Root exudates and rhizosphere microbiota in responding to long-term continuous cropping of tobacco.

Soil sickness a severe problem in tobacco production, leading to soil-borne diseases and reduce in tobacco yield. This occurs as a result of the interaction between root exudates and rhizosphere microorganisms, which is however, little studied until now. By combining the field investigation and pot experiment, we found the output yield consistently decreased during the first 10 years of continuous cropping in a tobacco field, but increased at the 15th year (15Y). The root exudate and rhizosphere bacterial community was further analyzed to reveal the underlying mechanism of the suppressive soil formation. Root exudate of 15Y tobacco enriched in amino acids and derivatives, while depleted in the typical autotoxins including phenolic acids and alkaloids. This was correlated to the low microbial diversity in 15Y, but also the changes in community composition and topological properties of the co-occurrence network. Especially, the reduced autotoxins were associated with low Actinobacteria abundance, low network complexity and high network modularity, which significantly correlated with the recovered output yield in 15Y. This study revealed the coevolution of rhizosphere microbiota and root exudate as the soil domesticated by continuous cropping of tobacco, and indicated a potential role of the autotoxins and theirs effect on the microbial community in the formation of suppressive soil.

The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR - Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

Associations of residential greenness exposure and ambient air pollutants with newly-diagnosed drug-resistant tuberculosis cases.

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.

Iron-related gene mutations driving global Mycobacterium tuberculosis transmission revealed by whole-genome sequencing.

BACKGROUND: Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. RESULTS: A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. CONCLUSIONS: Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.

Endothelial Gata6 deletion reduces monocyte recruitment and proinflammatory macrophage formation and attenuates atherosclerosis through Cmpk2-Nlrp3 pathways.

Endothelial dysfunction results in chronic vascular inflammation, which is critical for the development of atherosclerotic diseases. Transcription factor Gata6 has been reported to regulate vascular endothelial cell activation and inflammation in vitro. Here, we aimed to explore the roles and mechanisms of endothelial Gata6 in atherogenesis. Endothelial cell (EC) specific Gata6 deletion was generated in the ApoeKO hyperlipidemic atherosclerosis mouse model. Atherosclerotic lesion formation, endothelial inflammatory signaling, and endothelial-macrophage interaction were examined in vivo and in vitro by using cellular and molecular biological approaches. EC-GATA6 deletion mice exhibited a significant decrease in monocyte infiltration and atherosclerotic lesion compared to littermate control mice. Cytosine monophosphate kinase 2 (Cmpk2) was identified as a direct target gene of GATA6 and EC-GATA6 deletion decreased monocyte adherence, migration and pro-inflammatory macrophage foam cell formation through regulation of the CMPK2-Nlrp3 pathway. Endothelial target delivery of Cmpk2-shRNA by intercellular adhesion molecule 2 (Icam-2) promoter-driven AAV9 carrying the shRNA reversed the Gata6 upregulation mediated elevated Cmpk2 expression and further Nlrp3 activation and thus attenuated atherosclerosis. In addition, C-C motif chemokine ligand 5 (Ccl5) was also identified as a direct target gene of Gata6 to regulate monocyte adherence and migration influencing atherogenesis. This study provides direct in vivo evidence of EC-GATA6 involvement in the regulation of Cmpk2-Nlrp3, as well as Ccl5, on monocyte adherence and migration in atherosclerosis development and advances our understanding of the in vivo mechanisms of atherosclerotic lesion development, and meanwhile provides opportunities for future therapeutic interventions.

Focal breast edema and breast edema score on T2-weighted images provides valuable biological information for invasive breast cancer.

BACKGROUND: Various features extracted from breast MRI have the potential to serve as noninvasive biomarkers for the prediction of the biologic behavior of breast cancer. The purpose of this study was to investigate the value of focal breast edema and breast edema score (BES) on T2-weighted images in providing valuable biological information for breast cancer patients' personalized treatment. METHOD: Two hundred and five lesions in 201 patients with invasive breast cancer confirmed by surgery or biopsy in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from November 2018 to October 2019 were retrospectively recruited and analyzed in this study. Focal edema and BES were evaluated at fat-suppressed T2 weighted imaging. All the lesions were divided into two groups according to the presence of focal edema. The differences in clinicopathological characteristics between the two groups and between different BES were compared. RESULTS: Two hundred and five lesions in 201 patients with invasive breast cancer were retrospectively recruited and analyzed in this study. On the fat-suppressed T2WI, focal edema was detected in 102 of 205 lesions (49.8%). BES was positively correlated with tumor size (p < 0.001), histologic grade (p = 0.006), Ki-67 index (p < 0.001), and N stage (p = 0.007), and was negatively correlated with expression of ER and PR (p < 0.001). Higher BES was more likely to present in patients with non-luminal breast cancer (p < 0.001) and suggested the possibility of a higher N stage. CONCLUSIONS: Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness, in which non-luminal breast cancer is more inclined to present focal edema. Breast edema score, a novel and practical tool, helps guide the individualized treatment of patients with invasive breast cancer. CRITICAL RELEVANCE STATEMENT: Focal edema on T2WI of breast MRI indicates stronger tumor invasiveness. Breast edema score helps guide the individualized treatment of patients with invasive breast cancer.

Deep Learning Radiomics of Preoperative Breast MRI for Prediction of Axillary Lymph Node Metastasis in Breast Cancer.

The objective of this study is to develop a radiomic signature constructed from deep learning features and a nomogram for prediction of axillary lymph node metastasis (ALNM) in breast cancer patients. Preoperative magnetic resonance imaging data from 479 breast cancer patients with 488 lesions were studied. The included patients were divided into two cohorts by time (training/testing cohort, n = 366/122). Deep learning features were extracted from diffusion-weighted imaging-quantitatively measured apparent diffusion coefficient (DWI-ADC) imaging and dynamic contrast-enhanced MRI (DCE-MRI) by a pretrained neural network of DenseNet121. After the selection of both radiomic and clinicopathological features, deep learning signature and a nomogram were built for independent validation. Twenty-three deep learning features were automatically selected in the training cohort to establish the deep learning signature of ALNM. Three clinicopathological factors, including LN palpability (odds ratio (OR) = 6.04; 95% confidence interval (CI) = 3.06-12.54, P = 0.004), tumor size in MRI (OR = 1.45, 95% CI = 1.18-1.80, P = 0.104), and Ki-67 (OR = 1.01; 95% CI = 1.00-1.02, P = 0.099), were selected and combined with radiomic signature to build a combined nomogram. The nomogram showed excellent predictive ability for ALNM (AUC 0.80 and 0.71 in training and testing cohorts, respectively). The sensitivity, specificity, and accuracy were 65%, 80%, and 75%, respectively, in the testing cohort. MRI-based deep learning radiomics in patients with breast cancer could be used to predict ALNM, providing a noninvasive approach to structuring the treatment strategy.

Keggin-type polyoxometalate-based crown ether complex for lithium-sulfur batteries.

A novel supramolecular complex Li3Cl[(HPW12O40)(H24C12O6)3(CH3CN)2] {CR-PW12} was confirmed first to apply as a sulfur host in lithium-sulfur batteries. The {CR-PW12}@S cathode exhibits a reversible capacity of 1120 mA h g-1 at 1.0 C and excellent cycle stability.

MRI Radiomics Signature of Pediatric Medulloblastoma Improves Risk Stratification Beyond Clinical and Conventional MR Imaging Features.

BACKGROUND: Prognostic evaluation is important for personalized treatment in children with medulloblastoma (MB). Limited data are available for risk stratification using a radiomics-based model. PURPOSE: To evaluate the incremental value of an MRI radiomics signature in stratifying the risk of pediatric MB in terms of overall survival (OS). STUDY TYPE: Retrospective. SUBJECTS: A total of 111 children (mean age 5.82 years) with pathologically confirmed MB divided into training and validation cohorts (77 and 34 children, respectively). FIELD STRENGTH/SEQUENCE: A 3 T, contrast-enhanced T1-weighted imaging with inversion recovery. ASSESSMENT: The study endpoint was OS defined as the time between the preoperative MRI study and death or last follow-up. The radiomics signature model and a clinical-MRI model were developed for personalized OS prediction. An integrative model, which combined the radiomics signature and clinical-MRI features, was also built using multivariable Cox regression model. The performance of the three models was evaluated with the C-index. The performance of integrative model was assessed by calibration curve and decision curve analysis (DCA). STATISTICAL TESTS: Independent T-test, Mann-Whitney U test, Fisher's exact tests or chi-square test, logistic regression analysis, Kaplan-Meier survival analysis, C-index, intraclass correlation coefficients (ICC). P < 0.05 was considered statistically significant. RESULTS: The media OS was 2.83 years (3.87 ± 1.85 years). Two clinical and one conventional MR imaging features (remnant, adjuvant treatment, and peritumoral edema) were selected for clinical-MRI model building. The integrative model evaluated OS (C-index 0.823) better than either the radiomics signature (C-index 0.702) or the clinical-MRI model (C-index 0.771). And it also showed good performance in the validation cohort (C-indices: 0.786, 0.756, 0.721), which was validated by the good calibration (P > 0.05) and more benefit. DATA CONCLUSIONS: This study demonstrated that the integrative model, which combined radiomics signature, clinical, and conventional MRI features, showed best performance in OS evaluation for children with MB. The radiomics signature may confer incremental value over clinical-MRI features. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Soil Conditioner Affects Tobacco Rhizosphere Soil Microecology.

Reasonable fertilization management can increase nutrient content and enzyme activity in rhizosphere soil, and even increase soil microbial richness. However, different fertilizers could raise distinct influences on the soil properties, including soil environmental factors (physicochemical properties and enzymatic activities) and microbial community. Here, the effects of two soil amendments (microbial fertilizer and woody peat) on environmental factors and microbial community structure in tobacco rhizosphere soil were evaluated, with the correlations between microbes and environmental factors explored. As the results, microbial fertilizer could effectively alleviate soil acidification, increase available potassium and organic matter contents in soil, and was also beneficial to increase nitrate reductase activity in rhizosphere soil. Fertilizers cause changes in the abundance of certain microbes in the soil. Besides, it was shown that the candidate phyla Gal15, Acidobacterota, Latescibacterota, Mortierellommycota, Basidiomycota, and Rozellomycota in tobacco rhizosphere soil had significant correlation with soil environmental factors. Through the functional analysis of these populations, it can be deduced that the changes in the abundance of certain microorganisms may be an important reason for the differences in environmental factors. All these indicated that the differences of environmental factors in different treatments are closely related to the abundance of some special soil microorganisms. Studying the life activities of these microbes would provide good guidance for exploring the interaction among crops, soil, and microorganisms and improving crop yields.

Differences in microbial diversity and environmental factors in ploughing-treated tobacco soil.

During agricultural production, plowing affects the existing traits of the planted soil, including environmental factors (physicochemical properties and soil enzymatic activity) and microbial community, but whether deep tillage and conventional tillage cause differences in soil microecology are unknown. In this study, the 16S rRNA high-throughput sequencing technology was combined with soil environmental factor detection to analyze the differences in microbial diversity of smokey soils at different depths. As a result, the composition and structure of microbial community varied in different soil depth after plowing. Two dominant phyla, Actinobacteria and Acidobacteria, have varied a lot between the deep-plowing treatment HS3 (the sample in 10-20 cm depth after deep-plowing treatment) sample and the conventional tillage HC3 (treatment the sample in 10-20 cm depth after conventional tillage) sample. The abundance of Actinobacteria has increased significantly, while the abundance of Acidobacteria has decreased significantly. Moreover, deep tillage increased the activity of sucrase (S-SC) and nitrate reductase (NR) in samples with soil depth below 20 cm. In summary, deep tillage disturbed spatial microbial diversity and environmental factors significantly. This would provide new guidance for improving farmland management strategies, optimizing the activation methods of soil layers, further improving crop planting soil, and increasing crop yield.

NTCP Deficiency Affects the Levels of Circulating Bile Acids and Induces Osteoporosis.

Background: The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis. Methods: Ten NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model. Results: During the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice. Conclusions: Both mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.

Ralstonia solanacearum Infection Disturbed the Microbiome Structure Throughout the Whole Tobacco Crop Niche as Well as the Nitrogen Metabolism in Soil.

Infections of Ralstonia solanacearum result in huge agricultural and economic losses. As known, the proposal of effective biological measures for the control of soil disease depends on the complex interactions between pathogens, soil microbiota and soil properties, which remains to be studied. Previous studies have shown that the phosphorus availability increased pathobiome abundance and infection of rhizosphere microbial networks by Ralstonia. Similarly, as a nutrient necessary for plant growth, nitrogen has also been suggested to be strongly associated with Ralstonia infection. To further reveal the relationship between soil nitrogen content, soil nitrogen metabolism and Ralstonia pathogens, we investigated the effects of R. solanacearum infection on the whole tobacco niche and its soil nitrogen metabolism. The results demonstrated that Ralstonia infection resulted in a reduction of the ammonium nitrogen in soil and the total nitrogen in plant. The microbes in rhizosphere and the plant's endophytes were also significantly disturbed by the infection. Rhodanobacter which is involved in nitrogen metabolism significantly decreased. Moreover, the load of microbial nitrogen metabolism genes in the rhizosphere soil significantly varied after the infection, resulting in a stronger denitrification process in the diseased soil. These results suggest that the application management strategies of nitrogen fertilizing and a balanced regulation of the rhizosphere and the endophytic microbes could be promising strategies in the biological control of soil-borne secondary disasters.

Endothelial S1pr2 regulates post-ischemic angiogenesis via AKT/eNOS signaling pathway.

Aims: It is important to understand the mechanism that regulates post-ischemic angiogenesis and to explore a new therapeutic target for an effective improvement of revascularization in peripheral artery disease (PAD) patients. Post-ischemic angiogenesis is a highly orchestrated process, which involves vascular endothelial cells (ECs) proliferation, migration and assembly into capillaries. We found a significant reduction of S1pr2 (sphingosine 1-phosphate receptor 2) in endothelial cells after hindlimb ischemia (HLI). We thus hypothesized that EC-S1pr2 might be involved in the regulation of post-ischemic angiogenesis and blood flow recovery during peripheral arterial disease (PAD). Methods and Results: We generated both EC-specific S1pr2 loss-of-function and S1pr2 gain-of-function mice. Our study showed that EC-specific S1pr2 loss-of-function significantly enhanced post-ischemic angiogenesis and improved blood flow recovery upon femoral artery ligation, whereas the EC-specific S1pr2 gain-of-function severely hindered post-ischemic angiogenesis and reduced blood flow recovery in ischemic limbs. We next identified that S1pr2 inhibited AKT/eNOS signaling pathway, and thus inhibited EC proliferation/migration and angiogenic activity. As expected, pharmacological inhibition of S1pr2 by JTE013 improved post-ischemic angiogenesis and improved blood flow perfusion after femoral artery ligation. Moreover, we developed RGD-peptide magnetic nanoparticles packaging S1pr2-siRNA which specifically targeted ECs and achieved an efficient silencing of S1pr2 expression in ECs in vivo. This EC-targeted strategy to dampen S1pr2 significantly enhanced post-ischemic angiogenesis and boosted blood perfusion after HLI, supplying a novel therapy target for patients with peripheral arterial disease. Conclusions: This present study demonstrates that EC-expressing S1pr2 tightly controls post-ischemic angiogenesis and blood flow perfusion recovery. This research provides a novel strategy for EC-target knockdown of S1pr2 as a new therapeutic intervention for patients with peripheral artery disease.

Diagnostic potential of a circulating miRNA model associated with therapeutic effect in heart failure.

Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Astragalus polysaccharide: a review of its immunomodulatory effect.

The Astragalus polysaccharide is an important bioactive component derived from the dry root of Astragalus membranaceus. This review aims to provide a comprehensive overview of the research progress on the immunomodulatory effect of Astragalus polysaccharide and provide valuable reference information. We review the immunomodulatory effect of Astragalus polysaccharide on central and peripheral immune organs, including bone marrow, thymus, lymph nodes, spleen, and mucosal tissues. Furthermore, the immunomodulatory effect of Astragalus polysaccharide on a variety of immune cells is summarized. Studies have shown that Astragalus polysaccharide can promote the activities of macrophages, natural killer cells, dendritic cells, T lymphocytes, B lymphocytes and microglia and induce the expression of a variety of cytokines and chemokines. The immunomodulatory effect of Astragalus polysaccharide makes it promising for the treatment of many diseases, including cancer, infection, type 1 diabetes, asthma, and autoimmune disease. Among them, the anticancer effect is the most prominent. In short, Astragalus polysaccharide is a valuable immunomodulatory medicine, but further high-quality studies are warranted to corroborate its clinical efficacy.

An artificial intelligence system using maximum intensity projection MR images facilitates classification of non-mass enhancement breast lesions.

OBJECTIVES: To build an artificial intelligence (AI) system to classify benign and malignant non-mass enhancement (NME) lesions using maximum intensity projection (MIP) of early post-contrast subtracted breast MR images. METHODS: This retrospective study collected 965 pure NME lesions (539 benign and 426 malignant) confirmed by histopathology or follow-up in 903 women. The 754 NME lesions acquired by one MR scanner were randomly split into the training set, validation set, and test set A (482/121/151 lesions). The 211 NME lesions acquired by another MR scanner were used as test set B. The AI system was developed using ResNet-50 with the axial and sagittal MIP images. One senior and one junior radiologist reviewed the MIP images of each case independently and rated its Breast Imaging Reporting and Data System category. The performance of the AI system and the radiologists was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The AI system yielded AUCs of 0.859 and 0.816 in the test sets A and B, respectively. The AI system achieved comparable performance as the senior radiologist (p = 0.558, p = 0.041) and outperformed the junior radiologist (p < 0.001, p = 0.009) in both test sets A and B. After AI assistance, the AUC of the junior radiologist increased from 0.740 to 0.862 in test set A (p < 0.001) and from 0.732 to 0.843 in test set B (p < 0.001). CONCLUSION: Our MIP-based AI system yielded good applicability in classifying NME lesions in breast MRI and can assist the junior radiologist achieve better performance. KEY POINTS: • Our MIP-based AI system yielded good applicability in the dataset both from the same and a different MR scanner in predicting malignant NME lesions. • The AI system achieved comparable diagnostic performance with the senior radiologist and outperformed the junior radiologist. • This AI system can assist the junior radiologist achieve better performance in the classification of NME lesions in MRI.

MRI-based radiomics signature and clinical factor for predicting H3K27M mutation in pediatric high-grade gliomas located in the midline of the brain.

OBJECTIVE: To develop a nomogram based on MRI radiomics and clinical features for preoperatively predicting H3K27M mutation in pediatric high-grade gliomas (pHGGs) with a midline location of the brain. METHODS: The institutional database was reviewed to identify patients with pHGGs with a midline location of the brain who underwent tumor biopsy with preoperative MRI scans between June 2016 and June 2021. A total of 107 patients with pHGGs, including 79 patients with H3K27M mutation, were consecutively included and randomly divided into training and test sets. Radiomics features were extracted from fluid-attenuated inversion recovery (FLAIR), diffusion-weighted (DW) and post-contrast T1-weighted images, and apparent diffusion coefficient (ADC) maps. The minimum redundancy maximum relevance (MRMR) and least absolute shrinkage and selection operator (LASSO) logistic regression were performed for radiomics signature construction. Clinical and radiological features were analyzed to select clinical predictors. A nomogram was then developed by incorporating the radiomics signature and selected clinical predictors. RESULTS: Nine radiomics features were selected to construct the radiomics signature, which showed a favorable discriminatory ability in training and test sets with an area under the curve (AUC) of 0.95 and 0.92, respectively. Ring enhancement was identified as an independent clinical predictor (p < 0.01). The nomogram, constructed with radiomics signature and ring enhancement, showed good calibration and discrimination in training and testing sets (AUC: 0.95 and 0.90 respectively). CONCLUSIONS: The nomogram which combined radiomics signature and ring enhancement had a satisfactory ability to predict H3K27M mutation in pHGGs with a midline of the brain. KEY POINTS: • Conventional MRI features were not powerful enough to predict H3K27M mutation status in pediatric high-grade gliomas (pHGGs) with a midline location of the brain. • An MRI-based radiomics signature showed satisfactory ability to predict H3K27M mutation status of pHGGs located in the midline of the brain. • Associating the radiomics signature with clinical factors improved predictive performance.

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity.

Cellular senescence is associated with pleiotropic physiopathological processes, including aging and age-related diseases. The persistent DNA damage is a major stress leading to senescence, but the underlying molecular link remains elusive. Here, we identify La Ribonucleoprotein 7 (LARP7), a 7SK RNA binding protein, as an aging antagonist. DNA damage-mediated Ataxia Telangiectasia Mutated (ATM) activation triggers the extracellular shuttling and downregulation of LARP7, which dampens SIRT1 deacetylase activity, enhances p53 and NF-κB (p65) transcriptional activity by augmenting their acetylation, and thereby accelerates cellular senescence. Deletion of LARP7 leads to senescent cell accumulation and premature aging in rodent model. Furthermore, we show this ATM-LARP7-SIRT1-p53/p65 senescence axis is active in vascular senescence and atherogenesis, and preventing its activation substantially alleviates senescence and atherogenesis. Together, this study identifies LARP7 as a gatekeeper of senescence, and the altered ATM-LARP7-SIRT1-p53/p65 pathway plays an important role in DNA damage response (DDR)-mediated cellular senescence and atherosclerosis.