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The main focus of anticancer drug discovery is on developing medications that are gentle on normal cells and should have the ability to target multiple anti-cancer pathways. Liver cancer is becoming a worldwide epidemic due to the highest occurring and reoccurring rate in some countries. Calotropis procera is a xerophytic herbal plant growing wildly in Saudi Arabia. Due to its anti-angiogenic and anticancer capabilities, "C. procera" is a viable option for developing innovative anticancer medicines. However, no study has been done previously, to discover angiogenic and anti-cancer targets which are regulated by C. procera in liver cancer. In this study, leaves, stems, flowers, and seeds of C. procera were used to prepare crude extracts and were fractionated into four solvents of diverse polarities. These bioactivity-guided solvent fractions helped to identify useful compounds with minimal side effects. The phytoconstituents present in the leaves and stem were identified by GC-MS. In silico studies were done to predict the anti-cancer targets by major bioactive constituents present in leaves and stem extracts. A human angiogenesis antibody array was performed to profile novel angiogenic targets. The results from this study showed that C. procera extracts are an ideal anti-cancer remedy with minimum toxicity to normal cells as revealed by zebrafish in vivo toxicity screening assays. The novel antiangiogenic and anticancer targets identified in this study could be explored to design medication against liver cancer.
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Calotropis , Neoplasias Hepáticas , Extractos Vegetales , Pez Cebra , Calotropis/química , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Línea Celular Tumoral , Neoplasias de la Mama/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Hojas de la Planta/química , Femenino , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/química , Simulación por Computador , Fitoquímicos/farmacología , Fitoquímicos/química , Fitoquímicos/análisis , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/análisisRESUMEN
This research was aimed to evaluate the phytochemical profile, antifungal, anti-hyperglycemic, as well as antioxidant activity competence of different extracts of Athyrium asplenioides through in-vitro approach. The A. asplenioides crude methanol extract contained considerable quantity of pharmaceutically precious phytochemicals (saponins, tannins, quinones, flavonoid, phenols, steroid, and terpenoids) than others (acetone, ethyl acetate, and chloroform). Interestingly, the crude methanol extract showed remarkable antifungal activity against Candida species (C. krusei: 19.3 ± 2 mm > C. tropicalis: 18.4 ± 1 mm > C. albicans: 16.5 ± 1 mm > C. parapsilosis: 15.5 ± 2 mm > C. glabrate: 13.5 ± 2 mm > C. auris: 7.6 ± 1 mm) at a concentration of 20 mg mL-1. The crude methanol extract also showed remarkable anti-hyperglycemic activity on concentration basis. Surprisingly, remarkable free radicals scavenging potential against DPPH (76.38%) and ABTS (76.28%) free radicals at a concentration of 20 mg mL-1. According to the findings, the A. asplenioides crude methanol extract contains pharmaceutically valuable phytochemicals and may be useful for drug discovery.
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Antifúngicos , Extractos Vegetales , Antifúngicos/farmacología , Extractos Vegetales/farmacología , Metanol , Antioxidantes/farmacología , Fitoquímicos/farmacología , Flavonoides , Radicales Libres , Hipoglucemiantes/farmacologíaRESUMEN
In this study, thermally activated kaolinite clay is explored as a suitable material for dye removal applications, which gave rise to highly reactive silica species in a broad range of aluminosilicate clusters. Multinuclear NMR studies described it as a short-range network in which Al sites in IV, V, and VI are coordinated, and Si is present mainly as Si(Q4(1Al)). Critical parameters for methylene blue (MB) were determined by the Placket Burman Design (PBD) as initial dye concentration, contact time, adsorbent dosage, pH and size. The % of MB removal studied after optimizing the parameters by central composite design (CCD), based on Response Surface Methodology, was found to be 90%. The adsorption kinetics and thermodynamics were systematically studied and reported by fitting them into different models. The maximum removal of the dye reached 97.8 mg/g according to the Freundlich isotherm, accomplished through chemisorption, following a pseudo-second-order reaction and the process is thermodynamically spontaneous and endothermic. The line spectrum of X-ray photoelectron spectroscopy (XPS) shows the participation of Si, Al, O, Ca and Na of Metakaolin (AK) and nitrogen of MB in the adsorption process. The appropriate stabilization of the N atom of the chromophore on the Si and Al atom in AK resulting from the ionic interaction on the surface is established from an increase in the binding energy of Al and Si. A single bridging oxygen signal at 532.32eVcorresponding to AK after dye adsorption tends to form siloanol/aluminol, and their interaction is lowered to 531.58eV. Regeneration of adsorbent after thermal treatment without loss of efficiency proved.
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Azul de Metileno , Contaminantes Químicos del Agua , Azul de Metileno/química , Cinética , Contaminantes Químicos del Agua/química , Concentración de Iones de Hidrógeno , Termodinámica , AdsorciónRESUMEN
The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values < 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.
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Aspergillus oryzae/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos/toxicidad , Animales , Organismos Acuáticos/química , Ascomicetos , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Femenino , Hongos/química , Sedimentos Geológicos , Humanos , Océano Índico , Concentración 50 Inhibidora , Células MCF-7 , Estructura Molecular , Sesquiterpenos Policíclicos , Pez CebraRESUMEN
Graphene, purely sp2-hybridized, has already been extensively studied for magnetoelectronics, however, the magnetotransport properties of graphene fibers (GrFib) have not been explored very well to date. Herein, unique magnetotransport properties of graphene fibers are detected. All the GrFib-samples show the highest positive magnetoresistance (MR â¼ 60%) at room temperature (300 K) that gradually decreases (MR â¼ 37%) at low temperature (5 K), indicating quite different behavior for a graphene derivative. The MR of three different morphologies are compared: single graphene sheet (60-100% at 300 K and 100-110% at 5 K under an applied magnetic field of 5 T), graphene foam (GF-100% at 300 K and 158% at 5 K under an applied magnetic field of 5 T), and graphene fiber (60% at 300 K and 37% at 300 K under an applied magnetic field of 5 T), and found that each morphology has a different magnitude of MR under similar magnitude of magnetic field and temperature. Unlike graphene and GF, GrFib shows a decreasing trend of MR at low temperatures, violating commonly used weak anti-localization phenomena in graphene. Technologically, each morphology of graphene has a unique set of magnetotransport properties that can be considered for particular magnetoelectronic devices depending upon the mechanical, electrical, and magnetotransport properties.
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Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., ß-sitosterol (4), ß-sitosterol ß-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing's sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1-3 did not show any promising anthelmintic effects.
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Antraquinonas/farmacología , Cichorium intybus/química , Extractos Vegetales/química , Esteroles/farmacología , Antihelmínticos , Antraquinonas/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Medicina Tradicional , Estructura Molecular , Naftalenos/química , Esteroles/aislamiento & purificaciónRESUMEN
BACKGROUND: Bitter gourd (Momordica charantia) has attracted the focus of researchers owing to its excellent anti-diabetic action. The beneficial effect of Momordica charantia on heart has been reported by in vitro and in vivo studies. However the developmental toxicity or potential risk of M. charantia on fetus heart development is largely unknown. Hence this study was designed to find out the developmental toxicity of M. charantia using zebrafish (Danio rerio) embryos. METHODS: The crude extracts were prepared from fruit and seeds of M. charantia. The Zebrafish embryos were exposed to serial dilution of each of the crude extract. The biologically active fractions were fractionated by C18 column using high pressure liquid chromatography. Fourier-transform infrared spectroscopy and gas chromatography coupled with mass spectrophotometry was done to identify chemical constituents in fruit and seed extract of M. charantia. RESULTS: The seed extract of M. charantia was lethal with LD50 values of 50 µg/ml to zebrafish embryos and multiple anomalies were observed in zebrafish embryos at sub-lethal concentration. However, the fruit extract was much safe and exposing the zebrafish embryos even to 200 µg/ml did not result any lethality. The fruit extract induced severe cardiac hypertrophy in treated embryos. The time window treatment showed that M. charantia perturbed the cardiac myoblast specification process in treated zebrafish embryos. The Fourier-transform infrared spectroscopy analyses revealed diverse chemical group in the active fruit fraction and five new type of compounds were identified in the crude seeds extract of M. charantia by gas chromatography and mass spectrophotometry. CONCLUSION: The teratogenicity of seeds extract and cardiac toxicity by the fruit extract of M. charantia warned that the supplementation made from the fruit and seeds of M. charantia should be used with much care in pregnant diabetic patients to avoid possible damage to developing fetus.
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Momordica charantia/química , Extractos Vegetales/toxicidad , Pez Cebra/embriología , Animales , Femenino , Frutas/química , Frutas/toxicidad , Humanos , Dosificación Letal Mediana , Masculino , Momordica charantia/toxicidad , Extractos Vegetales/análisis , Semillas/química , Semillas/toxicidadRESUMEN
The electrical and photo-electrical properties of exfoliated MoS2 were investigated in the dark and in the presence of deep ultraviolet (DUV) light under various environmental conditions (vacuum, N2 gas, air, and O2 gas). We examined the effects of environmental gases on MoS2 flakes in the dark and after DUV illumination through Raman spectroscopy and found that DUV light induced red and blue shifts of peaks (E12 g and A1 g) position in the presence of N2 and O2 gases, respectively. In the dark, the threshold voltage in the transfer characteristics of few-layer (FL) MoS2 field-effect transistors (FETs) remained almost the same in vacuum and N2 gas but shifted toward positive gate voltages in air or O2 gas because of the adsorption of oxygen atoms/molecules on the MoS2 surface. We analyzed light detection parameters such as responsivity, detectivity, external quantum efficiency, linear dynamic range, and relaxation time to characterize the photoresponse behavior of FL-MoS2 FETs under various environmental conditions. All parameters were improved in their performances in N2 gas, but deteriorated in O2 gas environment. The photocurrent decayed with a large time constant in N2 gas, but decayed with a small time constant in O2 gas. We also investigated the characteristics of the devices after passivating by Al2O3 film on the MoS2 surface. The devices became almost hysteresis-free in the transfer characteristics and stable with improved mobility. Given its outstanding performance under DUV light, the passivated device may be potentially used for applications in MoS2-based integrated optoelectronic circuits, light sensing devices, and solar cells.
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Although the electronic properties of graphene layers can be modulated by various doping techniques, most of doping methods cost degradation of structural uniqueness or electrical mobility. It is matter of huge concern to develop a technique to improve the electrical properties of graphene while sustaining its superior properties. Here, we report the modification of electrical properties of single- bi- and trilayer graphene by chemical reaction with potassium nitrate (KNO3) solution. Raman spectroscopy and electrical transport measurements showed the n-doping effect of graphene by KNO3. The effect was most dominant in single layer graphene, and the mobility of single layer graphene was improved by the factor of more than 3. The chemical doping by using KNO3 provides a facile approach to improve the electrical properties of graphene layers sustaining their unique characteristics.
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Artificial intelligence (AI) has recently emerged as a unique developmental influence that is playing an important role in the development of medicine. The AI medium is showing the potential in unprecedented advancements in truth and efficiency. The intersection of AI has the potential to revolutionize drug discovery. However, AI also has limitations and experts should be aware of these data access and ethical issues. The use of AI techniques for drug discovery applications has increased considerably over the past few years, including combinatorial QSAR and QSPR, virtual screening, and denovo drug design. The purpose of this survey is to give a general overview of drug discovery based on artificial intelligence, and associated applications. We also highlighted the gaps present in the traditional method for drug designing. In addition, potential strategies and approaches to overcome current challenges are discussed to address the constraints of AI within this field. We hope that this survey plays a comprehensive role in understanding the potential of AI in drug discovery.
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One of the most fascinating 2D nanomaterials (NMs) ever found is various members of MXene family. Among them, the titanium-based MXenes, with more than 70% of publication-related investigations, are comparatively well studied, producing fundamental foundation for the 2D MXene family members with flexible properties, familiar with a variety of advanced novel technological applications. Nonetheless, there are still more candidates among transitional metals (TMs) that can function as MXene NMs in ways that go well beyond those that are now recognized. Systematized details of the preparations, characteristics, limitations, significant discoveries, and uses of the novel M-based MXenes (M-MXenes), where M stands for non-Ti TMs (M = Sc, V, Cr, Y, Zr, Nb, Mo, Hf, Ta, W, and Lu), are given. The exceptional qualities of the 2D non-Ti MXene outperform standard Ti-MXene in several applications. There is many advancement in top-down as well as bottom-up production of MXenes family members, which allows for exact control of the M-characteristics MXene NMs to contain cutting-edge applications. This study offers a systematic evaluation of existing research, covering everything in producing complex M-MXenes from primary limitations to the characterization and selection of their applications in accordance with their novel features. The development of double metal combinations, extension of additional metal candidates beyond group-(III-VI)B family, and subsequent development of the 2D TM carbide/TMs nitride/TM carbonitrides to 2D metal boride family are also included in this overview. The possibilities and further recommendations for the way of non-Ti MXene NMs are in the synthesis of NMs will discuss in detail in this critical evaluation.
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INTRODUCTION: Raw milk may contain pathogenic microorganisms harmful to humans, e.g., multidrug-resistant Escherichia coli non-O157:H7, which can cause severe colitis, hemolytic uremia, and meningitis in children. No studies are available on the prevalence of Shiga toxin-producing E. coli (STEC O157:H7) in sick or healthy dairy animals in the Khyber Pakhtunkhwa Province of Pakistan. AIM: This study aimed to isolate, characterize, and detect antibiotic resistance in STEC non-O157:H7 from unpasteurized milk of dairy bovines in this province. MATERIALS AND METHODS: We collected raw milk samples (n = 800) from dairy farms, street vendors, and milk shops from different parts of the Khyber Pakhtunkhwa Province. E. coli was isolated from these samples followed by latex agglutination tests for serotyping. The detection of STEC was conducted phenotypically and confirmed by the detection of virulence genes genotypically. An antibiogram of STEC isolates was performed against 12 antibiotics using the disc diffusion method. RESULTS: A total of 321 (40.12%) samples were found to be positive for E. coli in this study. These samples were processed for the presence of four virulence genes (Stx1, Stx2, ehxA, eae). Forty samples (5.0%) were STEC-positive. Of these, 38%, 25%, 19%, and 18% were positive for Stx1, Stx2, ehxA, and eae, respectively. Genotypically, we found that 1.37% of STEC isolates produced extended-spectrum beta-lactamase (ESBL) and contained the blaCTX M gene. Resistance to various antibiotics ranged from 18% to 77%. CONCLUSION: This study highlights the risk of virulent and multidrug-resistant STEC non-O157:H7 in raw milk and the need for proper quality surveillance and assurance plans to mitigate the potential public health threat.
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Layered two-dimensional (2D) materials have gained popularity thanks to their atomically thin physique and strong coupling with light. Here, we investigated a wide band gap (≥ 2 eV) 2D material, i.e., tin disulfide (SnS2), and decorated it with silver nanoparticles, Ag-NPs, for broadband photodetection. Our results show that the SnS2/Ag-NPs devices exhibit broadband photodetection ranging from the ultraviolet to near-infrared (250-1050 nm) spectrum with decreased rise/decay times from 8/20 s to 7/16 s under 250 nm wavelength light compared to the bare SnS2 device. This is attributed to the localized surface plasmon resonance effect and the wide band gap of SnS2 crystal. Furthermore, the HfO2-passivated SnS2/Ag-NPs devices exhibited high photodetection performance in terms of photoresponsivity (â¼12 500 A W-1), and external quantum efficiency (â¼6 × 106%), which are significantly higher compared to those of bare SnS2. Importantly, after HfO2 passivation, the SnS2/Ag-NPs photodetector maintained the stable performance for several weeks with merely â¼5.7% reduction in photoresponsivity. Lastly, we fabricated a flexible SnS2/Ag-NPs photodetector, which shows excellent and stable performance under various bending curvatures (0, 20, and 10 mm), as it retains â¼80% of its photoresponsivity up to 500 bending cycles. Thus, our study provides a simple route to realize broadband and stable photoactivity in flexible 2D material-based devices.
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Most commercial drones utilize a traditional proportional-integral-derivative (PID) controller because of its design simplicity. However, the traditional PID controller has certain limitations in terms of optimality and robustness; it is difficult to actively adjust the PID gains under some disturbances. In this study, we demonstrated an analog-digital hybrid computing platform based on double-gate SnS2 memtransistors to implement a self-tuning/energy-efficient PID controller in drones. The customized analog circuit with memtransistors executes the PID control algorithm with low power consumption; we experimentally verified that the energy consumption of the proposed hybrid computing-based PID controller is only 63% of that of the traditional PID controller. In addition, the precise tunability of analog conductance states in the memtransistor proved to be capable of reconfiguring the performance of the PID controller, where the developed self-tuning algorithm can automatically find the optimal PID control performance.
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The fixed-dose combination of Amlodipine Besylate (ADB) with Perindopril Tertbutylamine (PTBA) drug is used to treat patients with mild-to-moderate hypertension. In recent times researchers are interested to find the efficient analytical method development and validation for the simultaneous determination of ADB and PTBA in a fixed-dose, film-coated tablet. Therefore, the current study was performed with a reverse-phase liquid chromatography method developed to simultaneously analyze ADB and PTBA in film-coated tablets as fixed-dose combinations. The linearity of the proposed method was calculated by preparing six different mixtures of both ADB and PTBA in the mobile phase. The concentration of both the analytes was analyzed at 56mg/100 mL to 84mg/100 mL and 32mg/100 mL to 48mg/100 mL, respectively. The ratio of acetonitrile and phosphate buffer was 35:65. The flow rate was adjusted to 1.5 ml per minute to reduce the retention time. The validation study was performed for the parameters specificity, linearity, precision, range, limit of detection, limit of quantification, accuracy/biasness, and robustness. The relative percentage standard deviation for Perindopril Tertbutyl amine was 0.148%, and for Amlodipine is 0.312%. These results show that the advanced analysis method for simultaneous analysis of fixed-dose is precise. The theoretical IR spectra were also calculated by Gaussian 9.2 by employing the B3LYP functional at density functional theory (DFT) level study. All these parameters studied in this work authenticate the effectiveness of the developed validation method and ensure its repeatability/reproducibility accordingly. To the best of our knowledge, this is the first time to develop a new fast, and easy method for simultaneous identification and quantification of ADB and PTBA by high-performance liquid chromatography (HPLC) with a time-efficient and cost-effective approach.
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This review article attempts to provide a comprehensive review of the recent progress in cerium oxide (CeO2)-based resistive random-access memories (RRAMs). CeO2 is considered the most promising candidate because of its multiple oxidation states (Ce3+ and Ce4+), remarkable resistive-switching (RS) uniformity in DC mode, gradual resistance transition, cycling endurance, long data-retention period, and utilization of the RS mechanism as a dielectric layer, thereby exhibiting potential for neuromorphic computing. In this context, a detailed study of the filamentary mechanisms and their types is required. Accordingly, extensive studies on unipolar, bipolar, and threshold memristive behaviors are reviewed in this work. Furthermore, electrode-based (both symmetric and asymmetric) engineering is focused for the memristor's structures such as single-layer, bilayer (as an oxygen barrier layer), and doped switching-layer-based memristors have been proved to be unique CeO2-based synaptic devices. Hence, neuromorphic applications comprising spike-based learning processes, potentiation and depression characteristics, potentiation motion and synaptic weight decay process, short-term plasticity, and long-term plasticity are intensively studied. More recently, because learning based on Pavlov's dog experiment has been adopted as an advanced synoptic study, it is one of the primary topics of this review. Finally, CeO2-based memristors are considered promising compared to previously reported memristors for advanced synaptic study in the future, particularly by utilizing high-dielectric-constant oxide memristors.
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Transition metal dichalcogenides (TMDs) have gained significant attention as next-generation semiconductor materials that could potentially overcome the integration limits of silicon-based electronic devices. However, a challenge in utilizing TMDs as semiconductors is the lack of an established PN doping method to effectively control their electrical properties, unlike those of silicon-based semiconductors. Conventional PN doping methods, such as ion implantation, can induce lattice damage in TMDs. Thus, chemical doping methods that can control the Schottky barrier while minimizing lattice damage are desirable. Here, we focus on the molybdenum ditelluride (2H-MoTe2), which has a hexagonal phase and exhibits ambipolar field-effect transistor (FET) properties due to its direct band gap of 1.1 eV, enabling concurrent transport of electrons and holes. We demonstrate the fabrication of p- or n-type unipolar FETs in ambipolar MoTe2 FETs using self-assembled monolayers (SAMs) as chemical dopants. Specifically, we employ 1H,1H,2H,2H perfluorooctyltriethoxysilane and (3-aminopropyl)triethoxysilane as SAMs for chemical doping. The selective SAMs effectively increase the hole and electron charge transport capabilities in MoTe2 FETs by 18.4- and 4.6-fold, respectively, due to the dipole effect of the SAMs. Furthermore, the Raman shift of MoTe2 by SAM coating confirms the successful p- and n-type doping. Finally, we demonstrate the fabrication of complementary inverters using SAMs-doped MoTe2 FETs, which exhibit clear full-swing capability compared to undoped complementary inverters.
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In the quest for high-density integration and massive scalability, ferroelectric-based devices provide an achievable approach for nonvolatile crossbar array (CBA) architecture and neuromorphic computing. In this report, ferroelectric-semiconductor (Pt/BaTiO3/ZnO/Au) heterojunction-based devices are demonstrated to exhibit nonvolatile and synaptic characteristics. In this study, the ferroelectric (BaTiO3) layer was modulated at various growth temperatures of 350 °C, 450 °C, 550 °C and 650 °C. Growing temperature in the ferroelectric layer has a significant impact on resistive switching. The ferroelectricity of the BaTiO3 thin film enhanced by increasing temperature causes a substantial shift in the interface state density at heterojunction interface, which is crucial for self-rectification. Furthermore, this self-rectifying property advances to reduce the crosstalk problem without any selector device. Enhanced resistive switching and neuromorphic applications have been demonstrated using BaTiO3 heterostructure devices at 550 °C. The dynamic ferroelectric polarization switching in this heterojunction demonstrated linear conductance change in artificial synapses with 91 % recognition accuracy. Ferroelectric polarization reversal with a depletion region at the heterojunction interface is the responsible mechanism for the switching in these devices. Thus, these findings pave the way for designing low power high-density crossbar arrays and neuromorphic application based on ferroelectric-semiconductor heterostructures.
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Purpose: Curcumin (CUR) and piperine (PP) are bioactive compounds with prominent pharmacological activities that have been investigated for the treatment of various diseases. The aim of the present study is to develop Bio-SNEDDS for CUR and PP as a combined delivery system for cancer therapy. Methods: CUR and PP loaded Bio-SNEDDSs with varying compositions of bioactive lipid oils, surfactants, and cosolvents were prepared at room temperature. Bio-SNEDDSs were characterized using a Zetasizer Nano particle size analyzer and further examined by transmission electron microscopy (TEM) for morphology. The in vivo toxicity of the preparations of Bio-SNEDDS was investigated in wild-type zebrafish embryos and cytotoxicity in THP-1 (human leukemia monocytic cells), Jurkat (human T lymphocyte cells) and HUVEC (non-cancerous normal) cells. Results: Bio-SNEDDSs were successfully developed with black seed oil, Imwitor 988, Transcutol P and Cremophor RH40 at a ratio of 20/20/10/50 (%w/w). The droplet size, polydispersity index and zeta potential of the optimized Bio-SNEDDS were found to be 42.13 nm, 0.59, and -19.30 mV, respectively. Bio-SNEDDS showed a spherical structure evident by TEM analysis. The results showed that Bio-SNEDDS did not induce toxicity in zebrafish embryos at concentrations between 0.40 and 30.00 µg/mL. In TG (fli1: EGFP) embryos treated with Bio-SNEDDS, there was no change in the blood vessel structure. The O-dianisidine staining of Bio-SNEDDS treated embryos at 48 h post-fertilization also showed a significant reduction in the number of blood cells compared to mock (DMSO 0.1% V/V) treated embryos. Bio-SNEDDS induced significant levels of cytotoxicity in the hematological cell lines THP-1 and Jurkat, while low toxicity in normal HUVEC cell lines was observed with IC50 values of 18.63±0.23 µg/mL, 26.03 ± 1.5 µg/mL and 17.52 ± 0.22 µg/mL, respectively. Conclusion: Bio-SNEDDS exhibited enhanced anticancer activity and could thus be an important new pharmaceutical formulation to treat leukemia.
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Curcumina , Neoplasias Hematológicas , Leucemia , Nanopartículas , Animales , Humanos , Preparaciones Farmacéuticas , Curcumina/farmacología , Pez Cebra , Sistemas de Liberación de Medicamentos/métodos , Solubilidad , Administración Oral , Tensoactivos/química , Emulsiones/química , Nanopartículas/química , Disponibilidad BiológicaRESUMEN
Ticks pose a major threat to cattle health and production in Pakistan because they transmit pathogens of diseases like Babesiosis and Theileriosis. Hyalomma spp., found across Africa, Asia, and Europe, are especially problematic. This study explored biocontrol of Hyalomma spp. using spore-free fungal culture filtrates collected from dairy farm soil in Kohat, Pakistan. Three fungal species of the genera Alternaria, Aspergillus, and Penicillium were isolated, and their filtrates were tested against tick adults and larvae. Filtrate concentrations were prepared at different strengths. Data were taken after the exposure of adults and larvae ticks to various concentrations of the fungal filtrates. Results indicated that at 100% concentration, all fungal filtrates induced 100% mortality in adults and larvae. Decreasing filtrate concentration lowered tick mortality. The lowest concentration caused the least mortality. The effect was time- and dose-dependent. In conclusion, spore-free fungal culture filtrates can provide biocontrol of Hyalomma spp. in a time- and concentration-dependent manner. Further research should explore the active compounds causing mortality and optimal application methods. The process outlined here provides a natural biocontrol alternative to chemical pesticides to reduce tick infestations and associated cattle diseases in Pakistan.