The relationship of peripheral blood cell inflammatory biomarkers and psychological stress in unmedicated major depressive disorder.

BACKGROUND: Recent research has explored the linkage between major depressive disorder (MDD) and inflammation, especially via altered peripheral blood immune markers. However, the relationship between several novel leukocyte-derived ratios (LDR) and psychological stress in MDD remains uncertain. This study aimed to explore the relationship between LDR, clinical characteristics, recent life events, and childhood maltreatment in MDD patients. METHODS: A cross-sectional case-control study was conducted involving 59 healthy controls (HC) and 50 unmedicated MDD patients. Subjects underwent psychological assessments and peripheral blood measurements. LDR assessed in this study included neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), white blood cell-to-mean platelet volume ratio (WMR), systemic immune inflammation index (SII), multiplication of neutrophil and monocyte counts (MNM), and systemic inflammation response index (SIRI). RESULTS: MDD patients displayed significant alterations in WMR, PLR, and MNM compared to HC, as well as correlations between several LDR and various clinical features (duration of untreated psychosis and dNLR, the nine-item Patient Health Questionnaire and PLR, the 7-item Generalized Anxiety Disorder Questionnaire and SIRI (NLR and dNLR). There was a significant difference in the comparison of WMR in first-episode patients than in recurrent patients. Analyses further revealed an association between Life Event Scale total scores and NLR (dNLR). No correlation was found between Childhood Trauma Questionnaire total (or subscale) scores and LDR. Additionally, WMR and dNLR presented potential predictive value for distinguishing between MDD and HC. CONCLUSION: The study concludes that MDD and some clinical features are associated with alterations in some peripheral blood LDR. These findings emphasize the potential role of peripheral blood LDR in the pathogenesis and clinical heterogeneity of MDD.

Platelet-to-lymphocyte ratio and absolute monocyte count have prognostic potential in primary myelodysplastic neoplasms.

INTRODUCTION: The platelet-to-lymphocyte ratio (PLR), peripheral blood absolute monocyte count (AMC), and monocyte-to-lymphocyte ratio (MLR) are considered biomarkers of systemic immune and inflammation response. However, their prognostic potential in patients with myelodysplastic neoplasms (MDS) remains unclear. This study aimed to explore the predictive impact of PLR, MLR, and AMC on MDS outcomes. METHODS: In total, 334 patients with primary MDS were included between January 2016 and December 2021 and were retrospectively followed up until December 31, 2022. The prognostic significance of PLR, MLR, and AMC was assessed using univariate and multivariate analyses, and predictive models were generated to estimate MDS outcomes. The area under their receiver operating curves was computed to compare the predictive power of these models. RESULTS: Fifty-one patients had disease progression, and 103 patients died during follow-up. In multivariate analyses, a higher PLR was an adverse independent factor for overall survival (OS) (p = 0.011), whereas a higher AMC indicated shorter progression-free survival (p = 0.003). The prognostic model incorporating PLR, MLR, and AMC with the Revised International Prognostic Scoring System (IPSS-R) risk categorization showed higher performance in predicting OS than the model that only utilized the IPSS-R category. CONCLUSION: Elevated PLR and increased AMC had independent prognostic value for adverse outcomes in patients with MDS. PLR, MLR, and AMC enhanced the IPSS-R risk categorization for OS prediction in MDS.

Nitrous Oxide Use in Australian Health Care: Strategies to Reduce the Climate Impact.

Nitrous oxide is a useful inhaled analgesic. Due to its high global warming potential and ozone-depleting properties, the nitrous oxide emissions related to health care are being increasingly scrutinized. In this narrative review, we will discuss the clinical uses of nitrous oxide relevant to anesthetists, in addition to its contribution as a greenhouse gas. Using available data from Australia, we will explore potential strategies for reducing the impact of those emissions, which are likely to be applicable in other countries. These include destruction of captured nitrous oxide, minimizing nitrous oxide waste and reducing clinical use. Anesthesia clinicians are well placed to raise awareness with colleagues and consumers regarding the environmental impact of nitrous oxide and to promote cleaner alternatives. Reducing use is likely to be the most promising reduction strategy without large-scale changes to infrastructure and subsequent delay in action.

Assessment of Morphological Features and Imaging Characteristics of Patients with Intracranial Artery Dissection: A High-Resolution MRI Study.

BACKGROUND: Intracranial artery dissection (IAD) is a pathological dissection of the arterial wall. .However, the morphological features and imaging characteristics of patients with intracranial artery dissection (IAD) remain poorly understood. METHODS: The study reports on 70 IAD patients (30 culprit and 40 non-culprit). All participants underwent high-resolution magnetic resonance imaging (HR-MRI) scans. The morphological features and imaging characteristics of artery dissection were carefully investigated. Demographics and clinical characteristics of culprit and non-culprit patients were also collected. Apparent differences between the two groups, which could be used as biomarkers for ischemic event caused by the culprit dissection, were identified by receiver operating characteristic (ROC) curve analysis. RESULTS: The IAD patients studied could be classified into five different types on the basis of morphological features: classical dissection (n = 31), fusiform aneurysm (n = 2), long dissected aneurysm (n = 9), dolichoectatic dissecting aneurysm (n = 6), and saccular aneurysm (n = 22). The direct sites of artery dissection (double lumen and intimal flap) can be seen in most IAD patients on HR-MRI. Additionally, the presence of hypertension, double lumen and intimal flap were associated with culprit lesions and might be considered biomarkers for the ischemic event caused by the culprit dissection. CONCLUSIONS: Analysis showed that HR-MRI allowed easy visualization of abnormal morphology of artery dissection lesions. This was of great significance for the diagnosis of IAD and gave a better understanding of its pathophysiological mechanism.

Laboratory Evaluation of Fluidity of Heavy Oil Emulsions in Formation Pores Medium.

Heavy oil emulsions such as water in oil (W/O), oil in water (O/W), and water in oil in water (W/O/W) would be formed during the development of heavy oil reservoirs. The key to the efficient development of heavy oil reservoirs is to clarify the fluidity of heavy oil emulsions in formation pores medium. In this study, the main factors that determine the fluidity of heavy oil emulsion were analyzed under the condition of simulating the formation pores medium. The reasons for the difference between the viscosity of heavy oil emulsions in formation pores medium and the viscosity measured by laboratory rheometer were analyzed. Then, experiments have confirmed the shortcomings of the current screening and evaluation method of emulsified viscosity reducer. Finally, through experimental research and mechanism analysis, the mechanism of the emulsified viscosity reducer was studied and suggestions were made to improve the effect of emulsified viscosity reducer in the oil field. When heavy emulsions flow in a formation pores medium, since the size of the droplets would be larger than the size of the pores medium, when the heavy emulsion passes through the pores medium, it would receive additional resistance brought by the Jiamin effect. But when a rheometer is used for viscosity testing, this additional resistance is almost nonexistent. Therefore, the current method of viscosity test using rheometer cannot fully reflect the actual flow state of heavy oil emulsion in formation pores medium. The research in this paper proves that the larger the droplets of the emulsion, the less accurate the rheometer test results. Temperature, permeability, oil-water ratio, and the type of emulsified viscosity reducer all have a certain effect on the flow of heavy oil emulsion in formation pores medium. This article evaluated four types of emulsified viscosity reducers. When the viscosity test was performed by a rheometer, the results showed excellent viscosity-reducing effects. However, when simulating formation pores medium conditions, the effects of some types of emulsified viscosity reducers are not so good. It is no longer accurate to judge the effect of emulsified viscosity reducer by the way of measuring viscosity with a rheometer. It should be screened by the flow capacity of the heavy oil emulsions in formation pores medium. In oil field development, the contact area of heavy oil and emulsified viscosity reducer solution should be increased as much as possible and provide more time for the substitution effect of emulsified viscosity reducer molecules.

Characteristics of Weak-Gel Flooding and Its Application in LD10-1 Oilfield.

Weak gel is a kind of three-dimensional cross-linking system with low polymer concentration and appropriate cross-linking agents, dominated by intermolecular cross-linking, supplemented by intramolecular cross-linking, and with a weak cross-linking degree. In this paper, the microstructure and properties of the weak gel were observed and evaluated under different conditions. Seepage behavior experiments and parallel core displacement experiments were carried out to evaluate profile control and flooding performance of the weak gel. Under a certain polymer concentration, with the increase in cross-linker concentration, the reticular structure of the weak gel becomes more uniform and the strength of the weak gel was further enhanced. Weak gel has more retention in porous media and greater strength. The profile control and flooding performance of the weak gel are much better than those of the polymer. A field test of weak-gel flooding was successfully carried out in LD10-1 oilfield. Most of the production wells around the weak gel injection wells responded after weak-gel injection and the accumulative oil incremental oil production of the test area was 57.8 × 104 m3 up to December 2018.

Relationship between initial international normalized ratio and prognosis in patients with cardiogenic cerebral embolism.

BACKGROUND: Cardiogenic cerebral embolism is one of the most common causes of ischemic stroke. In general, cardioembolic stroke is associated with more severe neurological deficits and higher early mortality, as well as a worse functional outcome. Oral anticoagulant (OAC) therapy could reduce the risk of stroke significantly. However, several limitations have led to it being underused, which raises the failure of anticoagulant therapy. This study aimed to investigate the patients with atrial fibrillation presented cardioembolic stroke who underwent OAC therapy, and to assess treatment efficacy, and outcomes, especially the international normalized ratio (INR) value in the acute phase. METHODS: Clinical data of 306 patients with cardioembolic stroke and etiology of atrial fibrillation were retrospectively analyzed, and demographics, cardiovascular risk factors, embolic cardiopathy, CHADS2 and CHA2DS2-VASc score, HAS-BLED score, INR value, TOAST subtypes, OCSP classification, modified Rankin Scale (mRS) scores and prognosis were evaluated. RESULTS: The median score on the CHADS2 and CHA2DS2-VASc scales was 3 and 4, respectively; The median score on the HAS-BLED scale was 2. Only 33 patients (10.8%) were in therapeutic INR range at the onset of stroke. In the acute phase, 233 patients (76.1%) continued to use OAC therapy, and 73 patients were suspended. Eighteen patients (24.7%) resumed treatment after an average of 32 days. Thirty-nine of 251 survivors with nonvalvular atrial fibrillation were modified to novel oral anticoagulants (NOACs). At 3 months follow-up, patients with INR ≥1.7 had significantly better prognosis than those with INR <1.7, both in the percentage of patients with functional independence (78.9% vs. 41.2%) and in mortality (7.0% vs. 25.0%) (P<0.001). CONCLUSIONS: Patients presented cardioembolic stroke despite being treated with OAC, especially those with a subtherapeutic INR value, raises the failure of anticoagulant therapy. Despite the ineffectiveness of the OAC, the prognosis is better when the INR ≥1.7 at the initiation of the stroke.

Doubly Dynamic Hydrogel Formed by Combining Boronate Ester and Acylhydrazone Bonds.

The incorporation of double dynamic bonds into hydrogels provides an effective strategy to engineer their performance on demand. Herein, novel hydrogels were PREPARED by combining two kinetically distinct dynamic covalent bonds, boronate ester and acylhydrazone bonds, and the synergistic properties of the hydrogels were studied comprehensively. The functional diblock copolymers P(N-isopropyl acrylamide-co-N-acryloyl-3-aminophenylboronic acid)-b-(N-isopropyl acrylamide-co-diacetone acrylamide) (PAD) were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. The hydrogel was constructed by exploiting dynamic reaction of phenyboronic acid moieties with polyvinyl alcohol (PVA) and ketone moieties with adipic dihydrazide (ADH) without any catalyst. The active boronate ester linkage endows the hydrogel with fast gelation kinetics and self-healing ability, and the stable acylhydrazone linkage can enhance the mechanical property of the hydrogel. The difference in kinetics endows that the contribution of each linkage to mechanical strength of the hydrogel can be accurately estimated. Moreover, the mechanical property of the hydrogel can be readily engineered by changing the composition and solid content, as well as by controlling the formation or dissociation of the dynamic linkages. Thus, we provide a promising strategy to design and prepare multi-responsive hydrogels with tunable properties.

Downregulation of STAT1 induces the differentiation of neural stem cells through JNK pathway.

Neural stem cells (NSCs) generated neurons and glial cells. Thus, it is a preferable candidate to the cell replacement-based therapy against neural disorders. The signaling pathways that regulate differentiation of NSCs are widely studied. In the current study, we used in vitro culture system to elucidate the role of signal transducer and activator of transcription 1 (STAT1) in NSCs' differentiation. Downregulation of STAT1 inhibited the proliferation of NSCs. Meanwhile, we also found STAT1 regulation could control the differentiation of NSCs. More neurons and glia cells were generated from NSCs with STAT1 silencing. This process was mediated by the JNK/STAT1 signaling. STAT1 inhibitor promoted differentiation of NSCs. After transplantation, we observed more neurons generated from NSCs with shRNA-STAT1 treatment. Collectively, this work showed an efficient way to regulate neuronal differentiation of NSCs through regulating the STAT1 expression. This is likely to provide source and theoretical support to cell replacement based theory.

[Phenological characteristics of airborne pollen and its relationship with meteorological factors in Haidian District, Beijing, China during the period of 2012-2016]. / 2012­2016å¹´æµ·æ·€åŒºæ°”ä¼ èŠ±ç²‰ç‰©å€™ç‰¹å¾åŠå ¶ä¸Žæ°”è±¡è¦ç´ çš„å ³ç³».

We monitored the type and content of airborne pollen in Haidian District, Beijing City from 2012 to 2016 by the gravity precipitation method, and analyzed the variety of pollen, peak distribution features and changes of its content, and discontinuous variation of concentration. Multiple time scale analysis was carried out for pollen concentration by the ensemble empirical mode decomposition method (EEMD). The relationship between pollen concentration and meteorological factors was analyzed. The results indicated that during the research period, the main types of airborne pollen changed. Woody plants such as Cupressaceae and Salicaceae instead of herbaceous plants contributed the most content of pollen. There was no significant change of the yearly peak distribution of pollen concentration. The concentration in recent five years reduced, while the concentration of herbaceous plants (such as Scolopacjdae) increased. During the statistics period, pollen concentration showed discontinuous changes in early April, late May and early August. Pollen concentration had the change cycle of quasi 2 d, quasi 51 d and quasi 128 d. Among all meteorological factors, temperature played a dominant role in driving the concentration, which may significantly rise during 16 to 18 ℃. The impact of temperature changes on the daily concentration may be delayed and continuous; it is often highly related to the concentration 2-7 d later. Sunshine duration and wind speed had the most significant impact on daily pollen concentration.

Highly Efficient Degradation of Polyacrylamide by an Fe-Doped Ce0.75Zr0.25O2 Solid Solution/CF Composite Cathode in a Heterogeneous Electro-Fenton Process.

Polyacrylamide (PAM) in environmental water has become a major problem in water pollution management due to its high molecular mass, corrosion resistance, high viscosity, and nonabsorption by soil. The composite of Fe-doped Ce0.75Zr0.25O2 solid solution (Fe-Ce0.75Zr0.25O2) loaded on carbon felt (CF) was fabricated by a hydrothermal synthesis method, which was used as the cathode in a heterogeneous electro-Fenton system for the degradation of PAM. It showed that the degradation efficiency of PAM by the Fe-Ce0.75Zr0.25O2/CF cathode was 86% after 120 min and the molecular mass of PAM decreased by more than 90% after 300 min. Total organic carbon removal reached 78.86% in the presence of Fe-Ce0.75Zr0.25O2/CF, while the value was only 38.01% in the absence of Fe-Ce0.75Zr0.25O2. Further studies showed that the breaking of the chain begins with the amide bond, and then, the carbon chain was cracked into a short alkyl chain. As degradation progressed, both the complex viscosity and elasticity modulus of PAM solutions decreased nearly 50% at 300 min. It indicated that •OH were the most significant active species for the degradation of PAM. This novel Fe-Ce0.75Zr0.25O2/CF composite is an efficient and promising electrode for the removal of PAM in wastewater.

MANF improves the MPP+/MPTP-induced Parkinson's disease via improvement of mitochondrial function and inhibition of oxidative stress.

OBJECTIVE: This study aimed to investigate the therapeutic effect of mesencephalic astrocyte-derived neurotrophic factor (MANF) on the MPTP/MPP+-induced model of Parkinson's disease (PD) and the potential mechanism. METHODS: Male C57BL/6 mice PD model with MPTP-induced were randomly injected bilaterally with MANF or PBS into the striatum. Two weeks later, Rotarod test, immunohistochemistry, and detection of dopamine (DA) and its metabolites, superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) were performed. A cell model of PD was established by incubating SH-SY5Y cells with MPP+, cells were pretreated for 2 h with different concentrations of MANF before 24 h incubation with MPP+. Cell viability, expression of Bax, and Bcl-2, gene expression levels of Heme oxygenase 1 (HMOX1) and Superoxide dismutase 2 (SOD2), and mitochondrial transmembrane potential were detected. RESULTS: The latency reduction in PD mice was partially restored after MANF treatment (P<0.05); MANF significantly reduced the loss of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) (P<0.01); MANF significantly increased the striatal DA level in PD mice (P<0.05) and markedly increased the SOD activity (P<0.01) and GSH production (P<0.01). MANF pre-treatment significantly decreased the MPP+-induced reduction of cell viability (P<0.01), inhibited the ratio of Bax/Bcl-2 expression (P<0.01), activated gene expression levels of HMOX1 (P<0.01) and SOD2 (P<0.05), and reversed MPP+-induced loss of mitochondrial membrane potential (P<0.01). CONCLUSION: MANF can attenuate the neuronal lesion in MPTP/MPP+-induced PD mice, which may be related to the improvement of mitochondrial function and inhibition of oxidative stress.

AM1241 alleviates MPTP-induced Parkinson's disease and promotes the regeneration of DA neurons in PD mice.

The main pathological feature of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. In this study, we investigated the role of cannabinoid receptor 2 (CB2R) agonist AM1241 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in a mouse model of PD. Upon treatment with AM1241, the decreased CB2R level in the PD mouse brain was reversed and the behavior score markedly elevated, accompanied with a dose-dependent increase of dopamine and serotonin. In addition, western blot assay and immunostaining results suggested that AM1241 significantly activated PI3K/Akt/MEK phosphorylation and increased the expression of Parkin and PINK1, both in the substantia nigra and hippocampus. The mRNA expression analysis further demonstrated that AM1241 increased expression of the CB2R and activated Parkin/PINK1 signaling pathways. Furthermore, the increased number of TH-positive cells in the substantia nigra indicated that AM1241 regenerated DA neurons in PD mice, and could therefore be a potential candidate for PD treatment. The clear co-localization of CB2R and DA neurons suggested that AM1241 targeted CB2R, thus also identifying a novel target for PD treatment. In conclusion, the selective CB2 agonist AM1241 has a significant therapeutic effect on PD mice and resulted in regeneration of DA neurons following MPTP-induced neurotoxicity. The possible mechanisms underlying the neurogenesis effect of AM1241 might be the induction of CB2R expression and an increase in phosphorylation of the PI3K/AKT signaling pathway.

Nrf2-mediated neuroprotection by MANF against 6-OHDA-induced cell damage via PI3K/AKT/GSK3ß pathway.

Oxidative stress and apoptosis are thought to be broadly involved in the pathogenesis of Parkinson's disease. We previously reported that Mesencephalic astrocyte-derived neurotrophic factor (MANF) possesses anti-oxidation and anti-apoptotic effects against 6-OHDA-induced neurotoxicity, but the specific molecular mechanism remains unclear. In this study, we showed that MANF up-regulates the expression of nuclear factor erythroid 2-related factor (Nrf2) and promotes its translocation into the nucleus. The anti-oxidation and anti-apoptotic effects of MANF could be partially blocked by inhibitor or shRNA-mediated knockdown of Nrf2. Furthermore, MANF activated phospoinositide-3-kinase (PI3K)/Akt signaling and suppressed glycogen synthase kinase (GSK3ß) activation. PI3K inhibitor (LY49002) abolished effects of MANF on AKT phosphorylation, GSK3ß inactivation, Nrf2 nuclear translocation and subsequently abrogated MANF-mediates cytoprotection. Collectively, our findings indicated that MANF-mediated protection against 6-OHDA-induced cytotoxicity by potentiating the Nrf2-related survival mechanism through the PI3K/Akt/GSK3ß pathway.

Mesencephalic astrocyte-derived neurotrophic factor reduces cell apoptosis via upregulating HSP70 in SHSY-5Y cells.

BACKGROUND: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a new candidate growth factor for dopaminergic neurons against endoplasmic reticulum stress (ER stress). HSP70 family, a chaperon like heat shock protein family, was proved to be involved in the MANF induced survival pathway in 6-OHDA treated SHSY-5Y cells. However, the ER stress relative transcriptome, in MANF signaling cascades is still investigated. The involvement of HSP70, a 70kd member of HSP70 family, need further to be verified. METHODS: The cell apoptosis was assayed by MTT, TUNEL staining and western blot of cleaved Caspase-3. The differentially expressed genes in SHSY-5Y cells under different conditions (control, 6-OHDA, 6-OHDA + MANF) were investigated by RNA-seq. Expression of HSP70 was further confirmed by real-time PCR. RNAi knockdown for HSP70 was performed to investigate the role of HSP70 in the MANF signaling pathway. RESULTS: MANF inhibits 6-OHDA-induced apoptosis in SHSY-5Y cells. Six ER stress relative genes (HSP70, GRP78, xbp-1, ATF-4, ATF-6, MAPK) were found enriched in 6-OHDA + MANF treatment group. HSP70 was the most significantly up-regulated gene under 6-OHDA + MANF treatment in SHSY-5Y cells. RNAi knockdown for HSP70 inhibits the protective effects of MANF against 6-OHDA toxicity in SHSY-5Y cells. CONCLUSION: MANF exerts a protective role against 6-OHDA induced apoptosis in SHSY-5Y cells via up-regulating some ER stress genes, including HSP70 family members. The HSP70 expression level plays a key role in MANF-mediated survival pathway.

Characteristics of carbapenemase-producing Klebsiella pneumoniae as a cause of neonatal infection in Shandong, China.

The goal of the present study was to examine the characteristics of carbapenem-resistant Klebsiella pneumoniae as a cause of neonatal infection. A total of 37 carbapenem-resistant Klebsiella pneumoniae-positive newborns hospitalized in Shandong Provincial Hospital, China between April 2011 and October 2013 were examined. Antibiotic susceptibility testing was performed using the agar dilution method and the Etest. Resistance genes were assessed by polymerase chain reaction (PCR) and sequencing. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were used to determine the genotypes and homology of these isolates. Plasmids were analyzed by PFGE and conjugation experiments. The outer membrane proteins were examined by PCR and SDS-PAGE. All of the isolates were revealed to be resistant to the third and fourth generation cephalosporins and piperacillin-tazobactam. Tigecycline, colistin, levofloxacin and amikacin were successful against all of the isolates. The antibiotic resistance rates of aztreonam, gentamicin, trimethoprim-sulfamethoxazole and fosfomycin were 13.51, 48.64, 78.38 and 86.49%, respectively. Of the 37 cases, 25 isolates (67.57%) were blaNDM-1 positive, 13 isolates (35.14%) were blaIMP-4 positive and 1 isolate (2.70%) was blaIMP-8 positive. Two isolates carried both blaNDM-1 and blaIMP-4. The isolate carrying 2-4 plasmids and blaNDM-1 and blaIMP-4 was transferable between strains. SDS-PAGE data indicated that outer membrane proteins remained present. PFGE revealed 7 distinct clusters, and MLST reported the presence of ST20, ST17, ST54, ST705 and ST290 sequences, which indicated that there was clone and plasmid spread between newborns. The main resistance mechanism of carbapenem-resistant Klebsiella pneumoniae was that the isolates expressed the carbapenemase resistance of blaNDM-1 and blaIMP-4 genes. The current study indicates that early detection of these genes may be helpful in infection prevention and control.

Mesencephalic astrocyte-derived neurotrophic factor alleviated 6-OHDA-induced cell damage via ROS-AMPK/mTOR mediated autophagic inhibition.

Autophagy and apoptosis are commonly involved in the dopaminergic neuron damage in the pathogenesis of Parkinson's disease. Recently, the autophagy pathway is thought to be critical to the process of PD. Therefore, the regulation of autophagy may be a potential strategy for PD treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been reported to have neuroprotective effects through anti-apoptosis, anti-oxidative, and anti-inflammatory mechanisms in PD. In this study, we investigated the role of autophagy system in MANF-mediated neuroprotection against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Our results showed that MANF protected SH-SY5Y cells against 6-OHDA-induced cell viability decrease and apoptosis by inhibiting autophagy. Mitochondrion damage and energetic dysfunction triggered by reactive oxidative stress (ROS) accumulation were also alleviated by MANF treatment. Furthermore, MANF downregulated phosphorylation of AMP-activated protein kinase (AMPK), a cellular energy sensor and regulator, but upregulated phosphorylation of Mammalian target of rapamycin (mTOR) under energy depletion conditions, indicating AMPK/mTOR signaling pathway is involved in the autophagic inhibition of MANF. These results suggest that autophagic inhibition provides protective mechanism of MANF in 6-OHDA-induced SH-SY5Y cell death and this inhibition is associated with AMPK/mTOR pathway.

Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways.

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new evolutionary conserved neurotrophic factor (NTF), has been reported to protect midbrain dopaminergic neurons of neurodegenerative diseases such as Parkinson's disease (PD) model. Neural stem cells (NSCs) can play a role as the therapeutic tool in neurodegenerative diseases, but the inflammatory responses of central nervous system (CNS) appear to harm this function. Although studies have previously demonstrated the protective effect of MANF on neurons of CNS, it is lacking in making great efforts on the function of MANF on NSCs. The aim of this study was to investigate the antiinflammatory responses and signaling mechanisms of MANF on lipopolysaccharide (LPS)-induced NSCs. In the results, MANF decreased the proinflammatory cytokines of IL-1ß, TNF-α, and IFN-γ induced by LPS by regulating NF-κB and phosphorylation of p38-mitogen-activated protein kinases (MAPKs) pathways, neither p-JNK nor p-ERK signaling. These findings suggest that MANF can facilitate to protect the inflammatory responses of NSCs, and provide beneficial function for the application of NSCs in the therapy.

Integrative bioinformatics and proteomics-based discovery of an eEF2K inhibitor (cefatrizine) with ER stress modulation in breast cancer cells.

Eukaryotic elongation factor-2 kinase (eEF2K), a unique calcium/calmodulin-dependent protein kinase, is well known to regulate apoptosis, autophagy and ER stress in many types of human cancers. Therefore, eEF2K would be regarded as a promising therapeutic target; however, the eEF2K-regulated mechanism and its targeted inhibitor still remain to be discovered in cancer. Herein, we constructed a protein-protein interaction (PPI) network of eEF2K and achieved an eEF2K-regulated ER stress subnetwork by bioinformatics prediction. Then, we found that the differential protein expressions involved in ER stress in the context of si-eEF2K-treated MCF-7 and MDA-MB-436 cells by iTRAQ-based analyses, respectively. Integrated into these aforementioned results, we constructed a core eEF2K-regulated ER stress subnetwork in breast cancer cells. Subsequently, we screened a series of candidate compounds targeting eEF2K and discovered a novel eEF2K inhibitor (cefatrizine) with an anti-proliferative activity toward breast cancer cells. Moreover, we found that cefatrizine induced ER stress in both MCF-7 and MDA-MB-436 cells. Interestingly, we demonstrated that the mechanism of cefatrizine-induced ER stress was in good agreement with our bioinformatics and proteomics-based results. In conclusion, these results demonstrate that a novel eEF2K inhibitor (cefatrizine) induces ER stress in breast cancer cells by integrating bioinformatics prediction, proteomics analyses and experimental validation, which would provide a clue for exploring more mechanisms of eEF2K and its targeted inhibitors in cancer therapy.

Oil-water separation property of polymer-contained wastewater from polymer-flooding oilfields in Bohai Bay, China.

In this study, the effects of gravitational settling time, temperature, speed and time of centrifugation, flocculant type and dosage, bubble size and gas amount were investigated. The results show that the simple increase in settling time and temperature is of no use for oil-water separation of the three wastewater samples. As far as oil-water separation efficiency is concerned, increasing centrifugal speed and centrifugal time is highly effective for L sample, and has a certain effect on J sample, but is not valid for S sample. The flocculants are highly effective for S and L samples, and the oil-water separation efficiency increases with an increase in the concentration of inorganic cationic flocculants. There exist critical reagent concentrations for the organic cationic and the nonionic flocculants, wherein a higher or lower concentration of flocculant would cause a decrease in the treatment efficiency. Flotation is an effective approach for oil-water separation of polymer-contained wastewater from the three oilfields. The oil-water separation efficiency can be enhanced by increasing floatation agent concentration, flotation time and gas amount, and by decreasing bubble size.