Triplet-branch network with contrastive prior-knowledge embedding for disease grading.

Since different disease grades require different treatments from physicians, i.e., the low-grade patients may recover with follow-up observations whereas the high-grade may need immediate surgery, the accuracy of disease grading is pivotal in clinical practice. In this paper, we propose a Triplet-Branch Network with ContRastive priOr-knoWledge embeddiNg (TBN-CROWN) for the accurate disease grading, which enables physicians to accordingly take appropriate treatments. Specifically, our TBN-CROWN has three branches, which are implemented for representation learning, classifier learning and grade-related prior-knowledge learning, respectively. The former two branches deal with the issue of class-imbalanced training samples, while the latter one embeds the grade-related prior-knowledge via a novel auxiliary module, termed contrastive embedding module. The proposed auxiliary module takes the features embedded by different branches as input, and accordingly constructs positive and negative embeddings for the model to deploy grade-related prior-knowledge via contrastive learning. Extensive experiments on our private and two publicly available disease grading datasets show that our TBN-CROWN can effectively tackle the class-imbalance problem and yield a satisfactory grading accuracy for various diseases, such as fatigue fracture, ulcerative colitis, and diabetic retinopathy.

Immunoproteasome function maintains oncogenic gene expression in KMT2A-complex driven leukemia.

Pharmacologic targeting of chromatin-associated protein complexes has shown significant responses in KMT2A-rearranged (KMT2A-r) acute myeloid leukemia (AML) but resistance frequently develops to single agents. This points to a need for therapeutic combinations that target multiple mechanisms. To enhance our understanding of functional dependencies in KMT2A-r AML, we have used a proteomic approach to identify the catalytic immunoproteasome subunit PSMB8 as a specific vulnerability. Genetic and pharmacologic inactivation of PSMB8 results in impaired proliferation of murine and human leukemic cells while normal hematopoietic cells remain unaffected. Disruption of immunoproteasome function drives an increase in transcription factor BASP1 which in turn represses KMT2A-fusion protein target genes. Pharmacologic targeting of PSMB8 improves efficacy of Menin-inhibitors, synergistically reduces leukemia in human xenografts and shows preserved activity against Menin-inhibitor resistance mutations. This identifies and validates a cell-intrinsic mechanism whereby selective disruption of proteostasis results in altered transcription factor abundance and repression of oncogene-specific transcriptional networks. These data demonstrate that the immunoproteasome is a relevant therapeutic target in AML and that targeting the immunoproteasome in combination with Menin-inhibition could be a novel approach for treatment of KMT2A-r AML.

Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.

Scribble complex proteins can influence cell fate decisions and self-renewal capacity of hematopoietic cells. While specific cellular functions of Scribble complex members are conserved in mammalian hematopoiesis, they appear to be highly context dependent. Using CRISPR/Cas9-based genetic screening, we have identified Scribble complex-related liabilities in AML including LLGL1. Despite its reported suppressive function in HSC self-renewal, inactivation of LLGL1 in AML confirms its relevant role for proliferative capacity and development of AML. Its function was conserved in human and murine models of AML and across various genetic backgrounds. Inactivation of LLGL1 results in loss of stemness-associated gene-expression including HoxA-genes and induces a GMP-like phenotype in the leukemia stem cell compartment. Re-expression of HoxA9 facilitates functional and phenotypic rescue. Collectively, these data establish LLGL1 as a specific dependency and putative target in AML and emphasizes its cell-type specific functions.

Coordinatized lesion location analysis empowering ROI-based radiomics diagnosis on brain gliomas.

OBJECTIVES: To assess the value of coordinatized lesion location analysis (CLLA), in empowering ROI-based imaging diagnosis of gliomas by improving accuracy and generalization performances. METHODS: In this retrospective study, pre-operative contrasted T1-weighted and T2-weighted MR images were obtained from patients with gliomas from three centers: Jinling Hospital, Tiantan Hospital, and the Cancer Genome Atlas Program. Based on CLLA and ROI-based radiomic analyses, a fusion location-radiomics model was constructed to predict tumor grades, isocitrate dehydrogenase (IDH) status, and overall survival (OS). An inter-site cross-validation strategy was used for assessing the performances of the fusion model on accuracy and generalization with the value of area under the curve (AUC) and delta accuracy (ACC) (ACCtesting-ACCtraining). Comparisons of diagnostic performances were performed between the fusion model and the other two models constructed with location and radiomics analysis using DeLong's test and Wilcoxon signed ranks test. RESULTS: A total of 679 patients (mean age, 50 years ± 14 [standard deviation]; 388 men) were enrolled. Based on tumor location probabilistic maps, fusion location-radiomics models (averaged AUC values of grade/IDH/OS: 0.756/0.748/0.768) showed the highest accuracy in contrast to radiomics models (0.731/0.686/0.716) and location models (0.706/0.712/0.740). Notably, fusion models ([median Delta ACC: - 0.125, interquartile range: 0.130]) demonstrated improved generalization than that of radiomics model ([- 0.200, 0.195], p = 0.018). CONCLUSIONS: CLLA could empower ROI-based radiomics diagnosis of gliomas by improving the accuracy and generalization of the models. CLINICAL RELEVANCE STATEMENT: This study proposed a coordinatized lesion location analysis for glioma diagnosis, which could improve the performances of the conventional ROI-based radiomics model in accuracy and generalization. KEY POINTS: • Using coordinatized lesion location analysis, we mapped anatomic distribution patterns of gliomas with specific pathological and clinical features and constructed glioma prediction models. • We integrated coordinatized lesion location analysis into ROI-based analysis of radiomics to propose new fusion location-radiomics models. • Fusion location-radiomics models, with the advantages of being less influenced by variabilities, improved accuracy, and generalization performances of ROI-based radiomics models on predicting the diagnosis of gliomas.

Effects of anti-inflammatory therapies on glycemic control in type 2 diabetes mellitus.

Background: The overall evidence base of anti-inflammatory therapies in patients with type 2 diabetes mellitus (T2DM) has not been systematically evaluated. The purpose of this study was to assess the effects of anti-inflammatory therapies on glycemic control in patients with T2DM. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched up to 21 September 2022 for randomized controlled trials (RCTs) with anti-inflammatory therapies targeting the proinflammatory cytokines, cytokine receptors, and inflammation-associated nuclear transcription factors in the pathogenic processes of diabetes, such as interleukin-1ß (IL-1ß), interleukin-1ß receptor (IL-1ßR), tumor necrosis factor-α (TNF-α), and nuclear factor-κB (NF-κB). We synthesized data using mean difference (MD) and 95% confidence interval (CI). Heterogeneity between studies was assessed by I2 tests. Sensitivity and subgroup analyses were also conducted. Results: We included 16 RCTs comprising 3729 subjects in the meta-analyses. Anti-inflammatory therapies can significantly reduce the level of fasting plasma glucose (FPG) (MD = - 10.04; 95% CI: -17.69, - 2.40; P = 0.01), glycated haemoglobin (HbA1c) (MD = - 0.37; 95% CI: - 0.51, - 0.23; P < 0.00001), and C-reactive protein (CRP) (MD = - 1.05; 95% CI: - 1.50, - 0.60; P < 0.00001) compared with control, and therapies targeting IL-1ß in combination with TNF-α have better effects on T2DM than targeting IL-1ß or TNF-α alone. Subgroup analyses suggested that patients with short duration of T2DM may benefit more from anti-inflammatory therapies. Conclusion: Our meta-analyses indicate that anti-inflammatory therapies targeting the pathogenic processes of diabetes can significantly reduce the level of FPG, HbA1c, and CRP in patients with T2DM.

Polystyrene microplastics induce endoplasmic reticulum stress, apoptosis and inflammation by disrupting the gut microbiota in carp intestines.

Microplastics have been recognized as a widespread new pollutant in nature and have induced an increase in the occurrence of a variety of diseases in carp. An animal model of microplastic ingestion was successfully established in an aqueous environment. The gut microbiota was analysed using a metagenomic approach. The results showed a significant reduction in the relative abundances of Lactococcus garvieae, Bacteroides_paurosaccharolyticus, and Romboutsia_ilealis after PS-MPs treatment. The 16S Silva database was used to predict and analyse the known genes. Intestinal flora disorders related to infectious diseases, cancers, neurodegenerative diseases, endocrine and metabolic diseases, cardiovascular diseases, and other diseases were found. The intake of PS-MPs resulted in damage to carp intestinal tissue and apoptosis of intestinal epithelial cells. The levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α were significantly increased with the intake of PS-MPs. The gene and protein levels of GRP78, Caspase-3, Caspase-7, Caspase-9, Caspase-12, PERK, IRE1, and ATF6 were further examined in PS group. The occurrence of ERS and apoptosis in carp intestines was confirmed. These results suggest that the accumulation of PS-MPs in the aquatic environment can disturb the carp gut microbiota and induce ERS, apoptosis, and inflammation in the intestinal tissue.

Polystyrene microplastics induced inflammation with activating the TLR2 signal by excessive accumulation of ROS in hepatopancreas of carp (Cyprinus carpio).

Polystyrene microplastics (PS-MPs) affect the immune defense function on carp (Cyprinus carpio). The PS-MPs model of carp was established by feeding with PS-MPs particle size of 8 µm and concentration of 1000 ng/L water. Hepatopancreas function test revealed the activities of AKP, ALT, AST and LDH abnormal increase. PS-MPs induced tissue damage and lead to abnormal hepatopancreas function. The PS-MPs also induced a oxidative stress with the antioxidant enzymes SOD, CAT, GSH-PX, and T-AOC activities decreasing and reactive oxygen species (ROS) excessive accumulation. PS-MPs activated the Toll like receptor-2 (TLR2) signaling pathway. The mRNA and protein expressions of TLR2, Myeloid differentiation primary response 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), NF-κB p65, Tumor necrosis factor (TNF-α), Interleukin-1ß (IL-1ß), Inducible Nitric Oxide Synthase (iNOS), and cycooxygenase 2(COX2) was revealed increased in both hepatopancreas and hepatocytes with the qPCR and Western blotting analysis mode. ELISA showed the expressions of TNF-α, IL-1ß, iNOS, and COX2 inflammatory molecule were increased in both hepatopancreas and hepatocytes. The results showed that PS-MPs caused a serious injure in the hepatopancreas and brought serious effects on the inflammatory response of carp. The present study displayed the harm caused by PS-MPs in freshwater fish, and provided some suggestions and references for toxicological studies of microplastics in freshwater environment.

TBBPA induces inflammation, apoptosis, and necrosis of skeletal muscle in mice through the ROS/Nrf2/TNF-α signaling pathway.

Tetrabromobisphenol A (TBBPA) is present in large quantities in the environment due to its widespread use. And TBBPA is capable of accumulating in animals, entering the ecological chain and causing widespread damage to organisms. TBBPA is capable of causing the onset of oxidative stress, which induces tissue damage and cell death, which in turn affects the physiological function of tissues. Skeletal muscle is a critical tissue for maintaining growth, movement, and health in the body. However, the mechanism of TBBPA-induced skeletal muscle injury remains unclear. In this study, we constructed mouse skeletal muscle models (10, 20, and 40 mg/kg TBBPA) and mouse myoblasts (C2C12) cell models (2,4, and 8 µg/L TBBPA) at different concentrations. The results of this experiment showed that under TBBPA treatment, the levels of reactive oxygen species (ROS) and Malondialdehyde (MDA) in mouse skeletal and C2C12 cells were increased significantly, but the activities of some antioxidant enzymes decreased. TBBPA can inhibit Nuclear factor E2-related factor 2 (Nrf2) entry into the nucleus, thus affecting the expression of the Nrf2 downstream factors. With the increase of TBBPA concentration, the expression levels of inflammatory factors were significantly increased, while the anti-apoptotic factors were significantly decreased. The expression of pro-apoptotic factors increased in a dose-dependent manner. Programmed necrosis-related factors were also significantly elevated. Our results suggest that TBBPA induces oxidative stress and inflammation, apoptosis, and necrosis in the skeletal muscle of mice by regulating Nrf2/ROS/TNF-α signaling pathway.

Bariatric surgery and secondary hyperparathyroidism: a meta-analysis.

BACKGROUND: Obesity increases the risk of obesity-related medical problems. Weight loss after metabolic and bariatric surgery (MBS) has been well studied. However, the effects of MBS on parathyroid function remain unclear. OBJECTIVE: The objective of this study was to perform a meta-analysis to examine the impact of MBS on the risk of secondary hyperparathyroidism (SHPT). SETTING: The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. METHODS: The PubMed, Embase, Web of Science, and the Cochrane Library databases were systematically reviewed from inception to May 2022 to identify studies reporting quantitative measurements of SHPT risk pre-MBS and post-MBS. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated and compared. Effects were pooled using a random-effects or fixed-effects model. Subgroup analyses were performed according to the follow-up time and surgical procedure. RESULTS: The final meta-analysis included 9 studies with a total of 5585 patients. The mean follow-up time was 3.5 years (range 0.25-5). Overall, MBS appears to does not affect SHPT risk (OR = 1.34, 95% CI 0.81-2.20, I2 = 95%). Follow-up data showed no evidence of SHPT within 2 years following gastric bypass (GB) and sleeve gastrectomy procedures (OR = 1.42, 95% CI 0.66-3.07 for GB, OR = 0.39, 95% CI 0.09-1.62 for sleeve gastrectomy ). At the 2-year and long-term follow-up intervals, a marked increase in SHPT was detected for GB (OR = 6.06, 95% CI 3.39-10.85 for GB). In addition, the surgical procedure for GB decreased the likelihood of SHPT compared with the surgical procedure for biliopancreatic diversion with duodenal switch (OR = 0.29, 95% CI 0.17-0.49). CONCLUSIONS: Our meta-analysis indicated that GB appears to increase SHPT risk. Patients undergoing MBS should be aware of the risk of SHPT. Larger studies are needed to evaluate the outcomes and side effects and may eventually provide a better and more comprehensive understanding of the risks.

Bariatric Surgery and the Risk of Cerebrovascular Events: a Meta-analysis of 17 Studies Including 3,124,063 Subjects.

PURPOSE: To perform a meta-analysis of the literature to evaluate the prevalence of cerebrovascular comorbidities between patients undergoing bariatric surgery and those not undergoing bariatric surgery. MATERIALS AND METHODS: Studies about the risk of cerebrovascular disease both before and after bariatric surgery were systematically explored in multiple electronic databases, including PubMed, Web of Science, Cochrane Library, and Embase, from the time of database construction to May 2022. RESULTS: Seventeen studies with 3,124,063 patients were finally included in the meta-analysis. There was a statistically significant reduction in cerebrovascular event risk following bariatric surgery (OR 0.68; 95% CI 0.58 to 0.78; I2 = 87.9%). The results of our meta-analysis showed that bariatric surgery was associated with decreased cerebrovascular event risk in the USA, Sweden, the UK, and Germany but not in China or Finland. There was no significant difference in the incidence of cerebrovascular events among bariatric surgery patients compared to non-surgical patients for greater than or equal to 5 years, but the incidence of cerebrovascular events less than 5 years after bariatric surgery was significantly lower in the surgical patients compared to non-surgical patients in the USA population. CONCLUSION: Our meta-analysis suggested that bariatric surgery for severe obesity was associated with a reduced risk of cerebrovascular events in the USA, Sweden, the UK, and Germany. Bariatric surgery significantly reduced the risk of cerebrovascular events within 5 years, but there was no significant difference in the risk of cerebrovascular events for 5 or more years after bariatric surgery in the USA.

RP-Rs-fMRIomics as a Novel Imaging Analysis Strategy to Empower Diagnosis of Brain Gliomas.

Rs-fMRI can provide rich information about functional processes in the brain with a large array of imaging parameters and is also suitable for investigating the biological processes in cerebral gliomas. We aimed to propose an imaging analysis method of RP-Rs-fMRIomics by adopting omics analysis on rs-fMRI with exhaustive regional parameters and subsequently estimating its feasibility on the prediction diagnosis of gliomas. In this retrospective study, preoperative rs-fMRI data were acquired from patients confirmed with diffuse gliomas (n = 176). A total of 420 features were extracted through measuring 14 regional parameters of rs-fMRI as much as available currently in 10 specific narrow frequency bins and three parts of gliomas. With a randomly split training and testing dataset (ratio 7:3), four classifiers were implemented to construct and optimize RP-Rs-fMRIomics models for predicting glioma grade, IDH status and Karnofsky Performance Status scores. The RP-Rs-fMRIomics models (AUROC 0.988, 0.905, 0.801) were superior to the corresponding traditional single rs-fMRI index (AUROC 0.803, 0.731, 0.632) in predicting glioma grade, IDH and survival. The RP-Rs-fMRIomics analysis, featuring high interpretability, was competitive for prediction of glioma grading, IDH genotype and prognosis. The method expanded the clinical application of rs-fMRI and also contributed a new imaging analysis for brain tumor research.

Development and validation of a clinically applicable deep learning strategy (HONORS) for pulmonary nodule classification at CT: A retrospective multicentre study.

PURPOSE: To propose a practical strategy for the clinical application of deep learning algorithm, i.e., Hierarchical-Ordered Network-ORiented Strategy (HONORS), and a new approach to pulmonary nodule classification in various clinical scenarios, i.e., Filter-Guided Pyramid NETwork (FGP-NET). MATERIALS AND METHODS: We developed and validated FGP-NET on a collection of 2106 pulmonary nodules on computed tomography images which combined screened and clinically detected nodules, and performed external test (n = 341). The area under the curves (AUCs) of FGP-NET were assessed. A comparison study with a group of 126 skilled radiologists was conducted. On top of FGP-NET, we built up our HONORS which was composed of two solutions. In the Human Free Solution, we used the high sensitivity operating point for screened nodules, but the high specificity operating point for clinically detected nodules. In the Human-Machine Coupling Solution, we used the Youden point. RESULTS: FGP-NET achieved AUCs of 0.969 and 0.847 for internal and external test. The AUCs of the subsets of the external test set ranged from 0.890 to 0.942. The average sensitivity and specificity of the 126 radiologists were 72.2 ±â€¯15.1 % and 71.7 ±â€¯15.5 %, respectively, while a higher sensitivity (93.3 %) but a relatively inferior specificity (64.0 %) were achieved by FGP-NET. HONORS-guided FGP-NET identified benign nodules with high sensitivity (sensitivity,95.5 %; specificity, 72.5 %) in the screened nodules, and identified malignant nodules with high specificity (sensitivity, 31.0 %; specificity, 97.5 %) in the clinically detected nodules. These nodules could be reliably diagnosed without any intervention from radiologists, via the Human Free Solution. The remaining ambiguous nodules were diagnosed with high performance, which however required manual confirmation by radiologists, via the Human-Machine Coupling Solution. CONCLUSIONS: FGP-NET performed comparably to skilled radiologists in terms of diagnosing pulmonary nodules. HONORS, due to its high performance, might reliably contribute a second opinion, aiding in optimizing the clinical workflow.

Macrophage Heterogeneity in the Intestinal Cells of Salmon: Hints From Transcriptomic and Imaging Data.

The intestine has many types of cells that are present mostly in the epithelium and lamina propria. The importance of the intestinal cells for the mammalian mucosal immune system is well-established. However, there is no in-depth information about many of the intestinal cells in teleosts. In our previous study, we reported that adherent intestinal cells (AIC) predominantly express macrophage-related genes. To gather further evidence that AIC include macrophage-like cells, we compared their phagocytic activity and morphology with those of adherent head kidney cells (AKC), previously characterized as macrophage-like cells. We also compared equally abundant as well as differentially expressed mRNAs and miRNAs between AIC and AKC. AIC had lower phagocytic activity and were larger and more circular than macrophage-like AKC. RNA-Seq data revealed that there were 18309 mRNAs, with 59 miRNAs that were equally abundant between AIC and AKC. Integrative analysis of the mRNA and miRNA transcriptomes revealed macrophage heterogeneity in both AIC and AKC. In addition, analysis of AIC and AKC transcriptomes revealed functional characteristics of mucosal and systemic macrophages. Five pairs with significant negative correlations between miRNA and mRNAs were linked to macrophages and epithelial cells and their interaction could be pointing to macrophage activation and differentiation. The potential macrophage markers suggested in this study should be investigated under different immune conditions to understand the exact macrophage phenotypes.

Discrimination between transient and persistent subsolid pulmonary nodules on baseline CT using deep transfer learning.

OBJECTIVES: To develop and validate a deep learning model to discriminate transient from persistent subsolid nodules (SSNs) on baseline CT. METHODS: A cohort of 1414 SSNs, consisting of 319 transient SSNs in 168 individuals and 1095 persistent SSNs in 816 individuals, were identified on chest CT. The cohort was assigned by examination date into a development set of 996 SSNs, a tuning set of 212 SSNs, and a validation set of 206 SSNs. Our model was built by transfer learning, which was transferred from a well-performed deep learning model for pulmonary nodule classification. The performance of the model was compared with that of two experienced radiologists. Each nodule was categorized by Lung CT Screening Reporting and Data System (Lung-RADS) to further evaluate the performance and the potential clinical benefit of the model. Two methods were employed to visualize the learned features. RESULTS: Our model achieved an AUC of 0.926 on the validation set with an accuracy of 0.859, a sensitivity of 0.863, and a specificity of 0.858, and outperformed the radiologists. The model performed the best among Lung-RADS 2 nodules and maintained well performance among Lung-RADS 4 nodules. Feature visualization demonstrated the model's effectiveness in extracting features from images. CONCLUSIONS: The transfer learning model presented good performance on the discrimination between transient and persistent SSNs. A reliable diagnosis on nodule persistence can be achieved at baseline CT; thus, an early diagnosis as well as better patient care is available. KEY POINTS: • Deep learning can be used for the discrimination between transient and persistent subsolid nodules. • A transfer learning model can achieve good performance when it is transferred from a model with a similar task. • With the assistance of deep learning model, a reliable diagnosis on nodule persistence can be achieved at baseline CT, which can bring a better patient care strategy.

Application of Three-Dimensional Printing Technology in the Orbital Blowout Fracture Reconstruction.

The aim of this study was to investigate the clinical outcomes of orbital blowout fracture repair by using the three-dimensional (3D) printing-assisted fabrication of individual titanium mesh. Clinical and radiologic data were analyzed for 12 patients with orbital floor and/or medial wall fractures. Lower eyelid incision was used to expose the fractures. Preoperative computed tomographic data were input into an imaging software to rebuild a 3D orbit and mirror the unaffected side into the affected side to replace the demolished orbit. A resin model of the reshaped orbit was generated and used to develop an individual titanium mesh for repairing the fractured orbital. The surgical results were assessed by value of enophthalmos and a comparison of preoperative and postoperative orbital volume difference. All patients had a successful treatment outcome without any complications. Clinical significant enophthalmos were not observed after treatment, and diplopia were solved within 2 weeks postoperative. No extraocular muscle limitation was observed. Postoperative computed tomography scans demonstrated appropriate positioning of titanium mesh and there was no implant displacement. The postoperative orbital volume and enophthalmos difference between the 2 eyes decreased significantly than preoperative (P < 0.001). Three-dimensional printing-assisted fabrication of individual titanium mesh is appropriate for use in orbital blowout fracture.

Smart Bacterial Magnetic Nanoparticles for Tumor-Targeting Magnetic Resonance Imaging of HER2-Positive Breast Cancers.

Supersensitive magnetic resonance (MR) imaging requires contrast with extremely high r2 values. However, synthesized magnetic nanoparticles generally have a relatively low r2 relaxivity. Magnetosomes with high saturation magnetization and good biocompatibility have shown potential values as MR imaging contrast agents. Magnetosomes that target human epidermal growth factor receptor-2 (HER2) were prepared using genetic technology and low-frequency sonication. Anti-HER2 affibody of the ability to target HER2 was displayed on the membrane surface of the magnetosomes through the anchor protein MamC, allowing the bacterial nanoparticles to target tumors overexpressing HER2. The prepared nanoparticles exhibited a very high relaxivity of 599.74 mM-1 s-1 and better dispersion, and their ability to target HER2 was demonstrated both in vitro and in vivo. Also, the HER2-targeting magnetosomes significantly enhanced the MR imaging of orthotopic breast cancer models with or without HER2 expression using a 7.0 T scanner. In particular, tumors overexpressing HER2 demonstrated better MR imaging than HER2-negative tumors after intravenous administration of HER2-targeting magnetosomes, and the MR signals of the augmented contrast could be detected from 3 to 24 h. The magnetosomes did not cause any notable pathogenic effect in the animals. Therefore, we expect that noninvasive imaging of tumors using HER2-targeting magnetosomes has potential for clinical applications in the near future.

Contrast-enhanced ultrasound for differentiating benign from malignant solid small renal masses: comparison with contrast-enhanced CT.

PURPOSE: The study aimed to compare the diagnostic efficiency of contrast-enhanced ultrasound (CEUS) with that of contrast-enhanced computed tomography (CECT) in the evaluation of benign and malignant small renal masses (SRMs) (<4 cm) confirmed by pathology. METHODS: A total of 118 patients with 118 renal masses smaller than 4 cm diagnosed by both CEUS and CECT were enrolled in this study, including 25 benign lesions and 93 malignant lesions. All lesions were confirmed by histopathologic diagnosis after surgical resection. The diagnostic imaging studies of the patients were retrospectively reviewed by two independent ultrasonologists and two independent radiologists blinded to the CT or ultrasound findings and final histological results. All lesions on both CEUS and CECT were independently scored on a 3-point scale (1: benign, 2: equivocal, and 3: malignant). The concordance between interobserver agreement was interpreted using a weighted kappa statistic. The diagnostic efficiency of the evaluation of benign and malignant lesions was compared between CEUS and CECT. RESULTS: All the 118 included lesions were detected by both CEUS and CECT. In CEUS and CECT imaging evaluation of the 118 lesions, the weighted kappa value interpreting the concordance between interobserver agreement was 0.89 (95% CI 0.79-0.98) and 0.93 (95% CI 0.87-0.99), respectively. Both CEUS and CECT demonstrated good diagnostic performance in differential diagnosis of benign and malignant SRMs with sensitivity of 93.5% and 89.2%, specificity of 68% and 76%, PPV of 91.6% and 93.3%, NPV of 73.9% and 65.5%, and AUC of 0.808 and 0.826, respectively. There was no statistically significant difference in any of the diagnostic performance indices between these two methods (P > 0.05). However, the qualitative diagnosis of small papillary renal cell carcinoma (RCC) by CEUS was significantly better than that by CECT (P < 0.05), while there was no significant difference in qualitative diagnostic accuracy on other histotypes of SRMs between CEUS and CECT (P > 0.05). CONCLUSIONS: Both CEUS and CECT imaging modalities are effective for the differential diagnosis of benign and malignant SRMs. Furthermore, CEUS may be more effective than CECT for the qualitative diagnosis of small papillary RCC.

Molecular characterization of heat shock protein 90, 70 and 70 cognate cDNAs and their expression patterns during thermal stress and pupal diapause in the corn earworm.

Three heat shock protein transcripts, hsp90, hsp70, hsc70, isolated from the corn earworm, Helicoverpa zea, were evaluated for their responsiveness to diapause and thermal stress. These Hsps showed high homology to their counterparts in other species. A phylogenetic analysis of the Hsp90 sequence was consistent with the known classification of insects. Northern blot hybridization indicated the presence of hsp90 transcripts in all tissues, but expression in the brain-subesophageal complex was especially pronounced. The genomic organization of hsp90 examined by Southern blot suggested the presence of a single copy of hsp90 in the H. zea genome. The expression patterns after heat shock indicated that hsp70 and hsp90 were heat-inducible, although hsp70 was more strongly induced than hsp90, and hsc70 was indeed a constitutively expressed member of the hsp70 family. Expression of hsp70 and hsc70 were not altered by the diapause program, but hsp90 was down-regulated at this time. Low temperatures (0-4 degrees C) and recovery from low temperature elicited hsp70 and hsp90 responses, but not an hsc70 response. Thus, unlike several other species, H. zea does not up-regulate hsp70 during pupal diapause, but the down-regulation of hsp90 is consistent with the pattern observed in several other species during diapause. Our results also indicate that hsp90 and hsp70 are responsive to low temperature in both diapausing and nondiapausing pupae.

Molecular characterization and expression of prothoracicotropic hormone during development and pupal diapause in the cotton bollworm, Helicoverpa armigera.

Using a strategy of rapid amplification of cDNA ends, the cDNA encoding prothoracicotropic hormone (PTTH) was cloned from the brain of Helicoverpa armigera (Hearm). The Hearm-PTTH cDNA contains an open reading frame encoding a 226-amino acid preprohormone, which shows high identity with the closely related noctuid moths, Helicoverpa zea (98%) and Heliothis virescens (94%), and low identity with five species of Bombycoidea: Bombyx mori (57%), Manduca sexta (55%), Hyalophora cecropia (52%), Samia cynthia ricini (49%) and Antheraea peryni (48%). Hearm-PTTH cDNA shares important structural characterization known from other PTTHs, such as seven cysteine residues, proteolytic cleavage site, glycosylation site, and hydrophobic regions within the mature peptides. Northern blot analysis indicated a 0.9kb transcript present only in the brain. Using the more sensitive technique of RT-PCR, PTTH mRNA was also detected in the subesophageal ganglion, thoracic ganglion, abdominal ganglion, midgut and fat body. During the pupal stage, PTTH mRNA in the brain remained at a constant high level in nondiapausing individuals, was low in diapausing pupae, but increased again at diapause termination. The PTTH protein was detected only in the brain by Western blot analysis. Immunocytochemical results revealed that Hearm-PTTH is localized in two pairs of dorsolateral neurosecretory cells within the brain. Recombinant Hearm-PTTH was successfully expressed in E. coli, and purified recombinant-PTTH was effective in breaking pupal diapause. The results are consistent with a role for PTTH in the regulation of diapause in this species.