Heteroatom-doped carbon dots (C-dots) have captured widespread research interest owing to high fluorescence and biocompatibility for multimodal bioimaging applications. Here, we exemplify a rapid, ...facile synthesis of ethylenediamine (EDA)-functionalized transition metal ion (Mn2+, Fe2+, Co2+, and Ni2+)-doped C-dots via one-pot microwave (MW)-assisted pyrolysis at 800 W within 6 min using Citrus limon (lemon) extract as a carbon source. During MW pyrolysis, the precursor extract undergoes simultaneous carbonization and doping of metal ions onto C-dot surfaces in the presence of EDA. The EDA-functionalized transition metal ion-doped C-dots (i.e., Mn/C, Fe/C, Co/C, and Ni/C-dots) are collectively termed as TMCDs. The water-soluble TMCDs exhibited a size of 3.2 ± 0.485 nm and were enriched with amino and oxo functionalities and corresponding metal-oxide traces on the surfaces, as revealed from Fourier transfer infrared and X-ray photoelectron spectroscopy analyses. Interestingly, TMCDs demonstrated excitation-wavelength-dependent emission with brighter photoluminescence (PL) at 460 nm. Compared to pristine C-dots with a PL quantum yield (QY) of 48.31% and a fluorescence lifetime of 3.6 ns, the synthesized Mn/C, Fe/C, Co/C, and Ni/C-dots exhibited PL QY values of 35.71, 41.72, 75.07, and 50.84% as well as enhanced fluorescence lifetimes (τav) of 9.4, 8.6, 9.2, and 8.9 ns, respectively. The TMCDs significantly exhibited enhanced biocompatibility in human colon cancer cells (SW480) for fluorescence bioimaging and showed ferromagnetic and superparamagnetic behavior with vibrant T 1-contrast ability. Interestingly, the maximum longitudinal (r 1) relaxivity of 0.341 mM–1 s–1 was observed for Mn/C-dots in comparison to that of 3.1–3.5 mM–1 s–1 of clinically used Gd-DTPA magnetic resonance (MR)-contrast agent in vitro (1.5 T). Similarly, the maximum longitudinal relaxivity (r 1) of 0.356 mM–1 s–1 was observed for Ni/C-dots (1.5 T) with respect to 4.16 ± 0.02 mM–1 s–1 attained for Gd-DTPA in vivo (8.45 T). Thus, the rapid, energy-efficient MW-assisted pyrolysis presents lemon extract derived, EDA-functionalized TMCDs with enhanced PL and efficient T 1 contrast as potential magneto-fluorescent nanoprobes for dual-modality bioimaging applications.
OqxAB efflux pump has been found to mediate multidrug resistance (MDR) in various bacteria over the past decades. The updates on the nature and epidemiology of OqxAB efflux pump need to be fully ...reviewed to broaden our understanding of this MDR determinant.
A literature search using the keyword of "oqxAB" was conducted in the online databases of Pubmed and ISI Web of Science with no restriction on the date of publication. The 87 publications were included into this review as references due to their close relevance to the nature and/or epidemiology of OqxAB efflux pump.
The
gene generally locates on chromosome and/or plasmids flanked by IS26-like elements in clinical isolates of
and
, conferring low to intermediated resistance to quinoxalines, quinolones tigecycline, nitrofurantoin, several detergents and disinfectants (benzalkonium chloride, triclosan and SDS). It could co-spread with other antimicrobial resistance genes (
,
and
etc.), virulence genes and heavy metal resistance genes (
and
operons). Both RarA (activator) and OqxR (repressor) play important roles on regulation of the expression of OqxAB.
The dissemination of
gene may pose a great risk on food safety and public health. Further investigation and understanding of the natural functions, horizontal transfer, and regulation mechanism of the OqxAB efflux pump will aid in future strategies of antimicrobial usage.
The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and ...development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.
Fusarium mycotoxins are the most economically important fungal toxins. Fumonisins, zearalenone and trichothecenes (T-2 toxin, HT-2 toxin, deoxynivalenol, nivalenol etc) are the major representatives ...and most studied of Fusarium mycotoxins. The Fusarium mycotoxins contaminate cereal grains, animal feeds and human food products, and cause huge economic losses and pose a threat to animal and human health globally. Depending on the type, the toxicity of Fusarium mycotoxins and the mechanisms have been well investigated. Epigenetic modifications (DNA methylation, histone modifications and regulation of non-coding RNA) have been implicated in various human diseases and the toxicities in animals caused by Fusarium mycotoxins, including carcinogenesis, genotoxicity and reproductive disorders. On the basis of recently documented data, this review discussed the relationship between the epigenetic modifications and Fusarium mycotoxins-induced toxicities.
•Fusarium mycotoxins are the most economically important fungal toxins.•Epigenetic modifications has become an evolving trend in the field of toxicology of mycotoxins.•Epigenetic mechanisms are involved in the toxicities of Fusarium mycotoxins such as reproductive disorders.•The epigenetic regulating network of Fusarium mycotoxins induced toxicity is proposed.
The development of antibiotic resistance in bacteria is a major public health threat. Infection rates of resistant pathogens continue to rise against nearly all antimicrobials, which has led to ...development of different strategies to combat the antimicrobial resistance. In this review, we discuss how the newly popular CRISPR-cas system has been applied to combat antibiotic resistance in both extracellular and intracellular pathogens. We also review a recently developed method in which nano-size CRISPR complex was used without any phage to target the mecA gene. However, there is still challenge to practice these methods in field against emerging antimicrobial resistant pathogens.
A broad-spectrum microbiological inhibition method has been developed for rapidly screening different kinds of antibiotics such as β-lactam, aminoglycosides, tetracyclines, sulfonamides, macrolides, ...lincosamides and quinolones in milk, chicken egg and honey by using an easy sample preparation. The microbiological system in microtiter plates consists of an agar medium, a mixture of nutrients, test bacteria (
C953), bromocresol purple, and other supplements such as trimethoprim, chloramphenicol, streptomycin and enrofloxacin which helps to improve the detection capability of the microbiological system toward the chosen antibiotics. It was observed that the limit of detection of the kit used in present study for all kinds of antibiotics in milk were lower than or close to maximum residue limits determined by EU or CODEX. For chicken egg and honey, the detection capability of the kit was similar to that determined in milk. Moreover, it was revealed that the kit in present study was more sensitive to aminoglycosides, macrolides and quinolones in various matrixes than internationally available commercial kits. The false-positive and false-negative rates for both were 0%. The coefficient of variations among various factors was all less than 4%. Additionally, the quality guarantee period of the kit was more than 6 months at 4°C. A good correlation between the kit results and the LC-MS/MS results for milk was also observed, which revealed that the kit was reliable to screen antibiotics residues in incurred samples.
Valvular heart disease (VHD) is an active process involving a wide range of pathological changes. The major complications of VHD are stenosis and regurgitation, which are macroscopic phenomena, ...induced in part through cellular changes. Altered expression of mitochondria associated genes causes membrane potential depolarization, leading to the increased levels of apoptosis observed in cardiac dysfunction. Objective of this study is to find molecular medicine candidates that can control expression of the key mitochondria apoptosis regulatory genes. Present study aims to assess the way microRNA are involved in regulating mitochondrial apoptosis regulatory genes and observation of their expression in the heart valve dysfunction. Apoptotic genes PUMA and DRP1 were found to be highly expressed, whereas anti-apoptotic gene ARC was down regulated. The expression level of GATA-4 transcription factor was also reduced in cardiac valve tissues. MicroRNAs miR-15a and miR-29a were repressed, while miR-214 was up regulated. Furthermore, study showed that PUMA, DRP1 and ARC expression might be attenuated by their respective miRNAs. Our results indicate that mitochondria regulatory genes might be controlled by miR-15a, miR-29a and miR-214, in VHD patients. Present study may provide platform for future research regarding potential therapeutic role of miRNAs in CVDs.
•Disruption of mitochondrial membrane regulatory genes lead to apoptosis during cardiac valve dysfunction.•Pro-apoptotic PUMA and DRP1 are up regulated while anti-apoptotic ARC is down regulated in stenosis and regurgitation.•The expression of GATA-4 transcription factor is reduced in valve dysfunction during apoptosis.•miR-15a and miR-29a are repressed, while miR-214 is up regulated.•The level of ROS is high with reduced level of antioxidant enzymatic activities of SOD and CAT in VHD.
This paper describes a quadcopter manipulator system, an aerial robot with an extended workspace, its controller design, and experimental validation. The aerial robot is based on a quadcopter with a ...three degree of freedom robotic arm connected to the base of the vehicle. The work aims to create a stable airborne robot with a robotic arm that can work above and below the airframe, regardless of where the arm is attached. Integrating a robotic arm into an underactuated, unstable system like a quadcopter can enhance the vehicle's functionality while increasing instability. To execute a mission with accuracy and reliability during a real‐time task, the system must overcome the inter‐coupling effects and external disturbances. This work presents a novel design for a robust adaptive feedback linearization controller with a model reference adaptive controller and hardware implementation of the quadcopter manipulator system with plant uncertainties. The closed‐loop stability of the aerial robot and the tracking error convergence with the robust controller is analyzed using Lyapunov stability analysis. The quadcopter manipulator system is custom developed in the lab with an off‐the‐shelf quadcopter and a 3D‐printed robotic arm. The robotic system architecture is implemented using a Jetson Nano companion computer for autonomous onboard flight. Experiments were conducted on quadcopter manipulator system to evaluate the autonomous aerial robot's stability and trajectory tracking with the proposed controller.
The aims of the present study were to establish optimal doses and provide an alternate CO
for florfenicol against
based on pharmacokinetic-pharmacodynamic integration modeling. The recommended dose ...(30 mg/kg b.w.) were administered in healthy pigs through intramuscular and intravenous routes for pharmacokinetic studies. The main pharmacokinetic parameters of
, AUC
, AUC, Ke,
, MRT,
and Cl
, were estimated as 4.44 μg/ml, 88.85 μg⋅h/ml, 158.56 μg⋅h/ml, 0.048 h
, 14.46 h, 26.11 h, 4 h and 0.185 L/h⋅kg, respectively. The bioavailability of florfenicol was calculated to be 99.14% after I.M administration. A total of 124
from most cities of China were isolated to determine the minimum inhibitory concentration (MIC) of florfenicol. The MIC
and MIC
were calculated as 1 and 2 μg/ml. A serotype 2
(WH-2), with MIC value similar to MIC
, was selected as a representative for an
and
pharmacodynamics study. The MIC values of WH-2 in TSB and plasma were 2 μg/ml, and the MBC/MIC ratios were 2 in TSB and plasma. The MPC was detected to be 3.2 μg/ml. According to inhibitory sigmoid
model, plasma AUC
/MIC values of florfenicol versus
were 37.89, 44.02, and 46.42 h for the bactericidal, bacteriostatic, and elimination activity, respectively. Monte Carlo simulations the optimal doses for bactericidal, bacteriostatic, and elimination effects were calculated as 16.5, 19.17, and 20.14 mg/kg b.w. for 50% target attainment rates (TAR), and 21.55, 25.02, and 26.85 mg/kg b.w. for 90% TAR, respectively. The PK-PD cutoff value (CO
) analyzed from MCS for florfenicol against
was 1 μg/ml which could provide a sensitivity cutoff value. These results contributed an optimized alternative to clinical veterinary medicine and showed that the dose of 25.02 mg/kg florfenicol for 24 h could have a bactericidal action against
after I.M administration. However, it should be validated in clinical practice in the future investigations.
Multi-agent based small scaled smart grid reinforcement scheme is proposed to manage energy resources by enhancing resilience to supply power to critical loads in peak demand by leveraging demand ...side management (DSM) for smoothing load profile and optimal energy storage system (ESS) scheduling in response to grid cost. Interconnected microgrids comprise diverse energy resources that allow sharing energy to balance fluctuation by deploying a market that rewards cheap energy. Three stages are defined in this proposed scheme. In the first stage, without DER, consumption charges are reduced to 7.1% through DSM, but customer comfort is compromised. In the second stage, microgrids comprise RER; energy consumption-related charges are reduced to 92.2% by the feed-in tariff (FIT) Program. In the final stage, the inclusion of energy market for trading among microgrids (ESS, diesel and RER) resulting in reduced charges greater than charges incurred from the grid is defined by 122.1%. The findings show that the average power drawn from utility grid increased from 134.7kW to 205.3kW, and peak demand decreased from 591kW to 495kW. Integer linear programming optimization technique is applied to allow the optimal dispatch of microgrids generation to reduce the operation cost to 42.64%. Less reliance on the grid, flexible energy use, and avoiding costly electricity purchases are achieved through DSM, effective resources scheduling, and energy trading.
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