Icariin mitigates anxiety-like behaviors induced by hemorrhagic shock and resuscitation via inhibiting of astrocytic activation.

BACKGROUND: Abnormal activation of astrocytes in the amygdala contributes to anxiety after hemorrhagic shock and resuscitation (HSR). Nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-associated epigenetic reprogramming of astrocytic activation is crucial to anxiety. A bioactive monomer derived from Epimedium icariin (ICA) has been reported to modulate NF-κB signaling and astrocytic activation. PURPOSE: The present study aimed to investigate the effects of ICA on post-HSR anxiety disorders and its potential mechanism of action. METHODS: We first induced HSR in mice through a bleeding and re-transfusion model and selectively inhibited and activated astrocytes in the amygdala using chemogenetics. Then, ICA (40 mg/kg) was administered by oral gavage once daily for 21 days. Behavioral, electrophysiological, and pathological changes were assessed after HSR using the light-dark transition test, elevated plus maze, recording of local field potential (LFP), and immunofluorescence assays. RESULTS: Exposure to HSR reduced the duration of the light chamber and attenuated open-arm entries. Moreover, HSR exposure increased the theta oscillation power in the amygdala and upregulated NF-κB p65, H3K27ac, and H3K4me3 expression. Contrarily, chemogenetic inhibition of astrocytes significantly reversed these changes. Chemogenetic inhibition in astrocytes was simulated by ICA, but chemogenetic activation of astrocytes blocked the neuroprotective effects of ICA. CONCLUSION: ICA mitigated anxiety-like behaviors induced by HSR in mice via inhibiting astrocytic activation, which is possibly associated with NF-κB-induced epigenetic reprogramming.

[Short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures].

Objective To explore the short-term efficacy of digitally-assisted traditional Chinese medicine manual reduction combined with 3D printed splint in the treatment of AO type-A distal radius fractures, and explore the quantification of traditional Chinese medicine manual reduction and personalized improvement of splinting. Methods The clinical data of 50 patients with AO type-A distal radius fractures, who received treatment at the outpatient department of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital in Hebei Province, were retrospective analyzed. The patient cohort included 22 females and 28 males, with ages ranging from 25 to 75 years old. Among them, 27 cases presented with distal radius fractures on the left side, and 24 cases on the right side. The patients were categorized into two groups: treatment group (n=25) and control group(n=25). There were 13 males and 12 females in the treatment group, with an average age of (56.2±5.5) years old. Treatment approach for this group involved several steps. Initially, Mimics Research software was used to conduct comprehensive analysis of complete CT data from the affected limb, resulting in the creation of a three-dimensional model. Subsequently, 3D models of the bones and skin contours, stored as STL format files, were imported into the Materialise Magics 23.0 software for model processing and repair. This facilitated the simulation of reduction and recording of displacement data, effectively generating a "digital prescription" to guide and quantify traditional Chinese medicine manipulation procedures. Finally, a personalized 3D printed splint was applied for fixation treatment. There were 15 males and 10 females in the control group, with an average age of (53.32±5.28) years old. These patients were treated with manualreduction combined with traditional splinting. The clinical efficacy of the two groups was assessed in terms of fracture reduction quality, fracture healing time, Gartland-Werley wrist joint score and X-ray parameters (palminclination angle, ulnar deviation angle, radius height) at 6 weeks post-operatively. Results The treatment group exhibited a shorter duration for achieving clinical healing compared to the control group (P<0.05). Six weeks post-operatively, the treatment group demonstrated higher wrist joint function scores, and a higher proportion of excellent and good outcomes than the control group(P<0.05). The treatment group was superior to the control group in terms of imaging parameters 6 weeks post-operatively (P<0.05). Conclusion By quantifying skin contours through digital simulation prescription reduction, a personalized 3D printed splint is developed to effectively stabilize fractures, enhancing localized fixation while ensuring greater adherence, stability, and comfort. This innovative approach offers personalized treatment for AO type-A distal radius fractures and presents a novel, precise treatment strategy for consideration.

Oxepine-containing pyrazinopyrimidine alkaloids and quinolinone derivatives produced by Aspergillus versicolor AS-212, a deep-sea-derived endozoic fungus.

Four new oxepine-containing pyrazinopyrimidine alkaloids, versicoxepines A - D (1-4), two quinolinone alkaloid analogs including 3-hydroxy-6-methoxy-4-phenylquinolin-2(1H)-one (5) and 3-methoxy-6-hydroxy-4-phenylquinolin-2(1H)-one (6) which were new naturally occurring compounds, together with two known compounds (7 and 8) were isolated from Aspergillus versicolor AS-212, an endozoic fungus isolated from the deep-sea coral Hemicorallium cf. imperiale, which was collected from the Magellan Seamounts in the Western Pacific Ocean. Their structures were determined by extensive analysis of the spectroscopic and X-ray crystallographic data as well as by chiral HPLC analysis, ECD calculation, and DP4+ probability prediction. Structurally, versicoxepines B and C (2 and 3) represent the first example of a new oxepine-containing pyrazinopyrimidine alkaloid whose cyclic dipeptide moiety is composed of the same type of amino acid (Val or Ile). Compound 5 displayed antibacterial activity against aquatic pathogens, Vibrio harveyi and V. alginolyticus, with MICs of 8 µg/mL.

Five new verrucosidin derivatives from Penicillium polonicum, a deep-sea cold-seep sediment isolated fungus.

Five new verrucosidin derivatives, poloncosidins G-K (1-5), were isolated from the deep sea cold-seep sediment-derived fungus Penicillium polonicum CS-252. Their planar structures were elucidated by discreet analysis of the NMR spectroscopic and HRESIMS spectrometric data. The absolute configurations of compounds 1-5 were deduced from the combination of the modified Mosher's method and quantum chemical calculations of their ECD and NMR (with DP4+ probability analysis) data. The antimicrobial activities against several human- and aquatic-pathogenic bacteria of all the isolated compounds were evaluated and the structure-bioactivity relationship was briefly discussed.

FveARF2 negatively regulates fruit ripening and quality in strawberry.

Auxin response factors (ARFs) are transcription factors that play important roles in plants. ARF2 is a member of the ARF family and participates in many plant growth and developmental processes. However, the role of ARF2 in strawberry fruit quality remains unclear. In this study, FveARF2 was isolated from the woodland strawberry 'Ruegen' using reverse transcription-polymerase chain reaction (RT-PCR), which showed that FveARF2 expression levels were higher in the stem than in other organs of the 'Ruegen' strawberry. Moreover, FaARF2 was higher in the white fruit stage of cultivated strawberry fruit than in other stage. Subcellular localization analysis showed that FveARF2 is located in the nucleus, while transcriptional activation assays showed that FveARF2 inhibited transcription in yeast. Silencing FveARF2 in cultivated strawberry fruit revealed earlier coloration and higher soluble solid, sugar, and anthocyanin content in the transgenic fruit than in the control fruit, overexpression of FveARF2 in strawberry fruit delayed ripening and lower soluble solid, sugar, and anthocyanin content compared to the control fruit. Gene expression analysis indicated that the transcription levels of the fruit ripening genes FaSUT1, FaOMT, and FaCHS increased in FveARF2-RNAi fruit and decreased in FveARF2-OE fruit, when compared with the control. Furthermore, yeast one-hybrid (Y1H) and GUS activity experiments showed that FveARF2 can directly bind to the AuxRE (TGTCTC) element in the FaSUT1, FaOMT, and FaCHS promoters in vitro and in vivo. Potassium ion supplementation improved the quality of strawberry fruit, while silencing FveARF2 increased potassium ion content in transgenic fruit. The Y1H and GUS activity experiments also confirmed that FveARF2 could directly bind to the promoter of FveKT12, a potassium transporter gene, and inhibited its expression. Taken together, we found that FveARF2 can negatively regulate strawberry fruit ripening and quality, which provides new insight for further study of the molecular mechanism of strawberry fruit ripening.

Randomized trial estimating effects of hypnosis versus progressive muscle relaxation on medical students' test anxiety and attentional bias.

BACKGROUND: Test anxiety is prevalent among medical students and leads to impaired academic performance. Test-related attentional bias has been identified as an important maintaining factor in test-anxious individuals. AIM: To evaluate whether hypnosis and progressive muscle relaxation (PMR) could modify medical college students' test anxiety and attentional bias. METHODS: A total of 598 medical students were screened. The participants were divided into higher and lower test anxiety groups according to their scores on the test anxiety scale (TAS). Ninety medical college students with high TAS score were randomly assigned to a hypnosis or PMR group. Another 45 students with low TAS score were included, forming a baseline control group. The intervention was conducted weekly for 6 wk, and each session lasted approximately 30 min. The total intervention time and the number of intervention sessions for the hypnosis and PMR groups were equal. Data were collected at the pretest, posttest, and 2-mo follow-up. RESULTS: Hypnosis group participants had a significantly lower TAS score at posttest (t = -21.827, P < 0.001) and at follow-up (t = -14.824, P < 0.001), compared to that at pretest. PMR group participants also had a significantly lower TAS score at posttest (t = -10.777, P < 0.001) and at follow-up (t = -7.444, P < 0.001), compared to that at pretest. At the posttest level, the hypnosis group had a significantly lower TAS score than the PMR group (t = -3.664, P < 0.001). At the follow-up level, the hypnosis group also had a significantly lower TAS score than the PMR group (t = -2.943, P = 0.004). Clinically significant improvement was found in both the hypnosis and PMR groups (hypnosis = 64.0%; PMR = 62.22%). Hypnosis was more effective than PMR in reducing test anxiety among medical college students. Hypnosis could modify attentional bias toward threatening stimuli, but PMR could not. CONCLUSION: These results suggest that attentional bias plays an important role in test anxiety treatment.

Targeting thalamic circuits rescues motor and mood deficits in PD mice.

Although bradykinesia, tremor and rigidity are the hallmark motor defects in patients with Parkinson's disease (PD), patients also experience motor learning impairments and non-motor symptoms such as depression1. The neural circuit basis for these different symptoms of PD are not well understood. Although current treatments are effective for locomotion deficits in PD2,3, therapeutic strategies targeting motor learning deficits and non-motor symptoms are lacking4-6. Here we found that distinct parafascicular (PF) thalamic subpopulations project to caudate putamen (CPu), subthalamic nucleus (STN) and nucleus accumbens (NAc). Whereas PF→CPu and PF→STN circuits are critical for locomotion and motor learning, respectively, inhibition of the PF→NAc circuit induced a depression-like state. Whereas chemogenetically manipulating CPu-projecting PF neurons led to a long-term restoration of locomotion, optogenetic long-term potentiation (LTP) at PF→STN synapses restored motor learning behaviour in an acute mouse model of PD. Furthermore, activation of NAc-projecting PF neurons rescued depression-like phenotypes. Further, we identified nicotinic acetylcholine receptors capable of modulating PF circuits to rescue different PD phenotypes. Thus, targeting PF thalamic circuits may be an effective strategy for treating motor and non-motor deficits in PD.

Boosting the antioxidant potential of pasta by a premature stop mutation in wheat keto-acythiolase-2.

Phenolics are a class of chemical compounds possessing antioxidant activity, which are mainly located in the wheat (Triticum aestivum) bran. Different approaches have been used in food industry to increase the availability of phenolics. Compared to these methods, however, genetic improvement of the wheat antioxidant potential, is a cost-effective, easier and safer approach. Here, we showed a single premature stop mutation in the keto-acythiolase-2 (kat-2b) gene, which significantly improved the antioxidant potential of pasta by a 60 ± 16% increase in its antioxidant potential by increasing the accumulation of ferulic acid. These changes are likely determined by the increased transcription (46% higher) and activity (120% higher) of the phenylalanine lyase genes observed in the mutated line compared to the control. Even if more studies will need to be done, overall, this study suggested that the kat-2b mutant could represent an excellent genetic resource to improve wheat's antioxidant and health-promoting potential.

Isolation and Characterization of Antibacterial Carotane Sesquiterpenes from Artemisia argyi Associated Endophytic Trichoderma virens QA-8.

Carotane sesquiterpenes are commonly found in plants but are infrequently reported in the fungal kingdom. Chemical investigation of Trichoderma virens QA-8, an endophytic fungus associated with the inner root tissue of the grown medicinal herb Artemisia argyi H. Lév. and Vaniot, resulted in the isolation and characterization of five new carotane sesquiterpenes trichocarotins I-M (1-5), which have diverse substitution patterns, and seven known related analogues (6-12). The structures of these compounds were established on the basis of a detailed interpretation of their NMR and mass spectroscopic data, and the structures including the relative and absolute configurations of compounds 1-3, 5, 9, and 10 were confirmed by X-ray crystallographic analysis. In the antibacterial assays, all isolates exhibited potent activity against Escherichia coli EMBLC-1, with MIC values ranging from 0.5 to 32 µg/mL, while 7ß-hydroxy CAF-603 (7) strongly inhibited Micrococcus luteus QDIO-3 (MIC = 0.5 µg/mL). Structure-activity relationships of these compounds were discussed. The results from this study demonstrate that the endophytic fungus T. virens QA-8 from the planted medicinal herb A. argyi is a rich source of antibacterial carotane sesquiterpenes, and some of them might be interesting for further study to be developed as novel antibacterial agents.

Polyketides and Terpenoids with Potent Antibacterial Activities from the Artemisia argyi-Derived Fungus Trichoderma koningiopsis QA-3.

The AcOEt extract of Artemisia argyi-derived fungus Trichoderma koningiopsis QA-3 showed potent inhibitory activity against pathogenic bacteria. Fractionation of the extract resulted in the isolation of three new polyketides (1-3) and two new terpenoids (4 and 5), together with three known metabolites (6-8). Their chemical structures were analyzed by NMR spectra, ECD, HR-ESI-MS or HR-EI-MS, optical rotation, and X-ray crystallographic data, as well as by comparison with literature reports. In the antibacterial assays, 3-hydroxyharziandione (4) showed potent activity against human pathogen Escherichia coli with an MIC value of 0.5 µg/mL, while 6-(3-hydroxypent-1-en-1-yl)-2H-pyran-2-one exhibited strong activity against marine-derived aquatic pathogen Micrococcus luteus with an MIC value of 1.0 µg/mL.

[Effects of light quality on growth and icariin flavonoid content of Epimedium pseudowushanense under different light intensity].

In this study, the growth index including plant height, compound leaf area, specific leaf area, leaf water content, number of branches, and leaf biomass per plant and the icariin flavonoids such as epimedin A, epimedin B, epimedin C and icariin of Epimedium pseudowushanense were determined on 30 d and 60 d under light intensity(18.2±2.5) µmol·m~(-2)·s~(-1)(L1) and(90.9 ±2.5) µmol·m~(-2)·s~(-1)(L2), and white light as control, red light, blue light and yellow light were used as three light quality treatments, to study the effect of light quality on the growth and flavonoids accumulation of E. pseudowushanense. The E. pseudowushanense was sui-table for growth under L1 light intensity, the blue light treatment significantly reduced the leaf area, but had little effect on the stem height, the red light treatment and the yellow light treatment had no obvious effect on the stem height and leaf area, but the yellow light treatment significantly increased the germination of new branches, and had a sustained promoting effect, and the biomass was significantly higher than the white light treatment at 60 d. The content of icariin flavonoids in red light, blue light and yellow light treatment was higher than that in white light treatment at 30 d and 60 d under L1 light intensity, while yellow light treatment promoted the synthesis of icariin flavonoids to the largest extent, which was 1.8 and 1.9 times of white light treatment(30 d and 60 d).Under L2 light intensity, the effect of strong light on promoting stem germination became the main factor, while the yellow light treatment showed no significant effect on promoting stem germination, and the red light treatment exhibited a significant effect on reducing leaf area. Icariin flavonoids under red light, blue light and yellow light treatment were all lower than that under white light treatment, that is, the effect of white light treatment on the synthesis of icariin flavonoids is better than red light, blue light and yellow light treatment. When the time of strong light treatment was longer, the degradation range of icariin flavonoids in other light treatment appeared, while red light treatment promotes the synthesis of icariin flavonoids. Therefore, the influence of light quality on E. pseudowushanense is quite different under different light intensity, no matter from growth index or flavonoid content index. The results support that the biomass and icariin flavonoid content can be increased by providing appropriate red and yellow light.

Cytotoxic Thiodiketopiperazine Derivatives from the Deep Sea-Derived Fungus Epicoccum nigrum SD-388.

Four new thiodiketopiperazine alkaloids, namely, 5'-hydroxy-6'-ene-epicoccin G (1), 7-methoxy-7'-hydroxyepicoccin G (2), 8'-acetoxyepicoccin D (3), and 7'-demethoxyrostratin C (4), as well as a pair of new enantiomeric diketopiperazines, (±)-5-hydroxydiphenylalazine A (5), along with five known analogues (6-10), were isolated and identified from the culture extract of Epicoccum nigrum SD-388, a fungus obtained from deep-sea sediments (-4500 m). Their structures were established on the basis of detailed interpretation of the NMR spectroscopic and mass spectrometric data. X-ray crystallographic analysis confirmed the structures and established the absolute configurations of compounds 1-3, while the absolute configurations for compounds 4 and 5 were determined by ECD calculations. Compounds 4 and 10 showed potent activity against Huh7.5 liver tumor cells, which were comparable to that of the positive control, sorafenib, and the disulfide bridge at C-2/C-2' is likely essential for the activity.

Highly oxygenated polyketides produced by Trichoderma koningiopsis QA-3, an endophytic fungus obtained from the fresh roots of the medicinal plant Artemisia argyi.

Eight new highly oxygenated fungal polyketides, namely, 15-hydroxy-1,4,5,6-tetra-epi-koninginin G (1), 14-hydroxykoninginin E (2), koninginin U (3), 4'-hydroxykoninginin U (4), koninginin V (5), 14-ketokoninginin B (6), 14-hydroxykoninginin B (7), and 7-O-methylkoninginin B (8), together with six known related analogues (9-14), were isolated from Trichoderma koningiopsis QA-3, a fungus obtained from the inner root tissue of the well known medicinal plant Artemisia argyi. All these compounds are bicyclic polyketides, with compound 1 contains unusual hemiketal moiety at C-5 and compounds 2-14 having ketone group at C-1 and double bond at C-5(6). The structures and absolute configurations of the new compounds were established by spectroscopic analysis, X-ray crystal diffraction, modified Mosher's method, and ECD calculation. The absolute configurations of the known compounds 9, 10, and 12 were determined by X-ray crystal diffractions for the first time. The antimicrobial activities against human pathogen, marine-derived aquatic bacteria, and plant-pathogenic fungi of compounds 1-14 were evaluated, and compound 1 showed remarkable activity against aquatic pathogen Vibrio alginolyticus with MIC value 1 µg/mL, which is as active as that of the positive control.

Trichocadinins B-G: Antimicrobial Cadinane Sesquiterpenes from Trichoderma virens QA-8, an Endophytic Fungus Obtained from the Medicinal Plant Artemisia argyi.

Trichocadinins B-G (1-6), six new cadinane-type sesquiterpene derivatives, each with C-14 carboxyl functionality, were isolated from the culture extract of Trichoderma virens QA-8, an endophytic fungus obtained from the fresh inner tissue of the medicinal plant Artemisia argyi. Their structures were elucidated by interpretation of the NMR spectroscopic and mass spectrometric data. The structures and absolute configurations of compounds 1 and 3 were confirmed by X-ray crystallographic analysis. Compounds 1-3 showed antibacterial and antifungal activity.

[Effect of maternal exposure to Curcumae Rhizoma during pregnancy on neurodevelopment and apoptosis mechanism in offspring].

Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.

[Vertical change of cladoceran ephippial densities in the sediments of Lake Nanyi and its correlation with the nutrients]. / å—æ¼ªæ¹–æ²‰ç§¯ç‰©æžè§’ç±»åµéžå¯†åº¦çš„åž‚ç›´å˜åŒ–åŠå ¶ä¸Žè¥å »ç›çš„å ³ç³».

We examined the vertical variations of cladoceran ephippia in the sediments (1-28 cm) of Lake Nanyi. Nine cladoceran ephippia (Daphnia similoides sinensis, Daphnia galeata, Daphnia pulex, Ceriodaphnia sp., Moina micrura, Bosmina sp., Scapholeberis sp., Leydigia leydigii and Chydorus sp.) were identified. The ephippial densities of Daphnia species and small cladocerans ranged from 0 to 2.0 ind·g-1 DM and from 0 to 10 ind·g-1 DM, respectively. D. similoides sinensis and Ceriodaphnia sp. were respectively dominant species of large and small cladocerans in the sediments of Lake Nanyi. The ephippial densities of D. similoides sinensis had a significant negative correlation with total phosphorus content of sediments in the 1# sampling site of Lake Nanyi and had positive correlations with total nitrogen and total phosphorus contents in the 3# sampling site. In three sampling sites (except for total nitrogen contents in the 2# sampling site), there were significant positive relationships between the ephippial densities of Ceriodaphnia sp. and both total nitrogen and total phosphorus contents. Our results suggested that eutrophication and fish predation affected the historical succession of cladoceran community structure in Lake Nanyi.

[Discussion on related problems of model species of fungus： Paecilomyces hepialid].

Paecilomyces hepiali is a new species of fungus isolated from a field collection of Ophiocordyceps sinensis from Baima snow mountain, Diqing Tibetan Autonomous Prefecture, Yunnan Province by the Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences. The specimen was identified and named as Paecilomyces hepiali by Qing-Tao Chen, the professor of the Institute of Microbiology, Chinese Academy of Sciences (Paecilomyces hepiali) (2008), who identified a dried culture of living strain 82-2 as the holotype. Until now, the holotype (the voucher specimen) was deposited in the Herbarium of the Institute of Chinese Materia Medica (HICMM), China Academy of Chinese Medical Sciences, Beijing. The P. hepiali neotype designated by the paper "Neotypification of P. hepiali (Hypocreales)" published in TAXON 64 (1) by Yao Yi-Jian et al. in February 2015 is untenable.

Isorhynchophylline Attenuates MPP+-Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity.

Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP+-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP+-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway. IRN-mediated attenuation of endoplasmic reticulum modulator caspase-12 activation was abolished by diphenyleneiodonium (DPI) or IRE-1α shRNA, but not by SP600125 or pifithrin-α in MPP+-treated PC12 cells. Inhibitions of MPP+-induced both cytochrome c release and caspase-9 activation by IRN were blocked by pre-treatment with DPI or pifithrin-α, but not by IRE-1α shRNA. IRN blocks the generation of reactive oxygen species upstream of both ASK1/JNK pathway and IRE1/caspase-12 pathway. Altogether, our in vitro findings suggest that IRN possesses potent neuroprotective activity and may be a potential candidate for the treatment of PD.

DV21 decreases excitability of cortical pyramidal neurons and acts in epilepsy.

Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice. Furthermore, we also found that the antiepileptic effect of DV21 might be partly mediated through reducing the excitability of cortical pyramidal neurons by increasing M current, which are low-threshold non-inactivating voltage-gated potassium currents. Moreover, the application of XE991, an inhibitor of M current, could block most the antiepileptic effect of DV21. Taken together, our results indicated that DV21 might be a novel leading compound for the treatment of epilepsy.

[Optimization Study on the Nitrogen and Phosphorus Removal of Modified Two- sludge System Under the Condition of Low Carbon Source].

This paper explored the method of resolving insufficient carbon source in urban sewage by comparing and analyzing denitrification and phosphorus removal (NPR) effect between modified two-sludge system and traditional anaerobic-aerobic-anoxic process under the condition of low carbon source wastewater. The modified two-sludge system was the experimental reactor, which was optimized by adding two stages of micro-aeration (aeration rate 0.5 L · mm⁻¹) in the anoxic period of the original two-sludge system, and multi-stage anaerobic-aerobic-anoxic SBR was the control reactor. When the influent COD, ammonia nitrogen, SOP concentration were respectively 200, 35, 10 mg · L⁻¹, the NPR effect of the experimental reactor was hetter than that of thecontrol reactor with the removal efficiency of TN being 94.8% vs 60.9%, and TP removal being 96.5% vs 75%, respectively. The effluent SOP, ammonia, TN concentration of the experimental reactor were 0.35, 0.50, 1.82 mg · L⁻¹, respectively, which could fully meet the first class of A standard of the Pollutants Emission Standard of Urban Wastewater Treatment Firm (GB 18918-2002). Using the optimized treatment process, the largest amounts of nitrogen and phosphorus removal per unit carbon source (as COD) were 0.17 g · g⁻¹ and 0.048 g · g⁻¹ respectively, which could furthest solve the lower carbon concentration in current municipal wastewater.