Raman spectrum combined with deep learning for precise recognition of Carbapenem-resistant Enterobacteriaceae.

Carbapenem-resistant Enterobacteriaceae (CRE) is a major pathogen that poses a serious threat to human health. Unfortunately, currently, there are no effective measures to curb its rapid development. To address this, an in-depth study on the surface-enhanced Raman spectroscopy (SERS) of 22 strains of 7 categories of CRE using a gold silver composite SERS substrate was conducted. The residual networks with an attention mechanism to classify the SERS spectrum from three perspectives (pathogenic bacteria type, enzyme-producing subtype, and sensitive antibiotic type) were performed. The results show that the SERS spectrum measured by the composite SERS substrate was repeatable and consistent. The SERS spectrum of CRE showed varying degrees of species differences, and the strain difference in the SERS spectrum of CRE was closely related to the type of enzyme-producing subtype. The introduced attention mechanism improved the classification accuracy of the residual network (ResNet) model. The accuracy of CRE classification for different strains and enzyme-producing subtypes reached 94.0% and 96.13%, respectively. The accuracy of CRE classification by pathogen sensitive antibiotic combination reached 93.9%. This study is significant for guiding antibiotic use in CRE infection, as the sensitive antibiotic used in treatment can be predicted directly by measuring CRE spectra. Our study demonstrates the potential of combining SERS with deep learning algorithms to identify CRE without culture labels and classify its sensitive antibiotics. This approach provides a new idea for rapid and accurate clinical detection of CRE and has important significance for alleviating the rapid development of resistance to CRE.

Identification of a Novel Frameshift variant of the ATRX gene: a Case Report and Review of the genotype-phenotype relationship.

BACKGROUND: X-linked intellectual disability-hypotonic facies syndrome-1 (MRXHF1) and Alpha-thalassemia X-linked intellectual disability (ATR-X) syndrome are caused by pathogenic variant in the ATRX gene, a member of the switch/sucrose non-fermentable (SWI-SNF) protein family that exhibits chromatin remodeling activity. These syndromes show a wide spectrum of clinical manifestations, such as distinctive dysmorphic features, mild-to-profound intellectual disability, motor development delay, seizures, urogenital abnormalities, and gastrointestinal disorders. CASE PRESENTATION AND LITERATURE REVIEW: A 3-year-old boy from a Chinese non-consanguineous family was diagnosed with MRXHF1 by whole-exome sequencing. Comprehensive family history information was obtained. The Medline database was searched until 1st Aug 2023 for articles related to ATRX pathogenic variant. Data on gene/protein mutations and clinical symptoms were extracted. The proband showed intellectual disability, motor development delay, typical facial abnormalities, urogenital defect, behavior problems, and optical nerve dysplasia. A novel frameshift mutation c.399_400dup, (p.Leu134Cysfs*2) in the ATRX gene was the primary cause, which occurs right before the ATRXDNMT3-DNMT3L (ADD) domain of ATRX protein. Missense mutation is the most common variation type. The ADD and helicase-like domains are the most frequently affected domains. Epilepsy, congenital heart disease, urogenital defect, acoustic defect, and optical defect are more prevalent in patients with frameshift mutations compared to those with missense mutations. There are more urogenital defects with C-terminal frameshift mutations than with N-terminal frameshift mutations. CONCLUSION: We described a novel frameshift mutation in the ATRX gene in a patient with MRXHF1 syndrome and summarized the genotype-phenotype relationship of ATRX pathogenic variant by variation type and affected protein domain. The regulatory mechanism underlying ATRX variant requires comprehensive analysis in future studies.

Achieving Ultrahigh Effective Surface Charge Density of Direct-Current Triboelectric Nanogenerator in High Humidity.

As an emerging energy-harvesting technology, the triboelectric nanogenerator (TENG) is considered a powerful driving force toward the new-era of Internet of Things and artificial intelligence, but its output performance is dramatically influenced by environmental humidity. Herein, a direct current TENG (DC-TENG) based on the triboelectrification effect and electrostatic breakdown is reported to address the problem of output attenuation in high humidity environments for the conventional TENGs. It is found that high humidity not only enhances the sliding triboelectrification effect of hydrophobic triboelectric materials, but also promotes the electrostatic breakdown process for DC-TENG, thus contributing to the improvement of DC-TENG output. Furthermore, taking poly(vinyl chloride) film as the friction layer, the effective surface charge density of DC-TENG with microstructure-designed electrode achieves a milestone value of ≈2.97 mC m-2 under 90% relative humidity, which is almost 1.42-fold larger than that under 30% RH. This work not only establishes an effective methodology to boost the output performance of TENG in a high humidity environment, but also establishes a foundation for its practical applications in large-scale energy harvesting.

[Clinical and genetic analysis of three children patients with Kleefstra syndrome].

OBJECTIVE: To explore the genetic basis of three children with unexplained developmental delay/intellectual disability (DD/ID). METHODS: Peripheral blood samples were collected from the patients and subjected to chromosomal microarray analysis (CMA). RESULTS: Patient 1 was found to harbor a 190 kb deletion at 9q34.3, which encompassed most of EHMT1 (OMIM 607001), the key gene for Kleefstra syndrome (OMIM 610253). Patients 2 and 3 were siblings. CMA showed that they have shared four chromosomal copy number variations (CNVs) including a deletion at 9q34.3 which spanned 154 kb and 149 kb, respectively, and encompassed the EHMT1 and CACNA1B (OMIM 601012) genes. The remaining 3 CNVs were predicted to be with no clinical significance. CONCLUSION: Microdeletions at 9q33.4 probably underlay the pathogenesis of DD/ID in the three children, for which EHMT1 may be the key gene.

Rapid identification of the resistance of urinary tract pathogenic bacteria using deep learning-based spectroscopic analysis.

The resistance of urinary tract pathogenic bacteria to various antibiotics is increasing, which requires the rapid detection of infectious pathogens for accurate and timely antibiotic treatment. Here, we propose a rapid diagnosis strategy for the antibiotic resistance of bacteria in urinary tract infections (UTIs) based on surface-enhanced Raman scattering (SERS) using a positively charged gold nanoparticle planar solid SERS substrate. Then, an intelligent identification model for SERS spectra based on the deep learning technique is constructed to realize the rapid, ultrasensitive, and non-labeled detection of pathogenic bacteria. A total of 54,000 SERS spectra were collected from 18 isolates belonging to 6 species of common UTI bacteria in this work to realize identification of bacterial species, antibiotic sensitivity, and multidrug resistance (MDR) via convolutional neural networks (CNN). This method significantly simplify the Raman data processing processes without background removing and smoothing, however, achieving 96% above classification accuracy, which was significantly greater than the 85% accuracy of the traditional multivariate statistical analysis algorithm principal component analysis combined with the K-nearest neighbor (PCA-KNN). This work clearly elucidated the potential of combining SERS and deep learning technique to realize culture-free identification of pathogenic bacteria and their associated antibiotic sensitivity.

Potential miRNA-disease association prediction based on kernelized Bayesian matrix factorization.

Many biological experimental studies have confirmed that microRNAs (miRNAs) play a significant role in human complex diseases. Exploring miRNA-disease associations could be conducive to understanding disease pathogenesis at the molecular level and developing disease diagnostic biomarkers. However, since conducting traditional experiments is a costly and time-consuming way, plenty of computational models have been proposed to predict miRNA-disease associations. In this study, we presented a neoteric Bayesian model (KBMFMDA) that combines kernel-based nonlinear dimensionality reduction, matrix factorization and binary classification. The main idea of KBMFMDA is to project miRNAs and diseases into a unified subspace and estimate the association network in that subspace. KBMFMDA obtained the AUCs of 0.9132, 0.8708, 0.9008±0.0044 in global and local leave-one-out and five-fold cross validation. Moreover, KBMFMDA was applied to three important human cancers in three different kinds of case studies and most of the top 50 potential disease-related miRNAs were confirmed by many experimental reports.

Detection of Macromolecular Content in a Mixed Solution of Protein Macromolecules and Small Molecules Using a Weak Measurement Linear Differential System.

In this paper, we propose a linear differential detection system based on a frequency domain weak measurement. The system can be used for detecting optical substances. Moreover, we completed an experiment to detect himan serum albumin (HSA) content in a mixture of human serum albumin and l-proline via dialysis. This work also proves the differential function of the system. This experiment can be further extended to detecting protein content in a mixed solution that contains protein macromolecules and various small molecules. It is very important for detecting molecules without photomarking in solutions of complex biological samples. In this paper, the system has an optical resolution of 1.39 × 10-5, and resolution of 4.06 × 10-8 mol/L for himan serum protein solution.

Identification and characterization of colorectal cancer using Raman spectroscopy and feature selection techniques.

This study aims to detect colorectal cancer with near-infrared Raman spectroscopy and feature selection techniques. A total of 306 Raman spectra of colorectal cancer tissues and normal tissues are acquired from 44 colorectal cancer patients. Five diagnostically important Raman bands in the regions of 815-830, 935-945, 1131-1141, 1447-1457 and 1665-1675 cm(-1) related to proteins, nucleic acids and lipids of tissues are identified with the ant colony optimization (ACO) and support vector machine (SVM). The diagnostic models built with the identified Raman bands provide a diagnostic accuracy of 93.2% for identifying colorectal cancer from normal Raman spectroscopy. The study demonstrates that the Raman spectroscopy associated with ACO-SVM diagnostic algorithms has great potential to characterize and diagnose colorectal cancer.

Triboiontronics with temporal control of electrical double layer formation.

The nanoscale electrical double layer plays a crucial role in macroscopic ion adsorption and reaction kinetics. In this study, we achieve controllable ion migration by dynamically regulating asymmetric electrical double layer formation. This tailors the ionic-electronic coupling interface, leading to the development of triboiontronics. Controlling the charge-collecting layer coverage on dielectric substrates allows for charge collection and adjustment of the substrate-liquid contact electrification property. By dynamically managing the asymmetric electrical double layer formation between the dielectric substrate and liquids, we develop a direct-current triboiontronic nanogenerator. This nanogenerator produces a transferred charge density of 412.54 mC/m2, significantly exceeding that of current hydrovoltaic technology and conventional triboelectric nanogenerators. Additionally, incorporating redox reactions to the process enhances the peak power and transferred charge density to 38.64 W/m2 and 540.70 mC/m2, respectively.

Ionic Rectification by Dynamic Regulation of the Electric Double Layer at the Hydrogel Interface.

Hydrogels play a pivotal role in the realm of iontronics, contributing to the realization of futuristic human-machine interactions. The electric double layer (EDL) between the hydrogel and electrode provides an essential ionic-electronic coupling interface. While prior investigations primarily delved into elucidating the formation mechanism of the EDL, our study shifts the focus to showcasing the current generation through the mechanical modulation of the EDL at the hydrogel-metal interfaces. The dynamic EDL was constructed by the mechano-driven contact-separation process between the polyacrylamide (PAAm) hydrogel and Au. Influencing factors on the dynamic regulation of the EDL such as ion concentration, types of salt, contact-separation frequency, and deformation degree were investigated. Dehydration usually limits the practical applications of hydrogels, and it is a long-standing and difficult problem. However, it seemed to be able to slow the EDL formation process here, resulting in a sustained continuous direct current signal output. Such hydrogel iontronics could rectify the displacement electronic current of a triboelectric nanogenerator by the ionic current. The directional migration of ions could be further enhanced by using charge-collecting metals with different work functions, for example, Au and Al. It offers a paradigm to enable ionic rectification that could be seamlessly incorporated into electronic systems, ushering in a new era for efficient energy harvesting and biomimetic nervous systems.

Selenium and thyroid diseases.

Selenium, a non-metallic element, is a micronutrient essential for the biosynthesis of selenoproteins containing selenocysteine. In adults, the thyroid contains the highest amount of selenium per gram of tissue. Most known selenoproteins, such as glutathione peroxidase, are expressed in the thyroid and are involved in thyroid hormone metabolism, redox state regulation, and maintenance of cellular homeostasis. Some clinical studies have shown that lack of selenium will increase the prevalence of several kinds of thyroid diseases. Selenium treatment in patients with Graves' orbitopathy has been shown to delay disease progression and improve the quality of life. Selenium supplementation in Hashimoto's thyroiditis was associated with the decreased levels of anti-thyroid peroxidase antibody and improved thyroid ultrasound structure. In thyroid cancer, various selenium supplements have shown variable anticancer activity. However, published results remain the conflicting and more clinical evidence is still needed to determine the clinical significance of selenium. This article reviews the strong association between selenium and thyroid disease and provides new ideas for the clinical management of selenium in thyroid disease.

Association between abnormal lipid metabolism and tumor.

Metabolic Reprogramming is a sign of tumor, and as one of the three major substances metabolism, lipid has an obvious impact. Abnormal lipid metabolism is related to the occurrence of various diseases, and the proportion of people with abnormal lipid metabolism is increasing year by year. Lipid metabolism is involved in the occurrence, development, invasion, and metastasis of tumors by regulating various oncogenic signal pathways. The differences in lipid metabolism among different tumors are related to various factors such as tumor origin, regulation of lipid metabolism pathways, and diet. This article reviews the synthesis and regulatory pathways of lipids, as well as the research progress on cholesterol, triglycerides, sphingolipids, lipid related lipid rafts, adipocytes, lipid droplets, and lipid-lowering drugs in relation to tumors and their drug resistance. It also points out the limitations of current research and potential tumor treatment targets and drugs in the lipid metabolism pathway. Research and intervention on lipid metabolism abnormalities may provide new ideas for the treatment and survival prognosis of tumors.

Raman spectroscopy combined with deep learning for rapid detection of melanoma at the single cell level.

Melanoma is an aggressive and metastatic skin cancer caused by genetic mutations in melanocytes, and its incidence is increasing year by year. Understanding the gene mutation information of melanoma cases is very important for its precise treatment. The current diagnostic methods for melanoma include radiological, pharmacological, histological, cytological and molecular techniques, but the gold standard for diagnosis is still pathological biopsy, which is time consuming and destructive. Raman spectroscopy is a rapid, sensitive and nondestructive detection method. In this study, a total of 20,000 Surface-enhanced Raman scattering (SERS) spectra of melanocytes and melanoma cells were collected using a positively charged gold nanoparticles planar solid SERS substrate, and a classification network system based on convolutional neural networks (CNN) was constructed to achieve the classification of melanocytes and melanoma cells, wild-type and mutant melanoma cells and their drug resistance. Among them, the classification accuracy of melanocytes and melanoma cells was over 98%. Raman spectral differences between melanocytes and melanoma cells were analyzed and compared, and the response of cells to antitumor drugs were also evaluated. The results showed that Raman spectroscopy provided a basis for the medication of melanoma, and SERS spectra combined with CNN classification model realized classification of melanoma, which is of great significance for rapid diagnosis and identification of melanoma.

Rapid intracellular growth of gold nanostructures assisted by functionalized graphene oxide and its application for surface-enhanced Raman spectroscopy.

Hybridization of metal nanoparticles with graphene oxide for high performance surface-enhanced Raman scattering (SERS) has attracted overwhelming attention in recent years. Herein, a one-pot green route for intracellular synthesis of gold nanostructures assisted by poly(vinylpyrrolidone) (PVP)-functionalized graphene oxide (GO) was proposed. The hybrids obtained [GO/PVP/intracellularly grown gold nanoparticles (IGAuNs)] randomly scattered throughout the cell. Compared with the IGAuNs, the growth of GO/PVP/IGAuNs was remarkably accelerated, which could be attributed to the coordination of PVP enriched on GO. GO/PVP/IGAuNs could serve as excellent SERS probes for ultrasensitive detection of cellular components of cancer cells located in the cytoplasm, nucleoplasm, and nucleolus. The random intracellular distribution of GO/PVP/IGAuNs facilitated the effective Raman characterization of cellular components, which was confirmed by the uniform distribution of SERS signals in the Raman image. The SERS signals induced by GO/PVP/IGAuNs could be collected as early as 15 h, which allowed rapid detection of tumor cells. In conclusion, this facile and green strategy for fast intracellular growth of GO/PVP/IGAuNs offered great potential for biomedical applications.

Study on the propagation parameters of Bessel-Gaussian beams carrying optical vortices through atmospheric turbulence.

Based on the integral representation of Bessel function and the extended Huygens-Fresnel principle, an integral expression of the Wigner distribution function (WDF) for partially coherent Bessel-Gaussian beams (PBGBs) propagating through turbulent atmosphere has been obtained. Also, the analytical formulas of the M2-factor for PBGB propagation in such a medium have been derived, which can be applied to cases of different spatial power spectra of the refractive index fluctuations. The performed numerical results reveal that the M2-factor of a PBGB in turbulent atmosphere depends on the beam parameters of the initial input beam, the structure constants of the turbulent atmosphere, and the propagation distance. These results may be useful in long-distance optical communications in free space or in turbulent atmosphere.

A Self-Powered Dual-Type Signal Vector Sensor for Smart Robotics and Automatic Vehicles.

Automatic control systems are the most efficient technology for reducing labor cost while improving work efficiency. Vector motion monitoring is indispensable for the normal operation of automatic control systems. Here, a self-powered dual-type signal triboelectric nanogenerator (DS-TENG) is designed through integrating an alternating-current TENG and a direct-current TENG, which can monitor vector movement in real time based on pulse signal counts. As a result, the DS-TENG avoids the shortcoming of traditional self-powered sensors based on signal amplitude that is sensitive to the working environment, achieves a high sensing precision, and maintains stability after reciprocating motion of 500 000 cycles. Moreover, it realizes effective movement direction recognition by self-powered switching of signal type in reverse movement. This dual-type signal TENG exhibits high precision and automatic direction recognition in vector motion monitor and trajectory tracker, paving the way for the application of the self-powered TENG sensor in automatic control systems in the future.

Standardized measurement of dielectric materials' intrinsic triboelectric charge density through the suppression of air breakdown.

Triboelectric charge density and energy density are two crucial factors to assess the output capability of dielectric materials in a triboelectric nanogenerator (TENG). However, they are commonly limited by the breakdown effect, structural parameters, and environmental factors, failing to reflect the intrinsic triboelectric behavior of these materials. Moreover, a standardized strategy for quantifying their maximum values is needed. Here, by circumventing these limitations, we propose a standardized strategy employing a contact-separation TENG for assessing a dielectric material's maximum triboelectric charge and energy densities based on both theoretical analyses and experimental results. We find that a material's vacuum triboelectric charge density can be far higher than previously reported values, reaching a record-high of 1250 µC m-2 between polyvinyl chloride and copper. More importantly, the obtained values for a dielectric material through this method represent its intrinsic properties and correlates with its work function. This study provides a fundamental methodology for quantifying the triboelectric capability of dielectric materials and further highlights TENG's promising applications for energy harvesting.

Fast Synthesis of Au Nanoparticles on Metal-Phenolic Network for Sweat SERS Analysis.

The biochemical composition of sweat is closely related to the human physiological state, which provides a favorable window for the monitoring of human health status, especially for the athlete. Herein, an ultra-simple strategy based on the surface-enhanced Raman scattering (SERS) technique for sweat analysis is established. Metal-phenolic network (MPN), an outstanding organic-inorganic hybrid material, is adopted as the reductant and platform for the in situ formation of Au-MPN, which displays excellent SERS activity with the limit of detection to 10-15 M for 4-mercaptobenzoic acid (4-MBA). As an ultrasensitive SERS sensor, Au-MPN is capable of discriminating the molecular fingerprints of sweat components acquired from a volunteer after exercise, such as urea, uric acid, lactic acid, and amino acid. For pH sensing, Au-MPN/4-MBA efficiently presents the pH values of the volunteer's sweat, which can indicate the electrolyte metabolism during exercise. This MPN-based SERS sensing strategy unlocks a new route for the real-time physiological monitoring of human health.

Combining fiber optical tweezers and Raman spectroscopy for rapid identification of melanoma.

Cutaneous melanoma is a skin tumor with a high degree of malignancy and fatality rate, the incidence of which has increased in recent years. Therefore, a rapid and sensitive diagnostic technique of melanoma cells is urgently needed. In this paper, we present a new approach using fiber optical tweezers to manipulate melanoma cells to measure their Raman spectra. Then, combined with Principal Component Analysis and Support Vector Machines (PCA-SVM) classification model, to achieve the classification of common mutant, wild-type and drug-resistant melanoma cells. A total of 150 Raman spectra of 30 cells were collected from mutant, wild-type and drug-resistant melanoma cell lines, and the classification accuracy was 92%, 94%, 97.5%, respectively. These results suggest that the study of tumor cells based on fiber optical tweezers and Raman spectroscopy is a promising method for early and rapid identification and diagnosis of tumor cells.

A Tuning-Fork Triboelectric Nanogenerator with Frequency Multiplication for Efficient Mechanical Energy Harvesting.

As a new technology for high-entropy energy harvesting, a triboelectric nanogenerator (TENG) has broad applications in sensor networks and internet of things as a power source, but its average power density is limited by the fixed low-frequency output. Here, a frequency-multiplication TENG based on intrinsic high frequency of tuning fork is proposed which enables converting low-frequency mechanical energy into high-frequency electric energy. A tuning-fork TENG is used to systematically study the effects of intrinsic frequency, dielectric's thickness, and gap distance on its electric performance, and a total transferred charges of 4.3 µC and an average power density of 9.42 mW m-2 are realized at the triggering frequency of 0.2 Hz, which are 71 times and 5.7 times than that of the single-cycle output of conventional contact-separation TENG, respectively. Moreover, the crest factor also decreases from 3.5 to around 1.5. Then, a homemade tuning fork-like TENG is reasonably designed for harvesting ambient wind energy, achieving an average power density of 20.02 mW m-2 at a wind speed of 7 m s-1 . Specially, its impedance resistance is independent of the mechanical triggering frequency, simplifying the back-end power management circuit design. Therefore, the frequency-multiplication TENG shows a great potential for efficient distributed energy harvesting.