Swimming exercise prevents hippocampal dendritic spine changes and memory loss caused by aging: An application of a new semi-automated spine analysis software.

Dendritic spines are small, ratchet-like protrusions on neuronal dendrites that form synapses for receiving neuronal messages. Dendritic spine morphology is associated with synapse function. If neurons degrade or are damaged, the spine morphology of neurons changes. Given that most commercially available spine analysis software is expensive and complex, this study investigated a semi-automated spine analysis software, CTSpine, and used previously published data to verify the accuracy of the analysis results of this software. We also applied CTSpine to understand whether aging causes alterations in the hippocampal spine morphology and whether physical exercise can impede dendritic spine changes in 20 male Sprague Dawley rats. The spines of pyramidal cells in the hippocampal Cornu Ammonis 1 (CA1) region in the aging group were more enriched in filopodium type pattern than those in the control group, whereas the spines of the exercised aging group showed a similar pattern to that of the control. No significant changes were observed in neuronal dendritic spines in other hippocampal regions. However, long-term hippocampal memory was considerably decreased in the aging group, which was reversed to some extent in the exercised aging group. CTSpine, a self-developed semi-automatic spine analysis software, showed results similar to those noted in published data and can be effectively applied to the study of dendritic patterns, including neurodevelopment and disease.

Mitochondrial DNA leakage induces odontoblast inflammation via the cGAS-STING pathway.

BACKGROUND: Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts. METHODS: The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured. RESULTS: The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown. CONCLUSION: Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.

Asymmetry Analysis of the Resonance Curve in Resonant Integrated Optical Gyroscopes.

The Resonant Integrated Optic Gyroscope (RIOG) is a type of high accuracy gyroscope based on the Sagnac effect. A symmetrical resonance curve is very important to the performance of the RIOG. To further investigate and design a RIOG with a waveguide ring resonator, an in-depth research of the asymmetric resonance curve and its influence on the RIOG is fully developed. Four possible optical noises inducing the resonance curve asymmetry are analyzed and their mathematic models are established. These four optical noises are the normal mode effect, the backscattering noise, the backreflection noise and the polarization noise. Any asymmetry of the resonance curve will not only induce a large output bias error into the gyro output, but also seriously decrease the frequency discrimination parameter of the demodulation curve. By using a tunable fiber laser, the high aspect ratio silicon nitride WRR and the silicon dioxide WRR were tested. The experiment measured resonance curves can be well fitted with the theoretical simulation results. The experimental results show that a high aspect ratio silicon nitride waveguide can effectively suppress the polarization noise in the RIOG.

INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.

The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade.

Forensic Death Investigations of Dog Bite Injuries in 31 Cats.

Animal bite injuries are common in free-ranging cats in Taiwan, and most fatal animal bite events are presumed to be caused by dogs. However, speculation regarding animal abuse may occur when carcasses with prominent injuries are found by members of the general public. Local animal protection offices and veterinary clinicians sometimes face difficulties in convincing these individuals by identifying specific features of dog bite injuries in cat carcasses. Therefore, the present study analyzed injury patterns and distribution in 31 necropsied cats with animal bite injuries, and applied deoxyribonucleic acid (DNA) analysis for canine DNA identification in 13 cats. The main necropsy findings included puncture wounds (26 (83.9%)), linear or small, round contusions/abrasions (20 (64.5%)), lacerations/avulsions (17 (54.8%)), abdominal wall rupture/laceration (19 (61.3%)), herniation (16 (51.6%)), fractures (21 (67.7%)), broken claws (16 (51.6%)), and hair tufts on the body surface (28 (90.3%)). The most-commonly injured regions were the ventral thorax and axilla (23 (74.2%)), hind limbs (22 (71.0%)), shoulder-to-dorsal thorax (21 (67.7%)), back and flank (20 (64.5%)), abdomen (19 (61.3%)), neck (19 (61.3%)), and hip/tail/perineum (17 (54.8%)). Canine mitochondrial DNA was identified in 3 out of 11 cases (27.3%) that were sampled using wound swabs and in 4 out of 5 cases that had hair entrapped in broken claws. In conclusion, this study determined the distribution and features of dog bite injuries in cats and developed an elemental method using trace evidence for DNA identification in animal bites.

Mitochondrial DNA leakage exacerbates odontoblast inflammation through gasdermin D-mediated pyroptosis.

Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-ß was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-ß was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship.

[Electrical and optical phase transition properties of nano vanadium dioxide thin films].

Nano-vanadium dioxide thin films were prepared through thermal annealing vanadium oxide thin films deposited by dual ion beam sputtering. The nano-vanadium dioxide thin films changed its state from semiconductor phase to metal phase through heating by homemade system. Four point probe method and Fourier transform infrared spectrum technology were employed to measure and anaylze the electrical and optical semiconductor-to-metal phase transition properties of nano-vanadium dioxide thin films, respectively. The results show that there is an obvious discrepancy between the semiconductor-to-metal phase transition properties of electrical and optical phase transition. The nano-vanadium dioxide thin films' phase transiton temperature defined by electrical phase transiton property is 63 degrees C, higher than that defined by optical phase transiton property at 5 microm, 60 degrees C; and the temperature width of electrical phase transition duration is also wider than that of optical phase transiton duration. The semiconductor-to-metal phase transiton temperature defined by optical properties increases with increasing wavelength in the region of infrared wave band, and the occuring temperature of phase transiton from semiconductor to metal also increases with wavelength increasing, but the duration temperature width of transition decreases with wavelength increasing. The phase transition properties of nano-vanadium dioxide thin film has obvious relationship with wavelength in infrared wave band. The phase transition properties can be tuned through wavelength in infrared wave band, and the semiconductor-to-metal phase transition properties of nano vanadiium dioxide thin films can be better characterized by electrical property.

The Effect of Ganoderma Microsporum immunomodulatory proteins on alleviating PM2.5-induced inflammatory responses in pregnant rats and fine particulate matter-induced neurological damage in the offsprings.

Fine particulate matter 2.5 (PM2.5) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM2.5-induced inflammatory responses in mother rats, and PM2.5-induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM2.5-induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM2.5-induced modulation.

The expression of PD-1 and LAG-3 in periapical lesions.

Periapical lesions are the distinct result of chronic root canal infection and could generate severe bone resorption surrounding apical regions. Despite the local cytokine and cell-mediated immune responses, periapical lesions are also characterized by its auto-restrict inflammation. However, the detailed mechanism related to its auto-restriction of immune response is still unclear. Co-inhibitory immune checkpoints are important molecules which could negatively modulate immune response especially in T cell function. In this study we detected the expressional pattern of PD-1/LAG-3 in periapical lesions. Immunohistochemical staining showed that the inflammatory response including up-regulation of TNF-α and the infiltration of T cells, was severe in granuloma and restricted in periapical cyst. PD-1 and LAG-3 both could be detected in granuloma and cyst, while scarcely observed in control group. Exhausted T cells, characterized by PD-1 or LAG-3 positive, accumulated within granuloma and reduced in cyst. Our study revealed that in periapical lesions, T cell exhaustion characterized by PD-1 or LAG-3 positive, might contribute to the auto-restriction of inflammatory response in periapical lesions.

[The study of the behavior of exciton and photon within semiconductor microcavity under hydrostatic pressure].

We studied, for the first time, the strong coupling between exciton and cavity mode within semiconductor microcavity under hydrostatic pressure, and measured the Rabi splitting. The strong coupling between exciton and cavity mode, and so Rabi splitting appear clearly as the applied pressure reaches 0.37-0.41 GPa. The experiment result shows that hydrostatic pressure not only can tune the coupling between exciton and cavity mode effectively, but also can keep exciton property almost unchanged during the whole tuning procedure in contrast to other tuning method (temperature field et al). Our result agrees with the related theory very well. The Rabi splitting, extracted from fitting the measured mode-energy vs pressure curves with correspending theoretical model, is equal to 6 meV.

[Magnetic-field-induced nonthermal occupation of higher subbands in a three-barrier tunneling structure].

When injected electrons in a quantum well first experience an intersubband relaxation process before their escaping by tunneling through a double-barrier structure behind, the magnetic suppression of intersubband LO or LA phonon scattering can give rise to a noticeable nonthermal occupation in higher-lying subbands. That is clearly verified by the relative intensity ratio of the interband photoluminescence spectra for E2-HH1 and E1-HH1 transitions. The observed phenomenon may provide an effective method for controlling intersubband scattering rate, a central issue in so-called quantum cascade lasers, and facilitating the population inversion between subbands in quantum wells.

[Investigation on activities of hammerhead ribozyme embedded in genomic RNA of hepatitis delta virus].

OBJECTIVE: To develop HDV as a vehicle to deliver hammerhead ribozyme into hepatocytes, the effects of modified HDV was assessed on the activity of embedded hammerhead ribozyme in vitro and in vivo. METHODS: In vitro activity of ribozyme or HDV-driven ribozyme was assessed by incubating with the [alpha-32 P]-ATP labeled HBV RNA substrates at different temperature. Huh-7 cells were cotransfected with ribozyme or HDV-ribozyme chimera and HBV genome, by which inhibition of ribozymes on HBV transcription in vivo were examined. RESULTS: The results indicated that both temperature and secondary structure influenced the cleavage activity of HDV-driven ribozyme significantly. When the factors were eliminated, the HDV-driven ribozyme could act as well as its counterpart naked ribozyme. While in cultured cells the HDV-driven ribozyme had higher inhibition to HBV gene expression than that of ribozyme alone. CONCLUSION: The results demonstrated that HDV may weaken the activity of embedded ribozyme in vitro, but make it enhanced in cultured cells. Thus, this study could provide a useful evidence to develop HDV as vector for liver-special delivery of ribozyme to against chronic HBV infection.

[Molecular biological progress of hepatocyte growth factor (HGF)].

Hepatocyte growth factor (HGF) is a multifunctional growth factor which is a heterodimeric glycoprotein molecule. There are three truncated HGF variants: NK1, NK2, NK4. The structure of the promoter of HGF is very complicated, and the expression of HGF is regulated by various factors and regulatory elements. Because of the importance of HGF to human body, the genetic engineering expression and gene therapy investigation of HGF are being done.

[Construction and in vitro activity of specific dual-ribozyme against alpha 1 (I) and (III) procollagen genes].

Overexpression of procollagen gene can cause the extraordinary increase of collagen's synthesis and therefore lead to the keloid and hypertrophic scar. To utilize ribozyme to suppress the expression of procollagen genes, a eukaryotic expression recombinant plasmid containing a dual-ribozyme gene against alpha 1 (I) and alpha 1 (III) procollagen genes was constructed. The ribozyme from in vitro transcription was incubated with target transcripts from recombinant plasmids which separately contained the fragments of the second exons of pro alpha 1 (I) and pro alpha 1 (III) collagen genes under various experimental conditions. The results showed that the dual-ribozyme could efficiently catalyze the specific cleavage of the target RNAs at 37 degrees C, 42 degrees C, 50 degrees C and Mg2+ concentration from 10 mmol/L to 20 mmol/L. This work provided a basis for further study on the ribozyme to suppress the expression of procollagen genes and control the cicatrization.