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Yi-Ming Xu,1 Teng Zhang,1 Hai Xu,1 Liang Qi,1 Wei Zhang,1 Yu-Dong Zhang,1 Da-Shan Gao,2 Mei Yuan,1 Tong-Fu Yu1 1Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2 12sigma Technologies, San Diego, California, USACorrespondence: Mei Yuan; Tong-Fu YuDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, 300, Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, 210009 Tel +86-13405835354; +86-13813810516Fax +86-02568136861Email yuanmeijiangsu@163.com; njmu_ytf@163.comPurpose: The purpose of this study is to compare the detection performance of the 3-dimensional convolutional neural network (3D CNN)-based computer-aided detection (CAD) models with radiologists of different levels of experience in detecting pulmonary nodules on thin-section computed tomography (CT).Patients and Methods: We retrospectively reviewed 1109 consecutive patients who underwent follow-up thin-section CT at our institution. The 3D CNN model for nodule detection was re-trained and complemented by expert augmentation. The annotations of a consensus panel consisting of two expert radiologists determined the ground truth. The detection performance of the re-trained CAD model and three other radiologists at different levels of experience were tested using a free-response receiver operating characteristic (FROC) analysis in the test group.Results: The detection performance of the re-trained CAD model was significantly better than that of the pre-trained network (sensitivity: 93.09% vs 38.44%). The re-trained CAD model had a significantly better detection performance than radiologists (average sensitivity: 93.09% vs 50.22%), without significantly increasing the number of false positives per scan (1.64 vs 0.68). In the training set, 922 nodules less than 3 mm in size in 211 patients at high risk were recommended for follow-up CT according to the Fleischner Society Guidelines. Fifteen of 101 solid nodules were confirmed to be lung cancer.Conclusion: The re-trained 3D CNN-based CAD model, complemented by expert augmentation, was an accurate and efficient tool in identifying incidental pulmonary nodules for subsequent management.Keywords: computer-aided detection, computed tomography, pulmonary nodules, convolutional neural network

Wen Gao,1,* Jing He,1,* Shi-Dai Jin,1,* Jing Xu,1 Tong-Fu Yu,2 Wei Wang,3 Quan Zhu,2 Hui Dai,4 Hao Wu,1 Yi-Qian Liu,1 Yong-Qian Shu,1 Ren-Hua Guo1 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Medical Records Statistics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-Hua Guo; Yong-Qian ShuDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People’s Republic of ChinaEmail rhguo@njmu.edu.cn; shuyongqian@csco.org.cnBackground: The present study analyzed the relationship between clinical features and the T790M mutation in non-small cell lung cancer (NSCLC) patients resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment.Methods: NSCLC patients with resistance to first-generation EGFR-TKIs in which the disease control time was more than 6 months after initial TKI treatment were enrolled. T790M mutation analysis was performed using one of the following methods according to each manufacturer’s protocols: Cobas EGFR mutation test (41/105, 39.0%), digital PCR (42/105, 40.0%) or Scorpion amplification refractory mutation system (ARMS) (22/105, 21.0%). Sample type of T790M was from tissue only (53/105, 50.5%), plasma only (46/105, 43.8%), tissue and plasma (6/105, 5.7%).Results: Of 105 patients, 57 were T790M-positive and 48 were T790M-negative. T790M-positive patients had longer progression-free survival (PFS) after initial EGFR-TKI treatment (p = 0.019). T790M positivity was more frequent in patients treated with gefitinib than in those treated with icotinib (65% vs 40.54%, p = 0.018). The rate of T790M positivity was lower in patients with EGFR L858R (44.44%, 12/27) before TKI treatment than in those with EGFR 19del (72.0%, 36/50, p = 0.036). Patients who achieved PR after initial EGFR-TKI treatment had a higher rate of T790M positivity than those with SD (75.76% vs 50%, p = 0.023). There was no relationship between T790M status and age, gender, primary site, metastasis site, or treatment before TKI.Conclusion: Progression-free survival (PFS), drug type, response to initial EGFR-TKI treatment, and EGFR status before initial EGFR treatment were associated with the frequency of T790M mutation.Keywords: lung cancer, EGFR, T790M, gefitinib, icotinib

Introduction: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood., Objectives: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions., Methods: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean., Results: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5., Conclusion: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Objective: To investigate the imaging factors associated with postoperative cerebral infarction in adult patients aged 18 and above with ischemic Moyamoya disease. Methods: The clinical data of adult patients who underwent surgeries for ischemic Moyamoya disease in the Department of Neurosurgery at Peking University International Hospital from October 2015 to October 2020 were retrospectively analyzed. Of the 239 patients, 120 were male and 119 were female, with ages ranging from 18 to 63 (41.7±10.3) years. A total of 239 patients(290 cases) underwent direct and indirect combined revascularization (CR).Gender, age, surgical side, preoperative transient ischemic attack (TIA), presence of old cerebral infarction, and imaging features were compared between the patients with (48 cases) and without (242 cases) cerebral infarction within 1 week after surgery. Multivariate logistic binary regression model was used to analyze the imaging risk factors of postoperative cerebral infarction. Results: Cerebral infarction occurred in 48 cases(16.5%) among the 290 CR group within 1 week after surgery. The proportion of patients with TIA, old cerebral infarction, ICA stenosis, A1 segment stenosis, M1 segment stenosis, abnormal posterior cerebral artery (PCA), and unstable compensation before CR in the cerebral infarction group was higher than that in the non-cerebral infarction group ( P <0.05).Preoperative TIA ( OR =4.514, 95% CI : 1.920-10.611), old cerebral infarction ( OR =2.856,95% CI :1.176-6.936), A1 stenosis ( OR =7.027,95% CI :1.877-26.308), M1 stenosis ( OR =6.968,95% CI :2.162-22.459), abnormal PCA ( OR =4.114,95% CI :1.330-12.728)and unstable compensation ( OR =4.488,95% CI :1.194-16.865) were risk factors for cerebral infarction after CR surgery (all P <0.05). Conclusion: Among the imaging factors, TIA, old cerebral infarction, A1 stenosis, M1 stenosis, abnormal PCA and unstable compensation were risk factors for cerebral infarction in adult patients with ischemic Moyamoya disease treated by combined revascularization .

Background and Objectives: Self-perception of aging is an important psychosocial factor that can influence quality of life in older age. This review aimed to synthesize findings on the association between self-perception of aging and quality of life among older adults aged 60 and above., Research Design and Methods: A systematic search was conducted in 4 electronic databases (Ovid Medline, PsycInfo, CINAHL, and Web of Science). Studies conducted in English and including measures on the perception of aging and quality of life were included in this review. A total of 32 observational studies (21 cross-sectional, 8 longitudinal, 2 mixed-method, and 1 qualitative) met the inclusion criteria. Outcomes reported in the included studies were quality of life, physical health and functioning, psychological health, mental health, and general well-being., Results: Overall, 20 quantitative studies indicated a strong association between positive perception of aging and increased quality of life. Similarly, 9 quantitative studies demonstrated that negative perception of aging is associated with lower quality of life. Results of the mixed-method and qualitative studies indicated that older adults with higher morale and good physical capability had more positive perceptions of health., Discussion and Implications: These results suggest that promoting a positive perception of aging and a self-care attitude would help to enhance older adults' quality of life and should be incorporated into future health promotions and interventions., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Adaptation to drought and salt stresses is a fundamental part of plant cell physiology and is of great significance for crop production under environmental stress. Heat shock proteins (HSPs) are molecular chaperones that play a crucial role in folding, assembling, translocating, and degrading proteins. However, their underlying mechanisms and functions in stress tolerance remain elusive. Here, we identified the HSP TaHSP17.4 in wheat by analyzing the heat stress-induced transcriptome. Further analysis showed that TaHSP17.4 was significantly induced under drought, salt, and heat stress treatments. Intriguingly, yeast-two-hybrid analysis showed that TaHSP17.4 interacts with the HSP70/HSP90 organizing protein (HOP) TaHOP, which plays a significant role in linking HSP70 and HSP90. We found that TaHSP17.4- and TaHOP-overexpressing plants have a higher proline content and a lower malondialdehyde content than wild-type plants under stress conditions and display strong tolerance to drought, salt, and heat stress. Additionally, qRT-PCR analysis showed that stress-responsive genes relevant to reactive oxygen species scavenging and abscisic acid signaling pathways were significantly induced in TaHSP17.4- and TaHOP-overexpressing plants under stress conditions. Together, our findings provide insight into HSP functions in wheat and two novel candidate genes for improvement of wheat varieties., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

To investigate whether the combination scheme of deep learning score (DL-score) and radiomics can improve preoperative diagnosis in the presence of micropapillary/solid (MPP/SOL) patterns in lung adenocarcinoma (ADC). A retrospective cohort of 514 confirmed pathologically lung ADC in 512 patients after surgery was enrolled. The clinicoradiographic model (model 1) and radiomics model (model 2) were developed with logistic regression. The deep learning model (model 3) was constructed based on the deep learning score (DL-score). The combine model (model 4) was based on DL-score and R-score and clinicoradiographic variables. The performance of these models was evaluated with area under the receiver operating characteristic curve (AUC) and compared using DeLong's test internally and externally. The prediction nomogram was plotted, and clinical utility depicted with decision curve. The performance of model 1, model 2, model 3 and model 4 was supported by AUCs of 0.848, 0.896, 0.906, 0.921 in the Internal validation set, that of 0.700, 0.801, 0.730, 0.827 in external validation set, respectively. These models existed statistical significance in internal validation (model 4 vs model 3, P = 0.016; model 4 vs model 1, P = 0.009, respectively) and external validation (model 4 vs model 2, P = 0.036; model 4 vs model 3, P = 0.047; model 4 vs model 1, P = 0.016, respectively). The decision curve analysis (DCA) demonstrated that model 4 predicting the lung ADC with MPP/SOL structure would be more beneficial than the model 1and model 3 but comparable with the model 2. The combined model can improve preoperative diagnosis in the presence of MPP/SOL pattern in lung ADC in clinical practice., (© 2023. The Author(s).)

Agrobacterium rhizogenes is a soil bacteria with extensive infectivity, which can infect almost all dicotyledonous plants and a few monocotyledonous plants to induce root nodules. This is caused by the root-inducing plasmid, which contains genes responsible for the autonomous growth of root nodules and crown gall base synthesis. Structurally, it is similar to the tumor-inducing plasmid in that it mainly contains the Vir region, the T-DNA region, and the functional region of crown gall base synthesis. Its T-DNA is integrated into the nuclear genome of the plant with the assistance of Vir genes, causing hairy root disease in the host plant and the formation of hairy roots. The roots produced by Agrobacterium rhizogenes -infested plants are characterized by a fast growth rate, high degree of differentiation, physiological, biochemical, and genetic stability, and ease of manipulation and control. In particular, the hairy root system is an efficient and rapid research tool for plants that have no affinity for transformation by Agrobacterium rhizogenes and low transformation efficiency. The establishment of germinating root culture system for the production of secondary metabolites in the original plants through the genetic transformation of natural plants mediated by root-inducing plasmid in Agrobacterium rhizogenes has become a new technology combining plant genetic engineering and cell engineering. It has been widely used in a variety of plants for different molecular purposes, such as pathological analysis, gene function verification, and secondary metabolite research. Chimeric plants obtained by induction of Agrobacterium rhizogenes that can be expressed instantaneously and contemporarily are more rapidly obtained, compared to tissue culture and stably inheritable transgenic strains. In general, transgenic plants can be obtained in approximately one month., Competing Interests: Competing interestsThere are no conflicts of interest or competing interests., (Copyright © 2023 The Authors; exclusive licensee Bio-protocol LLC.)

In vivo imaging of cerebral ischemia/reperfusion injury remains an important challenge. We injected porous Ag/Au@SiO 2 bimetallic hollow nanoshells carrying anti-tropomyosin 4 as a molecular probe into mice with cerebral ischemia/reperfusion injury and observed microvascular changes in the brain using photoacoustic imaging with ultrasonography. At each measured time point, the total photoacoustic signal was significantly higher on the affected side than on the healthy side. Twelve hours after reperfusion, cerebral perfusion on the affected side increased, cerebrovascular injury worsened, and anti-tropomyosin 4 expression increased. Twenty-four hours after reperfusion and later, perfusion on the affected side declined slowly and stabilized after 1 week; brain injury was also alleviated. Histopathological and immunohistochemical examinations confirmed the brain injury tissue changes. The nanoshell molecular probe carrying anti-tropomyosin 4 has potential for use in early diagnosis of cerebral ischemia/reperfusion injury and evaluating its progression., Competing Interests: None

Despite their essential and multiple roles in biological processes, the molecular mechanism of Dof transcription factors (TFs) for responding to abiotic stresses is rarely reported in plants. We identified a soybean Dof gene GmDof41 which was involved in the responses to drought, salt, and exogenous ABA stresses. Overexpression of GmDof41 in soybean transgenic hairy roots attenuated H 2 O 2 accumulation and regulated proline homeostasis, resulting in the drought and salt tolerance. Yeast one-hybrid and electrophoretic mobility shift assay (EMSA) illustrated that GmDof41 was regulated by the DREB1-type protein GmDREB1B;1 that could improve drought and salt tolerance in plants. Further studies illustrated GmDof41 can directly bind to the promoter of GmDREB2A which encodes a DREB2-type protein and affects abiotic stress tolerance in plants. Collectively, our results suggested that GmDof41 positively regulated drought and salt tolerance by correlating with GmDREB1B;1 and GmDREB2A. This study provides an important basis for further exploring the abiotic stress-tolerance mechanism of Dof TFs in soybean., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Objective: The aim of the study is to investigate the diagnostic accuracy of radiomics on iodine maps from dual-energy computed tomography (DECT) in distinguishing lung cancer from benign pulmonary nodules., Methods: This retrospective study was approved by the institutional review board, and written informed consent was waived. A total of 109 patients with 55 malignant nodules and 62 benign nodules underwent contrast-enhanced DECT. Eight iodine uptake parameters on iodine maps generated by DECT were calculated and established a predictive model. Eighty-seven radiomics features of entire tumor were extracted from iodine maps and established a radiomics model. The iodine uptake model and radiomics model were independently built based on the highly reproducible features using the least absolute shrinkage and selection operator method. The diagnostic accuracy of 2 models were assessed using receiver operating curve analysis. For external validation, 47 patients (25 benign and 22 malignant) from another hospital were assigned to testing data set., Results: All iodine uptake features showed significant association with malignancy ( P < 0.01) and 2 selected features (mean value of virtual noncontrast images and mean value of vital part on contrast-enhanced image) constituted the iodine model. The radiomics model comprised 2 features (original shape sphericity and original glszm small area high gray level emphasis), which showed good discrimination both in the training cohort (area under the curve, 0.957) and validation cohort (area under the curve, 0.800). Radiomics model showed superior performance than iodine uptake model (accuracy, 89.7% vs 80.6%)., Conclusions: Radiomics model extracted from iodine maps provided a robust diagnostic tool for discriminating pulmonary malignant nodules and had high potential in clinical application., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: World Health Organization classification and Masaoka-Koga stage are widely used for thymic epithelial tumors (TETs). Reduced field-of-view (rFOV) diffusion-weighed imaging (DWI) proved to improve the image quality. Dynamic contrast-enhanced (DCE) MRI was commonly used in evaluating tumors., Purpose: To investigate the value of multiparametric MRI in evaluating TETs., Study Type: Retrospective., Subjects: Eighty-seven participants including 38 low risk (52.08 ± 14.19 years), 30 high risk (52.40 ± 11.35 years), and 19 thymic carcinoma patients (59.76 ± 10.78 years)., Field Strength/sequence: A 3 T, turbo spin echo imaging, echo planar imaging, volumetric interpolated breath-hold examination with radial acquisition trajectory., Assessment: DCE-MRI and apparent diffusion coefficient (ADC) variables were compared. Diagnostic performances of single significant factor and combined model were compared., Statistical Tests: Parameters were compared using one-way ANOVA or independent-samples t test. Logistic regression was employed to investigate the combined model. Receiver operating curves (ROC) and DeLong's test were used to compare the diagnostic efficiency., Results: ADC, K trans , and k ep values were significantly different among low-risk, high-risk and carcinoma group (ADC, 1.279 ± 0.345 × 10 -3  mm 2 /sec, 0.978 ± 0.260 × 10 -3  mm 2 /sec, 0.661 ± 0.134 × 10 -3  mm 2 /sec; K trans 0.167 ± 0.071 min -1 , 0.254 ± 0.136 min -1 , 0.393 ± 0.110 min -1 ; k ep 0.345 ± 0.113 min -1 , 0.560 ± 0.269 min -1 , 0.872 ± 0.149 min -1 ). They were significantly different for early stage and advanced stage (ADC, 1.270 ± 0.356 × 10 -3  mm 2 /sec vs. 0.845 ± 0.251 × 10 -3  mm 2 /sec; K trans 0.179 ± 0.092 min -1 vs. 0.304 ± 0.142 min -1 ; k ep 0.370 ± 0.181 min -1 vs. 0.674 ± 0.362 min -1 ). The combination of them had highest diagnostic efficiency for WHO classification (AUC, 0.925; sensitivity, 83.7%; specificity, 89.5%), clinical stage (AUC, 0.879; sensitivity, 80.9%; specificity, 82.5%)., Data Conclusion: Multiparametric MRI model may be useful for discriminating WHO classification and clinical stage of TETs., Evidence Level: 4 TECHNICAL EFFICIENCY: Stage 2., (© 2022 International Society for Magnetic Resonance in Medicine.)

PURPOSE The aim of this study was to evaluate the diagnostic performance of iodine uptake parameters using dual-energy computed tomography (DECT) in discriminating inflammatory nodules from malignant tumors. METHODS This retrospective study included 116 solid pulmonary nodules from 112 patients who were admitted to our hospital between January and September 2018. All nodules were confirmed by surgery or puncture. The degree of enhancement of a single-section region of interest was evalu ated. After total tumor volume-of-interest segmentation, the mean iodine density of the whole tumor was measured. Meanwhile, iodine uptake parameters, including total iodine uptake vol ume, total iodine concentration, vital iodine uptake volume, and vital iodine concentration, were calculated, and a predictive model was established. The overall ability to discriminate between inflammatory and malignant nodules was analyzed using an independent samples t-test for normally distributed variables. The diagnostic accuracy and prognostic performance of DECT parameters were evaluated and compared using receiver operating characteristic curve analysis and logistic regression analysis. A multivariate logistic regression analysis was used to determine the prognostic factors and goodness-of-fit of the whole tumor mean iodine and iodine uptake parameters for discriminating malignant nodules. RESULTS There were 116 non-calcified nodules, including 64 inflammatory nodules and 52 malignant nodules. The degree of enhancement in malignant nodules was significantly lower than that in inflammatory nodules (P=.043). All iodine uptake parameters in malignant nodules were signifi cantly higher than those in inflammatory nodules (P < .001). The area under the receiver operat ing curve value, accuracy, sensitivity, and specificity of the established model based on iodine uptake parameters were 0.803, 76.72%, 82.69%, and 84.37%, respectively, which exhibited bet ter diagnostic performance than the degree of enhancement on weighted average images with respective values of 0.609, 59.48%, 61.54%, and 59.38%. CONCLUSION The iodine uptake parameters of DECT exhibited better diagnostic accuracy in discriminating inflammatory nodules from malignant nodules than the degree of enhancement on weighted average images.

Background: Mammalian intestinal microbiomes are necessary for antagonizing systemic viral infections. However, very few studies have identified whether poultry commensal bacteria play a crucial role in protecting against systemic viral infections. Nephropathogenic infectious bronchitis virus (IBV) is a pathogenic coronavirus that causes high morbidity and multiorgan infection tropism in chickens., Results: In this study, we used broad-spectrum oral antibiotics (ABX) to treat specific pathogen free (SPF) chickens to deplete the microbiota before infection with nephropathogenic IBV to analyze the impact of microbiota on IBV infections in vivo. Depletion of the SPF chicken microbiota increases pathogenicity and viral burden following IBV infection. The gnotobiotic chicken infection model further demonstrated that intestinal microbes are resistant to nephropathogenic IBV infection. In addition, ABX-treated chickens showed a severe reduction in macrophage activation, impaired type I IFN production, and IFN-stimulated gene expression in peripheral blood mononuclear cells and the spleen. Lactobacillus isolated from SPF chickens could restore microbiota-depleted chicken macrophage activation and the IFNAR-dependent type I IFN response to limit IBV infection. Furthermore, exopolysaccharide metabolites of Lactobacillus spp. could induce IFN-β., Conclusions: This study revealed the resistance mechanism of SPF chicken intestinal microbiota to nephropathogenic IBV infection, providing new ideas for preventing and controlling nephropathogenic IBV. Video abstract., (© 2022. The Author(s).)

Abscisic acid (ABA) receptors are considered as the targeted manipulation of ABA sensitivity and water productivity in plants. Regulation of their stability or activity will directly affect ABA signalling. Mitogen-activated protein kinase (MAPK) cascades link multiple environmental and plant developmental cues. However, the molecular mechanism of ABA signalling and MAPK cascade interaction remains largely elusive. TaMPK3 overexpression decreases drought tolerance and wheat sensitivity to ABA, significantly weakening ABA's inhibitory effects on growth. Under drought stress, overexpression lines show lower survival rates, shoot fresh weight and proline content, but higher malondialdehyde levels at seedling stage, as well as decreased grain width and 1000 grain weight in both glasshouse and field conditions at the adult stage. TaMPK3-RNAi increases drought tolerance. TaMPK3 interaction with TaPYL4 leads to decreased TaPYL4 levels by promoting its ubiquitin-mediated degradation, whereas ABA treatment diminishes TaMPK3-TaPYL interactions. In addition, the expression of ABA signalling proteins is impaired in TaMPK3-overexpressing wheat plants under ABA treatment. The MPK3-PYL interaction module was found to be conserved across monocots and dicots. Our results suggest that the MPK3-PYL module could serve as a negative regulatory mechanism for balancing appropriate drought stress response with normal plant growth signalling in wheat., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

Objective: This study aimed to describe our experience of managing cesarean scar pregnancy (CSP) and outcomes depending on ultrasound imaging features., Methods: A retrospective, cohort observational study was performed on 31 consecutive patients with CSP at 6 to 9 weeks of gestation from April 2015 to January 2021. All patients were evaluated for the residual myometrial thickness (RMT), growth direction of the gestational sac (GS), blood flow, and chorionic parenchyma using ultrasonography. Patients underwent curettage or methotrexate (MTX) combined with curettage in CSP depending on the age of the GS. Blood loss of >500 mL with curettage was considered major bleeding., Results: Twenty-five (80.6%) patients had successful treatment, and six (19.4%) patients had major bleeding. The incidence of major bleeding was significantly higher in patients with >7 weeks of gestation, types II and III CSP, mixed and exogenous types of the growth direction of the GS, an RMT < 2 mm, and multiple lacunae formation in thickened chorionic parenchyma., Conclusions: The exogenous and mixed types of the GS, an RMT < 2 mm, and multiple lacunae in thickened chorionic parenchyma may be high-risk factors for major hemorrhage by curettage in CSP.

A rod-shaped, Gram-negative staining strain, FBM22 T , was isolated from a microbial fermentation bed substrate from a pig farm. Its colonies appeared yellow and were 0.5-1.2 mm in diameter. Cells were 0.3-0.5 μm wide, 0.5-0.83 μm long. Optimal growth occurred at 30 °C and pH 7.0-8.0; NaCl was not required for growth. The strain performed denitrification and nitrate reduction functions. And it could produce catalase. FBM22-1 T utilized the following organic substrates for growth: tyrosine, glutamic acid, D-glucose, and galactose. The novel isolate could degrade 2-nitropropane as carbon and nitrogen source. The dominant respiratory quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. C 18:1 ω7c, C 16:1 ω7c and/ or C 16:1 ω6c, and C 14:0 2-OH were the major (≥ 8%) fatty acids. The G+C content was 56.8 mol%. FBM22 T was found to be a member of the genus Sphingopyxis in the family Sphingomonadaceae of the class Alphaproteobacteria. It had the highest sequence similarity with the type strains Sphingopyxis terrae subsp. ummariensis UI2 T (96.47%) and Sphingopyxis terrae subsp. terrae NBRC 15098 T (96.40%). Furthermore, FBM22 T had 18.7% and 18.4% relatedness (based on digital DNA-DNA hybridization) with its two relatives (S. terrae subsp. ummariensis UI2 T and S. terrae subsp. terrae NBRC 15098 T ). The morphological, physiological, and genotypic differences identified in this study support the classification of FBM22 T as a novel species within the genus Sphingopyxis, for which the name Sphingopyxis yananensis sp. nov. is proposed. The type strain is FBM22 T (= KCTC 82290 T  = CCTC AB2020286 T )., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To evaluate the value of texture analysis based on dynamic contrast enhanced MRI (DCE-MRI) in the differential diagnosis of thymic carcinoma and thymic lymphoma. Sixty-nine patients with pathologically confirmed (thymic carcinoma, n = 32; thymic lymphoma, n = 37) were enrolled in this retrospective study. K trans , K ep and V e maps were automatically generated, and texture features were extracted, including mean, median, 5th/95th percentile, skewness, kurtosis, diff-variance, diff-entropy, contrast and entropy. The differences in parameters between the two groups were compared and the diagnostic efficacy was calculated. The K trans -related significant features yielded an area under the curve (AUC) of 0.769 (sensitivity 90.6%, specificity 51.4%) for the differentiation between thymic carcinoma and thymic lymphoma. The K ep -related significant features yielded an AUC of 0.780 (sensitivity 87.5%, specificity 62.2%). The V e -related significant features yielded an AUC of 0.807 (sensitivity 75.0%, specificity 78.4%). The combination of DCE-MRI textural features yielded an AUC of 0.962 (sensitivity 93.8%, specificity 89.2%). Five parameters were screened out, including age, K trans -entropy, K ep -entropy, V e -entropy, and V e -P95. The combination of these five parameters yielded the best discrimination efficiency (AUC of 0.943, 93.7% sensitivity, 81.1% specificity). Texture analysis of DCE-MRI may be helpful to distinguish thymic carcinoma from thymic lymphoma., (© 2022. The Author(s).)

Tubby-like proteins (TLPs) are transcription factors that are widely present in eukaryotes and generally participate in growth and developmental processes. Using genome databases, a total of 22 putative TLP genes were identified in the soybean genome, and unevenly distributed across 13 chromosomes. Phylogenetic analysis demonstrated that the predicted GmTLP proteins were divided into five groups (I-V). Gene structure, protein motifs, and conserved domains were analyzed to identify differences and common features among the GmTLPs. A three-dimensional protein model was built to show the typical structure of TLPs. Analysis of publicly available gene expression data showed that GmTLP genes were differentially expressed in response to abiotic stresses. Based on those data, GmTLP8 was selected to further explore the role of TLPs in soybean drought and salt stress responses. GmTLP8 overexpressors had improved tolerance to drought and salt stresses, whereas the opposite was true of GmTLP8 -RNAi lines. 3,3-diaminobenzidine and nitro blue tetrazolium staining and physiological indexes also showed that overexpression of GmTLP8 enhanced the tolerance of soybean to drought and salt stresses; in addition, downstream stress-responsive genes were upregulated in response to drought and salt stresses. This study provides new insights into the function of GmTLPs in response to abiotic stresses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Liu, Yu, Hou, Zheng, Chen, Zhou, Chen, Fu, Ma, Wei and Xu.)

TIFY proteins play crucial roles in plant abiotic and biotic stress responses. Our transcriptome data revealed several TIFY family genes with significantly upregulated expression under drought, salt, and ABA treatments. However, the functions of the GmTIFY family genes are still unknown in abiotic stresses. We identified 38 GmTIFY genes and found that TIFY10 homologous genes have the most duplication events, higher selection pressure, and more obvious response to abiotic stresses compared with other homologous genes. Expression pattern analysis showed that GmTIFY10e and GmTIFY10g genes were significantly induced by salt stress. Under salt stress, GmTIFY10e and GmTIFY10g transgenic Arabidopsis plants showed higher root lengths and fresh weights and had significantly better growth than the wild type (WT). In addition, overexpression of GmTIFY10e and GmTIFY10g genes in soybean improved salt tolerance by increasing the PRO, POD, and CAT contents and decreasing the MDA content; on the contrary, RNA interference plants showed sensitivity to salt stress. Overexpression of GmTIFY10e and GmTIFY10g in Arabidopsis and soybean could improve the salt tolerance of plants, while the RNAi of GmTIFY10e and GmTIFY10g significantly increased sensitivity to salt stress in soybean. Further analysis demonstrated that GmTIFY10e and GmTIFY10g genes changed the expression levels of genes related to the ABA signal pathway, including GmSnRK2 , GmPP2C , GmMYC2 , GmCAT1 , and GmPOD . This study provides a basis for comprehensive analysis of the role of soybean TIFY genes in stress response in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zheng, Jin, Liu, Kong, Wang, Yu, Chen, Zhou, Chen, Wang, Ma, Xu and Lan.)

Drought and salt stresses impose major constraints on soybean production worldwide. However, improving agronomically valuable soybean traits under drought conditions can be challenging due to trait complexity and multiple factors that influence yield. Here, we identified a nuclear factor Y C subunit (NF-YC) family transcription factor member, GmNF-YC14, which formed a heterotrimer with GmNF-YA16 and GmNF-YB2 to activate the GmPYR1-mediated abscisic acid (ABA) signalling pathway to regulate stress tolerance in soybean. Notably, we found that CRISPR/Cas9-generated GmNF-YC14 knockout mutants were more sensitive to drought than wild-type soybean plants. Furthermore, field trials showed that overexpression of GmNF-YC14 or GmPYR1 could increase yield per plant, grain plumpness, and stem base circumference, thus indicating improved adaptation of soybean plants to drought conditions. Taken together, our findings expand the known functional scope of the NF-Y transcription factor functions and raise important questions about the integration of ABA signalling pathways in plants. Moreover, GmNF-YC14 and GmPYR1 have potential for application in the improvement of drought tolerance in soybean plants., (© 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Background: Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals., Methods: From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured., Results: Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P < 0.001). Between-group comparisons were performed, and the PD group showed a higher SN positivity rate than the ET (χ2 = 94.898, P < 0.017), MSA (χ2 = 57.619, P < 0.017), and PSP (χ2 = 37.687, P < 0.017) groups. SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases, collectively or individually. The incidences of lenticular hyperechoic area significantly differed among the four patient groups (χ2 = 38.904, P < 0.001). Next, between-group comparisons were performed. The lenticular hyperechoic area was higher in the PD group than in the ET (χ2 = 6.714, P < 0.017) and MSA (χ2 = 18.680, P < 0.017) groups but lower than that in the PSP group (χ2 = 0.679, P > 0.017)., Conclusion: SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Under adverse conditions, such as sustained or chronic hyperglycemia or hyperlipidemia, ROS (reactive oxygen species) or/and ER-stress (endoplasmic reticulum stress) will be induced in pancreatic β cells. ROS or ER-stress damages β-cells even leads to apoptosis. Previously we found ROS or ER-stress resulted in JNK activation in β cells and overexpressing NR4A1 in MIN6 cells reduced JNK activation via modulating cbl-b expression and subsequent degrading the upstream JNK kinase (MKK4). To search other possible mechanisms, we found the mRNA level and protein level of MKP7 (a phosphatase for phospho-JNK) were dramatic reduced in pancreatic β cells in the islets from NR4A1 KO mice compared with that from wild type mice. To confirm what we found in animals, we applied pancreatic β cells (MIN6 cells) and found that the expression of MKP7 was increased in NR4A1-overexpression MIN6 cells. We further found that knocking down the expression of MKP7 increased the p-JNK level in pancreatic β cells upon treatment with TG or H 2 O 2 . After that, we figured out that NR4A1 did enhance the transactivation of the MKP7 promoter by physical association with two putative binding sites. In sum, NR4A1 attenuates JNK phosphorylation incurred by ER-stress or ROS partially via enhancing MKP7 expression, potentially decreases pancreatic β cell apoptosis induced by ROS or ER-stress. Our finding provides a clue for diabetes prevention.

Abiotic stresses, such as drought and salinity, severely affects the growth, development and productivity of the plants. The Catharanthus roseus RLK1-like (CrRLK1L) protein kinase family is involved in several processes in the plant life cycle. However, there have been few studies addressing the functions of CrRLK1L proteins in soybean. In this study, 38 CrRLK1L genes were identified in the soybean genome ( Glycine max Wm82.a2.v1). Phylogenetic analysis demonstrated that soybean CrRLK1L genes were grouped into clusters, cluster I, II, III. The chromosomal mapping demonstrated that 38 CrRLK1L genes were located in 14 of 20 soybean chromosomes. None were discovered on chromosomes 1, 4, 6, 7, 11, and 14. Gene structure analysis indicated that 73.6% soybean CrRLK1L genes were characterized by a lack of introns.15.7% soybean CrRLK1L genes only had one intron and 10.5% soybean CrRLK1L genes had more than one intron. Five genes were obtained from soybean drought- and salt-induced transcriptome databases and were found to be highly up-regulated. GmCrRLK1L20 was notably up-regulated under drought and salinity stresses, and was therefore studied further. Subcellular localization analysis revealed that the GmCrRLK1L20 protein was located in the cell membrane. The overexpression of the GmCrRLK1L20 gene in soybean hairy roots improved both drought tolerance and salt stresses and enhanced the expression of the stress-responsive genes GmMYB84 , GmWRKY40 , GmDREB-like , GmGST15 , GmNAC29 , and GmbZIP78 . These results indicated that GmCrRLK1L20 could play a vital role in defending against drought and salinity stresses in soybean., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Yu, Sun, Zheng, Chen, Zhou, Chen, Ma, Wei and Xu.)

Plant-specific WRKY transcription factors play important roles in regulating the expression of defense-responsive genes against pathogen attack. A multiple stress-responsive WRKY gene, ZmWRKY65, was identified in maize by screening salicylic acid (SA)-induced de novo transcriptomic sequences. The ZmWRKY65 protein was localized in the nucleus of mesophyll protoplasts. The analysis of the ZmWRKY65 promoter sequence indicated that it contains several stress-related transcriptional regulatory elements. Many environmental factors affecting the transcription of ZmWRKY65 gene, such as drought, salinity, high temperature and low temperature stress. Moreover, the transcription of ZmWRKY65 gene was also affected by the induction of defense related plant hormones such as SA and exogenous ABA. The results of seed germination and stomatal aperture assays indicated that transgenic Arabidopsis plants exhibit enhanced sensitivity to ABA and high concentrations of SA. Overexpression of ZmWRKY65 improved tolerance to both pathogen attack and abiotic stress in transgenic Arabidopsis plants and activated several stress-related genes such as RD29A, ERD10, and STZ as well as pathogenesis-related (PR) genes such as PR1, PR2 and PR5; these genes are involved in resistance to abiotic and biotic stresses in Arabidopsis. Together, this evidence implies that the ZmWRKY65 gene is involved in multiple stress signal transduction pathways.

Background: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images., Methods: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists., Results: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%)., Conclusions: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists., Trial Registration: Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

GRAS genes, which form a plant-specific transcription factor family, play an important role in plant growth and development and stress responses. However, the functions of GRAS genes in soybean ( Glycine max ) remain largely unknown. Here, 117 GRAS genes distributed on 20 chromosomes were identified in the soybean genome and were classified into 11 subfamilies. Of the soybean GRAS genes, 80.34% did not have intron insertions, and 54 pairs of genes accounted for 88.52% of duplication events (61 pairs). RNA-seq analysis demonstrated that most GmGRASs were expressed in 14 different soybean tissues examined and responded to multiple abiotic stresses. Results from quantitative real-time PCR analysis of six selected GmGRASs suggested that GmGRAS37 was significantly upregulated under drought and salt stress conditions and abscisic acid and brassinosteroid treatment; therefore, this gene was selected for further study. Subcellular localization analysis revealed that the GmGRAS37 protein was located in the plasma membrane, nucleus, and cytosol. Soybean hairy roots overexpressing GmGRAS37 had improved resistance to drought and salt stresses. In addition, these roots showed increased transcript levels of several drought- and salt-related genes. The results of this study provide the basis for comprehensive analysis of GRAS genes and insight into the abiotic stress response mechanism in soybean., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Wang, Yu, Fu, Su, Chen, Zhou, Chen, Guo, Ma, Wei and Xu.)

Sustained hyperglycaemia and hyperlipidaemia incur endoplasmic reticulum stress (ER stress) and reactive oxygen species (ROS) overproduction in pancreatic β-cells. ER stress or ROS causes c-Jun N-terminal kinase (JNK) activation, and the activated JNK triggers apoptosis in different cells. Nuclear receptor subfamily 4 group A member 1 (NR4A1) is an inducible multi-stress response factor. The aim of this study was to explore the role of NR4A1 in counteracting JNK activation induced by ER stress or ROS and the related mechanism. qPCR, Western blotting, dual-luciferase reporter and ChIP assays were applied to detect gene expression or regulation by NR4A1. Immunofluorescence was used to detect a specific protein expression in β-cells. Our data showed that NR4A1 reduced the phosphorylated JNK (p-JNK) in MIN6 cells encountering ER stress or ROS and reduced MKK4 protein in a proteasome-dependent manner. We found that NR4A1 increased the expression of cbl-b (an E3 ligase); knocking down cbl-b expression increased MKK4 and p-JNK levels under ER stress or ROS conditions. We elucidated that NR4A1 enhanced the transactivation of cbl-b promoter by physical association. We further confirmed that cbl-b expression in β-cells was reduced in NR4A1-knockout mice compared with WT mice. NR4A1 down-regulates JNK activation by ER stress or ROS in β-cells via enhancing cbl-b expression., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

NF-YA transcription factors function in modulating tolerance to abiotic stresses that are serious threats to crop yields. In this study, GmNFYA13 , an NF-YA gene in soybean, was strongly induced by salt, drought, ABA, and H 2 O 2 , and suppressed by tungstate, an ABA synthesis inhibitor. The GmNFYA13 transcripts were detected in different tissues in seedling and flowering stages, and the expression levels in roots were highest. GmNFYA13 is a nuclear localization protein with self-activating activity. Transgenic Arabidopsis plants overexpressing GmNFYA13 with higher transcript levels of stress-related genes showed ABA hypersensitivity and enhanced tolerance to salt and drought stresses compared with WT plants. Moreover, overexpression of GmNFYA13 resulted in higher salt and drought tolerance in OE soybean plants, while suppressing it produced the opposite results. In addition, GmNFYA13 could bind to the promoters of GmSALT3 , GmMYB84 , GmNCED3 , and GmRbohB to regulate their expression abundance in vivo . The data in this study suggested that GmNFYA13 enhanced salt and drought tolerance in soybean plants., (Copyright © 2020 Ma, Fu, Tang, Yu, Yin, Chen, Zhou, Chen, Xu and Ma.)

Triple-negative breast cancers (TNBCs) are associated with poor patient survival because of the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expressions. Our previous studies have shown that the triterpenoid saponin AG8 from Ardisia gigantifolia stapf. inhibits the proliferation of MDA-MB-231 cells. In this study, the effects of AG8 were further analyzed in different TNBC cell types: MDA-MB-231, BT-549, and MDA-MB-157 cells. AG8 inhibited the viability of MDA-MB-231, BT-549, and MDA-MB-157 cells in a dose-dependent manner and showed stronger cytotoxicity to African American (AA) and mesenchymal (M) subtypes than Caucasian (CA) and mesenchymal stem-like (MSL) subtypes, respectively. AG8 impaired the uptake of MitoTracker Red CMXRos by the mitochondria of TNBC cells in a dose-dependent manner, and this was recovered by N -acetyl-l-cysteine (NAC). AG8 affected GSH, SOD, and MDA levels of TNBC cells, but different TNBC subtypes had different sensitivities to AG8 and NAC. In addition, we found that AG8 increased the Bax/Bcl-2 ratio and the levels of cytoplasmic cytochrome c and significantly decreased phosphorylation of ERK and AKT in BT549 and MDA-MB-157 cells. AG8 elicited its anticancer effects through ROS generation, ERK and AKT activation, and by triggering mitochondrial apoptotic pathways in TNBC cells. AG8 had selective cytotoxic effects against the AA and M TNBC subtypes and markedly induced MDA-MB-157 (AA subtype) cell apoptosis through pathways that were not associated with ROS, which was different from the other two subtypes. The underlying mechanisms should be further investigated., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Li-Hua Mu et al.)

Brain-inspired synaptic transistors have been considered as a promising device for next-generation electronics. To mimic the behavior of a biological synapse, both data processing and nonvolatile memory capability are simultaneously required for a single electronic device. In this work, a simple approach to realize a synaptic transistor with improved memory characteristics is demonstrated by doping an ionic additive, tetrabutylammonium perchlorate (TBAP), into an active polymer semiconductor without using any extra charge storage layer. TBAP doping is first revealed to improve the memory window of a derived transistor memory device from 19 to 32 V (∼68% enhancement) with an on/off current ratio over 10 3 at V G = -10 V. Through morphological analysis and theoretical calculations, it is revealed that the association of anion with polymers enhances the charge retention capability of the polymer and facilitates the interchain interactions to result in improved memory characteristics. More critically, the doped device is shown to successfully mimic the synaptic behaviors, such as paired-pulse facilitation (PPF), excitatory and inhibitory postsynaptic currents, and spike-rate dependent plasticity. Notably, the TBAP-doped device is shown to deliver a PPF index of up to 204% in contrast to the negligible value of an undoped device. This study describes a novel approach to prepare a synaptic transistor by doping conjugated polymers, which can promote the future development of artificial neuromorphic systems.

Aim: To evaluate the value of using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived parameters to differentiate thymic carcinoma and thymic lymphoma based on semi-quantitative and quantitative models., Materials and Methods: Twenty-nine pathologically confirmed anterior mediastinum tumours in 29 patients were enrolled in this retrospective study, including 15 thymic carcinoma and 14 lymphoma patients. All the patients underwent pre-treatment mediastinum DCE-MRI. Both semi-quantitative and quantitative parameters were calculated and the volume transfer constant K trans , the flux rate constant between extravascular extracellular space and plasma k ep , the extravascular extracellular volume fraction v e were obtained based on a modified Tofts model. DCE-MRI derived parameters were compared between thymic carcinoma and thymic lymphoma groups., Results: Thymic carcinoma had significantly lower k ep (p=0.040) and higher v e (p=0.018) than thymic lymphoma; however, there were no significant differences on K trans and semi-quantitative parameters between the two groups. v e had the highest area under the curve (cut-off value, 0.282; area under the curve, 0.748; sensitivity, 71.4%; specificity, 80%). The combination of k ep and v e could increase the diagnostic performance significantly (area under the curve, 0.752; sensitivity, 57.1%; specificity, 93.3%)., Conclusion: DCE-MRI derived parameters may have value in the differentiating thymic carcinoma and thymic lymphoma., (Copyright © 2020. Published by Elsevier Ltd.)

Informed by the framing of queer Asia as disjunctive modernities, this article argues for the analytic relevance of class to Hong Kong queer culture amid proliferating sexual progress. Based on ethnographic research concerning a support group for middle-aged, working-class gay men in a non-governmental organization (NGO), the findings demonstrate how their understanding and experiences of class were displaced into the culturally specific discourses of aging and generational difference. By examining the ideological work underlying three sets of local discourses (namely, generational experiences, urban redevelopment, and industrial transformation), the analysis reveals a temporal logic of class relation that governed the informants' class displacements and, in turn, safeguarded the reproduction of inequalities in their lives. This article concludes by highlighting the interferential potential of class for understanding the queer cultural and subjective formations in other East Asian societies that went through similar processes of postwar economic development and class formation.

Background: Crop productivity is challenged by abiotic stresses, among which drought stress is the most common. NF-Y genes, especially NF-YA genes, regulate tolerance to abiotic stress., Results: Soybean NF-Y gene GmNFYA5 was identified to have the highest transcript level among all 21 NF-YA genes in soybean (Glycine max L.) under drought stress. Drought-induced transcript of GmNFYA5 was suppressed by the ABA synthesis inhibitor naproxen (NAP). GmNFYA5 transcript was detected in various tissues at vegetative and reproductive growth stages with higher levels in roots and leaves than in other tissues, which was consist with the GmNFYA5 promoter: GUS fusion assay. Overexpression of GmNFYA5 in transgenic Arabidopsis plants caused enhanced drought tolerance in seedlings by decreasing stomatal aperture and water loss from leaves. Overexpression and suppression of GmNFYA5 in soybean resulted in increased and decreased drought tolerance, respectively, relative to plants with an empty vector (EV). Transcript levels of ABA-dependent genes (ABI2, ABI3, NCED3, LEA3, RD29A, P5CS1, GmWRKY46, GmNCED2 and GmbZIP1) and ABA-independent genes (DREB1A, DREB2A, DREB2B, GmDREB1, GmDREB2 and GmDREB3) in transgenic plants overexpressing GmNFYA5 were higher than those of wild-type plants under drought stress; suppression of GmNFYA5 transcript produced opposite results. GmNFYA5 probably regulated the transcript abundance of GmDREB2 and GmbZIP1 by binding to the promoters in vivo., Conclusions: Our results suggested that overexpression of GmNFYA5 improved drought tolerance in soybean via both ABA-dependent and ABA-independent pathways.

Abiotic stresses, such as drought and salt, are major environmental stresses, affecting plant growth and crop productivity. Plant bZIP transcription factors (bZIPs) confer stress resistances in harsh environments and play important roles in each phase of plant growth processes. In this research, 15 soybean bZIP family members were identified from drought-induced de novo transcriptomic sequences of soybean, which were unevenly distributed across 12 soybean chromosomes. Promoter analysis showed that these 15 genes were rich in ABRE, MYB and MYC cis -acting elements which were reported to be involved in abiotic stress responses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that 15 GmbZIP genes could be induced by drought and salt stress. GmbZIP2 was significantly upregulated under stress conditions and thus was selected for further study. Subcellular localization analysis revealed that the GmbZIP2 protein was located in the cell nucleus. qRT-PCR results show that GmbZIP2 can be induced by multiple stresses. The overexpression of GmbZIP2 in Arabidopsis and soybean hairy roots could improve plant resistance to drought and salt stresses. The result of differential expression gene analysis shows that the overexpression of GmbZIP2 in soybean hairy roots could enhance the expression of the stress responsive genes GmMYB48 , GmWD40 , GmDHN15 , GmGST1 and GmLEA . These results indicate that soybean bZIP s played pivotal roles in plant resistance to abiotic stresses.

Stress associated proteins (SAPs) containing A20/AN1 zinc finger domains have emerged as novel regulators of stress responses. In this study, 27 SAP genes were identified in soybean. The phylogenetic relationships, exon-intron structure, domain structure, chromosomal localization, putative cis -acting elements, and expression patterns of SAPs in various tissues under abiotic stresses were analyzed. Among the soybean SAP genes, GmSAP1 6 was significantly induced by water deficit stress, salt, and abscisic acid (ABA) and selected for further analysis. GmSAP16 was located in the nucleus and cytoplasm. The overexpression of GmSAP16 in Arabidopsis improved drought and salt tolerance at different developmental stages and increased ABA sensitivity, as indicated by delayed seed germination and stomatal closure. The GmSAP16 transgenic Arabidopsis plants had a higher proline content and a lower water loss rate and malondialdehyde (MDA) content than wild type (WT) plants in response to stresses. The overexpression of GmSAP16 in soybean hairy roots enhanced drought and salt tolerance of soybean seedlings, with higher proline and chlorophyll contents and a lower MDA content than WT. RNA inference (RNAi) of GmSAP16 increased stress sensitivity. Stress-related genes, including GmDREB1B;1 , GmNCED3 , GmRD22 , GmDREB2 , GmNHX1 , and GmSOS1 , showed significant expression alterations in GmSAP16 -overexpressing and RNAi plants under stress treatments. These results indicate that soybean SAP genes play important roles in abiotic stress responses., (Copyright © 2019 Zhang, Zheng, Cao, Cui, Zhao, Yu, Chen, Zhou, Chen, Chai, Xu and Ma.)

Unexplained fever is one of the most common and difficult diagnostic problems faced daily by clinicians. This study evaluated the differences in health service utilization, health care expenditures, and quality of care provided to patients with unexplained fever before and after global budget (GB) implementation in Taiwan.The National Health Insurance Research Database was used for analyzing the health care expenditures and quality of care before and after implementation of the GB system. Patients diagnosed as having unexplained fever during 2000-2001 were recruited; their 2000-2001 and 2004-2005 data were considered baseline and postintervention data, respectively.Data of 259 patients with unexplained fever were analyzed. The mean lengths of stay (LOSs) before and after GB system implementation were 4.22 ± 0.35 days and 5.29 ± 0.70 days, respectively. The mean costs of different health care expenditures before and after implementation of the GB system were as follows: the mean diagnostic, drug, therapy, and total costs increased respectively from New Taiwan Dollar (NT$) 1440.05 ± NT$97.43, NT$3249.90 ± NT$1108.27, NT$421.03 ± NT$100.03, and NT$13,866.77 ± NT$2,114.95 before GB system implementation to NT$2224.34 ± NT$238.36, NT$4272.31 ± NT$1466.90, NT$2217.03 ± NT$672.20, and NT$22,856.41 ± NT$4,196.28 after implementation. The mean rates of revisiting the emergency department within 3 days and readmission within 14 days increased respectively from 10.5% ± 2.7% and 8.3% ± 2.4% before implementation to 6.3% ± 2.2% and 4.0% ± 1.7% after implementation.GB significantly increased LOS and incremental total costs for patients with unexplained fever; but improved the quality of care.

Autophagy is a catabolic biological process in the body. By targeting exogenous microorganisms and aged intracellular proteins and organelles and sending them to the lysosome for phagocytosis and degradation, autophagy contributes to energy recycling. When cells are stimulated by exogenous pathogenic microorganisms such as viruses, activation or inhibition of autophagy is often triggered. As autophagy has antiviral effects, many viruses may escape and resist the process by encoding viral proteins. At the same time, viruses can also use autophagy to enhance their replication or increase the persistence of latent infections. Here, we give a brief overview of autophagy and DNA viruses and comprehensively review the known interactions between human and animal DNA viruses and autophagy and the role and mechanisms of autophagy in viral DNA replication and DNA virus-induced innate and acquired immunity.

BRI1-EMS suppressor (BES)/brassinazole-resistant (BZR) family transcription factors are involved in a variety of physiological processes, but the biological functions of some BES/BZR transcription factors remain unknown; moreover, it is not clear if any of these proteins function in the regulation of plant stress responses. Here, wheat ( Triticum aestivum ) brassinazole-resistant 2 ( TaBZR2 )-overexpressing plants exhibited drought tolerant phenotypes, whereas downregulation of TaBZR2 in wheat by RNA interference resulted in elevated drought sensitivity. electrophoretic mobility shift assay and luciferase reporter analysis illustrate that TaBZR2 directly interacts with the gene promoter to activate the expression of T. aestivum glutathione s-transferase-1 ( TaGST1 ), which functions positively in scavenging drought-induced superoxide anions (O 2 - ). Moreover, TaBZR2 acts as a positive regulator in brassinosteroid (BR) signaling. Exogenous BR treatment enhanced TaBZR2-mediated O 2 - scavenging and antioxidant enzyme gene expression. Taken together, we demonstrate that a BES/BZR family transcription factor, TaBZR2, functions positively in drought responses by activating TaGST1 and mediates the crosstalk between BR and drought signaling pathways. Our results thus provide new insights into the mechanisms underlying how BES/BZR family transcription factors contribute to drought tolerance in wheat., (© 2019 American Society of Plant Biologists. All Rights Reserved.)

Objective: To construct a predictive model to discriminate adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) from invasive adenocarcinoma (IAC) appearing as pure ground-glass nodules (pGGNs) using computed tomography (CT) histogram analysis combined with morphological characteristics and to evaluate its diagnostic performance., Materials and Methods: Two hundred eighty-nine patients with surgically resected solitary pGGN and pathologically diagnosed with AIS, MIA, or IAC in our institution from January 2014 to May 2018 were enrolled in our study. Two hundred twenty-six pGGNs (79 AIS, 84 MIA, and 63 IAC) were randomly selected and assigned to a model-development cohort, and the remaining 63 pGGNs (11 AIS, 29 MIA and 23 IAC) were assigned to a validation cohort. The morphological characteristics were established as model A and histogram parameters as model B. The diagnostic performances of model A, model B, and model A + B were evaluated and compared via receiver operating curve (ROC) analysis and logistic regression analysis., Results: Entropy (odd ratio [OR] = 23.25, 95%CI: 6.83-79.15, p < 0.001), microvascular sign (OR = 8.62, 95%CI: 3.72-19.98, p < 0.001) and the maximum diameter (OR = 4.37, 95%CI: 2.44-7.84, p < 0.001) were identified as independent predictors in the IAC group. The area under the ROC (Az value), accuracy, sensitivity and specificity of model A + B were 0.896, 88.1%, 79.4% and 91.4%, respectively, exhibiting a significantly higher Az value than either model A or model B alone (0.785 vs 0.896, p < 0.001; 0.849 vs 0.896, p = 0.029). Model A + B also conveyed a good diagnostic performance in the validation cohort, with an Az value of 0.851., Conclusion: Histogram analysis combined with morphological characteristics exhibit a superior diagnostic performance in discriminating AIS-MIA from IAC appearing as pGGNs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Seventeen 13,28-epoxy triterpenoid saponins obtained from Ardisia gigantifolia STAPF. were evaluated their anti-proliferative activities on MCF-7 cells. The structure-activity relationship analysis indicated that CH 3 group at C-30, four saccharide units with L-rhamnose at R6 in the sugar units are crucial for the cytotoxic activity on MCF-7. Compounds 1, 2, 6, 7, 12, and 14 were selected to identify the anti-proliferative activity on the other three breast cancer cell lines (T47D, MDA-MB-231 and SK-BR-3). Compounds 2, 6, and 7 with good activity on MCF-7 also showed activity on T47D, MDA-MB-231, and SK-BR-3. Compounds 12 and 14 without cytotoxic activity on MCF-7 almost showed no activities on the other three cell lines. For the triple-negative breast cancer MDA-MB-231, Saponins 7 and 14 showed selective cytotoxic activity, 7 showed much more activity than 14, suggesting the six saccharide units in sugar units and CH 3 on C-30 were the key moieties for the anti-proliferative activities. Further molecular mechanism of saponin 7 was studied on inhibiting cell proliferation of MDA-MB-231 cells. Saponin 7 could enhance apoptosis, arrest cell cycles, decrease mitochondrial membrane potentials (MMPs), and considered the involvement of reactive oxygen species (ROS) may explain this conundrum.

Aim: To evaluate the predictive role of radiomics based on computed tomography (CT) in discriminating focal organising pneumonia (FOP) from peripheral lung adenocarcinoma (LA)., Materials and Methods: Institutional research board approval was obtained for this retrospective study. One hundred and seventeen patients with FOP and 109 patients with LA who underwent thin-section CT from January 2011 to August 2017 were reviewed systematically and analysed. The clinical and radiological features were established as model A and multi-feature-based radiomics as model B. The diagnostic performance of model A, model B, and model A+B were evaluated and compared via receiver operating characteristic (ROC) curve analysis and logistic regression analysis., Results: Sex, symptoms, necrosis, and the halo sign were identified as independent predictors of LA. The area under the ROC curve (Az value), accuracy, sensitivity, and specificity of model A were 0.839, 75.7%, 82.6%, and 69.2% respectively. Model B showed significantly higher accuracy than model A (83.6% versus 75.7%, p=0.032). The top four best-performing features, WavEnLH&#95;s-3, WavEnHH&#95;s-3, Teta3, and Volume, performed as independent factors for discriminating LA. Regression analysis indicated that model B had superior model fit than model A with Akaike information criterion (AIC) values of 73.6% versus 59.1%, respectively. Combining model A with model B is useful in achieving better diagnostic performance in discriminating FOP from LA: the Az value, accuracy, sensitivity, and specificity were 0.956, 87.6%, 85.3%, and 89.7% respectively., Conclusions: Radiomics based on CT exhibited better diagnostic accuracy and model fit than clinical and radiological features in discriminating FOP from LA. Combination of both achieved better diagnostic performance., (Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

To evaluate the status of parvovirus infection in free-range cows in a region of northeast China, nine serum samples were collected and analysed by sequencing and polymerase chain reaction. A new bovine parvovirus-2 (BPV2) was identified and named QQHE16. The genome of the virus is 5759 nucleotides long and retains two ORFs that are typical of the Parvovirinae family. Compared with reference BPV2 strains, BPV2 QQHE16 appeared to have a close relationship with strain BSRI isolated in the USA in 2013. A putative recombination breakpoint located at nucleotide position 2121 and in the interval between the non-structural gene and the VP gene was identified. From our analysis, we propose that strain QQHE16 originates from the natural recombination of strains ujs2665 and BSRI.

Plant calcium-dependent protein kinases (CDPKs) were reported to play important roles in plant resistance to abiotic stress. Foxtail millet cultivation "H138" was used for RNA-seq analysis. The data from drought-induced de novo transcriptomic sequences of foxtail millet showed that CDPKs were up- or down-regulated by drought to different degrees. In this study, 29 foxtail millet CDPKs were classified into four subgroups. These genes were unevenly distributed on nine foxtail millet chromosomes, and chromosomes 2, 3, and 9 contained the most SiCDPK members. Analysis of putative cis -acting elements showed that most foxtail millet CDPK genes contained the ABRE, LTR, HSE, MYB, MYC, DRE, CGTCA-motif, and TGACG-motif cis -acting elements, which could be activated by abiotic stresses. Real-time PCR analysis indicated that 29 SiCDPK genes experienced different degrees of induction under drought and ABA stresses. SiCDPK24 had the highest expression levels at 6 and 12 h of drought treatment and was chosen for further analysis. SiCDPK24 localized to the cell membrane and the nucleus of Arabidopsis mesophyll protoplasts. Western blot analysis showed that SiCDPK24 protein had autophosphorylation activity. Overexpression of SiCDPK24 in Arabidopsis enhanced drought resistance and improved the survival rate under drought stress. It also activated the expressions of nine stress-related genes, namely RD29A , RD29B , RD22 , KIN1 , COR15 , COR47 , LEA14 , CBF3/DREB1A , and DREB2A . These genes are involved in resistance to abiotic stresses in Arabidopsis . These results indicate that foxtail millet CDPK genes play important roles in resisting drought stress.