Chiral perovskite-CdSe/ZnS QDs composites with high circularly polarized luminescence performance achieved through additive-solvent engineering.

Chiral perovskite materials are being extensively studied as one of the most promising candidates for circularly polarized luminescence (CPL)-related applications. Balancing chirality and photoluminescence (PL) properties is of great importance for enhancing the value of the dissymmetry factor (glum), and a higher glum value indicates better CPL. Chiral perovskite/quantum dot (QD) composites emerge as an effective strategy for overcoming the dilemma that achieving strong chirality and PL in chiral perovskite while at the same time achieving high glum in this composite is very crucial. Here, we choose diphenyl sulfoxide (DPSO) as an additive in the precursor solution of chiral perovskite to regulate the lattice distortion. How structural variation affects the chiral optoelectronic properties of the chiral perovskite has been further investigated. We find that chiral perovskite/CdSe-ZnS QD composites with strong CPL have been achieved, and the calculated maximum |glum| of the composites increased over one order of magnitude after solvent-additive modulation (1.55 × 10-3 for R-DMF/QDs, 1.58 × 10-2 for R-NMP-DPSO/QDs, -2.63 × 10-3 for S-DMF/QDs, and -2.65 × 10-2 for S-NMP-DPSO/QDs), even at room temperature. Our findings suggest that solvent-additive modulation can effectively regulate the lattice distortion of chiral perovskite, enhancing the value of glum for chiral perovskite/CdSe-ZnS QD composites.

Achieving Simplified and Tunable Flexibility in Carborane-Based Emitters for Quantitative Vapochromic VOC Sensing.

Photoluminescence (PL) sensing of volatile organic compounds (VOCs) represents a convenient and economic detection method toward air pollutants. However, tetraphenylethylene (TPE)-based and recent carborane (Cb)-based sensors retained multiple sites that are responsive to VOC stimulation, making quantitative PL sensing rather challenging. Rendering the simplified and tunable flexibility in the PL sensors is key to achieve the quantitative target. In this work, we proposed a dimeric model of Cb-based emitters to deal with flexibility. Three emissive dibenzothiophene (DBT)-alkynylated carboranes (Cb-1/2/3) were designed and synthesized. Among them, Cb-3 contributed green and green-yellow emission in the crystals, as well as yellow and orange emission in the VOC-incorporated films, together unfolding its vapochromic properties. Crystallographic studies revealed that Cb-3 molecules were invariably dimerized in an interlocked fashion and the redshift in PL was caused by the successive through-space conjugation of DBT moieties. Theoretical calculations verified the thermodynamics stability of Cb-3 dimers and suggested that DBT could individually rotate different angles under the simulation of VOCs. Based on the above findings, we introduced DBT-alkynylated carboranes to detect the VOCs and established linear relationships between the photon energy at the PL maxima and the concentrations of benzene and tetrahydrofuran (THF) vapors. Aside from the successful implementation of quantitative vapochromic sensing, the fast response (6 s) and recovery (3∼5 s), as well as the good reusability, were also evidenced in the sensing of THF vapors.

3D-printed high-birefringence THz hollow-core anti-resonant fiber with an elliptical core.

A high-birefringence and low-loss terahertz (THz) hollow-core anti-resonant fiber (THz HC-ARF) is designed and analyzed numerically by the finite element method (FEM). The THz HC-ARF is composed of an elliptical tube as the core for high birefringence guidance and a pair of symmetrical slabs arranged vertically as the cladding to attain low loss. Numerical analysis indicates that the birefringence reaches 10-2 in the transmission window between 0.21 and 0.35 THz. The highest birefringence is 4.61 × 10-2 at 0.21 THz with a loss of 0.15 cm-1. To verify the theoretical results, the THz HC-ARF is produced by three-dimensional (3D) printing, and the transmission characteristics are determined by THz time-domain spectroscopy (THz-TDS). High birefringence in the range of 2.17 × 10-2 to 3.72 × 10-2 and low loss in the range of 0.12 to 0.18 cm-1 are demonstrated experimentally in the 0.2 to 0.27 THz transmission window. The highest birefringence is 3.72 × 10-2 at 0.22 THz and the corresponding loss is 0.18 cm-1. The THz HC-ARF shows the highest birefringence besides relatively low loss compared to similar THz HC-ARFs reported recently.

Genome-wide Analysis of Histone H3 Lysine 27 Trimethylation Profiles in Sciatic Nerve of Chronic Constriction Injury Rats.

The histone H3 lysine 27 trimethylation (H3K27me3) is one of the most important chromatin modifications, which is associated with injury-activated gene expression in Schwann cells (SCs). However, the alteration of genome-wide H3K27me3 enrichments in the development of neuropathic pain is still unknown. Here, we applied the chromatin immunoprecipitation sequencing (ChIP-seq) approach to identify the alteration of differential enrichments of H3K27me3 in chronic constriction injury (CCI) sciatic nerve of rats and potential molecular mechanisms underlying the development of neuropathic pain. Our results indicated that CCI increased the numbers of SCs displaying H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) and H3K27me3 in the sciatic nerve. ChIP-seq data showed that CCI significantly changed H3K27me3 enrichments on gene promoters in the sciatic nerve. Bioinformatics analyses exhibited that genes gaining H3K27me3 were mostly associated with regulation of cell proliferation, response to stress and oxidation-reduction process. Genes losing this mark were enriched in neuronal generation, and MAPK, cAMP as well as ERBB signaling pathways. Importantly, IL1A, CCL2, NOS2, S100A8, BDNF, GDNF, ERBB3 and C3 were identified as key genes in neuropathic pain. CCI led to significant upregulation of key genes in the sciatic nerve. EZH2 inhibitor reversed CCI-induced increases of H3K27me3 and key gene protein levels, which were accompanied by relieved mechanical allodynia and thermal hyperalgesia in CCI rats. These results indicate that genes with differential enrichments of H3K27me3 in SCs function in various cellular processes and pathways, and many are linked to neuropathic pain after peripheral nerve injury.

Calcitonin gene-related peptide regulates spinal microglial activation through the histone H3 lysine 27 trimethylation via enhancer of zeste homolog-2 in rats with neuropathic pain.

BACKGROUND: Calcitonin gene-related peptide (CGRP) as a mediator of microglial activation at the transcriptional level may facilitate nociceptive signaling. Trimethylation of H3 lysine 27 (H3K27me3) by enhancer of zeste homolog 2 (EZH2) is an epigenetic mark that regulates inflammatory-related gene expression after peripheral nerve injury. In this study, we explored the relationship between CGRP and H3K27me3 in microglial activation after nerve injury, and elucidated the underlying mechanisms in the pathogenesis of chronic neuropathic pain. METHODS: Microglial cells (BV2) were treated with CGRP and differentially enrichments of H3K27me3 on gene promoters were examined using ChIP-seq. A chronic constriction injury (CCI) rat model was used to evaluate the role of CGRP on microglial activation and EZH2/H3K27me3 signaling in CCI-induced neuropathic pain. RESULTS: Overexpressions of EZH2 and H3K27me3 were confirmed in spinal microglia of CCI rats by immunofluorescence. CGRP treatment induced the increased of H3K27me3 expression in the spinal dorsal horn and cultured microglial cells (BV2) through EZH2. ChIP-seq data indicated that CGRP significantly altered H3K27me3 enrichments on gene promoters in microglia following CGRP treatment, including 173 gaining H3K27me3 and 75 losing this mark, which mostly enriched in regulation of cell growth, phagosome, and inflammation. qRT-PCR verified expressions of representative candidate genes (TRAF3IP2, BCL2L11, ITGAM, DAB2, NLRP12, WNT3, ADAM10) and real-time cell analysis (RTCA) verified microglial proliferation. Additionally, CGRP treatment and CCI increased expressions of ITGAM, ADAM10, MCP-1, and CX3CR1, key mediators of microglial activation in spinal dorsal horn and cultured microglial cells. Such increased effects induced by CCI were suppressed by CGRP antagonist and EZH2 inhibitor, which were concurrently associated with the attenuated mechanical and thermal hyperalgesia in CCI rats. CONCLUSION: Our findings highly indicate that CGRP is implicated in the genesis of neuropathic pain through regulating microglial activation via EZH2-mediated H3K27me3 in the spinal dorsal horn.

Analyzing and modulating energy transfer in ternary-emissive system of quantum dot light-emitting diodes towards efficient emission.

The mechanisms for energy transfer including Förster resonance energy transfer (FRET) and radiative energy transfer in ternary-emissive system consists of blended-quantum dots (QDs, red-QDs blended with blue-QDs) emissive layer (EML) and blue-emissive hole-transport material that contained in quantum dot light-emitting diodes (QLEDs) are complicated. As the energy transfer could exhibit either positive or negative impact on QD's photoluminescence (PL) and electroluminescence (EL), it is important to analyze and modulate energy transfer in such ternary-emissive system to obtain high-efficiency QLEDs. In this work, we have demonstrated that proper B-QDs doping has a positive impact on R-QDs' PL and EL, where these improvements were attributed to the B-QDs' spacing effect on R-QDs which weakens homogeneous FRET among R-QDs and near 100% efficient heterogeneous FRET from B-QDs to R-QDs. With optimization based on the analysis of energy transfer, the PL quantum yield of blended-QDs (with R:B blending ratio of 90:10, in quality) film has been enhanced by 35% compared with that of unblended R-QDs film. Moreover, thanks to the spacing effect and high-efficiency FRET from B-QDs to R-QDs, the external quantum efficiency of QLEDs that integrate optimized blended-QDs (R:B=90:10) EML reaches 22.1%, which is 15% higher than that of the control sample (19.2%) with unblended R-QDs EML. This work provides a systematically analytical method to study the energy transfer in ternary-emissive system, and gives a valid reference for the analysis and development of the emerging QLEDs that with blended-QDs EML.

Effect of Interleukin-1ß on Gene Expression Signatures in Schwann Cells Associated with Neuropathic Pain.

Interleukin-1ß (IL-1ß) plays a critical role in the development of neuropathic pain through activation of Schwann cells (SCs) after nerve injury. Here, we applied an RNA sequencing (RNA-seq) approach to identify the effect of IL-1ß on gene signatures of a rat SC line (RSC96) and the potential molecular mechanisms underlying the development of neuropathic pain. RNA-seq data demonstrated a total of 57 significantly differentially expressed genes (DEGs) with 35 up-regulated and 22 down-regulated between SCs treated with IL-1ß, and control SCs without treatment. Bioinformatics analysis showed that key upregulated DEGs included those associated with immune and inflammation-related processes, neurotrophin production and SC proliferation. Five proteins encoded by key upregulated DEGs (Ceacam1, Hap1, Irs3, Lgi4 and Mif) were further verified by Western blot. Consistent with the RNA-Seq results, the expression of key genes was confirmed in SCs by immunofluorescence of the chronic constriction injury (CCI) sciatic nerve in rats. Furthermore, we demonstrated that treatment with IL-1ß resulted in an increase in p38/ERK phosphorylation, and activators of p38/ERK enhanced the effect of IL-1ß on the expression some of the key genes, whereas p38/ERK inhibitors reversed these effects. In conclusion, the present study highlights key genes involved in the development of neuropathic pain through activation of SCs after nerve injury. Identification of these genes and subsequent evidence of their mediation by IL-1ß treatment promote our understanding of molecular mechanisms of nerve injury induced neuropathic pain, and highlight potential molecular targets for the treatment of neuropathic pain.

Recovering the Thermally Activated Delayed Fluorescence in Aggregation-Induced Emitters of Carborane.

The aggregation-induced emission (AIE) behaviors of carborane-based hybrid emitters have been extensively reported, while their combinations with the thermally activated delayed fluorescence (TADF) are still scarce. We designed and synthesized three Janus carboranes (the chemical structures resemble the double-faced god, Janus) Cb-1/2/3 with different carbazole moieties. All of the Janus carboranes exhibited quenched emission in solution with ΦPL (quantum efficiency of photoluminescence (PL)) lower than 0.01. The PL performance was improved by proceeding to the aggregates in THF/water (ΦPL 0.17-0.35) and further improved in the crystals or solid with ΦPL up to 0.99 for Cb-1, 0.85 for Cb-2, and 0.61 for Cb-3, which agreed with the AIE enhancement. Although the PL of solid Cb-1/2/3 showed non-TADF properties with lifetimes only at several nanoseconds, the crystallographic studies have shown a root cause of π···π stacking that quenched the TADF, and the theoretical calculations forecasted small singlet-triplet energy gaps (ΔES-T) therein. According to these findings, TADF was recovered in Cb-1/2/3 by doping into 1,3-bis(carbazol-9-yl)benzene (mCP). The 10 wt % doped films of Cb-1/2/3 have achieved a trade-off of ΦPL (0.84 in Cb-3 and 0.83 in Cb-1) and delayed lifetime (up to 8 µs). The doped devices of organic light-emitting diodes incorporating Cb-1/2/3 achieved the highest external quantum efficiency at 10.1% and the maximized luminance of 5920 cd/m2 at a driving voltage of 8 V.

Analyses of gene expression profiles in the rat dorsal horn of the spinal cord using RNA sequencing in chronic constriction injury rats.

BACKGROUND: Neuropathic pain is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. METHODS: Wistar rats were employed for the establishment of the chronic constriction injury (CCI) models. Using the Illumina HiSeq 4000 platform, we examined differentially expressed genes (DEGs) in the rat dorsal horn by RNA sequencing (RNA-seq) between CCI and control groups. Then, enrichment analyses were performed for these DEGs using Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Hierarchical Cluster, and protein-protein interaction (PPI) network. RESULTS: A total of 63 DEGs were found significantly changed with 56 upregulated (e.g., Cxcl13, C1qc, Fcgr3a) and 7 downregulated (e.g., Dusp1) at 14 days after CCI. Quantitative reverse-transcribed PCR (qRT-PCR) verified changes in 13 randomly selected DEGs. GO and KEGG biological pathway analyses showed that the upregulated DEGs were mostly enriched in immune response-related biological processes, as well as 14 immune- and inflammation-related pathways. The downregulated DEGs were enriched in inactivation of mitogen-activated protein kinase (MAPK) activity. PPI network analysis showed that Cd68, C1qc, C1qa, Laptm5, and Fcgr3a were crucial nodes with high connectivity degrees. Most of these genes which have previously been linked to immune and inflammation-related pathways have not been reported in neuropathic pain (e.g., Laptm5, Fcgr3a). CONCLUSIONS: Our results revealed that immune and defense pathways may contribute to the generation of neuropathic pain after CCI. These mRNAs may represent new therapeutic targets for the treatment of neuropathic pain.

Efficient crystallization-induced emission in fluorenyl-tethered carboranes.

Fluorenyl-tethered o-carborane derivatives (Fl-Cb) as both mono- and di-aryl Cb assemblies were synthesized from the corresponding alkyne and B10H12(Et2S)2 in ca. 60% yields. Crystallographic studies of di-aryl examples show rigid head-to-tail or tail-to-tail packing, while for the mono-aryl examples, only loose packing was observed. In solution, the Fl-Cb compounds exhibit strong quenching of their emission, while aggregation in a mixed solvent results in an enhanced, but still weak, emission [0.11 quantum efficiency (Φ)]. Crystallization-induced emission was observed with the di-aryl examples [Φ up to 0.95]. The excitation spectra are broadened, consistent with considerable orbital degeneracy within the crystals. Theoretical calculations suggest that the inherent orbital degeneracy and the highly-ordered crystalline aggregates contribute to the excellent crystallization-induced emission in these Fl-Cb compounds.

Polarization dependence of plasmon enhanced fluorescence on Au nanorod array.

The spatial anisotropy of Au nanorod results in two distinct orientational modes by which the polarization orientation dependence of excitation and emission can be studied. In this work, a periodical distributed metallic nanostructure substrate, which contains an array of Au nanorods, is synthesized, and the polarization dependence of the plasmon enhanced fluorescence effect is investigated experimentally and numerically. It is found that the fluorescence emission enhancement of organic probe fluorophores located at the surface of Au nanorods depends on the polarization angle very sensitively. Different polarization orientations of the excitation light result in very different enhancement effects. As a result, the change of the polarization orientation of the excitation light can be a sensitive marker of surface chemistry and other possible practical applications.

Blue-shifted emission and enhanced quantum efficiency viaπ-bridge elongation in carbazole-carborane dyads.

Carbazole-carborane linear dyads and di(carbazole)-carborane V-shaped dyads with phenyleneethynylene-based bridges have been synthesized. The V-shaped dyads display the expected red-shifts in the location of their UV-Vis absorption maxima on bridge-lengthening, but show unusual blue-shifts in charge-transfer (CT) emission on the same π-system lengthening. These blue-shifts can be attributed to the 2n + 3 electron count within the carborane cluster in the excited state. The linear dyads luminesce via a combination of local excited (LE) and CT emission, with a red-shift in LE emission and a blue-shift in CT emission accompanying π-bridge elongation. A quantum efficiency as high as 86% in the solution state is achieved from the hybrid LE/CT emission. Time-dependent density functional theory (TD-DFT) calculations at the excited state of these compounds have clarified the photoluminescence blue-shift and suggested a typical cluster C-C bond elongation in the V-shaped dyads. Calculations on the elongated linear dyads have suggested that the electron density is localized at the phenyleneethynylene-containing bridge.

Upconversion Emission and Dual-Mode Sensing Characteristics of NaYF4:Yb3+/Er3+ Microcrystals at High and Ultralow Temperatures.

In this study, we investigate micrometer-sized NaYF4 crystals double-doped with Yb3+/Er3+ lanthanide ions, designed for temperature-sensing applications. In contrast to previous studies, which focused predominantly on the high-temperature regime, our investigation spans a comprehensive range of both high and ultralow temperatures. We explore the relationship between temperature and the upconversion luminescence (UCL) spectra in both frequency and time domains. Our findings highlight the strong dependence of these spectral characteristics of lanthanide-doped NaYF4 crystals on temperature. Furthermore, we introduce a dual-mode luminescence temperature measurement technique, leveraging the upconversion emission intensity ratio for both green and red emissions. This study also examines the correlation between temperature sensing, energy level disparities, and thermal coupling in Er3+ ions across various temperature scales. Our research contributes to advancing the understanding and application of lanthanide-doped materials, setting a foundation for future innovations in temperature sensing across diverse fields.

Spin Quantum Dot Light-Emitting Diodes Enabled by 2D Chiral Perovskite with Spin-Dependent Carrier Transport.

Chiral-induced spin selectivity (CISS) effect provides innovative approach to spintronics and quantum-based devices for chiral materials. Different from the conventional ferromagnetic devices, the application of CISS effect is potential to operate under room temperature and zero applied magnetic field. Low dimensional chiral perovskites by introducing chiral amines are beginning to show significant CISS effect for spin injection, but research on chiral perovskites is still in its infancy, especially on spin-light emitting diode (spin-LED) construction. Here, the spin-QLEDs enabled by 2D chiral perovskites as CISS layer for spin-dependent carrier injection and CdSe/ZnS quantum dots (QDs) as light emitting layer are reported. The regulation pattern of the chirality and thickness of chiral perovskites, which affects the circularly polarized electroluminescence (CP-EL) emission of spin-QLED, is discovered. Notably, the spin injection polarization of 2D chiral perovskites is higher than 80% and the CP-EL asymmetric factor (gCP-EL ) achieves up to 1.6 × 10-2 . Consequently, this work opens up a new and effective approach for high-performance spin-LEDs.

Enhancing the Performance of Perovskite Light-Emitting Diodes via Synergistic Effect of Defect Passivation and Dielectric Screening.

Metal halide perovskites, particularly the quasi-two-dimensional perovskite subclass, have exhibited considerable potential for next-generation electroluminescent materials for lighting and display. Nevertheless, the presence of defects within these perovskites has a substantial influence on the emission efficiency and durability of the devices. In this study, we revealed a synergistic passivation mechanism on perovskite films by using a dual-functional compound of potassium bromide. The dual functional potassium bromide on the one hand can passivate the defects of halide vacancies with bromine anions and, on the other hand, can screen the charged defects at the grain boundaries with potassium cations. This approach effectively reduces the probability of carriers quenching resulting from charged defects capture and consequently enhances the radiative recombination efficiency of perovskite thin films, leading to a significant enhancement of photoluminescence quantum yield to near-unity values (95%). Meanwhile, the potassium bromide treatment promoted the growth of homogeneous and smooth film, facilitating the charge carrier injection in the devices. Consequently, the perovskite light-emitting diodes based on this strategy achieve a maximum external quantum efficiency of ~ 21% and maximum luminance of ~ 60,000 cd m-2. This work provides a deeper insight into the passivation mechanism of ionic compound additives in perovskite with the solution method.

Unprecedented boron-functionalized carborane derivatives by facile and selective cobalt-induced B-H activation.

The 16-electron complex CpCoS2C2B10H10 (1) is found to react with the alkynes HC≡CC(O)R [R = methyl (Me), phenyl (Ph), styryl (St), ferrocenyl (Fc)] at ambient temperature to give two types of 17-electron cobalt complexes 2a-d and 3a-d containing unique B(3)/B(6)-norbornyl carborane moieties. A formation mechanism via a tandem sequence of metal-induced B-H activation, B-Cp formation, Cp delivery and Diels-Alder addition is proposed on the basis of DFT calculations. The reactivity of these paramagnetic 17-electron complexes has been studied: Exposed to a combination of air, moisture and silica, complexes 2a-d undergo alkyl C-S cleavage to give 16-electron complexes 4a-c containing a boron-norbornadienyl moiety, and simultaneous carboranyl C-S cleavage to afford cobalt-free carborane derivatives 5a-d containing a boron-norbornyl unit. Both 2a-d and 3a-d allow further alkyne insertion into the Co-S bond to generate cobalt-free boron-norbornyl carborane derivatives (Z/E)-7a-d and (Z/E)-8a-d, both containing a vinyl sulfido group. Addition of AlCl3 not only promotes the conversion of 2a-d, but also leads predominantly to (E)-9a-d as retro-Diels-Alder products. Upon heating, the isomerization from E to Z-configuration of the vinyl group and reorganization of the norbornyl moiety of (Z/E)-7a-d occur to lead to (Z)-9a-d as well as the unexpected [1,2]-H shifted products (Z)-10b,c. Thus, the 17-electron complexes 2a-d and 3a-d serve as intermediates for synthesis of variety of boron-functionalized carborane derivatives. In this study, efficient routes have been developed through cobalt-mediated B-H activation to prepare boron-functionalized carborane derivatives that are unavailable by conventional routes.

Protease-activated receptor 4 activation increases the expression of calcitonin gene-related peptide mRNA and protein in dorsal root ganglion neurons.

Accumulating evidence demonstrates that nociceptor activation evokes a rapid change in mRNA and protein levels of calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons. Although the colocalization of CGRP and protease-activated receptor-4 (PAR4), a potent modulator of pain processing and inflammation, was detected in DRG neurons, the role of PAR4 activation in the expression of CGRP has not been investigated. In the present study, the expression of CGRP and activation (phosphorylation) of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in rat DRG neurons were measured by immunofluorescence, real-time PCR, and Western blotting after AYPGKF-NH2 (selective PAR4-activating peptide; PAR4-AP) intraplantar injection or treatment of cultured DRG neurons. The expression of CGRP in cultured DRG neurons was also assessed after treatment with AYPGKF-NH2 with preaddition of PD98059 (an inhibitor for ERK1/2 pathway). Results showed that PAR4-AP intraplantar injection or treatment of cultured DRG neurons evoked significant increases in DRG cells displaying CGRP immunoreactivity and cytoplasmic and nuclear staining for phospho-ERK1/2 (p-ERK1/2). Percentages of total DRG neurons expressing both CGRP and PAR4 or p-ERK1/2 also increased significantly at 2 hr after PAR4-AP treatment. Real-time PCR and Western blotting showed that PAR4-AP treatment significantly increased expression of CGRP mRNA and protein levels in DRG neurons. The PAR4 activation-evoked CGRP expression both at mRNA and at protein levels was significantly inhibited after p-ERK1/2 was inhibited by PD98059. These results provide evidence that activation of PAR4 upregulates the expression of CGRP mRNA and protein levels in DRG neurons via the p-ERK1/2 signal pathway.

Capsaicin up-regulates protease-activated receptor-4 mRNA and protein in primary cultured dorsal root ganglion neurons.

Previous study has shown that there is a functional link between the transient receptor potential vanilloid type 1 (TRPV1) receptor and protease-activated receptor-4 (PAR4) in modulation of inflammation and pain. Capsaicin activation of TRPV1 is involved in enhancement of the expression of TRPV1 in mRNA and protein in dorsal root ganglion (DRG) in vivo. Whether capsaicin could influence expression of PAR4 in primary sensory neurons remains unknown. In the present study, expression of PAR4 in cultured rat DRG neurons was observed using immunofluorescence, real-time PCR and Western blots to examine whether increases in PAR4 mRNA and protein levels are induced by capsaicin treatment with or without pre-treatment of forskolin, a cyclic AMP/protein kinase A (cAMP/PKA) activator or PKA inhibitor fragment 14-22 (PKI14-22), a PKA inhibitor. Capsaicin treatment of cultured DRG neurons significantly increased the expression of PAR4 in mRNA and protein levels. The percentage of PAR4-, TRPV1-immunoreactive neurons and their co-localization in cultured DRG neurons increased significantly in the presence of capsaicin as compared with that in the absence of capsaicin. Compared with capsaicin-only group, pre-incubation with forskolin strongly enhanced the capsaicin-induced increase of PAR4 in mRNA and protein levels. Consistent with the involvement of PKA in the modulation of PAR4 expression, this evoked expression both at mRNA and protein levels was significantly inhibited after PKA was inhibited by pre-incubation with PKI14-22. Taken together, these results provide evidence that TRPV1 activation significantly increases the expression of PAR4 mRNA and protein levels in primary cultures of DRG neurons after capsaicin incubation. Effects of capsaicin on PAR4 expression appear to be mediated by cAMP/PKA signal pathways in DRG neurons.

Interleukin-1ß increased the expression of protease-activated receptor 4 mRNA and protein in dorsal root ganglion neurons.

Protease-activated receptor-4 (PAR4) is localized in primary sensory neurons and is believed to implicate in the modulation of nociceptive mechanisms. The pro-inflammatory cytokine interleukin-1ß (IL-1ß) is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. Previous studies have shown that IL-1ß enhances the expression of PAR4 in many cell types but the effect of this cytokine on primary sensory neuron PAR4 expression is less clear. In the present study, we evaluated in rat dorsal root ganglion (DRG) neurons the influence of IL-1ß on PAR4 mRNA and protein levels after IL-1ß intraplantar injection into the hind-paw or treatment of cultured DRG neurons. The expression of PAR4 in cultured DRG neurons was also assessed after treatment with IL-1ß with pre-addition of phorbol-12-myristate 13-acetate (PMA, a PKC activator) or chelerythrine chloride (a PKC inhibitor). We found that IL-1ß intraplantar injection into the hind-paw or long-term exposure of cultured DRG neurons to IL-1ß significantly increased the proportion of DRG neurons expressing PAR4 immunoreactivity. Real-time PCR and western blotting showed that IL-1ß treatment also significantly elevated PAR4 mRNA and protein levels in DRG neurons. This IL-1ß effect was enhanced in DRG neurons when DRG cultures were pre-treatment with the PMA. But pre-incubation with chelerythrine chloride strongly inhibited the IL-1ß-induced increase of PAR4 mRNA and protein levels. These results demonstrate that the expression of PAR4 mRNA and protein induced by IL-1ß is PKC signaling pathway dependent.