the design requirements. It can provide reference for the development of low-cost underwater 3D laser scanning system.

Spaceborne limb hyperspectral imager for ozone profile detection.

A spaceborne limb hyperspectral imager for ozone detection is designed and developed. The hyperspectral imager can provide the limb hyperspectral radiances images with wide-band and large dynamic range. It is composed of an off-axis parabolic telescope and prism dispersive off-axis aspheric spectrometer, and large dynamic range detection can be realized by using a band-attenuation filter. The spectral range is from 280nm to 1000nm, the field of view is 2.4° (limb vertical direction) × 0.02° (horizontal direction), and the focal length is 69mm. The design results meet the requirements of image quality and have the characteristics of small volume and light weight, thereby making it especially suitable for the application of space remote sensing unlike existing methods that utilize complicated scanning mirror and multiple color separators. The limb hyperspectral imager is measured and calibrated on ground. It detected limb hyperspectral radiances on Tiangong-2 spacecraft of China.

Optical design of double-grating and double wave band spectrometers using a common CCD.

A new type of optical system comprising double-grating and double wave band spectrometers is designed for atmospheric detection. The optical system can bring oxygen A band (758-778 nm) and water vapor absorption band (758-880 nm) on a charge-coupled device (CCD) at the same time for ultrahigh resolution spectrum measurement. Each absorbed band with three observation directions of atmospheric radiation is imaged in different positions of a common CCD. The spectral resolution is less than 0.07 nm in oxygen A band (758-778 nm), and the spectral resolution is less than 0.28 nm in water vapor absorption band (758-880 nm). Three end faces of the optical fiber are on the slit plane for each wave band, and each end face corresponds to an observation angle. The optical fiber core diameter is 600 µm, the slit width is 25 µm, and the slit length is 18.4 mm. The principle of smile correction is analyzed. The smile of the Czerny-Turner double-grating spectrometer can be compensated by using the tilt field lens in front of the focal plane. The design results corroborate that the maximum smile of the double-grating spectrometer is 5 µm and that the approach of correcting smile is effective. The stray light is analyzed, and the approaches of suppressing the stray light are proposed.

Tanshinone IIA Attenuates Sevoflurane Neurotoxicity in Neonatal Mice.

BACKGROUND: Sevoflurane is the most widely used inhalational anesthetic in pediatric medicine. Despite this, sevoflurane has been reported to exert potentially neurotoxic effects on the developing brain. Clinical interventions and treatments for these effects are limited. Tanshinone IIA (Tan IIA), extracted from Salvia miltiorrhiza (Danshen), has been documented to alleviate cognitive decline in traditional applications. Therefore, we hypothesized that preadministration of Tan IIA may attenuate sevoflurane-induced neurotoxicity, suggesting that Tan IIA is a new and promising drug capable of counteracting the effects of cognitive dysfunction produced by general anesthetics. METHODS: To test this hypothesis, neonatal C57 mice (P6) were exposed to 3% sevoflurane for 2 hours with or without Tan IIA pretreatment at a dose of 10 mg/kg or 20 mg/kg for 3 consecutive days. Cognitive behavior tests such as open field tests and fear conditioning were performed to evaluate locomotor and cognitive function at P31 and P32. At P8, other separate tests, including TdT mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, Western blotting, enzyme-linked immunosorbent assay, and electron microscopy, were performed. The mean differences among groups were compared using 1-way analysis of variance followed by Bonferroni post hoc multiple comparison tests. RESULTS: Repeated exposure to sevoflurane leads to significant cognitive impairment in mice, which may be explained by increased apoptosis, overexpression of neuroinflammatory markers, and changes in synaptic ultrastructure. Interestingly, preadministration of Tan IIA ameliorated these neurocognitive deficits, as shown by increased freezing percentages on the fear conditioning test (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, mean difference, 19, 99% confidence interval for difference, 6.4-31, P < .0001, n = 6). The treatment also reduced the percentage of TUNEL-positive nuclei (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 2.6, 0.73-4.5, P = .0004, n = 6) and the normalized expression of cleaved caspase-3 (sevoflurane versus sevoflurane+Tan IIA [20 mg/kg], 0.27, 0.02-0.51, P = .0046, n = 5). Moreover, it attenuated the production of the neuroinflammatory mediators interleukin (IL)-1ß and IL-6 (normalized sevoflurane versus sevoflurane+Tan IIA [20 mg/kg]: IL-1ß: 0.75, 0.47-1.0; P < .0001; IL-6: 0.66, 0.35-0.97; P < .0001; n = 10 per group). Finally, based on measurements of postsynaptic density, the treatment preserved synaptic ultrastructure (sevoflurane+Tan IIA [20 mg/kg] versus sevoflurane, 42, 20-66; P < .0001; n = 12 per group). CONCLUSIONS: These results indicate that Tan IIA can alleviate sevoflurane-induced neurobehavioral abnormalities and may decrease neuroapoptosis and neuroinflammation.

Optical system design of an atmospheric detector with nadir view and omnidirectional limb view.

A new type of optical system for atmospheric detection is designed by using the principle of panoramic imaging. Compared to the traditional ones, this optical system can observe nadir view and omnidirectional limb view at the same time, thus improving the efficiency and accuracy of the observation data inversion. The optical system consists of a front lens group, a panoramic annular lens, a relay lens group, and a narrowband filter. The nadir view and limb view are shared with the panoramic annular lens and the relay lens group. The narrowband filter is employed to select the specific band and restrain the stray light outside the band. This detector can monitor atmosphere conditions in the nadir field of view of 10° and the limb field of view of 360°×(70.9°-73.3°). Based on this optical design, we develop a prototype for the detector and use it for the field test. The results of experiments verify the feasibility of the optical system design.