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1.
Biosensors (Basel) ; 14(4)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38667171

RESUMO

Transition metal doping is an ideal strategy to construct multifunctional and efficient nanozymes for biosensing. In this work, a metal-doped CoMnOx nanozyme was designed and synthesized by hydrothermal reaction and high-temperature calcination. Based on its oxidase activity, an "on-off-on" smartphone sensing platform was established to detect ziram and Cu2+. The obtained flower-shaped CoMnOx could exhibit oxidase-, catalase-, and laccase-like activities. The oxidase activity mechanism of CoMnOx was deeply explored. O2 molecules adsorbed on the surface of CoMnOx were activated to produce a large amount of O2·-, and then, O2·- could extract acidic hydrogen from TMB to produce blue oxTMB. Meanwhile, TMB was oxidized directly to the blue product oxTMB via the high redox ability of Co species. According to the excellent oxidase-like activity of CoMnOx, a versatile colorimetric detection platform for ziram and Cu2+ was successfully constructed. The linear detection ranges for ziram and Cu2+ were 5~280 µM and 80~360 µM, and the detection limits were 1.475 µM and 3.906 µM, respectively. In addition, a portable smartphone platform for ziram and Cu2+ sensing was established for instant analysis, showing great application promise in the detection of real samples including environmental soil and water.


Assuntos
Técnicas Biossensoriais , Colorimetria , Cobre , Smartphone , Cobre/análise , Limite de Detecção , Lacase , Nanoestruturas
2.
Sci Data ; 11(1): 250, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413616

RESUMO

Antimicrobial resistance (AMR) poses a severe threat to global health. The wide distribution of environmental antibiotic resistance genes (ARGs), which can be transferred between microbiota, especially clinical pathogens and human commensals, contributed significantly to AMR. However, few databases on the spatiotemporal distribution, abundance, and health risk of ARGs from multiple environments have been developed, especially on the absolute level. In this study, we compiled the ARG occurrence data generated by a high-throughput quantitative PCR platform from 1,403 samples in 653 sampling sites across 18 provinces in China. The database possessed 291,870 records from five types of habitats on the abundance of 290 ARGs, as well as 8,057 records on the abundance of 30 mobile genetic elements (MGEs) from 2013 to 2020. These ARGs conferred resistance to major common types of antibiotics (a total of 15 types) and represented five major resistance mechanisms, as well as four risk ranks. The database can provide information for studies on the dynamics of ARGs and is useful for the health risk assessment of AMR.


Assuntos
Antibacterianos , Bases de Dados Genéticas , Resistência Microbiana a Medicamentos , Microbiota , Antibacterianos/farmacologia , China , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos
3.
bioRxiv ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-37398110

RESUMO

We present near-atomic-resolution cryo-EM structures of the mammalian voltage-gated potassium channel Kv1.2 in open, C-type inactivated, toxin-blocked and sodium-bound states at 3.2 Å, 2.5 Å, 3.2 Å, and 2.9Å. These structures, all obtained at nominally zero membrane potential in detergent micelles, reveal distinct ion-occupancy patterns in the selectivity filter. The first two structures are very similar to those reported in the related Shaker channel and the much-studied Kv1.2-2.1 chimeric channel. On the other hand, two new structures show unexpected patterns of ion occupancy. First, the toxin α-Dendrotoxin, like Charybdotoxin, is seen to attach to the negatively-charged channel outer mouth, and a lysine residue penetrates into the selectivity filter, with the terminal amine coordinated by carbonyls, partially disrupting the outermost ion-binding site. In the remainder of the filter two densities of bound ions are observed, rather than three as observed with other toxin-blocked Kv channels. Second, a structure of Kv1.2 in Na+ solution does not show collapse or destabilization of the selectivity filter, but instead shows an intact selectivity filter with ion density in each binding site. We also attempted to image the C-type inactivated Kv1.2 W366F channel in Na+ solution, but the protein conformation was seen to be highly variable and only a low-resolution structure could be obtained. These findings present new insights into the stability of the selectivity filter and the mechanism of toxin block of this intensively studied, voltage-gated potassium channel.

4.
Environ Sci Pollut Res Int ; 29(33): 49985-49997, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35224696

RESUMO

The ecological risks and health hazards of heavy metals pollution in Taihu Lake have received widespread concern. This study has developed a species-pollution dataset which includes a large amount of data on heavy metal pollution in Taihu fish. The heavy metal contamination poses a significant threat to human consumption, but no studies have been conducted to assess the risk of exposure to consumption of these fish and to make recommendations for their consumption. In this study, we systematically integrated the relevant data in the dataset, analyzed its contamination level using PI (single pollution index) and MPI (metal pollution index) models, and assessed health hazards of fish consumption using THQ (target hazard quotient) and ILCR (incremental lifetime cancer risk) models. Results showed that the contamination levels of heavy metals in fish varied in a feeding habit and living habit dependent manner. The risk of non-cancer health is the highest from consuming omnivorous fish, then from carnivorous and herbivorous fish. The ILCR model predicted that the long-term Taihu consumption of omnivorous fish may pose a potential carcinogenic risk, especially for children. In all, our study provided a comprehensive understanding on the risk of heavy metals in Taihu. Accordingly, it is recommended that children should try to choose herbivorous fish when consuming fish from Taihu Lake while avoiding long-term consumption of omnivorous fish.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Animais , Criança , China , Monitoramento Ambiental , Peixes , Contaminação de Alimentos/análise , Humanos , Lagos , Metais Pesados/análise , Medição de Risco , Poluentes Químicos da Água/análise
5.
Elife ; 102021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319232

RESUMO

ASIC1a is a proton-gated sodium channel involved in modulation of pain, fear, addiction, and ischemia-induced neuronal injury. We report isolation and characterization of alpaca-derived nanobodies (Nbs) that specifically target human ASIC1a. Cryo-electron microscopy of the human ASIC1a channel at pH 7.4 in complex with one of these, Nb.C1, yielded a structure at 2.9 Å resolution. It is revealed that Nb.C1 binds to a site overlapping with that of the Texas coral snake toxin (MitTx1) and the black mamba venom Mambalgin-1; however, the Nb.C1-binding site does not overlap with that of the inhibitory tarantula toxin psalmotoxin-1 (PcTx1). Fusion of Nb.C1 with PcTx1 in a single polypeptide markedly enhances the potency of PcTx1, whereas competition of Nb.C1 and MitTx1 for binding reduces channel activation by the toxin. Thus, Nb.C1 is a molecular tool for biochemical and structural studies of hASIC1a; a potential antidote to the pain-inducing component of coral snake bite; and a candidate to potentiate PcTx1-mediated inhibition of hASIC1a in vivo for therapeutic applications.


Assuntos
Canais Iônicos Sensíveis a Ácido/química , Anticorpos de Domínio Único/química , Canais Iônicos Sensíveis a Ácido/ultraestrutura , Animais , Camelídeos Americanos , Microscopia Crioeletrônica , Ligação Proteica , Anticorpos de Domínio Único/ultraestrutura
6.
Elife ; 82019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31045491

RESUMO

ASICs are proton-gated sodium channels expressed in neurons. Structures of chicken ASIC1 in three conformations have advanced understanding of proton-mediated gating; however, a molecular mechanism describing desensitization from open and pre-open states (steady-state desensitization or SSD) remains elusive. A distinct feature of the desensitized state is an 180o rotation of residues L415 and N416 in the ß11- ß12 linker that was proposed to mediate desensitization; whether and how it translates into desensitization has not been explored yet. Using electrophysiological measurements of injected Xenopus oocytes, we show that Q276 in ß9 strand works with L415 and N416 to mediate both types of desensitization in ASIC1a, ASIC2a and ASIC3. Q276 functions as a valve that enables or restricts rotation of L415 and N416 to keep the linker compressed, its relaxation lengthens openings and leads to sustained currents. At low proton concentrations, the proposed mechanism working in only one of three subunits of the channel is sufficient to induce SSD.


Assuntos
Canais Iônicos Sensíveis a Ácido/química , Canais Iônicos Sensíveis a Ácido/metabolismo , Sódio/metabolismo , Canais Iônicos Sensíveis a Ácido/genética , Substituição de Aminoácidos , Animais , Concentração de Íons de Hidrogênio , Mutagênese Sítio-Dirigida , Oócitos , Técnicas de Patch-Clamp , Conformação Proteica , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Xenopus
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