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Capsaicin activates primary afferent transient receptor potential vanilloid 1 (TRPV1) in the spinal dorsal horn and induces exaggerated glutamate release. This capsaicin action is followed by a lasting refractory state referred to as "capsaicin desensitization", which is considered a presynaptic event. In this study, using whole-cell recordings and holographic photostimulation, we reassessed this notion by investigating presynaptic glutamate release and the postsynaptic glutamate response during capsaicin administration. We found that both presynaptic synchronous glutamate release and the postsynaptic glutamate response were largely attenuated in this refractory state; in contrast, asynchronous release was exaggerated. Further behavioral studies revealed a quick increase in the mechanical pain threshold with intrathecal capsaicin administration. Taken together, both presynaptic synchronous glutamate release and the postsynaptic response are downregulated during capsaicin desensitization, and this desensitization may transiently increase the pain threshold. Since both presynaptic synchronous release and postsynaptic glutamate responses are attenuated, the traditional electrophysiological evidence supporting capsaicin desensitization as a presynaptic event should be reassessed., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Photo-thermo-refractive (PTR) glass doped with rare-earth ions has attracted considerable attention due to its excellent linear photosensitivity and laser performance. This study investigates the nonlinear photosensitive nanocrystallization induced by ultrafast laser irradiation in Nd-doped PTR glass. Phase contrast microscopy reveals that both Gaussian and Gaussian-Bessel beams can modulate the refractive index positively or negatively, depending on specific conditions. Notably, Gaussian-Bessel beams can significantly extend the thickness of the laser-modified layer. Optical spectra indicate the formation of silver nanoparticles, with concentration increasing as pulse energy increases. Furthermore, X-ray diffraction and transmission electron microscopy confirm the precipitation of nanocrystals with the composition of NaF following laser irradiation and thermal treatment, consistent with conventional PTR glass. The nonlinear optical characteristics of the treated sample are evaluated and successfully applied in a passive Q-switched laser, exhibiting both gain characteristics and saturable absorption. This study provides an effective strategy for multifunctional integrated on-chip devices that possess high damage thresholds and enhanced stability.

Background: Breast cancer is a malignancy characterized by chromosomal instability (CIN). This study aimed to examine the potential diagnostic value of chromosomal instability, detected by low-pass whole-genome sequencing (LPWGS), in the preoperative evaluation of sentinel lymph node metastasis (SLNM) in breast cancer., Methods: A retrospective investigation of clinical records from 29 patients with breast cancer revealed two distinct groups based on sentinel lymph node biopsy (SLNB) results: the SLN metastasis group (24 cases) and the SLN non-metastasis group (five cases). CIN and CIN scores were evaluated using LPWGS. An analysis of univariate data and binary logistic regression was employed to identify factors influencing SLNM, and a curve with receiver operating characteristics (ROC) was constructed to assess the diagnostic utility of CIN in predicting SLNM., Results: A significant association between the SLNM and CIN high groups was observed in breast cancer ( P =0.011). The CIN score in the metastasis group (17,665.055 ± 8,630.691) was higher than that in the non-metastasis group (9,247.973 ± 3,692.873), demonstrating a significant difference ( P =0.044). Univariate binary logistic regression analysis indicated that CIN was a significant predictor for SLNM (odds ratio: 4.036, 95% CI: 1.015-16.047, P =0.048). The AUC of CIN for preoperative diagnosis of SLNM was 0.808 (95%CI: 0.635-0.982, P =0.033), with a sensitivity value of 67.0% and specificity of 100.0% at a threshold of 13,563., Conclusion: Detecting CIN through LPWGS demonstrates diagnostic potential in predicting SLNM in patients with breast cancer before surgery. This approach offers a novel method for assessing axillary lymph node status in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zheng, Xu, Li, Lin and Hao.)

Introduction: The precipitation pattern has changed significantly in arid desert areas, yet it is not clear how the water use strategies of Tamarix ramosissima Ledeb. on coppice dunes along a natural precipitation gradient are affected., Methods: In this study, the hydrogen and oxygen isotope compositions of xylem water, soil water, precipitation, and groundwater were measured by stable isotope techniques in Huocheng, Mosuowan, and Tazhong. Additionally, the water use strategies of natural precipitation gradient were investigated in conjunction with the MixSIAR model., Results: The results indicated that the water sources of T. ramosissima exhibited significant variation from semi-arid to hyper-arid areas. In semi-arid areas, T. ramosissima mainly absorbed shallow, shallow-middle, and middle soil water; however, T. ramosissima shifted its primary water sources to middle and deep soil water in arid areas. In hyper-arid areas, it mainly utilized deep soil water and groundwater. In contrast, the water source contribution rate of T. ramosissima exhibited relative uniformity across each layer in an arid area. Notably, in hyper-arid areas, the proportion of groundwater by T. ramosissima was significantly high, reaching 60.2%. This is due to the relatively shallow groundwater supplementing the deep soil water content in the area. In conclusion, the proportion of shallow soil water decreased by 14.7% for T. ramosissima from semi-arid to hyper-arid areas, illustrating the occurrence of a gradual shift in potential water sources utilized by T. ramosissima from shallow to deep soil water and groundwater., Discussion: Therefore, T. ramosissima on coppice dunes shows flexible water use strategies in relation to precipitation and groundwater, reflecting its strong environmental adaptability. The findings hold significant implications for the conservation of water resources and vegetation restoration in arid areas., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Zhao, Zhou, Dong, Li and Li.)

Liquid fuel is flammable and hazardous, and a pool fire is one of the most serious disasters. Therefore, it is important to develop high-performance firefighting agents. To synthesize aqueous film-forming foam (AFFF) formulations, two C6 short-chain fluorocarbon surfactants Capstone 1157 (FC1157) and sodium perfluorohexylethyl sulfonate (SF852) with different hydrophilic groups were introduced, and three hydrocarbon surfactants sodium dodecyl sulfate (SDS), decyl glucoside (APG0810), and coco glucoside (APG0814) were chosen. The AFFF formulations based on the short-chain fluorocarbon-hydrocarbon compounding system were developed, and the firefighting performance of the formulations was assessed according to the standard pool fire extinction test. The results indicated that amphoteric FC1157 was slightly more effective than anionic SF852 in extinguishing small-scale pool fires and could reduce heat flux more effectively than SF852. Fluorocarbon surfactant FC1157 has been shown to suppress large pool fires much better than SF852, possibly due to its higher foam stability, higher foaming property, lower dynamic surface tension, and lower bubble coarsening rate. Both formulations we studied were more effective than commercial AFFF formulations. A concentration of 0.1-0.3% of FC1157 in an AFFF solution was optimal for extinguishing high-boiling-point oil fires.

With the increasing incidence of metabolic syndrome (MetS) worldwide and no consistent results on PCBs and MetS. A meta-analysis to explore their relationship was conducted. Given the high correlation and overlap of MetS with diabetes, analysis of diabetes risk, was used as a supplement to compare with MetS. Seven studies included MetS, 15 studies for diabetes, and one study included both outcomes. It was found that PCBs may not be a risk factor for MetS, but their high heterogeneity indicates that they are under-represented. In addition, our results showed that total PCBs might be a protective factor against diabetes. In the whole blood subgroup, which can reflect the accumulation of more than one body load, heterogeneity was reduced, and its OR value suggested that PCBs increased the risk of MetS in the whole blood biomaterial. DL-PCBs were positively associated with MetS and diabetes, while NDL-PCBs were negatively associated with diabetes. In the subgroup analysis of PCBs homologs, DL-PCB-126 and DL-PCB-118 were risk factors for MetS and diabetes, respectively. In addition, PCB-153 and 180 showed a dose-response relationship between them and diabetes mellitus, respectively. The results of total analysis of MetS and diabetes mellitus and subgroup analysis of PCBs were mixed, and this reason might be attributed to the different mechanisms of action and effect sizes of different PCBs, so based on subgroup results and in vivo and in vitro experiments, we considered PCBs to be a risk factor for MetS and diabetes. Due to various reasons, there are still many shortcomings in the evaluation of PCBs impact on human health, and more high-quality research are needed to further explore the role of PCBs of different species and congeners in MetS and diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is an abundance of epidemiological evidence and animal experiments concerning the correlation between cadmium exposure and adverse male reproductive health outcomes. However, the evidence remains inconclusive. We conducted a literature search from PubMed, Embase, and Web of Science over the past 3 decades. Pooled r and 95% confidence intervals (CIs) were derived from Cd levels of the type of biological materials and different outcome indicators to address the large heterogeneity of existing literature. Cd was negatively correlated with semen parameters (r = - 0.122, 95% CI - 0.151 to - 0.092) and positively correlated with sera sex hormones (r = 0.104, 95% CI 0.060 to 0.147). Among them, Cd in three different biological materials (blood, semen, and urine) was negatively correlated with semen parameters, while among sex hormones, only blood and urine were statistically positively correlated. In subgroup analysis, blood Cd was negatively correlated with semen density, sperm motility, sperm morphology, and sperm count. Semen Cd was negatively correlated with semen concentration. As for serum sex hormones, blood Cd had no statistical significance with three hormones, while semen Cd was negatively correlated with testosterone. In summary, cadmium exposure might be associated with the risk of a decline in sperm quality and abnormal levels of sex hormones., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

"Naked" ferroferric-oxide nanoparticles (FONPs) synthesized by a femtosecond laser ablation on a bulk stainless steel in liquid were applied to the Nd: YVO 4 laser to achieve passive Q-switched pulse laser output. Without the pollution of ligand, the inherent light characteristic of "naked" FONPs was unaffected. The analysis of the morphological characteristics, dominant chemical elements, and phase composition of the FONPs showed that they were mainly composed of Fe 3 O 4 , which was spherical with an average diameter of 40 nm. The electron transition and orbital splitting of the iron element's octahedral center position under the laser-driven were considered the primary mechanisms of saturable absorption of Fe 3 O 4 nanoparticles.

Zirconium carbide (ZrC), a novel representative of the MXene family, has attracted considerable interest because of its outstanding physicochemical properties and potential applications in optoelectronic devices. For improving its performance as an optical modulator for ultrashort lasers, there is a call to continue studying the nonlinear optical behavior of MXene ZrC. Herein, for the first time, MXene ZrC films were fabricated on fused silica by magnetron sputtering deposition technology and used as a saturable absorber (SA) optical modulator in a passive Q-switched Nd:YAG laser. The saturation absorption behaviors of the prepared ZrC films were characterized by the Z-scan method. Their morphology, band structure, damage threshold, carrier recovery time, and saturation absorption properties were analyzed. The experimental results show that the MXene ZrC SA films exhibit excellent nonlinear optical characteristics, with a saturation intensity of 48.4 MW/cm 2 , a large modulation depth of 6.9%, and an ultrashort recovery time of 2.72 ps. In addition, the damage threshold of MXene ZrC SA films was estimated to be greater than 0.2516 J/cm 2 . By integrating the ZrC SA film optical modulator into the oscillator of the Nd:YAG laser, we achieved stable operation of the Q-switched laser with a central wavelength at 1.06 μm, with the shortest pulse width of 78 ns. The results of this study demonstrate the potential use of MXene ZrC SA films as optical modulators in ultrashort lasers.

Streak tube imaging lidar (STIL) can obtain 4-D images of a target, and its performance is mainly determined by the streak tube sensor. To obtain a large field of view, we developed a streak tube with a photocathode length as large as 35.3 mm, which is larger than the commonly used ST-HDR (30 mm). At the same time, the temporal resolution and dynamic spatial resolution are 60 ps and 12 lp/mm, which are very suitable to obtain accurate target coordinates for 4-D imaging. In addition, the streak tube has a high detection sensitivity of 46 mA/W at 500 nm and, hence, prospects in remote imaging. To test the performance of the streak tube, an underwater STIL experiment was conducted. Echo signal processing was performed by means of a bandpass filter and a matched filter, and then the peak detection algorithm was used to reconstruct the image. The results indicate that a spatial resolution better than 9 mm is achieved in the limpid water with a depth of 20 m, and a range accuracy of 1 cm is achieved in the turbid water with a depth of 10 m. Such a performance suggests that the large-field streak tube is of great potential for underwater target imaging and other remote imaging applications.

Disruption of iron homeostasis in the brain of Parkinson's disease (PD) patients has been reported for many years, but the underlying mechanisms remain unclear. To investigate iron metabolism genes related to PTEN-induced kinase 1 (Pink1) and parkin (E3 ubiquitin ligase), two PD-associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, we conducted a genetic screen in Drosophila and found that altered expression of genes involved in iron metabolism, such as Drosophila ZIP13 (dZIP13) or transferrin1 (Tsf1), significantly influences the disease progression related to Pink1 but not parkin. Several phenotypes of Pink1 mutant and Pink1 RNAi but not parkin mutant were significantly rescued by over-expression (OE) of dZIP13 (dZIP13 OE) or silencing of Tsf1 (Tsf1 RNAi) in the flight muscles. The rescue effects of dZIP13 OE or Tsf1 RNAi were not exerted through mitochondrial disruption or mitophagy; instead, the iron levels in mitochondira were significantly increased, resulting in enhanced activities of enzymes participating in respiration and increased ATP synthesis. Consistently, the rescue effects of dZIP13 OE or Tsf1 RNAi on Pink1 RNAi can be inhibited by decreasing the iron levels in mitochondria through mitoferrin (dmfrn) RNAi. This study suggests that dZIP13, Tsf1, and dmfrn might act independently of parkin in a parallel pathway downstream of Pink1 by modulating respiration and indicates that manipulation of iron levels in mitochondria may provide a novel therapeutic strategy for PD associated with Pink1., (© 2022 International Society for Neurochemistry.)

Allosteric modulation represents an important approach in drug discovery because of its advantages in safety and selectivity. SOMCL-668 is the first selective and potent sigma-1 receptor allosteric modulator, discovered in our laboratory. The present work investigates the potential therapeutic effects of SOMCL-668 on phencyclidine (PCP)-induced schizophrenia-related behavior in mice and further elucidates underlying mechanisms for its antipsychotic-like effects. SOMCL-668 not only attenuated acute PCP-induced hyperactivity and PPI disruption, but also ameliorated social deficits and cognitive impairment induced by chronic PCP treatment. Pretreatment with the selective sigma-1 receptor antagonist BD1047 blocked the effects of SOMCL-668, indicating sigma-1 receptor-mediated responses. This was confirmed using sigma-1 receptor knockout mice, in which SOMCL-668 failed to ameliorate PPI disruption and hyperactivity induced by acute PCP and social deficits and cognitive impairment induced by chronic PCP treatment. Additionally, in vitro SOMCL-668 exerted positive modulation of sigma-1 receptor agonist-induced intrinsic plasticity in brain slices recorded by patch-clamp. Furthermore, in vivo lower dose of SOMCL-668 exerted positive modulation of improvement in social deficits and cognitive impairment induced by the selective sigma-1 agonist PRE084. Also, SOMCL-668 reversed chronic PCP-induced down-regulation in expression of frontal cortical p-AKT/AKT, p-CREB/CREB and BDNF in wide-type but not sigma-1 knockout mice. Moreover, administration of the PI3K/AKT inhibitor LY294002 abolished amelioration by SOMCL-668 of chronic PCP-induced schizophrenia-related behaviors by inhibition of BDNF expression. The present data provide initial, proof-of-concept evidence that allosteric modulation of the sigma-1 receptor may be a novel approach for the treatment of psychotic illness., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The occurrence and removal of 25 antibiotics, including ten quinolones (QNs), four macrolides (MLs), four tetracyclines (TCs) and seven sulfonamides (SNs), were analysed at two sewage treatment plants (STPs) with different treatment units in Guangxi Province, China. The results showed that 14 and 16 antibiotics were detected in the influent of the two STPs, with concentrations ranging from 13.7-4265.2 ng/L and 14.5-10761.7 ng/L, respectively. Among the antibiotics, TCs were the main type in the study area, accounting for more than 79% of the total concentration of all antibiotics. The antibiotic removal efficiencies of the different process units ranged from -56.73% to 100.0%. It was found that the SN removal efficiency of the multistage composite mobile bed membrane bioreactor (MBBR) process was better than that of the continuous-flow Intermission biological reactor (IBR) process, while the IBR process was better than the MBBR process in terms of removing TCs and MLs; however, there was no obvious difference in the QN removal efficiencies of these two processes. Redundancy analysis (RDA) showed a strong correlation between antibiotic concentration and chemical oxygen demand (COD). Risk assessments indicated that algae, followed by invertebrates and fish, were the most sensitive aquatic organisms to the detected antibiotics.

Matrix metalloproteinases (Mmps) are pivotal extracellular proteinases that have been implicated in tumour invasion and metastasis. Drosophila fat body is important for energy storage and utilization, as well as biosynthetic and metabolic activities. The fat body undergoes remodelling during metamorphosis which is characterized by the dissociation of the fat body into individual cells. Mmps play important roles in the regulation of fat body cell dissociation. Here we show that a zinc transporter fear-of-intimacy (foi) is necessary for the cell dissociation of fat body in Drosophila. The progression of fat body cell dissociation was delayed by fat body-specific foi knockdown while it was accelerated by foi overexpression (OE). In essence, these phenotypes are closely associated with intracellular zinc homeostasis, which can be modulated by dietary zinc intervention or genetic modulation of other zinc transporters. Further study indicated that Mmp1 and Mmp2 levels could be transcriptionally regulated by zinc in vivo. Consistently, the retarded fat body cell dissociation caused by Mmp1 or Mmp2 RNAi could be regulated by modulating the expression of foi. Further, by using Drosophila models of malignant tumour Raf GOF scrib -/- and Ras V12 lgl -/- , we showed that the tumour growth, invasion and migration could be markedly inhibited by foi knockdown. These findings demonstrate a close connection between zinc levels and cell dissociation in vivo, and also suggest that manipulation of zinc levels may provide a novel therapeutic strategy for cancer., (© 2021. The Author(s).)

Microfluidic chips and optical elements can be fabricated based on the nonlinear photosensitivity in photo-thermo-refractive (PTR) glass by controlling the growth of nanocrystals in the femtosecond (fs) laser-irradiated region. Here, we focus on CeO 2 and Sb 2 O 3 that play important roles in UV irradiation, experimentally investigate the effects of the dopants on the nonlinear photochemical process in PTR glass triggered by fs Gaussian-Bessel beams. The results show that the generation of Ag 0 atoms and the Ag nanoparticles can be improved by CeO 2 and Sb 2 O 3 co-doping. Besides, each multivalent ion in PTR glass possibly participates in the electron transfer processes and contributes to the generation of Ag 0 atoms. Finally, X-ray diffraction analysis reveals the precipitation of NaF nanocrystals with an average size of 10 to 12 nm after laser irradiation and thermal treatment, which is unrelated to the dopants.

Antireflection and superhydrophilicity performance are desirable for improving the properties of electronic devices. Here, we experimentally provide a strategy of femtosecond laser preparation to create micro-nanostructures on the graphite surface in an air environment. The modified graphite surface is covered with abundant micro-nano structures, and its average reflectance is measured to be 2.7% in the ultraviolet, visible and near-infrared regions (250 to 2250 nm). The wettability transformation of the surface from hydrophilicity to superhydrophilicity is realized. Besides, graphene oxide (GO) and graphene are proved to be formed on the sample surface. This micro-nanostructuring method, which demonstrates features of high efficiency, high controllability, and hazardous substances zero discharge, exhibits the application for functional surface.

Molybdenum carbide (Mo 2 C) is a two-dimensional (2D) MXene material which makes it a promising photoelectric material. In this study, reflective type MXene Mo 2 C thin films were coated on a silver mirror by a magnetron sputtering method and were subsequently used in a passively Q-switched solid-state pulsed laser generator at the central wavelengths of 1.06 and 1.34 μm, respectively. The fabricated thin films of reflective type MXene Mo 2 C exhibited large modulation depth of 6.86% and 5.38% at the central wavelengths of 1064 and 1342 nm, respectively. By inserting the Mo 2 C saturable absorbers (SAs) into V-shaped Nd:YAG laser, short pulses were generated having a pulse duration, pulse energy, and average output power of 254 ns, 2.96 μJ, and 275 mW, respectively, at a wavelength of 1.06 μm. Similarly, shorter laser pulses were obtained in Nd:YVO 4 laser at 1.34 μm. Our results illustrated potential of the 2D MXene Mo 2 C films for laser applications.

Interactions between gut microbiota not only regulate physical health, but also form a vital bridge between the environment and the host, thus helping the host to better adapt to the environment. The improvement of modern molecular sequencing techniques enables in-depth investigations of the gut microbiota of vertebrate herbivores without harming them. By sequencing the 16S rRNA V4-V5 region of the gut microbiota of both the captive and wild kiang in winter and summer, the diversity and function of the microbiota could be compared. The reasons for observed differences were discussed. The results showed that the dominant phyla of the kiang were Bacteroidetes and Firmicutes, and the structure and abundance of the gut microbiota differed significantly between seasons and environments. However, the relatively stable function of the gut microbiota supplies the host with increased adaptability to the environment. The diversity of the intestinal flora of the kiang is relatively low in captivity, which increases their risk to catch diseases to some extent. Therefore, importance should be attached to the impact of captivity on wildlife., (© 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Coordinated intracellular and extracellular signaling is critical to synapse development and functional neural circuit wiring. Here, we report that unesterified docosahexaenoic acid (DHA) regulates functional synapse formation in vivo via retinoid X receptor α (Rxra) signaling. Using Rxra conditional knockout (cKO) mice and virus-mediated transient gene expression, we show that endogenous Rxra plays important roles in regulating spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. We further show that the effects of RXRA are mediated through its DNA-binding domain in a cell-autonomous and reversible manner. Moreover, unesterified DHA increases spine formation and excitatory synaptic transmission in vivo in an Rxra-dependent fashion. Rxra cKO mice generally behave normally but show deficits in behavior tasks associated with social memory. Together, these results demonstrate that unesterified DHA signals through RXRA to regulate spinogenesis and functional synapse formation, providing insight into the mechanism through which DHA promotes brain development and cognitive function., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Deproteinization of crude polysaccharides in the residue from Lycium barbarum berries (LBBs) was conducted using the Sevag method. A Box-Behnken design based on single-factor experiments was employed to optimize the deproteinization technology. The results showed that the deproteinization conditions had significant effects on the extraction yield of polysaccharides and the residual protein content in Lycium barbarum polysaccharides (LBP). The experimental data were fitted to a second-order polynomial equation, using multiple regression analysis with a high coefficient of determination (R 2 ) value. The optimal conditions were as follows: a ratio of raw material to water extract concentrate from the residual LBBs of 0.15 g/mL; a ratio of chloroform to n-butyl alcohol of 2.17 mL/mL; and a ratio of water extract concentrate from residual LBBs to Sevag reagent of 0.50 mL/mL; with a maximum polysaccharide yield of 0.49% and minimum residual protein content of 0.087%. The results were confirmed through validation experiments. GPC analysis indicated that deproteinized LBP molecules became much more homogeneous. X-ray diffraction indicated that the hydrogen bonding of deproteinized LBP was weakened. This optimization of LBP should be a useful method for purification of crude LBP., (© 2020 The Authors.)

Exosome and microRNAs (miRs) are implicated in ischemia/reperfusion (I/R) process. In this study, I/R mouse model was established, and exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated, identified, and injected to I/R mice to observe nerve injury and microglia M1 polarization. The differentially expressed genes in I/R microglia from databases were analyzed, and miRs differentially expressed in exosomes-treated microglia were analyzed by microarray. miR-26b-5p expression in hUCMSCs was intervened. Besides, microglia was extracted and co-cultured with SH-SY5Y or PC12 cells in oxygen-glucose deprivation/reperfusion (OGD/R) models to simulate I/R in vivo . Additionally, Toll-like receptor (TLR) activator GS-9620 was added to microglia. Exosomes alleviated nerve injury and inhibited M1 polarization in microglia. After I/R modeling, CH25H expression in microglia was upregulated but decreased after exosome treatment. miR-26b-5p was upregulated in microglia after exosome treatment and could target CH25H. Reduction in exosomal miR-26b-5p reversed the effects of hUCMSCs-exos on microglia. TLR pathway was activated in microglia after I/R but exosomes prevented its activation. Exosomal miR-26b-5p could repress M1 polarization of microglia by targeting CH25H to inactivate the TLR pathway, so as to relieve nerve injury after cerebral I/R. This investigation may offer new approaches for I/R treatment.

Sensory experience regulates the structural and functional wiring of sensory cortices. In previous work, we showed that whisker deprivation (WD) from birth not only reduced excitatory synaptic transmission of layer (L) 2/3 pyramidal neurons of the correspondent barrel cortex in mice, but also cross-modally reduced synaptic transmission of L2/3 pyramidal neurons in other sensory cortices. Here, we used in utero electroporation, in combination with optical clearing, to examine the main morphological components regulating neural circuit wiring, namely presynaptic bouton density, spine density, as well as dendrite and axon arbor lengths. We found that WD from P0 to P14 reduced presynaptic bouton density in both L4 and L2/3 inputs to L2/3 pyramidal neurons, as well as spine density across the dendritic tree of L2/3 pyramidal neurons, in the barrel field of the primary somatosensory cortex. The cross-modal effects in the primary auditory cortex were manifested mostly as reduced dendrite and axon arbor size, as well as reduced bouton density of L2/3 inputs. Increasing sensory experience by rearing mice in an enriched environment rescued the effects of WD. Together, these results demonstrate that multiple morphological factors contribute to experience-dependent structural plasticity during early wiring of the sensory cortices., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antireflective surfaces, with their great potential applications, have attracted tremendous attention and have been the subject of extensive research in recent years. However, due to the significant optical impedance mismatch between a metal surface and free space, it is still a challenging issue to realize ultralow reflectance on a metal surface. To address this issue, we propose a two-step strategy for constructing antireflective structures on a Ti-6Al-4V (TC4) surface using nanosecond and femtosecond pulsed lasers in combination. By controlling the parameters of the nanosecond laser, microgrooves are first scratched on the TC4 surface to reduce the interface reflection. Then, the femtosecond laser is focused onto the sample surface with orthogonal scanning to induce deep air holes and nanoscale structures, which effectively enhances the broadband absorption. The antireflection mechanism of the dual-scale structures is discussed regarding morphological characterization and hemispherical reflectance measurements. Finally, the modified sample surface covered with micro-nano hybrid structures is characterized by an average reflectance of 3.1% over the wavelengths ranging from 250 nm to 2250 nm.

In this work, a Tungsten disulfide (WS 2 ) reflective saturable absorber (SA) fabricated using the Langmuir-Blodgett technique was used in a solid state Nd:YVO 4 laser operating at 1.34 µm. A Q-switched laser was constructed. The shortest pulse width was 409 ns with the repetition rate of 159 kHz, and the maximum output power was 338 mW. To the best of our knowledge, it is the first time that short laser pulses have been generated in a solid state laser at 1.34 µm using a reflective WS 2 SA fabricated by the Langmuir-Blodgett method.

Deficiency in the E3 ubiquitin ligase UBE3A leads to the neurodevelopmental disorder Angelman syndrome (AS), while additional dosage of UBE3A is linked to autism spectrum disorder. The mechanisms underlying the downstream effects of UBE3A gain or loss of function in these neurodevelopmental disorders are still not well understood, and effective treatments are lacking. Here, using stable-isotope labeling of amino acids in mammals and ubiquitination assays, we identify PTPA, an activator of protein phosphatase 2A (PP2A), as a bona fide ubiquitin ligase substrate of UBE3A. Maternal loss of Ube3a ( Ube3a m-/p+ ) increased PTPA level, promoted PP2A holoenzyme assembly, and elevated PP2A activity, while maternal 15q11-13 duplication containing Ube3a down-regulated PTPA level and lowered PP2A activity. Reducing PTPA level in vivo restored the defects in dendritic spine maturation in Ube3a m-/p+ mice. Moreover, pharmacological inhibition of PP2A activity with the small molecule LB-100 alleviated both reduction in excitatory synaptic transmission and motor impairment in Ube3a m-/p+ mice. Together, our results implicate a critical role of UBE3A-PTPA-PP2A signaling in the pathogenesis of UBE3A-related disorders and suggest that PP2A-based drugs could be potential therapeutic candidates for treatment of UBE3A-related disorders., Competing Interests: The authors declare no conflict of interest.

Upland buzzard ( Buteo hemilasius ), Saker falcon ( Falco cherrug ), and Himalayan vulture ( Gyps himalayensis ) are three common large raptors in the Sanjiangyuan National Park (SNP), China's first national park. Among them, Upland buzzard and Saker falcon play a significant role in controlling plateau rodent populations and reducing the transmission of pathogens carried by rodents. The Himalayan vulture can provide services for the redistribution and recycling of nutrients in the ecosystem, and play an irreplaceable role in the celestial burial culture of Tibetans in China. Exploring their habitat suitability is important for the protection of the three raptors. Our research was based on the current distribution of Upland buzzard, Saker falcon, and Himalayan vulture that we had extensively surveyed in the Sanjiangyuan National Park from 2016 to 2017. Combined with the correlation analysis of environmental variables, we utilized maximum entropy model (MaxEnt) to evaluate and compare the habitat suitability of the three species in the Sanjiangyuan National Park. Elevation, climate, and human disturbance factors, which had direct or indirect effects on species survival and reproduction, were all included in the model. Among them, elevation was the most important environmental variables affecting the suitability of habitats of three species. Temperature-related factor was another important predictor. The high (>60%) suitable habitat areas for Upland buzzard, Saker falcon, and Himalayan vulture were 73,017.63, 40,732.78, and 61,654.33 km 2 , respectively, accounted for 59.32%, 33.09%, and 50.08% of the Sanjiangyuan National Park and their total suitable area (i.e., the sum area of high and moderate habitats) reached 96.07%, 60.59%, and 93.70%, respectively. Besides, the three species have overlapping areas for the suitable habitats, which means that overlapping areas should be highly valued and protected. Therefore, understanding the distribution of suitable habitats of the three raptors can provide useful information and reasonable reference for us to put forward suggestions for their protection and regional management., Competing Interests: None declared.

Two-dimensional (2D) materials as saturable absorbers (SAs) have attracted intense interest for applications in pulsed laser generation because of their distinguishing optical properties. However, the existing methods of preparing SAs were insufficient. Here, we fabricated graphene oxide (GO) SAs by Langmuir-Blodgett (LB) methods for passively Q-switched Nd:YAG laser. The GO sheets were deposited on a quartz plate using the LB method. Two different LB-GO SAs grown under the surface pressure of 22 and 38 mN/m were obtained. Compared with the drop coating method, LB-GO SA exhibited more excellent uniformity, larger nonlinear performance and higher optical transparency. By inserting LB-GO SA into the Nd:YAG laser linear cavity, the short pulse duration of 156 ns and the average output power of 1.313 W were obtained. The slope efficiency was as high as 43.7%, due to low loss of the LB-GO SA. Our results illustrated a new way for preparing the SA using the LB technique.

Here, we report on a packaging method for silver nanodots (SNDs) by using high-silicate porous glass. Millions of nanopores, which are randomly distributed in porous glass, are used as cells for SND nucleation and growth during the initial chemical-reduction process. Then, the sample is annealed at a high-temperature in a reducing atmosphere to impel the further SND growth and nanopore collapse. The compact SND-embedded transparent glass is synthesized in the end. Morphology characterization shows that the SNDs that are encapsulated in the sample have a uniform size of 1.5 to 4.5 nm. Both the sample's saturable and reverse saturable absorptions are observed under the irradiation of 100 fs laser pulses at 800 nm. Saturable absorption's threshhold is characterized to be 1.4 × 10 11 W/cm 2 , which is much lower than what was ever reported. Furthermore, the SNDs-embedded silica as a saturable absorber (SA) has been demonstrated in the Q-switched Nd:YVO 4 laser. The pulse duration as short as 53 nanoseconds is obtained. To our knowledge, it is the first time that SNDs are used as a SA in the passively Q-switched all solid-state laser.

Acute infection, if not kept in check, can lead to systemic inflammatory responses in the brain. Here, we show that within 2 hr of systemic inflammation, PDGFRβ mural cells of blood vessels rapidly secrete chemokine CCL2, which in turn increases total neuronal excitability by promoting excitatory synaptic transmission in glutamatergic neurons of multiple brain regions. By single-cell RNA sequencing, we identified Col1a1 and Rgs5 subgroups of PDGFRβ cells as the main source of CCL2. Lipopolysaccharide (LPS)- or Poly(I:C)-treated pericyte culture medium induced similar effects in a CCL2-dependent manner. Importantly, in Pdgfrb-Cre;Ccl2 fl/fl mice, LPS-induced increase in excitatory synaptic transmission was significantly attenuated. These results demonstrate in vivo that PDGFRβ cells function as initial sensors of external insults by secreting CCL2, which relays the signal to the central nervous system. Through their gateway position in the brain, PDGFRβ cells are ideally positioned to respond rapidly to environmental changes and to coordinate responses., (Copyright © 2018 Elsevier Inc. All rights reserved.)

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, activates ionotropic GABAA receptors and metabotropic GABAB receptors in the central nervous system, respectively. In ventrolateral division of the midbrain periaqueductal gray (PAG), GABAB receptors play important roles in pain modulation. However, the role of endogenous GABA action in presynaptic GABAB receptors remains elusive. Using whole-cell recordings on acute PAG slices from adult rats, here, we show that ambient GABA exerts a tonic inhibition on presynaptic terminals by binding GABAB receptors. Extracellular GABA accumulated by nipecotic acid, which blocks GABA transporters, strengthened GABAB receptor-mediated presynaptic inhibition on both excitatory and inhibitory synapses. Our results indicate that PAG neurons experience GABAB receptor-mediated inhibition determined by GABA transporters. The accumulated GABA-mediated actions may indicate a therapeutic way.

The activation of γ-aminobutyric acid receptor subtype B (GABAB) receptors in the midbrain ventrolateral periaqueductal gray (vlPAG) induces both postsynaptic and presynaptic inhibition. Whereas the postsynaptic inhibition is mediated by G protein-coupled inwardly rectifying K channels, the presynaptic inhibition of neurotransmitter release is primarily mediated by voltage-gated calcium channels. Using whole-cell recordings from acute rat PAG slices, we report here that the bath application of 4-aminopyridine, a voltage-gated K channel blocker, increases the initial GABA and glutamate release probability (P) and reinstates P depressed by presynaptic GABAB receptor activation at inhibitory and excitatory synapses, respectively. However, Ba, which blocks G protein-coupled inwardly rectifying K channels, does not produce similar effects. Our data suggest that the blockade of presynaptic 4-aminopyridine-sensitive K channels in vlPAG facilitates neurotransmitter release and reinstates synaptic transmission that has been altered by presynaptic GABAB receptor activation. Because vlPAG is involved in the descending pain control system, the present results may have potential therapeutic applications.

Ischemic preconditioning (IPC) ameliorates ischemia/reperfusion (I/R) injury in a number of organs, and the glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway regulates I/R-induced proliferation and apoptosis in the central nervous system and heart. However, the function of this signaling pathway in IPC during liver I/R remains unclear. Thus, in this study, we aimed to investigte the role of the GSK-3β/β-catenin pathway during I/R and following ischemic preconditioning. For this purpose, 30 Sprague-Dawley rats were randomly divided into the sham-operated, the I/R and the IPC groups (n=10). Following reperfusion, liver pathology, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), maleic dialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed. Western blot analysis was performed to quantify the GSK-3β, Ser9-phospho-GSK-3β (p-GSK-3β), cytosolic and nuclear β-catenin, vascular endothelial growth factor (VEGF), Bcl-2 and survivin levels. In addition, the Bcl-2 and survivin mRNA levels were assessed by RT-qPCR. Compared with the sham-operated group, I/R increased serum ALT, AST and MDA activity and decreased SOD levels, while IPC significantly decreased serum ALT, AST and MDA activity and increased SOD levels, compared with the I/R group. Simultaneously, I/R increased p-GSK-3β protein expression, and decreased Bcl-2 and survivin protein and mRNA levels. IPC further increased the protein expression of p-GSK-3β, and also increased cytosolic and nuclear β-catenin and VEGF expression compared with the I/R group; the expression of Bcl-2 and survivin was also increased by IPC, both at the mRNA and protein level. The total GSK-3β expression remained unaltered in all the groups. In conclusion, our data demonstrate that IPC exerts protective effects against liver injury induced by I/R and activates the GSK-3β/β-catenin signaling pathway.

The ventrolateral midbrain periaqueductal gray (PAG) neurons have been intensively studied because of their pivotal role in the descending pain modulation system. Activation of GABAB receptors, one type of inhibitory G-protein-coupled receptors (GPCRs), in PAG neurons results in both presynaptic and postsynaptic inhibition. Acute desensitization is defined as rapid attenuation of receptor-mediated signaling. Recent studies report that multiple inhibitory GPCRs, including GABAB receptors, resist acute desensitization in the presynaptic but not postsynaptic compartments of certain neurons in mammal brains. In the present study, employing whole-cell voltage-clamp recordings on acute PAG slices from adult rats, we found that GABAB receptors resist acute desensitization to prolonged administration of baclofen (GABAB receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABAB receptors was independent of presynaptic alteration and vice versa. The GABAB receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABAB receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Elastin is not only one of fundamental components of arterial wall but also an albuminoid substance related to diseases such as aortic dissecting aneurysm. Distributions of elastic fiber in arterial wall were measured using image processing in animal experiment. Statistical results show that the elastic fiber content in arterial wall decreases along the ascending aorta, aortic arch and descending aorta, but the axial distribution of elastic fiber in aortic arch is uniform. Furthermore, the axial distributions in four representative circumferential positions nearly exhibit no notable differences. Hence, the circumferential distribution of elastic fiber in arterial wall is uniform. On the contrary, the radial distribution of elastic fiber in arterial wall is non-uniform, and the elastic fiber content in the internal layer decreased distinctly, compared with that in the middle layer and the external layer. Therefore, the blood vessel can be reasonably simplified as 3-dimensional symmetrical composite material with segments in axial direction and layers in radial direction to a certain extent.

A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of paroxetine in human saliva. Following liquid-liquid extraction of the drug and an internal standard (dibucaine), chromatographic separation was accomplished using a C18 analytical column with a mobile phase consisting of 0.05 mol/L sodium phosphate buffer, pH 5.0, and acetonitrile (A 30:70, v/v; B 60:40, v/v). Paroxetine and the internal standard were detected by ultraviolet absorbance at 205 nm. The average recoveries of the drug and internal standard were 92.5% and 89%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curve was linear over a concentration range of 4 ng/ml. The saliva level of paroxetine in patients with depression taking 10 to 40 mg/day of the drug was significantly correlated with the plasma level of paroxetine in each patient (r = 0.617, P < 0.004, n = 19). These data indicate that the saliva level of paroxetine could be a useful marker to predict the plasma level of the drug.