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Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2+ or Vgat+neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

Tall clonal grasses commonly display competitive advantages with nitrogen (N) enrichment. However, it is currently unknown whether the height is derived from the vegetative or reproductive module. Moreover, it is unclear whether the height of the vegetative or reproductive system regulates the probability of extinction and colonization, and determines species diversity. In this study, the impacts on clonal grasses were studied in a field experiment employing two frequencies (twice a year vs. monthly) crossing with nine N addition rates in a temperate grassland, China. We found that the N addition decreased species frequency and increased extinction probability, but did not change the species colonization probability. A low frequency of N addition decreased species frequency and colonization probability, but increased extinction probability. Moreover, we found that species reproductive height was the best index to predict the extinction probability of clonal grasses in N-enriched conditions. The low frequency of N addition may overestimate the negative effect from N deposition on clonal grass diversity, suggesting that a higher frequency of N addition is more suitable in assessing the ecological effects of N deposition. Overall, this study illustrates that reproductive height was associated with the clonal species extinction probability under N-enriched environment.

Background/Objectives: Levo-Stepholidine (l-SPD), a compound extracted from Chinese herbs, has the potential to treat psychotic disorders where cognitive deficits are a critical challenge. L-SPD displays a D1R agonism/D2R antagonism pharmacological profile, and its effect on cognitive function is still vague and lacks comprehensive study. Here, we investigated the impact of l-SPD on two core indexes of executive function, working memory and response inhibition, and learning and memory. Methods: Using a delayed alternation T-maze task (DAT), we investigated the impact of l-SPD on working memory, evaluated its effect on response inhibition using the stop-signal task (SST), and assessed the impact on learning and memory using trace fear conditioning in Sprague-Dawley rats. We further evaluated its effects on prefrontal glutamate receptor expression using western blot. Results: Rats receiving l-SPD made fewer errors in the T-maze, exhibited faster stop action in response to the stop signal, and showed longer-lasting memory retention. Molecular mechanism investigations reveal that l-SPD upregulates the expression of prefrontal glutamate receptors. These results demonstrate that l-SPD improves executive function and memory. Conclusions: Here, we show the enhancement effect of l-SPD on cognitive function, which provides essential implicants for the treatment of cognitive deficits, which is a critical unmet need in psychiatric care.

The versatile motion capability of snake robots offers themselves robust adaptability in varieties of challenging environments where traditional robots may be incapacitated. This study reports a novel flexible snake robot featuring a rigid–flexible coupling structure and multiple motion gaits. To better understand the robot’s behavior, a bending model for the soft actuator is established. Furthermore, a dynamic model is developed to map the relationship between the input air pressure and joint torque, which is the model base for controlling the robot effectively. Based on the wave motion generated by the joint coupling direction function in different planes, multiple motion gait planning methods of the snake-like robot are proposed. In order to evaluate the adaptability and maneuverability of the developed snake robot, extensive experiments were conducted in complex environments. The results demonstrate the robot’s effectiveness in navigating through intricate settings, underscoring its potential for applications in various fields.

The electromagnetic (EM) vibration noise of fractional-slot permanent magnet synchronous motors (PMSMs) has become increasingly prominent. This paper initiates by deriving the spatial and frequency characteristics of radial EM force density (REMFD) and presents a general expression linking the key parameters of the lowest nonzero order REMFD with the stator auxiliary slots. The effectiveness of the formulas and traceability analysis is verified using finite element analysis of prototypes with various pole-slot combinations and numbers of auxiliary slots. The addition of auxiliary slots typically reduces torque ripple, but also affects the average torque and the REMFD. Consequently, a comprehensive analysis and trade-off designs of the 10-pole 12-slot motors with a eccentric arc rotor and a three-arc-segment rotor, are conducted, covering the total harmonic distortion (THD) of the air-gap flux density, main REMFD harmonics, cogging torque, average torque, torque ripple and process. Finally, the EM noise are validated through multi-physics FEA models of multiple optimization schemes. Experimental tests on both the original cogging torque optimization prototype and newly proposed comprehensive process and performance optimization prototype substantiated the validity and precision of the previous analyses. Additionally, it is demonstrated that the lowest non-zero order REMFD significantly contributes to EM noise at even multiples of the frequency but lacks $6kf_{0}$ components. Tangential forces are identified as the primary contributors to $6kf_{0}$ EM noise.

1. Nitrogen (N) enrichment often decreases plant species richness in local communities, thus altering plant species–area relationships (SAR). However, whether N enrichment affects the SAR across global grasslands has not yet been well explored. Additionally, whether and how seasonal N enrichment alters the SAR remains unknown.2. This study employed data from global grasslands (meta-analysis) in combination with a seasonal field N addition experiment during the first 6 consecutive years (2014–2020) in a temperate grassland in northern China.3. We found that N addition did not alter the SAR slopes across global grasslands and our experimental grassland, but significantly reduced the intercepts (plant species richness at the 1 m2 plot scale). There was no significant difference among seasonal N treatments. The SAR intercepts were negatively correlated with increasing experimental years in our temperate grassland, without significant differences among the three seasonal N addition treatments, indicating a cumulative effect on the reduction in plant species richness at 1 m2 with N-enriched conditions.4. These results suggest that N enrichment affects the SAR in grassland ecosystems by reducing the SAR intercepts. Therefore, biodiversity conservation activities should be applied urgently in localities facing increasing atmospheric N deposition.

Persistent hyperplastic primary vitreous (PHPV) is a rare congenital developmental ocular disorder caused by incomplete regression of the embryonic hyaloid vasculature; bilateral presentations are even rarer. We report a 6-year-old child with bilateral PHPV who visited our hospital for strabismus, without exhibiting leukocoria, microphthalmia, and systemic diseases. These unique characteristics distinguish our case from other cases of PHPV. It is crucial to increase awareness of congenital eye disease in children and the importance of performing fundus examination with the pupils dilated.

Nitrogen (N) deposition decreases the temporal stability of ecosystem aboveground biomass production (ecosystem stability). However, little is known about how the responses of ecosystem stability differ based on seasonal N enrichment. By adding N in autumn, winter, or growing season, from October 2014 to May 2020, in a temperate grassland in northern China, we found that only N addition in autumn resulted in a significantly positive correlation between ecosystem mean aboveground net primary productivity (ANPP) and its standard deviation and significantly reduced ecosystem stability. Autumn N-induced reduction in ecosystem stability was associated with the vanished negative effect of community-wide species asynchrony (asynchronous dynamics among populations to environmental perturbations) on the standard deviation of ecosystem ANPP in combination with the emerged positive effect of dominance (Simpson's dominance index that indicates the relative weight of dominant species in a community). Our findings indicate that autumn N addition might overestimate the negative effect of annual atmospheric N deposition on ecosystem stability, suggesting that to better evaluate the influence of N deposition in temperate grasslands, both field experiments and global modeling should consider not only the annual N load but also its seasonal dynamics. Moreover, further studies should pay more attention to the alteration in the ecosystem temporal deviations, which might be more sensitive to human-induced environmental changes.

Perfect vortex beams (PVBs) possess the advantage of a stable light field distribution regardless of their topological charges, and thus they are extensively utilized in various applications, such as free-space optical communication, optical tweezers and laser processing. Herein, we report a new strategy to generate and modulate PVBs using coherent beam combining (CBC) technology. Both piston phase and tilting phase controlling methods have been successfully employed, and the corresponding properties of the generated PVBs have been fully investigated. Moreover, the number and position of the gaps in fractional perfect vortex beams (FPVBs) could be precisely controlled, and the relationships between these modulated parameters and the performance of FPVBs are uncovered. These simulation analysis results demonstrate the potential for flexible modulation of PVBs or FPVBs in the CBC system, indicating promising prospects for coherent beam arrays (CBAs) in laser beam shaping and achieving high-power structured light.

Aminoglycoside antibiotics (AGAs) are widely used in life-threatening infections, but they accumulate in cochlear hair cells (HCs) and result in hearing loss. Increases in adenosine triphosphate (ATP) concentrations and P2X7 receptor expression were observed after neomycin treatment. Here, we demonstrated that P2X7 receptor, which is a non-selective cation channel that is activated by high ATP concentrations, may participate in the process through which AGAs enter hair cells. Using transgenic knockout mice, we found that P2X7 receptor deficiency protects HCs against neomycin-induced injury in vitro and in vivo. Subsequently, we used fluorescent gentamicin–Fluor 594 to study the uptake of AGAs and found fluorescence labeling in wild-type mice but not in P2rx7−/− mice in vitro. In addition, knocking-out P2rx7 did not significantly alter the HC count and auditory signal transduction, but it did inhibit mitochondria-dependent oxidative stress and apoptosis in the cochlea after neomycin exposure. We thus conclude that the P2X7 receptor may be linked to the entry of AGAs into HCs and is likely to be a therapeutic target for auditory HC protection.

Fiber lasers have been widely used in medical care, industries, and scientific research in recent years. The coherent beam combining of fiber lasers with an internal phase control has drawn many interests at present, which is a promising method to achieve a large-scale optical phased array. In this article, we presented a cascaded internal phase control method to expand the internal all-fiber phased array. The method distributes the phase measurements to a series of internal Mach–Zender interferometers. Then, the phase of each loop is locked by the gradient descent algorithm. The electric control method to compensate π-ambiguity between channels is proposed. Finally, the phases of the three fiber beams are locked experimentally to verify the feasibility of the method, and the residue phase error is better than λ/22.

Abstract Background The study is to investigate the influence of high myopia on the consistency between optical coherence tomography (OCT) and visual field in primary open-angle glaucoma (POAG). Methods We enrolled 37 patients with POAG with high myopia (POAG-HM group), 27 patients with POAG without high myopia (POAG group), and 29 controls with high myopia (HM group). All subjects underwent Humphrey perimetry (30–2 and 10–2 algorithms). The peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured using Cirrus HD-OCT. Spearman’s rank correlation analysis was used to determine correlations between OCT and perimetric parameters. Agreement was analyzed by cross-classification and weighted κ statistics. Results In POAG group, the cross-classification analysis showed strong agreement between the inferior temporal GCIPL thickness and the mean sensitivity (MS) of 10–2 algorithms (κ = 0.5447, P = 0.0048), and good agreement between the superior and inferior RNFL thicknesses and 30–2 MS (κ = 0.4407 and 0.4815; P

The influence of thermal blooming on the propagation properties of higher-order mode (HOM) fiber laser array is studied by using the algorithm for simulating the laser beam propagation in the atmosphere. Based on the multiphase screen method and finite-difference method, the four-dimensional (4D) computer code of time-dependent propagation is designed to simulate the propagation of HOM fiber laser array through the atmosphere. In this study, the laser energy focusability of the LP11 mode beam array is investigated in detail for different beamlet arrangements, transverse wind speed, and the content of LP01 mode under the conditions of thermal blooming. In free space, the focal shape of the LP11 mode beam array depends on the arrangement of the second circle of the initial beam array, whereas the influence of the central beamlets is weak. The number of side lobes can be tailored by changing the arrangement of the beamlets. In contrast, under the conditions of thermal blooming, the central beamlet has a significant effect on focal beam shape. It is demonstrated that the laser energy focusability can be improved by rotating the central beamlet or increasing the transverse wind speed. As the content of the LP01 mode increases, the energy is gradually concentrated from the side lobes to the center lobe. Furthermore, the effects of initial beam array arrangements on the energy focus and focal shape are investigated. The optimal arrangement for obtaining high energy focusability is discussed in detail. These results could provide useful references for applications of the HOM beam array.

We theoretically propose and experimentally demonstrate a flexible approach to generate an arbitrary shape-invariant structured array beam during propagation with the prescribed intensity distribution. An algorithm for generating flexible desired phase is presented according the reverse engineering and Huygens–Fresnel theory. In this paper, we outline the theory for creating the shape-invariant array beams. The numerical simulation results show that the shape of generated array beams is invariant and its size increases gradually from the near field to the far field. The generation of shape-invariant structured array beams can be realized by the phase-only and amplitude-only elements encoded on the spatial light modulators. The generated arbitrary shape-invariant structured array beams are verified and are in excellent agreement with the theory.

The effects of the jet engine turbulence on a Gaussian Schell-Model (GSM) beam array propagating in a jet engine plume are studied theoretically. The analytical expressions of the cross-spectral density (CSD) function, the spectral degree of coherence (DOC) and the mean-squared beam width for a GSM beam array propagating through a jet engine plume region are derived based on the extended Huyens-Fresnel integral. It is found that the profile of spectral density and the DOC of a GSM beam array gradually transfer to an elliptical shape as the propagation distance increases, and the elliptical degree becomes greater with increasing source coherence length. Besides, as the source coherence length decreases, the effect of the jet engine turbulence on the beam broadening is smaller and the profile of the DOC appears sidelobes at short distance. It is also found that the values of effective coherence width nearly remain the same for different values of source coherence length after propagating a certain distance. Furthermore, the effects of the number of beamlets on the beam width and effective coherence width are investigated in detail.

Optogenetic stimulation of damaged peripheral nerves has advantages over electrical stimulation but it’s limited to single-site stimulation. Here the authors develop a spiral-shaped LED implant for precise optogenetic stimulation of peripheral nerve bundles at multiple sites and use it to induce distinct limb movements in mice.

The thermal blooming effect and the scaling laws of partially coherent beam (PCB) array propagating in the atmosphere are studied. The four-dimensional (4D) computer code of time-dependent propagation to simulate PCB array through the turbulent atmosphere is designed. Based on numerical simulation, the propagation properties of PCB array are investigated in detail. It is shown that, as the spatial coherence parameter β decreases, the relative beam width increases and the thermal blooming effect becomes more severe. However, the change of the energy Strehl ratio (SRE) versus spatial coherence parameter β is not monotonic because the energy is concentrated on the main lobe for fully coherent beam array. Besides, the scaling laws to estimate the thermal blooming effects of PCB array are investigated. The modified expression of the distortion parameter Nd of a focused PCB array is derived, which is efficient to evaluate the strength of the thermal blooming effects.

We correct a few typographical errors in the original manuscript.

Abstract Background In recent years, proinflammatory cytokine interleukin-1β (IL-1β) was considered to play a critical role in the pathogenesis of depression. In addition, P2X7 receptor (P2X7R), a member of the purinergic receptor family, which is predominantly present on microglia, as well as on astrocytes and neurons in lesser amounts in the central nervous system, was suggested to be involved in the processing and releasing of IL-1β. Here, we investigated the role of P2X7R in the pathogenesis of depression. Methods Male Sprague-Dawley rats were subjected to chronic unpredictable stressors (CUS) for 3 weeks. At the end of week 1, 2, and 3, extracellular ATP, caspase 1, IL-1β, and components and activation of NLRP3 inflammasome (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) were evaluated as biomarker of neuroinflammation. In separate experiments, the rats were microinjected with P2X7R agonists ATP, BzATP, and saline into the hippocampus, respectively, or exposed to CUS combined with hippocampal microinjection with P2X7R antagonist, BBG and A438079, and saline, respectively, for 3 weeks, followed by exposed to forced swimming test and open-field test. Moreover, we also evaluated the depressive and anxiety-like behavior of P2X7-null mice in forced swimming test, open-field test, and elevated plus maze. Results Along with stress accumulation, extracellular ATP, cleaved-caspase 1, IL-1β, and ASC were significantly enhanced in the hippocampus, but P2X7R and NLRP3 were not. Immunoprecipitation assay indicated that along with the accumulation of stress, assembly of NLRP3 inflammasome and cleaved caspase 1 in NLRP3 inflammasome were significantly increased. Moreover, antagonists of P2X7R, either BBG or A438079, prevented the development of depressive-like behaviors induced by chronic unpredictable stress in rats. Meanwhile, we could not observe any depressive-like or anxiety-like behaviors of P2X7-null mice after they had been exposed to CUS. The results implied that P2X7 knockout could impede the development of depressive-like and anxiety-like behaviors induced by CUS. In contrast, chronic administration of agonists of P2X7R, either ATP or BzATP, could induce depressive-like behaviors. Conclusions The activation of P2X7R and subsequent NLRP3 inflammasome in hippocampal microglial cells could mediate depressive-like behaviors, which suggests a new therapeutic target for the prevention and treatment of depression.

As a therapeutic target for neuropathic pain, the anti-nociceptive effects of α 2-adrenoceptors (α2AR) have attracted attention. Dexmedetomidine (DEX), a potent and highly selective α2AR agonist, has exhibited significant analgesic effects in neuropathic pain, but the underlying mechanism has remained elusive. The present study investigated the effect of DEX on Toll-like receptor (TLR)4 and nuclear factor (NF)-κB p65 expression, as well as the production of pro-inflammatory cytokines. The rat monoarthritis (MA) model was induced by intra-articular injection of complete Freund's adjuvant (CFA) at the ankle joint. After induction of MA, the rats were intrathecally treated with normal saline or DEX (2.5 μg) for 3 consecutive days. The concentration of interleukin-1β and -6 as well as tumor necrosis factor-α was examined by ELISA. The expression levels of TLR4 and NF-κB p65 were determined by western blot analysis and immunohistochemistry. The results indicated that the pro-inflammatory cytokines TLR4 and NF-κB p65 were significantly upregulated in MA rats. DEX treatment markedly reduced mechanical and thermal hyperalgesia, suppressed MA-induced elevation of the pro-inflammatory cytokines and inhibited the TLR4/NF-κB p65 pathway, while these effects were blocked by pre-treatment with the selective α2AR antagonist BRL44408 (15 μg) at 30 min prior to CFA injection. These results suggested that DEX has an anti-nociceptive effect via suppressing the TLR4/NF-κB p65 pathway. [ABSTRACT FROM AUTHOR]

Background: Sjogren's syndrome dry eye (SSDE) mainly affectsmiddle-aged women and can negatively affect women's psychological and social functioning. However, little is known about the correlation between vision-related quality of life (VR-QoL) and psychological status for women with SSDE. We therefore examined VR-QoL and psychological status in two groups of Chinese women: an SSDE group and a non-SSDE group. We also explored the associations between VR-QoL scores, sociodemographic measures, ophthalmologic parameters, and psychological status in women with SSDE. Methods: The case-control study recruited 30 female outpatients with SSDE and 30 without SSDE from the Eye and Ear, Nose, and Throat (ENT) Hospital of Fudan University. Demographic and ophthalmologic data were collected from all participants. Ophthalmologic examinations included best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time (TBUT) and Schirmer test. Data collected using the National Eye Institute's Visual Function Questionnaire (NEI-VFQ) and Ocular Surface Disease Index (OSDI) survey instruments were analyzed to identify potential differences in VR-QoL between the SSDE group and the non-SSDE group. We also used the Zung Self-Rating Anxiety and Self-Rating Depression Scales (SAS and SDS) to determine psychological status in both groups. Results: The SSDE group scored significantly lower than the non-SSDE group on the NEI-VFQ subscales of general health, general vision, and long-distance vision activities (all p < 0.05). The SSDE group achieved a significantly higher ocular symptoms score compared with the control group (p = 0.0256). The SAS and SDS scores of the SSDE group were significantly higher than the non-SSDE group (p = 0.0072 and 0.0162, respectively). The prevalence of anxiety and depression in the SSDE group was significantly higher than the non-SSDE group (p = 0.0240 and 0.0200, respectively). Nine of twelve NEI-VFQ subscales were negatively correlated with SAS/SDS scores (all p values were <0.05). The exceptions were social function, color vision and peripheral vision. The composite OSDI score and its three subscale scores for the women in the SSDE group were all positively correlated with overall SAS/SDS scores (all p values were <0.05). Conclusions: Both VR-QoL and psychological status were significantly worse in SSDE group than in the non-SSDE group. The VR-QoL of women with SSDE had a negative correlation with their anxiety and depression levels. [ABSTRACT FROM AUTHOR]

Background: Trigeminal nerve is a major source of the sensory input of the face, and trigeminal neuropathology models have been reported in rodents with injury to branches of the maxillary or mandibular division of the trigeminal nerve. Non-human primates are neuroanatomically more closely related to human than rodents; however, nerve injury studies in non-human primates are limited. Results: We describe here a nerve injury model of maxillary nerve compression (MNC) in the cynomolgus macaque monkey, Macaca fascicularis, and the initial characterization of the consequences of damage to this trigeminal nerve branch. The nerve injury from the compression appeared to be mild, as we did not observe overt changes inhome-cage behavior in the monkeys. When mechanical stimulation was applied to the facial area, monkeys with MNC displayed increased mechanical sensitivity, as the avoidance response scores were lower than those from the control animals. Such a change in mechanical sensitivity appeared to be somewhat bilateral, as the contralateral side also showed increased mechanical sensitivity, although the change on the ipsilateral side was more robust. Multiple-unit recording of the maxillary nerve showed a general pattern of increasing responsiveness to escalating force in mechanical stimulation on the contralateral side. Ipsilateral side of the maxillary nerve showed a lack of responsiveness to escalating force in mechanical stimulation, possibly reflecting a maximum stimulation threshold effect from sensitized nerve due to MNC injury. Conclusions: These results suggest that MNC may produce increased sensitivity of the ipsilateral maxillary nerve, and that this model may serve as a non-human primate model to evaluate the effect of injury to trigeminal nerve branches. [ABSTRACT FROM AUTHOR]

Although pains of various kinds top the list of complaints from women with endometriosis and are the most debilitating of the disease, little is known about the mechanism/mechanisms of endometriosis-associated pains. To test the hypothesis that women with endometriosis have generalized hyperalgesia which may be alleviated by a successful surgery, we recruited 100 patients with surgically and histologically confirmed endometriosis and 70 women without, and tested their responses to pain stimulations. Before the surgery, all patients rated their dysmenorrhea severity by Visual Analog scale (VAS) and went through an ischemic pain test (IPT) and an electrical pain test (EPT). The controls were also administrated with IPT/EPT. Three and 6 months after surgery, all patients were administrated with IPT/EPT and rated their severity of dysmenorrhea. We found that patients with endometriosis had significantly higher IPT VAS scores and lower EPT pain threshold than controls, but after surgery their IPT scores and EPT pain threshold were significantly and progressively improved, along with their dysmenorrhea severity. Thus, we conclude that women with endometriosis have generalized hyperalgesia, which was alleviated by surgery. Consequently, central sensitization may be a possible mechanism underlying various forms of pain associated with endometriosis, and its recognition should have important implications for the development of novel therapeutics and better clinical management of endometriosis. [ABSTRACT FROM PUBLISHER]