Medical image foundation models in assisting diagnosis of brain tumors: a pilot study.

OBJECTIVES: To build self-supervised foundation models for multicontrast MRI of the whole brain and evaluate their efficacy in assisting diagnosis of brain tumors. METHODS: In this retrospective study, foundation models were developed using 57,621 enhanced head MRI scans through self-supervised learning with a pretext task of cross-contrast context restoration with two different content dropout schemes. Downstream classifiers were constructed based on the pretrained foundation models and fine-tuned for brain tumor detection, discrimination, and molecular status prediction. Metrics including accuracy, sensitivity, specificity, and area under the ROC curve (AUC) were used to evaluate the performance. Convolutional neural networks trained exclusively on downstream task data were employed for comparative analysis. RESULTS: The pretrained foundation models demonstrated their ability to extract effective representations from multicontrast whole-brain volumes. The best classifiers, endowed with pretrained weights, showed remarkable performance with accuracies of 94.9, 92.3, and 80.4%, and corresponding AUC values of 0.981, 0.972, and 0.852 on independent test datasets in brain tumor detection, discrimination, and molecular status prediction, respectively. The classifiers with pretrained weights outperformed the convolutional classifiers trained from scratch by approximately 10% in terms of accuracy and AUC across all tasks. The saliency regions in the correctly predicted cases are mainly clustered around the tumors. Classifiers derived from the two dropout schemes differed significantly only in the detection of brain tumors. CONCLUSIONS: Foundation models obtained from self-supervised learning have demonstrated encouraging potential for scalability and interpretability in downstream brain tumor-related tasks and hold promise for extension to neurological diseases with diffusely distributed lesions. CLINICAL RELEVANCE STATEMENT: The application of our proposed method to the prediction of key molecular status in gliomas is expected to improve treatment planning and patient outcomes. Additionally, the foundation model we developed could serve as a cornerstone for advancing AI applications in the diagnosis of brain-related diseases.

Incidence of medical adhesive-related skin injury: a reduction by changing posture.

OBJECTIVE: Medical adhesive-related skin injuries (MARSI), defined as skin damage associated with the use of medical adhesive products or devices, are a common and under-reported condition that compromises skin integrity. The prevention and management of MARSI that can occur around the needle insertion site of a chest wall implantable port in hospitalised patients with a tumour remain challenging issues. The aim of this study was to explore whether the incidence of MARSI could be reduced by changing the body position during dressing changes. METHOD: Participants were recruited between May 2019 and November 2020 in the oncology department of a tertiary hospital. Patients were randomly assigned to Group AB (supine followed by semi-recumbent position) and Group BA (semi-recumbent followed by supine position) with a standard intervening recovery interval of 21-28 days. Assessments for typical MARSI included itching, the combination of erythema and oedema, and blisters in the port area, and were graded according to the level of severity. RESULTS: The itch intensity was significantly lower in phase B (semi-recumbent) compared to phase A (supine) (2.35±1.985 versus 5.31±1.332, respectively; p<0.01). Similarly, the severity of erythema and oedema was less severe when comparing phase B to phase A: grade 0 (64.9% versus 10.5%, respectively); grade 1 (28.1% versus 19.3%, respectively); grade 2 (3.5% versus 7.0%, respectively); grade 3 (1.8% versus 45.6%, respectively); and grade 4 (1.8% versus 17.5%, respectively) (Z=5.703; p<0.01). Blisters were found far less frequently in phase B than phase A (1.8% versus 56.1%, respectively; p<0.01). CONCLUSION: The study provided statistically significant evidence that patients in a semi-recumbent position receiving dressing at a chest wall implantable port had fewer and less severe injection site MARSI than when in a supine position. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

A cisplatin conjugate with tumor cell specificity exhibits antitumor effects in renal cancer models.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and is notorious for its resistance to both chemotherapy and small-molecule inhibitor targeted therapies. Subcellular targeted cancer therapy may thwart the resistance to produce a substantial effect. METHODS: We tested whether the resistance can be circumvented by subcellular targeted cancer therapy with DZ-CIS, which is a chemical conjugate of the tumor-cell specific heptamethine carbocyanine dye (HMCD) with cisplatin (CIS), a chemotherapeutic drug with limited use in ccRCC treatment because of frequent renal toxicity. RESULTS: DZ-CIS displayed cytocidal effects on Caki-1, 786-O, ACHN, and SN12C human ccRCC cell lines and mouse Renca cells in a dose-dependent manner and inhibited ACHN and Renca tumor formation in experimental mouse models. Noticeably, in tumor-bearing mice, repeated DZ-CIS use did not cause renal toxicity, in contrast to the CIS-treated control animals. In ccRCC tumors, DZ-CIS treatment inhibited proliferation markers but induced cell death marker levels. In addition, DZ-CIS at half maximal inhibitory concentration (IC50) sensitized Caki-1 cells to small-molecule mTOR inhibitors. Mechanistically, DZ-CIS selectively accumulated in ccRCC cells' subcellular organelles, where it damages the structure and function of mitochondria, leading to cytochrome C release, caspase activation, and apoptotic cancer cell death. CONCLUSIONS: Results from this study strongly suggest DZ-CIS be tested as a safe and effective subcellular targeted cancer therapy.

Artificial Intelligence Applications in Glioma With 1p/19q Co-Deletion: A Systematic Review.

As an important genomic marker for oligodendrogliomas, early determination of 1p/19q co-deletion status is critical for guiding therapy and predicting prognosis in patients with glioma. The purpose of this study is to systematically review the literature concerning the magnetic resonance imaging (MRI) with artificial intelligence (AI) methods for predicting 1p/19q co-deletion status in glioma. PubMed, Scopus, Embase, and IEEE Xplore were searched in accordance with the Preferred Reporting Items for systematic reviews and meta-analyses guidelines. Methodological quality of studies was assessed according to the Quality Assessment of Diagnostic Accuracy Studies-2. Finally, 28 studies were included in the quantitative analysis. Diagnostic test accuracy reached an area under the ROC curve of 0.71-0.98 were reported in 24 studies. The remaining four studies with no available AUC provided an accuracy of 0.75-0. 89. The included studies varied widely in terms of imaging sequences, input features, and modeling methods. The current review highlighted that integrating MRI with AI technology is a potential tool for determination 1p/19q status pre-operatively and noninvasively, which can possibly help clinical decision-making. However, the reliability and feasibility of this approach still need to be further validated and improved in a real clinical setting. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: 2.

Molecular characterization of chicken infectious anaemia virus (CIAV) in China during 2020-2021.

Chicken infectious anaemia virus (CIAV) has been identified as the causative agent of chicken infectious anaemia (CIA), causing huge economic losses to the poultry industry globally. In this study, a total of 573 clinical samples were collected from 197 broiler farms in 17 provinces of China during 2020-2021. Among them, 375 samples (375/573, 65.4%) were positive for CIAV by real-time PCR. The positive rate of CIAV detection between different regions of China ranged from 46.67% (North China) to 81.25% (Central China). The nucleotide sequences of the VP1 gene were obtained for 91 CIAV strains, whole genome sequencing was successful for 72 out of 91 strains. Phylogenetic analysis based on the VP1 gene revealed that 91 CIAV strains currently circulating in China belong to three genotypes (II, IIIa and IIIb), and most of the CIAV strains belong to genotype IIIa. Phylogenetic analysis of the whole genome showed that 71 CIAV strains belong to genotype IIIa, and one strain belongs to genotype II. Sequence analysis showed several amino acid substitutions in both the VP1, VP2 and VP3 proteins. Our results enhance the understanding of the molecular characterization of CIAV infection in China.RESEARCH HIGHLIGHTS A molecular systematic survey of CIAV in China during 2020-2021.CIAV genotype IIIa is the predominant genotype in China.

Uncovering potential diagnostic biomarkers of acute myocardial infarction based on machine learning and analyzing its relationship with immune cells.

BACKGROUND: Acute myocardial infarction (AMI) is a common cardiovascular disease. This study aimed to mine biomarkers associated with AMI to aid in clinical diagnosis and management. METHODS: All mRNA and miRNA data were downloaded from public database. Differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were identified using the metaMA and limma packages, respectively. Functional analysis of the DEmRNAs was performed. In order to explore the relationship between miRNA and mRNA, we construct miRNA-mRNA negative regulatory network. Potential biomarkers were identified based on machine learning. Subsequently, ROC and immune correlation analysis were performed on the identified key DEmRNA biomarkers. RESULTS: According to the false discovery rate < 0.05, 92 DEmRNAs and 272 DEmiRNAs were identified. GSEA analysis found that kegg_peroxisome was up-regulated in AMI and kegg_steroid_hormone_biosynthesis was down-regulated in AMI compared to normal controls. 5 key DEmRNA biomarkers were identified based on machine learning, and classification diagnostic models were constructed. The random forests (RF) model has the highest accuracy. This indicates that RF model has high diagnostic value and may contribute to the early diagnosis of AMI. ROC analysis found that the area under curve of 5 key DEmRNA biomarkers were all greater than 0.7. Pearson correlation analysis showed that 5 key DEmRNA biomarkers were correlated with most of the differential infiltrating immune cells. CONCLUSION: The identification of new molecular biomarkers provides potential research directions for exploring the molecular mechanism of AMI. Furthermore, it is important to explore new diagnostic genetic biomarkers for the diagnosis and treatment of AMI.

Glucocorticoids promote lung metastasis of pancreatic cancer cells through enhancing cell adhesion, migration and invasion.

Glucocorticoids (GCs) are the important stress hormones and widely prescribed as drugs. Although stress has been suggested as a promoter of tumor progression, the direct influence of GCs on metastasis of tumor is not fully understood. Metastasis is a major cause of death in pancreatic cancer patients. In the present study, we investigated the effect of GCs on progression of pancreatic cancer and elucidated the underlying mechanism. It was found that GCs significantly promote cell adhesion, migration, and invasion of pancreatic cancer cells in vitro and their lung metastasis in vivo. Further mechanistic studies showed that GCs notably up-regulate the expression of a trans-membrane glycoprotein, mucin 1 (MUC1) and increase the activation of AKT. Inhibiting MUC1 expression not only attenuates the activation of AKT, but also significantly reduces the promoting effects of GCs on cell adhesion, migration, invasion, and lung metastasis of pancreatic cancer cells. Moreover, GCs not only significantly up-regulate expression of Rho-associated kinase 1/2 (ROCK1/2) and matrix metalloproteinase 3 and 7 (MMP3/7), but also activate ROCK2, which are also involved in the pro-migratory and pro-invasive effects of GCs in pancreatic cancer cells. Taken together, our findings reveal that GCs promote metastasis of pancreatic cancer cells through complex mechanism. MUC1-PI3K/AKT pathway, ROCK1/2 and MMP3/7 are involved in the promoting effect of GCs on cell migration, invasion and metastasis in pancreatic cancer cells. These results suggest the importance of reducing stress and GCs administration in patients with pancreatic cancer to avoid an increased risk of cancer metastasis.

KRT13 promotes stemness and drives metastasis in breast cancer through a plakoglobin/c-Myc signaling pathway.

BACKGROUND: Keratins (KRTs) are intermediate filament proteins that interact with multiple regulatory proteins to initiate signaling cascades. Keratin 13 (KRT13) plays an important role in breast cancer progression and metastasis. The objective of this study is to elucidate the mechanism by which KRT13 promotes breast cancer growth and metastasis. METHODS: The function and mechanisms of KRT13 in breast cancer progression and metastasis were assessed by overexpression and knockdown followed by examination of altered behaviors in breast cancer cells and in xenograft tumor formation in mouse mammary fat pad. Human breast cancer specimens were examined by immunohistochemistry and multiplexed quantum dot labeling analysis to correlate KRT13 expression to breast cancer progression and metastasis. RESULTS: KRT13-overexpressing MCF7 cells displayed increased proliferation, invasion, migration and in vivo tumor growth and metastasis to bone and lung. Conversely, KRT13 knockdown inhibited the aggressive behaviors of HCC1954 cells. At the molecular level, KRT13 directly interacted with plakoglobin (PG, γ-catenin) to form complexes with desmoplakin (DSP). This complex interfered with PG expression and nuclear translocation and abrogated PG-mediated suppression of c-Myc expression, while the KRT13/PG/c-Myc signaling pathway increased epithelial to mesenchymal transition and stem cell-like phenotype. KRT13 expression in 58 human breast cancer tissues was up-regulated especially at the invasive front and in metastatic specimens (12/18) (p < 0.05). KRT13 up-regulation in primary breast cancer was associated with decreased overall patient survival. CONCLUSIONS: This study reveals that KRT13 promotes breast cancer cell growth and metastasis via a plakoglobin/c-Myc pathway. Our findings reveal a potential novel pathway for therapeutic targeting of breast cancer progression and metastasis.

The putative obtusifoliol 14α-demethylase OsCYP51H3 affects multiple aspects of rice growth and development.

Some members of the CYP51G subfamily has been shown to be obtusifoliol 14α-demethylase, key enzyme of the sterol and brassinosteroid (BR) biosynthesis, which mediate plant development and response to stresses. However, little is known about the functions of CYP51H subfamily in rice. Here, OsCYP51H3, an ortholog of rice OsCYP51G1 was identified. Compared with wild type, the mutants oscyp51H3 and OsCYP51H3-RNAi showed dwarf phenotype, late flowering, erected leaves, lower seed-setting rate, and smaller and shorter seeds. In contrast, the phenotypic changes of OsCYP51H3-OE plants are not obvious. Metabolomic analysis of oscyp51H3 mutant indicated that OsCYP51H3 may also encode an obtusifoliol 14α-demethylase involved in phytosterol and BR biosynthesis, but possibly not that of triterpenes. The RNA-seq results showed that OsCYP51H3 may affect the expression of a lot of genes related to rice development. These findings showed that OsCYP51H3 codes for a putative obtusifoliol 14α-demethylase involved in phytosterol and BR biosynthesis, and mediates rice development.

Epidemiological investigation of duck adenovirus 3 in southern China, during 2018-2020.

RESEARCH HIGHLIGHTSFirst report of the epidemiology of duck adenovirus 3 infection in China.Mutant DAdV-3 strains (truncated ORF67) became predominant.

Characterization and pathogenicity of a novel avian nephritis virus isolated in China.

ABSTRACTAvian nephritis virus infections of chicken flocks cause enteric and kidney disease, uneven growth, and runting stunting syndrome, leading to economic losses in the poultry industry. In this study, one ANV strain, designated as AH202017, was isolated from a diseased broiler flock in Anhui province, China, in 2020. Virus production in LMH cell culture was confirmed by real-time RT-PCR and immunofluorescence assay. The complete genome sequencing analysis indicated that AH202017 shares 77.5-85.5% identity with 12 reference strains in GenBank. Phylogenetic analysis of the capsid protein revealed that AH202017 is more closely related to VIC-6a/Australia/2014 belonging to ANV genotype 2. However, the phylogenetic tree, based on the ORF1a protein and ORF1b protein, indicated that AH202017 manifests a close relationship with GXJL815/China/2017 belonging to genotype 8. In infection experiments, four infected chickens showed depression and one chicken died at 6 days post-infection, corresponding to 5% mortality. The virus was shed daily in the faeces of infected chickens, and was found distributed in multiple organs. Macroscopic and microscopic lesions in the kidneys were observed. This is the first paper that describes the genomic characteristics and pathogenicity of a novel ANV strain in China. RESEARCH HIGHLIGHTSA novel ANV strain was isolated for the first time from diseased broilers in China.The ANV strain caused nephritis and 5% mortality rate in 1-day-old SPF chickens.

Exploring agreement and feasibility between virtual home visits and in-person home visits for peritoneal dialysis patients-a paired study.

INTRODUCTION: Virtual home visits may improve chronic disease management. However, whether they are suitable for peritoneal dialysis (PD) patients has not yet been fully investigated. This study aimed to compare the agreement and acceptance of virtual home visits and in-person home visits in PD patients. METHODS: This was a paired, single center, noninferiority trial. Participants received a virtual home visit and an in-person home visit simultaneously. A home visit checklist was built for standardization visits. The content was divided into three parts: domestic habits (57 items), bag exchange procedures (56 items), and exit site care (53 items). Satisfaction questionnaires for both patients and nurses were designed to assess attitudes toward home visits and socioeconomic effects. RESULTS: A total of 30 PD patients were enrolled in a single center. The information collected from virtual home visits and in-person home visits was found to be highly consistent. The perfect agreement was found in 52/57, 49/56, and 44/53 items (Cohen's kappa 0.81-1.00), substantial agreement in 4/57, 7/56, and 8/53 items (Cohen's kappa 0.61-0.80). Patients reported almost identical satisfaction for virtual home visits and in-person home visits (Z = 0.39, p = 0.70). PD nurses reported similar feasibility and patient cooperation for the two visit types (Z = 0.99, p = 0.33; Z = 1.65, p = 0.10, respectively). In addition, virtual home visits were found to be more cost-effective than in-person home visits. CONCLUSIONS: Virtual home visits information collection was similar to in-person home visits in PD. There were no differences in participant satisfaction and feasibility between the two visit types.

The inflammatory markers of multisystem inflammatory syndrome in children (MIS-C) and adolescents associated with COVID-19: A meta-analysis.

To conduct a systematic review and meta-analysis to characterize inflammatory markers in comparisons of multisystem inflammatory syndrome in children (MIS-C) versus severe/non-severe COVID-19, severe MIS-C versus non-severe MIS-C, and among age groups of MIS-C. Nine databases were searched for studies on inflammatory markers of MIS-C. After quality checks, data were pooled using a fixed or random effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen, and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty-one studies with 1735 participants yielded 787 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP, and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Severe MIS-C patients had higher levels of WBC, ANC, CRP, D-dimer, and ferritin than non-severe MIS-C patients. For MIS-C, younger children (0-5 years) had lower CRP and ferritin levels than middle-aged/older children/adolescents. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.

Candidate gene analysis of watermelon stripe pattern locus ClSP ongoing recombination suppression.

KEY MESSAGE: Using two segregating population, watermelon stripe pattern underlying gene ClSP was delimited to a 611.78 Kb region, consisting of four discrete haploblocks and ongoing recombination suppression. Stripe pattern is an important commodity trait in watermelon, displaying diverse types. In this study, two segregating populations were generated for genetic mapping the single dominant locus ClSP, which was finally delimited to a 611.78 Kb interval with suppression of recombination. According to polymorphism sites detected among genotypes, four discrete haploblocks were characterized in this target region. Based on reference genomes, 81 predicted genes were annotated in the ClSP interval, including seven transcription factors namely as candidate No1-No7. Meanwhile, the ortholog gene of cucumber ist responsible for the irregular stripes was considered as candidate No8. Strikingly, gene structures of No1-No5 completely varied from their reference descriptions and subsequently re-annotated. For instance, the original adjacent distribution candidates No2 and No3 were re-annotated as No2_3, while No4 and No5 were integrated as No4_5. Sequence analysis demonstrated the third polymorphism in CDS of re-annotated No4_5 resulting in truncated proteins in non-stripe plants. Furthermore, only No4_5 was down-regulated in light green stripes relative to dark green stripes. Transcriptome analysis identified 356 DEGs between dark green striped and light green striped peels, with genes involved in photosynthesis and chloroplast development down-regulated in light green stripes but calcium ion binding related genes up-regulated. Additionally, 38 DEGs were annotated as transcription factors, with the majority up-regulated in light green stripes, such as ERFs and WRKYs. This study not only contributes to a better understanding of the molecular mechanisms underlying watermelon stripe development, but also provides new insights into the genomic structure of ClSP locus and valuable candidates.

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis.

OBJECTIVE: A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19). METHODS: Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients. RESULTS: Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD (95% CI): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD (95% CI): 0.29 (-0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD (95% CI): 0.13 (-0.07, 0.32), p = 0.212] or AST [SMD (95% CI): 0.10 (-0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD (95% CI): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD (95% CI): 0.05 (-0.06, 0.16) p = 0.387] or AST [SMD (95% CI): 0.19 (-0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD (95% CI): -0.21 (-1.07, 0.64), p = 0.624] or troponin [SMD (95% CI): -0.07 (-0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test. CONCLUSIONS: The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.

Isolation and characterization of a recombinant Muscovy duck parvovirus circulating in Muscovy ducks in South China.

In 2019, flocks of Muscovy ducks presented with clinical signs typical of MDPV infection. The MDPV GD201911 strain was isolated by inoculating samples from positive birds into Muscovy duck embryos. Challenge with the isolate GD201911 caused typical MDPV disease symptoms and resulted in 25%-40% mortality, depending on the challenge dose, indicating the high pathogenicity of GD201911 for Muscovy ducks. Genome sequencing and phylogenetic analysis demonstrated that GD201911 clustered with recombinant MDPV strains, indicating that recombinant MDPV is circulating in China. Epidemiological monitoring should be performed continuously to assist with decision making for disease control.

High expression of microRNA20b is associated with malignant clinicopathological features and poor prognosis in breast phyllodes tumor.

BACKGROUND: microRNAs, which expound the transcriptional regulation of gene expression, have been validated as prognostic markers in many tumors. The deregulated expression of microRNAs has been shown to aid classification of tumors and predict outcome in many tumors including breast PTs. The aim of our study is to investigate the clinical significance and prognostic value of microRNAs in PTs to identify a biomarker which has the potential for predicting prognosis and target therapy. METHODS: Quantitative real-time PCR (qRT-PCR) was used to detect the expression level of microRNA20b in 123 breast PTs patients. The correlations between the expression of microRNA20b and clinicopathological parameters were investigated. The prognostic significance of microRNA20b was investigated by the Kaplan-Meier survival and Cox proportional hazards regression model. RESULTS: The expression level of microRNA20b increased with the increase in the tumor grade (p < 0.05). High expression of microRNA20b correlated with stromal overgrowth, marked stromal cellularity, high atypia of stromal cells, infiltrative tumor margin, high mitotic activity, tumor grade, local recurrence and metastasis (p < 0.05). High expression of microRNA20b correlated with the shorter disease-free survival (DFS) (log-rank test, p < 0.001). Multivariate Cox regression analysis showed that microRNA20b was an independent prognostic indicator for breast PTs patients. CONCLUSION: The study demonstrated the promising potential of applying microRNA20b as a prognostic biomarker in PT patients.

MOV10 sequesters the RNP of influenza A virus in the cytoplasm and is antagonized by viral NS1 protein.

MOV10 has emerged as an important host antiviral factor. MOV10 not only inhibits various viruses, including human immunodeficiency virus type 1, hepatitis C virus and vesicular stomatitis virus, but also restricts the activity of retroelements long interspersed nucleotide element-1, Alu, SVA and intracisternal A particles. Here, we report that MOV10 suppresses influenza A virus infection through interacting with viral nucleoprotein (NP), sequestering viral RNP in the cytoplasm and causing the degradation of viral vRNA. The antiviral activity of MOV10 depends on the integrity of P-bodies. We also found that the antiviral activity of MOV10 is partially countered by viral NS1 protein that interferes with the interaction of MOV10 with viral NP and causes MOV10 degradation through the lysosomal pathway. Moreover, NS1-defective influenza A virus is more susceptible to MOV10 restriction. Our data not only expand the antiviral spectrum of MOV10 but also reveal the NS1 protein as the first viral antagonist of MOV10.

Targeting Burkitt lymphoma with a tumor cell-specific heptamethine carbocyanine-cisplatin conjugate.

BACKGROUND: Burkitt lymphoma is a fast-growing mature B cell malignancy, whose genetic hallmark is translocation and activation of the c-myc gene. Prompt multiagent immunochemotherapy regimens can have favorable outcomes, but prognosis is poor in refractory or relapsed disease. We previously identified a novel family of near-infrared heptamethine carbocyanine fluorescent dyes (HMCD or DZ) with tumor-homing properties via organic anion-transporting peptides. These membrane carriers have uptake in tumor cells but not normal cells in cell culture, mouse and dog tumor models, patient-derived xenografts, and perfused kidney cancers in human patients. METHODS: Here we report the cytotoxic effects of a synthesized conjugate of DZ with cisplatin (CIS) on B cell lymphoma CA46, Daudi, Namalwa, Raji, and Ramos cell lines in cell culture and in xenograft tumor formation. Impaired mitochondrial membrane permeability was examined as the mechanism of DZ-CIS-induced lymphoma cell death. RESULTS: The new conjugate, DZ-CIS, is cytotoxic against Burkitt lymphoma cell lines and tumor models. DZ-CIS retains tumor-homing properties to mitochondrial and lysosomal compartments, does not accumulate in normal cells and tissues, and has no nephrotoxicity in mice. DZ-CIS accumulated in Burkitt lymphoma cells and tumors induces apoptosis and retards tumor cell growth in culture and xenograft tumor growth in mice. CONCLUSION: DZ-CIS downregulated c-myc and overcame CIS resistance in myc-driven TP53-mutated aggressive B cell Burkitt lymphoma. We propose that DZ-CIS could be used to treat relapsed/refractory aggressive Burkitt lymphomas.

The ABA-induced soybean ERF transcription factor gene GmERF75 plays a role in enhancing osmotic stress tolerance in Arabidopsis and soybean.

BACKGROUND: Ethylene-responsive factors (ERFs) play important roles in plant growth and development and the response to adverse environmental factors, including abiotic and biotic stresses. RESULTS: In the present study, we identified 160 soybean ERF genes distributed across 20 chromosomes that could be clustered into eight groups based on phylogenetic relationships. A highly ABA-responsive ERF gene, GmERF75, belonging to Group VII was further characterized. Subcellular localization analysis showed that the GmERF75 protein is localized in the nucleus, and qRT-PCR results showed that GmERF75 is responsive to multiple abiotic stresses and exogenous hormones. GmERF75-overexpressing Arabidopsis lines showed higher chlorophyll content compared to WT and mutants under osmotic stress. Two independent Arabidopsis mutations of AtERF71, a gene homologous to GmERF75, displayed shorter hypocotyls, and overexpression of GmERF75 in these mutants could rescue the short hypocotyl phenotypes. Overexpressing GmERF75 in soybean hairy roots improved root growth under exogenous ABA and salt stress. CONCLUSIONS: These results suggested that GmERF75 is an important plant transcription factor that plays a critical role in enhancing osmotic tolerance in both Arabidopsis and soybean.