Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated ...virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.
Objectives
Accurate and reproducible measurements of the pediatric airway are critical for diagnostic evaluation and management of subglottic and tracheal stenosis. The endoluminal functional lumen ...imaging probe (EndoFLIP) is a catheter‐based imaging probe which utilizes impedance planimetry to calculate luminal parameters, including cross‐sectional area and compliance. Herein, we demonstrate the feasibility of this system for multidimensional evaluation of the pediatric airway.
Methods
3D‐printed pediatric laryngotracheal models were created based on computed tomography scans, then artificially deformed to simulate both circumferential and posterior subglottic stenosis. Two observers made six measurements of the minimum cross‐sectional area (MCSA) and length of stenosis of each model with EndoFLIP. Agreement between observer measurements and model dimensions was evaluated using Lin's concordance correlation coefficient; inter‐observer reliability was assessed using intraclass correlation.
Results
Four models were created: two without pathology (MCSA: 132.4, 44.3 mm2) and two with subglottic stenosis (MCSA: 28.7, 59.7 mm2, stenotic length 27.8, 24.4 mm). Observer measurements of MCSA and length of stenosis demonstrated high concordance with the models (r = 0.99, 0.95, p < 0.001) with a mean error of 4.5% and 18.2% respectively. There was a low coefficient of variation (0.6%–2.8%) for measurements, indicating high precision. Interrater reliability was high for both MCSA and stenotic length (ICC: 0.99, 0.98).
Conclusions
The EndoFLIP system allows for accurate and reproducible measurements of cross‐sectional area and stenotic length in pediatric airway models. This method may provide further advantages in the evaluation of airway distensibility, as well as measurements of asymmetric airway pathology.
Level of Evidence
NA Laryngoscope, 134:108–112, 2024
Endoluminal functional imaging probes (EndoFLIP) can provide accurate and repeatable measurements of the diameter, length, and compliance of a stenotic pediatric airway model.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical ...characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted.
•Effects of long-term auditory stimuli on piglets’ physiology and immunity.•Piglets’ emotion and behaviors are affected under auditory stimuli.•Different types of auditory stimuli have different ...effects, music slowed down the decrease of welfare and alleviated the effects of environmental stress. While noise might induce stress and inflammation.•As an immune indicator, the concentration of S-IgA may be used to assessing piglets’ emotion.
The stress caused by sound is inevitable. The stress caused by noise and the positive effects of music can affect the endocrine of animals and their welfare. In this study, a total of 72 hybrid piglets (Large White × Duroc × Min pig) were randomly divided into 3 groups, including music (Mozart K.448, 60–70 dB), noise (recorded mechanical noise, 80-85 dB), and control (natural background sound, <40 dB) groups. S-IgA (secretory immunoglobulin A), IL-6 (interleukin-6), IL-8 (interleukin-8), and positive emotion-related behaviors were used as indicators to discuss whether noise induced stress and inflammation in piglets or whether music could have positive effects. Six hours of auditory exposure were given daily (10:00–16:00), which lasted for 56 days. Behavioral responses of the piglets were observed, and the concentrations of salivary S-IgA and serum IL-6 and IL-8 were measured. The results showed that the concentration of S-IgA increased in the noise and control groups on the 57th day (P < 0.05); S-IgA concentration in the music group was unchanged after long-term music exposure. The concentrations of IL-6 and IL-8 showed that long-term noise exposure might lead to stress and inflammation in piglets. Tail-wagging and play behaviors of the piglets in the music group were significantly greater than those in the noise and control groups, which implied that long-term music exposure improved the emotional state of the piglets in a restricted and barren environment.
The methylation index of branched tetraethers (MBT) and cyclization ratio of branched tetraethers (CBT) based on the distribution of branched glycerol dialkyl glycerol tetraethers (brGDGT) are useful ...proxies for the reconstruction of mean annual air temperature (MAT) and soil pH. Recently, a series of 6-methyl brGDGTs were identified which were previously co-eluted with 5-methyl brGDGTs. However, little is known about 6-methyl brGDGTs in the Qinghai–Tibetan Plateau (QTP), a critical region of the global climate system. Here, we analyze 30 surface soils covering a large area of the QTP, among which 6-methyl brGDGTs were the most abundant components (average 53 ± 17% of total brGDGT). The fractional abundance of 6-methyl brGDGTs showed a good correlation with soil pH, while the global MBT'5ME calibration overestimates MAT in the QTP. We therefore proposed a MBT5/6 index including both 5- and 6-methyl brGDGTs, presenting a strong correlation with MAT in QTP: MAT = −20.14 + 39.51 × MBT5/6 (n = 27, r2 = 0.82; RMSE = 1.3 °C). Another index, namely IBT (isomerization of branched tetraether), based on carbon skeleton isomerization of the 5-methyl to 6-methyl brGDGTs, is dependent on soil pH: pH = 6.77 − 1.56 × IBT (n = 27; r2 = 0.74, RMSE = 0.32). Our study suggests that changing the position of methyl group of brGDGTs may be another mechanism for some soil bacteria to adapt to the ambient pH change in addition to the well-known cyclization.
Sex-determining region Y box 6 (SOX6) has been described as a tumor-suppressor gene in several cancers. Our previous work has suggested that SOX6 upregulated p21(Waf1/Cip1)(p21) expression in a ...p53-dependent manner; however, the underlying mechanism has remained elusive. In this study, we confirmed that SOX6 can suppress cell proliferation in vitro and in vivo by stabilizing p53 protein and subsequently upregulating p21. Co-immunoprecipitation and immunocytofluorescence assays demonstrated that SOX6 can promote formation of the p14ARF-HDM2-p53 ternary complex by promoting translocation of p14ARF (p14 alternate reading frame tumor suppressor) to the nucleoplasm, thereby inhibiting HDM2-mediated p53 nuclear export and degradation. Chromatin immunoprecipitation combined with PCR assay proved that SOX6 can bind to a potential binding site in the regulatory region of the c-Myc gene. Furthermore, we confirmed that SOX6 can downregulate the expression of c-Myc, as well as its direct target gene nucleophosmin 1 (NPM1), and that the SOX6-induced downregulation of NPM1 is linked to translocation of p14ARF to the nucleoplasm. Finally, we showed that the highly conserved high-mobility group (HMG) domain of SOX6 is required for SOX6-mediated p53 stabilization and tumor inhibitory activity. Collectively, these results reveal a new mechanism of SOX6-mediated tumor suppression involving p21 upregulation via the p14ARF-HDM2-p53 axis in an HMG domain-dependent manner.
A critical challenge facing the basic long-pulse high-confinement operation scenario (H mode) for ITER is to control a magnetohydrodynamic (MHD) instability, known as the edge localized mode (ELM), ...which leads to cyclical high peak heat and particle fluxes at the plasma facing components. A breakthrough is made in the Experimental Advanced Superconducting Tokamak in achieving a new steady-state H mode without the presence of ELMs for a duration exceeding hundreds of energy confinement times, by using a novel technique of continuous real-time injection of a lithium (Li) aerosol into the edge plasma. The steady-state ELM-free H mode is accompanied by a strong edge coherent MHD mode (ECM) at a frequency of 35-40 kHz with a poloidal wavelength of 10.2 cm in the ion diamagnetic drift direction, providing continuous heat and particle exhaust, thus preventing the transient heat deposition on plasma facing components and impurity accumulation in the confined plasma. It is truly remarkable that Li injection appears to promote the growth of the ECM, owing to the increase in Li concentration and hence collisionality at the edge, as predicted by GYRO simulations. This new steady-state ELM-free H-mode regime, enabled by real-time Li injection, may open a new avenue for next-step fusion development.
Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour‐targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL‐12, a potent ...antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL‐12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity‐associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour‐targeting properties of Cl. sporogenes and by the sustained release of IL‐12 accompanying bacterial proliferation. This moderate local IL‐12 concentration would not induce the severe response in the entire body, that is inevitable when IL‐12 is administered directly. SIGNIFICANCE AND IMPACT OF THE STUDY: Interleukin‐12 (IL‐12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL‐12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL‐12 during the treatment process. This result may be accounted for by the excellent tumour‐targeting capacity of Cl. sporogenes, targeting IL‐12 directly to the tumour site instead of to the entire body.
In order to study how the statistical properties of the observational quantities of the turbulent molecular cloud models vary with different turbulence parameters, I use the artificially generated ...random numerical models based on Gaussian fields created by the code pyfc with different values of the 1D density Fourier spectral index β
n
, the turbulence driving parameter, i.e. the b parameter and the 1D Fourier velocity power spectral index β
v
. Then I calculate the line profiles of 13CO emission on every sight line. I derive the statistical properties of column density N, line intensity W, peak intensity T
peak and velocity dispersion V
rms on every sight line. I discover that as β
n
increases, (1) the standard deviations σln (N/〈N〉) and σln (W/〈W〉) of the logarithmic column density ln (N/〈N〉) and the logarithmic integrated intensity ln (W/〈W〉) increase; (2) the number of the low T
peak values becomes larger; (3) the probability distribution function (PDF) of V
rms inclines to left a little. As the b parameter increases, (1) the values of both σln (N/〈N〉) and σln (W/〈W〉) increase; (2) the numbers of both the low T
peak values and the saturated T
peak values become larger; (3) the PDF of V
rms inclines to left obviously. As β
v
increases, (1) the PDF of ln (W/〈W〉) remains generally unchanged; (2) the PDF of T
peak remains generally unchanged; (3) the PDF of V
rms inclines to left obviously. I also discuss the relationship among σ
N/〈N〉, Mach number, the b parameter and β
n
.
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