Multiple brain regions are involved in reaction to acute restraint stress in CYLD-knockout mice.

The lysine 63 deubiquitinase cylindromatosis (CYLD) is expressed at high levels in the brain and is considered to be involved in anxious and depressive behavior, cognitive inflexibility, and autism disorders. Previous research was limited in some brain regions, including the hippocampus, striatum, and amygdala. To better understand whether CYLD plays a role in adaptation to stress and which brain regions are involved, we analyzed the behavior of CYLD-knockout mice in the elevated plus maze (EPM) and light-dark box test (LDT) after acute restraint stress (ARS) and mapped their c-Fos immunoreactivity in brain sections. Here we report that CYLD deficiency leads to an unexpected reaction to ARS in mice, and is accompanied by significant neuronal activation of brain regions including the medial prefrontal cortex (mPFC), dorsal striatum (DS), nucleus accumbens (NAc), and basal lateral amygdala (BLA), but not ventral hippocampus (vHPC). Our findings show that CYLD participates in ARS-induced anxious behavior and that this involves multiple brain regions.

[Risk Factors of Rapidly Progressive Interstitial Lung Disease in Patients With Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis].

Objective: To investigate the conditions of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis combined with rapidly progressive interstitial lung disease (RPILD), and to analyze the risk factors. Methods: A total of 145 patients diagnosed with anti-MDA5 antibody-positive dermatomyositis at West China Hospital, Sichuan University between January 2018 and September 2021 were selected, and their general and clinical data were collected. The patients were divided into two groups, a RPILD group of patients with comorbid RPILD and a non-RPILD group of those who did not have comorbid RPILD. Factors that might affect whether patients with anti-MDA5 antibody-positive dermatomyositis also had comorbid RPILD were screened out and binary logistic regression analysis was performed. Results: Among the 145 patients with anti-MDA5 antibody-positive dermatomyositis, 32 (22.07%) patients had comorbid RPILD, while the remaining 113 (77.93%) did not have comorbid RPILD. Binary logistic regression analysis showed that lactate dehydrogenase≥370 IU/L (compared with <370 IU/L, OR=4.066, 95% CI: 1.616-10.230) and carcinoembryo antigen≥5 ng/mL (compared with <5 ng/mL, OR=6.070, 95% CI: 2.013-18.303) were risk factors for comorbid RPILD in patients with anti-MDA5 antibody-positive dermatomyositis ( ß>0, OR>1, P<0.05). Conclusion: It is recommended that close attention be given to changes in high-resolution chest CT and pulmonary functions in patients with lactate dehydrogenase≥370 IU/L and carcinoembryo antigen≥5 ng/mL. If rapid progression of lung disease is detected, it is necessary to strengthen the treatment of the lung disease, thereby improving the prognosis of patients.

Microglial activation in the dorsal striatum participates in anxiety-like behavior in Cyld knockout mice.

CYLD lysine 63 deubiquitinase (CYLD), that is mainly involved in immune responses and inflammation, is expressed at high levels in the brain, especially in the dorsal striatum, but its physiological function of CYLD in the brain remains unexplored. The present study investigated the effect of Cyld gene knockout on behavior relevant to the dorsal striatum, such as motor activity and depression-like and anxiety-like behavior. Microglia and the pro-inflammatory cytokines including interleukin (IL)-1 ß and tumor necrosis factor (TNF)- α were evaluated in the dorsal striatum to elucidate the underlying mechanism. Cyld knockout (Cyld-/-) mice exhibited anxiety-like behavior, but not motor deficits or depression-like behavior. Microglia were activated and the mRNA levels of IL-1 ß and TNF- α were increased in the dorsal striatum of Cyld-/- mice compared to Cyld+/+ mice. The microglial modulator minocycline partially reversed the anxiety-like behavior, microglial activation and increase in IL-1 ß and TNF- α mRNA and protein levels in the dorsal striatum of Cyld-/- mice. Collectively, these results suggest that Cyld knockout leading to microglial activation promotes IL-1 ß and TNF- α expression and acts as a critical pathway in the pathophysiology of anxiety.

[Analysis and monitoring of traditional Chinese medicines for tumor based on data mining].

The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.

Cordycepin improves behavioral-LTP and dendritic structure in hippocampal CA1 area of rats.

Cordycepin, an adenosine analog, has been reported to improve cognitive function, but which seems to be inconsistent with the reports showing that cordycepin inhibited long-term potentiation (LTP). Behavioral-LTP is usually used to study long-term synaptic plasticity induced by learning tasks in freely moving animals. In order to investigate simultaneously the effects of cordycepin on LTP and behavior in rats, we applied the model of behavioral-LTP induced by Y-maze learning task through recording population spikes in hippocampal CA1 region. Golgi staining and Sholl analysis were employed to assess the morphological structure of dendrites in pyramidal cells of hippocampal CA1 area, and western blotting was used to examine the level of adenosine A1 receptors and A2A receptors (A2AR). We found that cordycepin significantly improved behavioral-LTP magnitude, accompanied by increases in the total length of dendrites, the number of intersections and spine density but did not affect Y-maze learning task. Furthermore, cordycepin obviously reduced A2AR level without altering adenosine A1 receptors level; and the agonist of A2AR (CGS 21680) rather than antagonist (SCH 58261) could reverse the potentiation of behavioral-LTP induced by cordycepin. These results suggested that cordycepin improved behavioral-LTP and morphological structure of dendrite in hippocampal CA1 but did not contribute to the improvement of learning and memory. And cordycepin improved behavioral-LTP may be through reducing the level of A2AR in hippocampus. Collectively, the effects of cordycepin on cognitive function and LTP were complex and involved multiple mechanisms.

L-type VDCCs participate in behavioral-LTP and memory retention.

Although L-type voltage-dependent calcium channels (VDCCs) have been reported to display different even contrary actions on cognitive functions and long-term potentiation (LTP) formation, there is little information regarding the role of L-type VDCCs in behavioral LTP, a learning-induced LTP model, in the intact brain of freely behaving animals. Here we investigated the effects of verapamil, a non-selective blocker of L-type VDCCs, on behavioral LTP and cognitive functions. Population spikes (PS) were recorded by using electrophysiological methods to examine the role of verapamil in behavioral LTP in the hippocampal dentate gyrus (DG) region. Y-maze assay was used to evaluate the effects of verapamil on learning and memory. Electron microscope was used to observe the changes on synaptic ultrastructural morphology in hippocampal DG area. We found that intrahippocampal verapamil treatments had no significant changes on the PS amplitude during a 90min recordings period. However, intrahippocampal applications of verapamil, including pre- or post-training, reduced behavioral LTP magnitude and memory retention but did not prevent the induction of behavioral LTP and the acquisition of learning. The saline group with behaving trainings showed obvious increases in the number of smile synapses, the length of active zones and the thickness of postsynaptic density as compared to the baseline group, but verapamil with pre-training treatment almost returned these changes to the baseline levels except for the synaptic interface curvature. In conclusion, our results suggest that L-type VDCCs may only contribute to the magnitude of behavioral LTP and the memory maintenance with an activity-independent relationship. L-type VDCCs may be critical to new information long-term storage rather than acquisition in hippocampus.

Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice.

CONTEXT: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China. OBJECTIVE: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice. MATERIALS AND METHODS: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken. RESULTS: Compared with the model group, administration of 400 mg/kg BELE for 7 d in mice significantly decreased the serum ALT (56.25 U/L), AST (297.67 U/L), ALP (188.20 U/L), and TBIL (17.90 mol/L), along with the elevation of TP (64.67 g/L). In addition, BELE (100, 200, and 400 mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67 U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33 nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. DISCUSSION AND CONCLUSION: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.

[Plasma concentration and pharmacokinetics of ursolic acid carried in self-microemulsifying drug delivery system in rats studied by UPLC-MS/MS].

This study is to report the establishment of an UPLC-MS/MS method for the determination of plasma concentration of UA carried in self-microemulsifying drug delivery system (SMEDDS) and its pharmacokinetics in rats. It was used for determination and analysis when serum with internal standard was extracted from C18 solid-phase column. Acquity UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) was used for separation. The mobile phase was acetonitrile -0.1% ammonia with gradient elution at the flow rate of 0.2 mL x min(-1). The column temperature was 40 degrees C and the detection wave length was 210 nm. It was detected by negative ion using electrospray ionization source (ESI) and scanned by multiple reaction ion monitoring (MRM) mode. The liner relationship of UA was very good in the range of 1.19-3 815.00 ng x mL(-1) (r = 0.999 0). Recovery rate of different concentrations were 87.42%-89.95%. The precision of inter-day and intra-day were less than 11%. The method developed in our study was proved to be sensitive, rapid and simple. It is suitable for the pharmacokinetic study of UA-SMEDDS in rats.

Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice.

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Glioma-Stem-Cell-Derived Exosomes Remodeled Glioma-Associated Macrophage via NEAT1/miR-125a/STAT3 Pathway.

Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma.

Motor Function in MPTP-Treated Tree Shrews (Tupaia belangeri chinensis).

The tree shrew, a new experimental animal model, has been used to study a variety of diseases, especially diseases of the nervous system. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the gold standard for toxin-based animal models of Parkinson's disease (PD) because MPTP treatment replicates almost all of the pathological hallmarks of PD. Therefore, in this study, the effects of MPTP on the motor function of the tree shrew were examined. After five daily injections of a 3 mg/kg dose of MPTP, the motor function of MPTP-injected tree shrews decreased significantly, and the classic Parkinsonian symptoms of action and resting tremor, bradykinesia, posture abnormalities, and gait instability were observed in most MPTP-injected tree shrews. HPLC results also showed significantly reduced striatal dopamine and 3,4-dihydroxyphenylacetic acid levels in tree shrews after MPTP injection. Increased oxidative stress levels are usually considered to be the cause of dopaminergic neuron depletion in the presence of MPTP and were observed in the substantia nigra of MPTP-treated tree shrews, as indicated by a significant reduction in superoxide dismutase and glutathione peroxidase activity and increased levels of malondialdehyde. In addition, elevated α-synuclein mRNA levels in the midbrain of MPTP-treated tree shrews were observed. Furthermore, MPTP-treated tree shrews showed the classic Parkinsonian symptoms at a lower MPTP dosage compared with other animal models. Thus, the MPTP-treated tree shrew may be a potential animal model for studying the pathogenesis of PD.

[Simultaneous separation and detection of principal component isomer and related substances of raw material drug of ammonium glycyrrhizinate by RP-HPLC and structure confirmation].

A simple, fast and sensitive analytical method for the simultaneous separation and detection of 18alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B by RP-HPLC and drug quality standard was established. The structures of principal component isomer and related substances of raw material drug of ammonium glycyrrhizinate have been confirmed. Reference European Pharmacopoeia EP7.0 version, British Pharmacopoeia 2012 version, National Drug Standards of China (WS 1-XG-2002), domestic and international interrelated literature were referred to select the composition of mobile phase. The experimental parameters including salt concentration, pH, addition quantities of organic solvent, column temperature and flow rate were optimized. Finally, the assay was conducted on a Durashell-C18 column (250 mm x 4.6 mm, 5 microm) with 0.01 mol x mL(-1) ammonium perchlorate (add ammonia to adjust the pH value to 8.2) -methanol (48 : 52) as mobile phase at the flow rate of 0.8 mL x min(-1), and the detection wavelength was set at 254 nm. The column temperature was 50 degrees C and the injection volume was 10 microL. The MS, NMR, UV and RP-HPLC were used to confirm the structures of principal component isomer and related substances of raw material drug of ammonium glycyrrhizinate. Under the optimized separation conditions, the calibration curves of 18 alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B showed good linearity within the concentration of 0.50-100 microg x mL(-1) (r = 0.999 9). The detection limits for 18alpha-glycyrrhizinic acid, 18beta-glycyrrhizinic acid, related substance A and related substance B were 0.15, 0.10, 0.10, 0.15 microg x mL(-1) respectively. The method is sensitive, reproducible and the results are accurate and reliable. It can be used for chiral resolution of 18alpha-glycyrrhizinic acid, 18Pbeta-glycyrrhizinic acid, and detection content of principal component and related substances of raw material drug of ammonium glycyrrhizinate. It is concluded that the separation of principal component isomer of raw material drug of ammonium glycyrrhizinate and the validity of the substance's structure assignments of retention time being 1.2 in the European pharmacopoeia EP7.0 version, British pharmacopoeia 2012 version remains open to question. It may be of practical value for the quality control of raw material drug, preparation, and Chinese herbal medicine of ammonium glycyrrhizinate.

Anthracene derivative covalently immobilized on sensing membrane as a fluorescent carrier for water assay.

This article describes an optical chemical sensor based on a fluorescent dye 1-allyloxy-4-hydroxyanthracene-9, 10-dione (AHD) with terminal double bond, which is covalently bonded to quartz glass plate surface treated with a silanizing agent to prevent its leakage. The purpose of this work was to characterize and optimize the sensor for determining the water content in the acetone organic solvent. The sensor is resistant to swelling; the membrane possesses relatively long lifetime, short response and recovering time. The reversibility and reproducibility of the sensor are adequate for practical measurements.

Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.

Introduction: Vaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing. Methods: Vaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities. Results: The microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study. Conclusion: These findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.

Cordycepin improved the cognitive function through regulating adenosine A2A receptors in MPTP induced Parkinson's disease mice model.

BACKGROUND: Parkinson's disease (PD), the most common neurodegenerative disorder, primarily affects dopaminergic neurons in the substantia nigra (SN). In addition to severe motor dysfunction, PD patients appear apparent cognitive impairments in the late stage. Cognitive dysfunction is accompanied by synaptic transmission damage in the hippocampus. Cordycepin has been reported to alleviate cognitive impairments in neurodegenerative diseases. PURPOSE: The study aimed to estimate the protection roles of cordycepin on cognitive dysfunction in PD model and explore the potential mechanisms. METHODS: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to establish the PD model in vivo and in vitro experiments. In the in vivo experiments, the C57BL / 6 mice were intraperitoneally injected with MPTP and intragastric administration with cordycepin. Open field test (OFT) was used to estimate the exercise ability. Spontaneous alternation behavioral (SAB) and morris water maze (MWM) tests were used to evaluate the learning and memory abilities. The hippocampal slices from C57BL / 6 and Kunming mice in the in vitro experiments were used to record field excitatory postsynaptic potential (fEPSP) by electrophysiological methods. Western blotting was used to examine the level of tyrosine hydroxylase (TH) in the in vivo experiments and the levels of adenosine A1 and A2A receptors (A1R and A2AR) in the in vitro experiments, respectively. The drugs of MPTP, cordycepin, DPCPX and SCH58261 were perfused through dissolving in artificial cerebrospinal fluid. RESULTS: Cordycepin could significantly reduce the impairments on motor, exploration, spatial learning and memory induce by MPTP. MPTP reduced the amplitude of LTP in hippocampal CA1 area but cordycepin could improve LTP amplitudes. Cordycepin at dosage of 20 mg/kg also increased the TH level in SN. In the in vitro experiments, MPTP inhibited synaptic transmission in hippocampal Schaffer-CA1 pathway with a dose-dependent relationship, while cordycepin could reverse the inhibition of synaptic transmission. Furthermore, the roles of cordycepin on synaptic transmission could been attenuated in the presence of the antagonists of A1R and A2AR, DPCPX and SCH58261, respectively. Interestingly, the level of A2AR rather than A1R in hippocampus was significantly decreased in the cordycepin group as compared to the control. CONCLUSION: The present study has showed that cordycepin could improve cognitive function in the PD model induced by MPTP through regulating the adenosine A2A receptors. These findings were helpful to provide a new strategy for the dementia caused by Parkinson's disease.

A novel anticancer agent, SKLB70359, inhibits human hepatic carcinoma cells proliferation via G0/G1 cell cycle arrest and apoptosis induction.

Hepatocellular carcinoma is one of the most common cancers in worldwide. We previously reported a novel thienopyridine derivative 3-amino-6-(3,4-dichlorophenyl) thieno[2,3-b]pyridine-2-carboxamide (SKLB70359) which possesses anticancer activity against hepatocellular carcinoma. In present study, we further investigated its anticancer activity and possible mechanism. The SKLB70359 treatment decreased the viability of a panel of hepatocellular carcinoma cell lines in a concentration- and time-dependent manner with IC(50) 0.4 ~ 2.5 µM. The mechanism study showed that SKLB70359 induced G0/G1 cell cycle arrest and then led to apoptotic cell death of HepG2 cell. The SKLB70359 induced G0/G1 cell cycle arrest was characterized by down-regulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6 expression and up-regulation of p53, p21(WAF1). Activating of caspase-3 and caspase-9 was also observed. Meanwhile, proliferation inhibitory effect of SKLB70359 was associated with decreased level of phosphorylated p44/42 mitogen activated protein kinase (p44/42 MAPK) and phosphorylated retinoblastoma protein (Rb). Moreover, SKLB70359 exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, the findings in this study suggested that SKLB70359 have potential anticancer efficacy via G0/G1 cell cycle arrest and apoptosis induction. Its potential to be a candidate of anticancer agent is worth being further investigated.

The rare genera Picacharops Gauld and Sliochia Gauld (Hymenoptera, Ichneumonidae, Campopleginae) found in China, with description of two new species.

Two rare genera are newly reported for China: the Australasian Picacharops Gauld, 1984 and the Oriental Sliochia Gauld, 1976. A new species of these two monotypic genera (P. granulosus sp. nov. and S. adustifemur sp. nov., respectively) is described from China and illustrated. Keys to species of both genera are also provided.

Review of the genera Breviterebra Kusigemati, Charops Holmgren and Scenocharops Uchida (Hymenoptera, Ichneumonidae, Campopleginae) from China, with description of three new species.

Species of the genera Breviterebra Kusigemati, 1982, Charops Holmgren, 1859 and Scenocharops Uchida, 1932 (Hymenoptera, Ichneumonidae, Campopleginae) from China are revised. Of the 13 species recognized, three are described as new species: Breviterebra apicocrinis sp. nov., Charops mauroknemus sp. nov. and Scenocharops yunnanensis sp. nov. The genus Breviterebra Kusigemati and the species Scenocharps montanus Gupta Maheshwary, 1971 are recorded in China for the first time. The distribution area of C. brachypterus (Cameron), C. striatus (Uchida), S. flavipetiolus (Sonan) and S. parasae He in China are updated. DNA barcode fragment of the mitochondrial COI gene of B. apicocrinis sp. nov. is presented. Keys to Breviterebra, Charops and Scenocharops are provided.

Four rare genera of the subfamily Campopleginae (Hymenoptera: Ichneumonidae) from China, with description of three new species.

Five species of four rare genera Dolophron Förster, 1869, Genotropis Townes, 1970, Leptocampoplex Horstman, 1970 and Philositus Townes, 1970 of the family Ichneumonidae (Hymenoptera) are found in China, among which three genera Dolophron, Leptocampoplex and Philositus are firstly reported from China. Three new species D. granulosa sp. nov., G. mauroknema sp. nov., and P. parva sp. nov. are described and illustrated. Redescriptions of Genotropis clara Townes, 1970 and Leptocampoplex cremastoides (Holmgren, 1860) are given. Keys to species of each genus and the distribution map of China are also provided.

Mefunidone ameliorates lipopolysaccharide-induced acute lung injury through inhibiting MAPK signaling pathway and enhancing Nrf2 pathway.

BACKGROUND AND OBJECTIVE: Acute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms. METHODS: We investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs). RESULTS: MFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes. CONCLUSION: Our results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.