Anterior cingulate cortex orexin signaling mediates early-life stress-induced social impairment in females.

Early-life stress has long-term impacts on the structure and function of the anterior cingulate cortex (ACC), and raises the risk of adult neuropsychiatric disorders including social dysfunction. The underlying neural mechanisms, however, are still uncertain. Here, we show that, in female mice, maternal separation (MS) during the first three postnatal weeks results in social impairment accompanied with hypoactivity in pyramidal neurons (PNs) of the ACC. Activation of ACC PNs ameliorates MS-induced social impairment. Neuropeptide Hcrt, which encodes hypocretin (orexin), is the top down-regulated gene in the ACC of MS females. Activating ACC orexin terminals enhances the activity of ACC PNs and rescues the diminished sociability observed in MS females via an orexin receptor 2 (OxR2)-dependent mechanism. Our results suggest orexin signaling in the ACC is critical in mediating early-life stress-induced social impairment in females.

Surf4 collaborates with derlin-2 and derlin-1 to mediate cyclooxygenase-2 translocation to the cytosol for degradation.

Derlin family members participate in the retrotranslocation of endoplasmic reticulum (ER) lumen proteins to the cytosol for ER-associated degradation (ERAD); however, the proteins facilitating this retrotranslocation remain to be explored. Using CRISPR library screening, we have found that derlin-2 and surfeit locus protein 4 (Surf4) are candidates to facilitate degradation of cyclooxygenase-2 (COX-2, also known as PTGS2). Our results show that derlin-2 acts upstream of derlin-1 and that Surf4 acts downstream of derlin-2 and derlin-1 to facilitate COX-2 degradation. Knockdown of derlin-2 or Surf4 impedes the ubiquitylation of COX-2 and the interaction of COX-2 with caveolin-1 (Cav-1) and p97 (also known as VCP) in the cytosol. Additionally, COX-2 degradation is N-glycosylation dependent. Although derlin-2 facilitates degradation of N-glycosylated COX-2, the interaction between derlin-2 and COX-2 is independent of COX-2 N-glycosylation. Derlin-1, Surf4 and p97 preferentially interact with non-glycosylated COX-2, whereas Cav-1 preferentially interacts with N-glycosylated COX-2, regardless of the N-glycosylation pattern. Collectively, our results reveal that Surf4 collaborates with derlin-2 and derlin-1 to mediate COX-2 translocation from the ER lumen to the cytosol. The derlin-2-derlin-1-Surf4-Cav-1 machinery might represent a unique pathway to accelerate COX-2 degradation in ERAD.

Ligand-Controlled Cobalt-Catalyzed Regio-, Enantio-, and Diastereoselective Oxyheterocyclic Alkene Hydroalkylation.

Metal-hydride-catalyzed alkene hydroalkylation has been developed as an efficient method for C(sp3)-C(sp3) coupling with broad substrate availability and high functional group compatibility. However, auxiliary groups, a conjugated group or a chelation-directing group, are commonly required to attain high regio- and enantioselectivities. Herein, we reported a ligand-controlled cobalt-hydride-catalyzed regio-, enantio-, and diastereoselective oxyheterocyclic alkene hydroalkylation without chelation-directing groups. This reaction enables the hydroalkylation of conjugated and unconjugated oxyheterocyclic alkenes to deliver C2- or C3-alkylated tetrahydrofuran or tetrahydropyran in uniformly good yields and with high regio- and enantioselectivities. In addition, hydroalkylation of C2-substituted 2,5-dihydrofuran resulted in the simultaneous construction of 1,3-distereocenters, providing convenient access to polysubstituted tetrahydrofuran with multiple enantioenriched C(sp3) centers.

Arithmetic logic unit based on the metastructure with coherent absorption: erratum.

We present a corrigendum to our Letter [Opt. Lett.48, 5699 (2023)10.1364/OL.505761]. In section 3 of the original supplementary material, the absolute value is incorrectly taken in resolving the Kubo formula for describing the conductivity of graphene. Because this is a mistake with the conductivity of graphene, the coupling of the original structure is broken when the correct result is inserted into the code of the transfer matrix. So, the structure of the arithmetic logic unit (ALU), characteristic frequency point, and phase control have been modified accordingly. However, the ultimate function and the conclusion of this work remain unchanged.

Mechanism of NCNTs Growth on Foamed Nickel and Thus-Prepared PS Hydrogenation High-Performance Carrier NCNTs@FN.

Traditional heterogeneous catalysts are affected in the catalytic hydrogenation of PS by the scale effect, viscosity effect, adhesion effect, and conformational effect, resulting in poor activity and stability. Monolithic Pd-CNTs@FN catalysts could eliminate or weaken the impact of these negative effects. We grew nitrogen-doped carbon nanotubes (NCNTs) on monolithic-foamed nickel (FN) and investigate their growth mechanism. Meanwhile, the feasibility of using the NCNTs@FN carrier for PS hydrogenation reaction was also verified. The growth of NCNTs on FN can be divided into 3 stages: initial growth stage, stable growth stage, and supersaturation stage. Finally, a three-layer structure of NCNT layer, dense carbon layer, and FN skeleton is formed. Two types of structures, nickel-doped carbon nanotubes (NiCNTs) and C-Ni alloy, are formed by combining C and Ni, while four nitrogen-doped structures, NPD, NPR, NG, and NO, are formed by C and N. The prepared carrier exhibited an extremely outstanding specific surface area (2.829 × 106 cm2/g) and strength (no NCNTs falling off after 24 h 500 rpm agitation), as well as high catalytic activity for PS hydrogenation after loaded with Pd (2.13 ± 0.95 nm), with a TOF of up to 27.6 gPS/(gPd•h). After 8 repetitions of the catalyst, there was no significant decrease in activity. This proves the excellent performance of Pd-NCNTs@FN in polymer hydrogenation reactions, laying a solid foundation for further research on the mechanism of NCNTs promoting PS hydrogenation and regulating the growth of NCNTs.

A multiple cancer cell optical biosensing metastructure realized by CPA.

A one-dimensional optical biosensing metastructure (OBM) with graphene layers is presented in this paper. It is realized by coherent perfect absorption (CPA) and operates in the transverse electric mode. It shows a strong linear fitting relationship between the refractive index (RI) of the analysis layer and the frequency corresponding to the absorption peak, and the R-square is up to 1. Additionally, based on the principle of CPA, the OBM can realize the function of multiple cancer cell detection by adjusting the detection range by controlling the phase difference of coherent electromagnetic waves. Its detection ranges are 1.34-1.355 and 1.658-1.662. Thanks to its high-quality factor, great figure of merit, and low detection limit, whose best values are, respectively, 6.9 × 104, 1.2 × 104 RIU-1, and 3.6 × 10-6 RIU, the detection of weak changes in the RI of a cancer cell is possible. Additionally, its sensitivity can reach 26.57 THz RIU-1. This OBM based on CPA has major implications for advancing the study and investigation into the application of CPA. It also provides a simple and efficient approach to distinguish cancer cells and may be widely used in the biomedical field.

Transcriptome analysis of the endangered dung beetle Copris tripartitus (Coleoptera: Scarabaeidae) and characterization of genes associated to immunity, growth, and reproduction.

BACKGROUND: Dung beetles recycle organic matter through the decomposition of feces and support ecological balance. However, these insects are threatened by the indiscriminate use of agrochemicals and habitat destruction. Copris tripartitus Waterhouse (Coleoptera: Scarabaeidae), a dung beetle, is listed as a class-II Korean endangered species. Although the genetic diversity of C. tripartitus populations has been investigated through analysis of mitochondrial genes, genomic resources for this species remain limited. In this study, we analyzed the transcriptome of C. tripartitus to elucidate functions related to growth, immunity and reproduction for the purpose of informed conservation planning. RESULTS: The transcriptome of C. tripartitus was generated using next-generation Illumina sequencing and assembled de novo using a Trinity-based platform. In total, 98.59% of the raw sequence reads were processed as clean reads. These reads were assembled into 151,177 contigs, 101,352 transcripts, and 25,106 unigenes. A total of 23,450 unigenes (93.40%) were annotated to at least one database. The largest proportion of unigenes (92.76%) were annotated to the locally curated PANM-DB. A maximum of 5,512 unigenes had homologous sequences in Tribolium castaneum. Gene Ontology (GO) analysis revealed a maximum of 5,174 unigenes in the Molecular function category. Further, in Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, a total of 462 enzymes were associated with established biological pathways. Based on sequence homology to known proteins in PANM-DB, representative immunity, growth, and reproduction-related genes were screened. Potential immunity-related genes were categorized into pattern recognition receptors (PRRs), the Toll-like receptor signaling pathway, the MyD88- dependent pathway, endogenous ligands, immune effectors, antimicrobial peptides, apoptosis, and adaptation-related transcripts. Among PRRs, we conducted detailed in silico characterization of TLR-2, CTL, and PGRP_SC2-like. Repetitive elements such as long terminal repeats, short interspersed nuclear elements, long interspersed nuclear elements and DNA elements were enriched in the unigene sequences. A total of 1,493 SSRs were identified among all unigenes of C. tripartitus. CONCLUSIONS: This study provides a comprehensive resource for analysis of the genomic topography of the beetle C. tripartitus. The data presented here clarify the fitness phenotypes of this species in the wild and provide insight to support informed conservation planning.

Nickel-Catalyzed Remote Asymmetric Hydroalkylation of Alkenyl Ethers to Access Ethers of Chiral Dialkyl Carbinols.

Site- and enantio-selective alkyl-alkyl bond formation is privileged in the retrosynthetic analysis due to the universality of sp3-hybridized carbon atoms in organic molecules. Herein, we report a nickel-catalyzed remote asymmetric hydroalkylation of alkenyl ethers via synchronous implementation of alkene isomerization and enantioselective C(sp3)-C(sp3) bond formation. Regression analysis of catalyst structure-activity relationships accelerates the rational ligand modification through modular regulation. This reaction has several advantages for synthesizing chiral dialkyl carbinols and their ether derivatives, including the broad substrate scope, good functional group tolerance, excellent regioselectivity (>20:1 regioisomeric ratio), and high enantioselectivity (up to 95% enantiomeric excess).

Is Toxoplasma gondii infection a concern in individuals with rheumatic diseases? Evidence from a case-control study based on serological diagnosis.

Toxoplasma gondii infection in clinical cases of rheumatic diseases is increasing, whereas, the relationship between T. gondii infection and rheumatic diseases is still ambiguous and contradictory. Thus, the present case-control study based on serological diagnosis was carried out to identify the underlying relationship between T. gondii infection and rheumatic diseases in China. Serological results showed that rheumatic patients (17.25%, 79/458) had a significantly higher T. gondii seroprevalence than control subjects (10.70%, 49/458) (p = 0.004). However, the difference in T. gondii seroprevalence among clinical rheumatic disease forms was insignificant. Moreover, disease duration not effect the T. gondii seroprevalence in the included clinical rheumatic patients. Three risk factors (presence of cats at home, blood transfusion history, and consumption of raw shellfish) were identified through multivariate analysis to affect the T. gondii seroprevalence in the included clinical rheumatic patients. In conclusion, these results indicate that the latent T. gondii infection in clinical rheumatic patients should cause alarm and attention in the course of future scientific research or clinical treatment.

Arithmetic logic unit based on the metastructure with coherent absorption.

An arithmetic logic unit (ALU) based on the metastructure (MS) with coherent absorption (CA) is proposed in this Letter. The ALU can perform AND and exclusive OR logical operations at the same frequency point. So it can be regarded as an optical half-adder. By controlling the chemical potential of graphene and the phase difference of coherent electromagnetic waves (EWs), two different binary numbers are input into the ALU. The dynamic absorption peaks, which are generated based on the CA, output the outcomes of the carry-digit bit and non-carry sum bit. This ALU can be used in the field of optical processing and encryption, such as processing hamming code. This given ALU based on the MS with CA has major implications for advancing the study and investigation into the application of CA. Furthermore, it also provides a new, to the best of our knowledge, idea for the study of MS with logical operation.

Medical assistance in dying in Canada: A scoping review on the concept of suffering.

OBJECTIVES: Medical Assistance in Dying (MAiD) has been legal in Canada since June 2016. A person can receive MAiD if their suffering cannot be relieved under conditions that they consider acceptable. Informed consent requires that the person requesting MAiD has received all the information needed to make their decision; that is, medical diagnosis and prognosis, available treatments including palliative care. The evaluation of unbearable suffering is known to be challenging as suffering is often psychological, existential, and social in nature. While interventions to relieve suffering exist, it is unclear how suffering is assessed and addressed in the literature on MAiD practice. No scoping review exists on the topic in Canada. The aim of this study was to understand how the concept of suffering was approached within the Canadian MAiD grey (GL) and scientific (peer-reviewed) literature (SL), specifically: 1- How suffering is defined and assessed in the context of MAiD in Canada and 2- Which interventions in response to suffering are recommended within the process of obtaining informed consent for MAiD and throughout the process of MAiD itself. METHODS: A scoping review was conducted based on PRISMA-SR guidelines. SL articles (N = 1027) were identified from a review of 6 databases and GL documents (N = 537) were obtained from the provinces of Quebec, Ontario and British Columbia. Documents were analyzed using NVivo with coding by two-raters and continuous team discussions. RESULTS: A multidimensional definition of suffering, akin to the concept of total pain, is used. The assessment of suffering is based upon patients' reports. Tools to aid in the assessment are not comprehensively covered. Specific interventions to address suffering were often focused on active listening and the management of physical symptoms. No specific interventions were mentioned and there was no reference to clinical practice guidelines in the grey literature to address other components of suffering. The use of a multidisciplinary approach is suggested without specifying the nature of involvement. CONCLUSIONS: Our review indicates that published guidelines of MAID assessments could include clearer structure around the assessment and management of suffering, with suggestions of tools that may help clarify types of suffering and reference to clinical practice guidelines and interventions to holistically attend to patient suffering with an attention on non-physical symptoms. Guidelines would benefit from clearer explanations of how members of an interdisciplinary teams could be coherently coordinated.

The multiple physical quantity sensor based on cylindrical photonic crystals with XOR logic gates.

Based on cylindrical photonic crystals in one dimension, a multi-scale sensor device with a logic operation is being proposed. At the same time, it can satisfy the functions of refractive index (RI) and magnetic field detection. Under the modulation of an external magnetic field, sharp absorption peaks (APs) are obtained in the terahertz (THz) range. In a certain frequency range (AP value above 0.9), as the particular InSb layers are applied to two different magnetic fields, APs of the same frequency can be implemented to operate as XOR logic gates. The results show that with a change in the detected physical quantity, the frequency point of the corresponding AP also moves. Therefore, by adjusting the position of the AP, the magnetic field and RI can be sensed, and the device shows relatively excellent performance of 6879.88 and 6943.65 in terms of quality factor. In addition, the optimal performance of sensitivity, detection limit, and corresponding figure of merit is 0.01264(2πc/d0) T-1, 2.25 × 10-4 T, 227.23 T-1, and -0.003779(2πc/d0) RIU-1, 7.69 × 10-3 RIU, 67.74 RIU-1. In terms of overall sensors, the proposed device is highly innovative in structure and meets the requirements of multi-scale measurements.

Health-related quality of life of Chinese AIDS patients: a multi-region study.

OBJECTIVE: To assess the health-related quality of life (HRQOL) of Chinese AIDS patients in three regions (Shanghai, Zhejiang, and Henan) and to examine the relationship between region and the HRQOL. METHOD: A cross-sectional study was conducted from 2017 to 2018. Multistage stratified sampling was employed to recruit 1,273 AIDS patients from local Centers for Disease Control and Prevention. Data were collected by means of face-to-face interview using a structured questionnaire including the SF-12 and various rating scales. The multivariate linear and logistic regression models were performed to analyze the relationship of region and a variety of factors with the HRQOL and health utility. RESULTS: The three most affected dimensions were mental health, general health, and vitality as 18.2%, 18.0%, and 16.4% of the patients reported problems respectively. The mean (SD) scores of physical component summary (PCS) and mental component summary (MCS), were 48.19 (8.02) and 46.74 (10.71) respectively. The mean (SD) health utility score was 0.75 (0.13) assessed by the SF-6D derived from the SF-12. Region, age, employment status, individual income, government assistance and stigma significantly affected the patients' HRQOL (P < 0.01). BMI, opportunistic infection, treatment compliance and time of treatment were also found to be significant factors of the HRQOL. CONCLUSION: This study comprehensively estimated the HRQOL and health utility for the AIDS population in China, their HRQOL was mainly deteriorated in psychological dimensions, and geographical area may be closely related. Hence, close attention needs to be paid on the regional differences in HRQOL and the psychological problems of the patients.

Magnetic resonance imaging thicknesses and apparent diffusion coefficient values of the endometrium and junction zone in women of reproductive age.

BACKGROUND: The endometrium and uterine junction zone often change throughout the menstrual cycle. Some pathological conditions may appear normal in uterine imaging, which will lead to missed diagnosis and misdiagnosis. PURPOSE: To evaluate the changes in the thickness and apparent diffusion coefficient (ADC) values of the endometrium and uterine junction zone throughout the menstrual cycle in magnetic resonance imaging (MRI) of women of reproductive age. MATERIAL AND METHODS: Data were collected from 40 healthy women of reproductive age with regular menstrual cycles from January 2017 to April 2018. They underwent four total MRI sessions during the menstrual, proliferation, and early and late secretive phases. The main MRI sequences were T2-weighted (T2W) volume isotropic turbo spin echo acquisition (VISTA) spectral attenuated inversion recovery (SPAIR) and diffusion-weighted imaging (b = 0, 600, 800, 1000 s/mm2), which were used to measure the thicknesses and ADC values of endometrium and uterine junction zone. RESULTS: First, the endometrium was thinnest during the menstrual phase and thickest in the late secretive phase. Second, the uterine junction zone was thinnest in the late secretive phase and thickest in the menstrual phase. Third, the ADC values of the endometrium were lowest in the menstrual phase and peaked in the early secretive phase. Finally, the ADC values of the uterine junction zone were lowest in the menstrual phase and peaked in the late secretive phase. CONCLUSION: The endometrium and uterine junction zone showed cyclic changes. Radiologists should consider these changes in the thickness and ADC values when analyzing MRI images of the uterus.

Ligand-Controlled Cobalt-Catalyzed Regiodivergent Alkyne Hydroalkylation.

Regiodivergent alkyne hydroalkylation to generate different isomers of an alkene from the same alkyne starting material would be beneficial; however, it remains a challenge. Herein, we report a ligand-controlled cobalt-catalyzed regiodivergent alkyne hydroalkylation. The sensible selection of bisoxazoline (L1) and pyridine-oxazoline (L8) ligands led to reliable and predictable protocols that provided (E)-1,2-disubstituted and 1,1-disubstituted alkenes with high E/Z stereoselectivity and regioisomeric ratio starting from identical terminal alkyne and alkyl halide substrates and produced trisubstituted alkenes in the case of internal alkynes. This method exhibits a broad scope for terminal and internal alkynes with a wide range of activated and unactivated alkyl halides and shows excellent functional group compatibility.

Selective Exoenzymatic Labeling of Lipooligosaccharides of Neisseria gonorrhoeae with α2,6-Sialoside Analogues.

The interactions between bacteria and their host often rely on recognition processes that involve host or bacterial glycans. Glycoengineering techniques make it possible to modify and study the glycans on the host's eukaryotic cells, but only a few are available for the study of bacterial glycans. Here, we have adapted selective exoenzymatic labeling (SEEL), a chemical reporter strategy, to label the lipooligosaccharides of the bacterial pathogen Neisseria gonorrhoeae, using the recombinant glycosyltransferase ST6Gal1, and three synthetic CMP-sialic acid derivatives. We show that SEEL treatment does not affect cell viability and can introduce an α2,6-linked sialic acid with a reporter group on the lipooligosaccharides by Western blot, flow cytometry and fluorescent microscopy. This new bacterial glycoengineering technique allows for the precise modification, here with α2,6-sialoside derivatives, and direct detection of specific surface glycans on live bacteria, which will aid in further unravelling the precise biological functions of bacterial glycans.

High sensitivity multitasking non-reciprocity sensor using the photonic spin Hall effect.

A non-reciprocity sensor based on a layered structure with multitasking is proposed, which realizes biological detection and angle sensing. Through an asymmetrical arrangement of different dielectrics, the sensor obtains non-reciprocity on the forward and backward scales, thus achieving multi-scale sensing in different measurement ranges. The structure sets the analysis layer. Injecting the analyte into the analysis layers by locating the peak value of the photonic spin Hall effect (PSHE) displacement, cancer cells can accurately be distinguished from normal cells via refractive index (RI) detection on the forward scale. The measurement range is 1.569∼1.662, and the sensitivity (S) is 2.97 × 10-2 m/RIU. On the backward scale, the sensor is able to detect glucose solution with 0∼400 g/L concentrations (RI = 1.3323∼1.38), with S = 1.16 × 10-3 m/RIU. When the analysis layers are filled with air, high-precision angle sensing can be achieved in the terahertz range by locating the incident angle of the PSHE displacement peak; 30°âˆ¼45°, and 50°âˆ¼65° are the detection ranges, and the highest S can reach 0.032 THz/°. This sensor contributes to detecting cancer cells and biomedical blood glucose and offers a new way to the angle sensing.

Metallic-semiconducting transition and spin polarized-unpolarized transition in a single molecule with a negative Poisson's ratio.

Different from conventional materials, structures with a negative Poisson's ratio (NPR) contract/expand laterally under a longitudinal compressive/tensile strain, usually exhibiting peculiar features. Through first-principles calculations, we investigate the electronic and transport properties of Pd9B16 molecules. Its Poisson's ratio is found to be negative under uniaxial strain along a specific direction. By contacting with Au nanowires, atomic Au chains and atomic C chain electrodes, two kinds of transitions for transmission states could be realized by the modulation of the strain and the contacting site, i.e., metallic-semiconducting transition and spin polarized-unpolarized transition. Further analysis shows that it is the suppression and shifting of density of states, caused by the strain or contacting electrodes, that trigger the transitions. Those findings combine NPR and spintronics at the single-molecule level, which may throw light on the development of nanoelectronic devices.

Identification of circRNAs involved in the development of hepatocellular carcinoma after insufficient radiofrequency ablation.

Previous studies have reported that circular RNAs (circRNAs) play a key role in the pathogenesis and progression of various diseases. In the present study, we aimed to identify potential circRNAs associated with the progression of hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (IRFA). A xenograft mouse IRFA model was initially established, and immunohistochemical staining (IHC) and polymerase chain reaction (PCR) were performed to confirm the expression of programmed cell death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor-1 (VEGFR-1). CircRNA expression alterations were screened by next-generation sequencing (RNA-seq). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to predict the function of genes coding differentially expressed circRNAs. The selected circRNAs were validated utilizing PCR and Sanger sequencing. The relationships between circRNAs, microRNAs, PD-L1, and VEGFR-1 were predicted by bioinformatics. Overall, a total of 612 circRNAs were differentially expressed in IRFA-treated subcutaneous tumorigenesis tissue. Among them, 435 circRNAs were significantly upregulated and 177 circRNAs were downregulated. GO and KEGG analyses were employed to predict the functions of these circRNAs. Thereafter, quantitative reverse transcription PCR (qRT-PCR) assays determined that these seven circRNAs were overexpressed in the IRFA group, which was consistent with the RNA-seq results. Based on the bioinformatic analysis, seven circRNAs confirmed by Sanger sequencing were predicted to likely regulate PD-L1 and VEGFR-1 expression levels by functioning as sponges for microRNAs (miRNAs) and forming a circRNA-miRNA-PD-L1/VEGFR-1 regulatory network. Finally, IHC and qRT-PCR of PD-L1 and VEGFR-1 confirmed the activation of this pathway. Taken together, we report that differentially expressed circRNAs might simultaneously regulate PD-L1 and VEGFR-1 in the IRFA tissues, which provides a novel view of circRNAs in HCC progression after the IRFA procedure.

Red nucleus IL-33 facilitates the early development of mononeuropathic pain in male rats by inducing TNF-α through activating ERK, p38 MAPK, and JAK2/STAT3.

BACKGROUND: Our recent studies have identified that the red nucleus (RN) dual-directionally modulates the development and maintenance of mononeuropathic pain through secreting proinflammatory and anti-inflammatory cytokines. Here, we further explored the action of red nucleus IL-33 in the early development of mononeuropathic pain. METHODS: In this study, male rats with spared nerve injury (SNI) were used as mononeuropathic pain model. Immunohistochemistry, Western blotting, and behavioral testing were used to assess the expressions, cellular distributions, and actions of red nucleus IL-33 and its related downstream signaling molecules. RESULTS: IL-33 and its receptor ST2 were constitutively expressed in the RN in naive rats. After SNI, both IL-33 and ST2 were upregulated significantly at 3 days and peaked at 1 week post-injury, especially in RN neurons, oligodendrocytes, and microglia. Blockade of red nucleus IL-33 with anti-IL-33 neutralizing antibody attenuated SNI-induced mononeuropathic pain, while intrarubral administration of exogenous IL-33 evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 generated an algesic effect in the early development of SNI-induced mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3, suppression of NF-κB, ERK, p38 MAPK, and JAK2/STAT3 with corresponding inhibitors markedly attenuated SNI-induced mononeuropathic pain or IL-33-evoked mechanical hypersensitivity in naive rats. Red nucleus IL-33 contributed to SNI-induced mononeuropathic pain by stimulating TNF-α expression, which could be abolished by administration of inhibitors against ERK, p38 MAPK, and JAK2/STAT3, but not NF-κB. CONCLUSIONS: These results suggest that red nucleus IL-33 facilitates the early development of mononeuropathic pain through activating NF-κB, ERK, p38 MAPK, and JAK2/STAT3. IL-33 mediates algesic effect partly by inducing TNF-α through activating ERK, p38 MAPK and JAK2/STAT3.