A conserved methyltransferase active site residue of Zika virus NS5 is required for the restriction of STING activation and interferon expression.

Zika virus (ZIKV) is a re-emerging RNA virus and causes major public health events due to its link to severe neurological complications in foetuses and neonates. The cGAS-STING signalling pathway regulates innate immunity and plays an important role in the invasion of DNA and RNA viruses. This study reveals a distinct mechanism by which ZIKV restricts the cGAS-STING signalling to repress IFN-ß expression. ZIKV attenuates IFN-ß expression induced by DNA viruses (herpes simplex virus type 1, HSV-1) or two double-stranded DNAs (dsDNA90 and HSV120) in mouse embryonic fibroblasts (MEFs). Notably, ZIKV NS5, the viral RNA-dependent RNA polymerase, was responsible for the repression of IFN-ß. NS5 interacts with STING in the cytoplasm, suppresses IRF3 phosphorylation and nucleus localization and promotes the cleavage of STING K48-linked polyubiquitination. Furthermore, the NS5 methyltransferase (MTase) domain interacts with STING to restrict STING-induced IFN-ß expression. Interestingly, point mutation analyses of conserved methyltransferase active site residue D146 indicate that it is critical for repressing IFN-ß expression induced by STING stimulation in cGAS-STING signalling.

Metabolites and metabolic pathway analysis of sulfadimidine in carp (Cyprinus carpio) based on UHPLC-Q-orbitrap HRMS.

Sulfadimidine (SM2) is an N-substituted derivative of p-aminobenzenesulfonyl structure. This study aimed to analyze the metabolism of SM2 in carp (Cyprinus carpio). The carps were fed with SM2 at a dose of 200 mg/(kg · bw) and then killed. The blood, muscle, liver, kidney, gill, other guts, and carp aquaculture water samples were collected. The UHPLC-Q-Exactive Plus Orbitrap-MS was adopted for determining the metabolites of SM2 in the aforementioned samples. Twelve metabolites, which were divided into metabolites in vivo and metabolites in vitro, were identified using Compound Discoverer software. The metabolic pathways in vivo of SM2 in carp included acetylation, hydroxylation, glucoside conjugation, glycine conjugation, carboxylation, glucuronide conjugation, reduction, and methylation. The metabolic pathways in vitro included oxidation and acetylation. This study clarified the metabolites and metabolic pathways of SM2 in carp and provided a reference for further pharmacodynamic evaluation and use in aquaculture.

One step accurate phase demodulation from a closed fringe pattern with the convolutional neural network HRUnet.

Retrieving a phase map from a single closed fringe pattern is a challenging task in optical interferometry. In this paper, a convolutional neural network (CNN), HRUnet, is proposed to demodulate phase from a closed fringe pattern. The HRUnet, derived from the Unet model, adopts a high resolution network (HRnet) module to extract high resolution feature maps of the data and employs residual blocks to erase the gradient vanishing in the network. With the trained network, the unwrapped phase map can be directly obtained by feeding a scaled fringe pattern. The high accuracy of the phase map obtained from HRUnet is demonstrated by demodulation of both simulated data and actual fringe patterns. Compared results between HRUnet and two other CNNS are also provided, and the results proved that the performance of HRUnet in accuracy is superior to the two other counterparts.

Traceability of gushing water in the MiddleRoute of the South-to-North Water Diversion (Beijing section) through the river area.

To trace the origin of the gushing water in the riverine area of the Beijing section of The Middle Route of South-to-North Water Diversion Project, a dataset was established comprising water chemistry, three-dimensional fluorescence spectra, and stable isotopes for different water bodies. Results indicated significant differences in Electrical Conductivity (EC), Total Dissolved Solids (TDS), and Ca2+ concentration among the gushing water, river water, and the water from the Middle Route of South-to-North Water Diversion Project (MRSD). Analysis using parallel factor analysis (PARAFAC) and fluorescence index revealed that dissolved organic matter (DOM) in the MRSD mainly originated from endogenous sources, while the river water and gushing water showed influences from both endogenous and exogenous sources. Nitrate sources varied among the water bodies, with distinct contributions from domestic sewage and fertilizer sources. The evaporation lines of river water and gushing water exhibited similar intercepts and slopes, but their intercepts and slopes are much smaller than those of the MRSD, suggesting stronger kinetic evaporative fractionation. In conclusion, the gushing water in the riverine area of the MRSD was determined to originate from the river, providing a fast and efficient method for gushing water source identification.

Convergent Adaptation of Ootheca Formation as a Reproductive Strategy in Polyneoptera.

Insects have evolved numerous adaptations and colonized diverse terrestrial environments. Several polyneopterans, including dictyopterans (cockroaches and mantids) and locusts, have developed oothecae, but little is known about the molecular mechanism, physiological function, and evolutionary significance of ootheca formation. Here, we demonstrate that the cockroach asymmetric colleterial glands produce vitellogenins, proline-rich protein, and glycine-rich protein as major ootheca structural proteins (OSPs) that undergo sclerotization and melanization for ootheca formation through the cooperative protocatechuic acid pathway and dopachrome and dopaminechrome subpathway. Functionally, OSP sclerotization and melanization prevent eggs from losing water at warm and dry conditions, and thus effectively maintain embryo viability. Dictyopterans and locusts convergently evolved vitellogenins, apolipoprotein D, and laminins as OSPs, whereas within Dictyoptera, cockroaches and mantids independently developed glycine-rich protein and fibroins as OSPs. Highlighting the ecological-evolutionary importance, convergent ootheca formation represents a successful reproductive strategy in Polyneoptera that promoted the radiation and establishment of cockroaches, mantids, and locusts.

Evaluation of different diagnostic methods for spinal tuberculosis infection.

BACKGROUND AND PURPOSE: Tuberculosis (TB) is the most fatal infectious disease worldwide. Approximately 24.6% of tuberculosis cases are extrapulmonary and predominantly affect the spine. It is difficult to diagnose spinal TB (STB). We aimed to evaluate the diagnostic performance of the Mycobacteria Growth Indicator Tube (MGIT)-960 culture, T-SPOT.TB, Xpert Mycobacterium tuberculosis complex (MTB)/resistance to rifampin (RIF), and Metagenomic Next-Generation Sequencing (mNGS) to detect STB. METHODS: We assessed 126 patients presumed to have STB using these four methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using clinical diagnosis as a reference. RESULTS: Of the patients, 41 were diagnosed with STB and 85 with non-STB. In the STB group, the sensitivity, specificity, PPV, and NPV of the MGIT-960 culture were 29.3% (12/41), 100% (85/85), 100% (12/12), and 74.6% (85/114), respectively. The sensitivity, specificity, PPV, and NPV of T-SPOT.TB were 92.7% (38/41), 82.4% (70/85), 58.5% (31/53), and 95.9% (70/73), respectively. The sensitivity, specificity, PPV, and NPV of the Xpert MTB/RIF assay were 53.7% (22/41), 100% (85/85), 100% (22/22), and 81.7% (85/104), respectively. The sensitivity, specificity, PPV, and NPV of mNGS were 39.0% (16/41), 98.8% (84/85), 94.1% (16/17), and 77.1% (84/109), respectively. The sensitivity, specificity, PPV, and NPV of mNGS + Xpert MTB/RIF were 73.2% (30/41), 100% (85/85), 96.8% (30/31), and 72.0% (85/118), respectively. The sensitivity, specificity, PPV, and NPV of the mNGS + T-spot assay were 97.6% (40/41), 100% (85/85), 67.9% (38/56), and 75.9% (85/113), respectively. Moreover, the sensitivity, specificity, PPV, and NPV of T-spot + Xpert MTB/RIF were 95.1% (39/41), 100% (85/85), 72.2% (39/54), and 81.0% (85/105), respectively. CONCLUSIONS: T-SPOT.TB is the most effective method for diagnosing STB; however, Xpert MTB/RIF is more reliable and can detect RIF resistance. Clinicians can use mNGS to identify pathogens in patients with spinal infections; these pathogens appeared to be more meaningful in guiding the clinical management of patients in the non-STB group. The combination of Xpert MTB/RIF and mNGS can improve the early diagnosis rate and drug resistance detection, reduce the diagnostic cycle, and provide early targeted anti-TB treatment for patients with STB.

Mechanism of downward migration of quinolone antibiotics in antibiotics polluted natural soil replenishment water and its effect on soil microorganisms.

Reclaimed water is widely concerned as an effective recharge of groundwater and surface water, but trace organic pollutants produced by traditional wastewater treatment plants (WWTPs) would cause environmental pollution (water and soil) during infiltration. Therefore, the effects of reclaimed water containing ofloxacin (OFL) and ciprofloxacin (CIP) in antibiotics polluted natural soil (APNS) were investigated by simulating soil aquifer treatment systems (SATs). The experiment results showed that OFL and CIP in water were adsorbed and microbially degraded mainly at 30 cm, and the concentration of OFL and CIP in soil increased with depth, which were mainly due to the desorption from APNS. Concurrently, the change in replenishment water concentration also significantly affected OFL and CIP in pore water and soil. Although OFL and CIP inhibited the diversity of soil microbial community, they also promoted the growth of some microorganisms. As the dominant bacteria, Proteobacteria and Acidobacteriota can effectively participate in the degradation of OFL and CIP. The degradation effects of soil microorganisms on OFL and CIP were 45.48% and 42.39%, respectively, indicating that soil microorganisms selectively degraded pollutants. This experiment was carried out on APNS, which provided a reference for future studies on the migration of trace organic pollutants under natural conditions.

Egfr signaling promotes juvenile hormone biosynthesis in the German cockroach.

BACKGROUND: In insects, an interplay between the activities of distinct hormones, such as juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulates the progression through numerous life history hallmarks. As a crucial endocrine factor, JH is mainly synthesized in the corpora allata (CA) to regulate multiple physiological and developmental processes, including molting, metamorphosis, and reproduction. During the last century, significant progress has been achieved in elucidating the JH signal transduction pathway, while less progress has been made in dissecting the regulatory mechanism of JH biosynthesis. Previous work has shown that receptor tyrosine kinase (RTK) signaling regulates hormone biosynthesis in both insects and mammals. Here, we performed a systematic RNA interference (RNAi) screening to identify RTKs involved in regulating JH biosynthesis in the CA of adult Blattella germanica females. RESULTS: We found that the epidermal growth factor receptor (Egfr) is required for promoting JH biosynthesis in the CA of adult females. The Egf ligands Vein and Spitz activate Egfr, followed by Ras/Raf/ERK signaling, and finally activation of the downstream transcription factor Pointed (Pnt). Importantly, Pnt induces the transcriptional expression of two key enzyme-encoding genes in the JH biosynthesis pathway: juvenile hormone acid methyltransferase (JHAMT) and methyl farnesoate epoxidase (CYP15A1). Dual-luciferase reporter assay shows that Pnt is able to activate a promoter region of Jhamt. In addition, electrophoretic mobility shift assay confirms that Pnt directly binds to the - 941~ - 886 nt region of the Jhamt promoter. CONCLUSIONS: This study reveals the detailed molecular mechanism of Egfr signaling in promoting JH biosynthesis in the German cockroach, shedding light on the intricate regulation of JH biosynthesis during insect development.

A Pyramid Semi-Autoregressive Transformer with Rich Semantics for Sign Language Production.

As a typical sequence to sequence task, sign language production (SLP) aims to automatically translate spoken language sentences into the corresponding sign language sequences. The existing SLP methods can be classified into two categories: autoregressive and non-autoregressive SLP. The autoregressive methods suffer from high latency and error accumulation caused by the long-term dependence between current output and the previous poses. And non-autoregressive methods suffer from repetition and omission during the parallel decoding process. To remedy these issues in SLP, we propose a novel method named Pyramid Semi-Autoregressive Transformer with Rich Semantics (PSAT-RS) in this paper. In PSAT-RS, we first introduce a pyramid Semi-Autoregressive mechanism with dividing target sequence into groups in a coarse-to-fine manner, which globally keeps the autoregressive property while locally generating target frames. Meanwhile, the relaxed masked attention mechanism is adopted to make the decoder not only capture the pose sequences in the previous groups, but also pay attention to the current group. Finally, considering the importance of spatial-temporal information, we also design a Rich Semantics embedding (RS) module to encode the sequential information both on time dimension and spatial displacement into the same high-dimensional space. This significantly improves the coordination of joints motion, making the generated sign language videos more natural. Results of our experiments conducted on RWTH-PHOENIX-Weather-2014T and CSL datasets show that the proposed PSAT-RS is competitive to the state-of-the-art autoregressive and non-autoregressive SLP models, achieving a better trade-off between speed and accuracy.

Simultaneous determination of triazine herbicides and their metabolites in shellfish by HPLC-MS/MS combined with Q/E-Orbitrap HRMS.

Triazine herbicides are used extensively in agriculture and aquaculture worldwide because of their broad effectiveness in weed control. However, after they are discharged into the sea, they seriously contaminate aquatic ecosystems and threaten aquatic organisms, especially shellfish. Currently, there are no established methods for the detection and confirmation of triazine herbicides and their metabolites in biological matrixes. Hence, the food safety of aquatic products cannot be accurately evaluated, which creates a technical barrier against international aquatic product trade. In this study, for the first time, a method was developed for the analysis and confirmation of seven triazine herbicides and 13 metabolites in shellfish, based on alkaline acetonitrile extraction and neutral Al2O3 cartridge purification coupled with internal standard calibration. Specifically, quantitative and qualitative analysis was conducted using high-performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS/MS), and accurate identification was carried out by quadrupole orbitrap high-resolution mass spectrometry (Q/E Orbitrap HRMS). The results showed that target analytes demonstrated good linearity within the corresponding range (R2 > 0.995). The limit of detection and limit of quantitation of the proposed method were 0.1 and 0.3 µg/kg, respectively. The average recoveries of analytes were between 70.0% and 120% when spiked at three levels with blank oyster (Crassostrea gigas) as the matrix, and the relative standard deviations (RSDs) were all less than 12% (n=6). The proposed method was successfully applied for the detection of triazine herbicide residues in oyster samples during actual breeding, and the presence of DIP, HP, DEHA, and other metabolites in positive samples was confirmed by Q/E Orbitrap HRMS. This method exhibits high accuracy, high sensitivity, and good reproducibility. It has promising application prospects in the field of hazard analysis and the positive identification of aquatic products.

Integrated analysis of physiological, transcriptomics and metabolomics provides insights into detoxication disruption of PFOA exposure in Mytilus edulis.

Perfluorooctanoic acid (PFOA), a persistent environmental contaminant, resists environmental degradation and bioaccumulates in food chains. Lots of literatures have proved that PFOA exposure could disrupt detoxifying function in a variety of organisms, however, it still remained poorly known about this in mollusk. Here, we examined physiological, transcriptomic, and metabolomic responses to PFOA in Mytilus edulis, a model organism frequently used in studies of aquatic pollution. We aimed to characterize PFOA-induced stress responses and detoxification mechanisms. PFOA exposure significantly altered antioxidant enzyme activity levels and the abundances of lipid peroxidation products. In addition, transcriptomic analysis indicated that several genes associated with oxidative stress and detoxication were differentially expressed after PFOA exposure. In combination, transcriptomic and metabolomic analyses showed that PFOA exposure disturbed several metabolic processes in M. edulis, including the lipid metabolism, amino acid metabolism, and carbohydrate metabolism etc. Molecular examination and enzymes assay of PFOA-exposed M. edulis after a 7-day depuration period still did not recover to control levels. The Pathway enrichment analysis proved that several pathways related to detoxification, such as c-Jun N-terminal kinase (JNK) and p38-dependent mitogen-activated protein kinase (MAPK) pathway, Peroxisome proliferator-activated receptor γ (PPARγ) pathway etc, were obviously affected. The present work verifies firstly PFOA disruption to molluscan detoxification and identifies the key pathways to understand the molecular mechanisms thereof. This study provides new insights into the detoxication disruption invoked in response to PFOA exposure in M. edulis.

Simulation Study on the Dynamic Behaviors of Water-in-Oil Emulsified Droplets on Coalescing Fibers.

Although increasing superwetting membranes have been developed for separating oil-water emulsions based on the "size-sieving" mechanism, their pores are easily blocked and fouled by the intercepted emulsified droplets, which would result in a severe membrane fouling issue and a sharp decline in flux. Instead of droplet interception, a fiber-based coalescer separates oil/water emulsions by inducing the emulsified droplets to coalesce and transform into layered oil/water mixtures, exhibiting an ability to work continuously for a long time with high throughput, which makes it a promising technology for emulsion treatment. However, the underlying mechanism of the separation process is not well understood, which makes it difficult to further improve the separation performance. Hence, in this work, the dynamic behaviors of water-in-oil emulsified droplets on the surface of the coalescing fiber were numerically investigated based on the phase-field model. The attachment, transport, and detachment behaviors of droplets on fibers were directly observed, and the effects of fiber wettability, orientation, arrangement, and fluid speed were studied in detail. First, it was observed that the droplets will move downstream along the fiber surface under the effect of fluid shear, and the large droplets tend to coalesce with their downstream small droplets on the same fiber surface because they move faster compared to the small droplets. Second, it was found that the emulsified droplet will spontaneously transport to the intersection of two angled fibers under the drive of asymmetric Laplace pressure, which demonstrated that the emulsified droplets tend to gather at the intersection of fibers when permeating through a coalescing medium. Third, it was found that the detachment behaviors of droplets from the fiber surface are strongly affected by their size, fiber wettability, and fluid velocity. In addition, the results of our simulation show that the backside of two closely attached fibers can further inhibit the detachment of droplets. We truly believe that our research results are of significance to optimize the parameters of a fiber-based coalescer for separating oil-water emulsions and to develop novel oil/water separators.

Automatic method to monitor floating macroalgae blooms based on multilayer perceptron: case study of Yellow Sea using GOCI images.

Timely and accurate information about floating macroalgae blooms (MAB), including their distribution, movement, and duration, is crucial in order for local government and residents to grasp the whole picture, and then plan effectively to restrain economic damage. Plenty of threshold-based index methods have been developed to detect surface algae pixels in various ocean color data with different manners; however, these methods cannot be used for every satellite sensor because of the spectral band configuration. Also, these traditional methods generally require other reliable indicators, and even visual inspection, in order to achieve an acceptable mapping of MAB that appears under diverse environmental conditions (cloud, aerosol, and sun glint). To overcome these drawbacks, a machine learning algorithm named Multi-Layer Perceptron (MLP) was used in this paper to establish a novel automatic method to monitor MAB continuously in the Yellow Sea, using Geostationary Ocean Color Imager (GOCI) imagery. The method consists of two MLP models, which consider both spectral and spatial features of Rayleigh-corrected reflectance (Rrc) maps. Accuracy assessment and performance comparison showed that the proposed method has the capability to provide prediction maps of MAB with high accuracy (F1-score approaching 90% or more), and with more robustness than the traditional methods. Most importantly, the model is practically adaptable for other ocean color instruments. This allows customized models to be built and used for monitoring MAB in any regional areas. With the development of machine learning models, long-term mapping of MAB in global ocean is conducive to promoting the associated studies.

ICPMS-Based Specific Quantification of Phosphotyrosine: A Gallium-Tagging and Tyrosine-Phosphatase Mediated Strategy.

Low-abundance tyrosine phosphorylation is crucial to not only normal but also aberrant life processes. We designed and synthesized a photocleavable magnetic nanoparticle-based gallium tag for tagging and enrichment as well as UV-release of the phosphate-bearing molecules/ions in cells. HPLC/71Ga species-unspecific isotope dilution (71Ga-SUID) ICPMS was subsequently developed for specific and absolute quantification of phosphotyrosine (pY) under the assistance of a protein tyrosine phosphatase-1B (PTP-1B). pY quantification was thus achieved via determination of Ga in the Ga-phosphate complexes that come exclusively from the Ga-tagged pY. In this way, the method detection limit of pY reached down to 30 amol with the RSD lower than 5.70% (n = 5 at pmol level). Feasibility of this proposed method was validated using VNQIGTLSEpYIK, VNQIGTLpSEpYIK, and extracellular regulated protein kinase 1 peptide (-pTEpY-) standards with the recovery of more than 96% (n = 5). It was applied to the absolute quantification of pY in human breast cancer MCF-7 cells, indicating that pY increased by 1.60 nmol (61.1%) in 3.0 × 106 MCF-7 cells after 100 nM insulin stimulation. We believe that, not limited to pY quantification, this element-tagging and protease-specific reaction mediated ICPMS methodology will pave a simple path for ever more applications of ICPMS to the studies of quantitative protein post-translational modifications (PTMs) when suitable element-tags are designed and specific proteases are available toward targeted PTMs.

Multiview stereo and silhouette fusion via minimizing generalized reprojection error.

Accurate reconstruction of 3D geometrical shape from a set of calibrated 2D multiview images is an active yet challenging task in computer vision. The existing multiview stereo methods usually perform poorly in recovering deeply concave and thinly protruding structures, and suffer from several common problems like slow convergence, sensitivity to initial conditions, and high memory requirements. To address these issues, we propose a two-phase optimization method for generalized reprojection error minimization (TwGREM), where a generalized framework of reprojection error is proposed to integrate stereo and silhouette cues into a unified energy function. For the minimization of the function, we first introduce a convex relaxation on 3D volumetric grids which can be efficiently solved using variable splitting and Chambolle projection. Then, the resulting surface is parameterized as a triangle mesh and refined using surface evolution to obtain a high-quality 3D reconstruction. Our comparative experiments with several state-of-the-art methods show that the performance of TwGREM based 3D reconstruction is among the highest with respect to accuracy and efficiency, especially for data with smooth texture and sparsely sampled viewpoints.

Click chemistry mediated Eu-tagging: activity-based specific quantification and simultaneous activity evaluation of CYP3A4 using 153Eu species-unspecific isotope dilution inductively coupled plasma mass spectrometry.

P450 3A4 (CYP3A4) is one of the most important isoforms in the human cytochrome P450 superfamily. It was used as an example in this proof-of-concept study in order to demonstrate an activity-based labeling and then click chemistry (CC) mediated element-tagging strategy for simultaneously specific quantification and activity measurement of an enzyme using species-unspecific isotope dilution inductively coupled plasma mass spectrometry (SUID ICPMS). A dual functional hexynylated 17α-ethynylestradiol activity-based probe was synthesized for specifically labeling CYP3A4 and then CC-mediated Eu-tagging with an azido-DOTA-Eu complex for CYP3A4 quantification and activity measurement in human liver microsome and serum samples using (153)Eu SUID ICPMS. The LOD (3σ) of CYP3A4 reached 20.3 fmol when monitoring (151/153)Eu ICPMS signals, in addition to the merits of specificity and simultaneous activity measurement achieved. We believe that this activity-based CC-mediated element-tagging strategy will liberate more potential advantages of ICPMS in bioanalysis.

Accuracy of food portion size estimation from digital pictures acquired by a chest-worn camera.

OBJECTIVE: Accurate estimation of food portion size is of paramount importance in dietary studies. We have developed a small, chest-worn electronic device called eButton which automatically takes pictures of consumed foods for objective dietary assessment. From the acquired pictures, the food portion size can be calculated semi-automatically with the help of computer software. The aim of the present study is to evaluate the accuracy of the calculated food portion size (volumes) from eButton pictures. DESIGN: Participants wore an eButton during their lunch. The volume of food in each eButton picture was calculated using software. For comparison, three raters estimated the food volume by viewing the same picture. The actual volume was determined by physical measurement using seed displacement. SETTING: Dining room and offices in a research laboratory. SUBJECTS: Seven lab member volunteers. RESULTS: Images of 100 food samples (fifty Western and fifty Asian foods) were collected and each food volume was estimated from these images using software. The mean relative error between the estimated volume and the actual volume over all the samples was -2·8 % (95 % CI -6·8 %, 1·2 %) with sd of 20·4 %. For eighty-five samples, the food volumes determined by computer differed by no more than 30 % from the results of actual physical measurements. When the volume estimates by the computer and raters were compared, the computer estimates showed much less bias and variability. CONCLUSIONS: From the same eButton pictures, the computer-based method provides more objective and accurate estimates of food volume than the visual estimation method.

Pharmacokinetics of sulfamonomethoxine in tongue sole (Cynoglossus semilaevis) after intravenous and oral administration.

The pharmacokinetic profiles of sulfamonomethoxine (SMM) were investigated in flatfish tongue soles in the present study. After a single injection of SMM (40 mg/kg BW) to caudal vein of tongue sole at 20 °C, plasma drug concentration versus time data were best fitted to a three-compartment model, characterized with 0.2, 5.7, and 80.4 h for the half-life (t 1/2) of fast distribution, slow distribution, and elimination, respectively. The apparent volume of distribution was 0.1 L/kg, and the body clearance was 0.03 L/h/kg. After oral administration of SMM (200 mg/kg BW) to tongue soles at 20 °C, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t 1/2ka) and elimination (t 1/2ß ) were 1.7 and 95.7 h, respectively. The maximal absorption concentration (C max) was estimated as 58 mg/L at 2.5 h, and the mean systemic bioavailability (F) was 39.5 % in tongue soles after oral administration.

Hyaluronic acid filler-induced vascular occlusion-Three case reports and overview of prevention and treatment.

BACKGROUND: Vascular occlusion induced by hyaluronic acid injections is rare, but can lead to severe adverse events, including necrosis, blindness, and cerebral infarction. OBJECTIVE: This study aims to explore methods of reducing the risk of complications such as embolism induced by hyaluronic acid injection, and to study the impact of comprehensive systematic treatment on the prognosis of patients with hyaluronic acid embolism. METHODS: The clinical data of three female patients with vascular occlusion due to hyaluronic acid injection was analyzed. Their median age was 26 years, with symptoms presenting 1-6 h postinjection. Hospital stays averaged 6 days. Two patients had ptosis, diplopia, and severe pain after injection of eyebrows. The other, who had a nose enhancement, experienced facial skin color changes and intense pain. RESULTS: Two patients received comprehensive, systematic treatment based on injectable hyaluronidase. One patient self-discharged after receiving injectable hyaluronidase, antispasmodic, and vasodilator treatment on the night of embolism and returned to the hospital 3 days later with worsening embolism symptoms and received symptomatic treatment again. Two patients who received comprehensive, systematic treatment based on injectable hyaluronidase showed significant improvement, while the patient who did not undergo systematic treatment left scars on the face. CONCLUSION: Vascular occlusion caused by hyaluronic acid facial filling is a severe adverse event, and timely, comprehensive, systematic treatment can effectively improve irreversible damage caused by thrombosis, and even cure it.

Development of a Diagnostic Model for Differentiating Tuberculous Spondylitis and Pyogenic Spondylitis With MRI: A Multicenter Retrospective Observational Study.

STUDY DESIGN: Multicenter retrospective observational study. OBJECTIVE: This study aimed to distinguish tuberculous spondylitis (TS) from pyogenic spondylitis (PS) using magnetic resonance imaging (MRI). Further, a novel diagnostic model for differential diagnosis was developed. SUMMARY OF BACKGROUND DATA: TS and PS are the two most common spinal infections. Distinguishing between these types clinically is challenging. Delayed diagnosis can lead to deficits or kyphosis. Currently, there is a lack of radiology-based diagnostic models for TS and PS. METHODS: We obtained radiologic images from MRI imaging of patients with TS and PS and applied the least absolute shrinkage and selection operator regression to select the optimal features for a predictive model. Predictive models were built using multiple logistic regression analysis. Clinical utility was determined using decision curve analysis, and internal validation was performed using bootstrap resampling. RESULTS: A total of 201 patients with TS (n=105) or PS (n=96) were enrolled. We identified significant differences in MRI features between both groups. We found that noncontiguous multivertebral and single-vertebral body involvement were common in TS and PS, respectively. Vertebral bone lesions were more severe in the TS group than in the PS group (Z=-4.553, P <0.001). The patients in the TS group were also more prone to vertebral intraosseous, epidural, and paraspinal abscesses ( P <0.001). A total of 8 predictors were included in the diagnostic model. Analysis of the calibration curve and area under the receiver operating characteristic curve suggested that the model was well-calibrated with high prediction accuracy. CONCLUSIONS: This is the largest study comparing MRI features in TS and PS and the first to develop an MRI-based nomogram, which may help clinicians distinguish between TS and PS.