Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

INTRODUCTION: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. OBJECTIVES: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). METHODS: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. RESULTS: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

Ultra-broadband TM-pass polarizer based on anisotropic metamaterials in lithium niobate on an insulator.

An ultra-broadband TM-pass polarizer is designed, fabricated, and experimentally demonstrated based on subwavelength grating (SWG) metamaterials in a lithium niobate on an insulator (LNOI) platform. According to our simulation, the designed device is predicted to work at a 220 nm wavelength range from 1460 to 1680 nm, covering the S-, C-, L-, U-bands of optical fiber communication. By depositing and subsequently etching a silicon nitride thin film atop the LNOI chip, the SWG structures are formed successfully by using complementary metal-oxide semiconductor (CMOS)-compatible fabrication processes. The measured results show a high polarization extinction ratio larger than 20 dB and a relatively low insertion loss below 2.5 dB over a 130 nm wavelength range from 1500 to 1630 nm, mainly limited by the operation bandwidth of our laser source.

Ridge resonators with compact guided mode coupling.

Ridge resonators are a recently introduced integrated photonic circuit element based on bound states in the continuum (BICs) which can produce a single, sharp resonance over a broad wavelength range with high extinction ratio. However, to excite these resonators, a broad beam of laterally unbound slab mode is required, resulting in a large device footprint, which is not attractive for integrated photonic circuits. In this contribution, we propose and numerically validate a guided-mode waveguide structure that can be analogue to the BIC-based ridge resonators. Our simulations show that the proposed guided-mode waveguide structure can produce resonances with similar characteristics, yet with a significantly reduced footprint. Furthermore, we investigate the influence of the resonator's dimensions on the bandwidth of the resonance, demonstrating that resonances with Q-factors from low to very high (> 10000) are feasible. We believe that the reduced footprint and ability to design filters systematically make the guided-mode waveguide resonators an attractive photonic circuit component with particular value for foundry fabricated silicon photonic circuits.

Integrated lithium niobate optical mode (de)interleaver based on an asymmetric Y-junction.

Lithium niobate on insulator (LNOI) platforms promise unique advantages in realizing high-speed, large-capacity, and large-scale photonic integrated circuits (PICs) by leveraging lithium niobate's attractive material properties, which include electro-optic and nonlinear optic properties, low material loss, and a wide transparency window. Optical mode interleavers can increase the functionality of future PICs in LNOI by enabling optical mode division multiplexing (MDM) systems, allowing variable mode assignment while maintaining high channel utilization and capacity. In this Letter, we experimentally demonstrate an optical mode interleaver based on an asymmetric Y-junction on the LNOI platform, which exhibits an insertion loss of below 0.46 dB and modal cross talk of below -13.0 dB over a wavelength range of 1500-1600 nm. The demonstrated mode interleaver will be an attractive circuit component in future high-speed and large-capacity PICs due to its simple structure, scalability, and capacity for efficient and flexible mode manipulation on the LNOI platform.

High-speed electro-optic modulation in topological interface states of a one-dimensional lattice.

Electro-optic modulators are key components in data communication, microwave photonics, and quantum photonics. Modulation bandwidth, energy efficiency, and device dimension are crucial metrics of modulators. Here, we provide an important direction for the miniaturization of electro-optic modulators by reporting on ultracompact topological modulators. A topological interface state in a one-dimensional lattice is implemented on a thin-film lithium-niobate integrated platform. Due to the strong optical confinement of the interface state and the peaking enhancement of the electro-optic response, a topological cavity with a size of 1.6 × 140 µm2 enables a large modulation bandwidth of 104 GHz. The first topological modulator exhibits the most compact device size compared to reported LN modulators with bandwidths above 28 GHz, to the best of our knowledge. 100 Gb/s non-return-to-zero and 100 Gb/s four-level pulse amplitude modulation signals are generated. The switching energy is 5.4 fJ/bit, owing to the small electro-optic mode volume and low capacitance. The topological modulator accelerates the response time of topological photonic devices from the microsecond order to the picosecond order and provides an essential foundation for the implementation of large-scale lithium-niobate photonic integrated circuits.

Electrospun nanofiber-based indicatorpaper sensing platform for fluorescence and visualization detection of norfloxacin.

Norfloxacin (NOR) residues in water pose a serious threat to human health via the food chain, necessitating the development of a rapid on-site antibiotic detection technique. In this work, we utilize electrostatic spinning technology that combines polyacrylonitrile (PAN) fibers and adenosine triphosphate (ATP)-rare earth metal Tb3+ complexes (ATP/Tb) to construct a new ternary film-based sensor for sensitive, quick, and convenient field testing of NOR in water. The operating mechanism is that the ternary system produces gradually enhanced bright green fluorescence at increasing concentrations of NOR. The unique fluorescence property of the ternary systems is attributed to the use of ATP, rather than the commonly used adenosine monophosphate (AMP), to coordinate with Tb3+, which avoided the possible fluorescence quenching from competitive water binding. Benefiting from the PAN nanofiber's superior stability, acid, and alkali resistance, and flexibility as support, the ternary system exhibited a good linear response to NOR in a wide dynamic range of 0.04-30 µM at the detection limit of 16 nM. Additionally, the combination of a smartphone color recognition app allows for quick on-scene NOR detection. This film sensing strategy is instructive for the development of smart and portable sensing platforms for real-time detection of analytes such as antibiotics, pesticide residues, and hazardous materials in water bodies.

Development of a headspace-solid phase microextraction gas chromatography-high resolution mass spectrometry method for analyzing volatile organic compounds in urine: Application in breast cancer biomarker discovery.

BACKGROUND AND AIM: Breast cancer (BC) is the leading cause of cancer-related death in females. The development of non-invasive methods for the early diagnosis of BC still remains challenge. Here, we aimed to discover the urinary volatile organic compounds (VOCs) pattern of BC patients and identify potential VOC biomarkers for BC diagnosis. METHODS: Urine samples were analyzed by headspace-solid phase microextraction (HS-SPME) combined with gas chromatography-high resolution mass spectrometry (GC-HRMS). To assure reliable analysis, the factors influencing HS-SPME extraction efficiency were comprehensively investigated and optimized by combing the Plackett-Burman design (PBD) with the central composite design (CCD). The established HS-SPME/GC-HRMS method was validated and applied to analyze urine samples from BC patients (n = 80) and healthy controls (n = 88). RESULTS: A total number of 134 VOCs belonging to distinct chemical classes were identified by GC-HRMS. BC patients demonstrated unique urinary VOCs pattern. Orthogonal partial least squares-discriminant analysis (OPLS-DA) showed a clear separation between BC patients and healthy controls. Eight potential VOC biomarkers were identified using multivariate and univariate statistical analysis. The predictive ability of candidate VOC biomarkers was further investigated by the random forest (RF) algorithm. The candidate VOC biomarkers yielded 76.3% sensitivity and 85.4% specificity on the training set, and achieved 76.0% sensitivity and 92.3% specificity on the validation set. CONCLUSIONS: Overall, this work not only established a standardized HS-SPME/GC-HRMS approach for urinary VOCs analysis, but also highlighted the value of urinary VOCs for BC diagnosis. The knowledge gained from this study paves the way for early diagnosis of BC using urine in a non-invasive manner.

Integrated lithium niobate polarization beam splitter based on a photonic-crystal-assisted multimode interference coupler.

Lithium niobate on insulator (LNOI) is a promising platform for high-speed photonic integrated circuits (PICs) that are used for communication systems due to the excellent electro-optic properties of lithium niobate (LN). In such circuits, the high-speed electro-optical modulators and switches need to be integrated with passive circuit components that are used for routing the optical signals. Polarization beam splitters (PBSs) are one of the fundamental passive circuit components for high-speed PICs that can be used to (de)multiplex two orthogonal polarization optical modes, enabling on-chip polarization division multiplexing (PDM) systems, which are suitable for enhancing the data capacity of PICs. In this Letter, we design and experimentally demonstrate a high-performance PBS constructed by a photonic crystal (PC)-assisted multimode interference (MMI) coupler. The measured polarization extinction ratio (ER) of the fabricated device is 15 dB in the wavelength range from 1525 to 1565 nm, which makes them suitable for the high-speed and large data capacity PICs required for future communication systems.

T-Shaped Aptamer-Based LSPR Biosensor Using Ω-Shaped Fiber Optic for Rapid Detection of SARS-CoV-2.

SARS-CoV-2, especially the variant strains, is rapidly spreading around the world. Rapid detection methods for the virus are crucial for controlling the COVID-19 epidemic. Herein, a localized surface plasmonic resonance (LSPR) biosensor based on Ω-shaped fiber optic (Ω-FO) was developed for dual assays of SARS-CoV-2 monitoring. Due to its strong ability to control the orientation and density, a new T-shaped aptamer exhibits enhanced binding affinity toward N proteins. After being combined on the fiber optic surface, the T-shaped aptamer sensitively captured N proteins of SARS-CoV-2 for a direct assay. Further, core-shell structured gold/silver nanoparticles functionalized with a T-shaped aptamer (apt-Ag@AuNPs) can amplify the signal of N protein detection for a sandwich assay. The real-time analytical feature of the dual assays endows time-dependent sensitivity enhancement behavior, which provides a guideline to save analytical time. With those characteristics, the LSPR biosensor has been successfully used to rapidly identify 39 healthy volunteers and 39 COVID-19 patients infected with the ancestral or variant SARS-CoV-2. With the help of simple pretreatment, we obtain a true negative rate of 100% and a true positive rate of 92.3% with a short analysis time of 45 min using the direct assay. Further, the LSPR biosensor could also broaden the detection application range to the surface of cold-chain foods using a sandwich assay. Thus, the LSPR biosensor based on Ω-FO was demonstrated to have broad application potential to detect SARS-CoV-2 rapidly.

Wnt/ß-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.

Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/ß-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/ß-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/ß-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of ß-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/ß-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

Arbitrary access to optical carriers in silicon photonic mode/wavelength hybrid division multiplexing circuits.

The manipulation of optical modes directly in a multimode waveguide without affecting the transmission of undesired signal carriers is of significance to realize a flexible and simple structured optical network-on-chip. In this Letter, an arbitrary optical mode and wavelength carrier access scheme is proposed based on a series of multimode microring resonators and one multimode bus waveguide with constant width. As a proof-of-concept, a three-mode (de)multiplexing device is designed, fabricated, and experimentally demonstrated. A new, to the best of our knowledge, phase-matching idea is employed to keep the bus waveguide width constant. The mode coupling regions and transmission regions of the microring resonators are designed carefully to selectively couple and transmit different optical modes. The extinction ratio of the microring resonators is larger than 21.0 dB. The mode and wavelength cross-talk for directly (de)multiplexing are less than -12.8 dB and -19.0 dB, respectively. It would be a good candidate for future large-scale multidimensional optical networks.

Advances in pretreatment and analysis methods of aromatic hydrocarbons in soil.

Benzene compounds that are prevalent in the soil as organic pollutants mainly include BTEX (benzene, toluene, ethylbenzene, and three xylene isomers) and PAHs (polycyclic aromatic hydrocarbons). These pose a severe threat to many aspects of human health. Therefore, the accurate measurement of BTEX and PAHs concentrations in the soil is of great importance. The samples for analysis of BTEX and PAHs need to be suitable for the various detection methods after pretreatment, which include Soxhlet extraction, ultrasonic extraction, solid-phase microextraction, supercritical extraction, and needle trap. The detection techniques mainly consist of gas chromatography (GC), mass spectrometry (MS), and online sensors, and provide comprehensive information on contaminants in the soil. Their performance is evaluated in terms of sensitivity, selectivity, and recovery. Recently, there has been rapid progress in the pretreatment and analysis methods for the quantitative and qualitative analyses of BTEX and PAHs. Therefore, it is necessary to produce a timely and in-depth review of the emerging pretreatment and analysis methods, which is unfortunately absent from the recent literature. In this work, state-of-art extraction techniques and analytical methods have been summarized for the determination of BTEX and PAHs in soil, with a particular focus on the potential and limitations of the respective methods for different aromatic hydrocarbons. Accordingly, the paper will describe the basic methodological knowledge, as well as the recent advancement of pretreatment and analysis methods for samples containing BTEX and PAHs.

Direct Amination of Benzene with Molecular Nitrogen Enabled by Plasma-Liquid Interactions.

Nitrogen fixation is industrially realized by mass production of ammonia, the principal intermediate nitrogen source for N-containing organic molecules. Instead, direct C-N bond formation from dinitrogen (N2 ) is of great interest but remains a challenge. Here, by virtue of unique plasma-liquid interactions, we developed an environmentally benign one-pot approach to directly couple benzene and N2 , two naturally abundant yet chemically inert molecules, into value-added arylamines. Under the optimal conditions, an amination yield of 45 % was rapidly achieved, far better than the reported benzene amination efficiency using ammonia. A tentative reaction mechanism was proposed involving the long-lived N2 (A3 Σ u + ) and N2 + species, as evidenced by the key intermediates detected. With a deeper mechanistic understanding and by further optimizing the plasma reactor, the realization of cost-effective electrical amination of benzene with N2 could become reality.

Recent advances in integrated optical directed logic operations for high performance optical computing: a review.

Optical directed logic (DL) is a novel logic operation scheme that employs electrical signals as operands to control the working states of optical switches to perform the logic functions. This review first provides an overview of the concept and working principle of DL. The developing trends of DL computing are then discussed in detail, including the fundamental optical DL gates, combinational optical DL operations, reconfigurable logic computing, low power optical logic computing, and programmable photonic network. The concluding remarks provide an outlook on the DL future development and its impacts in optical computing.

High-speed electro-optic modulator based on silicon nitride loaded lithium niobate on an insulator platform.

Electro-optic (EO) modulators, which convert signals from the electrical to optical domain plays a key role in modern optical communication systems. Lithium niobate on insulator (LNOI) technology has emerged as a competitive solution to realize high-performance integrated EO modulators. In this Letter, we design and experimentally demonstrate a Mach-Zehnder interferometer-based modulator on a silicon nitride loaded LNOI platform, which not only takes full advantage of the excellent EO effect of LiNbO3, but also avoids the direct etching of LiNbO3 thin film. The measured half-wave voltage length product of the fabricated modulator is 2.24 V·cm, and the extinction ratio is ∼20dB. Moreover, the 3 dB EO bandwidth is ∼30GHz, while the modulated data rate for on-off key signals can reach up to 80 Gbps.

Trace detection of organophosphorus pesticides in vegetables via enrichment by magnetic zirconia and temperature-assisted ambient micro-fabricated glow discharge plasma desorption ionization mass spectrometry.

In this study, an innovative rapid detection technology for quickly screening and quantifying organophosphorus pesticides (OPPs) in vegetables was developed based on ambient micro-fabricated glow discharge plasma desorption/ionization mass spectrometry (MFGDP-MS), where Fe3O4/ZrO2 synthesized by a one-step coprecipitation was used for enrichment. It can not only effectively enrich OPPs, but can be separated by an external magnetic field, thereby simplifying the traditional steps of centrifugation and cleanup in sample preparation. The introduction of a temperature control system (TCS) can tackle the problem of the low ionization efficiency in MFGDP and expand its application range. Under optimized experimental conditions, the limits of detection (LODs) of the standard solution as low as 0.0068-0.7500 µg L-1 mm-2 were achieved, with relative standard deviations (RSDs) being less than 17.8%. Moreover, vegetable extracts were spiked to evaluate the accuracy of the method, and good recoveries (76.9-123.5%) were obtained. Remarkably, it took no more than 7 minutes from sample preparation to testing, resulting in significantly improved ability of the quantitative detection of plentiful samples.

Self-extending DNA-Mediated Isothermal Amplification System and Its Biosensing Applications.

Signal amplification is critical to achieving sensitive biosensing, but complex strategies often bring problems like system instability, false positive, or narrow target spectrum. Here, a self-extending DNA-mediated isothermal amplification (SEIA) system with simple reaction components is introduced to achieve rapid, robust, and significant signal amplification. In SEIA, based on spontaneous refolding of specific DNA domains and using the previous generation product as a template, a DNA strand can extend continuously in an approximate exponential growth pattern, which was accurately predicted by our formula and well supported by AFM results. Based on a set of proof-of-concept experiments, it was proved that the SEIA system can output different signals and flexibly integrate various functional nucleic acids, which makes it suitable for different scenarios and realizes broad-spectrum target detection. Taking into account the advantages of simplicity, flexibility, and efficiency, the SEIA system as an independent signal amplification module will enrich the toolbox of biosensing design.

Breath volatile organic compound analysis: an emerging method for gastric cancer detection.

Gastric cancer is a common malignancy, being the fifth most frequently diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide. Diagnosis of gastric cancer at the early stage is critical to effectively improve the survival rate. However, a substantial proportion of patients with gastric cancer in the early stages lack specific symptoms or are asymptomatic. Moreover, the imaging techniques currently used for gastric cancer screening, such as computed tomography and barium examination, are usually radioactive and have low sensitivity and specificity. Even though endoscopy has high accuracy for gastric cancer screening, its application is limited by the invasiveness of the technique. Breath analysis is an economic, effective, easy to perform, non-invasive detection method, and has no undesirable side effects on subjects. Extensive worldwide research has been conducted on breath volatile organic compounds (VOCs), which reveals its prospect as a potential method for gastric cancer detection. Many interesting results have been obtained and innovative methods have been introduced in this subject; hence, an extensive review would be beneficial. By providing a comprehensive list of breath VOCs identified by gastric cancer would promote further research in this field. This review summarizes the commonly used technologies for exhaled breath analysis, focusing on the application of analytical instruments in the detection of breath VOCs in gastric cancers, and the alterations in the profile of breath biomarkers in gastric cancer patients are discussed as well.

Diagnostic approach to thyroid cancer based on amino acid metabolomics in saliva by ultra-performance liquid chromatography with high resolution mass spectrometry.

Thyroid cancer is a malignant disease with dramatically low advanced-stage 10-year survival. Meanwhile, the metabolites in saliva are becoming a wealthy source of disease biomarkers. However, there is a lack of non-invasive analytical methods for the identification of biomarkers in saliva for the preoperative diagnosis of thyroid cancer. Therefore, we developed an ultra-high performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) method to simultaneously determine the metabolic levels of 10 amino acids in saliva, aiming to study the amino acid metabolism profile to promote early diagnosis of thyroid cancer. We tested unstimulated whole saliva from patients with papillary thyroid carcinoma (PTC; n = 61) and healthy controls (HC; n = 61), and used receiver operating characteristic (ROC) curves to establish the diagnostic value of potential markers. The method validation results showed good precision, linearity (R2 > 0.99), recovery (92.2 %-110.3 %), intra- and inter-day precision (RSD < 7 % and RSD < 9 %, respectively). The concentration of 10 amino acids was significantly different between PTC and HC in human salivary analysis (P < 0.05), the area under the curve (AUC) values of a single marker for the diagnosis of PTC were ranging from 0.678 to 0.833. A panel of alanine, valine, proline, phenylalanine was selected in combination yielded the AUC of 0.936, which will improve the accuracy of early diagnosis of thyroid cancer (sensitivity: 91.2 %; specificity: 85.2 %). This study proved the possibility of salivary amino acid biomarkers for PTC early diagnosis, providing a simple auxiliary way for the non-invasive diagnosis of thyroid cancer.

Hybridized nanolayer modified Ω-shaped fiber-optic synergistically enhances localized surface plasma resonance for ultrasensitive cytosensor and efficient photothermal therapy.

Inadequate sensitivity and side-effect are the main challenges to develop cytosensors combining with therapeutic potential simultaneously for cancer diagnosis and treatment. Herein, localized surface plasma resonance (LSPR) based on hybridized nanolayer modified Ω-shaped fiber-optic (HN/Ω-FO) was developed to integrate cytosensor and plasmonic photothermal treatment (PPT). On one hand, hybridized nanolayers improve the coverage of nanoparticles and refractive index sensitivity (RIS). Moreover, the hybridized nanoploymers of gold nanorods/gold nanoparticles (AuNRs/AuNPs) also result in intense enhancement in electronic field intensity (I). On the other hand, Ω-shaped fiber-optic (Ω-FO) led to strong bending loss in its bending part. To be specific, a majority of light escaped from fiber will interact with HN. Thus, HN/Ω-FO synergistically enhances the plasmonic, which achieved the goal of ultrasensitive cytosensor and highly-efficient plasmonic photothermal treatment (PPT). The proposed cytosensor exhibits ultrasensitivity for detection of cancer cells with a low limit of detection down to 2.6 cells/mL was realized just in 30 min. HN/Ω-FO-based LSPR exhibits unique characteristics of highly efficient, localized, and geometry-dependent heat distribution, which makes it suitable for PPT to only kill the cancer cells specifically on the surface or surrounding fiber-optic (FO) surface. Thus, HN/Ω-FO provides a new approach to couple cytosensor with PPT, indicating its great potential in clinical diagnosis and treatment.