Novel model of pyroptosis-related molecular signatures for prognosis prediction of clear cell renal cell carcinoma patients.

Background: Pyroptosis is a programmed death mode of inflammatory cells, which is closely related to tumor progression and tumor immunity. Clear cell renal cell carcinoma (ccRCC) is the major pathological type of renal cell carcinoma (RCC) with poor prognosis. Many theories have tried to clarify the mechanism in the development of ccRCC, but the role of pyroptosis in ccRCC has not been well described. The main purpose of this study is to explore the role of pyroptosis in ccRCC and establish a novel prognosis prediction model of pyroptosis-related molecular signatures for ccRCC. Methods: In the present study, we made a systematical analysis of the association between ccRCC RNA transcriptome sequencing data from The Cancer Genome Atlas (TCGA) database [which included 529 ccRCC patients who were randomized in a training cohort (n=265) and an internal validation cohort (n=264)] and 40 pyroptosis-related genes (PRGs), from which four genes (CASP9, GSDME, IL1B and TIRAP) were selected to construct a molecular prediction model of PRGs for ccRCC. In addition, a cohort of 114 ccRCC patients from Shanghai Eastern Hepatobiliary Surgery Hospital (EHSH) was used as external data to verify the effectiveness of the model by immunohistochemistry. Moreover, the biological functions of the four PRGs were also verified in ccRCC 786-O and 769-P cells by Western blot (WB), CCK-8 cell proliferation, and Transwell invasion assays. Results: The model was able to differentiate high-risk patients from low-risk patients, and this differentiation was consistent with their clinical survival outcomes. In addition, the four PRGs also affected the ability of cell proliferation and invasion in ccRCC. Conclusion: The prediction model of pyroptosis-related molecular markers developed in this study may prove to be a novel understanding for ccRCC.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

Few-Shot Object Detection in Remote Sensing Images via Data Clearing and Stationary Meta-Learning.

Nowadays, the focus on few-shot object detection (FSOD) is fueled by limited remote sensing data availability. In view of various challenges posed by remote sensing images (RSIs) and FSOD, we propose a meta-learning-based Balanced Few-Shot Object Detector (B-FSDet), built upon YOLOv9 (GELAN-C version). Firstly, addressing the problem of incompletely annotated objects that potentially breaks the balance of the few-shot principle, we propose a straightforward yet efficient data clearing strategy, which ensures balanced input of each category. Additionally, considering the significant variance fluctuations in output feature vectors from the support set that lead to reduced effectiveness in accurately representing object information for each class, we propose a stationary feature extraction module and corresponding stationary and fast prediction method, forming a stationary meta-learning mode. In the end, in consideration of the issue of minimal inter-class differences in RSIs, we propose inter-class discrimination support loss based on the stationary meta-learning mode to ensure the information provided for each class from the support set is balanced and easier to distinguish. Our proposed detector's performance is evaluated on the DIOR and NWPU VHR-10.v2 datasets, and comparative analysis with state-of-the-art detectors reveals promising performance.

Breast Cancer Growth on Serial MRI: Volume Doubling Time Based on 3-Dimensional Tumor Volume Assessment.

BACKGROUND: The volume doubling time (VDT) of breast cancer was most frequently calculated using the two-dimensional (2D) diameter, which is not reliable for irregular tumors. It was rarely investigated using three-dimensional (3D) imaging with tumor volume on serial magnetic resonance imaging (MRI). PURPOSE: To investigate the VDT of breast cancer using 3D tumor volume assessment on serial breast MRIs. STUDY TYPE: Retrospective. SUBJECTS: Sixty women (age at diagnosis: 57 ± 10 years) with breast cancer, assessed by two or more breast MRI examinations. The median interval time was 791 days (range: 70-3654 days). FIELD STRENGTH/SEQUENCE: 3-T, fast spin-echo T2-weighted imaging (T2WI), single-shot echo-planar diffusion-weighted imaging (DWI), and gradient echo dynamic contrast-enhanced imaging. ASSESSMENT: Three radiologists independently reviewed the morphological, DWI, and T2WI features of lesions. The whole tumor was segmented to measure the volume on contrast-enhanced images. The exponential growth model was fitted in the 11 patients with at least three MRI examinations. The VDT of breast cancer was calculated using the modified Schwartz equation. STATISTICAL TESTS: Mann-Whitney U test, Kruskal-Wallis test, Chi-squared test, intraclass correlation coefficients, and Fleiss kappa coefficients. A P-value <0.05 was considered statistically significant. The exponential growth model was evaluated using the adjusted R2 and root mean square error (RMSE). RESULTS: The median tumor diameter was 9.7 mm and 15.2 mm on the initial and final MRI, respectively. The median adjusted R2 and RMSE of the 11 exponential models were 0.97 and 15.8, respectively. The median VDT was 540 days (range: 68-2424 days). For invasive ductal carcinoma (N = 33), the median VDT of the non-luminal type was shorter than that of the luminal type (178 days vs. 478 days). On initial MRI, breast cancer manifesting as a focus or mass lesion showed a shorter VDT than that of a non-mass enhancement (NME) lesion (median VDT: 426 days vs. 665 days). DATA CONCLUSION: A shorter VDT was observed in breast cancer manifesting as focus or mass as compared to an NME lesion. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Histopathology of Ganglion Cells in the Proximal Resected Bowel Correlates With the Clinical Outcome in Hirschsprung Disease: A Pilot Study.

INTRODUCTION: Intraoperative leveling biopsy by identifying ganglion cells is crucial to determine surgical margin during surgery for Hirschsprung disease (HSCR). The anastomosis should be performed at least 5 cm proximal to the ganglionic segment to prevent transition zone pull-through. However, the length of the transition zone could be much longer than expected and the histological evaluation of the entire circumference of the proximal margin is recommended, which is time-consuming and not applicable for leveling biopsy. We found that the histopathologic features of ganglion cells varied in the examined bowel specimens and demonstrated a pattern similar to immature and degenerated neuron cells. We assumed that the histopathologic features of ganglion cells in the proximal resected bowel were associated with the clinical outcome and might guide the leveling biopsy. In this study, we described a histopathologic grade of ganglion cells based on the degree of maturity and degeneration. We assessed the correlation between the histopathological grade of ganglion cells in the proximal surgical margin and clinical outcome. METHODS: Three hundred fifty seven patients with HSCR treated between 2013 and 2020 were included. The ganglion cells were divided into six grades based on the histopathologic features in frozen sections. Medical records and detailed histopathologic results of intraoperative frozen sections were reviewed. Follow-up data were collected to evaluate clinical outcomes. The pediatric incontinence and constipation scoring system was used to predict bowel function. RESULTS: The histopathologic results of proximal resected bowel from 357 HSCR patients were presented as follows: Grade I in 52 patients (14.6%), Grade II in 186 patients (52.1%), Grade III in 107 patients (30.0%), and Grade IV in 12 patients (3.4%). The median follow-up time was 46.8 mo (13.0-97.6 mo). The histopathologic grade of ganglion cells from the proximal resected margin was significantly related to postoperative constipation problems and the incidence of Hirschsprung-associated enterocolitis. The results from the pediatric incontinence and constipation scoring system indicated a positive correlation between better postoperative bowel function and lower histopathologic grade of ganglion cells. CONCLUSIONS: This pilot study showed an association between the histopathologic features of ganglion cells in the proximal surgical margin and the clinical outcome. It may provide additional information for intraoperative pathologic consultation in leveling biopsy to prevent insufficient resection of the affected colon. A prospective study is warranted to validate these findings before clinical application.

Yeast UPS1 deficiency leads to UVC radiation sensitivity and shortened lifespan.

UPS1/YLR193C of Saccharomyces cerevisiae (S. cerevisiae) encodes a mitochondrial intermembrane space protein. A previous study found that Ups1p is needed for normal mitochondrial morphology and that UPS1 deficiency disrupts the intramitochondrial transport of phosphatidic acid in yeast cells and leads to an altered unfolded protein response and mTORC1 signaling activation. In this paper, we first provide evidence showing that the UPS1 gene is involved in the UVC-induced DNA damage response and aging. We show that UPS1 deficiency leads to sensitivity to ultraviolet C (UVC) radiation and that this effect is accompanied by elevated DNA damage, increased intracellular ROS levels, abnormal mitochondrial respiratory function, an increased early apoptosis rate, and shortened replicative lifespan and chronological lifespan. Moreover, we show that overexpression of the DNA damage-induced checkpoint gene RAD9 effectively eliminates the senescence-related defects observed in the UPS1-deficient strain. Collectively, these results suggest a novel role for UPS1 in the UVC-induced DNA damage response and aging.

GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma.

Since the application of immune checkpoint therapy (ICT) has gradually become a new strategy for clear cell renal cell carcinoma (ccRCC) treatment, biomarkers that predict the individual response to ICT is needed. This study aimed to identify a new clinical indicator for postoperative surveillance of ccRCC and prediction of ICT response. We investigated the GBP2 expression and its relation with immune cell infiltration in tumor microenvironment using public databases, clinical specimens and ccRCC cell lines. Bioinformatic analysis using public database revealed that GBP2 expression is higher in cancer tissues than in adherent normal tissues among different cancer types including ccRCC, and the same results were acquired from clinical tissue samples tested by Western Blot and PCR. In ccRCC cell lines, CCk-8 proliferation assay and apoptosis assessment suggested GBP2 facilitates the malignancy of ccRCC. 286 ccRCC patients were randomly divided into a training or validation cohort, and immunohistochemistry (IHC) and Kaplan-Meier analysis revealed that higher GBP2 expression is related to worse prognosis. C-index analysis implied that integrating GBP2 expression with TNM stage improved the accuracy in predicting prognosis of ccRCC patients compared to the solitary use of either. Bioinformatic analysis implied a relation between GBP2 and immunity, and GBP2 expression is positively related with suppressive immune markers in ccRCC microenvironment. Taken together, our study demonstrated the potential of GBP2 to sever as a prognostic predictor of ccRCC, and an association between GBP2 and tumor-infiltrating lymphocytes in ccRCC was observed, making it a promising indicator of ICT response.

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.

Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer.

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.

Weighted genes associated with the progression of retinoblastoma: Evidence from bioinformatic analysis.

Mechanisms underlying the development of malignant retinoblastoma (RB) remain largely unknown. The purpose of this study was to identify weighted genes that are associated with the progression of RB and to assess the usefulness of bioinformatic analysis in RB research. Bioinformatic analysis was performed to construct weighted gene co-expression and protein-protein interaction (PPI) networks and to predict long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA regulatory networks. RNA extracted from RB and adjacent retinal tissue was used to validate the results obtained from bioinformatic analysis, using a semi-quantitative PCR (qPCR) assay. Twenty-one modules were generated from 5000 most variably expressed genes. Both the light-yellow and red modules were significantly associated with the cellular anaplastic grade of RB. The genes clustered in the light-yellow module included protocadherin beta (PCDHBs) family members. The red module included 5 hub genes involved in cell division. According to the hypothesis that lncRNA may serve as a competing endogenous RNA (ceRNA) for miRNAs and modulates mRNA expression, a network was constructed between lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and cell division-related mRNAs. PCR analysis using 23 tumor tissues and 5 adjacent retinal tissue showed increased expression of PCDHB5 in tumor samples, and supported the predicted upregulation of mitotic checkpoint serine/threonine kinase (BUB1) by MALAT1 via miR-495-3p. Our study highlights the importance of bioinformatic analysis in identifying potential markers and mechanisms associated with the malignant transformation of RB, and provides evidence to suggest that PCDHB5 and the ceRNA regulatory network of MALAT1/miR-495-3p/BUB1 are involved in the progression of RB.

Radiogenomics of neuroblastoma in pediatric patients: CT-based radiomics signature in predicting MYCN amplification.

OBJECTIVES: To construct a CT-based radiomics signature and assess its performance in predicting MYCN amplification (MNA) in pediatric patients with neuroblastoma. METHODS: Seventy-eight pediatric patients with neuroblastoma were recruited (55 in training cohort and 23 in test cohort). Radiomics features were extracted automatically from the region of interest (ROI) manually delineated on the three-phase computed tomography (CT) images. Selected radiomics features were retained to construct radiomics signature and a radiomics score (rad-score) was calculated by using the radiomics signature-based formula. A clinical model was established with clinical factors, including clinicopathological data, and CT image features. A combined nomogram was developed with the incorporation of a radiomics signature and clinical factors. The predictive performance was assessed by receiver operating characteristics curve (ROC) analysis and decision curve analysis (DCA). RESULTS: The radiomics signature was constructed using 7 selected radiomics features. The clinical radiomics nomogram, which was based on the radiomics signature and two clinical factors, showed superior predictive performance compared with the clinical model alone (area under the curve (AUC) in the training cohort: 0.95 vs. 0.82, the test cohort: 0.91 vs. 0.70). The clinical utility of clinical radiomics nomogram was confirmed by DCA. CONCLUSIONS: This proposed CT-based radiomics signature was able to predict MNA. Combining the radiomics signature with clinical factors outperformed using clinical model alone for MNA prediction. KEY POINTS: • A CT-based radiomics signature has the ability to predict MYCN amplification (MNA) in neuroblastoma. • Both pre- and post-contrast CT images are valuable in predicting MNA. • Associating the radiomics signature with clinical factors improved the predictive performance of MNA, compared with clinical model alone.

Diagnosis of chronic prostatitis by noninvasive methods in elderly patients with benign prostatic hyperplasia in China.

Chronic prostatitis is hard to be identified in BPH patients in clinical works. This study aimed to diagnose chronic prostatitis in BPH patients by noninvasive methods. BPH patients who received transurethral resection of prostate from January 2014 to July 2015 were enrolled in current study. Patients were received examinations of PSA, sex hormones, inflammatory cytokines, metabolic panel and transrectal ultrasonography. According to histological results, patients were divided into two group of BPH with/without prostatitis. Logistic regression was used to find risk factors of chronic prostatitis. As a result, 181 men with an average age of 72.15 ± 8.41 years were enrolled in this study, including 116 patients with prostatitis and 65 patients without prostatitis. The storage sub-score, PSA and IL-2R were significantly higher in patients with prostatitis than those without prostatitis. Based on logistic regression analysis, the above three parameters were also the risk factors of BPH with prostatitis. The diagnostic model was calculated as: 0.317 × storage sub-score + 0.092 × PSA + 0.003 × IL-2R - 4.296. The AUC was 0.725. Histological prostatitis in BPH patients can be diagnosed by the combination of serum IL-2R, PSA and storage sub-score. Identification of chronic prostatitis in BPH patients could more efficiently alleviate urinary symptoms and reduce the risk of disease progression.

Resveratrol could attenuate prostatic inflammation in rats with Oestradiol-induced chronic prostatitis.

To evaluate the effect of resveratrol in rats with chronic prostatitis, 24 rats were randomly divided into the negative control, vehicle-treated and resveratrol groups. The rats in the vehicle-treated group and the resveratrol group were injected subcutaneously with 17-ß-oestradiol (0.25 mg/kg) daily for 6 weeks while the rats in the control group were injected with equivalent normal saline. From the 45th day, the rats in the resveratrol group were given resveratrol (10 mg/kg) by gavage per day while the rest rats were given normal saline. After 55 days, all the rats were sacrificed and the prostatic tissue was removed. Morphological changes were examined by light microscope after H&E staining. The expressions of IL-6, IL-8 and TNF-α were determined through ELISA and immunohistochemical staining. As a result, significant inflammatory cell infiltration and fibroblastic hyperplasia were observed in prostatic stroma in the vehicle-treated group compared with the negative control group, as well as the high expression of IL-6, IL-8 and TNF-α. After resveratrol treatment, inflammatory cell infiltration and fibroblastic hyperplasia were shown prominently reduced. Meanwhile, the expression of IL-6, IL-8 and TNF-α was significantly suppressed. For conclusion, resveratrol could attenuate the prostatic inflammation and downregulate the expression of IL-6, IL-8 and TNF-α in rat with oestradiol-induced chronic prostatitis.

Cancer associated fibroblasts tailored tumor microenvironment of therapy resistance in gastrointestinal cancers.

Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with heavy cancer-related mortalities. Even if continued development of therapy methods, therapy resistance has been a great obstruction for cancer treatment and thereby inevitably leads to depressed final mortality. Peritumoral cancer associated fibroblasts (CAFs), a versatile population assisting cancer cells to build a facilitated tumor microenvironment (TME), has been demonstrated exerting a promotion influence on cancer proliferation, migration, invasion, metastasis, and also therapy resistance. In this review, we provide an update progress in describing how CAFs mediate therapy resistance in GI by various means, meanwhile highlight the crosstalk between CAFs and cancer cells and present some vital signaling pathways activated by CAFs in this resistant process. Furthermore, we discuss the current advances in adopting novel drugs against CAFs and how the knowledge contributing to improved therapy efficacy in clinical practice. In sum, CAFs create a therapy-resistant TME in several aspects of GI progression, although some key problems about distinguishing CAFs subpopulations and controversial issues on pleiotropic CAFs in medication need to be solved for subsequent clinical application. Predictably, targeting therapy-resistant CAFs is a promising adjunctive treatment to benefit GI patients.

Meconium peritonitis due to fetal appendiceal perforation: two case reports and a brief review of the literature.

BACKGROUND: Meconium peritonitis is an infrequent congenital disease usually caused by perforation of the fetal digestive tract. Meconium peritonitis resulting from intrauterine appendiceal perforation has been rarely reported and is often overlooked during pregnancy. We herein report two cases of fetal appendiceal perforation. CASE PRESENTATION: Two neonates were found to have intestinal distension and gradually increasing ascites antenatally. After birth, diagnostic abdominal punctures revealed meconium peritonitis. Urgent surgery showed both neonates had developed gangrenous appendicitis in utero. Pathological examination supported the diagnosis of fetal appendiceal perforation in both neonates, and one also had deformity of cecal duplication. In the present report, we also review the presentation, diagnosis, pathology, management, and recent literature of fetal appendiceal perforation. CONCLUSION: Meconium peritonitis due to fetal appendiceal perforation is extremely rare, and preoperative diagnosis is almost impossible. However, clinicians should be aware of abnormal gastrointestinal manifestations in the fetus during the antenatal examination. For neonates with severe meconium peritonitis, an early operation with careful intraoperative exploration is necessary.

Magnetic resonance imaging features for differentiating breast papilloma with high-risk or malignant lesions from benign papilloma: a retrospective study on 158 patients.

BACKGROUND: Benign breast papilloma is currently managed with conservative management with close observation. In contrast, papilloma with high-risk or malignant lesions warrants surgical excision. The purpose of our study was to investigate magnetic resonance imaging (MRI) features of breast papilloma and to identify imaging diagnostic indicators for papilloma with high-risk or malignant lesions. METHODS: MRI features of 175 surgically confirmed papillomas on 158 patients were retrospectively reviewed. The 175 cases included 132 cases of benign papilloma and 43 cases of papilloma with high-risk or malignant lesions. The MRI features of these lesions were classified into three types: mass, non-mass enhancement (NME), and occult lesion. The occult lesion was defined as the presence of only ductal dilation without any enhanced lesions on MRI. For a mass lesion, the mixed mass-NME lesion was considered if linear, segmental or regional enhanced lesion was found adjacent to the mass. Clinical and MRI features were compared by univariate and multivariate analysis between the benign papilloma and the papilloma with high-risk or malignant lesions. RESULTS: Multivariate logistic regression analysis demonstrated that clinical characteristics including being or older than 50 years (odds ratio [OR] = 4.506), having bloody nipple discharge (OR = 4.499), and concurrent breast cancer (OR = 5.083) were significant indicators for papilloma with high-risk or malignant lesions. On MRI, most papillomas presented as mass (n = 135, 77.1%), and fewer as NME (n = 37, 21.1%) and occult lesion (n = 3, 1.7%). For the mass lesion, the logistic regression analysis demonstrated that a mass size exceeding 10 mm (OR = 2.956) and mixed mass-NME lesion (OR = 4.143) were independent risk indicators for a papilloma with high-risk or malignant lesions. For the NME lesion, the segmental or regional distribution was more commonly observed in the papilloma with high-risk or malignant lesions (61.5%) than the benign papilloma (12.5%) (P = 0.006). All the cases of occult lesions were benign papillomas. CONCLUSIONS: MRI features including a mass size exceeding 10 mm, mixed mass-NME lesion, and NMEs with segmental or regional distribution indicate a papilloma with high-risk or malignant lesions.

Latitudinal and longitudinal clines of phenotypic plasticity in the invasive herb Solidago canadensis in China.

Phenotypic plasticity is thought to be important for plants in variable environments. The climatic variability hypothesis poses that populations at higher latitudes, due to the stronger variation in temperature, there should be more plastic in response to temperature than populations at lower latitudes. Similarly, populations at locations with stronger precipitation fluctuations should be more plastic in response to water availability than populations at locations with less variable precipitation. We sampled seven and nine populations of Solidago canadensis, a North American native that is invasive in China, along a latitudinal (temperature variability) and a longitudinal (precipitation variability) gradient, respectively, in China, and grew them under two temperature treatments and two water-availability treatments, respectively. Among the four traits with significant variation in plasticity among populations in response to temperature, plasticity of leaf length-to-width ratio was significantly positively correlated with latitude and temperature seasonality of the populations. In addition, root/shoot ratio and water-use efficiency showed significant variation in plasticity among populations in response to water availability, and plasticities of these two traits were significantly negatively correlated with longitude and positively correlated with precipitation seasonality. The observed geographic clines in plasticity suggest that phenotypic plasticity of S. canadensis may have evolved rapidly in regions with different climatic conditions, and this may have contributed to the spread of this invasive species.

Low doses of CMV induce autoimmune-mediated and inflammatory responses in bile duct epithelia of regulatory T cell-depleted neonatal mice.

Recent studies have indicated that perinatal infection with cytomegalovirus (CMV) may promote bile duct damage in biliary atresia (BA) and that the decreased regulatory T cell (Treg) percentage associated with BA may further amplify the bile duct damage. Although a majority of BA patients have had previous CMV infections and lower percentages of Tregs, it is unknown whether an initial exposure to a low dose of CMV could induce exaggerated and progressive biliary injury. A Treg-depleted neonatal mouse was infected with low-dose CMV (LD-CMV) as a model to study BA patients. LD-CMV infection in Treg-depleted mice induced extensive inflammation in both the intrahepatic and extrahepatic bile ducts, accompanied with injury to and atresia of intrahepatic bile ducts and partial obstruction of the extrahepatic bile ducts. Serum total and direct bilirubin amounts were also elevated. Evidence for the involvement of cellular and humoral autoimmune responses in LD-CMV-infection of Treg-depleted mice was also obtained through detection of increased percentages of CD3 and CD8 mononuclear cells and serum autoantibodies reactive to bile duct epithelial proteins, one of which was identified as α-enolase. Depletion of Tregs that can lead to the decreased inhibition of aberrantly activated hepatic T-lymphocytes and generation of autoantibodies may lead to further injury. Increased hepatic expression of Th1-related genes (TNF-α), IFN-γ-activated genes (STAT-1) and Th1 cytokines (TNF-α, lymphotactin, IL-12p40 and MIP -1γ) were also identified. In conclusion, autoimmune-mediated and inflammatory responses induced by LD-CMV infection in Treg-depleted mice results in increased intrahepatic and extrahepatic bile duct injury and contributed to disease progression.

Comparison of Endobronchial Ultrasound-Guided Fine Needle Aspiration and Video-Assisted Mediastinoscopy for Mediastinal Staging of Lung Cancer.

Video-assisted mediastinoscopy (VAM) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are the two most commonly used invasive methods for mediastinal staging of lung cancer. The objective of this review is to assess and compare the overall diagnostic values of VAM and EBUS-TBNA. PubMed, Embase, Web of Science and the Cochrane Library were searched for studies that evaluated EBUS-TBNA or VAM accuracy. Quantitative meta-analysis was used to pool sensitivity and specificity, and study quality was evaluated. Meta-regression was applied to indirectly compare EBUS-TBNA and VAM after adjusting quality score, study design, and station number. A total of ten studies with 999 EBUS-TBNA patients and seven studies with 915 VAM patients were included. Since the pooled specificity was 100% for both modalities, sensitivity was mainly analyzed. The pooled sensitivities for EBUS-TBNA and VAM were 0.84 (95% CI 0.79-0.88) and 0.86 (95% CI 0.82-0.90), respectively. Subgroup analyses of quality score, study design, station number and rapid on-site cytologic evaluation showed no significant influence on the overall sensitivity of the two modalities. After adjusting quality score, study design, and station number, the pooled sensitivities of VAM and EBUS-TBNA were not significantly different. However, more procedural complications and fewer false negatives (FN) were found with VAM than EBUS-TBNA. VAM and EBUS exhibited equally high diagnostic accuracy for mediastinal staging of lung cancer. Due to lower morbidity with EBUS-TBNA and fewer FN with VAM, EBUS-TBNA should be performed first, followed by VAM in the case of a negative needle result.

In Vivo Molecular MRI Imaging of Prostate Cancer by Targeting PSMA with Polypeptide-Labeled Superparamagnetic Iron Oxide Nanoparticles.

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.