Clemastine-induced enhancement of hippocampal myelination alleviates memory impairment in mice with chronic pain.

Patients with chronic pain often experience memory impairment, but the underlying mechanisms remain elusive. The myelin sheath is crucial for rapid and accurate action potential conduction, playing a pivotal role in the development of cognitive abilities in the central nervous system. The study reveals that myelin degradation occurs in the hippocampus of chronic constriction injury (CCI) mice, which display both chronic pain and memory impairment. Using fiber photometry, we observed diminished task-related neuronal activity in the hippocampus of CCI mice. Interestingly, the repeated administration with clemastine, which promotes myelination, counteracts the CCI-induced myelin loss and reduced neuronal activity. Notably, clemastine specifically ameliorates the impaired memory without affecting chronic pain in CCI mice. Overall, our findings highlight the significant role of myelin abnormalities in CCI-induced memory impairment, suggesting a potential therapeutic approach for treating memory impairments associated with neuropathic pain.

Efficacy and safety of perioperative application of ketamine on postoperative depression: A meta-analysis of randomized controlled studies.

Ketamine, a commonly used general anesthetic, can produce rapid and sustained antidepressant effect. However, the efficacy and safety of the perioperative application of ketamine on postoperative depression remains uncertain. We performed a meta-analysis to determine the effect of perioperative intravenous administration of ketamine on postoperative depression. Randomized controlled trials comparing ketamine with placebo in patients were included. Primary outcome was postoperative depression scores. Secondary outcomes included postoperative visual analog scale (VAS) scores for pain and adverse effects associated with ketamine. Fifteen studies with 1697 patients receiving ketamine and 1462 controls were enrolled. Compared with the controls, the ketamine group showed a reduction in postoperative depression scores, by a standardized mean difference (SMD) of -0.97, 95% confidence interval [CI, -1.27, -0.66], P < 0.001, I2 = 72% on postoperative day (POD) 1; SMD-0.65, 95% CI [-1.12, -0.17], P < 0.001, I2 = 94% on POD 3; SMD-0.30, 95% CI [-0.45, -0.14], P < 0.001, I2 = 0% on POD 7; and SMD-0.25, 95% CI [-0.38, -0.11], P < 0.001, I2 = 59% over the long term. Ketamine reduced VAS pain scores on POD 1 (SMD-0.93, 95% CI [-1.58, -0.29], P = 0.005, I2 = 97%), but no significant difference was found between the two groups on PODs 3 and 7 or over the long term. However, ketamine administration distinctly increased the risk of adverse effects, including nausea and vomiting (risk ratio [RR] 1.40, 95% CI [1.12, 1.75], P = 0.003, I2 = 30%), headache (RR 2.47, 95% CI [1.41, 4.32], P = 0.002, I2 = 19%), hallucination (RR 15.35, 95% CI [6.24, 37.34], P < 0.001, I2 = 89%), and dizziness (RR 3.48, 95% CI [2.68, 4.50], P < 0.001, I2 = 89%) compared with the controls. In conclusion, perioperative application of ketamine reduces postoperative depression and pain scores with increased risk of adverse effects.

Nanobody peptide conjugate: a novel CD163 based broad neutralizing strategy against porcine reproductive and respiratory syndrome virus.

BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a prevalent swine pathogen, which has caused adverse impact on the global swine industry for almost 30 years. However, due to the immune suppression caused by the virus and the genetic diversity in PRRSV, no virus-targeting broad neutralizing strategy has been successfully developed yet. Antiviral peptide and nanobody have attracted extensive attention with the ease in production and the efficacy in practice. In this study, four new fusion proteins named nanobody peptide conjugates (NPCs) were developed by combining PRRSV specific non-neutralizing nanobodies with CD163-derived peptides targeting the receptor binding domain (RBD) of PRRSV proteins. RESULTS: Four NPCs were successfully constructed using two nanobodies against PRRSV N and nsp9 individually, recombining with two antiviral peptides 4H7 or 8H2 from porcine CD163 respectively. All four NPCs demonstrated specific capability of binding to PRRSV and broad inhibitory effect against various lineages of PRRSV in a dose-dependent manner. NPCs interfere with the binding of the RBD of PRRSV proteins to CD163 in the PRRSV pre-attachment stage by CD163 epitope peptides in the assistance of Nb components. NPCs also suppress viral replication during the stage of post-attachment, and the inhibitory effects depend on the antiviral functions of Nb parts in NPCs, including the interference in long viral RNA synthesis, NF-κB and IFN-ß activation. Moreover, an interaction was predicted between aa K31 and T32 sites of neutralizing domain 4H7 of NPC-N/nsp9-4H7 and the motif 171NLRLTG176 of PRRSV GP2a. The motif 28SSS30 of neutralizing domain 8H2 of NPC-N/nsp9-8H2 could also form hydrogens to bind with the motif 152NAFLP156 of PRRSV GP3. The study provides valuable insights into the structural characteristics and potential functional implications of the RBD of PRRSV proteins. Finally, as indicated in a mouse model, NPC intranasally inoculated in vivo for 12-24 h sustains the significant neutralizing activity against PRRSV. These findings inspire the potential of NPC as a preventive measure to reduce the transmission risk in the host population against respiratory infectious agents like PRRSV. CONCLUSION: The aim of the current study was to develop a peptide based bioactive compound to neutralize various PRRSV strains. The new antiviral NPC (nanobody peptide conjugate) consists of a specific nanobody targeting the viral protein and a neutralizing CD163 epitope peptide for virus blocking and provides significant antiviral activity. The study will greatly promote the antiviral drug R&D against PRRSV and enlighten a new strategy against other viral diseases.

Single-cell RNA sequencing analysis to evaluate antimony exposure effects on cell-lineage communications within the Drosophila testicular niche.

The increasing production and prevalence of antimony (Sb)-related products raise concerns regarding its potential hazards to reproductive health. Upon environmental exposure, Sb reportedly induces testicular toxicity during spermatogenesis; moreover, it is known to affect various testicular cell populations, particularly germline stem cell populations. However, the cell-cell communication resulting from Sb exposure within the testicular niche remains poorly understood. To address this gap, herein we analyzed testicular single-cell RNA sequencing data from Sb-exposed Drosophila. Our findings revealed that the epidermal growth factor receptor (EGFR) and WNT signaling pathways were associated with the stem cell niche in Drosophila testes, which may disrupt the homeostasis of the testicular niche in Drosophila. Furthermore, we identified several ligand-receptor pairs, facilitating the elucidation of intercellular crosstalk involved in Sb-mediated reproductive toxicology. We employed scRNA-seq analysis and conducted functional verification to investigate the expression patterns of core downstream factors associated with EGFR and WNT signatures in the testes under the influence of Sb exposure. Altogether, our results shed light on the potential mechanisms of Sb exposure-mediated testicular cell-lineage communications.

A Novel Method for Precision Measurement and Result Optimization of Detuning Angle for KDP Crystals.

In this paper, we investigate the theory of energy distribution when divergent light undergoes harmonic conversion in KDP crystals, and based on this theory, we design and construct a precision measuring instrument for the detuning angle of (KDP) Crystals (MIDC). The device can obtain the detuning angle of the crystal by a single measurement with an average measurement error of 72.78 urad. At the same time, it also has the function of scanning the full aperture of the crystals. Using the MIDC, it is possible to quickly measure the KDP crystal at a single point and quickly scan the crystal detuning angle at full aperture. In addition, we conduct a theoretical study on the variation of detuning angle caused by gravity-influencing factors under online conditions, propose an optimization formula for the offline measurement results of detuning angle, and calculate the optimized values of detuning angle for two kinds of crystals under 45° online conditions. We finally study the error source of the MIDC device, analyze the trend of the influence of positioning errors of the crystal and optical elements on the detuning angle measurement results, and provide theoretical support for the error monitoring and correction of MIDC.

Contribution of activating lateral hypothalamus-lateral habenula circuit to nerve trauma-induced neuropathic pain in mice.

Neuropathic pain, a severe clinical symptom, significantly affects the quality of life in the patients. The molecular mechanisms underlying neuropathic pain have been the focus of research in recent decades; however, the neuronal circuit-mediated mechanisms associated with this disorder remain poorly understood. Here, we report that a projection from the lateral hypothalamus (LH) glutamatergic neurons to the lateral habenula (LHb), an excitatory LH-LHb neuronal circuit, participates in nerve injury-induced nociceptive hypersensitivity. LH glutamatergic neurons are activated and display enhanced responses to normally non-noxious stimuli following chronic constriction injury. Chemogenetic inhibition of LH glutamatergic neurons or excitatory LH-LHb circuit blocked CCI-induced nociceptive hypersensitivity. Activation of the LH-LHb circuit led to augmented responses to mechanical and thermal stimuli in mice without nerve injury. These findings suggest that LH neurons and their triggered LH-LHb circuit participate in central mechanisms underlying neuropathic pain and may be targets for the treatment of this disorder.

Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation.

INTRODUCTION: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. METHODS: Both female and male mice received a single intraperitoneal injection of 100 µg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. RESULTS: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. CONCLUSIONS: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.

Influence of samarium modification on the phase-change performance and phase structure of tin antimonide.

This work presents the optimization of the crystallization behavior and reliability of Sn15Sb85thin films by doping Sm element. The phase transition behaviors induced by thermal were investigated byin situresistance measurement. With the addition of Sm element, Sn15Sb85film exhibits the superior crystallization temperature (232 °C) and data conservation (172.32 °C for 10 years), larger activation energy of crystallization (4.91 eV) and crystalline resistance (∼103Ω), which contributes to the increased thermal stability of the amorphous state and decrease in the programming energy. The Sm-doping can broaden the energy band gap from 0.55 to 1.07 eV. The amorphous Sm and Sn compositions could retard grain growth and refine grain size from 21.13 to 11.13 nm, combining with x-ray diffraction and x-ray photoelectron spectroscopy. The surface morphology of Sn15Sb85film becomes smoother after Sm doping as determined by atomic force microscopy images, resulting in the improved interfacial reliability. Phase change memory devices based on Sm0.095(Sn15Sb85)0.905films can successfully achieve the complete SET and RESET reversible operation process with high operating speed (200 ns) and low power consumption (1.6 × 10-10J). The results suggest that doping the proper concentration of Sm element will be an effectual solution to adapt and optimize the crystallization properties of Sn15Sb85phase change material.

Simultaneously achieving high performance of thermal stability and power consumption via doping yttrium in Sn15Sb85thin film.

The effects of yttrium dopants on the phase change behavior and microstructure of Sn15Sb85films have been systematically investigated. The yttrium-doped Sn15Sb85film has the higher phase transition temperature, ten year data retention ability and crystallization activation energy, which represent a great improvement in thermal stability and data retention. X-ray diffraction, transmission electron microscopy and x-ray photoelectron spectroscopy reveal that the amorphous Sn and Y components restrict the grain growth and decrease the grain size. Raman mode typically associated with Sb is altered when the substance crystallized. Atomic force microscopy results show that the surface morphology of the doped films becomes smoother. T-shaped phase change storage cells based on yttrium-doped Sn15Sb85films exhibit the lower power consumption. The results demonstrate that the crystallization characteristics of Sn15Sb85film can be tuned and optimized through the yttrium dopant for the excellent performances of phase change memory.

PACAP/PAC1-R activation contributes to hyperalgesia in 6-OHDA-induced Parkinson's disease model rats via promoting excitatory synaptic transmission of spinal dorsal horn neurons.

Pain is a common annoying non-motor symptom in Parkinson's disease (PD) that causes distress to patients. Treatment for PD pain remains a big challenge, as its underlying mechanisms are elusive. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1-R play important roles in regulating a variety of pathophysiological processes. In this study, we investigated whether PACAP/PAC1-R signaling was involved in the mechanisms of PD pain. 6-hydroxydopamine (6-OHDA)-induced PD model was established in rats. Behavioral tests, electrophysiological and Western blotting analysis were conducted 3 weeks later. We found that 6-OHDA rats had significantly lower mechanical paw withdrawal 50% threshold in von Frey filament test and shorter tail flick latency, while mRNA levels of Pacap and Adcyap1r1 (gene encoding PAC1-R) in the spinal dorsal horn were significantly upregulated. Whole-cell recordings from coronal spinal cord slices at L4-L6 revealed that the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in dorsal horn neurons was significantly increased, which was reversed by application of a PAC1-R antagonist PACAP 6-38 (250 nM). Furthermore, we demonstrated that intrathecal microinjection of PACAP 6-38 (0.125, 0.5, 2 µg) dose-dependently ameliorated the mechanical and thermal hyperalgesia in 6-OHDA rats. Inhibition of PACAP/PAC1-R signaling significantly suppressed the activation of Ca2+/calmodulin-dependent protein kinase II and extracellular signal-regulated kinase (ERK) in spinal dorsal horn of 6-OHDA rats. Microinjection of pAAV-Adcyap1r1 into L4-L6 spinal dorsal horn alleviated hyperalgesia in 6-OHDA rats. Intrathecal microinjection of ERK antagonist PD98059 (10 µg) significantly alleviated hyperalgesia in 6-OHDA rats associated with the inhibition of sEPSCs in dorsal horn neurons. In addition, we found that serum PACAP-38 concentration was significantly increased in PD patients with pain, and positively correlated with numerical rating scale score. In conclusion, activation of PACAP/PAC1-R induces the development of PD pain and targeting PACAP/PAC1-R is an alternative strategy for treating PD pain.

Melanin-like polydopamine nanoparticles mediating anti-inflammatory and rescuing synaptic loss for inflammatory depression therapy.

Inflammatory depression is closely related to neuroinflammation. However, current anti-inflammatory drugs have low permeability to cross blood-brain barrier with difficulties reaching the central nervous system to provide therapeutic effectiveness. To overcome this limitation, the nano-based drug delivery technology was used to synthesize melanin-like polydopamine nanoparticles (PDA NPs) (~ 250 nm) which can cross the blood-brain barrier. Importantly, PDA NPs with abundant phenolic hydroxyl groups function as excellent free radical scavengers to attenuate cell damage caused by reactive oxygen species or acute inflammation. In vitro experiments revealed that PDA NPs exhibited excellent antioxidative properties. Next, we aimed to investigate the therapeutic effect of PDA NPs on inflammatory depression through intraperitoneal injection to the lipopolysaccharide-induced inflammatory depression model in mice. PDA NPs significantly reversed the depression-like behavior. PDA NPs was also found to reduce the peripheral and central inflammation induced by LPS, showing that alleviated splenomegaly, reduced serum inflammatory cytokines, inhibited microglial activation and restored synaptic loss. Various experiments also showed that PDA NPs had good biocompatibility both in vivo and in vitro. Our work suggested that PDA NPs may be biocompatible nano-drugs in treating inflammatory depression but their clinical application requires further study.

DSSS Signal Detection Based on CNN.

With the wide application of direct sequence spread spectrum (DSSS) signals, the comprehensive performance of DSSS communication systems has been continuously improved, making the electronic reconnaissance link in communication countermeasures more difficult. Electronic reconnaissance technology, as the fundamental means of modern electronic warfare, mainly includes signal detection, recognition, and parameter estimation. At present, research on DSSS detection algorithms is mostly based on the correlation characteristics of DSSS signals, and autocorrelation algorithm is the most mature and widely used method in practical engineering. With the continuous development of deep learning, deep-learning-based methods have gradually been introduced to replace traditional algorithms in the field of signal processing. This paper proposes a spread spectrum signal detection method based on convolutional neural network (CNN). Through experimental analysis, the detection performance of the CNN model proposed in this paper on DSSS signals in various situations has been compared and analyzed with traditional autocorrelation detection methods for different signal-to-noise ratios. The experiments verified the estimation performance of the model in this paper under different signal-to-noise ratios, different spreading code lengths, different spreading code types, and different modulation methods and compared it with the autocorrelation detection algorithm. It was found that the detection performance of the model in this paper was higher than that of the autocorrelation detection method, and the overall performance was improved by 4 dB.

Period Estimation of Spread Spectrum Codes Based on ResNet.

In order to more effectively monitor and interfere with enemy signals, it is particularly important to accurately and efficiently identify the intercepted signals and estimate their parameters in the increasingly complex electromagnetic environment. Therefore, in non-cooperative situations, it is of great practical significance to study how to accurately detect direct sequence spread spectrum (DSSS) signals in real time and estimate their parameters. The traditional time-delay correlation algorithm encounters the challenges such as peak energy leakage and false peak interference. As an alternative, this paper introduces a Pseudo-Noise (PN) code period estimation method utilizing a one-dimensional (1D) convolutional neural network based on the residual network (CNN-ResNet). This method transforms the problem of spread spectrum code period estimation into a multi-classification problem of spread spectrum code length estimation. Firstly, the In-phase/Quadrature(I/Q) two-way of the received DSSS signals is directly input into the CNN-ResNet model, which will automatically learn the characteristics of the DSSS signal with different PN code lengths and then estimate the PN code length. Simulation experiments are conducted using a data set with DSSS signals ranging from -20 to 10 dB in terms of signal-to-noise ratios (SNRs). Upon training and verifying the model using BPSK modulation, it is then put to the test with QPSK-modulated signals, and the estimation performance was analyzed through metrics such as loss function, accuracy rate, recall rate, and confusion matrix. The results demonstrate that the 1D CNN-ResNet proposed in this paper is capable of effectively estimating the PN code period of the non-cooperative DSSS signal, exhibiting robust generalization abilities.

Knowledge mapping of extracellular vesicles in wound healing: A bibliometric analysis (2002-2022).

Extracellular vesicles in wound healing have become an active research field with substantial value and potential. Nevertheless, there are few bibliometric studies in this field. We aimed to visualise the research hot spots and trends of extracellular vesicles in wound healing using a bibliometric analysis to help understand the future development of basic and clinical research. The articles and reviews regarding extracellular vesicles in the wound healing were selected from the Web of Science Core Collection. VOSviewers, CiteSpace and R package "bibliometric" were used to conduct this bibliometric analysis. A total of 1225 articles from 56 countries led by China and the United States were included. The number of publications related to extracellular vesicles increased year by year. Shanghai Jiaotong University, Huazhong University of Science and Technology, Sun Yat-sen University and Central South University are the main research institutions. International Journal of Molecular Sciences is the most popular journal in this field, while Stem Cell Research & Therapy is the most frequently cited journal. These papers come from 7546 authors, among which Zhang Wei has published the most papers and Zhang Bin has the most cocited papers. The research on the treatment strategy of extracellular vesicles in the process of wound healing is the main topic in this field. "exosomes", "miRNA", "angiogenesis", "regenerative medicine", "inflammation" and "diabetic wound" are the main key words of emerging research hotspots. This is the first bibliometric study, which comprehensively summarises the research trend and development of extracellular vesicles and exocrine bodies in wound healing. These informations determine the latest research frontiers and hot directions, and provide reference for the study of extracellular vesicles and exosomes.

Porcine Reproductive and Respiratory Syndrome Virus nsp11 Antagonizes Broad Antiviral Effects of MCPIP1 by Inducing Interleukin-17 Expression.

Monocyte chemotactic protein-induced protein 1 (MCPIP1) is an inflammatory regulator in immune response and has broad antiviral effects by targeting viral RNA. Porcine reproductive and respiratory syndrome virus (PRRSV), a major viral pathogen in pigs, causes immune suppression leading to coinfection of swine pathogens, but the mechanisms are not fully clarified. In this study, MCPIP1 expression was found to be significantly upregulated in lungs of PRRSV-infected piglets, as well as in Marc-145 and porcine pulmonary alveolar macrophage (PAM) cells upon PRRSV stimulation. MCPIP1 overexpression significantly inhibited PRRSV replication, while MCPIP1 knockdown increased the virus titer. Various mutations in RNase functional domains of MCPIP1 impaired the inhibitory activity against PRRSV, while those in deubiquitinase domains failed to do so. MCPIP1 expression started to decrease from 60 h after PRRSV infection in PAMs. Meanwhile, infection with higher dose of PRRSV further downregulated MCPIP1, indicating the antagonizing effects from PRRSV against MCPIP1. Moreover, it was confirmed that MCPIP1 expression was downregulated in 3D4 cells with either interleukin-17 (IL-17) or nsp11 overexpression, while IL-17 inhibitor abolished the decrease of MCPIP1 caused by nsp11, indicating nsp11 employs IL-17 induction to inhibit MCPIP1. Furthermore, the PRRSV nsp11 mutant with a deficiency in IL-17 induction showed the recovered expression of MCPIP1 in infected cells, inspiring a strategy for virus attenuation. This is the first report about the role of MCPIP1 against PRRSV and the function of PRRSV nsp11 against innate immunity to facilitate virus replication via IL-17. The study not only illuminates PRRSV infection machinery but also enlightens alternative antiviral strategies, such as vaccine candidates. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses the innate immunity and leads to coinfection of swine pathogens. Monocyte chemotactic protein-induced protein 1 (MCPIP1) is a broad-spectrum host antiviral protein. Therefore, to further clarify the mechanism of PRRSV against innate immunity, we explored the relationship between MCPIP1 and PRRSV infection. The results showed that MCPIP1 inhibited PRRSV infection in the early stage of virus infection. Importantly, PRRSV nsp11 subsequently employed IL-17 induction to suppress MCPIP1 expression and antagonized anti-PRRSV effects. Furthermore, PRRSV with mutation of nsp11 S74A failed to induce MCPIP1 reduction. These findings confirmed the function of MCPIP1 against PRRSV and revealed that PRRSV nsp11 plays an important role in virus against innate immunity. This study enlightens a new strategy to develop safer attenuated vaccines against PRRSV by nsp11 mutation.

High-power yellow DSR pulses generated from a mode-locked Dy:ZBLAN fiber laser.

Ultrafast yellow lasers are in high demand in recent biomedical and medical applications; however, direct emission of mode-locked pulses in yellow at the high-power level still presents a huge technical challenge to date. By integrating the nonlinear polarization rotation (NPR) scheme into a Dy:ZBLAN fiber laser, dissipative soliton resonance pulses at ∼575 nm are demonstrated for the first time, to the best of our knowledge. The average output power reaches ∼240 mW at maximum, which is an improvement of almost two orders of magnitude over those reported from the latest mode-locked visible fiber lasers. The laser scheme combines a piece of large-core Dy:ZBLAN gain fiber and free-space NPR components designated at the yellow bandwidth. The maximal pulse energy is 2.4 nJ at the repetition rate of ∼100 MHz and the minimal pulse duration is 83 ps. The achieved wavelength of 575 nm is the shortest ever reached from a fiber-based mode-locked laser to date.

Ultrafast true-green Ho:ZBLAN fiber laser inspired by the TD3 AI algorithm.

Ultrafast lasers in the true-green spectrum, which are scarce due to the "green gap" in semiconductor materials, are in high demand for the surging field of biomedical photonics. One ideal candidate for efficient green lasing is Ho:ZBLAN fiber, as ZBLAN-hosted fibers have already reached picosecond dissipative soliton resonance (DSR) in the yellow. When attempting to push the DSR mode locking further into the green, traditional manual cavity tuning is faced with extreme difficulty, as the emission regime for these fiber lasers is so deeply concealed. Breakthroughs in artificial intelligence (AI), however, provide the opportunity to fulfill the task in a fully automated manner. This work, inspired by the emerging twin delayed deep deterministic policy gradient (TD3) algorithm, represents the first application, to the best of our knowledge, of the TD3 AI algorithm to generate picosecond emissions at the unprecedented true-green wavelength of ∼545 nm. The study thus extends the ongoing AI technique further into the ultrafast photonics region.

Fiber selectivity of peripheral neuropathy in patients with Parkinson's disease.

OBJECTIVE: To determine the function of each type of peripheral nerve fiber and investigate the possible role of levodopa (LD) in peripheral neuropathy (PN) in Parkinson's disease (PD) patients. METHODS: We enrolled 60 patients with idiopathic PD. All PD patients were divided into three groups: levodopa exposure >3 years (LELD), levodopa exposure ≤3 years (SELD) and de novo patients with PD (NOLD). The current perception threshold (CPT), which was measured by Neurometer at 2000, 250 and 5 Hz, the level of homocysteine, Vitamin B12 and folic acid in plasma, were compared with those of sex- and age-matched healthy controls (HCs). RESULTS: Current perception threshold was higher at 250 Hz (p < .05) and 5 Hz (p < .05) in the LELD group than the NOLD, SELD, and control group. CPT was lower at 5 Hz in the NOLD than in the HCs group (p < .05). The CPT of the more affected side of PD patients was positively correlated with H-Y stage at 5 Hz current stimulation (r = .42, p = .01). Multivariate logistic regression analysis showed that elevated homocysteine levels were the risk factor of sensory nerve injury in PD patients (p < .01). Serum homocysteine levels were positively correlated with levodopa (LD) daily dose, LD equivalent daily dose, and LD cumulative lifetime dose (p < .05). CONCLUSIONS: Peripheral neuropathy in PD patients can occur in the early stage of PD exhibiting as hyperesthesia and is fiber selectivity, especially for Aδ and C nerve fibers. PN in PD patients is related to PD itself and long-term LD exposure. Elevated plasma homocysteine is a risk factor for PN in PD patients.

Matrix metalloproteinase-14 regulates collagen degradation and migration of mononuclear cells during infection with genotype VII Newcastle disease virus.

Upregulation of matrix metalloproteinase (MMP)-14, a major driven force of extracellular-matrix (ECM) remodelling and cell migration, correlates with ECM breakdown and pathologic manifestation of genotype VII Newcastle disease virus (NDV) in chickens. However, the functional relevance between MMP-14 and pathogenesis of genotype VII NDV remains to be investigated. In this study, expression, biofunction and regulation of MMP-14 induced by genotype VII NDV were analysed in chicken peripheral blood mononuclear cells (PBMCs). The results showed that JS5/05 significantly increased expression and membrane accumulation of MMP-14 in PBMCs, correlating to enhanced collagen degradation and cell migration. Specific MMP-14 inhibition significantly impaired collagen degradation and migration of JS5/05-infected cells, suggesting dependence of these features on MMP-14. In addition, MMP-14 upregulation correlated with activation of the extracellular signal-regulated kinase (ERK) pathway upon JS5/05 infection, and blockage of the ERK signalling significantly suppressed MMP-14-mediated collagen degradation and migration of JS5/05-infected cells. Using a panel of chimeric NDVs derived from gene exchange between genotype VII and IV NDV, the fusion and haemagglutinin-neuraminidase genes were identified as the major viral determinants for MMP-14 expression and activity. In conclusion, MMP-14 was defined as a critical regulator of collagen degradation and cell migration of chicken PBMCs infected with genotype VII NDV, which may contribute to pathology of the virus. Our findings add novel information to the body of knowledge regarding virus-host biology and NDV pathogenesis.

Sex and onset-age-related features of excessive daytime sleepiness and night-time sleep in patients with Parkinson's disease.

BACKGROUND: The clinical characteristics of Parkinson's disease (PD) differ between men and women, and late- and early-onset patients, including motor symptoms and some nonmotor symptoms, such as cognition, anxiety, and depression. OBJECTIVE: To explore the features of excessive daytime sleepiness (EDS) and night-time sleep quality in PD patients of different sexes and age at onset (AAO). METHODS: Demographic data and clinical characteristics of 586 PD patients were collected. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to investigate the daytime drowsiness and nocturnal sleep. Multivariate logistic regression analysis was used to explore the risk factors of EDS and poor night-time sleep quality. RESULTS: Sleep disorders were common in PD patients. EDS was more prominent in men than in women. There was no significant difference in ESS scores between late-onset PD (LOPD) and early-onset PD. LOPD patients had a higher probability of poor night-time sleep quality. Male sex, disease duration, and depression were risk factors for EDS. In all patients of both sexes and all AAO, depression was a risk factor for poor night-time sleep. CONCLUSION: More attention should be paid to sleep disorders of PD patients, especially male LOPD patients. Depression is a common risk factor for EDS and poor sleep quality in PD patients.