Most half-sandwich metal anticancer complexes are non-fluorescent, which results in an uncertain mechanism of action (MoA). We designed and synthesized eight fluorescent half-sandwich iridium (Ir) ...and ruthenium (Ru) complexes by introducing rhodamine derivatives into the N^N-chelating ligand. These complexes have features of bio-imaging and anticancer agents and may merit future development as novel anticancer agents.
Metallothioneins (MTs) are low molecular weight cysteine-rich proteins that bind to metals. Owing to their high cysteine (Cys) content, MTs are effective mediators of heavy metal detoxification. To ...enhance the heavy metal binding ability of MT from the freshwater crab Sinopotamon henanense (ShMT), sequence-based multiple sequence alignment (MSA) and structure-based molecular docking simulation (MDS) were conducted in order to identify amino acid residues that could be mutated to bolster such metal-binding activity. Site-directed mutagenesis was then used to modify the primary structure of ShMT, and the recombinant proteins were further enhanced using the SUMO fusion expression system to yield SUMO-ShMT1, SUMO-ShMT2, and SUMO-ShMT3 harboring one-, two-, and three- point mutations, respectively. The resultant modified proteins were primarily expressed in a soluble form and exhibited the ability to readily bind to heavy metals. Importantly, these modified proteins exhibited significantly enhanced heavy metal binding capacities, and they improved Cd2+, Cu2+ and Zn2+ tolerance and bioaccumulation in Escherichia coli (E. coli) in a manner dependent upon the number of introduced point mutations (SUMO-ShMT3 > SUMO-ShMT2 > SUMO-ShMT1 > SUMO-ShMT > control). Indeed, E. coli cells harboring the pET28a-SUMO-ShMT3 expression vector exhibited maximal Cd2+, Cu2+, and Zn2+ bioaccumulation that was increased by 1.86 ± 0.02-, 1.71 ± 0.03-, and 2.13 ± 0.02-fold relative to that in E. coli harboring the pET28a-SUMO-ShMT vector. The present study offers a basis for the preparation of genetically engineered bacteria that are better able to bioaccumulate and tolerate heavy metals, thus providing a foundation for biological heavy metal water pollution treatment.
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•ShMT1, ShMT2 and ShMT3 were obtained by site-directed mutagenesis.•ShMT3 can bind 9 divalent metal ions, which is 1.5 times as much as ShMT.•Cd2+ bioaccumulation of ShMT3 is the highest (2.053 ± 0.251μmol/g in DW).•ShMT3 is effective mediators to treat heavy metals in wastewater.
The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the ...progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/β-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with β-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical β-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM.
Abstract
In this work, we focus on Mg–Fe–O and Mg–Ni–O with Mg-rich compositions as positive-electrode materials for magnesium rechargeable batteries, and prepare them by a thermal decomposition of ...precipitates obtained by a solution method. It is indicated from X-ray diffraction patterns that the Mg–Fe–O and Mg–Ni–O samples have the spinel and rocksalt structures, respectively. X-ray absorption near edge structures indicate that Fe and Ni are trivalent and divalent, respectively, in the Mg-rich oxides. From charge/discharge cycle test, it is demonstrated that the Mg–Fe–O shows higher discharge capacity than the other and then has good cycle performance while keeping a discharge capacity over 100 mA h g
–1
. To gain deeper understanding on a relationship between the electrode properties and the crystal structure of the Mg–Fe–O, the crystal structure is investigated by a Rietveld refinement using a synchrotron X-ray diffraction profile and an analysis on total correlation functions. It is indicated from these studies that a vacant octahedral site in the spinel structure is partially occupied by the excess Mg in the synthesized sample. This structural feature might result in a stable charge/discharge cycle performance of the Mg-rich Mg–Fe–O.
Proper water and fertilizer management strategies are essential for alfalfa cultivation in arid areas. However, at present, the optimal amounts of subsurface irrigation and nitrogen (N) supply for ...alfalfa (
L.) cultivation are still unclear. Therefore, a field experiment was conducted in 2022 in Yinchuan, Ningxia, China, to explore the effects of different subsurface irrigation levels (W
, 50% of ET
(crop evapotranspiration); W
, 75% of ET
; W
, 100% of ET
) and N application rates (N
, 0 kg/ha; N
, 75 kg/ha; N
, 150 kg/ha; N
, 225 kg/ha; N
, 300 kg/ha) on alfalfa yield, crop water productivity (CWP), N use efficiency (NUE), quality, and economic benefits. Besides, the least squares method and multiple regression analysis were used to explore the optimal water and N combination for alfalfa cultivation under subsurface irrigation. The results showed that the alfalfa yield, crude ash content, and partial factor productivity from applied N (PFPN) were the highest under W
level, but there was no difference in PFPN compared with that under W
level. The branch number (BN), leaf area index (LAI), yield, CWP, irrigation water productivity (IWP), crude protein content (CPC), and economic benefits increased and then decreased with the increase of N application rate, reaching a maximum at the N
or N
level, while the NUE and PFPN decreased with the increase of N application rate. Considering the yield, CWP, NUE, quality, and economic benefits, W
N
treatment was the optimal for alfalfa cultivation under subsurface irrigation. Besides, when the irrigation volume and N application rate were 69.8 ~ 88.7% of ET
and 145 ~ 190 kg/ha, respectively (confidence interval: 85%), the yield, CPC, and economic benefits reached more than 85% of the maximum. This study will provide technique reference for the water and N management in alfalfa cultivation in Northwest China.
Small GTP binding protein Rac1 is a component of NADPH oxidases and is essential for superoxide-induced cell death. Rac1 is activated by guanine nucleotide exchange factors (GEFs), and this ...activation can be blocked by regulator of chromosome condensation 2 (RCC2), which binds the switch regions of Rac1 to prevent access from GEFs.
Three cancer cell lines with up- or down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1 signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2 expression in lung cancer and ovarian cancer were studied using immunochemistry stain of tumor tissue arrays.
Forced RCC2 expression in tumor cells blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2 knock down in these cells resulted in increased apoptosis to STS treatment. The protective activity of RCC2 on apoptosis was revoked by a constitutively activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in 88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non-neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with RCC2 overexpression would be more resistant to these drugs. Tumor cells with forced RCC2 expression indeed had significant difference in drug sensitivity compared to parental cells using a panel of common chemotherapeutic drugs.
RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression in tumor can be a useful marker for predicting chemotherapeutic response.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inchworm robots are typical insect bionic robots that are able to move in narrow space such as pipelines, which expand the range of robot application. In this paper, the motion control method of the ...bionic sucker inchworm robot (BSIR) based on MPC is proposed, which enables the inchworm robot to achieve "Ω" motion gait and steering gait on vertical and horizontal planes of different materials. Firstly, the negative pressure suction cup imitating octopus tentacles (NPSC-IOT) is designed and the sucker control model is proposed. Under negative pressure control, the adsorption pressure of the sucker is adjusted to satisfy the needs of the trunk structure movement. Secondly, the bionic sucker controller based on MPC is designed, and the closed-loop control is realized by using the data feedback from the air pressure sensor. Thirdly, BSIR with installed NPSC-IOT as the robot's tentacles is developed. Finally, the experiment verifies the feasibility of the bionic sucker controller based on MPC to control BSIR to achieve ' Ω ' motion gait and steering gait on vertical and horizontal planes of different materials. The experimental results show that BSIR is able to achieve "Ω" gait and turning gait on vertical and horizontal surfaces of glass, tiles, white gray walls, and metal.
To evaluate whether chelerythrine (CHT) exhibited antifungal activity against
and
and to explore the underlying mechanisms.
Broth microdilution assay and
model were used to evaluate the antifungal ...effect
and
, respectively. Mechanism studies were investigated by morphogenesis observation, Fluo-3/AM, DCFH-DA and rhodamine6G assay, respectively.
CHT exhibited antifungal activity against
and preformed biofilms with minimum inhibitory concentrations ranged from 2 to 16 μg/ml. Besides, CHT protected
larvae infected by
. Mechanisms studies revealed that CHT inhibited hyphal growth, increased intracellular calcium concentration, induced accumulation of reactive oxygen species and inhibited drug transporter activity.
CHT exhibited antifungal activity against
.
The miniaturization of biological and chemical analytical devices by micro-electro-mechanical-systems (MEMS) technology has posed a vital influence on such fields as medical diagnostics, microbial ...detection and other bio-analysis. Among many miniaturized analytical devices, the polymerase chain reaction (PCR) microchip/microdevices are studied extensively, and thus great progress has been made on aspects of on-chip micromachining (fabrication, bonding and sealing), choice of substrate materials, surface chemistry and architecture of reaction vessel, handling of necessary sample fluid, controlling of three or two-step temperature thermocycling, detection of amplified nucleic acid products, integration with other analytical functional units such as sample preparation, capillary electrophoresis (CE), DNA microarray hybridization, etc. However, little has been done on the review of above-mentioned facets of the PCR microchips/microdevices including the two formats of flow-through and stationary chamber in spite of several earlier reviews Zorbas, H. Miniature continuous-flow polymerase chain reaction: a breakthrough? Angew Chem Int Ed 1999; 38 (8):1055–1058; Krishnan, M., Namasivayam, V., Lin, R., Pal, R., Burns, M.A. Microfabricated reaction and separation systems. Curr Opin Biotechnol 2001; 12:92–98; Schneegaβ, I., Köhler, J.M. Flow-through polymerase chain reactions in chip themocyclers. Rev Mol Biotechnol 2001; 82:101–121; deMello, A.J. DNA amplification: does ‘small’ really mean ‘efficient’? Lab Chip 2001; 1: 24N–29N; Mariella, Jr. R. MEMS for bio-assays. Biomed Microdevices 2002; 4 (2):77–87; deMello AJ. Microfluidics: DNA amplification moves on. Nature 2003; 422:28–29; Kricka, L.J., Wilding, P. Microchip PCR. Anal BioAnal Chem 2003; 377:820–825. In this review, we survey the advances of the above aspects among the PCR microfluidic devices in detail. Finally, we also illuminate the potential and practical applications of PCR microfluidics to some fields such as microbial detection and disease diagnosis, based on the DNA/RNA templates used in PCR microfluidics. It is noted, especially, that this review is to help a novice in the field of on-chip PCR amplification to more easily find the original papers, because this review covers almost all of the papers related to on-chip PCR microfluidics.
Sepsis continues to overwhelm hospital systems with its high mortality rate and prevalence. A strategy to reduce the strain of sepsis on hospital systems is to develop a diagnostic/prognostic measure ...that identifies patients who are more susceptible to septic death. Current biomarkers fail to achieve this outcome, as they only have moderate diagnostic power and limited prognostic capabilities. Sepsis disrupts a multitude of pathways in many different organ systems, making the identification of a single powerful biomarker difficult to achieve. However, a common feature of many of these perturbed pathways is the increased generation of reactive oxygen species (ROS), which can alter gene expression, changes in which may precede the clinical manifestation of severe sepsis. Therefore, the aim of this study was to evaluate whether ROS-related circulating molecular signature can be used as a tool to predict sepsis survival. Here we created a ROS-related gene signature and used two Gene Expression Omnibus datasets from whole blood samples of septic patients to generate a 37-gene molecular signature that can predict survival of sepsis patients. Our results indicate that peripheral blood gene expression data can be used to predict the survival of sepsis patients by assessing the gene expression pattern of free radical-associated -related genes in patients, warranting further exploration.
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