Inhibition clathrin mediated endocytosis: Pitstop 1 and Pitstop 2 chimeras.

Twenty-five chimera compounds of Pitstop® 1 and 2 were synthesised and screened for their ability to block the clathrin terminal domain-amphiphysin protein-protein interaction (NTD-PPI using an ELISA) and clathrin mediated endocytosis (CME) in cells.  Library 1 was based on Pitstop 2, but no notable clathrin PPI or in-cell activity was observed.  With the Pitstop 1, 16 analogues were produced with 1,8-naphthalic imide core as a foundation.  Analogues with methylene spaced linkers and simple amides showed a modest to good range of PPI inhibition (7.6 to 42.5 mM, naphthyl 39 and 4-nitrophenyl 40 respectively) activity.  These data reveal the importance of the naphthalene sulfonate moiety, with no des-SO3 analogue displaying PPI inhibition.  This was consistent with the observed analogue docked poses within the clathrin terminal domain Site 1 binding pocket.  Further modifications targeted the naphthalene imide moiety, with the installation of 5-Br (45a), 5-OH (45c) and 5-propyl ether (45d) moieties.  Among them, the OH 45c and propyl ether 45d retained PPI inhibition, with propyl ether 45d being the most active with a PPI inhibition IC50 = 7.3 mM.  This is 2x more potent than Pitstop® 2 and 3x more potent than Pitstop 1.

Photocatalytic degradation of methylene blue under visible light by cobalt ferrite nanoparticles/graphene quantum dots.

A simple approach was developed to synthesize cobalt ferrite nanoparticles/graphene quantum dots (CF/GQDs). The material was prepared from a homogeneous mixture of iron nitrate, cobalt nitrate, and starch at 140, 180 and 200 °C in a 24 h thermal hydrolysis process. The obtained materials were characterised by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, Fourier-transform infrared spectroscopy, photoluminescence spectroscopy, vibrating-sample magnetometry, and nitrogen adsorption/desorption isotherms. Cobalt ferrite crystals of around 8-10 nm and graphene quantum dots formed directly at 200 °C. Stacking GQDs sheets onto the CF nanoparticles resulted in CF/GQDs nanoparticles. The nanocomposite exhibits satisfactory fluorescent and superparamagnetic properties, which are vital for catalytic applications. The CF/GQDs catalyse significantly the degradation of methylene blue (MB) under visible light. The catalyst can be recycled with an external magnetic field and displays suitable stability. Also, it was reused in three successive experiments with a loss of efficiency of about 5%. The CF/GQDs are considered as an efficient photocatalyst for MB degradation and other dyes.

First report of the damaging pest Meloidogyne enterolobii parasitizing mulberry (Morus alba L.) in Vietnam.

Mulberry (Morus alba L.) is highly important crop in Vietnam, playing a key role in the country's economy through sericulture, food supply, pharmaceuticals, and beverage industries (Nguyen et al., 2018; Rohela et al., 2020). Recently, many mulberry-growing areas in Lam Dong, Vietnam have reported severe symptoms associated with nematode infection, including yellowing leaves, stunted growth, and severe root galling, leading to a significant decline in mulberry productivity. From April to December 2022, twenty soil and root samples from mulberry-growing areas in Lam Dong (Da Teh: 11°28'48.11"N; 107°28'23.74"E elevation: 133m; Lam Ha 11°48'25.13"N; 108°14'7.13"E elevation: 848m) were collected to uncover the presence of Meloidogyne enterolobii parasitizing mulberry in Vietnam. One nematode population was randomly selected for characterizing in this study among analyzed nematode populations. Females were extracted from heavily galled roots (Fig. S1) from a single mulberry tree in Lam Dong, Vietnam, using a needle and forceps (Subbotin et al., 2021). The perineal patterns of adult females (n = 10) have an oval shape, with clearly visible phasmids, along with a prominently high and squared dorsal arch. The striae are smooth and coarse, while the perivulval region remains devoid of striae. The lateral lines appear indistinct, and the tail tip is easily observable. Morphometric measurements were as follows: body length = 585 ± 78 (464-724) µm, body width = 367 ± 75 (271-529) µm, neck length = 221.5 ± 30.7 (167-269.6) µm, stylet length = 13.1 ± 1.2 (11.4-15.1) µm, vulva-slit length 16.3±2.3 (10.4-18) µm, vulva-anus distance = 16.8±3.0 (11.4-18) µm, anus-tail tip distance = 10.3±2.1 (6.9-14.2) µm, interphasmidial distance = 15.9 ± 3.7 (10.3-23.4) µm. The morphology of this nematode population is highly in agreement with the original description of M. enterolobii (Yang & Eisenback, 1983). This population was also identified using the D2-D3 of 28S rRNA and 18S rRNA (Powers et al., 2017; Subbotin et al., 2006) regions. The D2-D3 of 28S rRNA sequences from this study (accession numbers: OR889633) exhibited 99.5-99.8% similarity to the sequences of M. enterolobii from GenBank (accession numbers: OR214950 and ON496981). While the 18S rRNA sequences (accession numbers: OR896547) showed 99.2-99.3% similarity to the sequences of M. enterolobii from GenBank (accession numbers: MZ955995, MZ531901, and MW488150). To carry out Koch's postulates, 2000 J2s from collected M. enterolobii egg masses (initial population) were inoculated on two-month-old plantlets of mulberry (n = 6), planted on 2L pots within a screenhouse, non-inoculated plantlets (n=6) served as negative controls. After 90 days post-inoculation, nematode reproduction factors (RF = final density (nematodes were extracted from the whole root system and corresponding soil samples (Subbotin et al., 2021)) / initial population) and root damage symptoms were evaluated. The inoculated plantlets exhibited consistent yellowing leaves, stunting, and root galling symptoms (Fig. S1), mirroring observations from the field, with an average RF of 11.5. Control plants displayed no symptoms. Root-knot nematodes extracted from the roots were identified as M. enterolobii through molecular analyses of D2-D3 of 28S and 18S rRNA regions (GenBank accession numbers: OR889634 (D2-D3 of 28S) and OR896548 (18S)), thereby confirming that mulberry acts as a host for M. enterolobii. Currently, this nematode has been reported to be associated with two different host plants, including guava (Trinh et al., 2022) and pomelo (Le et al., 2023). Our discovery marks the first documented case of Meloidogyne enterolobii parasitizing mulberry in Vietnam. While the impact on mulberry productivity remains to be really important for sericulture food supply, pharmaceuticals, and beverage industries; the aggressive nature of M. enterolobii, as observed in the field and confirmed by the screenhouse tests, raises concerns about potential economic losses in mulberry production. Therefore, further investigations are needed to assess the extent of M. enterolobii infestation in mulberry orchards and to develop effective control measures to safeguard the sustainability of mulberry cultivation in Vietnam.

Development of Cupriavidus necator H16 as a host for heterologous production of formate dehydrogenase I of Methylorubrum extorquens: Possibilities and limitations.

The discovery of formate dehydrogenase (Me-FDH1) from Methylorubrum extorquens has provided an avenue for sustainable CO2 fixation and utilization. However, the mass production of Me-FDH1 is challenging due to the presence of its unique tungsto-bis-metalopterin guanine dinucleotide (W-bis-MGD) cofactor, limiting its practical applications. In this study, C. necator H16 is proposed as a host for the large-scale production of Me-FDH1, utilizing fructose as a carbon source and its inherent machinery for cofactor synthesis. In a minimal salt medium, C. necator H16 could produce active Me-FDH1, which exhibited a specific activity of 80 to 100 U/mg for CO2 conversion to formate. In fed batch bioreactor experiments, approximately 50 g CDW/L (cell dry weight/L) and 10,000 U/L Me-FDH1 were achieved within 50 h. This study highlights C. necator H16 as the recombinant host for Me-FDH1, paving the way for the future development of efficient mass-production methods for this crucial enzyme.

Data on chemical composition of coffee husks and lignin microparticles as their extracted product.

Coffee husks are an abundant and underutilized biomass waste released from coffee production. Experimental analysis showed that coffee husks consisted of 39.2 ± 0.2 wt% cellulose, 12.6 ± 0.1 wt% hemicellulose, 23.3 ± 0.1 wt% Klason lignin, 2.9 ± 0.4 wt% acid-soluble lignin, 8.7 ± 0.2 wt% extractives, and 9.5 ± 0.2 wt% ash. Moreover, different minor elements, including K, Ca, Mg, Al, Fe, Ti, S, and Si, were found. Subsequently, coffee husks were used for the extraction of lignin using an alkaline treatment. As a result, lignin microparticles were formed with a relatively uniform size of 0.55 ± 0.11 mm. Altogether, the current article provided useful data for the valorization of coffee husks and the primary properties of lignin microparticles for further use.

Spray-dried Solid Lipid Nanoparticles for Enhancing Berberine Bioavailability via Oral Administration.

BACKGROUND: Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities, especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer's disease. However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations via this route. METHODS: BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN's cytotoxicity for loading BBR was determined with human embryonic kidney cells (HEK293). RESULTS: Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150% compared to the control sample at 100 µg/mL BBR-unloaded SLNs. CONCLUSION: Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.

Superiority of left heart deformation in early anthracycline-related cardiac dysfunction detection.

OBJECTIVE: This study aimed to assess the incidence of early cancer therapy-related cardiac dysfunction (CTRCD) and the characteristics of left and right heart deformations during anthracycline chemotherapy. METHODS: We prospectively enrolled a cohort of 351 chemotherapy-naïve women with breast cancer and cardiovascular risk factors who were scheduled to receive anthracycline. The left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (LV-GLS) and right ventricular and left atrial longitudinal strains were evaluated using echocardiography at baseline, before every subsequent cycles and at 3 weeks after the final anthracycline dose. CTRCD was defined as a new LVEF reduction by ≥10 percentage points to an LVEF<50% and/or a new relative decline in GLS by >15% from the baseline value. RESULTS: Eighteen (5.1%) patients had evidence of asymptomatic CTRCD during anthracycline treatment, and 50% developed CTRCD before completing the chemotherapy regimen. In the CTRCD group, while LV-GLS decrease significantly after the first dose of anthracycline, the reduction of right ventricular free-wall longitudinal strain and left atrial reservoir strain were observed after the second dose. Other strain indices could not be used to identify early CTRCD. CONCLUSIONS: Cardiotoxicity appeared soon after the initiation of anthracycline chemotherapy. Among the left-heart and right-heart mechanics, LV-GLS remains the best deformation indicator for detecting early CTRCD.

RP-HPLC-Based Flavonoid Profiling Accompanied with Multivariate Analysis: An Efficient Approach for Quality Assessment of Houttuynia cordata Thunb Leaves and Their Commercial Products.

Chemical profiling for quality monitoring and evaluation of medicinal plants is gaining attention. This study aims to develop an HPLC method followed by multivariate analysis to obtain HPLC profiles of five specific flavonoids, including rutin (1), hyperin (2), isoquercitrin (3), quercitrin (4), and quercetin (5) from Houttuynia cordata leaves and powder products and assess the quality of H. cordata samples. Eventually, we successfully established HPLC-based flavonoid profiles and quantified the contents of 32 H. cordata fresh leave samples and four powder products. The study also quantified the contents of those five essential flavonoids using an optimized RP-HPLC method. Peak areas of samples were then investigated with principal component analysis (PCA) and hierarchical cluster analysis (HCA) to evaluate the similarity and variance. Principal components in PCA strongly influenced by hyperin and quercetin showed that the samples were clustered into subgroups, demonstrating H. cordata samples' quality. The results of HCA showed the similarity and divided the samples into seven subgroups. In conclusion, we have successfully developed a practical methodology that combined the HPLC-based flavonoid profiling and multivariate analysis for the quantification and quality control of H. cordata samples from fresh leaves and powder products. For further studies, we will consider various environmental factors, including climate and soil factors, to investigate their effects on the flavonoid contents of H. cordata.

The sulfonadyns: a class of aryl sulfonamides inhibiting dynamin I GTPase and clathrin mediated endocytosis are anti-seizure in animal models.

We show that dansylcadaverine (1) a known in-cell inhibitor of clathrin mediated endocytosis (CME), moderately inhibits dynamin I (dynI) GTPase activity (IC50 45 µM) and transferrin (Tfn) endocytosis in U2OS cells (IC50 205 µM). Synthesis gave a new class of GTP-competitive dynamin inhibitors, the Sulfonadyns™. The introduction of a terminal cinnamyl moiety greatly enhanced dynI inhibition. Rigid diamine or amide links between the dansyl and cinnamyl moieties were detrimental to dynI inhibition. Compounds with in vitro inhibition of dynI activity <10 µM were tested in-cell for inhibition of CME. These data unveiled a number of compounds, e.g. analogues 33 ((E)-N-(6-{[(3-(4-bromophenyl)-2-propen-1-yl]amino}hexyl)-5-isoquinolinesulfonamide)) and 47 ((E)-N-(3-{[3-(4-bromophenyl)-2-propen-1-yl]amino}propyl)-1-naphthalenesulfonamide)isomers that showed dyn IC50 <4 µM, IC50(CME) <30 µM and IC50(SVE) from 12-265 µM. Both analogues (33 and 47) are at least 10 times more potent that the initial lead, dansylcadaverine (1). Enzyme kinetics revealed these sulfonamide analogues as being GTP competitive inhibitors of dynI. Sulfonadyn-47, the most potent SVE inhibitor observed (IC50(SVE) = 12.3 µM), significantly increased seizure threshold in a 6 Hz mouse psychomotor seizure test at 30 (p = 0.003) and 100 mg kg-1 ip (p < 0.0001), with similar anti-seizure efficacy to the established anti-seizure medication, sodium valproate (400 mg kg-1). The Sulfonadyn™ class of drugs target dynamin and show promise as novel leads for future anti-seizure medications.

Dataset of food delivery app users at a public university: Insights into digital transformation.

The food delivery apps (FDAs) have facilitated the connection between food service providers and consumers, enabling online ordering through smartphones and offline delivery in Vietnam. The Covid-19 pandemic has significantly impacted the food and beverage industry, accelerating the process of digital transformation and promoting sustainability through online-to-offline service. The usage of FDAs amongst consumers has exhibited a discernible escalation, primarily attributable to its ability to expedite the delivery of food in a hassle-free and convenient manner. Given the ongoing pandemic and the swift increase in demand for online food ordering services, particularly among the younger demographic, it has become imperative to comprehend the drivers that impel consumers to adopt these applications. This article aims to present a dataset pertaining to the decision-making factors that university students in Danang, Vietnam, take into account when they use FDAs and express positive feedback about them on the internet. The survey was conducted between September 2022 and January 2023 and gathered 346 usable responses. The results provide novel perspectives on the adoption of FDAs by university students, which is an emerging technology in the food and beverage sector. This dataset could be useful to various stakeholders, such as service providers, small and medium enterprises (SMEs), and vendors operating on these platforms, as it can help them acquire valuable insights into their customers' preferences and behavior. In addition, the dataset can serve as a basis for conducting comparative research in different universities or countries.

Impacts of COVID-19 crisis and some related factors on the mental health of 37150 Vietnamese students: a cross-sectional online study.

BACKGROUND: University students are vulnerable to changes due to COVID-19 pandemic. Although warning has been made about the impact of this crisis on students' mental health, there are barely any sufficient study. This work investigated how the pandemic affected the mental health of students at the Vietnam National University of Ho Chi Minh City (VNU-HCMC) and efficiency of available mental health supportive methods. METHODS: An online survey was conducted among students at Vietnam National University of Ho Chi Minh City (VNU-HCMC) from October 18, 2021, to October 25, 2021. Microsoft Excel 16.51 (Microsoft, USA) and R language, Epi packages 2.44 and 4.1.1 (rdrr.io) were used for data analysis. RESULTS: Thirty-seven thousand one hundred fifty students participated in the survey, including 48.4% female and 51.6% male. Online learning pressure was mainly recorded (65.1%). Many students suffered from sleeping disorders (56.2%). Some reported being victims of abuse (5.9%). Female students expressed a significantly higher level of distress than males, particularly the feeling of ambiguity about the purpose of life (p-value < 0.0001, OR: 0.94, 95% CI: [0.95-0.98]). Third-year students suffered higher stress levels than others, especially in online learning (68.8%, p-value < 0.05). Mental health statuses among students of different lockdown status regions were not significantly different. Therefore, lockdown status did not affect the stress levels of students which suggested that poor mental health outcomes seemed to root in the suspension of everyday university life rather than the prohibition of going out. CONCLUSIONS: During COVID-19, students experienced lots of stress and mental problems. These findings underscore the importance of academic and innovative activities, bringing attention to the needs of interactive study and extra-curricular activities.

Functional Graphene for Peritumoral Brain Microenvironment Modulation Therapy in Glioblastoma.

Peritumoral brain invasion is the main target to cure glioblastoma. Chemoradiotherapy and targeted therapies fail to combat peritumoral relapse. Brain inaccessibility and tumor heterogeneity explain this failure, combined with overlooking the peritumor microenvironment. Reduce graphene oxide (rGO) provides a unique opportunity to modulate the local brain microenvironment. Multimodal graphene impacts are reported on glioblastoma cells in vitro but fail when translated in vivo because of low diffusion. This issue is solved by developing a new rGO formulation involving ultramixing during the functionalization with polyethyleneimine (PEI) leading to the formation of highly water-stable rGO-PEI. Wide mice brain diffusion and biocompatibility are demonstrated. Using an invasive GL261 model, an anti-invasive effect is observed. A major unexpected modification of the peritumoral area is also observed with the neutralization of gliosis. In vitro, mechanistic investigations are performed using primary astrocytes and cytokine array. The result suggests that direct contact of rGO-PEIUT neutralizes astrogliosis, decreasing several proinflammatory cytokines that would explain a bystander tumor anti-invasive effect. rGO also significantly downregulates several proinvasive/protumoral cytokines at the tumor cell level. The results open the way to a new microenvironment anti-invasive nanotherapy using a new graphene nanomaterial that is optimized for in vivo brain delivery.

Antioxidant and Antibacterial Activity of Four Tannins Isolated from Different Sources and Their Effect on the Shelf-Life Extension of Vacuum-Packed Minced Meat.

Four tannin samples extracted from chestnut wood (tannin oenologique, TO), grape (tannin VR grape, TVG), oak gall (tannin galalcool, TG), and oak tree (tannin VR supra elegance, TE) were evaluated for antioxidant and antibacterial activity. The highest total phenolic content (TPC) values were observed in the order of TVG > TG > TE > TO (p < 0.05). The antioxidant activities of all samples were determined in terms of DPPH radical scavenging activity, reducing power, metal-chelating activity, and linoleic acid peroxidation assay. The antioxidant activities of all samples vary and no correlation was observed with the respective TPC values of each sample. Antibacterial activities indicate that all samples showed more or less inhibitory effects against selected Gram-positive and Gram-negative bacteria. Based on antioxidant and antibacterial activity, TO and TVG were selected for the beef mince quality preservation study during refrigerated storage. Both TO and TVG at two different concentrations, 0.25 and 0.5%, could cease the chemical and microbial changes as compared to the control sample. Although total viable count (TVC) did not show a significant difference, the H2S-producing bacteria count was lower in all samples treated with TO and TVG compared to sodium metabisulfite (SMS) and the control sample (p < 0.05). Therefore, TO and TVG could be promising natural food preservatives during refrigerated storage.

Wiskostatin and other carbazole scaffolds as off target inhibitors of dynamin I GTPase activity and endocytosis.

Wiskostatin (1-(3,6-dibromo-9H-carbazol-9-yl)-3-(dimethylamino)propan-2-ol) (1) is a carbazole-based compound reported as a specific and relatively potent inhibitor of the N-WASP actin remodelling complex (S-isomer EC50 = 4.35 µM; R-isomer EC50 = 3.44 µM). An NMR solution structure showed that wiskostatin interacts with a cleft in the regulatory GTPase binding domain of N-WASP. However, numerous studies have reported wiskostatin's actions on membrane transport and cytokinesis that are independent of the N-WASP-Arp2/3 complex pathway, but offer limited alternative explanation. The large GTPase, dynamin has established functional roles in these pathways. This study reveals that wiskostatin and its analogues, as well as other carbazole-based compounds, are inhibitors of helical dynamin GTPase activity and endocytosis. We characterise the effects of wiskostatin on in vitro dynamin GTPase activity, in-cell endocytosis, and determine the importance of wiskostatin functional groups on these activities through design and synthesis of libraries of wiskostatin analogues. We also examine whether other carbazole-based scaffolds frequently used in research or the clinic also modulate dynamin and endocytosis. Understanding off-targets for compounds used as research tools is important to be able to confidently interpret their action on biological systems, particularly when the target and off-targets affect overlapping mechanisms (e.g. cytokinesis and endocytosis). Herein we demonstrate that wiskostatin is a dynamin inhibitor (IC50 20.7 ± 1.2 µM) and a potent inhibitor of clathrin mediated endocytosis (IC50 = 6.9 ± 0.3 µM). Synthesis of wiskostatin analogues gave rise to 1-(9H-carbazol-9-yl)-3-((4-methylbenzyl)amino)propan-2-ol (35) and 1-(9H-carbazol-9-yl)-3-((4-chlorobenzyl)amino)propan-2-ol (43) as potent dynamin inhibitors (IC50 = 1.0 ± 0.2 µM), and (S)-1-(3,6-dibromo-9H-carbazol-9-yl)-3-(dimethylamino)propan-2-ol (8a) and (R)-1-(3,6-dibromo-9H-carbazol-9-yl)-3-(dimethylamino)propan-2-ol (8b) that are amongst the most potent inhibitors of clathrin mediated endocytosis yet reported (IC50 = 2.3 ± 3.3 and 2.1 ± 1.7 µM, respectively).

Optimization for a New XY Positioning Mechanism by Artificial Neural Network-Based Metaheuristic Algorithms.

This paper devotes a new method in modeling and optimizing to handle the optimization of the XY positioning mechanism. The fitness functions and constraints of the mechanism are formulated via proposing a combination of artificial neural network (ANN) and particle swarm optimization (PSO) methods. Next, the PSO is hybridized with the grey wolf optimization, namely PSO-GWO, which is applied to three scenarios in handling the single objective function. In order to search the multiple functions for the mechanism, the multiobjective optimization genetic algorithm (MOGA) is applied to the last scenario. The achieved results showed that the fitness functions are well-formulated using the PSO-based ANN method. In the scenario 1, the stroke achieved by the PSO-GWO (1852.9842 µm) is better than that gained from the GWO (1802.8087 µm). In the scenarios 2, the stress gained from the PSO-GWO (243.3183 MPa) is lower than that achieved from the GWO (245.0401 MPa). In the scenario 3, the safety factor retrieved from the PSO-GWO (1.9767) is greater than that achieved from the GWO (1.9278). In the scenario 4, by using MOGA, the optimal results found that the stroke is about (1741.3 µm) and the safety factor is 1.8929. The prediction results are well-fitted with the numerical and experimental verifications. The results of this paper are expected to facilitate the synthesis and analysis of compliant mechanisms and related engineering designs.

Design and Optimization for a New XYZ Micropositioner with Embedded Displacement Sensor for Biomaterial Sample Probing Application.

An XYZ compliant micropositioner has been widely mentioned in precision engineering, but the displacements in the X, Y, and Z directions are often not the same. In this study, a design and optimization for a new XYZ micropositioner are developed to obtain three same displacements in three axes. The proposed micropositioner is a planar mechanism whose advantage is a generation of three motions with only two actuators. In the design strategy, the proposed micropositioner is designed by a combination of a symmetrical four-lever displacement amplifier, a symmetrical parallel guiding mechanism, and a symmetrical parallel redirection mechanism. The Z-shaped hinges are used to gain motion in the Z-axis displacement. Four flexure right-circular hinges are combined with two rigid joints and two flexure leaf hinges to permit two large X-and-Y displacements. The symmetrical four-lever displacement amplifier is designed to increase the micropositioner's travel. The displacement sensor is built by embedding the strain gauges on the hinges of the micropositioner, which is developed to measure the travel of the micropositioner. The behaviors and performances of the micropositioner are modeled by using the Taguchi-based response surface methodology. Additionally, the geometrical factors of the XYZ micropositioner are optimized by teaching-learning-based optimization. The optimized design parameters are defined with an A of 0.9 mm, a B of 0.8 mm, a C of 0.57 mm, and a D of 0.7 mm. The safety factor gains 1.85, while the displacement achieves 515.7278 µm. The developed micropositioner is a potential option for biomedical sample testing in a nanoindentation system.

Modeling and Optimization for a New Compliant 2-dof Stage for Locating Biomaterial Samples by an Efficient Approach of a Kinetostatic Analysis-Based Method and Neural Network Algorithm.

The nanoindentation technique is employed to characterize the behaviors of biomaterials. Nevertheless, there is a lack of development of a miniaturized precise positioner for in situ nanoindentation. Besides, modeling behaviors of the positioner are restricted due to its complex kinematic characteristics. Therefore, this paper proposes a novel compliant two degrees of freedom (dof) stage for positioning a biomaterial sample in in situ nanoindentation. In addition, a new modeling and dimensional optimization synthesis method of the stage is developed. The proposed effective methodology is developed based on a kinetostatic analysis-based calculation method, the Lagrange approach, and a neural network algorithm. With an increased advance in artificial intelligence, a neural network algorithm is proposed to extend the applicability of artificial neural networks in optimizing the parameters of the stage. First, the 2-dof stage is built via a combination of an eight-lever displacement amplifier and a symmetric parallelogram mechanism. Second, a chain of mathematical equations of the 2-dof stage is constructed using a kinetostatic analysis-based method to calculate the ratio of displacement amplification and the input stiffness of the 2-dof stage. Then, the Lagrange method is utilized to formulate the dynamic equation of the 2-dof stage. Finally, a neural network algorithm is adopted to maximize the natural first frequency of the proposed stage. The optimal results determined that the frequency of the stage can achieve a high value of 112.0995 Hz. Besides, the formed mathematical models were relatively precise by comprising the simulation verifications.

Electrochemical modification of carbon nanotube fibres.

Covalent modification of the surface of carbon nanotube fibres (CNTFs) through electrochemical reduction of para-substituted phenyldiazonium salts and electrochemical oxidation of an aliphatic diamine is described. Following these strategies, diverse surface functionalities have been introduced while preserving the fibre bulk properties. The corresponding modified CNTFs were fully characterised by Raman spectroscopy, X-ray photoelectron spectroscopy, energy dispersive X-Ray, scanning electron microscopy and electrochemical impedance spectroscopy, exhibiting different surface properties from those of the unmodified CNTFs.

Extraction of curcumin from turmeric residue (Curcuma longa L.) using deep eutectic solvents and surfactant solvents.

Using waste materials to extract biologically active ingredients with green solvents is a new trend for sustainable development. Herein, different types of deep eutectic solvents (DESs) and surfactant solvents (SSs) were used to extract curcumin from turmeric residues (TRs), among which choline chloride-propylene glycol (ChCl-Pro) showed the highest yield. The optimized extraction conditions included a ChCl : Pro ratio of 1 : 2, water content in the DESs of 20%, solid : liquid ratio of 1 : 40 maintained for 60 min at 50 °C, and a TR particle size of 0.18 mm. The extraction yield was 54.2 mg g-1, which was 1.31 times higher than when methanol was used as a solvent. Distilled water was used to recover curcumin from the DES extract with a recovery yield of 99.7%. Furthermore, the antioxidant and acetylcholinesterase (AChE) inhibitory activities of the recovered curcumin were evaluated, with IC50 values of 25.58 ± 0.51 and 19.12 ± 0.83 µg mL-1, respectively. This study highlights the promising potential of using green solvents to extract bioactive compounds from waste materials.

Pyrimidyn-Based Dynamin Inhibitors as Novel Cytotoxic Agents.

Five focused libraries of pyrimidine-based dynamin GTPase inhibitors, in total 69 compounds were synthesised, and their dynamin inhibition and broad-spectrum cytotoxicity examined. Dynamin plays a crucial role in mitosis, and as such inhibition of dynamin was expected to broadly correlate with the observed cytotoxicity. The pyrimidines synthesised ranged from mono-substituted to trisubstituted. The highest levels of dynamin inhibition were noted with di- and tri- substituted pyrimidines, especially those with pendent amino alkyl chains. Short chains and simple heterocyclic rings reduced dynamin activity. There were three levels of dynamin activity noted: 1-10, 10-25 and 25-60 µM. Screening of these compounds in a panel of cancer cell lines: SW480 (colon), HT29 (colon), SMA (spontaneous murine astrocytoma), MCF-7 (breast), BE2-C (glioblastoma), SJ-G2 (neuroblastoma), MIA (pancreas), A2780 (ovarian), A431 (skin), H460 (lung), U87 (glioblastoma) and DU145 (prostate) cell lines reveal a good correlation between the observed dynamin inhibition and the observed cytotoxicity. The most active analogues (31 a,b) developed returned average GI50 values of 1.0 and 0.78 µM across the twelve cell lines examined. These active analogues were: N2 -(3-dimethylaminopropyl)-N4 -dodecyl-6-methylpyrimidine-2,4-diamine (31 a) and N4 -(3-dimethylaminopropyl)-N2 -dodecyl-6-methylpyrimidine-2,4-diamine (31 b).