Integrated Studies on Male Reproductive Toxicity of Bis(2-ethylhexyl)-tetrabromophthalate: in Silico, in Vitro, ex Vivo, and in Vivo.

Bis(2-ethylhexyl)tetrabromophthalate (TBPH) has been widely detected in the environment and organisms; thus, its toxic effects on male reproduction were systematically studied. First, we found that TBPH can stably bind to the androgen receptor (AR) based on in silico molecular docking results and observed an antagonistic activity, but not agonistic activity, on the AR signaling pathway using a constructed AR-GRIP1 yeast assay. Subsequently, we validated the adverse effects on male germ cells by observing inhibited androgen production and proliferation in Leydig cells upon in vitro exposure and affected general motility and motive tracks of zebrafish sperm upon ex vivo exposure. Finally, the in vivo reproductive toxicity was demonstrated in male zebrafish by reduced mating behavior in F0 generation when paired with unexposed females and abnormal development of their offspring. In addition, reduced sperm motility and impaired germ cells in male zebrafish were also observed, which may be related to the disturbed homeostasis of sex hormones. Notably, the specifically suppressed AR in the brain provides further evidence for the antagonistic effects as above-mentioned. These results confirmed that TBPH affected male reproduction through a classical nuclear receptor-mediated pathway, which would be helpful for assessing the ecological and health risks of TBPH.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver.

An emerging environmental contaminant, bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), can bioaccumulate in the liver and affect hepatic lipid metabolism. However, the in-depth mechanism has yet to be comprehensively explored. In this study, we utilized transgenic zebrafish Tg (Apo14: GFP) to image the interference of TBPH on zebrafish liver development and lipid metabolism at the early development stage. Using integrated lipidomic and transcriptomic analyses to profile the lipid remodeling effect, we uncovered the potential effects of TBPH on lipophagy-related signaling pathways in zebrafish larvae. Decreased lipid contents accompanied by enhanced lipophagy were confirmed by the measurements of Oil Red O staining and transmission electron microscopy in liver tissues. Particularly, the regulatory role of the foxo1 factor was validated via its transcriptional inhibitor. Double immunofluorescence staining integrated with biochemical analysis indicated that the enhanced lipophagy and mitochondrial fatty acid oxidation induced by TBPH were reversed by the foxo1 inhibitor. To summarize, our study reveals, for the first time, the essential role of foxo1-mediated lipophagy in TBPH-induced lipid metabolic disorders and hepatoxicity, providing new insights for metabolic disease studies and ecological health risk assessment of TBPH.

Bis(2-ethylhexyl)-tetrabromophthalate Poses a Higher Exposure Risk and Induces Gender-Specific Metabolic Disruptions in Zebrafish Liver.

Bis(2-ethylhexyl)-tetrabromophthalate (TBPH), a typical novel brominated flame retardant, has been ubiquitously identified in various environmental and biotic media. Consequently, there is an urgent need for precise risk assessment based on a comprehensive understanding of internal exposure and the corresponding toxic effects on specific tissues. In this study, we first investigated the toxicokinetic characteristics of TBPH in different tissues using the classical pseudo-first-order toxicokinetic model. We found that TBPH was prone to accumulate in the liver rather than in the gonad, brain, and muscle of both female and male zebrafish, highlighting a higher internal exposure risk for the liver. Furthermore, long-term exposure to TBPH at environmentally relevant concentrations led to increased visceral fat accumulation, signaling potential abnormal liver function. Hepatic transcriptome analysis predominantly implicated glycolipid metabolism pathways. However, alterations in the profile of associated genes and biochemical indicators revealed gender-specific responses following TBPH exposure. Besides, histopathological observations as well as the inflammatory response in the liver confirmed the development of nonalcoholic fatty liver disease, particularly in male zebrafish. Altogether, our findings highlight a higher internal exposure risk for the liver, enhancing our understanding of the gender-specific metabolic-disrupting potential associated with TBPH exposure.

Tailoring electrode surface charge to achieve discrimination and quantification of chemically similar small molecules with electrochemical aptamers.

Electrochemical biosensors based on structure-switching aptamers offer many advantages because they can operate directly in complex samples and offer the potential to integrate with miniaturized electronics. Unfortunately, these biosensors often suffer from cross-reactivity problems when measuring a target in samples containing other chemically similar molecules, such as precursors or metabolites. While some progress has been made in selecting highly specific aptamers, the discovery of these reagents remains slow and costly. In this work, we demonstrate a novel strategy to distinguish molecules with miniscule difference in chemical composition (such as a single hydroxyl group) - with cross reactive aptamer probes - by tuning the charge state of the surface on which the aptamer probes are immobilized. As an exemplar, we show that our strategy can distinguish between DOX and many structurally similar analytes, including its primary metabolite doxorubicinol (DOXol). We then demonstrate the ability to accurately quantify mixtures of these two molecules based on their differential response to sensors with different surface-charge properties. We believe this methodology is general and can be extended to a broad range of applications.

Multi- and Transgenerational Developmental Impairments Are Induced by Decabromodiphenyl Ethane (DBDPE) in Zebrafish Larvae.

A novel brominated flame retardant decabromodiphenyl ethane (DBDPE) has become a ubiquitous emerging pollutant; hence, the knowledge of its long-term toxic effects and underlying mechanism would be critical for further health risk assessment. In the present study, the multi- and transgenerational toxicity of DBDPE was investigated in zebrafish upon a life cycle exposure at environmentally relevant concentrations. The significantly increased malformation rate and declined survival rate specifically occurred in unexposed F2 larvae suggested transgenerational development toxicity by DBDPE. The changing profiles revealed by transcriptome and DNA methylome confirmed an increased susceptibility in F2 larvae and figured out potential disruptions of glycolipid metabolism, mitochondrial energy metabolism, and neurodevelopment. The changes of biochemical indicators such as ATP production confirmed a disturbance in the energy metabolism, whereas the alterations of neurotransmitter contents and light-dark stimulated behavior provided further evidence for multi- and transgenerational neurotoxicity in zebrafish. Our findings also highlighted the necessity for considering the long-term impacts when evaluating the health of wild animals as well as human beings by emerging pollutants.

Niclosamide Exposure at Environmentally Relevant Concentrations Efficaciously Inhibited the Growth and Disturbed the Liver-Gut Axis of Adult Male Zebrafish.

In the current study, adult male zebrafish fed a normal diet (ND) or high-fat diet (HFD) were exposed to niclosamide (NIC) at environmentally relevant concentrations to reveal the accumulation and distribution in different tissues and evaluate the effects on liver-gut axis. Chemical analysis indicated that the liver bore a greater burden of NIC compared with the brain and gonads in adult zebrafish, and the HFD-fed fish bore greater burden in their liver and brain than those ND-fed fish. The indications from body weight, growth rate, body mass index, micro-CT images, biochemical and pathological changes confirmed that NIC can efficaciously curb weight gain and improve overloads of in plasma insulin and glucose in HFD-fed zebrafish. However, the potential effects on liver-gut axis in ND-fed zebrafish were also elucidated: NIC disturbed mitochondrial energy production, inhibited the glycemic and triacylglycerol biosynthesis but promoted triacylglycerol and free fatty acid catabolism, therefore reduced lipid accumulation in hepatocytes; NIC also impaired the physical barrier, evoked inflammatory and oxidative stress and led to microbiota dysbiosis in the intestine. There findings highlighted the necessity for evaluating its potential impacts on the health of wild animals as well as human beings upon long-term exposure.

Actively Controllable Solid-Phase Microextraction in a Hierarchically Organized Block Copolymer-Nanopore Electrode Array Sensor for Charge-Selective Detection of Bacterial Metabolites.

Pseudomonas aeruginosa produces a number of phenazine metabolites, including pyocyanin (PYO), phenazine-1-carboxamide (PCN), and phenazine-1-carboxylic acid (PCA). Among these, PYO has been most widely studied as a biomarker of P. aeruginosa infection. However, despite its broad-spectrum antibiotic properties and its role as a precursor in the biosynthetic route leading to other secondary phenazines, PCA has attracted less attention, partially due to its relatively low concentration and interference from other highly abundant phenazines. This challenge is addressed here by constructing a hierarchically organized nanostructure consisting of a pH-responsive block copolymer (BCP) membrane with nanopore electrode arrays (NEAs) filled with gold nanoparticles (AuNPs) to separate and detect PCA in bacterial environments. The BCP@NEA strategy is designed such that adjusting the pH of the bacterial medium to 4.5, which is above the pKa of PCA but below the pKa of PYO and PCN, ensures that PCA is negatively charged and can be selectively transported across the BCP membrane. At pH 4.5, only PCA is transported into the AuNP-filled NEAs, while PYO and PCN are blocked. Structural characterization illustrates the rigorous spatial segregation of the AuNPs in the NEA nanopore volume, allowing PCA secreted from P. aeruginosa to be quantitatively determined as a function of incubation time using square-wave voltammetry and surface-enhanced Raman spectroscopy. The strategy proposed in this study can be extended by changing the nature of the hydrophilic block and subsequently applied to detect other redox-active metabolites at a low concentration in complex biological samples and, thus, help understand metabolism in microbial communities.

Single Entity Electrochemistry in Nanopore Electrode Arrays: Ion Transport Meets Electron Transfer in Confined Geometries.

Electrochemical measurements conducted in confined volumes provide a powerful and direct means to address scientific questions at the nexus of nanoscience, biotechnology, and chemical analysis. How are electron transfer and ion transport coupled in confined volumes and how does understanding them require moving beyond macroscopic theories? Also, how do these coupled processes impact electrochemical detection and processing? We address these questions by studying a special type of confined-volume architecture, the nanopore electrode array, or NEA, which is designed to be commensurate in size with physical scaling lengths, such as the Debye length, a concordance that offers performance characteristics not available in larger scale structures.The experiments described here depend critically on carefully constructed nanoscale architectures that can usefully control molecular transport and electrochemical reactivity. We begin by considering the experimental constraints that guide the design and fabrication of zero-dimensional nanopore arrays with multiple embedded electrodes. These zero-dimensional structures are nearly ideal for exploring how permselectivity and unscreened ion migration can be combined to amplify signals and improve selectivity by enabling highly efficient redox cycling. Our studies also highlight the benefits of arrays, in that molecules escaping from a single nanopore are efficiently captured by neighboring pores and returned to the population of active redox species being measured, benefits that arise from coupling ion accumulation and migration. These tools for manipulating redox species are well-positioned to explore single molecule and single particle electron transfer events through spectroelectrochemistry, studies which are enabled by the electrochemical zero-mode waveguide (ZMW), a special hybrid nanophotonic/nanoelectronic architecture in which the lower ring electrode of an NEA nanopore functions both as a working electrode to initiate electron transfer reactions and as the optical cladding layer of a ZMW. While the work described here is largely exploratory and fundamental, we believe that the development of NEAs will enable important applications that emerge directly from the unique coupled transport and electron-transfer capabilities of NEAs, including in situ molecular separation and detection with external stimuli, redox-based electrochemical rectification in individually encapsulated nanopores, and coupled sorters and analyzers for nanoparticles.

Analysis of dental and basal bone arch form correlations in skeletal Class â ¡ malocclusion.

INTRODUCTION: This study aimed to establish mathematical equations to describe the dental and basal arch forms in skeletal Class II malocclusion and to investigate correlations between these forms to facilitate clinical diagnosis and treatment design. METHODS: Cone-beam computed tomography images of 60 patients (30 each with skeletal Class II malocclusion and normal occlusion) were subjected to 3-dimensional volume rendering, image reconstruction, and measurement. Using a computer program written in Java on the Eclipse platform (Eclipse Foundation, Ottawa, Canada), a beta function was used to establish mathematical models of dental and basal bone arch forms, and model-fitting was performed. RESULTS: A mathematical model was developed to describe the dental and basal arch forms in skeletal Class II malocclusion. The maxillary and mandibular dental arch lengths were significantly longer in skeletal Class II malocclusion than in normal occlusion, whereas the width of the maxillary molar segment was smaller. The maxillary molar and mandibular intercranial segments in the basal arch were significantly longer in skeletal Class II malocclusion than in normal occlusion, whereas the mandibular intercranial segment width was smaller. CONCLUSIONS: The dental arch and basal bone arch forms in the maxilla and mandible follow individual curves, described by a beta function. In skeletal Class II malocclusion, the dental and basal arches are discrepant in horizontal and anteroposterior dimensions, which should be considered during orthodontic treatment planning to improve arch matching.

Electrowetting-Mediated Transport to Produce Electrochemical Transistor Action in Nanopore Electrode Arrays.

Understanding water behavior in confined volumes is important in applications ranging from water purification to healthcare devices. Especially relevant are wetting and dewetting phenomena which can be switched by external stimuli, such as light and electric fields. Here, these behaviors are exploited for electrochemical processing by voltage-directed ion transport in nanochannels contained within nanopore arrays in which each nanopore presents three electrodes. The top and middle electrodes (TE and ME) are in direct contact with the nanopore volume, but the bottom electrode (BE) is buried beneath a 70 nm silicon nitride (SiNx ) insulating layer. Electrochemical transistor operation is realized when small, defect-mediated channels are opened in the SiNx . These defect channels exhibit voltage-driven wetting that mediates the mass transport of redox species to/from the BE. When BE is held at a potential maintaining the defect channels in the wetted state, setting the potential of ME at either positive or negative overpotential results in strong electrochemical rectification with rectification factors up to 440. By directing the voltage-induced electrowetting of defect channels, these three-electrode nanopore structures can achieve precise gating and ion/molecule separation, and, as such, may be useful for applications such as water purification and drug delivery.

Engineering the Interaction Dynamics between Nano-Topographical Immunocyte-Templated Micromotors across Scales from Ions to Cells.

Manufacturing mobile artificial micromotors with structural design factors, such as morphology nanoroughness and surface chemistry, can improve the capture efficiency through enhancing contact interactions with their surrounding targets. Understanding the interplay of such parameters targeting high locomotion performance and high capture efficiency at the same time is of paramount importance, yet, has so far been overlooked. Here, an immunocyte-templated nano-topographical micromotor is engineered and their interactions with various targets across multiple scales, from ions to cells are investigated. The macrophage templated nanorough micromotor demonstrates significantly increased surface interactions and significantly improved and highly efficient removal of targets from complex aqueous solutions, including in plasma and diluted blood, when compared to smooth synthetic material templated micromotors with the same size and surface chemistry. These results suggest that the surface nanoroughness of the micromotors for the locomotion performance and interactions with the multiscale targets should be considered simultaneously, for they are highly interconnected in design considerations impacting applications across scales.

Electrochemical Surface-Enhanced Raman Spectroscopy of Pyocyanin Secreted by Pseudomonas aeruginosa Communities.

Pyocyanin (PYO) is one of many toxins secreted by the opportunistic human pathogenic bacterium Pseudomonas aeruginosa. Direct detection of PYO in biofilms is crucial because PYO can provide important information about infection-related virulence mechanisms in P. aeruginosa. Because PYO is both redox-active and Raman-active, we seek to simultaneously acquire both spectroscopic and redox state information about PYO. The combination of surface-enhanced Raman spectroscopy (SERS) and voltammetry is used here to provide insights into the molecular redox behavior of PYO while controlling the SERS and electrochemical (EC) response of PYO with external stimuli, such as pH and applied potential. Furthermore, PYO secretion from biofilms of different P. aeruginosa strains is compared. Both SERS spectra and EC behavior are observed to change with pH, and several pH-dependent bands are identified in the SERS spectra, which can potentially be used to probe the local environment. Comparison of the voltammetric behavior of wild-type and a PYO-deficient mutant unequivocally identifies PYO as a major component of the secretome. Spectroelectrochemical studies of the PYO standard reveal decreasing SERS intensities of PYO bands under reducing conditions. Extending these experiments to pellicle biofilms shows similar behavior with applied potential, and SERS imaging indicates that secreted PYO is localized in regions approximately the size of P. aeruginosa cells. The in situ spectroelectrochemical biofilm characterization approach developed here suggests that EC-SERS monitoring of secreted molecules can be used diagnostically and correlated with the progress of infection.

Tunable optical metamaterial-based sensors enabled by closed bipolar electrochemistry.

Enabled by the proliferation of nanoscale fabrication techniques required to create spatially-repeating, sub-wavelength structures to manipulate the behavior of visible-wavelength radiation, optical metamaterials are of increasing interest. Here we develop and characterize a chemical sensing approach based on electrochemical tuning of the optical response function of large-area, inexpensive nanoaperture metamaterials at visible and near-IR wavelengths. Nanosphere lithography is used to create an ordered array of sub-wavelength apertures in a Au film. The spacing of these apertures is established during fabrication, based on the size of the polystyrene nanospheres. Tunable shifts in the transmission spectrum can be produced post-fabrication by electrodeposition of a dissimilar metal, Ag, using the nanoaperture film as one electrode in a 2-electrode closed bipolar electrochemical (CBE) cell, altering hole size, film thickness, and film composition while maintaining hole spacing dictated by the original pattern. Optical transmission spectra acquired under galvanostatic conditions can be expressed as a linear combination of the initial and final (saturated) spectra, and the resulting response function exhibits a sigmoidal response with respect to the amount of charge (or metal) deposited. This architecture is then used to perform optical coulometry of model analytes in a CBE-based analyte-reporter dual cell device, thus expanding the capability of CBE-based sensors. Increasing the exposed electrode area of the analyte cell increases the response of the device, while modifying the circuit resistance alters the balance between sensitivity and dynamic range. These tunable nanoaperture metamaterials exhibit enhanced sensitivity compared to CBE electrochromic reporter cells to the µM to nM concentration range, suggesting further avenues for development of CBE-based chemical sensors as well as application to inexpensive, point-of-care diagnostic devices.

Whole-Cell Pseudomonas aeruginosa Localized Surface Plasmon Resonance Aptasensor.

The detection of whole-cell Pseudomonas aeruginosa presents an intriguing challenge with direct applications in health care and the prevention of nosocomial infection. To address this problem, a localized surface plasmon resonance (LSPR) based sensing platform was developed to detect whole-cell Pseudomonas aeruginosa strain PAO1 using a surface-confined aptamer as an affinity reagent. Nanosphere lithography (NSL) was used to fabricate a sensor surface containing a hexagonal array of Au nanotriangles. The sensor surface was subsequently modified with biotinylated polyethylene glycol (Bt-PEG) thiol/PEG thiol (1:3), neutravidin, and biotinylated aptamer in a sandwich format. The 1:3 (v/v) ratio of Bt-PEG thiol/PEG thiol was specifically chosen to maximize PAO1 binding while minimizing nonspecific adsorption and steric hindrance. In contrast to prior whole-cell LSPR work, the LSPR wavelength shift was shown to be linearly related to bacterial concentration over the range of 10-103 cfu mL-1. This LSPR sensing platform is rapid (∼3 h for detection), sensitive (down to the level of a single bacterium), selective for detection of Pseudomonas strain PAO1 over other strains, and exhibits a clinically relevant dynamic range and excellent shelf life (≥2 months) when stored at ambient conditions. This versatile LSPR sensing platform should be extendable to a wide range of supermolecular analytes, including both bacteria and viruses, by switching affinity reagents, and it has potential to be used in point-of-care and field-based applications.

Voltage-Gated Nanoparticle Transport and Collisions in Attoliter-Volume Nanopore Electrode Arrays.

Single nanoparticle analysis can reveal how particle-to-particle heterogeneity affects ensemble properties derived from traditional bulk measurements. High-bandwidth, low noise electrochemical measurements are needed to examine the fast heterogeneous electron-transfer behavior of single nanoparticles with sufficient fidelity to resolve the behavior of individual nanoparticles. Herein, nanopore electrode arrays (NEAs) are fabricated in which each pore supports two vertically spaced, individually addressable electrodes. The top ring electrode serves as a particle gate to control the transport of silver nanoparticles (AgNPs) within individual attoliter volume NEAs nanopores, as shown by redox collisions of AgNPs collisions at the bottom disk electrode. The AgNP-nanoporeis system has wide-ranging technological applications as well as fundamental interest, since the transport of AgNPs within the NEA mimics the transport of ions through cell membranes via voltage-gated ion channels. A voltage threshold is observed above which AgNPs are able to access the bottom electrode of the NEAs, i.e., a minimum potential at the gate electrode is required to switch between few and many observed collision events on the collector electrode. It is further shown that this threshold voltage is strongly dependent on the applied voltage at both electrodes as well as the size of AgNPs, as shown both experimentally and through finite-element modeling. Overall, this study provides a precise method of monitoring nanoparticle transport and in situ redox reactions within nanoconfined spaces at the single particle level.

The association between missing teeth and non-alcoholic fatty liver disease in adults.

AIMS: Long-term oral chronic inflammatory process is closely related to systemic inflammation, which is a main mechanism involved in non-alcoholic fatty liver disease (NAFLD). Tooth loss could reflect the accumulation of oral local inflammation, implying that number of missing teeth may associate with NAFLD. This study evaluated the association between missing teeth and presence of NAFLD in a general population. MATERIALS AND METHODS: A cross-sectional study of 24,470 adults was carried out from the Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study. The self-reported number of missing teeth (excluding third molars) was recorded and classified into four categories: 0, 1-2, 3-5, and ≥6. The NAFLD was diagnosed by the liver ultrasonography. Associations were analysed by adjusted multivariable logistic regression. RESULTS: The multivariable-adjusted odds ratios (95% confidence interval) of NAFLD across the categories of missing teeth were as follows: in males, 1.00 (reference), 1.04 (0.93-1.16), 1.06 (0.90-1.24), and 1.40 (1.09-1.81) (p for trend = 0.04); in females, 1.00 (reference), 0.98 (0.83-1.15), 1.11 (0.90-1.37), and 1.07 (0.77-1.48) (p for trend = 0.45). CONCLUSIONS: The number of missing teeth was associated with a higher presence of NAFLD in males but not females.

Electrochemistry at single molecule occupancy in nanopore-confined recessed ring-disk electrode arrays.

Electrochemical reactions at nanoscale structures possess unique characteristics, e.g. fast mass transport, high signal-to-noise ratio at low concentration, and insignificant ohmic losses even at low electrolyte concentrations. These properties motivate the fabrication of high density, laterally ordered arrays of nanopores, embedding vertically stacked metal-insulator-metal electrode structures and exhibiting precisely controlled pore size and interpore spacing for use in redox cycling. These nanoscale recessed ring-disk electrode (RRDE) arrays exhibit current amplification factors, AFRC, as large as 55-fold with Ru(NH3)62/3+, indicative of capture efficiencies at the top and bottom electrodes, Φt,b, exceeding 99%. Finite element simulations performed to investigate the concentration distribution of redox species and to assess operating characteristics are in excellent agreement with experiment. AFRC increases as the pore diameter, at constant pore spacing, increases in the range 200-500 nm and as the pore spacing, at constant pore diameter, decreases in the range 1000-460 nm. Optimized nanoscale RRDE arrays exhibit a linear current response with concentration ranging from 0.1 µM to 10 mM and a small capacitive current with scan rate up to 100 V s-1. At the lowest concentrations, the average pore occupancy is 〈n〉 ∼ 0.13 molecule establishing productive electrochemical signals at occupancies at and below the single molecule level in these nanoscale RRDE arrays.

Closed bipolar electrode-enabled dual-cell electrochromic detectors for chemical sensing.

Bipolar electrodes (BPE) are electrically floating metallic elements placed in electrified fluids that enable the coupling of anodic and cathodic redox reactions at the opposite ends by electron transfer through the electrode. One particularly compelling application allows electron transfer reactions at one end of a closed BPE to be read out optically by inducing a redox-initiated change in the optical response function of a reporter system at the other end. Here, a BPE-enabled method for electrochemical sensing based on the electrochromic response of a methyl viologen (MV) reporter is developed, characterized, and rendered in a field-deployable format. BPE-enabled devices based on two thin-layer-cells of ITO and Pt were fabricated to couple an analytical reaction in one cell with an MV reporter reaction, producing a color change in the complementary cell. Using Fe(CN)63/4- as a model analyte, the electrochemically induced color change of MV was determined initially by measuring its absorbance via a CCD camera coupled to a microscope. Then, smartphone-based detection and RGB analysis were employed to further simplify the sensing scheme. Both methods produced a linear relationship between the analyte concentration, the quantity of MV generated, and the colorimetric response, yielding a limit of detection of 1.0 µM. Similar responses were observed in the detection of dopamine and acetaminophen. Further evolution of the device replaced the potentiostat with batteries to control potential, demonstrating the simplicity and portability of the device. Finally, the physical separation of the reporter and analytical cells renders the device competent to detect analytes in different (e.g. non-aqueous) phases, as demonstrated by using the electrochromic behavior of aqueous MV to detect ferrocene in acetonitrile in the analytical cell.

A comprehensive bibliometric analysis (2000-2022) on the mapping of knowledge regarding immunotherapeutic treatments for advanced, recurrent, or metastatic cervical cancer.

Background: Despite extensive literature on therapeutic strategies for cervical cancer, a bibliometric analysis specifically focused on immunotherapy for advanced, recurrent, or metastatic (A/R/M) cervical malignancies remains unexplored. This study aims to address this gap by presenting a comprehensive overview that includes general characteristics, research focal points, the trajectory of evolution, and current emerging trends in this under-researched area. Methods: A systematic search was conducted using the Web of Science Core Collection (WOSCC) to identify articles related to A/R/M cervical cancer published between 2000 and 2022. Citespace and VOS viewer were the primary tools used to identify research focal points, intriguing future patterns, and to evaluate contributions and co-occurrences among authors, institutions, countries, and journals. Results: A total of 1,001 original articles were identified, involving 6,387 authors from 66 countries and 1,474 institutions, and published across 366 academic journals. The United States contributed most significantly. The most productive researcher was Van der Burg SH from Leiden University Medical Center. The International Journal of Cancer and Cancer Research were identified as the most productive and influential journals, respectively. Analysis of co-citation clusters highlighted 25 clusters, primarily focusing on potential predictive biomarkers, dendritic cell-based tumor vaccines, therapeutic HPV vaccinations, peptide-based cancer vaccines, tumor immune microenvironments, and adoptive cell transfer (ACT). The latest significant trends in A/R/M cervical cancer immunotherapy research included ACT, CAR-T, and immune checkpoint inhibitors (ICIs), as revealed by keyword and reference burst detection. Conclusion: This pioneering study provides a detailed landscape of immunotherapy research in A/R/M cervical cancer. It underscores the importance of global collaboration, enriches our understanding of the immunology of A/R/M cervical cancer, expands on potential beneficiaries of immunotherapy, and explores clinical applications of various therapies, including therapeutic vaccines, adoptive cell transfer, and ICIs, particularly in combination with established treatments such as chemotherapy, radiotherapy, and targeted therapy.

Mutation characteristics of cancer susceptibility genes in Chinese ovarian cancer patients.

Introduction: The association between mutations in susceptibility genes and the occurrence of ovarian cancer has been extensively studied. Previous research has primarily concentrated on genes involved in the homologous recombination repair pathway, particularly BRCA1 and BRCA2. However, a wider range of genes related to the DNA damage response pathways has not been fully explored. Methods: To investigate the mutation characteristics of cancer susceptibility genes in the Chinese ovarian cancer population and the associations between gene mutations and clinical data, this study initially gathered a total of 1171 Chinese ovarian cancer samples and compiled a dataset of germline mutations in 171 genes. Results: In this study, it was determined that MC1R and PRKDC were high-frequency ovarian cancer susceptibility genes in the Chinese population, exhibiting notable distinctions from those in European and American populations; moreover high-frequency mutation genes, such as MC1R: c.359T>C and PRKDC: c.10681T>A, typically had high-frequency mutation sites. Furthermore, we identified c.8187G>T as a characteristic mutation of BRCA2 in the Chinese population, and the CHEK2 mutation was significantly associated with the early onset of ovarian cancer, while the CDH1 and FAM175A mutations were more prevalent in Northeast China. Additionally, Fanconi anemia pathway-related genes were significantly associated with ovarian carcinogenesis. Conclusion: In summary, this research provided fundamental data support for the optimization of ovarian cancer gene screening policies and the determination of treatment, and contributed to the precise intervention and management of patients.