Targeting key players in Alzheimer's disease: bioactive compounds from Moringa oleifera, Desmodium gangeticum, and Centella asiatica as potential therapeutics.

Alzheimer's Disease (AD) is one of the critical reasons for dementia around the world, with a huge number of cases being reported every year. The breakdown of Amyloid Precursor Protein (APP) plays a crucial role in AD development. The Beta-site APP Cleaving Enzyme 1 (BACE1) is a highly significant proteolytic enzyme found to be critically involved in the APP breakdown process and generates beta-amyloid plaques in the extracellular neuronal membrane. In this study, we have used natural compounds with cognitive and neuroprotective activities from three plants, Centella asiatica, Moringa oleifera, and Desmodium gangeticum to inhibit the activity of BACE1. We have identified nine compounds out of 73 compounds filtered out from the three plants showing high affinity with the catalytic dyad region of BACE1 through molecular docking studies. Interestingly, the 200 ns molecular dynamics simulation study further confirmed the stability of the complexes formed between 9 compounds and the BACE1 protein. Furthermore, the free energy calculations also revealed these complexes possess favorable energies. Astilbin, Delphinidin 3-glucoside, and kaempferol 7-O-glucoside showed good binding affinity and structural stability when compared to other compounds and the control CNP520. Following a preliminary screening, the Astilbin compound was chosen based on the grounds of binding affinity, ADMET Properties, Hbond formation, Molecular Dynamic simulation, and MM-PBSA studies. A subsequent 1microsecond molecular dynamics simulation was conducted for the Astilbin complex. Through microsecond simulation, it was found that Astilbin alters BACE1's behavior and induces conformational rearrangements. Thus, this study opens a gateway to inhibit the activity of BACE1 protein through Astilbin thereby disclosing the possibility of managing Alzheimer's Disease.Communicated by Ramaswamy H. Sarma.

Molecular crosstalk between COVID-19 and Alzheimer's disease using microarray and RNA-seq datasets: A system biology approach.

Objective: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The clinical and epidemiological analysis reported the association between SARS-CoV-2 and neurological diseases. Among neurological diseases, Alzheimer's disease (AD) has developed as a crucial comorbidity of SARS-CoV-2. This study aimed to understand the common transcriptional signatures between SARS-CoV-2 and AD. Materials and methods: System biology approaches were used to compare the datasets of AD and COVID-19 to identify the genetic association. For this, we have integrated three human whole transcriptomic datasets for COVID-19 and five microarray datasets for AD. We have identified differentially expressed genes for all the datasets and constructed a protein-protein interaction (PPI) network. Hub genes were identified from the PPI network, and hub genes-associated regulatory molecules (transcription factors and miRNAs) were identified for further validation. Results: A total of 9,500 differentially expressed genes (DEGs) were identified for AD and 7,000 DEGs for COVID-19. Gene ontology analysis resulted in 37 molecular functions, 79 cellular components, and 129 biological processes were found to be commonly enriched in AD and COVID-19. We identified 26 hub genes which includes AKT1, ALB, BDNF, CD4, CDH1, DLG4, EGF, EGFR, FN1, GAPDH, INS, ITGB1, ACTB, SRC, TP53, CDC42, RUNX2, HSPA8, PSMD2, GFAP, VAMP2, MAPK8, CAV1, GNB1, RBX1, and ITGA2B. Specific miRNA targets associated with Alzheimer's disease and COVID-19 were identified through miRNA target prediction. In addition, we found hub genes-transcription factor and hub genes-drugs interaction. We also performed pathway analysis for the hub genes and found that several cell signaling pathways are enriched, such as PI3K-AKT, Neurotrophin, Rap1, Ras, and JAK-STAT. Conclusion: Our results suggest that the identified hub genes could be diagnostic biomarkers and potential therapeutic drug targets for COVID-19 patients with AD comorbidity.

Experimental data on analysis of a horizontal axis small wind turbine with blade tip power system using permanent magnetic generator.

The data on performance parameters of a horizontal axis small wind turbine (HAWT) with blade tip power system (BTPS) using permanent magnetic generator is presented. The tests are carried out for low wind velocities ranging from 7 m/s to 10 m/s. The data is acquired using data acquisition system equipped with Labview© software and the processed data is represented in terms of non-dimensional parameters, namely power coefficient (Cp), torque coefficient (CT) and tip speed ratio (λ). Moreover, as permanent magnetic generator is used in this HAWT with BTPS, the frictional as well as other losses are significantly reduced. This is reflected in terms of non-dimensional electrical power coefficient. The mechanical and electrical power coefficient values are closer with respect to each other. This measured data at laboratory conditions provides a benchmark for future open field environment tests and numerical simulation studies of this small wind turbine.

Experimental data of the study on H-rotor with semi-elliptic shaped bladed vertical axis wind turbine.

The performance and load test data of the proposed H-rotor with semi-elliptical shaped blade vertical axis wind turbine is carried out at the laboratory using 1 m diameter axial fan. India has a long coastline and low-wind velocity ranging from 3 to 10 m/s which is available everywhere in the country irrespective of climatic conditions. The data article is carried out at different aspect ratios along with tilt of the blades and without tilting of the blades. These data sets provide the researchers to further study experimentally as well as numerically in order to enhance the performance of the proposed VAWT. The data presented here are measured at wind velocity ranging from 3 to 6 m/s. The raw data captured using data acquisition system are processed and presented in a form so as to compare it with other typical VAWT.

Data set on the experimental investigations of a helical Savonius style VAWT with and without end plates.

The performance test on a helical Savonius style VAWT are carried out with end plates and without end plates for low wind velocities from 3 m/s to 6 m/s. The raw data measured using instruments are recorded using digital acquisition system. These data are processed and presented as dimensionless parameters namely, coefficient of power, coefficient of torque and tip speed ratio in order to compare it with other VAWTs.

Data set on optimized biodiesel production and formulation of emulsified Eucalyptus teriticornisis biodiesel for usage in compression ignition engine.

This data article presents the experimental values pertaining to the bio-oil extraction, optimizing biodiesel production and formulation of emulsified fuel blends of E.tereticornisis bio-oil for its use in compression ignition engine. The E.tereticornisis leaves were collected from the interior region of Puducherry, India. Soxhlet extraction process, in the presence of n-hexane, yielded 5.2% of bio-oil. Based on the free fatty acid content, base catalysed transesterification process was adopted along with use of sodium hydroxide and methanol. Optimization of biodiesel yield was carried out by varying the operating parameters. A biodiesel yield of 74.19% was obtained at eighty minutes reaction duration, 1.8 l/g ms of sodium hydroxide, 70 °C reaction temperature and 8:1 oil to molar ratio. Furthermore, the physiochemical properties improved by emulsifying the obtained biodiesel with 5% of water in presence of surfactant through experiments carried out based on Taguchi׳s DOE method.

Carbon Wrapping Effect on Sulfur/Polyacrylonitrile Composite Cathode Materials for Lithium Sulfur Batteries.

A sulfur-Polyacrylonitrile (PAN)-acetylene black (AB) composite was synthesized via thermal treatment processes. The as-prepared ternary composite was characterized by expending transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) and electrochemical investigations. The improved electrochemical performance can be attributed to the formation of PAN layer, which can keep a tight contact between carbon and sulfur which leads to improve the conductivity. Moreover, the PAN can also act as a flexible cushion to accommodate volume changes of sulfur cathode as well as a barrier to trap soluble polysulfide intermediates during the charge-discharge process. The PAN-S-AB composite exhibits discharge capacity of 620 mAh/g even after 50 cycles with appreciable sustainability. Therefore, the resulting PAN/S/AB composite exhibited as a desirable cathode material for Li-S battery with great performance.

Optical and field-emission properties of ZnO nanostructures deposited using high-pressure pulsed laser deposition.

ZnO nanostructures were deposited on GaN (0001), Al2O3 (0001), and Si (100) substrates using a high-pressure pulsed laser deposition (PLD) method. Vertically aligned hexagonal-pyramidal ZnO nanorods were obtained on the Al2O3 and Si substrates whereas interlinked ZnO nanowalls were obtained on the GaN substrates. A growth mechanism has been proposed for the formation of ZnO nanowalls based on different growth rates of ZnO polar and nonpolar planes. Both ZnO nanorods and nanowalls exhibit a strong E2H vibration mode in the micro-Raman spectra. The corresponding fluorescence spectra of ZnO nanorods and nanowalls showed near band emission at 3.28 eV. The ZnO nanorods grown on the Si substrates exhibited better crystalline and optical properties compared with the ZnO structures grown on the GaN and Al2O3 substrates. The high aspect ratio, good vertical alignment, and better crystallinity of the ZnO nanorods with tapered tips exhibited promising field emission performance with a low turn-on field of 2 V/µm, a high current density of 7.7 mA/cm2, and a large field enhancement factor.

Lamotrigine for schizophrenia.

BACKGROUND: Treating the 20-30% of people with schizophrenia whose symptoms are resistant to treatment can be problematic. Adding lamotrigine to ongoing antipsychotic treatment has shown to be of benefit in preliminary studies. OBJECTIVES: To evaluate the effects of adjuvant lamotrigine for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (February 2006) and inspected references of all identified studies for further trials. We contacted relevant authors of trials for additional information. SELECTION CRITERIA: We included all clinical randomised trials comparing lamotrigine with placebo or other antipsychotic augmentation strategies. DATA COLLECTION AND ANALYSIS: We extracted data independently. For homogenous dichotomous data we calculated random effects relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: We found five relevant trials (total n=537), but no usable data on service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment or economic outcomes. Overall, reporting of data was poor. Those data we were able to use suggested that equal proportions of people allocated lamotrigine or placebo had no global response (n=208, 1 RCT, RR 1.06 CI 0.73 to 1.54). There was no significant difference between groups in the proportions of people whose mental state did not improve (n=297, 3 RCT, RR 1.26 CI 0.81 to 1.97). There was, however, a significant reduction in the PANSS total scores (n=67, 2 RCT, WMD -16.88 CI -8.57 to -25.18, p=0.0001), positive symptom sub-scale scores (n=65, 2 RCTs, WMD -5.10 CI -8.86 to -1.34) and negative symptom sub-scale scores (n=67, 2 RCTs, WMD -5.25, CI -7.07 to -3.43). Most cognitive measures showed no differences (n=329, 2 RCTs, RR not attaining BACS composite score of 0.5 1.10 CI 0.59 to 2.04). The proportion of participants leaving studies was about 25% at 12 weeks (n=537, 5 RCTs, RR 0.96 CI 0.71 to 1.29). The lamotrigine group did experience the outcome of any adverse effects significantly more frequent than people allocated placebo (n=429, 2 RCTs, RR 1.19 CI 1.02 to 1.38, NNH 10 CI 5 to 90). Among the many effects listed, only nausea was found to be significantly more (9%) in the lamotrigine group compared with placebo (n=465, 3 RCTs, RR 2.26 CI 1.05 to 4.88). AUTHORS' CONCLUSIONS: Evidence for use of lamotrigine as an adjuvant for people with schizophrenia is not robust and large well-designed, conducted and reported real-world randomised trials are needed to determine its place in everyday clinical practice.