Deep learning based approach for automated characterization of large marine microplastic particles.

The rapidly growing concern of marine microplastic pollution has drawn attentions globally. Microplastic particles are normally subjected to visual characterization prior to more sophisticated chemical analyses. However, the misidentification rate of current visual inspection approaches remains high. This study proposed a state-of-the-art deep learning-based approach, Mask R-CNN, to locate, classify, and segment large marine microplastic particles with various shapes (fiber, fragment, pellet, and rod). A microplastic dataset including 3000 images was established to train and validate this Mask R-CNN algorithm, which was backboned by a Resnet 101 architecture and could be tuned in less than 8 h. The fully trained Mask R-CNN algorithm was compared with U-Net in characterizing microplastics against various backgrounds. The results showed that the algorithm could achieve Precision = 93.30%, Recall = 95.40%, F1 score = 94.34%, APbb (Average precision of bounding box) = 92.7%, and APm (Average precision of mask) = 82.6% in a 250 images test dataset. The algorithm could also achieve a processing speed of 12.5 FPS. The results obtained in this study implied that the Mask R-CNN algorithm is a promising microplastic characterization method that can be potentially used in the future for large-scale surveys.

Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology for in vivo bacterial ablation.

The nonselective membrane disruption of antimicrobial peptides (AMPs) helps in combating the antibacterial resistance. But their overall positive charges lead to undesirable hemolysis and toxicity toward normal living cells, as well as the rapid clearance from blood circulation. In consequence, developing smart AMPs to optimize the antimicrobial outcomes is highly urgent. Relying on the local acidity of microbial infection sites, in this work, we designed an acidity-triggered charge reversal nanotherapeutics with adaptable geometrical morphology for bacterial targeting and optimized therapy. C16-A3K4-CONH2 was proposed and the ε-amino groups in lysine residues were acylated by dimethylmaleic amide (DMA), enabling the generated C16-A3K4(DMA)-CONH2 to self-assemble into negatively charged spherical nanostructure, which relieved the protein adsorption and prolonged blood circulation in vivo. After the access of C16-A3K4(DMA)-CONH2 into the microbial infection sites, acid-sensitive ß-carboxylic amide would hydrolyze to regenerate the positive C16-A3K4-CONH2 to destabilize the negatively charged bacterial membrane. In the meanwhile, attractively, the self-assembled spherical nanoparticle transformed to rod-like nanostructure, which was in favor of the efficient binding with bacterial membranes due to the larger contact area. Our results showed that the acid-activated AMP nanotherapeutics exhibited strong and broad-spectrum antimicrobial activities against Yeast, Gram-positive Staphylococcus aureus, Gram-negative Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, the biocompatible lipopeptide nanotherapeutics dramatically improved the dermapostasis caused by bacterial infection. The strategy of merging pathology-activated therapeutic function and morphological adaptation to augment therapeutic outcomes shows the great potential for bacterial inhibition. STATEMENT OF SIGNIFICANCE: The overall positive charges of antimicrobial peptides (AMPs) lead to undesirable hemolysis and nonselective toxicity, as well as the rapid clearance from blood circulation. Infection-activated lipopeptide nanotherapeutics with adaptable geometrical morphology were developed to address these issues. The self-assembled lipopeptide was pre-decorated to reverse the positive charge to reduce the hemolysis and nonselective cytotoxicity. After accessing the acidic infection sites, the nanotherapeutics recovered the positive charge to destabilize negatively charged bacterial membranes. Meanwhile, the morphology of self-assembled nanotherapeutics transformed from spherical nanoparticles to rod-like nanostructures in the lesion site, facilitating the improved association with bacterial membranes to boost the therapeutic efficiency. These results provide new design rationale for AMPs developed for bacterial inhibition.

Photoresponsive Solid Nanochannels Membranes: Design and Applications.

Light stimuli have notable advantages over other environmental stimuli, such as more precise spatial and temporal regulation, and the ability to serve as an energy source to power the system. In nature, photoresponsive nanochannels are important components of organisms, with examples including the rhodopsin channels in optic nerve cells and photoresponsive protein channels in the photosynthesis system of plants. Inspired by biological channels, scientists have constructed various photoresponsive, smart solid-state nanochannels membranes for a range of applications. In this review, the methods and applications of photosensitive nanochannels membranes are summarized. The authors believe that this review will inspire researchers to further develop multifunctional artificial nanochannels for applications in the fields of biosensors, stimuli-responsive smart devices, and nanofluidic devices, among others.

Three New Hydroxyphenylacetic Acid Derivatives and A New Alkaloid from Endophytic Fungus Mortierella sp. in Epimedium acuminatum Franch. and Their Antibacterial Activity.

Three new hydroxyphenylacetic acid derivatives, stachylines E-G (1-3), and a new alkaloid, mortieridinone (4), along with six known compounds (5-10), were isolated from endophytic fungus Mortierella sp. in Epimedium acuminatum Franch. Their structures were determined by their spectroscopic analyses and by comparison with the literature data. Compounds 7 and 10 showed selective antibacterial activity against tested multidrug-resistant bacteria with minimum inhibitory concentration (MIC) values ranging from 25 to 3.13 µg/mL.

VARAdb: a comprehensive variation annotation database for human.

With the study of human diseases and biological processes increasing, a large number of non-coding variants have been identified and facilitated. The rapid accumulation of genetic and epigenomic information has resulted in an urgent need to collect and process data to explore the regulation of non-coding variants. Here, we developed a comprehensive variation annotation database for human (VARAdb, http://www.licpathway.net/VARAdb/), which specifically considers non-coding variants. VARAdb provides annotation information for 577,283,813 variations and novel variants, prioritizes variations based on scores using nine annotation categories, and supports pathway downstream analysis. Importantly, VARAdb integrates a large amount of genetic and epigenomic data into five annotation sections, which include 'Variation information', 'Regulatory information', 'Related genes', 'Chromatin accessibility' and 'Chromatin interaction'. The detailed annotation information consists of motif changes, risk SNPs, LD SNPs, eQTLs, clinical variant-drug-gene pairs, sequence conservation, somatic mutations, enhancers, super enhancers, promoters, transcription factors, chromatin states, histone modifications, chromatin accessibility regions and chromatin interactions. This database is a user-friendly interface to query, browse and visualize variations and related annotation information. VARAdb is a useful resource for selecting potential functional variations and interpreting their effects on human diseases and biological processes.

Facile one-step synthesis of quaternary AgInZnS quantum dots and their applications for causing bioeffects and detecting Cu2.

Water-soluble AgInZnS quantum dots (AIZS QDs) were synthesized with glutathione (GSH) as a stabilizer by a facile one-step method based on a hydrothermal reaction between the nitrate salts of the corresponding metals and sodium sulfide as a sulfide precursor at 110 °C. The optimal reaction conditions (temperature, time, pH, and the molar ratios of the precursors) were studied. According to the data from TEM, XPS, and XRD, AIZS QDs were characterized with excellent optical properties. The results showed that the aqueous-dispersible AIZS QDs were quasi-spherical and their average diameter was 3.51 nm. Furthermore, the cytotoxicity of AIZS QDs was investigated by microcalorimetry and microscopy techniques (confocal microscopy and TEM). The data revealed that AIZS QDs exhibited low toxicity, biocompatibility, and good water stability, due to which they could be used as a fluorescent probe for bioimaging and labeling. In addition, AIZS QDs could be used as a sensor to detect Cu2+ because the fluorescence of AIZS QDs was quenched by Cu2+.

The interactions of CdTe quantum dots with serum albumin and subsequent cytotoxicity: the influence of homologous ligands.

With spreading applications of fluorescent quantum dots (QDs) in biomedical fields in recent years, there is increasing concern over their toxicity. Among various factors, surface ligands play critical roles. Previous studies usually employed QDs with different kinds of surface ligands, but general principles were difficult to be obtained since it was hard to compare these surface ligands with varied chemical structures without common features. Herein, the physicochemical properties of two types of CdTe QDs were kept very similar, but different in the surface ligands with mercaptoacetic acid (TGA) and 3-mercaptopropionic acid (MPA), respectively. These two types of homologous ligands only had a difference in one methylene group (-CH2-). The interactions of the two types of CdTe QDs with bovine serum albumin (BSA), which was one of the main components of cell culture, were studied by fluorescence, UV-vis absorption, and circular dichroism spectroscopy. It was found that the fluorescence quenching of BSA by CdTe QDs followed a static quenching mechanism, and there was no obvious difference in the Stern-Volmer quenching constants and binding constants. The thermodynamic parameters of the two types of QDs were similar. BSA underwent conformational changes upon association with these QDs. By comparing the cytotoxicity of these two types of QDs, TGA-capped QDs were found to be less cytotoxic than MPA-capped QDs. Besides, in the presence of serum proteins, the cytotoxicity of the QDs was reduced. QDs in the absence of serum proteins had a higher internalization efficiency, compared with those in the medium with serum. To the best of our knowledge, this is a rare study focusing on surface ligands with such small variations at the biomolecular and cellular levels. These findings can provide new insights for the design and applications of QDs in complex biological media.

Sleep state misperception in schizophrenia: Are negative symptoms at work?

OBJECTIVE: This study investigates subjective and objective sleep quality to ascertain whether there is a sleep state misperception in schizophrenia patients, as well as analyze potential effect factors. METHODS: A total of 148 inpatients with schizophrenia admitted to Beijing HuiLongGuan Hospital were enrolled in this study. The quality of objective sleep was assessed by polysomnography (PSG). On the second day after the successful completion of the PSG evaluation, an interview was arranged to collect patients' recorded subjective evaluation on sleep time, sleep latency, and wake times. Demographic information was collected from an interview, medical records were reviewed, and psychiatric symptoms were assessed using the Positive And Negative Symptom Scale (PANSS). RESULTS: The main finding of this study was that schizophrenic patients exhibited sleep state misperception with a pattern of overestimation of total sleep time (TST) as well as sleep efficiency (SE), and an underestimation of sleep onset latency (SOL). Regarding the ±standard deviation of the differences between subjective and objective TST as a clinical acceptable range, the patients were divided into three groups: the overestimate group, the normal group, and the underestimate group. The differences of total PANSS score, especially the PANSS-N score in the overestimate group, the normal group and the underestimate group were significant, and there were significant differences between the overestimate group and the other groups. CONCLUSION: A comprehensive evaluation of the subjective and objective sleep quality in patients with schizophrenia is needed, especially when negative symptoms are severe.

An electrochemical and surface plasmon resonance study of adsorption actions of DNA by Escherichia coli.

In this work, we proposed an immobilization scheme targeting Escherichia coli bacterial cells onto gold surface utilizing polypeptide RGD's binding specificity to gold particles. Adsorption kinetics of extracellular Herring Sperm DNA on E. coli was then studied using electrochemical methods along with surface plasmon resonance spectroscopy through this immobilization scheme. The adsorption equilibrium constants of DNA adsorbing to E. coli from electrochemical method and surface plasmon resonance spectroscopy, were (5.596±0.462)×105 L mol(-1) and (1.24±0.361)×105 L mol(-1), accordingly. Importantly, this is the first study that used an electrochemical method to express the adsorptive action of DNA by E. coli.

Adhesion of quantum dots-induced membrane damage of Escherichia coli.

The toxicity of CdTe QDs modified with three different ligands, namely mercaptopropionic acid (MPA), N-acetyl-L-cysteine (NAC), and glutathione (GSH), were investigated via microcalorimetric, spectroscopic, and microscopic methods. The three ligand-modified QDs have nearly identical hydrodynamic size. The results of the calorimetric experiments and optical density measurements indicate that the QDs inhibited the growth of Gram-negative Escherichia coli. The toxicity order of the three QDs is MPA-CdTe QDs>GSH-CdTe QDs>NAC-CdTe QDs. The inhibitory effects of the QDs, cadmium chloride (CdCl(2)), MPA, and the CdCl(2) and MPA mixture on E. coli growth indicate that the toxicity mechanism of QDs may be related to their bacterial adhesion. When dispersed in the cell suspensions, QDs tend to have their high surface energy reduced through adsorption to the bacterial surface, as confirmed by transmission electron microscopy and inductively coupled plasma atomic emission spectroscopy results. Furthermore, the effect of QDs on the membrane fluidity and permeability was investigated. GSH-CdTe QDs have a greater effect on the membrane function of E. coli than those of MPA-CdTe and NAC-CdTe QDs. This result may be attributed to the stronger lipophilicity of GSH compared with those of MPA and NAC.

Spectroscopic studies on the interactions between CdTe quantum dots coated with different ligands and human serum albumin.

This paper investigates the interactions between human serum albumin (HSA) and CdTe quantum dots (QDs) with nearly identical hydrodynamic size, but capped with four different ligands (MPA, NAC, and GSH are negatively charged; CA is positively charged) under physiological conditions. The investigation was carried out using fluorescence spectroscopy, circular dichroism (CD) spectra, UV-vis spectroscopy, and dynamic light scattering (DLS). The results of fluorescence quenching and UV-vis absorption spectra experiments indicated the formation of the complex of HSA and negatively charged QDs (MPA-CdTe, NAC-CdTe, and GSH-CdTe), which was also reconfirmed by the increasing of the hydrodynamic radius of QDs. The K(a) values of the three negatively charged QDs are of the same order of magnitude, indicating that the interactions are related to the nanoparticle itself rather than the ligands. ΔH<0 and ΔS>0 implied that the electrostatic interactions play predominant roles in the adsorption process. Furthermore, it was also proven that QDs can induce the conformational changes of HSA from the CD spectra and the three-dimensional fluorescence spectra of HSA. However, our results demonstrate that the interaction mechanism between the positively charged QDs (CA-CdTe) and HSA is significantly different from negatively charged QDs. For CA-CdTe QDs, both the static and dynamic quenching occur within the investigated range of concentrations. According to the DLS results, some large-size agglomeration also emerged.

Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA.

Chlorpyrifos (CPF) is a widely used organophosphate insecticide which could bind with human serum albumin (HSA) and bovine serum albumin (BSA). The binding behavior was studied employing fluorescence, three-dimensional fluorescence, Circular dichroism (CD) spectroscopy, UV-vis absorption spectroscopy, electrochemistry and molecular modeling methods. The fluorescence spectra revealed that CPF causes the quenching of the fluorescence emission of serum albumin. Stern-Volmer plots were made and quenching constants were thus obtained. The results suggested the formation of the complexes of CPF with serum albumins, which were in good agreement with the results from electrochemical experiments. Association constants at 25°C were 3.039 × 10(5) mol L(-1) for HSA, and 0.3307 × 10(5) mol L(-1) for BSA, which could affect the distribution, metabolism, and excretion of pesticide. The alterations of protein secondary structure in the presence of CPF were confirmed by the evidences from UV and CD spectra. Site competitive experiments also suggested that the primary binding site for CPF on serum albumin is close to tryptophan residues 214 of HSA and 212 of BSA, which was further confirmed by molecular modeling.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil adduct with antioxidant and anticancer properties.

A novel pH-sensitive (±)-α-tocopherol-5-fluorouracil (VE-5-FU) adduct with antioxidant and anticancer properties for antioxidant-based cancer chemoprevention was synthesized and utilized for selective drug release in the stomach.

Synthesis of a novel hydrazone derivative and biophysical studies of its interactions with bovine serum albumin by spectroscopic, electrochemical, and molecular docking methods.

Hydrazone derivatives possess potential antitumor activities based on modulation of the iron metabolism in cancer cell. A novel hydrazone, N'-(2,4-dimethoxybenzylidene)-2-hydroxybenzohydrazide (DBH), has been synthesized and characterized, which is an analogue of 311 possessing potent anticancer activity. The interactions between DBH and bovine serum albumin (BSA) have been investigated systematically by fluorescence, molecular docking, circular dichroism (CD), UV-vis absorption, and electrochemical impedance spectroscopy (EIS) methods under physiological conditions. The fluorescence quenching observed is attributed to the formation of a complex between BSA and DBH, and the reverse temperature effect of the fluorescence quenching has been found and discussed. The primary binding pattern is determined by hydrophobic interaction occurring in Sudlow's site I of BSA. DBH could slightly change the secondary structure and induce unfolding of the polypeptides of protein. An average binding distance of ~4.0 nm has been determined on the basis of the Förster resonance energy theory (FRET). The effects of iron on the system of DBH-BSA have also been investigated. It is found that iron could compete against BSA to bind DBH. All of these results are supported by a docking study using a BSA crystal model. It is shown that DBH can efficiently bind with BSA and be transported to the focuses needed. Subsequent antitumor test and detailed anticancer mechanism are undergoing in our lab.

Binding interaction of quinclorac with bovine serum albumin: a biophysical study.

Quinclorac (QUC) is a new class of highly selective auxin herbicides. The interaction between QUC and bovine serum albumin (BSA) was investigated by fluorescence spectroscopy, synchronous fluorescence, three-dimensional fluorescence, CD spectroscopy and UV-vis absorption spectroscopy under simulative physiological condition. It was proved that the probable quenching mechanism of BSA by quinclorac was dynamic quenching. The Stern-Volmer quenching model has been successfully applied and the activation energy of the interaction as much as 8.03 kJ mol(-1), corresponding thermodynamic parameters DeltaH(theta), DeltaS(theta) and DeltaG(theta) were calculated. The results indicated that the acting forces between QUC and BSA were mainly hydrogen bonding and van der Waals forces. According to the Förster non-radiation energy transfer theory, the average binding distance between donor (BSA) and acceptor (QUC) was obtained (r=3.12 nm). The alterations of protein secondary structure in the presence of QUC were confirmed by the evidences from three-dimensional fluorescence, synchronous fluorescence and CD spectroscopy. Furthermore, the site marker competitive experiments indicated that the binding of QUC to BSA primarily took place in Sudlow site I.