Transcription factor VvWRKY70 inhibits both norisoprenoid and flavonol biosynthesis in grape.

Norisoprenoids and flavonols are important secondary metabolites in grape berries (Vitis vinifera L.). The former is a class of ubiquitous flavor and fragrance compounds produced by the cleavage of carotenoids, and the latter, which is derived from the flavonoid metabolic pathway, has been proposed as a general quality marker for red grapes. However, the transcriptional regulatory mechanisms underlying norisoprenoid and flavonol production are still not fully understood. In this study, we characterized a transcription factor, VvWRKY70, as a repressor of both norisoprenoid and flavonol biosynthesis in grape berries, and its expression was downregulated by light and high-temperature treatment. Overexpressing VvWRKY70 in grape calli reduced norisoprenoid and flavonol production, particularly under light exposure or at high temperature, by repressing the expression of several related genes in the isoprenoid and flavonoid metabolic pathways. VvWRKY70 downregulated ß-CAROTENE HYDROXYLASE 2 (VvBCH2) and CHALCONE SYNTHASE 3 (VvCHS3) expression based on yeast 1-hybrid analysis combined with electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR. We discuss the role of VvWRKY70 in the coordinated regulatory network of isoprenoid and flavonoid metabolism. These findings provide a theoretical basis to improve flavor, color, and other comprehensive qualities of fruit crops and their processing products.

Improvement of diabetes-induced spinal cord axon injury with taurine via nerve growth factor-dependent Akt/mTOR pathway.

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF-pAKT-mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway.

Photoredox/copper-catalyzed gem-difluoroalkylation-cyanation of 1,3-enynes.

A photoredox/copper-catalyzed 1,4-difunctionalization of 1,3-enynes with readily available difluoroalkylating reagents and TMSCN was developed. This reaction proceeded at mild conditions, affording the corresponding difluoroalkylated allenes in good yields with high functional-group tolerance and excellent regioselectivity.

Genetically encoded libraries and spider venoms as emerging sources for crop protective peptides.

Agricultural crops are targeted by various pathogens (fungi, bacteria, and viruses) and pests (herbivorous arthropods). Antimicrobial and insecticidal peptides are increasingly recognized as eco-friendly tools for crop protection due to their low propensity for resistance development and the fact that they are fully biodegradable. However, historical challenges have hindered their development, including poor stability, limited availability, reproducibility issues, high production costs, and unwanted toxicity. Toxicity is a primary concern because crop-protective peptides interact with various organisms of environmental and economic significance. This review focuses on the potential of genetically encoded peptide libraries like the use of two-hybrid-based methods for antimicrobial peptides identification and insecticidal spider venom peptides as two main approaches for targeting plant pathogens and pests. We discuss some key findings and challenges regarding the practical application of each strategy. We conclude that genetically encoded peptide library- and spider venom-derived crop protective peptides offer a sustainable and environmentally responsible approach for addressing modern crop protection needs in the agricultural sector.

Cocaine and amphetamine-regulated transcript improves myocardial ischemia-reperfusion injury through PI3K/AKT signalling pathway.

Myocardial ischemia-reperfusion injury (MIRI) is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction. It has been shown that cocaine and amphetamine-regulated transcript (CART) can ameliorate cerebral ischemia-reperfusion (I/R) injury, but the effect of CART on MIRI has not been studied yet. Here, we revealed that CART protected the heart during I/R process by inhibiting apoptosis and excessive autophagy, indicating that CART would be a potential drug candidate for the treatment of MIRI. Further analysis showed that CART upregulated the activation of phospho-AKT, leading to downregulation of lactate dehydrogenase (LDH) release, apoptosis, oxidative stress and excessive autophagy after I/R, which was inhibited by PI3K inhibitor, LY294002. Collectively, CART attenuated MIRI through inhibition of cardiomyocytes apoptosis and excessive autophagy, and the protective effect was dependent on PI3K/AKT signalling pathway.

Functional changes in fusional vergence-related brain areas and correlation with clinical features in intermittent exotropia using functional magnetic resonance imaging.

To explore the functional changes of the frontal eye field (FEF) and relevant brain regions and its role in the pathogenesis of intermittent exotropia (IXT) children via functional magnetic resonance imaging (fMRI). Twenty-four IXT children (mean age, 11.83 ± 1.93 years) and 28 normal control (NC) subjects (mean age, 11.11 ± 1.50 years) were recruited. During fMRI scans, the IXT children and NCs were provided with static visual stimuli (to evoke sensory fusion) and dynamic visual stimuli (to evoke motor fusion and vergence eye movements) with binocular disparity. Brain activation in the relevant brain regions and clinical characteristics were evaluated. Group differences of brain activation and brain-behavior correlations were investigated. For dynamic and static visual disparity relative to no visual disparity, reduced brain activation in the right FEF and right inferior occipital gyrus (IOG), and increased brain activation in the left middle temporal gyrus complex (MT+) were found in the IXT children compared with NCs. Significant positive correlations between the fusional vergence amplitude and the brain activation values were found in the right FEF, right IPL, and left cerebellum in the NC group. Positive correlations between brain activation values and Newcastle Control Scores (NCS) were found in the left MT+ in the IXT group. For dynamic visual disparity relative to static visual disparity, reduced brain activation in the right middle occipital gyrus, left cerebellum, and bilateral IPL was found in the IXT children compared with NCs. Significant positive correlations between brain activation values and the fusional vergence amplitude were found in the right FEF and right cerebellum in the NC group. Negative correlations between brain activation values and NCS were found in the right middle occipital gyrus, right cerebellum, left IPL, and right FEF in the IXT group. These results suggest that the reduced brain activation in the right FEF, left IPL, and cerebellum may play an important role in the pathogenesis of IXT by influencing fusional vergence function. While the increased brain activation in the left MT+ may compensate for this dysfunction in IXT children.

Syringaresinol protects against diabetic nephropathy by inhibiting pyroptosis via NRF2-mediated antioxidant pathway.

Diabetic nephropathy (DN) is one of the serious complications of diabetes that has limited treatment options. As a lytic inflammatory cell death, pyroptosis plays an important role in the pathogenesis of DN. Syringaresinol (SYR) possesses anti-inflammatory and antioxidant properties. However, the therapeutic effects and the underlying mechanism of SYR in DN remain unclear. Herein, we showed that SYR treatment ameliorated renal hypertrophy, fibrosis, mesangial expansion, glomerular basement membrane thickening, and podocyte foot process effacement in streptozotocin (STZ)-induced diabetic mice. Mechanistically, SYR prevented the abundance of pyroptosis-related proteins such as NOD-like receptor family pyrin domain containing 3 (NLRP3), cysteinyl aspartate-specific proteinase 1 (Caspase-1), and gasdermin D (GSDMD), and the biosynthesis of inflammatory cytokines interleukin 1ß (IL-1ß) and interleukin 18 (IL-18). In addition, SYR promoted the nuclear translocation of nuclear factor E2-related factor 2 (NRF2) and enhanced the downstream antioxidant enzymes heme oxygenase 1 (HO-1) and manganese superoxide dismutase (MnSOD), thereby effectively decreasing excess reactive oxygen species (ROS). Most importantly, knockout of NRF2 abolished SYR-mediated renoprotection and anti-pyroptotic activities in NRF2-KO diabetic mice. Collectively, SYR inhibited the NLRP3/Caspase-1/GSDMD pyroptosis pathway by upregulating NRF2 signaling in DN. These findings suggested that SYR may be promising a therapeutic option for DN.

Diurnal Variations in High Time-Resolved Molecular Distributions and Formation Mechanisms of Biogenic Secondary Organic Aerosols at Mt. Huang, East China.

The molecular characteristics and formation mechanism of biogenic secondary organic aerosols (BSOAs) in the forested atmosphere are poorly known. Here, we report the temporal variations in and formation processes of BSOA tracers derived from isoprene, monoterpenes, and ß caryophyllene in PM2.5 samples collected at the foot of Mt. Huang (483 m a. s. l) in East China during the summer of 2019 with a 3 h time resolution. The concentrations of nearly all of the detected species, including organic carbon (OC), elemental carbon (EC), levoglucosan, and SIA (sum of SO42-, NO3-, and NH4+), were higher at night (19:00-7:00 of the next day) than in the daytime (7:00-19:00). In addition, air pollutants that accumulated by the dynamic transport of the mountain breeze at night were also a crucial reason for the higher BSOA tracers. Most of the BSOA tracers exhibited higher concentrations at night than in the daytime and peaked at 1:00 to 4:00 or 4:00 to 7:00. Those BSOA tracers presented strong correlations with O3 in the daytime rather than at night, indicating that BSOAs in the daytime were primarily derived from the photo-oxidation of BVOCs with O3. The close correlations of BSOA tracers with SO42- and particle acidity (pHis) suggest that BSOAs were primarily derived from the acid-catalyzed aqueous-phase oxidation. Considering the higher relative humidity and LWC concentration at night, the promoted aqueous oxidation was the essential reason for the higher concentrations of BSOA tracers at night. Moreover, levoglucosan exhibited a robust correlation with BSOA tracers, especially ß-caryophyllinic acid, suggesting that biomass burning from long-distance transport exerted a significant impact on BSOA formation. Based on a tracer-based method, the estimated concentrations of secondary organic carbon (SOC) derived from isoprene, monoterpenes, and ß caryophyllene at night (0.90 ± 0.57 µgC m-3) were higher than those (0.53 ± 0.34 µgC m-3) in the daytime, accounting for 14.5 ± 8.5% and 12.2 ± 5.0% of OC, respectively. Our results reveal that the BSOA formation at the foot of Mt. Huang was promoted by the mountain-valley breezes and anthropogenic pollutants from long-range transport.

Systemic Methotrexate Treatment in 42 Children with Severe Plaque Psoriasis: A Retrospective Study in China.

BACKGROUND: The scientific evidence of methotrexate (MTX) in children with severe plaque psoriasis is scarce. OBJECTIVES: To retrospectively evaluate the efficacy and safety of oral MTX in children with severe plaque psoriasis in a single center in China. METHODS: We enrolled 42 children with severe plaque psoriasis who were administrated MTX. Efficacy was evaluated by the psoriasis area and severity index (PASI) score, physician global assessment (PGA) score, and body surface area (BSA) score. The Children's Dermatology Life Quality Index (CDLQI) score and safety data were recorded. RESULTS: Among 42 children (22 males, 20 females), the mean age was 11.2 years old. The initial weight-based dosage of oral MTX ranged from 0.1 to 0.3 mg/kg weekly. Overall, 80.6 and 47.2% of patients achieved PASI75 (at least 75% improvement from baseline in PASI score) and PASI90 (at least 90% improvement from baseline in PASI score) at week 12, respectively. 72.2% of patients achieved PGA 0/1 at week 12. BSA and PGA scores significantly decreased from baseline from week 4, accompanied by CDLQI score improvement from week 8. The steady effect of MTX could be reached at week 16. Elevated liver enzymes (28.6%) and infections (28.6%) were the most common side effects. Relapse was recorded in 9 (30.0%) of 30 patients, and the mean posttherapy disease-free interval was 7.2 months. CONCLUSIONS: MTX is an effective and safe option for children with severe plaque psoriasis with adequate monitoring.

Abnormal expression of histone acetylases in CD8+ T cells of patients with severe aplastic anemia.

INTRODUCTION: We aimed to investigate the balance between the mRNA levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in CD8+ T cells of patients with severe aplastic anemia (SAA). METHODS: Twenty untreated SAA patients, 18 remission SAA patients (R-SAA), and 22 normal controls were evaluated. The mRNA expression levels of HATs, HDACs, and IFNG in CD8+ T cells were measured by real-time quantitative reverse transcription polymerase chain reaction. RESULTS: Histone acetylase EP300 and CREBBP mRNA levels were significantly elevated in CD8+ T cells of SAA patients compared with the normal controls (both p < 0.05). No significant differences were observed in HDAC1 and HDAC7 mRNA between SAA patients and the normal controls. There was an obvious positive correlation between IFNG and EP300 (r = 0.5126, p < 0.01), and CREBBP (r = 0.4663, p < 0.05), respectively, in SAA and R-SAA patients. In addition, EP300 and CREBBP mRNA levels were clearly correlated with clinical parameters of peripheral blood and bone marrow in those patients. CONCLUSION: Our findings suggest that EP300 and CREBBP are increased in CD8+ T cells of SAA patients and are correlated with disease severity. The imbalances in HATs and HDACs may play a role in activating CD8+ T cells to promote the immune pathogenesis of SAA.

Enhanced CO2 Electrochemical Reduction Performance over Cu@AuCu Catalysts at High Noble Metal Utilization Efficiency.

The electrochemical CO2 reduction reaction (CO2RR) represents a viable alternative to help close the anthropogenic carbon cycle and convert intermittent electricity from renewable energy sources to chemical energy in the form of value-added chemicals. The development of economic catalysts possessing high faradaic efficiency (FE) and mass activity (MA) toward CO2RR is critical in accelerating CO2 utilization technology. Herein, an elaborate Au-Cu catalyst where an alloyed AuCu shell caps on a Cu core (Cu@AuCu) is developed and evaluated for CO2-to-CO electrochemical conversion. Specific roles of Cu and Au for CO2RR are revealed in the alloyed core-shell structure, respectively, and a compositional-dependent volcano-plot is disclosed for the Cu@AuCu catalysts toward selective CO production. As a result, the Au2-Cu8 alloyed core-shell catalyst (only 17% Au content) achieves an FECO value as high as 94% and an MACO of 439 mA/mgAu at -0.8 V (vs RHE), superior to the values for pure Au, reflecting its high noble metal utilization efficiency.

Taurine ameliorates axonal damage in sciatic nerve of diabetic rats and high glucose exposed DRG neuron by PI3K/Akt/mTOR-dependent pathway.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and axonopathy is its main pathological feature. Previous studies suggested an advantage of taurine against diabetes. However, there are few reports which study the effect of taurine against axonopathy. In this study, we confirmed that taurine significantly decreased blood glucose level, mitigated insulin resistance and improved dysfunctional nerve conduction in diabetic rats. Taurine corrected damaged axonal morphology of sciatic nerve in diabetic rats and induced axon outgrowth of Dorsal root ganglion (DRG) neurons exposed to high glucose. Taurine up-regulated phosphorylation levels of PI3K, Akt, and mTOR in sciatic nerve of diabetic rats and DRG neurons exposed to high glucose. However, Akt and mTOR inhibitors (MK-2206 and Rapamycin) blocked the effect of taurine on improving axonal damage. These results indicate that taurine ameliorates axonal damage in sciatic nerve of diabetic rats by activating PI3K/Akt/mTOR signal pathway. Our findings provide taurine as a potential candidate for axonopathy and a new evidence for elucidating protective mechanism of taurine on DPN.

Heterogeneous Dynamics of Polymer Melts Exerted by Chain Loops Anchored on the Substrate: Insights from Molecular Dynamics Simulation.

Understanding polymer-substrate interfacial dynamics at the molecular level is crucial for tailoring the properties of polymer ultrathin films (PUFs). Herein, through coarse-grained molecular dynamics simulation, the effect of length (Nloop) and rigidity (Kloop) of loop chains on the dynamics of linear chains is systematically explored, in which the loop chains are adsorbed on a solid substrate and the linear chains are covered on the loop chains. It is found that there is an optimal Kloop, which strongly confines the motion of the linear chains. Meanwhile, compared to increasing the rigidity of the loop chains, increasing the length of the loop chains can more effectively confine the motion of the linear chains. More interestingly, we observe that the mismatch of the length (ΔN) and rigidity (ΔK) between the loop and linear chains leads to dynamic asymmetry (ΔDc). The relationship between the ΔN, ΔK, and ΔDc are found to follow the mathematical expression of ΔDc ∼ (ΔN)α(ΔK)ß, in which the values of α and ß are around 4.58 and 0.83, separately. Remarkably, using the Gaussian process regression model, we construct a master curve of diffusion coefficient on the segmental and chain length scales of the linear chains as a function of Nloop and Kloop, which is further validated by our simulated prediction. In general, this work provides a fundamental understanding of polymer interfacial dynamics at the molecular level, enlightening some rational principles for manipulating the physical properties of PUFs.

Chemometric QSAR modeling of acute oral toxicity of Polycyclic Aromatic Hydrocarbons (PAHs) to rat using simple 2D descriptors and interspecies toxicity modeling with mouse.

The information of the acute oral toxicity for most polycyclic aromatic hydrocarbons (PAHs) in mammals are lacking due to limited experimental resources, leading to a need to develop reliable in silico methods to evaluate the toxicity endpoint. In this study, we developed the quantitative structure-activity relationship (QSAR) models by genetic algorithm (GA) and multiple linear regression (MLR) for the rat acute oral toxicity (LD50) of PAHs following the strict validation principles of QSAR modeling recommended by OECD. The best QSAR model comprised eight simple 2D descriptors with definite physicochemical meaning, which showed that maximum atom-type electrotopological state, van der Waals surface area, mean atomic van der Waals volume, and total number of bonds are main influencing factors for the toxicity endpoint. A true external set (554 compounds) without rat acute oral toxicity values, and 22 limit test compounds, were firstly predicted along with reliability assessment. We also compared our proposed model with the OPERA predictions and recently published literature to prove the prediction reliability. Furthermore, the interspecies toxicity (iST) models of PAHs between rat and mouse were also established, validated and employed for filling data gap. Overall, our developed models should be applicable to new or untested or not yet synthesized PAHs falling within the applicability domain (AD) of the models for rapid acute oral toxicity prediction, thus being important for environmental or personal exposure risk assessment under regulatory frameworks.

Spatial pattern matching analysis of grain production and rainfall in the Ziya River Basin.

The exploratory spatial data analysis (ESDA) method, which includes global spatial autocorrelation and local spatial autocorrelation, is used to analyze the spatial pattern of the annual grain production and annual grain production increment in the Ziya River Basin from 2007 to 2017. Then, the spatial mismatch index is used to analyze the spatial mismatch relationship between the annual grain output and annual precipitation in the Ziya River Basin in 2015. The results showed that (1) the spatial pattern of the annual grain production in the Ziya River Basin is stable, with Low-Low clusters and High-High clusters concentrated on the left and right sides of the Ziya River Basin, respectively. The overall difference in the annual grain production of each district and county increased gradually from 2013 to 2017. (2) The local spatial correlation structure of the annual grain production of adjacent districts and counties in the Ziya River Basin had strong stability, and its space-time transition had a certain path dependence or spatial-locking characteristics. The reason why the High-High clusters are concentrated on the right side of the Ziya River is that there are large cultivated areas, such as the Shijin irrigation district, on the right side of the Ziya River Basin. (3) A spatial change rule "the proportion of grain production is low and the proportion of rainfall is high" changed to "the proportion of grain production and rainfall is balanced" and then to "the proportion of grain production is high and the proportion of rainfall is low" in the Ziya River Basin in 2015. The Shijin irrigation district is mainly located in the area where the spatial mismatch between the annual grain output and the average annual rainfall in the Ziya River Basin in 2015 is assessed as grade V, which indicates that the spatial mismatch between the annual grain output and the annual average rainfall is serious. In summary, grain production in the Shijin irrigation district has been increasing annually, while the supply of water for irrigation has not increased as much. There is a serious deficit between the irrigation water supply and the water demand for grain production in the Shijin irrigation district. Therefore, it is necessary to plan for the development and utilization of surface water and groundwater resources and to adjust the planting structure in the Shijin irrigation district for the purpose of saving water.

Taurine protects against myelin damage of sciatic nerve in diabetic peripheral neuropathy rats by controlling apoptosis of schwann cells via NGF/Akt/GSK3ß pathway.

Diabetic peripheral neuropathy is a common complications of Type 2 Diabetes and its main pathological feature is myelin sheath damage of peripheral nerve that was induced by Schwann cells (SCs) apoptosis. Increasing evidence suggested that taurine might play a role in improving DPN because of its ability to prevent SCs apoptosis. In this study, we explore the effect of taurine on preventing SCs apoptosis and its underlying mechanism. Sprague Dawley rats were treated with streptozotocin to establish the diabetes model. Rats were randomly divided into control, diabetes, taurine treatment (as giving 0.5%, 1% and 2% taurine in drinking water) groups. RSC96 cell (a rat SCs line) was used for intervention experiments in vitro. Results showed that taurine significantly corrected morphology of damaged myelin sheath and inhibited SCs apoptosis in sciatic nerve of diabetic rats. Moreover, taurine prevented apoptosis of RSC96 cells exposed to high glucose. Mechanistically, taurine up-regulated NGF expression and phosphorylation levels of Akt and GSK3ß, while, blocking activation of NGF and phosphorylation of Akt and GSK3ß increased apoptosis of high glucose-exposed RSC96 cells with taurine supplement. These results revealed taurine improved the myelin sheath damage of sciatic nerve in diabetic rats by controlling SCs apoptosis via NGF/Akt/GSK3ß signaling pathways, which provides some clues that taurine might be effective and feasible candidate for the treatment of DPN.

Identification of novel KMT2D mutations in two Chinese children with Kabuki syndrome: a case report and systematic literature review.

BACKGROUND: Kabuki syndrome (KS) is a rare pediatric congenital disorder with multiple congenital anomalies and intellectual disabilities, which is inherited in an autosomal dominant manner. Mutations in KMT2D and KDM6A have been proven to be the primary cause in most cases of KS. CASE PRESENTATION: Here we report two Chinese boys with clinical features of KS referred to our hospital for clinical diagnosis. Next-generation sequencing was performed on MiSeq to analyze the genetic mutations in both patients. In both, two novel de novo mutations in KMT2D gene (c.5235delA, p.(A1746Lfs*39) and c.7048G > A, p.(Q2350*)) were detected, both of which were subsequently confirmed by the two-generation pedigree analysis based on Sanger sequencing. A systematic literature review of previously reported mutational spectrum of KMT2D was also conducted. CONCLUSIONS: Two novel de novo mutations in KMT2D gene were identified and considered to be pathogenic in both of KS patients. Our data adds information to the growing knowledge on the mutational spectrum of KS.

Engineered 3D tumour model for study of glioblastoma aggressiveness and drug evaluation on a detachably assembled microfluidic device.

3D models of tumours have emerged as an advanced technique in pharmacology and tumour cell biology, in particular for studying malignant tumours such as glioblastoma multiforme (GBM). Herein, we developed a 3D GBM model on a detachably assembled microfluidic device, which could be used to study GBM aggressiveness and for anti-GBM drug testing. Fundamental characteristics of the GBM microenvironment in terms of 3D tissue organisation, extracellular matrices and blood flow were reproduced in vitro by serial manipulations in the integrated microfluidic device, including GBM spheroid self-assembly, embedding in a collagen matrix, and continuous perfusion culture, respectively. We could realize multiple spheroids parallel manipulation, whilst, compartmentalized culture, in a highly flexible manner. This method facilitated investigations into the viability, proliferation, invasiveness and phenotype transition of GBM in a 3D microenvironment and under continuous stimulation by drugs. Anti-invasion effect of resveratrol, a naturally isolated polyphenol, was innovatively evaluated using this in vitro 3D GBM model. Temozolomide and the combination of resveratrol and temozolomide were also evaluated as control. This scalable model enables research into GBM in a more physiologically relevant microenvironment, which renders it promising for use in translational or personalised medicine to examine the impact of, or identify combinations of, therapeutic agents.

Polymer Amplified Enantioselectivity in the Fluorescent Recognition of Prolinol.

A 1,1'-bi-2-naphthol (BINOL)-aldehyde-based polymer has been synthesized that exhibits enantioselective fluorescent enhancement toward prolinol. It is found that the polymer shows greatly amplified enantioselectivity over the parent small-molecule sensor under the same conditions. This is attributed to the photoinduced electron transfer processes between the BINOL units in the polymer chain as well as the different steric environment provided by the polymer.

Enhanced Neuroprotective Effects of Combination Therapy with Bone Marrow-Derived Mesenchymal Stem Cells and Ginkgo biloba Extract (EGb761) in a Rat Model of Experimental Autoimmune Encephalomyelitis.

OBJECTIVES: We investigated whether Ginkgo biloba extract (EGb761) can provide neuroprotective effects and enhance the efficacy of bone marrow-derived mesenchymal stem cells (BMSCs) in a rat model of experimental autoimmune encephalomyelitis (EAE). METHODS: We examined the synergistic action of BMSCs combined with EGb761 treatment in EAE rats. The immunized rats received an intravenous injection of BMSCs or intraperitoneal administration of EGb761 or both on the day of the onset of clinical symptoms and for the following 21 days. Clinical severity scores were recorded daily and histopathological examination of the spinal cord and cytokine concentrations in the serum were studied on days 14 and 31 postimmunization. RESULTS: Our results showed that combined treatment with BMSCs and EGb761 further decreased the disease severity, maximal clinical score and number of infiltrated mononuclear cells, especially CD3-positive T cells. We observed that the demyelination score and the density of axonal loss in the spinal cord were significantly reduced in mice receiving the combination therapy. The serum concentrations of the phosphorylated neurofilament heavy chain, tumor necrosis factor-α and interferon-γ were reduced in the combination-treatment group. CONCLUSION: Our results suggest that combined treatment with BMSCs and EGb761 have a synergistic effect in rats with EAE by inhibiting the secretion of proinflammatory cytokines, demyelination and protecting axons and neurons.