A convenient and real-time fluorometric assay with the assistance of copper ions based on aggregation and disaggregation of carbon quantum dots (CQDs) was developed to achieve highly sensitive ...detection of alkaline phosphatase activity. CQDs and pyrophosphate anions (PPi) were used as the fluorescent indicator and substrate for ALP activity assessment respectively. Richness of carboxyl groups on the surface of CQDs enables their severe aggregation triggered by copper ions, which results in effective fluorescence quenching. Under the catalytic hydrolysis of ALP, PPi can be rapidly transformed to phosphate ions. Stronger affinity of phosphate ions to copper ions than carboxyl groups is taken advantage of to achieve fluorescence recovery induced by re-dispersion of CQDs in the presence of ALP and PPi. Quantitative evaluation of ALP activity in a broad range from 16.7 to 782.6 U/L with the detection limit of 1.1 U/L can be realized in this way, which endows the assay with high enough sensitivity for practical detection in human serum. This strategy broadens the sensing application of fluorescent CQDs with excellent biocompatibility, and provides an example based on disaggregation in optical probe development.
Herd immunity achieved through mass vaccination is an effective approach to prevent contagious diseases. Nonetheless, emerging SARS-CoV-2 variants with frequent mutations largely evaded humoral ...immunity induced by Spike-based COVID-19 vaccines. Herein, we develop a lipid nanoparticle (LNP)-formulated mRNA-based T-cell-inducing antigen, which targeted three SARS-CoV-2 proteome regions that enriched human HLA-I epitopes (HLA-EPs). Immunization of HLA-EPs induces potent cellular responses to prevent SARS-CoV-2 infection in humanized HLA-A*02:01/DR1 and HLA-A*11:01/DR1 transgenic mice. Of note, the sequences of HLA-EPs are highly conserved among SARS-CoV-2 variants of concern. In humanized HLA-transgenic mice and female rhesus macaques, dual immunization with the LNP-formulated mRNAs encoding HLA-EPs and the receptor-binding domain of the SARS-CoV-2 B.1.351 variant (RBD
) is more efficacious in preventing infection of SARS-CoV-2 Beta and Omicron BA.1 variants than single immunization of LNP-RBD
. This study demonstrates the necessity to strengthen the vaccine effectiveness by comprehensively stimulating both humoral and cellular responses, thereby offering insight for optimizing the design of COVID-19 vaccines.
Flight Maneuver Recognition (FMR) refers to the automatic recognition of a series of aircraft flight patterns and is a key technology in many fields. The chaotic nature of its input data and the ...professional complexity of the identification process make it difficult and expensive to identify, and none of the existing models have general generalization capabilities. A general framework is proposed in this paper, which can be used for all kinds of flight tasks, independent of the aircraft type. We first preprocessed the raw data with unsupervised clustering method, segmented it into maneuver sequences, then reconstructed the sequences in phase space, calculated their approximate entropy, quantitatively characterized the sequence complexity, and distinguished the flight maneuvers. Experiments on a real flight training dataset have shown that the framework can quickly and correctly identify various flight maneuvers for multiple aircraft types with minimal human intervention.
Convenient and simultaneous detection of multiple biomarkers such as DNA and proteins with biocompatible materials and good analytical performance still remains a challenge. Herein, we report the ...respective and simultaneous detection of DNA and bovine α-thrombin (thrombin) entirely based on biocompatible carbon materials through a specially designed fluorescence on-off-on process. Colorful fluorescence, high emission efficiency, good photostability and excellent compatibility enables graphene quantum dots (GQDs) as the best choice for fluorophores in bioprobes, and thus two-colored GQDs as labeling fluorophores were chemically bonded with specific oligonucleotide sequence and aptamer to prepare two probes targeting the DNA and thrombin, respectively. Each probe can be assembled on the graphene oxide (GO) platform spontaneously by π-π stacking and electrostatic attraction; as a result, fast electron transfer in the assembly efficiently quenches the fluorescence of probe. The presence of DNA or thrombin can trigger the self-recognition between capturing a nucleotide sequence and its target DNA or between thrombin and its aptamer due to their specific hybridization and duplex DNA structures or the formation of apatamer-substrate complex, which is taken advantage of in order to achieve a separate quantitative analysis of DNA and thrombin. A dual-functional biosensor for simultaneous detection of DNA and thrombin was also constructed by self-assembly of two probes with distinct colors and GO platform, and was further evaluated with the presence of various concentrations of DNA and thrombin. Both biosensors serving as a general detection model for multiple species exhibit outstanding analytical performance, and are expected to be applied in vivo because of the excellent biocompatibility of their used materials.
An ultrasensitive nanosensor based on fluorescence resonance energy transfer (FRET) between biocompatible graphene quantum dots and carbon nanotubes for DNA detection was reported. We take advantage ...of good biocompatibility and strong fluorescence of graphene quantum dots, base pairing specificity of DNA and unique fluorescence resonance energy transfer between graphene quantum dots and carbon nanotubes to achieve the analysis of low concentrations of DNA. Graphene quantum dots with high quantum yield up to 0.20 were prepared and served as the fluorophore of DNA probe. FRET process between graphene quantum dots-labeled probe and oxidized carbon nanotubes is easily achieved due to their efficient self-assembly through specific π–π interaction. This nanosensor can distinguish complementary and mismatched nucleic acid sequences with high sensitivity and good reproducibility. The detection method based on this nanosensor possesses a broad linear span of up to 133.0nM and ultralow detection limit of 0.4nM. The constructed nanosensor is expected to be highly biocompatible because of all its components with excellent biocompatibility.
•Specific fluorescence “on-off-on” process between GQDs-probe and CNTs is achieved.•FRET between GQDs and CNTs was employed to achieve quantitative analysis of DNA.•The nanosensor can identify DNA sequence with high sensitivity and selectivity.•The nanosensor shows excellent performance in trace analysis of DNA.•All the materials involved in the sensing system are of excellent biocompatibility.
Twenty five Imine resveratrol analogues (IRAs) were synthesized, replacing the CC bond in resveratrol with CN bond, as well as substitution modifications on aromatic rings. Radical scavenging ...activities against DPPH, along with singlet oxygen quenching capacities were evaluated, and further confirmed using density functional theory calculations (DFT). It was found that IRAs bearing ortho-OH on B ring have better radical scavenging activities against DPPH than resveratrol, these compounds were also found to be effective 1O2 quenchers. Theoretical studies on the reaction mechanism of these compounds with 1O2 suggest that the 1,3-addition to a double bond with a –OH group with the formation of allylic hydroperoxide is the most probable reaction route.
This study aimed to evaluate the spatiotemporal distribution of patients with hepatitis C virus (HCV) and the factors influencing this distribution in Jiangsu Province, China, from 2011 to 2020.
The ...incidence of reported HCV in Jiangsu Province from 2011 to 2020 was obtained from the Chinese Information System for Disease Control and Prevention (CISDCP). R and GeoDa software were used to visualize the spatiotemporal distribution and the spatial autocorrelation of HCV. A Bayesian spatiotemporal model was constructed to explore the spatiotemporal distribution of HCV in Jiangsu Province and to further analyze the factors related to HCV.
A total of 31,778 HCV patients were registered in Jiangsu Province. The registered incidence rate of HCV increased from 2.60/100,000 people in 2011 to 4.96/100,000 people in 2020, an increase of 190.77%. Moran's
ranged from 0.099 to 0.354 (
< 0.05) from 2011 to 2019, indicating a positive spatial correlation overall. The relative risk (
) of the urbanization rate, the most important factor affecting the spread of HCV in Jiangsu Province, was 1.254 (95% confidence interval: 1.141-1.376), while other factors had no significance.
The reported HCV incidence rate integrally increased in the whole Jiangsu Province, whereas the spatial aggregation of HCV incidence was gradually weakening. Our study highlighted the importance of health education for the floating population and reasonable allocation of medical resources in the future health work.
Methionine aminopeptidase (MetAP) carries out an important cotranslational N-terminal methionine excision of nascent proteins and represents a potential target to develop antibacterial and ...antitubercular drugs. We cloned one of the two MetAPs in Mycobacterium tuberculosis (MtMetAP1c from the mapB gene) and purified it to homogeneity as an apoenzyme. Its activity required a divalent metal ion, and Co(II), Ni(II), Mn(II), and Fe(II) were among activators of the enzyme. Co(II) and Fe(II) had the tightest binding, while Ni(II) was the most efficient cofactor for the catalysis. MtMetAP1c was also functional in E. coli cells because a plasmid-expressed MtMetAP1c complemented the essential function of MetAP in E. coli and supported the cell growth. A set of potent MtMetAP1c inhibitors were identified, and they showed high selectivity toward the Fe(II)-form, the Mn(II)-form, or the Co(II) and Ni(II) forms of the enzyme, respectively. These metalloform selective inhibitors were used to assign the metalloform of the cellular MtMetAP1c. The fact that only the Fe(II)-form selective inhibitors inhibited the cellular MtMetAP1c activity and inhibited the MtMetAP1c-complemented cell growth suggests that Fe(II) is the native metal used by MtMetAP1c in an E. coli cellular environment. Finally, X-ray structures of MtMetAP1c in complex with three metalloform-selective inhibitors were analyzed, which showed different binding modes and different interactions with metal ions and active site residues.
The sensitive detection of heavy metal ions in the organism and aquatic ecosystem using nanosensors based on environment friendly and biocompatible materials still remains a challenge. A fluorescent ...turn-on nanosensor for lead (II) detection based on biocompatible graphene quantum dots and graphene oxide by employment of Pb(2+)-induced G-quadruplex formation was reported. Graphene quantum dots with high quantum yield, good biocompatibility were prepared and served as the fluorophore of Pb(2+) probe. Fluorescence turn-off of graphene quantum dots is easily achieved through efficient photoinduced electron transfer between graphene quantum dots and graphene oxide, and subsequent fluorescence turn-on process is due to the formation of G-quadraplex aptamer-Pb(2+) complex triggered by the addition of Pb(2+). This nanosensor can distinguish Pb(2+) ion from other ions with high sensitivity and good reproducibility. The detection method based on this nanosensor possesses a fast response time of one minute, a broad linear span of up to 400.0 nM and ultralow detection limit of 0.6 nM.
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