Human cytomegalovirus exploits interferon-induced transmembrane proteins to facilitate morphogenesis of the virion assembly compartment

Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we identified a new function of IFITMs during the very late stage of virus replication, i.e., virion assembly. Virus entry and assembly both involve vesicle transport and membrane fusion; thus, a common biochemical activity of IFITMs is likely to be involved. Therefore, our findings may provide a new platform for dissecting the molecular mechanism of action of IFITMs during the blocking or enhancement of virus infection, which are under intense investigation in this field

Development and validation of a dynamic nomogram based on conventional ultrasound and contrast-enhanced ultrasound for stratifying the risk of central lymph node metastasis in papillary thyroid carcinoma preoperatively

PurposeThe aim of this study was to develop and validate a dynamic nomogram by combining conventional ultrasound (US) and contrast-enhanced US (CEUS) to preoperatively evaluate the probability of central lymph node metastases (CLNMs) for patients with papillary thyroid carcinoma (PTC).MethodsA total of 216 patients with PTC confirmed pathologically were included in this retrospective and prospective study, and they were divided into the training and validation cohorts, respectively. Each cohort was divided into the CLNM (+) and CLNM (−) groups. The least absolute shrinkage and selection operator (LASSO) regression method was applied to select the most useful predictive features for CLNM in the training cohort, and these features were incorporated into a multivariate logistic regression analysis to develop the nomogram. The nomogram’s discrimination, calibration, and clinical usefulness were assessed in the training and validation cohorts.ResultsIn the training and validation cohorts, the dynamic nomogram (https://clnmpredictionmodel.shinyapps.io/PTCCLNM/) had an area under the receiver operator characteristic curve (AUC) of 0.844 (95% CI, 0.755–0.905) and 0.827 (95% CI, 0.747–0.906), respectively. The Hosmer–Lemeshow test and calibration curve showed that the nomogram had good calibration (p = 0.385, p = 0.285). Decision curve analysis (DCA) showed that the nomogram has more predictive value of CLNM than US or CEUS features alone in a wide range of high-risk threshold. A Nomo-score of 0.428 as the cutoff value had a good performance to stratify high-risk and low-risk groups.ConclusionA dynamic nomogram combining US and CEUS features can be applied to risk stratification of CLNM in patients with PTC in clinical practice

The triggering process of an X-class solar flare on a small quadrupolar active region

The occurrence of X-class solar flares and their potential impact on the space weather often receive great attention than other flares. But predicting when and where an X-class flare will occur is still a challenge. With the multi-wavelength observation from the Solar Dynamics Observatory and FengYun- 3E satellite, we investigate the triggering of a GOES X1.0 flare occurring in the NOAA active region (AR) 12887. Our results show that this unique X-class flare is bred in a relatively small but complex quadrupolar AR. Before the X-class flare, two filaments (F1 and F2) exist below a null-point topology of the quadrupolar AR. Magnetic field extrapolation and observation reveal that F1 and F2 correspond to two magnetic flux ropes with the same chirality and their adjacent feet rooted at nonconjugated opposite polarities, respectively. Interestingly, these two polarities collide rapidly, accompanied by photospheric magnetic flux emergence, cancellation and shear motion in the AR center. Above this site, F1 and F2 subsequently intersect and merge to a longer filament (F3) via a tether-cutting-like reconnection process. As a result, the F3 rises and erupts, involving the large-scale arcades overlying filament and the quadrupolar magnetic field above the AR, and eventually leads to the eruption of the X-class flare with a quasi-X-shaped flare ribbon and a coronal mass ejection. It suggests that the rapid collision of nonconjugated opposite polarities provides a key condition for the triggering of this X-class flare, and also provides a featured case for flare trigger mechanism and space weather forecasting.Comment: 24 pages, 7 figures, accepted for publication in Ap

Prediction of wheat SPAD using integrated multispectral and support vector machines

Rapidly obtaining the chlorophyll content of crop leaves is of great significance for timely diagnosis of crop health and effective field management. Multispectral imagery obtained from unmanned aerial vehicles (UAV) is being used to remotely sense the SPAD (Soil and Plant Analyzer Development) values of wheat crops. However, existing research has not yet fully considered the impact of different growth stages and crop populations on the accuracy of SPAD estimation. In this study, 300 materials from winter wheat natural populations in Xinjiang, collected between 2020 to 2022, were analyzed. UAV multispectral images were obtained in the experimental area, and vegetation indices were extracted to analyze the correlation between the selected vegetation indices and SPAD values. The input variables for the model were screened, and a support vector machine (SVM) model was constructed to estimate SPAD values during the heading, flowering, and filling stages under different water stresses. The aim was to provide a method for the rapid acquisition of winter wheat SPAD values. The results showed that the SPAD values under normal irrigation were higher than those under water restriction. Multiple vegetation indices were significantly correlated with SPAD values. In the prediction model construction of SPAD, the different models had high estimation accuracy under both normal irrigation and water limitation treatments, with correlation coefficients of predicted and measured values under normal irrigation in different environments the value of r from 0.59 to 0.81 and RMSE from 2.15 to 11.64, compared to RE from 0.10% to 1.00%; and under drought stress in different environments, correlation coefficients of predicted and measured values of r was 0.69–0.79, RMSE was 2.30–12.94, and RE was 0.10%–1.30%. This study demonstrated that the optimal combination of feature selection methods and machine learning algorithms can lead to a more accurate estimation of winter wheat SPAD values. In summary, the SVM model based on UAV multispectral images can rapidly and accurately estimate winter wheat SPAD value

Fracture and self-sensing characteristics of super-fine stainless wire reinforced reactive powder concrete

YesSuper-fine stainless wire (SSW) can not only form widely distributed enhancing, toughening and conductive network in reactive powder concrete (RPC) at low dosage level, but also improve weak interface area and refine cracks due to its micron scale diameter and large specific surface. In addition, the crack resistance zone generated by SSWs and RPC matrix together has potential to further enhance the fracture properties of composites. Therefore, fracture and self-sensing characteristics of SSW reinforced RPC composites were investigated in this paper. Experimental results indicated that adding 1.5 vol. % of SSW leads to 183.1% increase in the initial cracking load of RPC specimens under three-point bending load. Based on two parameter fracture model calculations, an increase of 203.4% in fracture toughness as well as an increase of 113.3% in crack tip opening displacement of the composites reinforced with 1.5% SSWs are achieved. According to double-K fracture model calculations, the initiation fracture toughness and unstable fracture toughness of the composites are enhanced by 185.2% and 179.2%, respectively. The increment for fracture energy of the composites reaches up to 1017.1% because of the emergence of blunt and tortuous cracks. The mixed mode Ⅰ-Ⅱ fracture toughness of the composites is increased by 177.1% under four-point shearing load. The initial angle of mixed mode Ⅰ-Ⅱ cracks of the composites decreases with the increase of SSW content. The initiation and propagation of cracks in the composites can be monitored by their change in electrical resistivity. The excellent fracture toughness of the composites is of great significance for the improvement of structure safety in serviceability limit states, and the self-sensing ability of the composites can also provide early warning for the degradation of structure safety.National Key Research and Development Program of China (2018YFC0705601), the National Science Foundation of China (51578110), China Postdoctoral Science Fundation (2019M651116) and the Fundamental Research Funds for the Central Universities in China (DUT18GJ203)

Self-Sensing CFRP Fabric for Structural Strengthening and Damage Detection of Reinforced Concrete Structures

This paper presents a concept of a Self-sensing Carbon Fiber Reinforced Polymer (SCFRP) system, which integrates the piezoceramic transducers with the common concrete strengthening materials, CFRP fabric. This integration provides the SCFRP fabric with the ability to monitor the structural health condition when the SCFRP fabric is applied on reinforced concrete structures. In order to validate the feasibility of this system, several three-point bending beam (3PBB) specimens were fabricated and tested before and after the specimens were reinforced with the proposed SCFRP fabric. In addition, the specimens with the low (C25) and high (C40) concrete grades were also experimentally investigated to evaluate the reinforced effectiveness of the SCFRP fabric. Finally, the experimental results demonstrate that the proposed SCFRP fabric can significantly improve the bearing capacity of the concrete structures, and provided the reinforced concrete structures with an ability of self-sensing their health condition

Hsp90 Interacts With Tm-22 and Is Essential for Tm-22-Mediated Resistance to Tobacco mosaic virus

The tomato resistance gene Tm-22 encodes a coiled coil-nucleotide binding site-leucine rich repeat type resistance protein and confers effective immune response against tobamoviruses by detecting the presence of viral movement proteins (MPs). In this study, we show that the Nicotiana benthamiana Heat shock protein 90-kD (Hsp90) interacts with Tm-22. Silencing of Hsp90 reduced Tm-22-mediated resistance to Tobacco mosaic virus (TMV) and the steady-state levels of Tm-22 protein. Further, Hsp90 associates with SGT1 in yeast and in plant cells. These results suggest that Hsp90-SGT1 complex takes part in Tm-22-mediated TMV resistance by functioning as chaperone to regulate Tm-22 stability