We report a novel colorimetric biosensor based on non-aggregation Au@Ag core-shell nanoparticles to detect methamphetamine and cocaine. The biosensor consisted of a reporter probe (RP) that is a ...specific single-stranded DNA (ssDNA) sequence coated on Au@Ag nanoparticles, a capture probe (CP) conjugated with magnetic beads, and an illicit drug-binding DNA aptamer (Apt). Au@Ag nanoparticles were synthesized by seed growth and characterized by scanning electron microscope (SEM), high-resolution transmission electron microscopy (HR-TEM), and UV–vis spectra. Methamphetamine (METH) was used as an example to evaluate the feasibility of the biosensor and to optimize the detection conditions. We demonstrated that this sensing platform was able to detect as low as 0.1nM (14.9ngL−1) METH with a negligible interference from other common illicit drugs. Various concentrations of METH were spiked into urines, and the biosensor yielded recoveries more than 83.1%. In addition, the biosensor also showed a high sensitivity to detect cocaine. These results demonstrated that our colorimetric sensor holds promise to be implemented as a visual sensing platform to detect multiple illicit drugs in biological samples and environmental matrices.
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•A novel colorimetric biosensor was developed for illicit drug detection.•The biosensor was highly sensitive for methamphetamine and cocaine detection.•The recovery of methamphetamine was more than 83.1%.•It has great potential as a generic platform for screening illicit drugs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The introduction of immune checkpoint inhibitors has demonstrated significant improvements in survival for subsets of cancer patients. However, they carry significant and sometimes life-threatening ...toxicities. Prompt prediction and monitoring of immune toxicities have the potential to maximise the benefits of immune checkpoint therapy. Herein, we develop a digital nanopillar SERS platform that achieves real-time single cytokine counting and enables dynamic tracking of immune toxicities in cancer patients receiving immune checkpoint inhibitor treatment - broader applications are anticipated in other disease indications. By analysing four prospective cytokine biomarkers that initiate inflammatory responses, the digital nanopillar SERS assay achieves both highly specific and highly sensitive cytokine detection down to attomolar level. Significantly, we report the capability of the assay to longitudinally monitor 10 melanoma patients during immune inhibitor blockade treatment. Here, we show that elevated cytokine concentrations predict for higher risk of developing severe immune toxicities in our pilot cohort of patients.
Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is activated by the neuron specific activators p35/p39 and plays many important roles in neuronal development. However, aberrant ...activation of Cdk5 is believed to be associated with the pathogenesis of several neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Here in the present study, enhanced Cdk5 activity was observed in mouse models of AD; whereas soluble amyloid-β oligomers (Aβ), which contribute to synaptic failures during AD pathogenesis, induced Cdk5 hyperactivation in cultured hippocampal neurons. Inhibition of Cdk5 activity by pharmacological or genetic approaches reversed dendritic spine loss caused by soluble amyloid-β oligomers (Aβ) treatment. Interestingly, we found that the anti-diabetes drug pioglitazone could inhibit Cdk5 activity by decreasing p35 protein level. More importantly, pioglitazone treatment corrected long-term potentiation (LTP) deficit caused by Aβ exposure in cultured slices and pioglitazone administration rescued impaired LTP and spatial memory in AD mouse models. Taken together, our study describes an unanticipated role of pioglitazone in alleviating AD and reveals a potential therapeutic drug for AD curing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The acquisition of agricultural land is a crucial aspect of survival for numerous rural communities, serving as a fundamental tool for combating poverty and food insecurity and promoting equitable ...sustainable economic progress. The expropriation of land offers a promising prospect for remedying past inequities and promoting both economic progress and food sufficiency. Limited research has examined the association between land expropriation and food security, livelihood shocks, and the well-being of rural households worldwide. Therefore, this research explores the implications of land expropriation on food security, livelihood shocks, and well-being of land lost rural communities. The data were collected from 384 farmers selected through stratified sampling techniques using face-to-face surveys in rural China. The data were analyzed using descriptive and logit regression models. The descriptive findings showed that land expropriation has detrimental effects on the livelihood, food security, and well-being of the farmers. Furthermore, these impacts are more harmful among land-expropriated households with a lower educational level, a large family size, and women farmers in less developed rural communities. The econometric results evinced that gender, age, education level, marital status, family size, and negative changes in income all significantly affect the impact of land expropriation on the food security of farmers. Similarly, the findings revealed that farmers with lower education levels were more likely to be affected by land loss as compared to farmers with medium and high education levels. Farmers with complete land loss were 1.70 times more likely to suffer livelihood shocks than those with partial land loss. The results also evinced that the well-being of all farmers was not affected equally, and some farmers' well-being was affected more than others due to various socioeconomic backgrounds. Therefore, this study suggests the implementation of public policies that provide support to farmers who have been marginalized due to land acquisition.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Ulcerative colitis (UC) is a chronic, incurable condition characterized by mucosal inflammation and intestinal epithelial cell (IEC) damage. The circadian clock gene NR1D1, implicated in ...UC and the critical mitophagy process for epithelial repair, needs further exploration regarding its role in mitophagy regulation in UC. Methods: We created a jet lag mouse model and induced colitis with dextran sulfate sodium (DSS), investigating NR1D1’s role. Intestinal-specific Nr1d1 knockout mice were also generated. RNA sequencing, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays helped ascertain NR1D1’s regulatory effect on BNIP3 expression. The mitochondrial state in IECs was assessed through transmission electron microscopy, while confocal microscopy evaluated mitophagy-associated protein expression in colon tissue and CCD841 cells. Cell apoptosis and reactive oxygen species (ROS) were measured via flow cytometry. Results: We observed reduced NR1D1 expression in the IECs of UC patients, accentuated under jet lag and DSS exposure in mice. NR1D1 ablation led to disrupted immune homeostasis and declined mitophagy in IECs. NR1D1, usually a transcriptional repressor, was a positive regulator of BNIP3 expression, leading to impaired mitophagy, cellular inflammation, and apoptosis. Administering the NR1D1 agonist SR9009 ameliorated colitis symptoms, primarily by rectifying defective mitophagy. Conclusions: Our results suggest that NR1D1 bridges the circadian clock and UC, controlling BNIP3-mediated mitophagy and representing a potential therapeutic target. Its agonist, SR9009, shows promise in UC symptom alleviation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nitrogen (N) is an essential mineral element for plants and is the main component of protein, nucleic acid, phospholipid, chlorophyll, hormones, vitamins and alkaloids. It is involved in all stages ...of plant growth and development. Low-N stress seriously hinders plant growth and reduces yield and quality. Plants have evolved a series of elaborate regulatory mechanisms for N uptake and assimilation to cope with different soil N states. After N is absorbed and utilized by plants, it plays important regulatory roles in phytohormones, microRNA (miRNA), root development and mycorrhizal symbiosis to cope with environmental stress. Here, we highlight the research progress on the regulation mechanisms for N absorption and assimilation. Then, we emphasize the regulation roles of N regarding hormone signals, miRNA, lateral root growth, drought resistance, anthocyanin synthesis and mycorrhizal symbiosis. A thorough understanding of N uptake, utilization and interaction with other biological processes is helpful to improve N use efficiency and to breed plants with “less-input-more-output”.
Abstract
Background
Lysine 2-hydroxyisobutyrylation (K
hib
) is a newly discovered protein posttranslational modification (PTM) and is involved in the broad-spectrum regulation of cellular processes ...that are found in both prokaryotic and eukaryotic cells, including in plants. The Chinese herb rhubarb (Dahuang) is one of the most widely used traditional Chinese medicines in clinical applications. To better understand the physiological activities and mechanism of treating diseases with the herb, it is necessary to conduct intensive research on rhubarb. However, K
hib
modification has not been reported thus far in rhubarb.
Results
In this study, we performed the first global analysis of K
hib
-modified proteins in rhubarb by using sensitive affinity enrichment combined with high-accuracy HPLC-MS/MS tandem spectrometry. A total of 4333 overlapping K
hib
modification peptides matched on 1525 K
hib
-containing proteins were identified in three independent tests. Bioinformatics analysis showed that these K
hib
-containing proteins are involved in a wide range of cellular processes, particularly in protein biosynthesis and central carbon metabolism and are distributed mainly in chloroplasts, cytoplasm, nucleus and mitochondria. In addition, the amino acid sequence motif analysis showed that a negatively charged side chain residue (E), a positively charged residue (K), and an uncharged residue with the smallest side chain (G) were strongly preferred around the K
hib
site, and a total of 13 K
hib
modification motifs were identified. These identified motifs can be classified into three motif patterns, and some motif patterns are unique to rhubarb and have not been identified in other plants to date.
Conclusions
A total of 4333 K
hib
-modified peptides on 1525 proteins were identified. The K
hib
-modified proteins are mainly distributed in the chloroplast, cytoplasm, nucleus and mitochondria, and involved in a wide range of cellular processes. Moreover, three types of amino acid sequence motif patterns, including EK
hib
/K
hib
E, GK
hib
and k.kkk….K
hib
….kkkkk, were extracted from a total of 13 K
hib
-modified peptides. This study provides comprehensive K
hib
-proteome resource of rhubarb. The findings from the study contribute to a better understanding of the physiological roles of K
hib
modification, and the K
hib
proteome data will facilitate further investigations of the roles and mechanisms of K
hib
modification in rhubarb.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Precision cancer medicine necessitates a personalized treatment plan for each individual patient. Given cancer’s heterogeneity and dynamic nature, the plot of patient-specific signatures composed of ...multiple cancer circulating biomarkers is useful to reveal the complete tumor landscape for guiding precision medicine. As an emerging new technology, surface-enhanced Raman scattering (SERS) shows the intrinsic advantage of performing multiplexed detection with the extremely narrow Raman spectral line widths. In this review, we first discuss the design principle of SERS nanotags to enable the detection of multiple circulating biomarkers, highlighting the important roles of plasmonic nanostructures and triple bond-modulated Raman reporters. Following this, we detail the use of isotropic and anisotropic nanostructures as SERS enhancement substrates for amplifying Raman signals in multi-biomarker detection. Furthermore, we present the triple bond-modulated molecules as Raman reporters in SERS nanotags to expand the multiplexing capability for biomarker measurements. Finally, we offer critical insights into the challenges and perspectives of SERS nanotags for cancer diagnosis, particularly from the aspect of future clinical transition. It is expected that this review can facilitate the design of more functional SERS nanotags with high sensitivity and multiplexing capability to assist early and accurate cancer screening. We also believe our review will be of interest in the fields of molecular imaging, biomedicine, and analytical chemistry.
PD-1 inhibitors, as one of commonly used immune checkpoint inhibitors, enable T-cell activation and prevent immune escape by blocking the PD-1/PD-L1 signaling pathway. They have transformed the ...treatment landscape for cancer in recent years, due to the advantages of significantly prolonging patients' survival and improving their life quality. However, the ensuing unpredictable immune-related adverse effects (irAEs) plague clinicians, such as colitis and even potentially fatal events like intestinal perforation and obstruction. Therefore, understanding the clinical manifestations and grading criteria, underlying mechanisms, available diverse therapies, accessible biomarkers, and basis for risk stratification is of great importance for the management. Current evidence suggests that irAEs may be a marker of clinical benefit to immunotherapy in patients, so whether to discontinue PD-1 inhibitors after the onset of irAEs and rechallenge after remission of irAEs requires further evaluation of potential risk-reward ratios as well as more data from large-scale prospective studies to fully validate. At the end, the rare gastrointestinal toxicity events caused by PD-1 inhibitors are also sorted out. This review provides a summary of available data on the gastrointestinal toxicity profile caused by PD-1 inhibitors, with the aim of raising clinicians' awareness in daily practice, so that patients can safely benefit from therapy.
•Numerical simulations reveal that curvature has weak effects on Rayleigh wave.•Double probes clamped by arc guide rail can be used for Rayleigh wave detection.•The information of surface cracks is ...assessed by Amplitude decay of Rayleigh wave.•Different characteristics of cracks are quantified by fitting curve.
In this paper, different characteristics of micro-cracks on the surface of turbine blades have been successfully evaluated based on the detection of Rayleigh ultrasonic wave by numerical simulation and experimental study. The quantitative relationship between the maximum amplitude of Rayleigh ultrasonic wave and the features of cracks including width, depth, excitation position, and inclination angle was established. Numerical calculations of different curvature models show that curvature has no significant effect on the propagation of Rayleigh ultrasonic wave. According to the developed multi-functional ultrasonic equipment, cracks on complex surfaces can be detected by clamping two probes on the arc guide rail. The experimental results verify the validity of the numerical simulations. It gives an excellent basis for the effective automatic detection of cracks on the surface of turbine blades. This research provides a suitable method and new equipment for rapid quantitative inspection of turbine blades.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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