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关键词： HDX-MS   Epitope mapping   C-Reactive protein   IVD reagents   Biochemical analysis  

摘要： C-Reactive protein (CRP) is an important marker for in vitro diagnosis (IVD) of inflammation. However, CRP immunotur-bidimetric kits from different manufacturers exhibit inconsistency in evaluation, making clinical diagnosis challenging. The use of immunological methods in diagnosis means that the differences in epitopes across kits may directly lead to inconsistent results. Therefore, to provide consistent results, it is essential to perform epitope mapping of different kits. The composition of antibodies in a single kit is typically complex, with a combination of polyclonal antibodies or monoclonal antibodies. Here, we show an epitope screening strategy for complex antibodies in a kit based on hydrogen-deuterium exchange mass spectrometry (HDX-MS). We applied this workflow to successfully map the epitopes for three kits from three different manufacturers and compared their quantitative results. We obtained different quantitative results using kits from different manufacturers upon epitope mapping, confirming the correlation between the quantitative results and the epitopes. Thus, we have established a workflow based on HDX-MS to screen epitopes in IVD kits. This work helps determine the quantitative accuracy of a kit based on structural information, can guide the design and production of IVD reagents, and further improves the accuracy of IVD.

关键词： carcinoma   neoplasms   pathology   surgical  

摘要： Conjunctival squamous intraepithelial neoplasia (CSIN) represents the in situ precursor of squamous cell carcinoma. The graded severity of intraepithelial dysplasia is considered a measure of risk for progression to invasive carcinoma. The range of cytoarchitectural changes in CSIN overlaps those of reactive atypia, squamous epithelial papilloma and in situ sebaceous carcinoma. Pseudoepitheliomatous hyperplasia and benign hereditary dyskeratosis of the conjunctiva are conditions without risk of neoplastic transform that are potentially mistaken for CSIN.

关键词： omega-3 polyunsaturated fatty acids   Arrhythmias   G protein-coupled receptor 120   NLRP3 inflammasomes   Peroxisome proliferator-activated receptor gamma  

摘要： The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been shown to attenuate inflammation processes, whereas the molecular mechanisms remain unclear. This study was aimed at figuring out the differential effects of EPA and DHA on fatal arrhythmias and whether the signaling pathway could be a target after myocardial infarction, an inflammatory status. Male Wistar rats after ligating coronary artery were randomized to either vehicle, EPA, or DHA for 4 weeks. Postinfarction was associated with increased myocardial norepinephrine levels and sympathetic innervation. Furthermore, infarction was associated with the activation of NLRP3 inflammasomes and increased the protein and expression of IL-1 beta and nerve growth factor (NGF). These changes were blunted after adding either EPA or DHA with a greater extent of EPA than DHA. Immunoblotting and immunohistochemical analysis showed that EPA had significantly lower phosphorylation of PPAR gamma at Ser 112 compared with DHA. Arrhythmic severity during programmed stimulation in the infarcted rats treated with EPA was significantly lower than those treated with DHA. Specific inhibition of GPR120 by AH-7614 and PPAR gamma by T0070907 reduced the EPA-or DHA-related attenuation of IL-1 beta and NGF release. Besides, AH-7614 treatment partially reduced the PPAR gamma levels, whereas T0070907 administration did not affect the GPR120 levels. These results suggest that EPA was more effective than DHA in prevention of fatal arrhythmias by inhibiting NLRP3 inflammasome and sympathetic innervation through activation of PPARy-mediated GPR120-dependent and -independent signaling pathways in infarcted hearts. (C) 2022 The Author(s). Published by Elsevier Inc.

关键词： Nociceptive information processing   Synaptic plasticity   Excitation-inhibition balance   Frequency-coded information   Spinal cord stimulation   GABA   Adenosine  

摘要： Networks of the dorsal horn of the spinal cord process nociceptive information from the periphery. In these networks, the excitation-inhibition balance is critical to shape this nociceptive information and to gate it to the brain where it is interpreted as pain. Our aim was to define whether short-term plasticity of inhibitory connections could tune this inhibition-excitation balance by differentially controlling excitatory and inhibitory microcircuits. To this end, we used spinal cord slices from adult mice expressing enhanced green fluorescent protein (eGFP) under the GAD65 promoter and recorded from both eGFP+ (putative inhibitory) and eGFP- (putative excitatory) neurons of lamina II while stimulating single presynaptic GABAergic interneurons at various frequencies. Our results indicate that GABAergic neurons of lamina II simultaneously contact eGFP- and eGFP+ neurons, but these connections display very different frequency-dependent short-term plasticities. Connections onto eGFP- interneurons displayed limited frequency-dependent changes and strong time-dependent summation of inhibitory synaptic currents that was however subjected to a tonic activity-dependent inhibition involving A1 adenosine receptors. By contrast, GABAergic connections onto eGFP+ interneurons expressed pronounced frequency-dependent depression, thus favoring disinhibition at these synapses by a mechanism involving the activation of GABA(B) autoreceptors at low frequency. Interestingly, the balance favors inhibition at frequencies associated with intense pain, whereas it favors excitation at frequencies associated with low pain. Therefore, these target-specific and frequency-specific plasticities allow to tune the balance between inhibition and disinhibition while processing frequency-coded information from primary afferents. These short-term plasticities and their modulation by A1 and GABA(B) receptors might represent an interesting target in pain-alleviating strategies.

关键词： Batteries   DC-DC power converters   Topology   DC-AC power converters   Modulation   Load flow   Voltage control   Differential power processing converter (DPPC)   energy storage system (ESS)   multiport converter   photovoltaic (PV)   space vector pulsewidth modulation (SVPWM) strategy  

摘要： Due to the unpredictable and fluctuating nature of solar photovoltaic (PV), energy storage systems (ESS), such as batteries, are always integrated with PV systems to smooth the power supply. In this article, a multiport dc-ac converter (MPC) with differential power processing dc-dc converter (DPPC) is proposed for battery ESS integrated PV systems. The MPC is capable of regulating most of active power among PV, battery and ac grid, and only the differential power (partial power) needs to be handled by the dc-dc converter. Hence, the major merits of higher integration, higher efficiency, and lower cost can be achieved by the proposed configuration. A new cooperative control scheme for the MPC and DPPC is investigated, aiming at realizing flexible active power flow. Besides, a modified space vector pulsewidth modulation is developed for the MPC, taking into the consideration of the voltage variation of both PV and battery. The active power controllability of the MPC and the power rating of the DPPC are quantitatively analyzed. The effectiveness of the proposed configuration, control and modulation schemes is validated by experimental results.

关键词： Thyroid neoplasm   Thyroid carcinoma   Follicular   Anti-thyroglobulin antibody   Thyroglobulin  

摘要： Purpose Distinguishing follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) before surgery is inherently challenging owing to the lack of malignant features on ultrasound, poor sensitivity of fine-needle biopsy, and the absence of definitive markers. We investigated whether thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid stimulating hormone (TSH) can help differentiate FTC from FTA. Methods Data pertaining to 319 patients with follicular neoplasms were retrospectively analyzed. We compared the serum markers between patients with confirmed FTC and FTA. We also analyzed the prevalence of FTC in different subgroups of patients based on serum marker levels. Results TgAb was a risk factor for FTC. Compared to TgAb <= 11.68 IU/mL group, the odds ratio (OR) for FTC in TgAb 11.69-30.50 IU/mL group and TgAb >30.50 IU/mL group were 2.206 (1.114-4.369, P = 0.023) and 3.247 (1.684-6.260, P < 0.001), respectively. The prevalence of malignancy in TgAb >30.50 IU/mL group was significantly higher than in the TgAb <= 11.68 IU/mL group (32.9 vs. 13.1%, P = 0.001). In patients with TgAb (-) status, Tg was another risk factor for FTC. Compared to Tg <= 38.51 ng/mL group, OR of Tg >434.60 ng/mL group was 3.836 (1.625-9.058, P = 0.002);the prevalence of malignancy in the Tg >434.60 ng/mL group was 47.2% and higher than other groups. Conclusions TgAb and Tg levels may be useful markers for preoperative differential diagnosis of follicular neoplasms. Higher TgAb and Tg levels were associated with greater malignant risk. Thus, we should be cautious of preoperative TgAb and Tg in follicular neoplasms.

关键词： differential code bias (DCB)   global navigation satellite systems (GNSS)   multi-GNSS experiments (MGEX)   total electron content (TEC)  

摘要： Global navigation satellite system (GNSS) differential code bias (DCB) is one of main errors in ionospheric modeling and applications. Accurate estimation of multiple types of GNSS DCBs is important for GNSS positioning, navigation, and timing, as well as ionospheric modeling. In this study, a novel method of multi-GNSS DCB estimation is proposed without using an ionospheric function model and global ionosphere map (GIM), namely independent GNSS DCB estimation (IGDE). Firstly, ionospheric observations are extracted based on the geometry-free combination of dual-frequency multi-GNSS code observations. Secondly, the VTEC of the station represented by the weighted mean VTEC value of the ionospheric pierce points (IPPs) at each epoch is estimated as a parameter together with the combined receiver and satellite DCBs (RSDCBs). Last, the estimated RSDCBs are used as new observations, whose weight is calculated from estimated covariances, and thus the satellite and receiver DCBs of multi-GNSS are estimated. Nineteen types of multi-GNSS satellite DCBs are estimated based on 200-day observations from more than 300 multi-GNSS experiment (MGEX) stations, and the performance of the proposed method is evaluated by comparing with MGEX products. The results show that the mean RMS value is 0.12, 0.23, 0.21, 0.13, and 0.11 ns for GPS, GLONASS, BDS, Galileo, and QZSS DCBs, respectively, with respect to MGEX products, and the stability of estimated GPS, GLONASS, BDS, Galileo, and QZSS DCBs is 0.07, 0.06, 0.13, 0.11, and 0.11 ns, respectively. The proposed method shows good performance of multi-GNSS DCB estimation in low-solar-activity periods.

关键词： Cryptobiosis   Extreme environments   Global warming   Transcriptomics   Tardigrade  

摘要： Tardigrades are renowned for their extreme stress tolerance, which includes the ability to endure complete desiccation, high levels of radiation and very low sub-zero temperatures. Nevertheless, tardigrades appear to be vulnerable to high temperatures and thus the potential effects of global warming. Here, we provide the first analysis of transcriptome data obtained from heat stressed specimens of the eutardigrade Ramazzottius varieornatus, with the aim of providing new insights into the molecular processes affected by high temperatures. Specifically, we compare RNA-seq datasets obtained from active, heat-exposed (35 degrees C) tardigrades to that of active controls kept at 5 degrees C. Our data reveal a surprising shift in transcription, involving 9634 differentially expressed transcripts, corresponding to >35% of the transcriptome. The latter data are in striking contrast to the hitherto observed constitutive expression underlying tardigrade extreme stress tolerance and entrance into the latent state of life, known as cryptobiosis. Thus, when examining the molecular response, heat-stress appears to be more stressful for R. varieornatus than extreme conditions, such as desiccation or freezing. A gene ontology analysis reveals that the heat stress response involves a change in transcription and presumably translation, including an adjustment of metabolism, and, putatively, preparation for encystment and subsequent diapause. Among the differentially expressed transcripts we find heat-shock proteins as well as the eutardigrade specific proteins (CAHS, SAHS, MAHS, RvLEAM, and Dsup). The latter proteins thus seem to contribute to a general stress response, and may not be directly related to cryptobiosis.

关键词： angiomyofibroblastoma   angiomyxoma   myofibroblast   retroperitoneal neoplasms   soft tissue tumor   solitary fibrous tumor   PEComa   review  

摘要： The retroperitoneal soft tissues, extending from the pelvic floor to the level of the diaphragm, are the source of a variety of mesenchymal neoplasms with overlapping features and distinct clinical behaviors, making their distinction of crucial importance. Herein, we report a rare retroperitoneal angiomyofibroblastoma (AMFB) that presented as a right abdominal mass in a 25-year-old woman and that clinically simulated a primary renal carcinoma. The patient underwent complete surgical resection showing a well-circumscribed tumor adjacent to but separate from the right kidney. It was comprised of irregular, often anastomosing islands and cords of plump to spindled cells in a collagenous stroma with numerous thin-walled vessels. The tumor cells clustered around the vessels and admixed with moderate numbers of adipocytes. There was neither significant nuclear atypia nor mitotic activity. Immunohistochemically, the tumor cells showed strong reactivity for desmin, diffuse expression of estrogen and progesterone receptors, retained nuclear expression of retinoblastoma protein, and absent CD34 expression. The immunomorphological features were these of a "lipomatous variant" of AMFB of the retroperitoneum. The occurrence of AMFB in the retroperitoneum is unexpected since it mostly develops in the lower genital tract of young women, making its recognition in this rare location difficult. As a consequence, more common pelvic or retroperitoneal soft tissue neoplasms may represent the primary diagnostic considerations. We, therefore, review a variety of soft tissue tumors occurring in the pelvis/retroperitoneum that, to some degree, may mimic AMFB, and present key findings to assist in accurate diagnosis.

关键词： Incompressible Flow   Flow Velocity   Critical Reynolds Number   Finite Element Formulation   Velocity Profiles   Peclet Number   Vortex Breakdown   Kinetic Energy   Computing   Parabolized Stability Equations  

摘要： The global linear stability of a 2-D viscous incompressible flow through a slightly divergent finite length channel is investigated using the stream function-vorticity formulation. The flow problem is studied under inlet-outlet nonperiodic boundary conditions using a stabilized finite element method. The perturbation eigenmodes, growth rates, as well as perturbation enstrophy transfer mechanisms are analyzed to demonstrate the inlet-outlet interactions of the base flow and the perturbation enstrophy. Results show that slightly divergent channel brings the critical Reynolds number to a low value. The eigenmode is different from the classical normal mode of perturbations. It is also found that slight divergence moves the maximum envelope of the least-stable eigenmode upstream in the flow bulk. Exchange of stability is eventually triggered above the critical Reynolds number as analyzed in the transfer mechanism for the perturbation enstrophy.