A MELET- and IFE-based UV-visible luminescent ratiometric probe for quantization of mercury(II) and nitrofurantoin in environmental sewage.

A novel fluorimetric ratiometric probe of green and eco-friendily nitrogen-enriched, oxygen-doped carbon nanodots (Cnanodots) was prepared for the quantitative analysis of mercury(II) (HgII) and nitrofurantoin (Nit) in the environmental sewage. The Cnanodots exhibits dual-emission peaks respectively at 345 and 445 nm under 285 nm excitation, with excitation-independent properties. Unexpectedly, this Cnanodots displays two obvious ratiometric responses to HgII and Nit through decreasing the signal at 345 nm and remaining invariable at 445 nm. Experimental results confirm that the highly sensitive analysis of HgII and Nit are achieved respectively based on matching energy-level electron transfer and inner filter effect mechanisms. The fluorescence (FL) ratiometric intensity of [FL345nm/FL445nm] expresses a good linear relationship with the concentration of HgII in the scope of 0.01-20 µM, while the logarithm of [Log(FL0345nm-FL345nm)] on the quenching degree of the probe by Nit also shows a good linear correlation within the range of 0.01-100 µM. The detection limits were calculated to be 4.14 nM for HgII, and 7.84 nM for Nit. Moreover, recovery experiments of Cnanodots for HgII and Nit sensing in real sewage samples obtained satisfactory results, comfirming the feasibility of practical application.

Atrimonas thermophila gen. nov., sp. nov., a novel anaerobic thermophilic bacterium of the phylum Atribacterota isolated from deep subsurface gas field and proposal of Atrimonadaceae fam. nov. within the class Atribacteria in the phylum Atribacterota.

A novel anaerobic, thermophilic bacterium of the class Atribacteria, strain M15T, was isolated from a high-temperature gas reservoir, Japan. Cells of strain M15T were gram-negative, short oval-shaped, and lacked flagella. Growth occurred at 45-75 °C (optimum 70-75 °C) and pH 6.5-8.5 (optimum pH 7.5-8.0) and was fast under optimal conditions (doubling time 11.4 h). Yeast extract was required for growth. Fermentative growth with glucose, arabinose, xylose, and cellobiose was observed. The major fermentative end products of glucose were acetate and hydrogen. The major cellular fatty acids were C16:0, iso-C15:0, and C18:0. The genomic G + C content was 46.0 mol%. Fluorescence and electron microscopy observations revealed the intracellular localization of genomic DNA surrounded by a membrane in the cells of strain M15T as reported in a sole validly described species of the class Atribacteria in the phylum Atribacterota, Atribacter laminatus strain RT761T, suggesting that the unique morphological traits are widely shared in this class. Phylogenetic analyses indicated that strain M15T belongs to a distinct family-level lineage in the class Atribacteria and shows low similarities to Atribacter laminatus strain RT761T (16S rRNA gene sequence identity of 90.1 %, average nucleotide identity [ANI] of 66.1 %, average amino acid identity [AAI] of 55.8 %). Phenotypic traits of strain M15T (thermophilic, fast-growing, relatively high G + C content, etc.) were clearly distinct from A. laminatus. Based on these phenotypic and genomic properties, we propose a novel genus and species, Atrimonas thermophila gen. nov., sp. nov. for strain M15T (=JCM39389T, =KCTC25731T) representing a novel family Atrimonadaceae fam., nov. in the class Atribacteria.

Integrated Physiologic and Proteomic Analyses Reveal the Molecular Mechanism of Navicula sp. in Response to Ultraviolet Irradiation Stress.

With the continuous development of space station construction, space ecosystem research has attracted increasing attention. However, the complicated responses of different candidate plants and algae to radiation stress remain unclear. The present study, using integrated physiologic and proteomic analyses, was carried out to reveal the molecular mechanism of Navicula sp. in response to ultraviolet (UV) irradiation stress. Under 12~24 h of high-dose UV irradiation conditions, the contents of chlorophyll and soluble proteins in Navicula sp. cells were significantly higher than those in the control and 4~8 h of low-dose UV irradiation groups. The activity of catalase (CAT) increased with the extension of irradiation time, and the activity of superoxide dismutase (SOD) decreased first and then increased. Furthermore, differential volcano plot analysis of the proteomic data of Navicula sp. samples found only one protein with a significant difference. Differential protein GO analysis unveiled that UV irradiation can activate the antioxidant system of Navicula sp. and further impact photosynthesis by affecting the photoreaction and chlorophyll synthesis of Navicula sp. The most significant differences in KEGG pathway analysis were also associated with photosynthesis. The above results indicate that Navicula sp. has good UV radiation resistance ability by regulating its photosynthetic pigment content, photosynthetic activity, and antioxidant system, making it a potential candidate for the future development of space ecosystems.

Research progress in stem cell therapy for Wilson disease.

Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive disorder characterized by disorganized copper metabolism caused by mutations in the ATP7B gene. Currently, the main treatment options for WD involve medications such as d-penicillamine, trientine hydrochloride, zinc acetate, and liver transplantation. However, there are challenges that encompass issues of poor compliance, adverse effects, and limited availability of liver sources that persist. Stem cell therapy for WD is currently a promising area of research. Due to the advancement in stem cell directed differentiation technology in vitro and the availability of sufficient stem cell donors, it is expected to be a potential treatment option for the permanent correction of abnormal copper metabolism. This article discusses the research progress of stem cell therapy for WD from various sources, as well as the challenges and future prospects of the clinical application of stem cell therapy for WD.

Electrochemical biosensors for pathogenic microorganisms detection based on recognition elements.

The worldwide spread of pathogenic microorganisms poses a significant risk to human health. Electrochemical biosensors have emerged as dependable analytical tools for the point-of-care detection of pathogens and can effectively compensate for the limitations of conventional techniques. Real-time analysis, high throughput, portability, and rapidity make them pioneering tools for on-site detection of pathogens. Herein, this work comprehensively reviews the recent advances in electrochemical biosensors for pathogen detection, focusing on those based on the classification of recognition elements, and summarizes their principles, current challenges, and prospects. This review was conducted by a systematic search of PubMed and Web of Science databases to obtain relevant literature and construct a basic framework. A total of 171 publications were included after online screening and data extraction to obtain information of the research advances in electrochemical biosensors for pathogen detection. According to the findings, the research of electrochemical biosensors in pathogen detection has been increasing yearly in the past 3 years, which has a broad development prospect, but most of the biosensors have performance or economic limitations and are still in the primary stage. Therefore, significant research and funding are required to fuel the rapid development of electrochemical biosensors. The overview comprehensively evaluates the recent advances in different types of electrochemical biosensors utilized in pathogen detection, with a view to providing insights into future research directions in biosensors.

Gold-copper-doped lanthanide luminescent metal-organic backbone induced self-enhanced molecularly imprinted ECL sensors for ultra-sensitive detection of chlorpyrifos.

Herein, a self-enhanced molecularly imprinted polymer luminescence (MIP-ECL) sensing platform based on gold-copper doped Tb-MOFs (Au@Cu:Tb-MOFs) was constructed for ultra-sensitive detection of chlorpyrifos (CPF). In this work, Au@Cu:Tb-MOFs as co-reaction promoters greatly improve the ECL emission signal, while Au@Cu:Tb-MOFs were used as cathode emitters. And chlorpyrifos and 4,7-bis(thiophene-2-yl)benzo [c][1,2,5] thiadiazole were electropolymerized on electrode surface to form MIP, where this films with thiophene derivatives could greatly improve ECL signal. Notably, the introduction of MIP as recognition elements enabled specific identification of target analytes, in which molecular docking technique validated target analyte and functional monomers are tightly bound through Pi-alkyl interaction. As the concentration of CPF increases, the ECL signal gradually decreases, showing a good linear relationship in the range of 0.1-106 pg/mL with a low detection limit (LOD) of 0.029 pg/mL. Moreover, actual sample testing experiment of this method displayed a special correlation in organophosphorus detection and development potential in actual sample analysis.

Portable glucose sensing analysis based on laser-induced graphene composite electrode.

In this work, a portable electrochemical glucose sensor was studied based on a laser-induced graphene (LIG) composite electrode. A flexible graphene electrode was prepared using LIG technology. Poly(3,4-ethylene dioxythiophene) (PEDOT) and gold nanoparticles (Au NPs) were deposited on the electrode surface by potentiostatic deposition to obtain a composite electrode with good conductivity and stability. Glucose oxidase (GOx) was then immobilized using glutaraldehyde (GA) to create an LIG/PEDOT/Au/GOx micro-sensing interface. The concentration of glucose solution is directly related to the current value by chronoamperometry. Results show that the sensor based on the LIG/PEDOT/Au/GOx flexible electrode can detect glucose solutions within a concentration range of 0.5 × 10-5 to 2.5 × 10-3 mol L-1. The modified LIG electrode provides the resulting glucose sensor with an excellent sensitivity of 341.67 µA mM-1 cm-2 and an ultra-low limit of detection (S/N = 3) of 0.2 × 10-5 mol L-1. The prepared sensor exhibits high sensitivity, stability, and selectivity, making it suitable for analyzing biological fluid samples. The composite electrode is user-friendly, and can be built into a portable biosensor device through smartphone detection. Thus, the developed sensor has the potential to be applied in point-of-care platforms such as environmental monitoring, public health, and food safety.

Photoelectrochemical sensor for the detection of Escherichia coli O157:H7 based on TPA-NO2 and dual-functional polythiophene films.

The detection of Escherichia coli (E. coli) is of great significance for the environment and human health. Herein, a photoelectrochemical (PEC) detection strategy based on molecularly imprinted polymers (MIPs) was proposed for the sensitive detection of E. coli. 4,4',4″-Trinitrotriphenylamine (TPA-NO2) was prepared using a simple nitration reaction. Subsequently, MIP films were polymerized on the surface of TPA-NO2 using 1,3-dihydrothieno[3,2-d]pyrimidine-2,4-dione as the functional monomer with the dual functions of specific recognition and sensitization. The linear range was 10-108 CFU/mL and the limit of detection was 10 CFU/mL. It showed favorable recoveries in real sample tests of milk, orange juice and tomato. Additionally, the ability of functional monomers to bind excellently with E. coli was verified using molecular docking techniques. This research provided broader possibilities for constructing MIPs-PEC sensors and analyzing the interaction mechanism between E. coli and functional monomers.

Reactive Molecular Dynamics Simulations of Polystyrene Pyrolysis.

Polymers' controlled pyrolysis is an economical and environmentally friendly solution to prepare activated carbon. However, due to the experimental difficulty in measuring the dependence between microstructure and pyrolysis parameters at high temperatures, the unknown pyrolysis mechanism hinders access to the target products with desirable morphologies and performances. In this study, we investigate the pyrolysis process of polystyrene (PS) under different heating rates and temperatures employing reactive molecular dynamics (ReaxFF-MD) simulations. A clear profile of the generation of pyrolysis products determined by the temperature and heating rate is constructed. It is found that the heating rate affects the type and amount of pyrolysis intermediates and their timing, and that low-rate heating helps yield more diverse pyrolysis intermediates. While the temperature affects the pyrolytic structure of the final equilibrium products, either too low or too high a target temperature is detrimental to generating large areas of the graphitized structure. The reduced time plots (RTPs) with simulation results predict a PS pyrolytic activation energy of 159.74 kJ/mol. The established theoretical evolution process matches experiments well, thus, contributing to preparing target activated carbons by referring to the regulatory mechanism of pyrolytic microstructure.

An eco-friendly fluorometric assay for high-sensitive meloxicam quantitation in biological matrices.

Meloxicam (Mel), as a powerful and effective anti-inflammatory drug, is commonly employed for the treatment of various inflammatory diseases; however, the use of Mel at high doses or for extended periods could cause severe side effects in human visceral organs. Therefore, a simple, rapid, and reliable method is urgently needed to monitor Mel in biological samples. Herein, novel water-soluble luminescent nano-carbon dots (nano-Cdots) with outstanding physicochemical properties were prepared by a one-pot high-temperature hydrothermal process of ellagic acid and guanidine. The nano-Cdots were further used as an optical probe for the sensitive detection of Mel in serum samples through the cooperative mechanisms of the inner filter effect and photoelectron transfer. By employing this sensor, an excellent linear correlation was achieved between the relative luminescent intensity [(PL0 - PL)/PL0] and the concentration of Mel in the range of 0.1 to 200 µM, with a limit of detection of 34.68 nM (3σ/k). This sensor was effectively employed for the analysis of Mel in real serum samples, implying its potential development prospects for the advancement of drug analysis with carbon-based probes.

[A multi-stage and multi-epitope vaccine against Mycobacterium tuberculosis based on an immunoinformatics approach].

Objectives To develop a multi-stage and multi-epitope vaccine, which consists of epitopes from the early secretory and latency-associated antigens of Mycobacterium tuberculosis (MTB). Methods The B-cell, cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes of 12 proteins were predicted using an immunoinformatics. The epitopes with antigenicity, without cytotoxicity and sensitization, were further screened to construct the multi-epitope vaccine. Furthermore, the proposed vaccine underwent physicochemical properties analysis and secondary structure prediction as well as 3D structure modeling, refinement and validation. Then the refined model was docked with TLR4. Finally, an immune simulation of the vaccine was carried out. Results The proposed vaccine, which consists of 12 B-cell, 11 CTL and 12 HTL epitopes, had a flexible and stable globular conformation as well as a thermostable and hydrophilic structure. A stable interaction of the vaccine with TLR4 was confirmed by molecular docking. The efficiency of the candidate vaccine to trigger effective cellular and humoral immune responses was assessed by immune simulation. Conclusion A multi-stage multi-epitope MTB vaccine construction strategy based on immunoinformatics is proposed, which is expected to prevent both active and latent MTB infection.

Synergism of Photo-Induced Electron Transfer and Aggregation-Induced Quenching Mechanisms for Highly Sensitive Detection of Silver Ion and Captopril.

Carbon-based nanoprobes, with excellent physicochemical performance and biocompatibility, are a kind of ideal nanomaterial for biosensing. Herein, we designed and prepared novel oxygen-doped nitrogen-enrichment carbon nanoribbons (ONCNs) with an excellent optical performance and uniform morphology, which could be used as a dual-mode fluorescence probe for the detection of Ag+ ion and captopril (Ctl) based on the synergism of photo-induced electron transfer and aggregation-induced quenching mechanisms. By recording the changes in fluorescent intensities of ONCNs, the Ag+ ion and Ctl concentrations can be easily tested in real samples. The results displayed that two good linear relationships existed between the change in fluorescent intensity of ONCNs and the concentrations of Ag+ ion and Ctl in the ranges of 3 µM to 30 µM and 1 µM to 30 µM, with the detection limit of 0.78 µM and 74 nM, respectively. The proposed sensing platform has also been successfully applied for the Ctl analysis in commercial tablet samples based on its high selectivity, proving its value in practical applications.

Antimicrobial Peptides: A Promising Strategy for Anti-tuberculosis Therapeutics.

The high global burden of tuberculosis (TB) and the increasing emergence of the drugresistant (DR) strain of Mycobacterium tuberculosis (Mtb) emphasize the urgent need for novel antimycobacterial agents. Antimicrobial peptides (AMPs) are small peptides widely existing in a variety of organisms and usually have amphiphilic cationic structures, which have a selective affinity to the negatively charged bacterial cell wall. Besides direct bactericidal mechanisms, including interacting with the bacterial cell membrane and interfering with the biosynthesis of the cell wall, DNA, or protein, some AMPs are involved in the host's innate immunity. AMPs are promising alternative or complementary agents for the treatment of DR-TB, given their various antibacterial mechanisms and low cytotoxicity. A large number of AMPs, synthetic or natural, from human to bacteriophage sources, have displayed potent anti-mycobacterial activity in vitro and in vivo. In this review, we summarized the features, antimycobacterial activity, and mechanisms of action of the AMPs according to their sources. Although AMPs have not yet met the expectations for clinical application due to their low bioavailabilities, high cost, and difficulties in large-scale production, their potent antimycobacterial activity and action mechanisms, which are different from conventional antibiotics, make them promising antibacterial agents against DR-Mtb in the future.

Quantitative Evaluation of the Carrier Separation Performance of Heterojunction Photocatalysts: The Case of g-C3N4/SrTiO3.

Heterojunction photocatalysts are of great interest in the energy and environmental fields, because of their potential to significantly increase the efficiency of harvesting solar energy. Advances in design have been hampered by the continued use of only qualitative analyses. Quantitative evaluation of the carrier separation performance is urgently needed for the design and application of heterojunction photocatalysts. Taking the g-C3N4/SrTiO3 heterojunction as an example, we address the conventional energy band and electronic structure issues by first-principles analysis. After interface coupling, the band edge alignment reverses from that of the respective isolated states of the heterojunction components, suggesting new ways of thinking about the catalytic mechanism of the heterojunction. More significantly, we show the carrier separation performance of heterojunction photocatalysts can be quantitatively predicted by the nonadiabatic molecular dynamics method, enabling more precisely directed research and promoting the quantified design and application of heterojunction photocatalysis, making a contribution of great scientific significance.

Age-related changes in excitatory and inhibitory intra-cortical circuits in auditory cortex of C57Bl/6 mice.

A common impairment in aging is age-related hearing loss (presbycusis), which manifests as impaired spectrotemporal processing. Aging is accompanied by alteration in normal inhibitory (GABA) neurotransmission, and changes in excitatory (NMDA and AMPA) synapses in the auditory cortex (ACtx). However, the circuits affected by these synaptic changes remain unknown. Mice of the C57Bl/6J strain show premature age-related hearing loss and changes in functional responses in ACtx. We thus investigated how auditory cortical microcircuits change with age by comparing young (∼ 6 weeks) and aged (>1 year old) C57Bl/6J mice. We performed laser scanning photostimulation (LSPS) combined with whole-cell patch clamp recordings from Layer (L) 2/3 cells in primary auditory cortex (A1) of young adult and aged C57Bl/6J mice. We found that L2/3 cells in aged C57Bl/6J mice display functional hypoconnectivity of both excitatory and inhibitory circuits. Compared to cells from young C57Bl/6 mice, cells from aged C57Bl/6J mice have fewer excitatory connections with weaker connection strength. Whereas young adult and aged C57Bl/6J mice have similar amounts of inhibitory connections, the strength of local inhibition is weaker in the aged group. We confirmed these results by recording miniature excitatory (mEPSCs) and inhibitory synaptic currents (mIPSCs). Our results suggest a specific reduction in excitatory and inhibitory intralaminar cortical circuits in aged C57Bl/6J mice compared with young adult animals. We speculate that these unbalanced changes in cortical circuits contribute to the functional manifestations of age-related hearing loss.

Echinacoside exerts its protective effects in a type 2 diabetes mellitus injury model via the AKT pathway.

Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.

Loss of oligodendrocyte ErbB receptor signaling leads to hypomyelination, reduced density of parvalbumin-expressing interneurons, and inhibitory function in the auditory cortex.

For a long time, myelin was thought to be restricted to excitatory neurons, and studies on dysmyelination focused primarily on excitatory cells. Recent evidence showed that axons of inhibitory neurons in the neocortex are also myelinated, but the role of myelin on inhibitory circuits remains unknown. Here we studied the impact of mild hypomyelination on both excitatory and inhibitory connectivity in the primary auditory cortex (A1) with well-characterized mouse models of hypomyelination due to loss of oligodendrocyte ErbB receptor signaling. Using laser-scanning photostimulation, we found that mice with mild hypomyelination have reduced functional inhibitory connections to A1 L2/3 neurons without changes in excitatory connections, resulting in altered excitatory/inhibitory balance. These effects are not associated with altered expression of GABAergic and glutamatergic synaptic components, but with reduced density of parvalbumin-positive (PV+ ) neurons, axons, and synaptic terminals, which reflect reduced PV expression by interneurons rather than PV+ neuronal loss. While immunostaining shows that hypomyelination occurs in both PV+ and PV- axons, there is a strong correlation between MBP and PV expression, suggesting that myelination influences PV expression. Together, the results indicate that mild hypomyelination impacts A1 neuronal networks, reducing inhibitory activity, and shifting networks towards excitation.

Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats.

OBJECTIVE: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H2O2) and explore the underlying mechanisms. METHODS: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H2O2-stimulated apoptosis. CONCLUSION: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

Microstructure Evolution and Its Correlation with Performance in Nitrogen-Containing Porous Carbon Prepared by Polypyrrole Carbonization: Insights from Hybrid Calculations.

The preparation of nitrogen-containing porous carbon (NCPC) materials by controlled carbonization is an exciting topic due to their high surface area and good conductivity for use in the fields of electrochemical energy storage and conversion. However, the poor controllability of amorphous porous carbon prepared by carbonization has always been a tough problem due to the unclear carbonation mechanism, which thus makes it hard to reveal the microstructure-performance relationship. To address this, here, we comprehensively employed reactive molecular dynamics (ReaxFF-MD) simulations and first-principles calculations, together with machine learning technologies, to clarify the carbonation process of polypyrrole, including the deprotonation and formation of pore structures with temperature, as well as the relationship between microstructure, conductance, and pore size. This work constructed ring expressions for PPy thermal conversion at the atomic level. It revealed the structural factors that determine the conductivity and pore size of carbonized products. More significantly, physically interpretable machine learning models were determined to quantitatively express structure factors and performance structure-activity relationships. Our study also confirmed that deprotonation preferentially occurred by desorbing the dihydrogen atom on nitrogen atoms during the carbonization of PPy. This theoretical work clearly reproduces the microstructure evolution of polypyrrole on an atomic scale that is hard to do via experimentation, thus paving a new way to the design and development of nitrogen-containing porous carbon materials with controllable morphology and performance.

Maximizing Performance of a Hybrid MnO2/Ni Electrochemical Actuator through Tailoring Lattice Tunnels and Cation Vacancies.

Electrochemical actuators play a key role in converting electrical energy to mechanical energy. However, a low actuation stress and an unsatisfied strain response rate strongly limit the extensive applications of the actuators. Here, we report hybrid manganese dioxide (MnO2) fabricated by introducing ramsdellite (R-MnO2) and Mn vacancies into birnessite (δ-MnO2) nanosheets, which in situ grew on the surface of a nickel (Ni) film, forming a hybrid MnO2/Ni actuator. The actuator demonstrated a rapid strain response of 0.88% s-1 (5.3% intrinsic strain in 6 s) and a large actuation stress of 244 MPa owing to the special R-MnO2 with a high density of sodium ion (Na+)-accessible lattice tunnels, Mn vacancies, and also a high Young's modulus of the hybrid MnO2/Ni composite. Besides, the cyclic stability of the actuator was realized after 1.2 × 104 cycles of electric stimulation under a frequency of 0.05 Hz. The finding of the novel hybrid MnO2/Ni actuator may provide a new strategy to maximize the actuating performance evidently through tailoring the lattice tunnel structure and introducing cation vacancies into electrochemical electrode materials.