Visible-Light-Promoted Radical Cascade Cyclization of 2-Vinyl Benzimidazoles: Access to Benzo[4,5]imidazo[1,2-b]isoquinolin- 11(6H)-ones.

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

Head-to-head comparison of perfluorobutane contrast-enhanced US and multiparametric MRI for breast cancer: a prospective, multicenter study.

BACKGROUND: Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency. PATIENTS AND METHODS: This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions. RESULTS: In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online. CONCLUSIONS: PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

The Chromosome-Level Genome Assembly of Bean Blossom Thrips (Megalurothrips usitatus) Reveals an Expansion of Protein Digestion-Related Genes in Adaption to High-Protein Host Plants.

Megalurothrips usitatus (Bagnall) is a destructive pest of legumes, such as cowpea. The biology, population dynamics and control strategies of this pest have been well studied. However, the lack of a high-quality reference genome for M. usitatus has hindered the understanding of key biological questions, such as the mechanism of adaptation to feed preferentially on high-protein host plants and the resistance to proteinase inhibitors (PIs). In this study, we generated a high-resolution chromosome-level reference genome assembly (247.82 Mb, 16 chromosomes) of M. usitatus by combining Oxford Nanopore Technologies (ONT) and Hi-C sequencing. The genome assembly showed higher proportions of GC and repeat content compared to other Thripinae species. Genome annotation revealed 18,624 protein-coding genes, including 4613 paralogs that were preferentially located in TE-rich regions. GO and KEGG enrichment analyses of the paralogs revealed significant enrichment in digestion-related genes. Genome-wide identification uncovered 506 putative digestion-related enzymes; of those, proteases, especially their subgroup serine proteases (SPs), are significantly enriched in paralogs. We hypothesized that the diversity and expansion of the digestion-related genes, especially SPs, could be driven by mobile elements (TEs), which promote the adaptive evolution of M. usitatus to high-protein host plants with high serine protease inhibitors (SPIs). The current study provides a valuable genomic resource for understanding the genetic variation among different pest species adapting to different plant hosts.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

Singlet Fission Dynamics in Tetracene Single Crystals Probed by Polarization-Dependent Two-Dimensional Electronic Spectroscopy.

The exact mechanism of endothermic singlet fission in crystalline polyacene remains to be clarified. It has been elusive whether the excess energy of vibrational hot states and the upper branch of Davydov splitting is important for the energy compensation. Here, we probe the excited-state specified singlet fission dynamics in tetracene single crystals by polarization-dependent two-dimensional electronic spectroscopy (2DES). While a major spectral transfer with a characteristic lifetime of 86 ps is observed to be largely independent of the excitation energy due to formation of the spatially separated triplet pairs (1(T···T)), the excitation-energy dependent subpicosecond dynamics show marked differences for different states probed, implying the possible involvement of a coherently formed triplet pair state (1(TT)). Analysis of coherent vibrational modes suggests the coupling to high energy modes may offset the energy difference between singlet and triplet pair states. Moreover, the beating map of the low frequency mode indicates a vibrational hot state violating the aggregation behavior of Davydov exciton, which can be explained as a resonance of the 1(TT) state. These results suggest that the coherent vibronic mixing between local excitation and triplet pair states is essential for the singlet fission dynamics in molecule aggregates.

Multi-feature Fusion Network on Gray Scale Ultrasonography: Effective Differentiation of Adenolymphoma and Pleomorphic Adenoma.

RATIONALE AND OBJECTIVES: to develop a deep learning radiomics graph network (DLRN) that integrates deep learning features extracted from gray scale ultrasonography, radiomics features and clinical features, for distinguishing parotid pleomorphic adenoma (PA) from adenolymphoma (AL) MATERIALS AND METHODS: A total of 287 patients (162 in training cohort, 70 in internal validation cohort and 55 in external validation cohort) from two centers with histologically confirmed PA or AL were enrolled. Deep transfer learning features and radiomics features extracted from gray scale ultrasound images were input to machine learning classifiers including logistic regression (LR), support vector machines (SVM), KNN, RandomForest (RF), ExtraTrees, XGBoost, LightGBM, and MLP to construct deep transfer learning radiomics (DTL) models and Rad models respectively. Deep learning radiomics (DLR) models were constructed by integrating the two features and DLR signatures were generated. Clinical features were further combined with the signatures to develop a DLRN model. The performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis, calibration, decision curve analysis (DCA), and the Hosmer-Lemeshow test. RESULTS: In the internal validation cohort and external validation cohort, comparing to Clinic (AUC=0.767 and 0.777), Rad (AUC=0.841 and 0.748), DTL (AUC=0.740 and 0.825) and DLR (AUC=0.863 and 0.859), the DLRN model showed greatest discriminatory ability (AUC=0.908 and 0.908) showed optimal discriminatory ability. CONCLUSION: The DLRN model built based on gray scale ultrasonography significantly improved the diagnostic performance for benign salivary gland tumors. It can provide clinicians with a non-invasive and accurate diagnostic approach, which holds important clinical significance and value. Ensemble of multiple models helped alleviate overfitting on the small dataset compared to using Resnet50 alone.

Sevelamer reverses liver fibrosis by deactivation of hepatic stellate cells.

Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.

EEG-based Objective Quality Assessment of Interrupted Speech.

As an important dimension of speech degradation, interruption destroys the acoustic waveform information of a speech signal and seriously affects the quality rating in speech perception. Existing studies assessing the quality of interrupted speech mainly focus on subjective methods. This work used event-related potentials (ERPs) to objectively investigate the effects of two interruption factors (i.e., interruption duty cycle and interruption rate) on the perceived quality of the periodically interrupted speech. An oddball-paradigm based ERP experiment was designed, and the periodically interrupted stimuli were presented to participants in the ERP experiment. Meanwhile, participants were instructed to provide their subjective quality ratings of interrupted speech under the same interruption conditions. The experimental results showed that the degree of both interruption duty cycle and interruption rate affected the peak latency of mismatch negativity (MMN) of the collected ERP response, with a smaller MMN peak latency under conditions with a smaller interruption duty cycle or a larger interruption rate. These findings are largely consistent with the subjective quality rating results, suggesting that the peak latency of MMN response can be potentially used as an objective quality indicator of the periodically interrupted speech.

Analysis of ecological quality changes and influencing factors in Xiangjiang River Basin.

The Xiangjiang River Basin is an important part of the Yangtze River Basin and an important area in Hunan Province. Thus, taking steps to protect the ecological sustainability of the Xiangjiang River Basin, such as the construction of the protection of ecological security in Hunan Province and the Yangtze River Protection Law, is important for national projects However, research on the ecological quality of the Xiangjiang River Basin is mostly biased toward the evaluation of ecosystem services or an individual ecological index. Furthermore, a long-term evaluation of multiple indicators is lacking. Therefore, based on Google Earth Engine and geographic detectors, the remote sensing ecological index was used to evaluate this area. The year-by-year research on the Xiangjiang River Basin from 2001 to 2020 clarified its past ecological quality change trend, explored the reasons for the ecological quality change, and provided a basis for protecting its ecological quality. The following results are presented. (1) Regarding spatial distribution, areas with poor ecological environments are mainly distributed at the centers of Chang-Zhu-Tan, Hengyang, and various districts and counties. (2) Regarding the time variation, the ecological quality of the Xiangjiang River Basin from 2001 to 2020 showed a slight downward trend, with a downward slope of approximately - 0.0000357143; a rapid increase, with a growth rate of approximately 0.00395; And an overall improvement over 20 years. The areas with declining ecological quality are mainly located in the Chang-Zhu-Tan urban agglomeration, the city center of Hengyang, and the county centers of various county towns. (3) The factor detection results show that human factors play a key role in population density and land use, with average q values of 0.429 and 0.353, respectively. Among natural factors, elevation and slope play a key role, with average q values of 0.230 and 0.351, respectively; hence, Land use directly affect on the ecological quality in a location. These findings will provide important information for managers to formulate ecological restoration measures for the Xiangjiang River.

Chromosome-level genome assembly of the flower thrips Frankliniella intonsa.

As an economically important insect pest, the flower thrips Frankliniella intonsa (Trybom) causes great damage to host plants by directly feeding and indirectly transmitting various pathogenic viruses. The lack of a well-assembled genomic resource has hindered our understanding of the genetic basis and evolution of F. intonsa. In this study, we used Oxford Nanopore Technology (ONT) long reads and High-through chromosome conformation capture (Hi-C) linked reads to construct a high-quality reference genome assembly of F. intonsa, with a total size of 225.5 Mb and a contig N50 of 3.37 Mb. By performing the Hi-C analysis, we anchored 91.68% of the contigs into 15 pseudochromosomes. Genomic annotation uncovered 17,581 protein-coding genes and identified 20.09% of the sequences as repeat elements. BUSCO analysis estimated over 98% of genome completeness. Our study is at the first time to report the chromosome-scale genome for the species of the genus Frankliniella. It provides a valuable genomic resource for further biological research and pest management of the thrips.

Radiomic nomogram for discriminating parotid pleomorphic adenoma from parotid adenolymphoma based on grayscale ultrasonography.

Objectives: To differentiate parotid pleomorphic adenoma (PA) from adenolymphoma (AL) using radiomics of grayscale ultrasonography in combination with clinical features. Methods: This retrospective study aimed to analyze the clinical and radiographic characteristics of 162 cases from December 2019 to March 2023. The study population consisted of a training cohort of 113 patients and a validation cohort of 49 patients. Grayscale ultrasonography was processed using ITP-Snap software and Python to delineate regions of interest (ROIs) and extract radiomic features. Univariate analysis, Spearman's correlation, greedy recursive elimination strategy, and least absolute shrinkage and selection operator (LASSO) correlation were employed to select relevant radiographic features. Subsequently, eight machine learning methods (LR, SVM, KNN, RandomForest, ExtraTrees, XGBoost, LightGBM, and MLP) were employed to build a quantitative radiomic model using the selected features. A radiomic nomogram was developed through the utilization of multivariate logistic regression analysis, integrating both clinical and radiomic data. The accuracy of the nomogram was assessed using receiver operating characteristic (ROC) curve analysis, calibration, decision curve analysis (DCA), and the Hosmer-Lemeshow test. Results: To differentiate PA from AL, the radiomic model using SVM showed optimal discriminatory ability (accuracy = 0.929 and 0.857, sensitivity = 0.946 and 0.800, specificity = 0.921 and 0.897, positive predictive value = 0.854 and 0.842, and negative predictive value = 0.972 and 0.867 in the training and validation cohorts, respectively). A nomogram incorporating rad-Signature and clinical features achieved an area under the ROC curve (AUC) of 0.983 (95% confidence interval [CI]: 0.965-1) and 0.910 (95% CI: 0.830-0.990) in the training and validation cohorts, respectively. Decision curve analysis showed that the nomogram and radiomic model outperformed the clinical-factor model in terms of clinical usefulness. Conclusion: A nomogram based on grayscale ultrasonic radiomics and clinical features served as a non-invasive tool capable of differentiating PA and AL.

Ultrasonographic misdiagnosis of multicystic mesothelioma of the omentum: A case report.

RATIONALE: Multicystic Mesothelioma (MM) is very rare and preoperative diagnosis is difficult. PATIENT CONCERNS: We report a case of a 34-year-old man with solid abdominal cystic echo mass. Physical examination showed that the patient had a flat and soft abdomen without tenderness or rebound pain, no fluid wave tremor, and no obvious abdominal mass was touched. The patient complained of repeated abdominal distention with nausea for 5 days. Sonographic examination suspected pseudomyxoma peritoneum. DIAGNOSIS: Conventional ultrasound examination showed a cystic solid echo mass in the right abdominal cavity of the patient, with uneven internal echo and honeycomb change, and clear boundary with surrounding organs. Color Doppler suggested that the blood flow in the mass was not obvious. Contrast-enhanced computed tomography of the abdomen revealed hypodensity foci in hepatic and renal crypts and right paracolic sulcus. INTERVENTIONS: Laparoscopic resection of the mass was performed, and the postoperative pathological findings were polycystic mesothelioma (greater omentum). OUTCOMES: After mass resection, all laboratory tests and abdominal ultrasound were normal, and abdominal distension and nausea disappeared. LESSONS: Improved ultrasound diagnosis of MM is useful for clinical decision-making.

The Relationship Between Cancer and Functional and Structural Markers of Subclinical Atherosclerosis: A Systematic Review and Meta-Analysis.

Objectives: The relationship between cancer and subclinical atherosclerosis has always been the focus of people's attention. We conducted a systematic review and meta-analysis by evaluating the effects of cancer on functional and structural markers of subclinical atherosclerosis:intima-media thickness (IMT), pulse wave velocity (PWV), and flow-mediated vasodilation (FMD). Methods: A comprehensive and systematic literature search was conducted on the internet. Sensitivity analysis, publication bias, standard mean difference (SMD), corresponding 95% confidence interval (95% CI), and subgroup analysis were performed for all relevant research indicators in the retrieved literature. Results: Forty-six studies were included, including 3,729 cancer patients and 2,404 healthy controls. Cancer patients had significantly thicker IMT [SMD (95%CI) = 0.290 (0.069 to 0.511), P = 0.010] and higher PWV [SMD (95%CI) = 0.392 (0.136 to 0.647), P = 0.003] compared with healthy controls. There was no significant difference in FMD [SMD (95% CI) = -0.192 (-0.527 to 0.144), P > 0.05). After subgrouping by age, male proportion, and treatment, the analysis results of IMT ≥ 50 years old, PWV and FMD < 50 years old, male proportion ≥50%, chemotherapy group, IMT and PWV radiotherapy group, and PWV endocrine therapy group were statistically significant (P < 0.05). There were no significant differences in other subgroup analyses, overall sensitivity analysis, and publication bias (p < 0.05). Conclusions: Cancer may promote subclinical atherosclerosis, and change the functional and structural markers of subclinical atherosclerosis such as IMT and PWV. Early intervention and prevention should be pursued.

Intersystem Crossing in Acceptor-Donor-Acceptor Type Organic Photovoltaic Molecules Promoted by Symmetry Breaking in Polar Environments.

The intramolecular electron push-pulling effect has been widely applied to manipulate the excited states in organic photovoltaic (OPV) molecules toward efficient photocurrent generation in working devices with bias fields. However, the effect of field induced polar environments on the excited-state dynamics remains largely unexplored. Here, we investigate the polar environment effect on excited dynamics in acceptor-donor-acceptor type OPV molecules dissolved in solvents with different polarities. By combining ultrafast transient absorption spectroscopy and quantum chemical computation, we observe the stabilization of excited states induced by symmetry breaking in the polar solvent in the molecules exhibiting strong electron push-pulling effects. The stabilized excited states undergo faster intersystem crossing processes with reduced singlet-triplet energy gaps. The findings suggest that the dynamics of charge generation and recombination may be controlled by manipulating the polar environment and electron push-pulling effect to improve the device performance.

Two new species of the genus Criotettix Bolivar (Orthoptera: Tetrigoidea: Scelimenidae) from Zhejiang, China.

Two new species of the genus are described from Zhejiang, China in this paper. The new species Criotettix jinningensis sp. nov. is similar to Criotettix strivertexoides Zheng, Wei Li, 2009, but differs in width of vertex narrower than diameter of eye; pronotum shorter, not reaching the end of hind tibiae; width of fore wing 1.3 times width of mid leg femur and hind wing not reaching the end of pronotum. The new species Criotettix pananensis sp. nov. is similar to Criotettix transpi-noides Zheng, Bai Xu, 2012, it differs from latter by width of vertex narrower than diameter of eye; pronotum with parallel lateral keels and without a pair short longitudinal keels between shoulders; hind femur without projection in upper keel and hind wing extending over the end of pronotum. The type specimens are deposited in the College of Life Sciences, Hebei University, Baoding, China.

A Speech-Level-Based Segmented Model to Decode the Dynamic Auditory Attention States in the Competing Speaker Scenes.

In the competing speaker environments, human listeners need to focus or switch their auditory attention according to dynamic intentions. The reliable cortical tracking ability to the speech envelope is an effective feature for decoding the target speech from the neural signals. Moreover, previous studies revealed that the root mean square (RMS)-level-based speech segmentation made a great contribution to the target speech perception with the modulation of sustained auditory attention. This study further investigated the effect of the RMS-level-based speech segmentation on the auditory attention decoding (AAD) performance with both sustained and switched attention in the competing speaker auditory scenes. Objective biomarkers derived from the cortical activities were also developed to index the dynamic auditory attention states. In the current study, subjects were asked to concentrate or switch their attention between two competing speaker streams. The neural responses to the higher- and lower-RMS-level speech segments were analyzed via the linear temporal response function (TRF) before and after the attention switching from one to the other speaker stream. Furthermore, the AAD performance decoded by the unified TRF decoding model was compared to that by the speech-RMS-level-based segmented decoding model with the dynamic change of the auditory attention states. The results showed that the weight of the typical TRF component approximately 100-ms time lag was sensitive to the switching of the auditory attention. Compared to the unified AAD model, the segmented AAD model improved attention decoding performance under both the sustained and switched auditory attention modulations in a wide range of signal-to-masker ratios (SMRs). In the competing speaker scenes, the TRF weight and AAD accuracy could be used as effective indicators to detect the changes of the auditory attention. In addition, with a wide range of SMRs (i.e., from 6 to -6 dB in this study), the segmented AAD model showed the robust decoding performance even with short decision window length, suggesting that this speech-RMS-level-based model has the potential to decode dynamic attention states in the realistic auditory scenarios.

Ultrasound-Guided Percutaneous Ethanol-Paclitaxel Combined Therapy for Rabbit VX2 Liver Tumors.

BACKGROUND: It is difficult to achieve whole tumor ablation using percutaneous ethanol ablation therapy (PEAT) due to the limited diffusion of ethanol. PURPOSE: To determine whether chemotherapy can be an adjuvant therapy to benefit PEAT, we investigated ultrasound-guided percutaneous ethanol-paclitaxel combined therapy (PEPCT) of VX2 carcinoma, a rabbit liver cancer model. MATERIALS AND METHODS: A six-arm study was designed to quantify the correlation between paclitaxel (PTX) dose and tumor necrosis or cell proliferation, including sham group (2 mL saline, n=6), incremented dose of PTX (0, 12.5, 25, 37.5 mg) in 2.0 mL ethanol (n=6) and a conventional PEAT group (n=6) as comparison. The test was followed by contrast-enhanced ultrasonic (CEUS) before 7-day sacrifice, tumor harvest, and sectioning. Tumor necrosis ratio was radiologically and histologically quantified; modified proliferation index (m-PI) was proposed to quantify the PTX's pharmacological effects. A linear regression model was set to correlate the PTX dose with tumor necrosis ratio or cell proliferation index. The difference of radiological, histological necrosis ratio (HNR) and modified PI in six groups was analyzed via Kruskal-Wallis H-test, Welch analysis of variance and one-way ANOVA. RESULTS: Incremental increases of PTX (0, 12.5, 25, 37.5 mg) correlated with greater fraction of tumor necrosis (R2 = 0.946, P<0.001 for radiological necrosis ratio [RNR], R2 = 0.843, P<0.001 forHNR), indicating that one week after procedure PTX's anti-proliferation and ethanol's dehydration co-induced severe tumor necrosis. Correlation analysis further testified a significant association between PTX dose and m-PI (R2 = 0.860, P<0.001). CONCLUSION: These results suggest a clear role for PTX-induced cytotoxicity and support the use of chemotherapeutic drugs in ablation therapy.

The transcription factor of the Hippo signaling pathway, LmSd, regulates wing development in Locusta migratoria.

Scalloped (Sd) is transcription factor that regulates cell proliferation and organ growth in the Hippo pathway. In the present research, LmSd was identified and characterized, and found to encode an N-terminal TEA domain and a C-terminal YBD domain. qRT-PCR showed that the LmSd transcription level was highest in the fifth-instar nymphs and very little was expressed in embryos. Tissue-specific analyses showed that LmSd was highly expressed in the wing. Immunohistochemistry indicated that LmSd was highly abundant in the head, prothorax, and legs during embryonic development. LmSd dsRNA injection resulted in significantly down-regulated transcription and protein expression levels compared with dsGFP injection. Gene silencing of LmSd resulted in deformed wings that were curved, wrinkled, and failed to fully expand. Approximately 40% of the nymphs had wing pads that were not able to close normally during molting from fifth-instar nymphs into adults. After silencing of LmSd, the transcription levels of cell division genes were suppressed and the expression levels of apoptosis genes were significantly up-regulated. Our results reveal that LmSd plays an important role in wing formation and development by controlling cell proliferation and inhibiting apoptosis.

S100A8 and S100A9 promote endothelial cell activation through the RAGE­mediated mammalian target of rapamycin complex 2 pathway.

S100 calcium binding protein A8 (S100A8) and A9 (S100A9) belong to the S100 family of calcium­binding proteins and have important roles in inflammation. They increase endothelial cell proliferation, thereby affecting inflammation, angiogenesis and tumorigenesis. However, the mechanism of action of S100A8/9 in endothelial cells needs further study. Therefore, the present study sought to investigate the effects of S100A8/9 on the proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) and their mechanism of action. The viability of HUVECs was determined through a Cell Counting Kit­8 assay. The effect of S100A8/9 on the proliferation of HUVECs was detected by flow cytometry. Migration was evaluated by a Transwell migration assay. Apoptosis was evaluated by Annexin V­FITC and PI staining via flow cytometry. Western blot analysis and reverse transcription­quantitative polymerase chain reaction assays were performed to evaluate the activation of the phosphatidylinositol 3­phosphate kinase (PI3K)/Akt/mTOR pathway and mTOR complex 2 (mTORC2). We previously confirmed that S100A8/9 were consistently overexpressed at 1 and 7 days post­surgery in a rabbit vein graft model, which is the period when apoptosis changes to proliferation in neointimal hyperplasia. In the present study, proliferation, viability and migration were increased after treating HUVECs with S100A8/9. S100A8/9 stimulated the PI3K/Akt/mTOR pathway and mTORC2, which was significantly suppressed by a receptor for advanced glycation end products (RAGE)­blocking antibody. Furthermore, depleting expression of RAGE or mTORC2 protein components (rapamycin­insensitive companion of mTOR) by small interfering RNA was found to reduce the cell viability, migration and angiogenesis of S100A8/9­treated HUVECs. The development of neointimal hyperplasia is a complex process initiated by damage to endothelial cells. In conclusion, S100A8/9 has an important role in intimal hyperplasia by promoting cell growth and angiogenesis via RAGE signaling and activation of mTORC2.

Nanosized drug-eluting bead for transcatheter arterial chemoembolization (ND-TACE).

Commercially available drug-eluting embolization beads (100-500 µm) reduced the occurrence of adverse events related to an anticancer drug, but were unascertained to remarkably benefit the transcatheter arterial chemoembolization (TACE) treatment of intermediate-stage liver cancer. Dextran-coated arsenite nanoparticles with the size ranging from 400 to 600 nm were developed as a nanosized drug-eluting bead (NDEB) for chemoembolization therapy of the rabbit VX2 liver tumor. We fully characterized their relevant physicochemistry and drug release properties. Their hemolysis was investigated before vessel embolization. The introduction of the NDEB allowed continuous embolization of tumor feeding vessels and sustained release of arsenic trioxide, thereby causing severe tumor necrosis and reduced vascularity. Sonography including B mode ultrasound, color Doppler flow imaging (CDFI) and dynamic contrast-enhanced ultrasound (CEUS) were performed to evaluate the tumor vascularity and viability. Additionally, its hepatotoxicity was tolerable at a medium dose. NDEB-TACE might be an effective therapeutic strategy for interventional therapy.