Impacts of the COVID-19 pandemic on pediatric and adult patients with hemophilia.

BACKGROUND: The coronavirus disease 2019 (COVID-19)-associated mortality rate of hemophilia patients is similar to that of the general population, but the risk of hospitalization and bleeding is higher. However, the specific impact of this infection on hemophilia patients remains unknown. We aimed to investigate the impact of the pandemic on the infection susceptibility, symptoms, drug use, and social intercourse of patients with hemophilia. METHODS: A survey was distributed to 265 patients with hemophilia (185 adults and 80 children) in the Fujian hemophilia therapeutic center (Fuzhou City, China) during the COVID-19 pandemic, and data were collected between January 2022 and January 2023. The impacts of SARS-CoV-2 infection on hemophilia symptoms, drug use, and social intercourse of these patients were investigated, and the association between the recovery time and disease conditions was explored in infected patients. RESULTS: During the pandemic, compared with adult patients, pediatric patients had significantly reduced social intercourse and outdoor activities because of the fear of contracting COVID-19 (85.0% vs. 66.5%). Bleeding events were also significantly fewer in children than in adults (61.2% vs. 81.1%). The SARS-CoV-2 infection rate was significantly higher in patients living in urban areas than in those living in rural areas (74.3% vs. 53.6%). The duration of symptomatic recovery from COVID-19 was not significantly associated with hemorrhage, type and classification of hemophilia, presence of inhibitors, complications, and vaccination status. CONCLUSION: Having COVID-19 infection did not significantly influence the symptoms and treatments in patients with hemophilia. Pediatric patients had significantly fewer bleeding events than adults.

Targeted gene sequencing and transcriptome sequencing reveal characteristics of NUP98 rearrangement in pediatric acute myeloid leukemia.

BACKGROUND: NUP98 rearrangements (NUP98-r) are rare but overrepresented mutations in pediatric acute myeloid leukemia (AML) patients. NUP98-r is often associated with chemotherapy resistance and a particularly poor prognosis. Therefore, characterizing pediatric AML with NUP98-r to identify aberrations is critically important. METHODS: Here, we retrospectively analyzed the clinicopathological features, genomic and transcriptomic landscapes, treatments, and outcomes of pediatric patients with AML. RESULTS: Nine patients with NUP98-r mutations were identified in our cohort of 142 patients. Ten mutated genes were detected in patients with NUP98-r. The frequency of FLT3-ITD mutations differed significantly between the groups harboring NUP98-r and those without NUP98-r (P = 0.035). Unsupervised hierarchical clustering via RNA sequencing data from 21 AML patients revealed that NUP98-r samples clustered together, strongly suggesting a distinct subtype. Compared with that in the non-NUP98-r fusion and no fusion groups, CMAHP expression was significantly upregulated in the NUP98-r samples (P < 0.001 and P = 0.001, respectively). Multivariate Cox regression analyses demonstrated that patients harboring NUP98-r (P < 0.001) and WT1 mutations (P = 0.030) had worse relapse-free survival, and patients harboring NUP98-r (P < 0.008) presented lower overall survival. CONCLUSIONS: These investigations contribute to the understanding of the molecular characteristics, risk stratification, and prognostic evaluation of pediatric AML patients.

Life-course obesity and heart failure: a two-sample Mendelian randomization study.

Heart failure is a multifaceted clinical syndrome, with obesity identified as a significant modifiable risk factor. This study employed a two-sample Mendelian randomization (MR) design, incorporating obesity data across life stages, to elucidate the causal link between obesity and heart failure. Data on heart failure from the 2023 Finngen database and genetic predictors of obesity from the IEU OpenGWAS project were analyzed using the IVW method, MR-Egger regression, weighted median, simple mode, weighted mode, and scatter plots. Heterogeneity was assessed with Cochran's Q test, and horizontal pleiotropy with MR-Egger intercept test. Sensitivity to single-nucleotide polymorphisms (SNPs) was tested via leave-one-out analysis, and funnel plots were utilized for visual inspection of horizontal pleiotropy. Statistical powers were also calculated. The MR analysis findings indicate a significant relationship between birth weight and the likelihood of developing heart failure (Odds Ratio [OR] 1.134, 95% Confidence Interval [CI] 1.033-1.245, P = 0.008). In addition, a heightened childhood BMI was found to be a significant predictor of heart failure risk (OR 1.307, 95% CI 1.144-1.494, P = 8.51E-05), as was childhood obesity (OR 1.123, 95% CI 1.074-1.173, P = 2.37E-07). Furthermore, adult BMI sex-combined exhibited a strong correlation with the risk of heart failure (OR 2.365, 95% CI 2.128-2.629, P = 1.91E-57). Sensitivity analyses provided further support for the reliability of these results, with no significant indication of horizontal pleiotropy observed. This study shows that obesity, including childhood obesity, is linked to a higher risk of heart failure. These findings highlight the urgent need for early weight management interventions in public health and clinical settings to reduce heart failure rates.

Zoonotic outbreak risk prediction with long short-term memory models: a case study with schistosomiasis, echinococcosis, and leptospirosis.

BACKGROUND: Zoonotic infections, characterized with huge pathogen diversity, wide affecting area and great society harm, have become a major global public health problem. Early and accurate prediction of their outbreaks is crucial for disease control. The aim of this study was to develop zoonotic diseases risk predictive models based on time-series incidence data and three zoonotic diseases in mainland China were employed as cases. METHODS: The incidence data for schistosomiasis, echinococcosis, and leptospirosis were downloaded from the Scientific Data Centre of the National Ministry of Health of China, and were processed by interpolation, dynamic curve reconstruction and time series decomposition. Data were decomposed into three distinct components: the trend component, the seasonal component, and the residual component. The trend component was used as input to construct the Long Short-Term Memory (LSTM) prediction model, while the seasonal component was used in the comparison of the periods and amplitudes. Finaly, the accuracy of the hybrid LSTM prediction model was comprehensive evaluated. RESULTS: This study employed trend series of incidence numbers and incidence rates of three zoonotic diseases for modeling. The prediction results of the model showed that the predicted incidence number and incidence rate were very close to the real incidence data. Model evaluation revealed that the prediction error of the hybrid LSTM model was smaller than that of the single LSTM. Thus, these results demonstrate that using trending sequences as input sequences for the model leads to better-fitting predictive models. CONCLUSIONS: Our study successfully developed LSTM hybrid models for disease outbreak risk prediction using three zoonotic diseases as case studies. We demonstrate that the LSTM, when combined with time series decomposition, delivers more accurate results compared to conventional LSTM models using the raw data series. Disease outbreak trends can be predicted more accurately using hybrid models.

Simultaneous Presentation of Dexamethasone and Nerve Growth Factor via Layered Carbon Nanotubes and Polypyrrole to Interface Neural Cells.

The implantation of neural electrodes usually induces acute and chronic inflammation, which can result in the formation of glial scars encapsulating the implanted electrodes and the loss of neurons near the active electrode sites. Local presentation of anti-inflammatory drugs or neural protective factors has been evidenced as an effective strategy to modulate inflammatory responses and promote electrode-neuron integration. Here, a novel delivery system for the simultaneous presentation of both anti-inflammatory drugs (dexamethasone, Dex) and nerve-growth-promoting factors (nerve growth factor, NGF) from the electrode sites was developed via layer-structured carbon nanotubes and conductive polymers. The modified electrodes exhibited higher charge storage capacitance and lower electrochemical impedance compared to unmodified electrodes and electrodes coated with polypyrrole/Dex. Dex released from the functional coating under controlled electrochemical stimulation was able to inhibit the lipopolysaccharide-induced secretion or mRNA transcription of inflammatory cytokines, including nitric oxide, TNF-α, and IL-6 in RAW264.7 cells, and control the activation of cultured astrocytes. In addition, the functional coatings did not show a toxic effect on PC12 cells and primary neural cells but exhibited promoted activities on the adhesion, growth, and neurite extension of neural cells.

14, 15-EET alleviates neurological impairment through maintaining mitochondrial dynamics equilibrium via AMPK/SIRT1/FoxO1 signal pathways in mice with cerebral ischemia reperfusion.

AIM: To explore whether 14, 15-EET regulates mitochondrial dynamics to exert neuroprotective effects after cerebral ischemia-reperfusion and its underlying mechanisms. METHODS: The mouse middle cerebral artery occlusion reperfusion model was used to observe brain infarct volume and neuronal apoptosis by TTC staining and Tunel assay, modified neurological severity score to detect neurological impairment, HE staining and Nissl staining to observe neuron damage, western blot and immunofluorescence methods to detect the expression of mitochondrial dynamics-related proteins, transmission electron microscopy, and Golgi-Cox staining to detect mitochondrial morphology and neuronal dendritic spines. RESULTS: 14, 15-EET reduced the neuronal apoptosis and cerebral infarction volume induced by middle cerebral artery occlusion reperfusion (MCAO/R), inhibited the degradation of dendritic spines, maintained the structural integrity of neurons, and alleviated neurological impairment. Cerebral ischemia-reperfusion induces mitochondrial dynamics disorders, upregulates the expression of the mitochondrial division protein Fis 1, and inhibits the expression of mitochondrial fusion proteins MFN1, MFN2, and OPA1, while 14, 15-EET treatment reverses this process. Mechanistic studies have shown that 14, 15-EET promotes the phosphorylation of AMPK, upregulates the expression of SIRT1 and phosphorylation of FoxO1, thereby inhibiting mitochondrial division and promoting mitochondrial fusion, preserving mitochondrial dynamics, maintaining neuronal morphological and structural integrity, and alleviating neurological impairment induced by middle cerebral artery occlusion reperfusion. Compound C treatment diminishes the neuroprotective effect of 14, 15-EET following MCAO/R in mice. CONCLUSION: This study elucidates the novel neuroprotective mechanism of 14, 15-EET, providing a novel approach for the development of drugs based on mitochondrial dynamics.

Identification and Functional Characterization of Tyrosine Decarboxylase from Rehmannia glutinosa.

Rehmannia glutinosa is an important medicinal plant that has long been used in Chinese traditional medicine. Acteoside, one of the bioactive components from R. glutinosa, possessed various pharmacological activities for human health; however, the molecular mechanism of acteoside formation is not fully understood. In the current study, a novel tyrosine decarboxylase (designated as RgTyDC2) was identified from the R. glutinosa transcriptome. Biochemical analysis of RgTyDC2 showed RgTyDC2 uses tyrosine and dopa as the substrate to produce tyramine and dopamine, respectively, and it displays higher catalytic efficiency toward tyrosine than dopa. Moreover, the transcript level of RgTyDC2 was consistent with the accumulation pattern of acteoside in R. glutinosa, supporting its possible role in the biosynthesis of acteoside in vivo.

In situ polymerization of conducting polymers around living neural cells: Cellular effect study.

Conducting polymer has been directly polymerized around living neural cells or in the cortex with the aim of creating an intimate contact between implantable electrical devices and electrogenetic cells. The long term cellular effect after conductive polymer coating, a critical issue for practical applications, has not been reported. In this study, poly(3,4-ethylenedioxythiophene) PEDOT was directly polymerized around the living primary neural and PC12 cells under varying current densities, potentials and charge-balanced current pulses. The cell morphology, nuclei evolution, and cell viability post PEDOT polymerization were studied at different time points. The aim of this study was to investigate the immediate and long-term cellular response towards in-situ polymerization of conductive polymers and to provide experimental information on the feasibility of this technique in practical applications.

Polyurethane foam dressings ameliorating local adverse effects of azacitidine: a randomized controlled trial.

This study investigated the use of polyurethane foam dressings to prevent local adverse reactions of subcutaneous azacitidine injection. Patients receiving a subcutaneous azacitidine injection were randomly divided into experimental and control groups. A total of 55 patients were included in each group. A polyurethane foam dressing was used to cover the injection site of patients in the experimental group. Conventional treatment was used in the control group. Injection site pain and local skin reactions were assessed after the intervention in both groups. The score and duration of pain, the incidence and duration of local skin adverse reactions, and the incidence of severe reactions in the experimental group were significantly lower than in the control group (p < 0.05). Polyurethane foam dressing can effectively reduce local adverse reactions of subcutaneous injection of azacitidine, relieve pain, shorten the duration of local pain and adverse reactions, and improve the quality of nursing.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of locally advanced esophageal cancer: a population-based analysis.

AIM: Currently, the optimal treatment strategy for locally advanced esophageal cancer (LAEC) remains controversial. We perform the present study to compare the outcomes of LAEC treated with neoadjuvant chemotherapy (neo-CT) or chemoradiotherapy (neo-CRT). MATERIALS AND METHODS: A population cohort with histologically diagnosed of esophageal cancer was identified from SEER database between 2004 and 2015. The Kaplan-Meier method and Cox-regression proportional hazards model were used to assess the impact of neoadjuvant treatment regimens on the cause-specific survival (CSS) and overall survival (OS) of LAEC. A propensity score model was utilized to balance baseline covariates. RESULTS: After propensity score matching, a total of 1986 LAEC patients were included for analysis, 1,655 patients treated with neo-CRT and 331 with neo-CT, respectively. The survival outcomes of LAEC treated with neo-CRT were comparable to those treated with neo-CT in terms of 5-year OS (39% vs. 36%, p = 0.63) and CSS (51% vs. 51%, p = 0.77). In the multivariate Cox analyses, sex, histological grade, ypT stage, ypN( +), and number of LN examined were independent factors for predicting OS and CSS among LAEC treated with neoadjuvant treatment. CONCLUSION: The present study based on large cohort demonstrated that no significant survival difference was observed between LAEC patients treated with neo-CRT versus neo-CT. However, the results needed to be confirmed in well-designed prospective trials.

Aerosol water content enhancement leads to changes in the major formation mechanisms of nitrate and secondary organic aerosols in winter over the North China Plain.

In recent years, severe air pollution still frequently occurs in winter despite the effective implementation of clean air actions in China. Therefore, field measurements of particle composition and gas precursors were collected from December 1, 2018 to January 15, 2019 at an urban site in a central Chinese city to investigate the existing mechanisms of pollution. The hourly averaged PM2.5 concentration during the campaign was 92.7 µg m-3, with nitrate and organic aerosol (OA) demonstrated as the principal components. Generally, NO2 oxidation in the daytime was observed as the major mechanism for nitrate generation, and aerosol water content (AWC) showed its influential role with the associated increases in the nitrogen oxidation and nitrate partitioning ratios. When AWC increased from dozens to hundreds of µg m-3 after the afternoon, nocturnal N2O5 hydrolysis was demonstrated as the overriding mechanism and provoked extreme contamination of nitrates. Five sources of organic aerosols (OAs) were identified: hydrocarbon-like OAs (HOAs, 16.5%), coal combustion OAs (CCOAs, 19.2%), biomass burning OAs (BBOAs, 9.9%), semi-volatile oxygenated OAs (SV-OOAs, 29.4%), and low-volatile oxygenated OAs (LV-OOAs, 25.0%). SV-OOAs and LV-OOAs were identified as gasSOAs and aqSOAs according to their sensitivities to the atmospheric oxidation capacity and AWC. In addition, aqueous-phase processing was found to be the dominant pathway for SOA formation when the AWC concentration was higher than 80 µg m-3. As an influential factor for nitrate and SOA formation, AWC could be greatly affected by RH and the concentrations of inorganic species. Sulfate, which was mainly contributed by anthropogenic emissions, was demonstrated to be a significant factor for active aqueous phase reactions, although SO2 has been dramatically reduced in recent years. Above all, this study revealed the significant role of AWC in current pollution episode in winter, and will assist in establishing future measures for pollution mitigation.

Large air pressure changes triggered by P-SV ground motion in a cave in northern Taiwan.

Acoustic-gravity waves are generally considered to be one of the major factors that drive changes of the total electron content in the ionosphere. However, causal mechanisms of couplings between sources in the lithosphere and responses in the atmosphere and the ionosphere are not fully understood, yet. A barometer in the cave of the SBCB station records an unusual phenomenon of larger amplitudes in air pressure changes inside than those at the Xinwu station (outside). Accordingly, the comparison between the recorded data at the SBCB and Xinwu station can drive investigations of potential sources of the unusual phenomenon. Analytical results of phase angle differences reveal that the air pressure outside the cave at the Xinwu station often leads air pressure changes inside at the SBCB station at relatively low frequency bands. In contrast, the larger pressure changes at frequencies > ~ 5 × 10-4 Hz inside the cave at the SBCB station lead smaller changes outside at the Xinwu station. To expose causal mechanisms of the unusual phenomenon, continuous seismic waveforms are further conducted for examination. When the horizontal and vertical ground velocities of ground vibrations yield a difference in the phase angle close to 90°, coherence values between the air pressure changes and ground vibrations become large. This suggests that the pressure-shear vertical ground vibrations can drive air pressure changes. Meanwhile, the results shed light on investigating the existence of acoustic waves near the Earth's surface using a partially confined space underground due to that the assumptions of the waves can propagate upward into the atmosphere driving changes in the ionosphere.

Characteristics and sources of non-methane VOCs and their roles in SOA formation during autumn in a central Chinese city.

Volatile organic compounds (VOCs) are essential in secondary organic aerosol (SOA) formation due to their dual roles as precursors and oxidant producers. In order to explore the dominant contributions of SOA formation from VOCs in central China, 53 VOC species were observed with proton transfer reaction-mass spectrometry (PTR-MS) and canister grab samples in Xinxiang, a mid-sized city located in Henan Province, from November 5th to December 3rd, 2018. The result showed that anthropogenic emissions were intensive compared with many studies in the world. Among the observed VOCs, benzene and toluene had the largest SOA formation potential (SOAFP), and their contributions in SOA formation kept stable with the aggravation of pollution. Among VOCs, formaldehyde was the strongest radical contributor, and the contribution of acetaldehyde was also found significant in this study, especially in polluted periods. Based on the positive matrix factorization (PMF) model, benzenoids (mainly single-ring aromatics) were majorly emitted from chemical process, solvent evaporation, and residential heating, with a total fraction of 75%, and these sources were estimated to have largest SOAFP. However, thermal power generation, chemical process, and solvent evaporation had highest radical contribution rates. According to the backward trajectory analysis, the VOC concentrations were dominated by local emissions. Emissions in the surrounding provinces occupied fractions of 33%-42% in the five sources. Therefore, regional collaborative emission reduction is also important.

Source apportionment of fine organic carbon (OC) using receptor modelling at a rural site of Beijing: Insight into seasonal and diurnal variation of source contributions.

This study was designed to investigate the seasonal characteristics and apportion the sources of organic carbon during non-haze days (<75 µg m-3) and haze (≥75 µg m-3) events at Pinggu, a rural Beijing site. Time-resolved concentrations of carbonaceous aerosols and organic molecular tracers were measured during the winter of 2016 and summer 2017, and a Chemical Mass Balance (CMB) model was applied to estimate the average source contributions. The concentration of OC in winter is comparable with previous studies, but relatively low during the summer. The CMB model apportioned seven separate primary sources, which explained on average 73.8% on haze days and 81.2% on non-haze days of the organic carbon in winter, including vegetative detritus, biomass burning, gasoline vehicles, diesel vehicles, industrial coal combustion, residential coal combustion and cooking. A slightly lower percentage of OC was apportioned in the summer campaign with 64.5% and 78.7% accounted for. The other unapportioned OC is considered to consist of secondary organic carbon (SOC). During haze episodes in winter, coal combustion and SOC were the dominant sources of organic carbon with 23.3% and 26.2%, respectively, followed by biomass burning emissions (20%), whereas in summer, industrial coal combustion and SOC were important contributors. Diurnal contribution cycles for coal combustion and biomass burning OC showed a peak at 6-9 pm, suggesting domestic heating and cooking were the main sources of organic aerosols in this rural area. Backward trajectory analysis showed that high OC concentrations were measured when the air mass was from the south, suggesting that the organic aerosols in Pinggu were affected by both local emissions and regional transport from central Beijing and Hebei province during haze episodes. The source apportionment by CMB is compared with the results of a Positive Matrix Factorization (PMF) analysis of ACSM data for non-refractory PM1, showing generally good agreement.

An Active Repetitive Learning Control Method for Lateral Suspension Systems of High-Speed Trains.

This article presents a novel perspective to improve the ride quality of high-speed trains (HSTs), namely, by virtue of the periodicity of lateral dynamics to suppress the lateral vibration of HST. To resolve the contradiction between the complex HST model and the effective controller design, a simplified three-degrees-of-freedom (3-DOF) quarter-vehicle model is first employed for controller design, while a 17-DOF full-vehicle model is built for efficiency verification, where periodic and random track irregularities are considered, respectively. An active repetitive learning control (RLC) method is proposed to achieve the periodic tracking control, where the learning convergence is proved rigorously in a Lyapunov way. The configuration of RLC-based lateral suspensions is economical in the sense that only four actuators and six sensors are needed. It is verified by simulation that, compared with the dynamic matrix controller, the proposed RLC controller has greatly reduced the lateral vibration of a vehicle body, especially the lateral acceleration in the frequency range of (0, 3] Hz to which human body is strongly sensitive.

A cyanide-sensing detector in aqueous solution based on anion-π interaction-driven electron transfer.

A "turn on" fluorescent and colorimetric sensor, HAT(CN)6, was developed for the light-up detection of cyanide. It was implemented through its strong anion-π interaction, inducing thermal CN- → HAT(CN)6 electron transfer, to give the dianion product [HAT(CN)6]2-, which exhibits unexpected fluorescence. The sensor shows high selectivity, rapid response and a low detection limit towards CN- in aqueous solution, hence indicating its enormous potential in practical applications.

Structure of a Thyrotropin Receptor Monoclonal Antibody Variable Region Provides Insight into Potential Mechanisms for its Inverse Agonist Activity.

BACKGROUND: The high constitutive, or ligand-independent, activity of the thyrotropin receptor (TSHR) is of clinical importance in some thyroid conditions, particularly well-differentiated thyroid carcinoma remnants following incomplete ablative therapy (surgery and radioiodine). Under these conditions, even total suppression of TSH by thyroid hormone administration does not fully reduce TSHR activity, a driver of thyrocyte growth. METHODS: CS-17 is a murine monoclonal antibody that has inverse agonist activity in that it suppresses TSHR constitutive activity. This study crystallized the CS-17 Fab and determined its atomic structure at a resolution of 3.4 Å. RESULTS: In silico docking of this structure to that of the TSHR extracellular domain was accomplished by targeting to TSHR residue tyrosine 195 (Y195) known to contribute to the CS-17 epitope. High affinity interaction between these two molecules, primarily by the CS-17 immunoglobulin heavy chain, was validated by energetic analysis (KD of 8.7 × 10-11 M), as well as by previously obtained data on a number of individual TSHR amino acids in three regions whose mutagenesis reduced CS-17 binding as detected by flow cytometry. CONCLUSIONS: Structural insight at atomic resolution of a TSHR antibody with inverse agonist activity opens the way for the development of a molecule with therapeutic potential, particularly in thyroid carcinoma. For this purpose, CS-17 will require "humanization" by substitution of its constant region (Fc component). In addition, with its epitope defined, the CS-17 affinity can be increased further by mutagenesis of selected amino acids in its heavy- and light-chain complementarity determining regions.

Screening of different sample types associated with sheep and cattle for the presence of nematophagous fungi in China.

A total of 1502 samples, including feces of sheep (793) and cattle (348), pasture soil (118), dung compost (147) and barn soil (96), were examined between October 2012 and August 2014 to discover potential strains of nematophagous fungi for the biological control of livestock-parasitic nematodes. These samples were collected from 87 sites located in 48 counties of 20 provinces (autonomous regions/municipalities) of China. Fungi were identified down to a species level. Four hundred and seventy-seven isolates, which were distributed in 8 genera and 28 taxa, were identified as nematophagous fungi. Nematode-trapping fungi included 17 species and one unidentified species of Arthrobotrys, two of Dactylella, Drechslerella dactyloides, and Duddingtonia flagrans. Five identified species and two unidentified species of endoparasitic fungi were isolated. The predominant species from all regions were Arthrobotrys oligospora, followed by Arthrobotrys musiformis, Arthrobotrys (Monacrosporium) thaumasiun, and Arthrobotrys (Monacrosporium) microscaphoides. Species with adhesive networks were the most frequently isolated. Among the endoparasitic fungi, Podocrella harposporifera (Harposporium anguillulae) was the most common species, followed by Harposporium lilliputanum and Harposporium arcuatum. Based on Shannon diversity index, the diversity levels of nematophagous fungi were relatively higher in samples associated with cattle, barn soil, and subtropical monsoon climate zone. Three species isolated from this study, namely, Duddingtonia flagrans, Arthrobotrys salina (Monacrosporium salinum), and Arthrobotrys oligospora var. sarmatica, are newly recorded in China, and 20 species (including one unidentified species) are newly recorded in sheep and cattle barn soils worldwide.

A novel cascade strategy with supramolecular and chemodosimetric methods for designing a fluorescent ratiometric detector hypersensitive to trace water.

An intensely fluorescent zinc-salicylideneimine complex (-Zn(II)) was developed as a fluorescent ratiometric detector for the quantitative determination of trace water contents both in THF and methanol. It works based on a water-triggered cascade process: the dissociation reaction of the supramolecular ensemble and the subsequent hydrolysis reaction of its ligand.

A unique mouse strain that develops spontaneous, iodine-accelerated, pathogenic antibodies to the human thyrotrophin receptor.

Abs that stimulate the thyrotropin receptor (TSHR), the cause of Graves' hyperthyroidism, only develop in humans. TSHR Abs can be induced in mice by immunization, but studying pathogenesis and therapeutic intervention requires a model without immunization. Spontaneous, iodine-accelerated, thyroid autoimmunity develops in NOD.H2(h4) mice associated with thyroglobulin and thyroid-peroxidase, but not TSHR, Abs. We hypothesized that transferring the human TSHR A-subunit to NOD.H2(h4) mice would result in loss of tolerance to this protein. BALB/c human TSHR A-subunit mice were bred to NOD.H2(h4) mice, and transgenic offspring were repeatedly backcrossed to NOD.H2(h4) mice. All offspring developed Abs to thyroglobulin and thyroid-peroxidase. However, only TSHR-transgenic NOD.H2(h4) mice (TSHR/NOD.H2(h4)) developed pathogenic TSHR Abs as detected using clinical Graves' disease assays. As in humans, TSHR/NOD.H2(h4) female mice were more prone than male mice to developing pathogenic TSHR Abs. Fortunately, in view of the confounding effect of excess thyroid hormone on immune responses, spontaneously arising pathogenic human TSHR Abs cross-react poorly with the mouse TSHR and do not cause thyrotoxicosis. In summary, the TSHR/NOD.H2(h4) mouse strain develops spontaneous, iodine-accelerated, pathogenic TSHR Abs in female mice, providing a unique model to investigate disease pathogenesis and test novel TSHR Ag-specific immunotherapies aimed at curing Graves' disease in humans.