Designing antimicrobial peptides using deep learning and molecular dynamic simulations.

With the emergence of multidrug-resistant bacteria, antimicrobial peptides (AMPs) offer promising options for replacing traditional antibiotics to treat bacterial infections, but discovering and designing AMPs using traditional methods is a time-consuming and costly process. Deep learning has been applied to the de novo design of AMPs and address AMP classification with high efficiency. In this study, several natural language processing models were combined to design and identify AMPs, i.e. sequence generative adversarial nets, bidirectional encoder representations from transformers and multilayer perceptron. Then, six candidate AMPs were screened by AlphaFold2 structure prediction and molecular dynamic simulations. These peptides show low homology with known AMPs and belong to a novel class of AMPs. After initial bioactivity testing, one of the peptides, A-222, showed inhibition against gram-positive and gram-negative bacteria. The structural analysis of this novel peptide A-222 obtained by nuclear magnetic resonance confirmed the presence of an alpha-helix, which was consistent with the results predicted by AlphaFold2. We then performed a structure-activity relationship study to design a new series of peptide analogs and found that the activities of these analogs could be increased by 4-8-fold against Stenotrophomonas maltophilia WH 006 and Pseudomonas aeruginosa PAO1. Overall, deep learning shows great potential in accelerating the discovery of novel AMPs and holds promise as an important tool for developing novel AMPs.

A pragmatic clinical trial assessing the effect of a targeted notification and clinical support pathway on the diagnostic evaluation and treatment of individuals with left ventricular hypertrophy (NOTIFY-LVH).

BACKGROUND: Electronic health records contain vast amounts of cardiovascular data, including potential clues suggesting unrecognized conditions. One important example is the identification of left ventricular hypertrophy (LVH) on echocardiography. If the underlying causes are untreated, individuals are at increased risk of developing clinically significant pathology. As the most common cause of LVH, hypertension accounts for more cardiovascular deaths than any other modifiable risk factor. Contemporary healthcare systems have suboptimal mechanisms for detecting and effectively implementing hypertension treatment before downstream consequences develop. Thus, there is an urgent need to validate alternative intervention strategies for individuals with preexisting-but potentially unrecognized-LVH. METHODS: Through a randomized pragmatic trial within a large integrated healthcare system, we will study the impact of a centralized clinical support pathway on the diagnosis and treatment of hypertension and other LVH-associated diseases in individuals with echocardiographic evidence of concentric LVH. Approximately 600 individuals who are not treated for hypertension and who do not have a known cardiomyopathy will be randomized. The intervention will be directed by population health coordinators who will notify longitudinal clinicians and offer to assist with the diagnostic evaluation of LVH. Our hypothesis is that an intervention that alerts clinicians to the presence of LVH will increase the detection and treatment of hypertension and the diagnosis of alternative causes of thickened myocardium. The primary outcome is the initiation of an antihypertensive medication. Secondary outcomes include new hypertension diagnoses and new cardiomyopathy diagnoses. The trial began in March 2023 and outcomes will be assessed 12 months from the start of follow-up. CONCLUSION: The NOTIFY-LVH trial will assess the efficacy of a centralized intervention to improve the detection and treatment of hypertension and LVH-associated diseases. Additionally, it will serve as a proof-of-concept for how to effectively utilize previously collected electronic health data to improve the recognition and management of a broad range of chronic cardiovascular conditions. TRIAL REGISTRATION: NCT05713916.

Synergistic Poly(lactic acid) Antibacterial Surface Combining Superhydrophobicity for Antiadhesion and Chlorophyll for Photodynamic Therapy.

The problem of nosocomial infections caused by bacterial growth on material surfaces is an urgent threat to public health. Although numerous materials and methods have been explored to fight against infections, the methods are complicated and the materials are slightly toxic. It is highly desirable to develop an antibacterial strategy that kills bacteria effectively without drug resistance and cytotoxicity. Herein, we present a synergistic antibacterial polylactic acid (PLA) surface with superhydrophobic antibacterial adhesion and photodynamic bactericidal activity. Initially, the surface displayed low-adhesion superhydrophobicity and resisted most bacterial adhesion. Furthermore, completely non-toxic chlorophyll possessed excellent photodynamic bactericidal properties under non-toxic visible light, which was incorporated into micro-/nanoscale PLA surfaces. We achieved efficient antibacterial activity using completely non-toxic materials and a facile non-solvent-induced phase separation process. This non-toxic, simple, good biocompatible, and no drug-resistant strategy has great advantages in combating bacterial infections.

Dipeptide nanoparticle and aptamer-based hybrid fluorescence platform for enrofloxacin determination.

A novel fluorescence platform was fabricated for enrofloxacin determination by using cDNA-modified dipeptide fluorescence nanoparticles (FDNP-cDNA) and aptamer-modified magnetic Fe3O4 nanoparticles (Fe3O4-Apt). The FDNP were prepared via tryptophan-phenylalanine self-assembling. When magnetic Fe3O4-Apt incubated with standard solution or sample extracts, the target enrofloxacin was selectively captured by the aptamer on the surface of the Fe3O4 nanoparticles. After removing interference by washing with phosphate-buffered saline, the FDNP-cDNA was added, which can bind to the aptamer on the surface of the Fe3O4 nanoparticles not occupied by the analyte. The higher the concentration of the target enrofloxacin in the standard or sample solution is, the less the FDNP-cDNA can be bound with the Fe3O4 nanoparticles, and the more the FDNP-cDNA can be observed in the supernatant. Fluorescence intensity (Ex/Em = 310/380 nm) increased linearly in the enrofloxacin concentration range 0.70 to 10.0 ng/mL with a detection limit of 0.26 ng/mL (S/N = 3). Good recoveries (88.17-99.30%) were obtained in spiked lake water, chicken, and eel samples with relative standard deviation of 2.7-6.2% (n = 3).

Pressure Injury Development, Mitigation, and Outcomes of Patients Proned for Acute Respiratory Distress Syndrome.

OBJECTIVE: To describe trends and risk factors for pressure injuries (PIs) in adult critical care patients proned to alleviate acute respiratory distress syndrome secondary to COVID-19 and examine the effectiveness of products and strategies used to mitigate PIs. METHODS: The authors conducted a retrospective chart review between April 9 and June 8, 2020. Demographic data were analyzed using descriptive statistics. Differences between groups with and without PIs were analyzed. RESULTS: Among 147 patients, significant PI risk factors included male sex (P = .019), high body mass index (>40 kg/m2; P = .020), low Braden Scale score (<12; P = .018), and low-dose vasopressor therapy (P = .020). Taping endotracheal tubes (ETTs) caused significantly fewer facial PIs than commercial ETT holders (P < .0001). Maximum prone duration/session was a significant risk factor for anterior PIs (P = .016), which dropped 71% with newer pressure redistribution products. d-Dimer greater than 3,200 µg/mL (P = .042) was a significant risk factor for sacrococcygeal PIs while supine. Mortality was 30%; significant risk factors included age older than 60 years (P = .005), Sequential Organ Failure Assessment score greater than 11 (P = .003), and comorbid congestive heart failure (P = .016). CONCLUSIONS: Taping the ETT, limiting the maximum duration of prone positioning to less than 32 hours, and frequent repositioning while supine may reduce the number of modifiable risk factors for PIs. Standardized methods for testing products for PI prevention will inform individualized patient care.

Two regulatory factors of Vibrio cholerae activating the mannose-sensitive haemagglutinin pilus expression is important for biofilm formation and colonization in mice.

Vibrio cholerae the causative agent of cholera, uses a large number of coordinated transcriptional regulatory events to transition from its environmental reservoir to the host intestine, which is its preferred colonization site. Transcription of the mannose-sensitive haemagglutinin pilus (MSHA), which aids the persistence of V. cholerae in aquatic environments, but causes its clearance by host immune defenses, was found to be regulated by a yet unknown mechanism during the infection cycle of V. cholerae. In this study, genomic expression library screening revealed that two regulators, VC1371 and VcRfaH, are able to positively activate the transcription of MSHA operon. VC1371 is localized and active in the cell membrane. Deletion of vc1371 or VcrfaH genes in V. cholerae resulted in less MshA protein production and less efficiency of biofilm formation compared to that in the wild-type strain. An adult mouse model showed that the mutants with vc1371 or VcrfaH deletion colonized less efficiently than the wild-type; the VcrfaH deletion mutant showed less colonization efficiency in the infant mouse model. The findings strongly suggested that the two regulators, namely VC1371 and VcRfaH, which are involved in the regulation of MSHA expression, play an important role in V. cholerae biofilm formation and colonization in mice.

Evaluation of ultrahigh-resolution optical coherence tomography for basal cell carcinoma, seborrheic keratosis, and nevus.

BACKGROUND: Basal cell carcinoma, seborrheic keratosis, and nevus are common skin conditions. Though most of the skin diseases can be distinguished from each other by physician's naked eyes, the diagnostic accuracy is not 100%. The accurate diagnosis and assessment of three diseases make a big difference on the clinical management. Nowadays, biopsy is still the gold standard for diagnosis even it is invasive, time-consuming, and painful. Ultrahigh-resolution optical coherence tomography is an emerging technology that can produce in situ, cellular-resolution, real-time, continuous, 3D images in a noninvasive way. MATERIALS AND METHODS: In our study, four basal cell carcinoma patients, five seborrheic keratosis patients, and 10 nevus patients who were diagnosed by histology were studied by ultrahigh-resolution optical coherence tomography after visual examination by experienced dermatologists. Cellular contrast was utilized to clearly identify the features of the three skin diseases. RESULTS: The features including such as hyperkeratosis (horn pseudocysts), papillomatosis, intraepidermal nests, elongated, and expanded rete ridge can be visualized in seborrheic keratosis. Tumor nodular, mucin surrounding with tumor (retraction space in histopathology), tumor subtype, and necrosis were featured in basal cell carcinoma. Pigment was characterized in epidermis and dermis. The comparison of ultrahigh-resolution optical coherence tomography images reveals a strong correlation with histological images. CONCLUSION: Ultrahigh-resolution optical coherence tomography can complement existing diagnostic techniques for investigating seborrheic keratosis, basal cell carcinoma and nevus, and show enormous potential in vivo applications for the three skin diseases in the future.

Development of a Broad-Specific Competitive ELISA for First-Generation Cephalosporin Antibiotics in Animal-Derived Foods Samples.

The abuse of antibiotics, such as the cephalosporins in livestock and aquaculture productions, usually causes the widespread antibiotic resistance due to their growth-promoting effects. In this study, cephalexin was chosen as the hapten molecule to prepare a broad-spectrum rabbit polyclonal antibody for cephalosporin antibiotics. The obtained antibody exhibited broad cross-reactivity ranging from 0.05% to 100% with 10 cephalosporins. Based on this antibody, we developed a broad-specific indirect competitive ELISA (ic-ELISA) for cefalexin, cefradine, cefadroxil and cefazolin with the half maximal inhibitory concentration (IC50) ranging from 0.72 to 2.99 ng/mL in working buffer. For animal-derived food samples with spiked cephalosporins, the ic-ELISA exhibited an excellent recovery ranging from 72.3% to 95.6%. To verify the accuracy of this proposed ic-ELISA, its detection performance was evaluated utilizing the high-performance liquid chromatography with satisfactory results. This study confirmed that: firstly, the prepared antibody can be used as a class-specific recognition element to develop immunoassays for cephalosporin antibiotics; and secondly, the developed ic-ELISA provided a new tool for broad-spectrum detection of first-generation cephalosporins in animal-derived foods.

Evaluation of Volatile Compounds in Milks Fermented Using Traditional Starter Cultures and Probiotics Based on Odor Activity Value and Chemometric Techniques.

The volatile components of milks fermented using traditional starter cultures (Streptococcus thermophilus and Lactobacillus bulgaricus) and probiotics (Lactobacillus lactis, Lactobacillus bifidus, Lactobacillus casei, and Lactobacillus plantarum) were investigated by means of gas chromatography-mass spectrometry (GC-MS) combined with simultaneous distillation extraction (SDE). A total of 53 volatile compounds were detected, being 10 aldehydes, 11 ketones, 10 acids, 11 hydrocarbons, 7 benzene derivatives, and 4 other compounds. The starter culture was found to significantly affect the composition of volatile components in the fermented milks. Ketones and hydrocarbons were the dominant compounds in milk before fermentation, while acids were dominant compounds in the fermented samples. Compared with probiotics, there was greater abundance of volatile components in fermented milks with traditional strains. The importance of each volatile compound was assessed on the basis of odor, thresholds, and odor activity values (OAVs). Of the volatile compounds, 31 of them were found to be odor-active compounds (OAV > 1). The component with the highest OAVs in most samples was (E,E)-2,4-decadienal. Heatmap analysis and principal component analysis were employed to characterize the volatile profiles of milks fermented by different starter cultures. The results could help to better understand the influence of starter cultures on the odor quality of milks.

Cellular resolution corneal imaging with extended imaging range.

Current optical coherence tomography (OCT) technology, which is used for imaging the eye's anterior segment, has been established as a clinical gold standard for the diagnosis of corneal diseases. However, the cellular resolution level information that is critical for many clinical applications is still not available. The major technical challenges toward cellular resolution OCT imaging are the limited ranging depth and depth of focus (DOF). In this work, we present a novel ultrahigh resolution OCT system that achieves an isotropic spatial resolution of <2 µm in tissue. The proposed system could approximately double the ranging depth and extend the DOF using the dual-spectrometer design and the forward-model based digital refocusing method, respectively. We demonstrate that the novel system is capable of visualizing the full thickness of the pig cornea over the ranging depth of 3.5 mm and the border of the corneal endothelial cells 8 times Rayleigh range away from the focal plane. This technology has the potential to realize cellular resolution corneal imaging in vivo.

RETRACTED: Triptolide inhibits viability and migration while promotes apoptosis in nephroblastoma cells by regulation of miR-193b-3p.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief as panels from Figure 1E appear similar to panels from Figures 1G, 3D and 5D. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Activity Improvement and Vital Amino Acid Identification on the Marine-Derived Quorum Quenching Enzyme MomL by Protein Engineering.

MomL is a marine-derived quorum-quenching (QQ) lactonase which can degrade various N-acyl homoserine lactones (AHLs). Intentional modification of MomL may lead to a highly efficient QQ enzyme with broad application potential. In this study, we used a rapid and efficient method combining error-prone polymerase chain reaction (epPCR), high-throughput screening and site-directed mutagenesis to identify highly active MomL mutants. In this way, we obtained two candidate mutants, MomLI144V and MomLV149A. These two mutants exhibited enhanced activities and blocked the production of pathogenic factors of Pectobacterium carotovorum subsp. carotovorum (Pcc). Besides, seven amino acids which are vital for MomL enzyme activity were identified. Substitutions of these amino acids (E238G/K205E/L254R) in MomL led to almost complete loss of its QQ activity. We then tested the effect of MomL and its mutants on Pcc-infected Chinese cabbage. The results indicated that MomL and its mutants (MomLL254R, MomLI144V, MomLV149A) significantly decreased the pathogenicity of Pcc. This study provides an efficient method for QQ enzyme modification and gives us new clues for further investigation on the catalytic mechanism of QQ lactonase.

Fluorometric determination of ciprofloxacin using molecularly imprinted polymer and polystyrene microparticles doped with europium(III)(DBM)3phen.

The authors describe a microparticle-based system for the detection of the fluoroquinolone antibiotic ciprofloxacin. The method is using the tris(dibenzoylmethane)(1,10-phenanthroline)europium(III) luminophore in polystyrene microparticles along with a molecularly imprinted polymer (MIP) for ciprofloxacin. If ciprofloxacin is captured by the MIP, it quenches the fluorescence of the luminophores. Fluorescence drops linearly in the 0.5-100 µg L-1 ciprofloxacin concentration range, and the detection limit is 92 ng L-1. The method was applied to the analysis of fish samples to assess the analytical performance of the probe. Recoveries ranged from 85.4 to 86.6%, and relative standard deviations between 2.1 and 3.9% (for n = 5). Graphical abstract Schematic presentation of a microparticle-based probe using the tris(dibenzoylmethane)(1,10-phenanthroline)europium(III) luminophore in polystyrene particles along with a molecularly imprinted polymer for ciprofloxacin. After removal of template, carboxylic groups left in the probe can bind to ciprofloxacin through hydrogen bonds.

Preliminary Research on the Nonlinear Ultrasonic Detection of the Porosity of Porous Material Based on Dynamic Wavelet Fingerprint Technology.

Porosity is an important characteristic of porous material, which affects mechanical and material properties. In order to solve the problem that the large distribution range of pore size of porous materials leads to the large detection errors of porosity, the non-linear ultrasonic testing technique is applied. A graphite composite was used as the experimental object in the study. As the accuracy of porosity is directly related with feature extraction, the dynamic wavelet fingerprint (DWFP) technology was utilized to extract the feature parameter of the ultrasonic signals. The effects of the wavelet function, scale factor, and white slice ratio on the extraction of the nonlinear feature are discussed. The SEM photos were conducted using gray value to identify the aperture. The relationship between pore diameter and detection accuracy was studied. Its results show that the DWFP technology could identify the second harmonic component well, and the extracted nonlinear feature could be used for the quantitative trait of porosity. The larger the proportion of the small diameter holes and the smaller the aperture distribution range was, the smaller the error was. This preliminary research aimed to improve the nondestructive testing accuracy of porosity and it is beneficial to the application of porous material in the manufacturing field.

Self-assembly of phospholipid molecules in solutions under shear flows: Microstructures and phase diagrams.

Shear-induced microstructures and their phase diagrams were investigated for phospholipid molecules in aqueous solution by dissipative particle dynamic simulation. Self-assembled microstructures, including spherical and cylindrical micelles, spherical vesicles, lamellae, undulated lamellae, perforated lamellae, and continuous networks, were observed under various shear flows and phospholipid concentrations, where the spatial inhomogeneity and symmetry were analysed. A series of phase diagrams were constructed based on the chain lengths under various phospholipid concentrations. The phase distributions showed that the structures with spherical symmetry could be shear-induced to structures with cylindrical symmetry in the dilute solutions. In the semi-concentrated solutions, the lamellae were located in most spaces under zero shear flows, which could be shear-induced into undulated lamellae and then into cylindrical micelles. For the concentrated solutions, the strong shear flows oriented the directions of multilayer lamellae and phase transitions appeared between several cylindrical network structures. These observations on shear-induced microstructures and their distributions revealed a promising approach that could be used to design bio-microstructures based on phospholipid molecules under shear flows.

Extending the depth of focus of fiber-optic optical coherence tomography using a chromatic dual-focus design.

We report a dual-focus fiber-optic probe designed to extend depth of focus (DOF) in high-resolution endoscopic optical coherence tomography. We exploited the broad spectral bandwidth of a supercontinuum source and, in the fiber probe, the foci of the 750-1000 nm and 1100-1450 nm inputs were axially chromatically shifted. The interference signals from the two spectral bands were measured with a Si camera-based spectrometer and an InGaAs camera-based spectrometer, respectively. We verified the feasibility of the design using a phantom composed of microparticles and swine small intestine tissue ex vivo. The results showed that a transverse resolution below 5 µm over 300 µm could be maintained, and that the extended DOF was 2 times larger than that of the single focus probe via the use of dual spectral band inputs and a chromatic focal shift.

Energy Harvesting Technologies for Achieving Self-Powered Wireless Sensor Networks in Machine Condition Monitoring: A Review.

Condition monitoring can reduce machine breakdown losses, increase productivity and operation safety, and therefore deliver significant benefits to many industries. The emergence of wireless sensor networks (WSNs) with smart processing ability play an ever-growing role in online condition monitoring of machines. WSNs are cost-effective networking systems for machine condition monitoring. It avoids cable usage and eases system deployment in industry, which leads to significant savings. Powering the nodes is one of the major challenges for a true WSN system, especially when positioned at inaccessible or dangerous locations and in harsh environments. Promising energy harvesting technologies have attracted the attention of engineers because they convert microwatt or milliwatt level power from the environment to implement maintenance-free machine condition monitoring systems with WSNs. The motivation of this review is to investigate the energy sources, stimulate the application of energy harvesting based WSNs, and evaluate the improvement of energy harvesting systems for mechanical condition monitoring. This paper overviews the principles of a number of energy harvesting technologies applicable to industrial machines by investigating the power consumption of WSNs and the potential energy sources in mechanical systems. Many models or prototypes with different features are reviewed, especially in the mechanical field. Energy harvesting technologies are evaluated for further development according to the comparison of their advantages and disadvantages. Finally, a discussion of the challenges and potential future research of energy harvesting systems powering WSNs for machine condition monitoring is made.

Multifiber angular compounding optical coherence tomography for speckle reduction.

We report on an integrated fiber optic design to implement multifiber angular compounding optical coherence tomography, which enables angular compounding for speckle reduction. A multi-facet fiber array delivers three light beams to the sample with different incident angles. Back-reflective/back-scattered signals from these channels were simultaneously detected by a three-channel spectrometer. The axial and lateral resolution was measured to be ∼3 and ∼3.5 µm, respectively, in air with ∼100 dB sensitivity. We conducted ex vivo experiments on a rat esophagus to demonstrate a contrast to noise improvement of 1.58.

Characterization and bioactivities of a novel polysaccharide obtained from Gracilariopsis lemaneiformis.

Gracilariopsis lemaneiformis is a type of red alga that contains seaweed polysaccharide agar. In this study, a novel non-agar seaweed polysaccharide fraction named GCP (short of crude polysaccharide obtained from Gracilariopsis lemaneiformis) was isolated from Gracilariopsis lemaneiformis. Structural analysis showed that GCP shows triple helical chain conformation when dissolved in water and has many branches and long side chains. Also, 1→3 linkage is the major linkage and the sugar structures are galactopyranose configurations linked by ß-type glycosidic linkages. Two macromolecular substance fractions (GCP-1 and GCP-2) were purified by DEAE Sepharose Fast Flow column chromatography. Moreover, a splenocyte damage assay and splenocyte proliferation assay were used to analyse the bioactivities of GCP, GCP-1 and GCP-2. It was demonstrated that polysaccharides could protect splenocyte damaged by H2O2; GCP-2 shows a greatest protection rate, that is, 92.8%, which significantly enhanced the splenocyte proliferation, and GCP showed the highest proliferation rate, 9.30%. The results suggested that this type of novel non-agar polysaccharide displayed remarkable antioxidant and immunomodulatory activities and early alkali treatment could decrease the activities. It may represent a potential material for health food and clinical medicines.