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Apolipoprotein E4 (apoE4) is closely related to late-onset depression (LOD). In addition, the benefits of metformin treatment of depression have been documented in a range of rodent studies and human trials, but few studies have probed into the effect of metformin on and the related mechanism in depressed elderly mice, especially in those APOE4 carriers. Here, we treated 13-month-old apoE3-targeted replacement (TR) and apoE4-TR mice with an intragastric administration of metformin (300 mg/kg/d) or normal saline for 5 months. We found that metformin exerted antidepressant effects on apoE4 mice, including reduced immobility time in TST and FST, and increased ratios of time and distance in the central area of OFT. Importantly, compared with apoE3 mice, apoE4 mice showed a higher expression of lactate dehydrogenase (LDH) and pyruvate dehydrogenase kinase (PDK1 and PDK4) in the hippocampus. The increased LDH level was rescued by metformin treatment. Moreover, the metformin administration increased the levels of transcriptional factor NRF-1 and TFAM, mtDNA, and most mitochondrial complex subunits in apoE-TR mice. Furthermore, it upregulated the expressions of antioxidant enzymes, such as MnSOD, GPX1, and GSR1/2. Interestingly, apoE4 blunted the hypoglycemic effect of metformin in aged mice. These data suggest that metformin ameliorates the depression-like behaviors probably by improving glucose metabolism and mitochondria biogenesis in the hippocampus of aged apoE4 mice. These findings imply that chronic metformin treatment can improve apoE4-mediated LOD, providing mechanistic insights for apoE4- and age-based depression prevention and therapy.

Extractive denitrification (EDN) of shale oil using ionic liquids (ILs) as the extracting agent has good industrial prospects. In such processes, ILs with higher selectivity to N-compounds and lower solubility in shale oil are desired to improve the EDN efficiency, and reduce the loss of ILs and the contamination of shale oil. In the present study, we employed COSMO-RS to calculate the selectivity of 70 ILs to the typical N-compounds (pyridine, quinoline and indole). The influence of the IL structural characteristics, composition of shale oil and properties of N-compounds are investigated from a micro-level view with the σ-surface and σ-profile. The selectivity strongly depends on anionic species and it is greatly influenced by hydrogen bonding (HB) and π–π interaction between N-compounds and ILs. ILs composed of [H2PO4]− and [MeSO3]− with larger HB donor energy show higher selectivity to the basic N-compounds, while ILs composed of [Ac]− with larger π-electron cloud density show higher selectivity to the non-basic N-compounds. Anions with stronger polarity have lower solubility in shale oil. Moreover, experimental determinations of EDN indicated that [C4py][H2PO4]/[C4mim][H2PO4] and [C2mim][Ac]/[C2py][Ac] have good EDN performance for quinoline/pyridine with efficiency of 100% and for indole with efficiency of 91%, respectively. This work presents a theoretical basis to design and select ILs having higher selectivity for N-compounds and lower solubility in shale oil for use in denitrification.

PARK7 mutations are accountable for the inherited Parkinson's disease. An induced pluripotent stem cell (iPSC) line FJMUUHi001-A was generated by expressing five reprogramming factors, OCT3/4, SOX2, c-MYC, KLF4 and BCL-XL, in peripheral blood mononuclear cells from a 32-year old patient carrying a homozygous mutation of c.189dupA in PARK7. The iPSCs with a normal karyotype had the abilities to differentiate into three germ layers and expressed pluripotency markers without detectable residual plasmids. The cell line FJMUUHi001-A carrying the truncating protein PARK7 could be a useful tool to help comprehend the function of PARK7 in the iPSCs and differentiated cells from them.

The automation equipment and software with Human-Machine interaction interface are gradually popularized and applied in manufacturing enterprises. Due to the limitation of manpower level of the enterprise and the complicated and tedious operation methods, this promotion process is greatly hindered. Aiming at the automatic detection of controls, especially those with label images in Human-Machine interaction interface, a method to classify and identify the label images by combining image processing and deep learning is proposed in this paper. A dataset containing 20 types of control labels was collected and the traditional CNN network and Siamese neural network (SNN) were combined to cluster and classify them. According to the experimental results, the classification and identification accuracy of SNN on the test set can reach near 97%, which proved that the method proposed in this paper could classify and recognize controls with label images with a high accuracy.

Background: Abnormal energy metabolism is often documented in the brain of patients and rodents with depression. In metabolic stress, acetate serves as an important source of acetyl coenzyme A (Ac-CoA). However, its exact role and underlying mechanism remain to be investigated. Method: We used chronic social failure stress (CSDS) to induce depression-like phenotype of C57BL/6J mice. The drugs were administered by gavage. We evaluated the depressive symptoms by sucrose preference test, social interaction, tail suspension test and forced swimming test. The dendritic branches and spine density were detected by Golgi staining, mRNA level was analyzed by real-time quantitative RT-PCR, protein expression level was detected by western blot, and the content of Ac-CoA was detected by ELISA kit. Result: The present study found that acetate supplementation significantly improved the depression-like behaviors of mice either in acute forced swimming test (FST) or in CSDS model and that acetate administration enhanced the dendritic branches and spine density of the CA1 pyramidal neurons. Moreover, the down-regulated levels of BDNF and TrkB were rescued in the acetate-treated mice. Of note, chronic acetate treatment obviously lowered the transcription level of HDAC2, HDAC5, HDAC7, HDAC8, increased the transcription level of HAT and P300, and boosted the content of Ac-CoA in the nucleus, which facilitated the acetylation levels of histone H3 and H4. Limitations: The effect of acetate supplementation on other brain regions is not further elucidated. Conclusion: These findings indicate that acetate supplementation can produce antidepressant-like effects by increasing histone acetylation and improving synaptic plasticity in hippocampus.

The susceptibility to depression has been attributed to the chronic stress and genetic factors but still fails to identify definite biomarkers. The present study aimed to investigate the role of disrupted Notch signaling in the medial prefrontal cortex of the chronic social defeat stress (CSDS) mice and Wistar Kyoto (WKY) rats. RNA-sequencing and quantitative real-time PCR analyses evidenced the involvement of Notch signaling pathway in depression. Western blotting reported an increased level of Notch2 and NF-κB and a decreased level of Hes1 and Bcl2/Bax ratio both in the susceptible mice when compared with the control or resilient ones and in the depression WKY rats when compared with the Wistar or non-depression WKY groups. Further analysis showed that the above-mentioned changes were significantly correlated with the depression-like behaviors and that the elicited Notch2 strongly correlated with the upregulated NF-κB, not with the downregulated Hes1 or Bcl2/Bax ratio. In conclusion, the increased Notch2/NF-κB signaling in the medial prefrontal cortex may mediate depression susceptibility, providing a potential diagnostic biomarker or therapeutic target for treating major depressive disorder.

Background: Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown.Methods: In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo.Results: CircARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p.Conclusion: In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

Parkinson’s disease (PD) is a common dyskinesia disease, the mitochondrial unfolded protein response (mtUPR) may be directly or indirectly involved in the occurrence and development of PD, although the exact mechanism is unclear. We established a dopaminergic neuronal-like cell model of PD, by overexpression of PGC-1α to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1α and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24 h after MPP+ treatment in SH-SY5Y cells, which the protein and transcription levels of the proteases and molecular chaperones reached maximal. The proteases and molecular chaperones were significantly increased when overexpressed PGC-1α, which indicated that PGC-1α overexpression activated the mtUPR, and PGC-1α had a protective effect on SH-SY5Y cells. The expression levels of PGC-1α and LRPPRC were significantly improved in the PGC-1α overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1α overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1α may activate mtUPR, reducing the oxidative stress injury induced by MPP+ through LRPPRC signaling, thus maintain mitochondrial homeostasis.

SummaryBackgroundSARS-CoV-2 is a novel human coronavirus, there is no specific antiviral drugs. It has been proved that host-cell-expressed CD147 could bind spike protein of SARS-CoV-2 and involve in host cell invasion. Antibody against CD147 could block the infection of SARS-CoV-2. We aimed to assess the efficacy and safety of meplazumab, a humanized anti-CD147 antibody, as add-on therapy in patients with COVID-19 pneumonia.MethodsAll patients received recommended strategy fromChinese Clinical Guidance for COVID-19 Pneumonia Diagnosis and Treatmentsreleased by National Health Commission of China. Eligible patients were add-on administered 10 mg meplazumab intravenously at days 1, 2, and 5. Patients hospitalized in the same period were observed as concurrent control. The endpoints include virological clearance rate, case severity, chest radiographic, and laboratory test. This trial was approved by the Ethics Committee of Institution at the Tangdu hospital, and registered with ClinicalTrials.gov, NCT 04275245.Findings17 patients were enrolled and assigned to meplazumab group between Feb 3, 2020 and Feb 10, 2020. 11 hospitalized patients served as concurrent control. Baseline characteristics were generally balanced across two groups. Compared to control group, meplazumab treatment significantly improved the discharged (p=0.005) and case severity (p=0.021) in patients. The time to virus negative in meplazumab group was reduced than that in control group (median 3, 95%CI[1.5-4.5] vs. 13, [6.5-19.5]; p=0.045, HR=0.374, 95%CI[0.143-0.978]). The percentages of patients recovered to the normal lymphocyte count and CRP concentration were also increased remarkably and rapidly in meplazumab group. No adverse effect was found in meplazumab-treated patients.InterpretationMeplazumab efficiently improved the recovery of patients with SARS-CoV-2 pneumonia with a favorable safety profile. Our results support to carry out a large-scale investigation of meplazumab as a treatment for COVID-19 pneumonia.FundingNational Science and Technology Major Project.

For the problem of automatic discernment of controls in human-machine interaction interface, the detection and classification methods of controls based on image processing and machine learning are studied. Firstly, image processing algorithm is used to obtain a series of proposal rectangle boxes for human-machine interaction interface. Then, by using the label image in the control, the control category can be identified by machine learning algorithm. In this paper, a data set containing 19 types of control label image is produced, and CNN methods are used to classify them. The experimental results show that the proposal rectangle boxes in the human-machine interactive interface can be captured effectively by combining the image morphology processing algorithm. The rectangular controls can be filtered out by using the label image in the control. The discernment accuracy of CNN model based on VGG16 on verification set can reach more than 97%.

Supply chain is an important support for value creation, and product is the carrier for realizing the value. The coordination between product architecture design and supply chain management is the premise for enterprises to cope with rapid changes and meet the market demands. The view that product architecture and supply chain interact with each other has been confirmed by many scholars, but the influence mechanism between the two is still unclear. We collected data from 221 companies and drew the following conclusions through analysis. (1) product architecture has a significant impact on supply chain performance. The modularity of product architecture, the degree of standardization of interface, and the reuse of components have a significant positive impact on supply chain performance. (2) supply chain centralization can enhance the effect of product architecture on supply chain performance. When supply chain concentration is high, product architecture is easier to play its advantages, thereby improving supply chain performance.

A series of ethanolamine based deep eutectic solvents (DESs), which have strong basicity, were firstly applied in wheat straw pretreatment. Typically, choline chloride: monoethanolamine (C:M) as the best solvent among these DESs can remove 71.4% lignin and reserve 93.7% cellulose (70 °C, L/S mass ratio of 20:1, 9 h), and improve the enzymatic hydrolysis of residue, i.e., 89.8% cellulose and 62.0% xylan conversion. The pretreatment capacity of C:M is comparable to other solvents while C:M has several advantages, e.g., lower cost with cheap materials and simpler preparation process, mild conditions and lower polysaccharide loss. The XRD, SEM and FT-IR results verified that the polysaccharide conversion and sugars yield were enhanced by the removal of lignin in the pretreatment process. The basic ethanolamine based DESs are promising solvents for industrial application of wheat straw pretreatment.

Ionic liquids (ILs) are intensively studied in the oxidative desulfurization of diesel fuel, where ILs act as both extractants and catalysts with adding another oxidant such as H2O2 solution. Some thiophenic sulfur compounds can be effectively removed from some model diesel fuels with this method, while it is hard to reduce the sulfur content to a desirable level like less than 10 ppm with this method when people investigated the real diesel fuels. In this work, we developed a new combination desulfurization method, first oxidative desulfurization by ILs as both extractants and catalysts with 30 w% H2O2 as oxidant, then followed by desulfurization by solvent extraction. Four ILs and ten solvents were investigated for real diesel fuels. The effects of different factors on desulfurization performance were systematically studied, e.g., ILs species, solvents species, temperature, time, IL/oil mass ratio, extractant/oil mass ratio, multiple desulfurization, regeneration of ILs and solvents. The results show such a combination method is effective to reduce the sulfur content in real diesel fuels to a desirable level, e.g., the sulfur content in FCC diesel fuel was reduced to 8.1 ppm from original 150 ppm after one step oxidation by [(CH2)4SO3HMIm][Tos] (ILs/oil mass ratio of 1/2; 3 h, 348.15 K, O/S molar ratio of 40/1) and two-step extraction by DMF (extractant/oil mass ratio 1/2, 30 min, 298.15 K). ILs and solvents can be regenerated and recycled with negligible activity loss.

Previous studies have demonstrated myelin deficits in Alzheimer's disease (AD). However, it is still unclear whether myelin deficits occur at early stage of AD. Our study aimed to investigate myelin deficits in 5XFAD mice dynamically in different cognition-associated brain regions at early stage of AD. Transmission electron microscopy (TEM) was applied to detect myelin changes in late-myelinating regions such as prelimbic area (PrL), retrosplenial granular cortex (Rsg), field CA1 of hippocampus (CA1) and entorhinal cortex (ERC) respectively at different stages (1, 2, 3 and 5 months of age) in 5XFAD mouse model. In addition, we assessed spatial learning and memory with Morris water maze (MWM) in 5XFAD mice. Myelin deficits in 5XFAD mice started from 1 month of age and this deterioration continued during ageing, whereas the same myelin abnormality could only be observed in 5-month-old wild-type mice. Additionally, the g-ratio (an index associated with myelin thickness) was increased in 1-month-old 5XFAD mice in the regions including PrL, CA1 and ERC, compared to wild-type mice. As animals aged, the increased g-ratio in 5XFAD appeared in more regions of the brain. Moreover, 5XFAD mice showed spatial memory deficits from 1 month of age and spatial learning deficits from 2 months of age. In conclusion, myelin deficits occurred at an early stage and progressed with ageing in 5XFAD mouse model. Notably, a sequential myelin change was detected in cognition-associated brain regions. Combined with cognitive examinations, this study suggests that myelin changes might contribute to cognitive dysfunction.

The green solvent ionic liquids (ILs) are getting attention in variety of industries, because of their unique properties. Few studies explain the hydrodynamics of ILs, but the comparison with conventional amine solvents in CO2 capture process has not so far been reported. The primary target of this research is to develop a state of the art computational fluid dynamics (CFD) model that would be useful to understate hydrodynamic parameters of both ILs and conventional amine solvents in a glance. In present study, three ILs are investigated inside a 3D flat bubble column and their higher viscosities are examined vigilantly by comparison with three amine solvents. The flow pattern, liquid velocity magnitude, CO2 holdup and bubble size distribution are explained. It is reported that current CFD model may be used for higher viscous ILs and amine solvents. Compared with amine solvents, CO2 plume meandering behavior was not observed and very low gas holdup was obtain in ILs. The velocity magnitude of ILs increased with the height in bubble column, but a decreasing trend with column height was followed in the case of amine solvents. CO2 exhibited non-coalescence behavior in ILs, but coalescence and breakup phenomena were seen in amine solvents. Finally, baffled type industrial tray column is also investigated and some useful hydrodynamic aspects in the comparison of pure ionic liquid, 90%-solution of ionic liquid and 30%-solution of MEA are drawn. The experimentally validated CFD model would be useful for switching to ILs from corrosive amine solvents and further investigation of new economical ILs.

Environmental pollution aroused by accumulation of waste PET has attracted worldwide attention. Metal chloride as Lewis acid catalyst has excellent catalytic performance in enormous organic reaction. However, the high solubility of the metal chloride in ethylene glycol and the residue of metal ions in the product will have an adverse impact on the subsequent process. In this work, polymer ionic liquid containing [NTf2]− which is insoluble in ethylene glycol at room temperature was synthesized and used to immobilize metal ions to catalyze glycolysis of PET. After reaction, the polymer ionic liquid-metal ion catalyst could be recovered at room temperature by simple filtration. PET conversion reached 95.4% and BHET yield reached 77.8% using PIL-Zn2+ as catalyst at 195 °C for 120 min. Ionic liquid was characterized by FT-IR, NMR and ESI-MS. Interaction between ionic liquid and metal ions was characterized by FT-IR. The interaction energy of polymer ionic liquid-metal ion complex is higher than that of ethylene glycol-metal ion complex by DFT calculation (Density functional calculation). The both content of metal ion in polymer ionic liquid-metal ion complex and catalytic performance of as-synthesized catalysts did not obviously decrease after the catalyst was reused for five times. This work mainly provided a way of recovering catalyst and promote development of glycolysis of PET.

Objective: To review recent research advances on tau, a major player in Alzheimer’s disease (AD) pathogenesis, a biomarker for AD onset, and potential target for AD therapy. Data Sources: This review was based on a comprehensive search using online literature databases, including PubMed, Web of Science, and Google Scholar. Study Selection: Literature search was based on the following keywords: Alzheimer’s disease, tau protein, biomarker, cerebrospinal fluid (CSF), therapeutics, plasma, imaging, propagation, spreading, seeding, prion, conformational templating, and posttranslational modification. Relevant articles were carefully reviewed, with no exclusions applied to study design and publication type. Results: Amyloid plaques enriched with extracellular amyloid beta (Aβ) and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks of AD. Although the Aβ hypothesis has dominated AD research for many years, clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset. The research focus in AD has recently shifted to the role of tau in AD. In addition to phosphorylation, tau is acetylated and proteolytically cleaved, which also contribute to its physiological and pathological functions. Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis. Techniques to detect tau at minute levels in CSF and blood have been developed, and improved tracers have facilitated tau imaging in the brain. These advances have potential to accurately determine tau levels at early diagnostic stages in AD. Given that tau is a potential therapeutic target, anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention. Conclusion: Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD. Key words: Alzheimer’s Disease; Biomarker; Immunotherapy; Tau Imaging; Tau Protein; Transcellular Propagation

New solvents for pretreating wheat straw, mixtures of cholinium amino acids ionic liquids ([Ch][AA] ILs) and glycerol, were developed. As a typical result, 50% cholinium alanine-glycerol is capable of removing 67.6% lignin while reserving 95.1% cellulose (90°C, L/S mass ratio of 20:1, 6h) and the conversions of cellulose and xylan are 89.7% and 70.9%, respectively, which is comparable to the pretreatment capability of other solvents, while [Ch][AA]-glycerol mixtures have desirable advantages, e.g., biocompatibility, lower cost with adding glycerol than pure IL, much lower pretreatment temperature (typically100°C) than that by glycerol (typically200°C). Lignin removal and polysaccharide conversion are dependent on [Ch][AA] content and pH of pretreatment solvents. [Ch][AA] not only remove lignin in wheat straw effectively but also swell cellulose while not remarkably dissolve cellulose with high cellulose reservation, favoring the enzymatic hydrolysis. Such mixtures of ILs and co-solvents are potential solvents for pretreating biomass.

With the increasing awareness of environmental protection, the degradation of waste plastic has attracted more and more attention. In this study, the glycolysis of PET and PBT which are widely used in daily life were investigated using CoFe2O4@ZIF-8/ZIF-67 composite as catalyst. Moreover, the glycolysis of PET/PBT mixed plastic was also studied. The result showed that CoFe2O4@ZIF-8/ZIF-67 has ideally catalytic effect in glycolysis of plastic, especially in glycolysis of PET/PBT mixed plastic. PET/PBT (5 g), CoFe2O4@ZIF-8/ZIF-67 (0.05 g) and ethylene glycol (25 g) were at 200 °C for 60 min, plastic conversion is up to 100% and BHET yield reached 84.3%. The main product of glycolysis of PBT and PET/PBT was characterized and confirmed to be bis(hydroxyalkyl) terephthalate (BHET). The result of UPLC indicated that purity of main product of glycolysis of PET/PBT was 92%. The as-synthesized catalysts were characterized by XRD, FT-IR, SEM, TGA, N2 adsorption–desorption and VSM. The catalytic performance of catalysts was significantly influenced by external BET surface area. More importantly, the magnetic catalyst could be collected quickly by external magnetic field. The catalytic performance of CoFe2O4@ZIF-8/ZIF-67 did not obviously decrease and element content of Zn and Co in catalyst was just decreased by less than 10% after it was reused for five times.

The accumulation of waste PET leads to serious environmental problem. PET degradation has been hot topic and is studied by lots of researchers. At present, numerous catalysts have been developed, among which ionic liquid catalyst is attractive due to its excellent advantages like convenient recycling and highly catalytic effect. In this work, a series of ionic liquids based on 1,1,3,3-tetramethylguanidine (TMG) were synthesized and used as catalyst of PET degradation. The influence of different structure of cation and different metal salt on PET degradation were studied. DFT calculation showed that the interaction between the ionic liquid and ethylene glycol can be changed by adjustment of the structure of the cation. At optimal condition, using [C6TMG]Cl/2ZnCl2 as catalyst, PET conversion was 100% and BHET yield was 92.7%. To our best knowledge, this is first report about ionic liquid catalyst of PET degradation with superior BHET yield. Catalytic effect of [C6TMG]Cl/2ZnCl2 did not obviously decrease after it was reused for six times. Moreover, the degradation of commercial beverage bottles was investigated using [C6TMG]Cl/2ZnCl2 as the catalyst, the BHET yield of 84% was obtained, and the quality purity of the product was 90%. In addition, possible mechanism was explored.

The catalytic effect of nanoparticles was significantly affected by its size and surface property. In this work, a series of ionic liquids were synthesized and used as surfactant to modify CoFe2O4 MNP. XRD, FT-IR, TEM and VSM were performed to characterize modified CoFe2O4. The modified CoFe2O4 MNP with average size of 7 nm was obtained and it was so well dispersed in ethylene glycol that ethylene glycol based magnetic fluid was obtained. Modified CoFe2O4 MNP was used as catalyst for glycolysis of PET and showed excellent catalytic effect. The influence of ionic liquids surfactant and experimental factors on glycolysis were investigated. Under optimal condition, PET (5 g), catalyst (CoFe2O4/C10-OAC, 0.1 g) and EG (25 g) at 195 °C for 2.5 h, the PET conversion was 100% and BHET yield was 95.4%. More importantly, this catalyst can be collected by external magnetic field and its catalytic effect did not obviously decrease after it was reused for ten times. This work provided a new type of highly efficient catalyst of glycolysis of PET.

An innovative benign process for recovery lactic acid from its fermentation broth is proposed using a novel hyper-cross-linked meso-micropore resin and water as eluent. This work focuses on modeling the competitive adsorption behaviors of glucose, lactic acid and acetic acid ternary mixture and explosion of the adsorption mechanism. The characterization results showed the resin had a large BET surface area and specific pore structure with hydrophobic properties. By analysis of the physicochemical properties of the solutes and the resin, the mechanism of the separation is proposed as hydrophobic effect and size-exclusion. Subsequently three chromatographic models were applied to predict the competitive breakthrough curves of the ternary mixture under different operating conditions. The pore diffusion was the major limiting factor for the adsorption process, which was consistent with the BET results. The novel HD-06 resin can be a good potential adsorbent for the future SMB continuous separation process.

We synthesized one quaternary ammonium polymeric ionic liquids (PILs)P[VBTHEA]Cl and three imidazolium PILs of P[VEIm]Br, P[VEIm]BF4, P[VEIm]PF6 by free-radical polymerization in solution. These PILs were characterized by FT-IR, 1H-NMR, 13C-NMR, TGA, XRD and SEM. Their CO2 adsorption capacities were measured under different pressures and temperatures by constant-volume technique. It was observed that quaternary ammonium PILs of P[VBTHEA]Cl have higher adsorption capacity for CO2 than those imidazolium PILs, following P[VBTHEA]Cl > P[VEIm]PF6 > P[VEIm]BF4 > P[VEIm]Br, which may be ascribed to higher positive charge density on ammonium cation than that on imidazolium cation and thus stronger interaction with CO2, consistent with the results from dual-mode adsorption model that ammonium PILs have much higher CO2 bulk absorption than imidazolium PILs. CO2 adsorption capacity of P[VBTHEA]Cl is 9.02 mg/g under 295 K and 1 bar, which is comparable to that of some other PILs, and is much higher than that of the corresponding ILs monomer. These PILs have good adsorption selectivity for CO2 over N2 and regeneration efficiency.

The present study focuses upon the effect of the impeller on sinking and floating behavior of suspending particles in stirred tank reactor, employing computational fluid dynamics (CFD) simulation where factorial design is used to investigate the main and interaction effects of design parameters on the particle distribution performance of four typical impeller designs. Factorial design results show the effect of diameter and width of the impeller and off-bottom clearance on sinking particles is different from that of floating particles and regression equations for sinking particles and floating particles are achieved separately. Meanwhile, optimal equations which quantitatively reveal the effect of impeller factors on suspension quality and energy input is established for impeller improvement. Besides the development of computational models, the combination of CFD simulation with factorial design method provides a useful approach to gain insight into the suspension behavior of sinking and floating particles, also it guides to optimize the impeller design.

This study was aimed to simulate a new ionic liquids (ILs)-based CO 2 capture process which is useful to capture CO 2 from model flue gas, by using two promising CO 2 absorbents, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF 6 ]). Thermodynamic properties such as vapor pressure, heat capacity and density were modeled. Vapor-liquid equilibrium (VLE) data were calculated by Redlich-Kwong (R-K) equation and NRTL model. The calculated VLE data were in good agreement with the experimental values. This ILs-based CO 2 capture process is characterized with few advantages such as there is no issue of water; solvent (ILs) loss is negligible as compared to monoethanolamine (MEA)-based CO 2 capture process (e.g., 0.299 g/tCO 2 for [bmim][BF 4 ] and 0.391 g/tCO 2 for [bmim][PF 6 ] respectively, while 178 g/tCO 2 for MEA); potential corrosion risk is excluded; the energy consumption in [bmim][BF 4 ]- and [bmim][PF 6 ]-based processes are lowered up to 26.7% and 24.8% respectively than that in MEA-based process. Thus, such an ILs-based CO 2 capture process is more competitive than traditional MEA-based CO 2 capture process.

To lower viscosity and possible negative effect on mass/heat transfer in industrial operation, we prepared a new absorption system to separate propylene from propane, i.e., ionic liquids (ILs)-organic solvent-cuprous salt. The absorption system is constructed by IL of 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]); organic solvent of pyridine, N,N-dimethylformamide (DMF) or N-methyl-2-pyrrolidone (NMP); cuprous chloride (CuCl). We experimentally measured the absorption capability and selectivity of such a new system for pure propylene, propane or their mixture at 1–7 bar and 298–318 K. We investigated different factors such as temperature, pressure, species of organic solvent, Cu+ concentration and regeneration and recycling of absorbents. The addition of organic solvent significantly lowers the viscosity of absorption system (approximately one order of magnitude lower). Organic solvent interestingly enhances the absorption capability for propylene while suppresses the absorption selectivity slightly. Species of solvent has a huge effect on separation performance. [Bmim][Cl]-pyridine-CuCl gives the best separation performance, e.g., in the absorption of a mixture of 50 mol% propylene and 50 mol% propane, the solubility of propylene in [Bmim][Cl]-pyridine-CuCl-2M (mass ratio of [Bmim][Cl]:pyridine, 10:1) is 0.064 mol/L at 298 K/2 bar while that of propane is 0.0105 mol/L with absorption selectivity of 6.1, which is comparable to some other ILs-Ag+ or ILs-Cu+ absorption systems. Such an absorption system can be regenerated through temperature and pressure swing and recycled without remarkable activity loss. Therefore, this new system is a good potential absorbent for separating propylene and propane.

Isobaric vapor–liquid equilibrium (VLE) values at 101.3 kPa of binary methyl acetate + methanol, binary methyl acetate + ionic liquids (ILs), binary methanol + ILs, and ternary methyl acetate + methanol + ILs are measured, where the ILs are 1,3-dimethylimidazolium dimethylphosphate ([MMIM][DMP]), 1-ethyl-3-methylimidazolium diethylphosphate ([EMIM][DEP]), and 1-butyl-3-methylimidazolium dibutylphosphate ([BMIM][DBP]). The azeotropic point of methyl acetate + methanol is removed with addition of ILs, and [MMIM][DMP] gives the largest effect, followed by [EMIM][DEP] and [BMIM][DBP]. Salting-out effect from ILs is observed where the relative volatility of methyl acetate is increased. The minimum amount of such phosphate ILs required to break the azeotropic point is remarkably less than that of some other ILs; also such phosphate ILs are fluorine-free and easily prepared with cheaper starting materials. The experimental VLE data are correlated well with electrolyte NRTL model.

Conventional activated carbon used in decolorization of citric acid fermentation broth has the disadvantage of high citric acid loss. In this study, a novel biomass-based carbon material, namely HBCM, was prepared via H3PO4 activation of hydrothermally treated corncob. The material was fully characterized by SEM, BET, TG, FTIR, XPS and pHpzc. The results showed that the material's SBET was as high as 1720 m2 g−1 and several weak-acid functional groups existed on its surface, which contributed to efficient decolorization with low citric acid loss. By adjusting the solution pH value to around 7, nearly no citric acid was lost. Furthermore, the adsorption behavior of pigments on HBCM was systematically investigated under optimized pH. The results indicated that the adsorption was spontaneous and endothermic. Intra-particle diffusion was the rate-limiting step. By comparing FTIR data before and after adsorption, it was found that oxygen-containing functional groups on the HBCM surface participated in pigment adsorption. Overall, the tailor-made HBCM performed excellently with a 99% decolorization ratio and nearly no citric acid loss under optimum operating conditions. It could be a potential adsorbent in the removal of pigments from citric acid fermentation broth.

Background: Amyloid β (Aβ) deposits and the endoplasmic reticulum stress (ERS) are both well established in the development and progression of Alzheimer's disease (AD). However, the mechanism and role of Aβ-induced ERS in AD-associated pathological progression remain to be elucidated. Methods: The five familial AD (5×FAD) mice and wild-type (WT) mice aged 2, 7, and 12 months were used in the present study. Morris water maze test was used to evaluate their cognitive performance. Immunofluorescence and Western blot analyses were used to examine the dynamic changes of pro-apoptotic (CCAAT/enhancer-binding protein homologous protein [CHOP] and cleaved caspase-12) and anti-apoptotic factors (chaperone glucose-regulated protein [GRP] 78 and endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway. Results: Compared with age-matched WT mice, 5×FAD mice showed higher cleaved caspase-3, lower neuron-positive staining at the age of 12 months, but earlier cognitive deficit at the age of 7 months (all P < 0.05). Interestingly, for 2-month-old 5×FAD mice, the related proteins involved in the ERS-associated UPR pathway, including CHOP, cleaved caspase-12, GRP 78, and SYVN1, were significantly increased when compared with those in age-matched WT mice (all P < 0.05). Moreover, ERS occurred mainly in neurons, not in astrocytes. Conclusions: These findings suggest that compared with those of age-matched WT mice, ERS-associated pro-apoptotic and anti-apoptotic proteins are upregulated in 2-month-old 5×FAD mice, consistent with intracellular Aβ aggregation in neurons.

Extractive and oxidative desulfurization of fuel oil using ionic liquids (ILs) as solvents have been intensively studied recently. In such processes, the mutual solubility of ILs and fuel oil is an issue that has to be addressed, and less mutual solubility is desired. In this work, we synthesized five kinds of ILs, i.e., [C1pyr]H2PO4, [C1pyr]Cl/ZnCl2, [BMIM]H2PO4, [BMIM]Cl/ZnCl2, [BPy]H2PO4 and studied their mutual solubility with fuel oil by employing experiment and conductor-like screening model for real solvents (COSMO-RS). A variety of factors such as time, IL structure, temperature, polar component in ILs and composition of fuel oil on the mutual solubility were investigated, and σ-profiles were used to understand the mutual solubility. ILs, which investigated in this work, composed of anions with stronger HB acceptor capacity and cations with stronger HB donor capacity, dissolving some polar components such as water and methanol, are more soluble in fuel oils with more polar components; while the fuel oils are more soluble in ILs with anions that have strong HB acceptor capacity and with cations that have strong HB donor capacity. The factors uncovered will provide some information for researchers, the factors affecting the mutual solubility of ILs and fuel oil and is expected to contribute to the rational selection of conditions and ILs for desulfurization.

Compelling evidence supports vascular contributions to cognitive impairment and dementia (VCID) including Alzheimer’s disease (AD), but the underlying pathogenic mechanisms and treatments are not fully understood. Cis P-tau is an early driver of neurodegeneration resulting from traumatic brain injury, but its role in VCID remains unclear. Here, we found robust cis P-tau despite no tau tangles in patients with VCID and in mice modeling key aspects of clinical VCID, likely because of the inhibition of its isomerase Pin1 by DAPK1. Elimination of cis P-tau in VCID mice using cis-targeted immunotherapy, brain-specific Pin1 overexpression, or DAPK1 knockout effectively rescues VCID-like neurodegeneration and cognitive impairment in executive function. Cis mAb also prevents and ameliorates progression of AD-like neurodegeneration and memory loss in mice. Furthermore, single-cell RNA sequencing revealed that young VCID mice display diverse cortical cell type–specific transcriptomic changes resembling old patients with AD, and the vast majority of these global changes were recovered by cis-targeted immunotherapy. Moreover, purified soluble cis P-tau was sufficient to induce progressive neurodegeneration and brain dysfunction by causing axonopathy and conserved transcriptomic signature found in VCID mice and patients with AD with early pathology. Thus, cis P-tau might play a major role in mediating VCID and AD, and antibody targeting it may be useful for early diagnosis, prevention, and treatment of cognitive impairment and dementia after neurovascular insults and in AD.

In order to enhance the growth performance of S. cerevisiae under harsh environmental conditions, mutant XCG001, which tolerates up to 1.5M NaCl, was isolated via adaptive laboratory evolution (ALE). Comparisons made via transcriptome data of XCG001 and the wild-type strain identified ELO2 as being associated with osmotic tolerance. Overexpression of ELO2 increased the contents of inositol phosphorylceramide (IPC, t18:0/26:0), mannosylinositol phosphorylceramide (MIPC, t18:0/22:0(2OH)), MIPC (d18:0/22:0), MIPC (d20:0/24:0), mannosyldiinositol phosphorylceramide (M(IP)2C, d20:0/26:0), M(IP)2C (t18:0/26:0(2OH)) and M(IP)2C (d20:0/26:0(2OH)) by 88.3-, 166.9-, 63.3-, 23.9-, 27.9-, 113.8- and 208.1-fold at 1.0 M NaCl, respectively, compared those of strain XCG002. As a result, membrane integrity, cell growth and cell survival of the ELO2 overexpression strain (XCG010) increased by 24.4%, 29% and 22.1% at 1.0 M NaCl, respectively, compared those of strain XCG002. The findings provided a novel strategy for engineering complex sphingolipids to enhance osmotic tolerance.IMPORTANCEThis study demonstrated a novel strategy for manipulation membrane complex sphingolipids to enhance S. cerevisiae tolerance to osmotic stress. Osmotic tolerance was related to sphingolipid acyl chain elongase, Elo2, via transcriptome analysis of the wild-type strain and an osmotic tolerant strain generated from ALE. Overexpression of ELO2 increased complex sphingolipid with longer acyl chain, thus improved membrane integrity and osmotic tolerance.

Background: This study explored the predictive value of 3D-ASL for vertebral artery stenosis (VAS) in individuals at risk of stroke. Methods: A total of 43 participants at risk of stroke were enrolled in our study. All participants underwent 3D-ASL and carotid artery computed tomography angiography (CTA) or cervical vascular ultrasound. Cerebral blood flow (CBF) was measured in the left and right frontal lobes, temporal lobes, parietal lobes, occipital lobes, basal ganglia, thalamus, cerebellum, and hippocampus. Calculate the CBF BI (CBF BI means: The absolute value of the difference in cerebral blood flow in the corresponding brain regions on the left and right sides of the enrolled personnel) of the corresponding brain regions of the left and right between the VAS group and the non-VAS group respectively. To evaluate the predictive value of 3D-ASL for vascular stenosis in participants at risk of stroke, we used two-sample t-tests to determine if there were significant differences in BI. Results: Among 43 participants at risk of stroke we recruited, 20 participants with vertebral artery stenosis (the VAS group) and 23 without vertebral artery stenosis (the non-VAS group). There were significant differences in BI of the occipital lobe between the VAS group and the non-VAS group (p < 0.05). According to the occipital lobe BI value, the receiver operating characteristic curve (ROC) demonstrated best diagnostic limits of 10.46 ml/(100g×min). Conclusion: Using 3D-ASL to detect cerebral blood flow and calculate the difference of bilateral occipital cerebral blood flow which can help to diagnose vertebral artery stenosis in high risk population of stroke.

C-X-C motif chemokine ligand 8 (CXCL8) is involved in tumor proliferation, migration, and invasion. However, the function of CXCL8 in colorectal cancer (CRC) is controversial. Here, we analyzed RNA-sequencing (RNA-seq) data to identify differentially expressed genes and pathways according to gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with CRC. The levels of the mRNA encoding CXCL8 were significantly increased in early and advanced stages of CRC, as well as in metastases and nonmetastasis cases using RNA-seq analysis (n = 91). These findings were consistent with immunohistochemical analysis of CXCL8 expression (n = 87). Protein-protein interaction (PPI) prediction combined with transcriptional profiling data revealed that CXCL8 levels positively correlated with cAMP responsive element binding protein 1 (CREB1)/ribosomal protein S6 kinase B1 (RPS6KB1) expression, which promotes cell proliferation and differentiation in high expression, while inversely correlated with the expression of Bcl2 associated agonist of cell death (BAD) protein to inhibit apoptosis during the progression of CRC. These findings provide compelling clinical and molecular evidence to support the conclusion that CXCL8 contributes to the genesis and progression of CRC.

Aim: Salivary miRNA can be easily accessible biomarkers of alcohol dependence (AD). Materials & methods: The miRNA transcriptome in the saliva of 56 African–Americans (AAs; 28 AD patients/28 controls) and 64 European–Americans (EAs; 32 AD patients/32 controls) was profiled using small RNA sequencing. Differentially expressed miRNAs were identified. Salivary miRNAs were used to predict the AD presence using machine learning with Random Forests. Results: Seven miRNAs were differentially expressed in AA AD patients, and five miRNAs were differentially expressed in EA AD patients. The AD prediction accuracy based on top five miRNAs (ranked by Gini index) was 79.1 and 72.2% in AAs and EAs, respectively. Conclusion: This study provided the first evidence that salivary miRNAs are AD biomarkers.

Background Metformin, a first-line antiglycemic drug, has been reported to have anti-depressant effects in patients with type 2 diabetes; however, its exact role and underlying mechanism still need to be investigated. Method C57BL/6J mice were subjected to the Chronic social defeat stress (SDS) and drug administration (Control + Vehicle, SDS + Vehicle, SDS + MET (200 mg kg−1), SDS + FLUOX (3 mg kg−1), SDS + MET + FLUOX). And the depression phenotypes were evaluated by the sucrose preference test, social interaction, tail suspension test and forced swimming test. The potential mechanisms underlying the effects of metformin on depression was discussed by using Chromatin immunoprecipitation, Quantitative real-time PCR mRNA expression analysis and Western blot in vivo and in primary cultured hippocampal neurons. Result The metformin treatment counteracted the development of depression-like behaviors in mice suffering SDS when administered alone and enhanced the anti-depressant effect of fluoxetine when combined with fluoxetine. Further RNA sequencing analysis revealed that metformin treatment prevented the transcriptional changes in the medial prefrontal cortex (mPFC) of the animals and Golgi staining indicated favorable morphological changes in the neurite plasticity of CA1 pyramidal neurons, which approximated to those found in unstressed mice. At a molecular level, metformin significantly upregulated the expression of the brain-derived neurotrophic factor (BDNF) by increasing the histone acetylation along with the BDNF promoter, which was attributed to the activation of AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB). Conclusion Our findings suggest that metformin can produce antidepressant effects, which provides empirical insights into the clinical value of metformin in the prevention and therapy of depression.

Supplemental material, JCB893600 Supplemental Material for Severity of white matter hyperintensities: Lesion patterns, cognition, and microstructural changes by Weiyi Zeng, Yaojing Chen, Zhibao Zhu, Shudan Gao, Jianan Xia, Xiaochun Chen, Jianjun Jia and Zhanjun Zhang in Journal of Cerebral Blood Flow & Metabolism

The environmental impacts of foreign direct investment (FDI) and foreign trade have attracted much attention recently. This paper employs panel quantile regression to explore the effects of FDI and foreign trade on Chinese provincial CO2 emissions for the period of 1997-2014. The results indicate that the effect of FDI on CO2 emissions is negative and significant except at the 5th and 10th quantiles. Foreign trade has a significant negative effect on CO2 emissions at upper quantiles, and the degree of the effect increases gradually with the increase of CO2 emissions. The results also suggest that the inverted U-shaped environmental Kuznets curve (EKC) is valid only in the least and most polluted provinces. Nevertheless, the positive indirect effects of FDI and foreign trade on CO2 emissions are greater than the negative direct effects; thus the total effects are positive. Finally, several policy implications are proposed for China based on the empirical results obtained.

18F-Labelled pyrrolopyrimidines were synthesized and evaluated as positron emission tomography (PET) probes to determine leucine-rich repeat kinase 2 (LRRK2) expression in the brain. With pyrrolopyrimidine derivative PF-06447475 as the lead compound, two in vivo-stable 18F-labelled pyrrolopyrimidines ([18F]1 and [18F]2) were synthesized automatically at radiochemical yields 8–10% (non-decay-corrected) with molar activities of 0.95 and 0.5 GBq/μmol, respectively. The measured Kd of 6.90 nM for 1 and 14.27 nM for 2 demonstrated high affinities for LRRK2. The LRRK2 G2019S mice had higher uptakes (P