Copper nanoparticles lead to reproductive dysfunction by affecting key enzymes of ovarian hormone synthesis and metabolism in female rats.

Studies on the general toxicity of copper nanoparticles (Cu NPs) have been conducted extensively, but their effects on reproductive toxicity remain unclear. In this study, we evaluated the toxic effect of Cu NPs on pregnant rats and their litter. The comparative in vivo toxicity of Cu ions, Cu NPs, and Cu microparticles (MPs) was studied in a 17-day repeated oral-dose experiment at the doses of 60, 120, and 180 mg/kg/day in pregnant rats. The pregnancy rate, mean live litter size, and number of dams decreased when exposed to Cu NPs. Moreover, Cu NPs caused a dose-dependent increase in ovarian Cu levels. The metabolomics results showed that Cu NPs caused reproductive dysfunction by altering sex hormones. In addition, in vivo and in vitro experiments showed that the ovarian cytochrome P450 enzymes (CYP450), responsible for hormone production, were significantly upregulated, whereas the enzymes responsible for hormone metabolism were significantly inhibited, resulting in a metabolic imbalance in some ovarian hormones. Furthermore, the results revealed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways significantly participated in the regulation of ovarian CYP enzyme expression. Overall, the results of the in vivo and in vitro toxicity experiments with Cu ions, Cu NPs, and Cu MPs suggested that toxicity from nanoscale Cu particles poses a more serious reproductive threat than microscale Cu as Cu NPs could directly damage the ovary and affect the metabolism of ovarian hormones.

The Ubiquitin E3 Ligase MaLUL2 Is Involved in High Temperature-Induced Green Ripening in Banana Fruit.

Harvested banana fruit ripened under warm temperatures above 24 °C remain green peel, leading to severe economic loss. E3 ubiquitin-ligases, as the major components in the ubiquitination pathway, have been implicated to play important roles in temperature-stress responses. However, the molecular mechanism underlying high temperature-triggered stay-green ripening bananas in association with E3 ubiquitin-ligases, remains largely unknown. In this study, a RING-type E3 ubiquitin ligase termed MaLUL2, was isolated and characterized from banana fruit. The MaLUL2 gene contains 1095 nucleotides and encodes a protein with 365 amino acids. The MaLUL2 protein contains a domain associated with RING2 (DAR2) and a RING domain, which are the typical characteristics of RING-type E3 ligases. MaLUL2 expression was up-regulated during high temperature-induced green ripening. Subcellular localization showed that MaLUL2 localized in the nucleus, cytoplasm, and plasma membrane. MaLUL2 displayed E3 ubiquitin ligase activity in vitro. More importantly, transient overexpression of MaLUL2 in banana fruit peel increased the level of ubiquitination in vivo and led to a stay-green phenotype, accompanying with decreased expression of chlorophyll catabolic genes. Collectively, these findings suggest that MaLUL2 might act as a negative regulator of chlorophyll degradation and provide novel insights into the regulatory mechanism of high temperature-induced green ripening bananas.

Golf ball-like MoS2 nanosheet arrays anchored onto carbon nanofibers for electrochemical detection of dopamine.

Arrays of molybdenum(IV) disulfide nanosheets resembling the shape of golf balls (MoS2 NSBs) were deposited on carbon nanofibers (CNFs), which are shown to enable superior electrochemical detection of dopamine without any interference by uric acid. The MoS2 NSBs have a diameter of ∼ 2 µm and are made up of numerous bent nanosheets. MoS2 NSBs are connected by the CNFs through the center of the balls. Figures of merit for the resulting electrode include (a) a sensitivity of 6.24 µA·µM-1·cm-2, (b) a low working voltage (+0.17 V vs. Ag/AgCl), and (c) a low limit of detection (36 nM at S/N = 3). The electrode is selective over uric acid, reproducible and stable. It was applied to the determination of dopamine in spiked urine samples. The recoveries at levels of 10, 20 and 40 µM of DA are 101.6, 99.8 and 107.8%. Graphical abstract Schematic presentation of the golf ball-like MoS2 nanosheet balls/carbon nanofibers (MoS2 NSB/CNFs) by electrospining and hydrothermal process to detect dopamine (DA).

BrTCP7 Transcription Factor Is Associated with MeJA-Promoted Leaf Senescence by Activating the Expression of BrOPR3 and BrRCCR.

The plant hormone jasmonic acid (JA) has been recognized as an important promoter of leaf senescence in plants. However, upstream transcription factors (TFs) that control JA biosynthesis during JA-promoted leaf senescence remain unknown. In this study, we report the possible involvement of a TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) TF BrTCP7 in methyl jasmonate (MeJA)-promoted leaf senescence in Chinese flowering cabbage. Exogenous MeJA treatment reduced maximum quantum yield (Fv/Fm) and total chlorophyll content, accompanied by the increased expression of senescence marker and chlorophyll catabolic genes, and accelerated leaf senescence. To further understand the transcriptional regulation of MeJA-promoted leaf senescence, a class I member of TCP TFs BrTCP7 was examined. BrTCP7 is a nuclear protein and possesses trans-activation ability through subcellular localization and transcriptional activity assays. A higher level of BrTCP7 transcript was detected in senescing leaves, and its expression was up-regulated by MeJA. The electrophoretic mobility shift assay and transient expression assay showed that BrTCP7 binds to the promoter regions of a JA biosynthetic gene BrOPR3 encoding OPDA reductase3 (OPR3) and a chlorophyll catabolic gene BrRCCR encoding red chlorophyll catabolite reductase (RCCR), activating their transcriptions. Taken together, these findings reveal that BrTCP7 is associated with MeJA-promoted leaf senescence at least partly by activating JA biosynthesis and chlorophyll catabolism, thus expanding our knowledge of the transcriptional mechanism of JA-mediated leaf senescence.

Activation of the Transcription of BrGA20ox3 by a BrTCP21 Transcription Factor Is Associated with Gibberellin-Delayed Leaf Senescence in Chinese Flowering Cabbage during Storage.

Several lines of evidence have implicated the involvement of the phytohormone gibberellin (GA) in modulating leaf senescence in plants. However, upstream transcription factors (TFs) that regulate GA biosynthesis in association with GA-mediated leaf senescence remain elusive. In the current study, we report the possible involvement of a TEOSINTE BRANCHED1/CYCLOIDEA/PCF (TCP) TF BrTCP21 in GA-delayed leaf senescence in Chinese flowering cabbage. Exogenous GA3 treatment maintained a higher value of maximum PSII quantum yield (Fv/Fm) and total chlorophyll content, accompanied by the repression of the expression of senescence-associated genes and chlorophyll catabolic genes, which led to the delay of leaf senescence. A class I member of TCP TFs BrTCP21, was further isolated and characterized. The transcript level of BrTCP21 was low in senescing leaves, and decreased following leaf senescence, while GA3 could keep a higher expression level of BrTCP21. BrTCP21 was further found to be a nuclear protein and exhibit trans-activation ability through transient-expression analysis in tobacco leaves. Intriguingly, the electrophoretic mobility shift assay (EMSA) and transient expression assay illustrated that BrTCP21 bound to the promoter region of a GA biosynthetic gene BrGA20ox3, and activated its transcription. Collectively, these observations reveal that BrTCP21 is associated with GA-delayed leaf senescence, at least partly through the activation of the GA biosynthetic pathway. These findings expand our knowledge on the transcriptional mechanism of GA-mediated leaf senescence.

lgtF effects of Haemophilus parasuis LOS induced inflammation through regulation of NF-κB and MAPKs signaling pathways.

The lgtF gene encodes a glucosyltransferase responsible for adding a glucose to the first sugar of heptose I in the synthesis of lipooligosaccharides (LOS). To study the function of lgtF, we constructed an lgtF mutant (ΔlgtF) from Haemophilus parasuis SC096 using a natural transformation system. A highly purified preparation of LOS from ΔlgtF (ΔlgtF-LOS) exhibited an obvious truncation in structure compared to the LOS of the wild-type SC096 strain (WT-LOS). The ΔlgtF-LOS also displayed a significantly reduced ability to induce inflammatory cytokine mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), IL-1ß, IL-6 and IL-8 in porcine alveolar macrophages (PAMs) in comparison with the WT-LOS. Furthermore, we also found that ΔlgtF-LOS-treated cells had significantly decreased phospho-p65 and phospho-p38, and inhibited IκBα degradation. These findings suggested that the lgtF gene mediated LOS induction of pro-inflammatory cytokines in PAMs by regulating the NF-κB and MAPKs signaling pathways during H. parasuis infection.

Deletion of the rfaE gene in Haemophilus parasuis SC096 strain attenuates serum resistance, adhesion and invasion.

In Haemophilus parasuis, the lipooligosaccharide (LOS) has been identified as an important virulence factor. The rfa gene cluster encodes enzymes for LOS core biosynthesis. In order to investigate the role of the rfaE gene, we generated an rfaE deficient mutant (ΔrfaE) of a H. parasuis SC096 by a natural transformation method. The purified preparation of LOS from the ΔrfaE mutant strain showed truncated LOS structure on silver-stained SDS-PAGE. Compared to the wild-type SC096 strain, the generation time of ΔrfaE mutant strain was significantly extended from 59 min to 69 min. The ΔrfaE mutant strain caused an approximately 30-fold reductions in survival rate in 50% sera and 36-fold reductions in survival rate in 90% sera, respectively (p < 0.001). In adhesion and invasion assays, the ΔrfaE mutant strain had 10-fold less efficient adherence and 12-fold reductions in invasion of the porcine umbilicus vein endothelial cells (PUVEC) and porcine kidney epithelial cells (PK-15), respectively (p < 0.001). However, the complemented strain could restore the above phenotypes. Hence, the above results suggested that the rfaE gene participated in the pathogenicity of H. parasuis SC096 strain.

Activation of Inflammasomes and Relevant Modulators for the Treatment of Microglia-mediated Neuroinflammation in Ischemic Stroke.

As the brain's resident immune patrol, microglia mediate endogenous immune responses to central nervous system injury in ischemic stroke, thereby eliciting either neuroprotective or neurotoxic effects. The association of microglia-mediated neuroinflammation with the progression of ischemic stroke is evident through diverse signaling pathways, notably involving inflammasomes. Within microglia, inflammasomes play a pivotal role in promoting the maturation of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), facilitating pyroptosis, and triggering immune infiltration, ultimately leading to neuronal cell dysfunction. Addressing the persistent and widespread inflammation holds promise as a breakthrough in enhancing the treatment of ischemic stroke.

Breviscapine protects against pathological cardiac hypertrophy by targeting FOXO3a-mitofusin-1 mediated mitochondrial fusion.

Forkhead box O3a (FOXO3a)-mediated mitochondrial dysfunction plays a pivotal effect on cardiac hypertrophy and heart failure (HF). However, the role and underlying mechanisms of FOXO3a, regulated by breviscapine (BRE), on mitochondrial function in HF therapy remain unclear. This study reveals that BRE-induced nuclear translocation of FOXO3a facilitates mitofusin-1 (MFN-1)-dependent mitochondrial fusion in cardiac hypertrophy and HF. BRE effectively promotes cardiac function and ameliorates cardiac remodeling in pressure overload-induced mice. In addition, BRE mitigates phenylephrine (PE)-induced cardiac hypertrophy in cardiomyocytes and fibrosis remodeling in fibroblasts by inhibiting ROS production and promoting mitochondrial fusion, respectively. Transcriptomics analysis underscores the close association between the FOXO pathway and the protective effect of BRE against HF, with FOXO3a emerging as a potential target of BRE. BRE potentiates the nuclear translocation of FOXO3a by attenuating its phosphorylation, other than its acetylation in cardiac hypertrophy. Mechanistically, over-expression of FOXO3a significantly inhibits cardiac hypertrophy and mitochondrial injury by promoting MFN-1-mediated mitochondrial fusion. Furthermore, BRE demonstrates its ability to substantially curb cardiac hypertrophy, reduce mitochondrial ROS production, and enhance MFN-1-mediated mitochondrial fusion through a FOXO3a-dependent mechanism. In conclusion, nuclear FOXO3a translocation induced by BRE presents a successful therapeutic avenue for addressing cardiac hypertrophy and HF through promoting MFN-1-dependent mitochondrial fusion.

LASP1 in the nucleus accumbens modulates methamphetamine-induced conditioned place preference in mice.

Methamphetamine (METH) is a highly addictive and widely abused drug that causes complex adaptive changes in the brain's reward system, such as the nucleus accumbens (NAc). LASP1 (LIM and SH 3 domain protein 1) as an actin-binding protein, regulates synaptic plasticity. However, the role and mechanism by which NAc LASP1 contributes to METH addiction remains unclear. In this study, adult male C57BL/6J mice underwent repeated METH exposure or METH-induced conditioned place preference (CPP). Western blotting and immunohistochemistry were used to determine LASP1 expression in the NAc. Furthermore, LASP1 knockdown or overexpression using adeno-associated virus (AAV) administration via stereotactic injection into the NAc was used to observe the corresponding effects on CPP. We found that repeated METH exposure and METH-induced CPP upregulated LASP1 expression in the NAc. LASP1 silencing in the NAc reversed METH-induced CPP and reduced PSD95, NR2A, and NR2B expression, whereas LASP1 overexpression in the NAc enhanced CPP acquisition, accompanied by increased PSD95, NR2A, and NR2B expression. Our findings demonstrate an important role of NAc LASP1 in modulating METH induced drug-seeking behavior and the underlying mechanism may be related to regulate the expression of synapse-associated proteins in the NAc. These results reveal a novel molecular regulator of the actions of METH on the NAc and provide a new strategy for treating METH addiction.

Oral edaravone ameliorates behavioral deficits and pathologies in a valproic acid-induced rat model of autism spectrum disorder.

Autism spectrum disorder (ASD) is neurodevelopmental disorder with a high incidence rate, characterized by social deficits and repetitive behaviors. There is currently no effective management available to treat the core symptoms of ASD; however, oxidative stress has been implicated in its pathogenesis. Edaravone (EDA), a free-radical scavenger, is used to treat amyotrophic lateral sclerosis (ALS) and acute ischemic stroke (AIS). Here, we hypothesized that an oral formula of EDA may have therapeutic efficacy in the treatment of core ASD symptoms. A rat model of autism was established by prenatal exposure to valproic acid (VPA), and the offsprings were orally treated with EDA at low (3 mg/kg), medium (10 mg/kg), and high (30 mg/kg) doses once daily for 28 days starting from postnatal day 25 (PND25). Oral EDA administration alleviated the core symptoms in VPA rats in a dose-dependent manner, including repetitive stereotypical behaviors and impaired social interaction. Furthermore, oral administration of EDA significantly reduced oxidative stress in a dose-dependent manner, as evidenced by a reduction in oxidative stress markers and an increase in antioxidants in the blood and brain. In addition, oral EDA significantly attenuated downstream pathologies, including synaptic and mitochondrial damage in the brain. Proteomic analysis further revealed that EDA corrected the imbalance in brain oxidative reduction and mitochondrial proteins induced by prenatal VPA administration. Overall, these findings demonstrate that oral EDA has therapeutic potential for ASD by targeting the oxidative stress pathway of disease pathogenesis and paves the way towards clinical studies.

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites.

Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level. Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics. Results: SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS. Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

High-cholesterol diet promotes depression- and anxiety-like behaviors in mice by impact gut microbe and neuroinflammation.

Neuropsychiatric disorders, including anxiety and depression, are one of the most common mental illnesses worldwide. A growing body of evidence shows that there is a complex relationship between dietary patterns and mental health. In our study, C57BL/6J mice were divided into three groups: control diet group (CON, 10 % kcal fat), high-cholesterol diet model group (HCD, 42.0 % kcal fat + 1.25 % kcal Cholesterol), and chronic restraint stress group (CRS, 10 % kcal fat) which as a positive control group for the depression model. Six weeks later, depressive- and anxiety-like behavior were evaluated for using the OFT, SPT and TST. Glucose intolerance and liver fat were detected by IGTT and liver lipid kit. The expression of peripheral and central inflammation was detected by LEGEND plex kits. 5-HT (also named 5-hydroxytryptamine, 5-HT) and related receptors expression were monitored by ELISA, RT-PCR and Western blot. Meantime, gut microbe of stool samples was performed by 16S rRNA gene sequencing. Similar to CRS model, short-term HCD intervention induced anxiety and depression-like behavior behavioral abnormalities in mice. HCD consumption resulted in significantly increased body weight, liver fat (LDL-C, TC, TG), peripheral inflammation (IL-1ß, MCP-1, IL-17A) and neuroinflammation (MCP-1). The concentration of 5-HT increased in the hippocampus, meanwhile, the expression of 5-HT receptor HTR2A was distinct in different regions of the brain tissue. More importantly, we found that compared with the CON diet, HCD induced the decrease of intestinal flora diversity, especially the decrease the relative abundance of Akkermansia_muciniphila, which was statistically significant. Further, Pearson correlation analysis showed that Akkermansia_muciniphila was significantly negatively correlated with the concentration of MCP-1, IL-17A in serum and 5-HT in hippocampus. Therefore, we speculated that the disorder of neuroinflammation induced by HCD consumption promotes depression- and anxiety-like behaviors in mice through the gut microbe.

[Studying the changes of the related serum complement immune indexes in patients with occupational medicamentosa-like dermatitis induced by trichloroethylene and workers occupationally exposed to trichloroethylene].

OBJECTIVE: To explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE. METHODS: The blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored. RESULTS: C3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01). CONCLUSION: The type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.

Macleaya cordata extract modulates inflammation via inhibition of the NF-κB and MAPK signaling pathways in porcine alveolar macrophages induced by Glaesserella parasuis.

Glässer's disease in pigs is associated with infection by Glaesserella parasuis and is characterized by pneumonia-like symptoms, fibrinous polyserositis, polyarthritis, and meningitis. Macleaya cordata, a commonly used traditional Chinese medication, has been shown to have anti-inflammatory, antiviral, antioxidative, antimicrobial, insecticidal, and antitumor properties. However, the anti-inflammatory effects of M. cordata on G. parasuis stimulation are still poorly understood. This study explored the anti-inflammatory effects and mechanisms of M. cordata extract on G. parasuis-induced inflammatory responses, via the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, in porcine alveolar macrophages (PAMs). Porcine alveolar macrophages, when stimulated with G. parasuis, initiated transcription of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α). Furthermore, p65, IκBα, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) phosphorylation were upregulated via the NF-κB and MAPK signaling pathways. However, treatment with M. cordata extract inhibited transcription of IL-1α, IL-1ß, IL-6, IL-8, and TNF-α and reduced p65, IκBα, p38, ERK, and JNK phosphorylation, by inhibiting activation of the NF-κB and MAPK signaling pathways in PAMs induced by G. parasuis. These findings reveal that M. cordata extract can reverse the inflammatory effect initiated by G. parasuis in vitro and that it possesses significant immunosuppression activity; thus, it may offer a novel strategy for controlling and treating G. parasuis infection.

La maladie de Glässer chez les porcs est associée avec une infection par Glaesserella parasuis et est caractérisée par des symptômes similaires à une pneumonie, une polysérosite fibrineuse, une polyarthrite et une méningite. Macleaya cordata, un médicament utilisé couramment en médecine traditionnelle chinoise, a été montré comme ayant des propriétés anti-inflammatoire, antivirale, anti-oxydative, antimicrobienne, insecticide et anti-tumeur. Toutefois, les effets anti-inflammatoires de M. cordata sur une stimulation par G. parasuis sont toujours peu compris. La présente étude explore les effets et mécanismes anti-inflammatoires d'un extrait de M. cordata sur les réponses inflammatoires induites par G. parasuis, via le facteur nucléaire-kappa B (NF-κB) et la voie de signalisation de la protéine kinase activée par les mitogènes (MAPK), dans les macrophages alvéolaires porcins (PAMs). Les PAMs, lorsque stimulés par G. parasuis, ont initié la transcription des interleukines (IL)-1α, IL-1ß, IL-6, IL-8, et le facteur de nécrose des tumeurs alpha (TNF-α). Également, la phosphorylation de p65, IκBα, p38, de la kinase régulée par signal extracellulaire (ERK), et de la kinase c-Jun N-terminal (JNK) était régulée à la hausse via les voies de signalisation NF-κB and MAPK. Toutefois, le traitement avec l'extrait de M. cordata a inhibé la transcription d'IL-1α, IL-1ß, IL-6, IL-8, et TNF-α et a diminué la phosphorylation de p65, IκBα, p38, ERK, et JNK, en inhibant les voies de signalisation de NF-κB et MAPK dans les PAMs induits par G. parasuis. Ces trouvailles révèlent qu'un extrait de M. cordata peut renverser l'effet inflammatoire initié par G. parasuis in vitro et qu'il possède une activité immunosuppressive significative; ainsi, ceci pourrait offrir une nouvelle stratégie pour limiter et traiter l'infection par G. parasuis.(Traduit par Docteur Serge Messier).

Environmental enrichment ameliorates high-fat diet induced olfactory deficit and decrease of parvalbumin neurons in the olfactory bulb in mice.

Overweight induced by high-fat diet (HFD) represents one of the major health concerns in modern societies, which can cause lasting peripheral and central metabolic disorders in all age groups. Specifically, childhood obesity could lead to life-long impact on brain development and functioning. On the other hand, environmental enrichment (EE) has been demonstrated to be beneficial for learning and memory. Here, we explored the impact of high-fat diet on olfaction and organization of olfactory bulb cells in adolescent mice, and the effect of EE intervention thereon. Puberty mice (3-week-old) fed with HFD for 10 weeks exhibited poorer odor sensitivity and olfactory memory relative to controls consuming standard chows. The behavioral deficits were rescued in the HFD group with EE intervention. Neuroanatomically, parvalbumin (PV) interneurons in the olfactory bulb (OB) were reduced in the HFD-fed animals relative to control, while EE intervention also normalized this alteration. In contrast, cells expressing calbindin (CB), doublecortin (DCX) in the OB were not altered. Our findings suggest that PV interneurons may play a crucial role in mediating the HFD-induced olfactory deficit in adolescent mice, and can also serve a protective effect of EE against the functional deficit.

Epigallocatechin-3-Gallate Ameliorates Acute Lung Damage by Inhibiting Quorum-Sensing-Related Virulence Factors of Pseudomonas aeruginosa.

The superbug Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens. With declining options for antibiotic-resistant infections, new medicines are of utmost importance to combat with P. aeruginosa. In our previous study, we demonstrated that Epigallocatechin-3-gallate (EGCG) can inhibit the production of quorum sensing (QS)-regulated virulence factors in vitro. Accordingly, the protective effect and molecular mechanisms of EGCG against P. aeruginosa-induced pneumonia were studied in a mouse model. The results indicated that EGCG significantly lessened histopathological changes and increased the survival rates of mice infected with P. aeruginosa. EGCG effectively alleviated lung injury by reducing the expression of virulence factors and bacterial burden. In addition, EGCG downregulated the production of pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-17, and increased the expression of anti-inflammatory cytokines IL-4 and IL-10. Thus, the experimental results supported for the first time that EGCG improved lung damage in P. aeruginosa infection by inhibiting the production of QS-related virulence factors in vivo.

Physiological and transcription analyses reveal regulatory pathways of 6-benzylaminopurine delaying leaf senescence and maintaining quality in postharvest Chinese flowering cabbage.

The regulatory role of cytokinins (CTKs) in leaf senescence has been documented in different species, including Chinese flowering cabbage. However, its physiological and molecular basis relatively remains unknown. In this study, exogenous application of a CTK analogue 6-benzylaminopurine (6-BA) significantly retarded leaf senescence of Chinese flowering cabbage, with less chlorophyll degradation and lower accumulation of reactive oxygen species (ROS) and malondialdehyde compared with the control group. Meanwhile, higher levels of soluble sugars and proteins, flavonoids, cellulose, amino acids, total phenols, procanthocyanins, and vitamin C were retained in 6-BA-treated leaves. 6-BA treatment also prevented the decline in endogenous CTK content and the increase in ethylene, abscisic acid, and jasmonic acid contents. Moreover, the comparative transcriptome analysis revealed that a total of 21,895 differently expressed genes (DEGs) were identified from four comparisons of 6-BA treatment versus the control during senescence. Further analysis showed that most of the identified DEGs were enriched in ROS, respiratory metabolism, and phytohormone pathways, and a total of 50 classes of transcription factors that were possibly involved in modulating these DEGs were obtained. The transcriptional levels of 18 DEGs were verified by Quantitative real-time PCR (qRT-PCR), which confirmed the accuracy of the transcriptomic data. Overall, these findings and data provide a comprehensive view of physiological and molecular events concerning with the CTK-mediated leaf senescence and -maintained quality in economical leafy vegetables.

The effect of Macleaya cordata extract on in vitro ruminal fermentation and methanogenesis.

Methane production is the main gas energy loss in ruminants and generates a powerful greenhouse gas that contributes to climate changes. Macleaya cordata is a plant commonly utilized additive in livestock diet as it contains various chemical compounds with beneficial health effects. This study aimed to explore the influence of M. cordata extract on in vitro methanogenesis and rumen fermentation. Three cannulated Jingjiang cattle were used as rumen fluid donors. The mixture of rumen fluid and a buffer (60 ml, 1:2 volume ratio) was treated with 6 different concentrations of M. cordata extract (0.01%, 0.11%, 0.21%, 0.31%, 0.41%, and 0.51%) and incubated for 12 and 24 hr. The control sample, with no addition of plant extract, was also analyzed. At each time point, pH, total gas, methane, dry matter (DM) digestibility, neutral detergent fiber (NDF), acid detergent fiber (ADF), ammonia nitrogen (NH3-N), microbial protein (MCP), and volatile fatty acids (VFA) concentrations were determined. Total gas production decreased with increasing the amount of M. cordata extract at all time points. Methane production also decreased dose-dependently with M. cordata extract after 3, 6, 9, and 12 hr of incubation, but increased after 24 hr. M. cordata extract decreased the concentration of NH3-N and VFA, and the amount of acetic, propionic, and butyric acid. M. cordata extract decreased the MCP concentration after 12 hr, but its level returned to the initial value after 24 hr. Supplementation with 0.01, 0.11, and 0.21% of M. cordata extract did not affect the DM digestibility. However, supplementation with 0.31, 0.41, and 0.51% of M. cordata extract significantly decreased the DM digestibility. Supplementation with 0.11% of M. cordata extract effectively reduced methane production without affecting the DM digestion in vitro. However, its effect on in vivo methane production, rumen fermentation, and ruminant production requires further investigation.

[Sources of Nitrate in Groundwater and Its Environmental Effects in Karst Trough Valleys: A Case Study of an Underground River System in the Longfeng Trough Valley, Chongqing].

Water samples from the two underground rivers (Fenghuang River and Longju River) and samples of the dry and wet deposition of atmospheric dissolved inorganic nitrogen were taken from the Longfeng karst trough valley located in the Zhongliang mountain in the suburbs of Chongqing from May 2017 to April 2018. Anions, cations, δ15 N(NO3-), δ18 O(NO3-), δ18 O(H2O), and δ13C(DIC) isotope data were used to investigate the NO3- source and its environmental effects. The results showed:① The hydrochemistry of the two underground rivers is of the type HCO3-Ca. The NO3- concentration varied from 17.58 to 32.58 mg·L-1, with an average of 24.02 mg·L-1, and was slightly higher in rainy season than the dry season, revealing that the underground rivers were polluted. ② The δ15 N(NO3-) value ranged from -3.14‰ to 12.67‰, with an average value of 7.45‰. The δ18 O(NO3-) value ranged from -0.77‰ to 12.05‰ with an average value of 2.90‰, and was higher in the dry season than the rainy season, indicating that animal excreta and domestic sewage were main NO3- sources throughout the year. In addition, rainfall, fertilizer, and soil nitrogen were the NO3- sources during the rainy season. There are no significant differences between the NO3- sources of the two underground rivers, and nitrification is the main nitrogen conversion process. ③ The molar ratio of (Ca2++Mg2+)/HCO3- varied from 0.65 to 0.82. That of the Fenghuang River was 0.75 and that of the Longju River was 0.70. The δ13C(DIC) value ranged from -12.46‰ to -9.20‰, with a mean of -11.10‰ in the Longju River and -10.72‰ in the Fenghuang River. These values indicated that the HNO3 derived from the nitrification of NH4+ was involved in the weathering of carbonate rocks. ④ HNO3 dissolved carbonate rocks and aggravated the chemical weathering of carbonate rock in the basin, contributing 8% of the DIC in groundwater, and 9% and 7% in Fenghuang River and Longju River, respectively.