DeepBindBC: A practical deep learning method for identifying native-like protein-ligand complexes in virtual screening.

Identifying native-like protein-ligand complexes (PLCs) from an abundance of docking decoys is critical for large-scale virtual drug screening in early-stage drug discovery lead searching efforts. Providing reliable prediction is still a challenge for most current affinity predicting models because of a lack of non-binding data during model training, lost critical physical-chemical features, and difficulties in learning abstract information with limited neural layers. In this work, we proposed a deep learning model, DeepBindBC, for classifying putative ligands as binding or non-binding. Our model incorporates information on non-binding interactions, making it more suitable for real applications. ResNet model architecture and more detailed atom type representation guarantee implicit features can be learned more accurately. Here, we show that DeepBindBC outperforms Autodock Vina, Pafnucy, and DLSCORE for three DUD.E testing sets. Moreover, DeepBindBC identified a novel human pancreatic α-amylase binder validated by a fluorescence spectral experiment (Ka = 1.0 × 105 M). Furthermore, DeepBindBC can be used as a core component of a hybrid virtual screening pipeline that incorporating many other complementary methods, such as DFCNN, Autodock Vina docking, and pocket molecular dynamics simulation. Additionally, an online web server based on the model is available at http://cbblab.siat.ac.cn/DeepBindBC/index.php for the user's convenience. Our model and the web server provide alternative tools in the early steps of drug discovery by providing accurate identification of native-like PLCs.

Downregulation of hsa-miR-135b-5p Inhibits Cell Proliferation, Migration, and Invasion in Colon Adenocarcinoma.

Colon cancer is the most common malignant tumor of the gastrointestinal tract, and approximately 80%-90% of colon cancers are colon adenocarcinomas (COADs). This study aimed to screen key microRNAs (miRNAs) associated with COAD. Differentially expressed (DE) miRNAs were screened between COAD and adjacent cancer samples based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas obtained from datasets. The miRNAs of interest were validated using quantitative real-time polymerase chain reaction. Moreover, the effects of hsa-miR-135b-5p on the biological behavior of COAD cells were observed. To obtain the target genes of hsa-miR-135b-5p, transcriptome sequencing of the SW480 cells was performed, followed by protein-protein interaction (PPI) network and hsa-miR-135b-5p-target gene regulatory network construction and prognostic analysis. Downregulation of hsa-miR-135b-5p significantly inhibited SW480 cell proliferation, migration, and invasion and significantly facilitated apoptosis (P < 0.05). A total of 3384 DEmRNAs were screened, and enrichment analysis showed that the upregulated mRNAs were enriched in 25 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 326 Gene Ontology Biological Processes (GO-BPs) while the downregulated mRNAs were enriched in 20 KEGG pathways and 276 GO-BPs. A PPI network was then constructed, and H2BC14, H2BC3, and H4C11 had a higher degree. In addition, a total of 352 hsa-miR-135b-5p-gene regulatory relationships were identified. Prognostic analysis showed that FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B had prognostic significance (P < 0.05). In addition, the validation analysis results showed that FOXN2, NSA2, and DESI1 were significantly expressed between the miR-135b-5p-inhibitor and negative control groups (P < 0.05). Therefore, downregulation of hsa-miR-135b-5p inhibits cell proliferation, migration, and invasion in COAD, and carcinogenesis may function by targeting FOXN2, NSA2, MYCBP, DIRAS2, DESI1, and RAB33B.

A novel machine learning based approach for iPS progenitor cell identification.

Identification of induced pluripotent stem (iPS) progenitor cells, the iPS forming cells in early stage of reprogramming, could provide valuable information for studying the origin and underlying mechanism of iPS cells. However, it is very difficult to identify experimentally since there are no biomarkers known for early progenitor cells, and only about 6 days after reprogramming initiation, iPS cells can be experimentally determined via fluorescent probes. What is more, the ratio of progenitor cells during early reprograming period is below 5%, which is too low to capture experimentally in the early stage. In this paper, we propose a novel computational approach for the identification of iPS progenitor cells based on machine learning and microscopic image analysis. Firstly, we record the reprogramming process using a live cell imaging system after 48 hours of infection with retroviruses expressing Oct4, Sox2 and Klf4, later iPS progenitor cells and normal murine embryonic fibroblasts (MEFs) within 3 to 5 days after infection are labeled by retrospectively tracing the time-lapse microscopic image. We then calculate 11 types of cell morphological and motion features such as area, speed, etc., and select best time windows for modeling and perform feature selection. Finally, a prediction model using XGBoost is built based on the selected six types of features and best time windows. Our model allows several missing values/frames in the sample datasets, thus it is applicable to a wide range of scenarios. Cross-validation, holdout validation and independent test experiments show that the minimum precision is above 52%, that is, the ratio of predicted progenitor cells within 3 to 5 days after viral infection is above 52%. The results also confirm that the morphology and motion pattern of iPS progenitor cells is different from that of normal MEFs, which helps with the machine learning methods for iPS progenitor cell identification.

DJ-1 alleviates anoxia and hypoglycemia injury in cardiac microvascular via AKT and GSH.

Cardiac microvascular damage, which is often caused by anoxia and hypoglycemia, is associated with the development of cardiac injury. DJ-1 encodes a peptidase C56 protein family related protein, is has been linked to oxidative stress in various cells such as neurons, COPD epithelial cells, and macrophages. However, the effect of DJ-1 towards oxidative stress caused by anoxia and hypoglycemia of cardiac microvascular endothelial cells (CMEC) remains unclear. In this study, we investigated the role and underlying molecular mechanism of DJ-1 in CMEC with anoxia/hypoglycemic (A/H) injury. We found that the mRNA and the protein expression of DJ-1 in CMEC with A/H injury were significantly downregulated. DJ-1 overexpression by pcDNA.3.1-DJ-1 transfection elevated cell viability while it inhibited LDH leakage, cell apoptosis, caspase-3 activity, ROS level, and MDA contents, while knockdown of DJ-1 has the opposite results. In addition, tube formation was increased in DJ-1 overexpression, while it was decreased in DJ-1 knockdown CMEC with A/H injury. In addition, our results indicated that DJ-1 can regulate glutathione (GSH) levels by modulating AKT activity in CMEC with A/H injury. The downregulation of AKT and GSH may remove the protective role of DJ-1 against A/H injury in CMEC. Taken together, this study showed that DJ-1 upregulation protected CMEC against A/H injury via the AKT/GSH signaling pathway.

In utero and postnatal exposure to environmental tobacco smoke, blood pressure, and hypertension in children: the Seven Northeastern Cities study.

To evaluate the association of environmental tobacco smoke (ETS) exposure with hypertension and blood pressure (BP) in children, a sample of 9,354 children, aged 5-17 years, was studied from seven northeastern cities of China in 2012-2013. The results showesd that significant associations were observed for hypertension with ETS exposure in utero [odds ratio (OR) 1.36, 95% confidence interval (CI) 1.18-1.57], with current major ETS exposure from fathers (1.38, 1.21-1.57) or anyone (1.26, 1.12-1.42), and with intensity of ETS exposure greater than 1 cigarette per day (ORs ranged from 1.20 to 1.35). For SBP, significant associations were only observed in children with major ETS exposure from father and with cigarettes smoking >10/day. When stratified by sex, more significant associations were found in girls than in boys. In conclusion, prenatal and postnatal ETS exposure was significantly associated with increased odds of hypertension in children, especially in girls.

MyD88 overexpression deteriorates Ang-II-induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum of rats.

INTRODUCTION: Erectile dysfunction (ED) is a common sexual problem for men and the exploration of its treatment is still in mire demand. We aim to investigate the role of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the pathogenesis of angiotensin II (Ang-II) induced ED. METHODS: Male Sprague-Dawlay rats were treated with Ang-II and intracavernous pressure (ICP) was measured to confirm the occurrence of ED. The corpus cavernosum penises of rats were transfected with plasmids to overexpressed MyD88. Inflammatory and vascular parameters including myeloperoxidase (MPO), cyclooxygenase2 (COX2), endothelial nitric oxide synthase (eNOS), malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), and cytokines in treated and untreated ED rats were measured. Flow cytometry was used to determine the apoptosis of endothelial cells of corpus cavernosum penises of rats. RESULTS: Ang-II-induced ED rats were found to contain upregulated TLR4, MyD88, MPO, and COX2, and downregulated eNOS. MyD88 overexpression deteriorates cavernous structural damage, reduces ICP and ICP/MAP values and reverses the therapeutic effect of anti-TLR4 antibodies in rats with Ang-II-induced ED. Moreover, overexpression of MyD88 further upregulated MPO and COX2, downregulated eNOS, promoted oxidative stress, inflammation, and cell apoptosis rate via positively regulating the TLR4/MyD88 signaling pathway, while anti-TLR4 antibodies downregulated MPO and COX2, upregulated eNOS, suppressed oxidative stress, inflammation, and cell apoptosis rate via inactivating the TLR4/MyD88 signaling pathway in the rat corpus cavernosum penises. Furthermore, MyD88 overexpression promotes oxidative stress and inflammation and reverses the effect of anti-TLR4 antibodies in the penis of ED rats. CONCLUSION: MyD88 overexpression deteriorates Ang-II-induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum rats.

Unambiguous Identification of Carbon Location on the N Site in Semi-insulating GaN.

Carbon (C) doping is essential for producing semi-insulating GaN for power electronics. However, to date the nature of C doped GaN, especially the lattice site occupation, is not yet well understood. In this work, we clarify the lattice site of C in GaN using polarized Fourier-transform infrared and Raman spectroscopies, in combination with first-principles calculations. Two local vibrational modes (LVMs) at 766 and 774 cm^{-1} in C doped GaN are observed. The 766 cm^{-1} mode is assigned to the nondegenerate A_{1} mode vibrating along the c axis, whereas the 774 cm^{-1} mode is ascribed to the doubly degenerate E mode confined in the plane perpendicular to the c axis. The two LVMs are identified to originate from isolated C_{N}^{-} with local C_{3v} symmetry. Experimental data and calculations are in outstanding agreement both for the positions and the intensity ratios of the LVMs. We thus provide unambiguous evidence of the substitutional C atoms occupying the N site with a -1 charge state in GaN and therefore bring essential information to a long-standing controversy.

The predicted target gene validation, function, and prognosis studies of miRNA-22 in colorectal cancer tissue.

MicroRNAs are known as small, non-coding, and single-stranded RNAs which can regulate cell proliferation, differentiation, and apoptosis and involve in the development of tumors. In this study, colorectal cancer tissue morphological change in different prognosis in patients was observed by hematoxylin and eosin staining. Thereafter, differentially expressed miR-22 and TIAM1 gene were detected using quantitative polymerase chain reaction and western blot in different colorectal cancer tissues. Meanwhile, luciferase reporter gene system was used to verify the relationship between miR-22 and TIAM1. Eventually, the survival curve was plotted according to follow-up records of patients with colorectal cancer and the expression levels of miR-22 and TIAM1 in different tumor tissues. The hematoxylin and eosin results showed the poor pathological features in the 1-year survival group. The expression level of miR-22 was upregulated and TIAM1 was inhibited, correlating with the extension of patients' survival time. Our results indicated that miR-22 and TIAM1 might play a regulatory role in the occurrence and development of colorectal cancer which were consistent with the survival curve analysis results. Furthermore, the luciferase in miR-22 co-transfected with pmiR-RB-REPORT- TIAM1 group was significantly lower than pmiR-RB-REPORT- TIAM1-mut and Si groups. Collectively, these data suggest that miR-22 may suppress the expression of its target gene TIAM1. The low miR-22 level or the high TIAM1 level will indicate the poor prognosis in colorectal cancer patients.

Gypenoside Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting Cardiomyocytes Apoptosis via Inhibition of CHOP Pathway and Activation of PI3K/Akt Pathway In Vivo and In Vitro.

BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is believed to be the major cause for detriments in coronary heart diseases, but few effective therapies for prevention or treatment of I/R injury are available. Gypenoside (GP) is the predominant effective component of Gynostemma pentaphyllum and possesses capacities against inflammation and oxidation. In the present study, the role of GP in ameliorating myocardial I/R injury was investigated. METHODS: effect GP on the cardiac structure of I/R injured rats was assessed by H&E and TTC staining. Then the influence of GP on the cardiac function of rat model was determined by measuring hemodynamics parameters, levels of lactate dehydrogenase (LDH) and creatine kinase (CK). Thereafter, effect of GP on apoptotic process was evaluated with both rat and cell models. The production of molecules related to ER stress and apoptosis was quantified for revelation of pathways involved in the myocardial protective effect of GP. RESULTS: Impairments in cardiac structure due to I/R injury was ameliorated by GP treatment. And it was evidently demonstrated that administration of GP not only effectively decreased the apoptotic rates in both rat and cell models but also markedly improved the cardiac function of I/R injured rats. In addition, results of western blotting revealed that the GP inhibited ER-stress and apoptosis through the blockade of CHOP pathway and activation of PI3K/Akt pathway. CONCLUSION: the current study showed the potential of GP to alleviate myocardial I/R injury and preliminarily uncovered the underling mechanism driving this treatment.

Nanoparticle Loading Induced Morphological Transitions and Size Fractionation of Coassemblies from PS-b-PAA with Quantum Dots.

Inorganic nanoparticles play a very important role in the fabrication and regulation of desirable hybrid structures with block copolymers. In this study, polystyrene-b-poly(acrylic acid) (PS48-b-PAA67) and oleic acid-capped CdSe/CdS core/shell quantum dots (QDs) are coassembled in tetrahydrofuran (THF) through gradual water addition. QDs are incorporated into the hydrophilic PAA blocks because of the strong coordination between PAA blocks and the surface of QDs. Increasing the weight fraction of QDs (ω = 0-0.44) leads to morphological transitions from hybrid spherical micelles to large compound micelles (LCMs) and then to bowl-shaped structures. The coassembly process is monitored using transmission electron microscopy (TEM). Formation mechanism of different morphologies is further proposed in which the PAA blocks bridging QDs manipulates the polymer chain mobility and the resulting morphology. Furthermore, the size and size distribution of assemblies serving as drug carriers will influence the circulation time, organ distribution and cell entry pathway of assemblies. Therefore, it is important to prepare or isolate assemblies with monodisperse or narrow size distribution for biomedical applications. Here, the centrifugation and membrane filtration techniques are applied to fractionate polydisperse coassemblies, and the results indicate that both techniques provide effective size fractionation.

Downregulation of miR-210 protected bupivacaine-induced neurotoxicity in dorsal root ganglion.

Local anesthetic may cause neurotoxicity in developing neurons. In this study, we examined the molecular mechanisms of microRNA-210 (miR-210) in regulating bupivacaine-induced dorsal root ganglia (DRG) neurotoxicity in vitro. Young mouse (P30) DRG explants were cultured in vitro and treated with 5 mM bupivacaine to induce neurotoxicity. QRT-PCR was used to evaluate the expression profiles of miRNAs within 24 h after bupivacaine treatment. MiR-210 was downregulated in DRG, and its effects on bupivacaine-induced neurotoxicity were evaluated by apoptosis and neurite growth assays, respectively. Putative downstream target of miR-210 in DRG, BDNF, was evaluated by dual-luciferase assay, qRT-PCR, and western blot, respectively. BDNF was then knocked down by siRNA to assess its associated effects in regulating DRG neurotoxicity. Within the initial 24 h after bupivacaine treatment, various patterns of miRNA expression were observed, whereas miR-210 was constantly upregulated. Application of miR-210 inhibitor efficiently downregulated endogenous miR-210, protected apoptosis and neurite retraction in bupivacaine damaged DRG neurons. Using dual-luciferase assay, qRT-PCR, and western blot, BDNF was confirmed to the downstream target of miR-210 in DRG. SiRNA-mediated BDNF downregulation reversed the effect of miR-210 downregulation in DRG neurotoxicity. MiR-210, through the regulation of BDNF, plays important role in anesthetics-induced DRG neurotoxicity.

Tongxinluo Induces nNOS Expression Through ERK Activation: Possible Contribution to the Effects of Tongxinluo to Attenuate Vasoconstriction.

BACKGROUND AND OBJECTIVE: Vasoconstriction and hypersensitivity to the vasoconstrictive action of serotonin occurs in the early stage of atherosclerosis. Vascular neural nitric oxide synthase (nNOS) plays an important role in the regulation of vascular tone and is vasoprotective against atherosclerosis. In this study, we intended to investigate the possible role of nNOS in mediating the effect of Chinese medicine Tongxinluo (TXL) to attenuate vasoconstriction induced by the chronic injury in the collared carotid artery. METHODS: Twenty-four male Wistar Kyoto rats were assigned to 2 treatments (n = 12): vehicle and TXL (400 mg·kg·d). After 2 weeks of treatment, adventitia injury was induced by placing a silicone collar around the left carotid artery for 2 weeks. Blood flow and vascular reactivity to serotonin were determined, and carotid arteries were harvested for morphometry, RT-PCR, and Western blotting analysis. Expression of nNOS and phosphorylated ERK1/2 was also analyzed in primary cultured vascular smooth muscle cells after TXL and/or ERK kinase inhibitor treatment. RESULTS: Adventitia injury induced by the placement of a silicone collar around the carotid artery for 2 weeks led to chronic vasoconstriction and vascular hypersensitivity to serotonin, which was attenuated by TXL treatment. TXL improved the carotid blood flow and normalized the vascular hypersensitivity to serotonin in collared carotid arteries. The expression of nNOS and phosphorylated ERK1/2 was increased by TXL treatment in both collared carotid artery and vascular smooth muscle cells indicating a possible contribution of ERK1/2 and nNOS signaling to the beneficial effects of TXL. Moreover, we showed that the effect of TXL to increase nNOS expression was mediated by the phosphorylated ERK1/2 since the effect could be abolished by the ERK kinase inhibitor PD98059. CONCLUSIONS: TXL increases nNOS expression in the collared carotid artery through activation of ERK1/2 signaling, which may have contributed to the attenuation of vasoconstriction induced by the collar-induced adventitia injury.

Diagnostic value of (99m)Tc-3PRGD2 scintimammography for differentiation of malignant from benign breast lesions: Comparison of visual and semi-quantitative analysis.

OBJECTIVE: To compare the diagnostic value of visual and semi-quantitative analysis of technetium-99m-poly-ethylene glycol, 4-arginine-glycine-aspartic acid ((99m)Tc-3PRGD2) scintimammography (SMG) for better differentiation of benign from malignant breast masses, and also investigate the incremental role of semi-quantitative index of SMG. SUBJECTS AND METHODS: A total of 72 patients with breast lesions were included in the study. Technetium-99m-3PRGD2 SMG was performed with single photon emission computed tomography (SPET) at 60 min after intravenous injection of 749 ± 86MBq of the radiotracer. Images were evaluated by visual interpretation and semi-quantitative indices of tumor to non-tumor (T/N) ratios, which were compared with pathology results. Receiver operating characteristics (ROC) curve analyses were performed to determine the optimal visual grade, to calculate cut-off values of semi-quantitative indices, and to compare visual and semi-quantitative diagnostic values. RESULTS: Among the 72 patients, 89 lesions were confirmed by histopathology after fine needle aspiration biopsy or surgery, 48 malignant and 41 benign lesions. The mean T/N ratio of (99m)Tc-3PRGD2 SMG in malignant lesions was significantly higher than that in benign lesions (P<0.05). When grade 2 of the disease was used as cut-off value for the detection of primary breast cancer, the sensitivity, specificity and accuracy were 81.3%, 70.7%, and 76.4%, respectively. When a T/N ratio of 2.01 was used as cut-off value, the sensitivity, specificity and accuracy were 79.2%, 75.6%, and 77.5%, respectively. According to ROC analysis, the area under the curve for semi-quantitative analysis was higher than that for visual analysis, but the statistical difference was not significant (P=0.372). Compared with visual analysis or semi-quantitative analysis alone, the sensitivity, specificity and accuracy of visual analysis combined with semi-quantitative analysis in diagnosing primary breast cancer were higher, being: 87.5%, 82.9%, and 85.4%, respectively. The area under the curve was 0.891. CONCLUSION: Results of the present study suggest that the semi-quantitative and visual analysis statistically showed similar results. The semi-quantitative analysis provided incremental value additive to visual analysis of (99m)Tc-3PRGD2 SMG for the detection of breast cancer. It seems from our results that, when the tumor was located in the medial part of the breast, the semi-quantitative analysis gave better diagnostic results.

The diagnostic role of 99mTc-dual receptor targeted probe and targeted peptide bombesin (RGD-BBN) SPET/CT in the detection of malignant and benign breast tumors and axillary lymph nodes compared to ultrasound.

OBJECTIVE: This study aimed to explore the diagnostic role of a new dual receptor-targeted probe, integrin ανß3 and gastrin releasing peptide receptor (GRPR) targeted peptide Glu-c(RGDyK)-bombesin (RGD-BBN) labeled with technetium-99m ((99m)Tc-RGD-BBN), using single photon emission tomography/computed tomography (SPET/CT) in the detection of breast tumor in comparison to ultrasound (US). SUBJECTS AND METHODS: One hundred and twenty six female patients with suspicious breast lesions who had already been scheduled for biopsy or surgery were enrolled in this study. All patients had previously underwent breast US and (99m)Tc-RGD-BBN SPET/CT. The US findings were evaluated according to the breast imaging report and the data system (BI-RADS). Technetium-99m-RGD-BBN SPET/CT images were interpreted independently by two experienced nuclear medicine physicians. A final diagnosis was made by histopathology of the specimens. A total of 130 lesions, 77 malignant and 53 benign lesions were ascertained. One hundred and twelve breast lesions, 69 malignant and 43 benign lesions were above 10mm in diameter and 18 breast lesions (8 malignant lesions and 10 benign lesions) were below 10mm. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of (99m)Tc-RGD-BBN SPET/CT and US for breast lesions were 93.5% vs. 81.8% (P<0.05), 79.2% vs. 75.5% (P>0.05), 86.7% vs. 82.9% (P>0.05), 89.4% vs. 74.1% (P<0.05) and 87.7% vs. 79.2% (P>0.05). Technetium-99m-RGD-BBN SPET/CT detected all lesions ≥10mm and US only detected 57 (P<0.05). In malignant lesions <10mm, US was superior than (99m)Tc-RGD-BBN SPET/CT (75.0% vs. 37.5%, P<0.05). There was no significant difference between the two methods no matter the size of the benign lesions. The overall sensitivity and specificity of (99m)Tc-RGD-BBN SPET/CT and US for axillae lymph nodes were 87.5% vs. 71.9% (P<0.05) and 77.6% vs. 68.9% (P>0.05), respectively. For the metastatic lymph nodes of <10mm, the sensitivity of (99m)Tc-RGD-BBN SPET/CT and of US was 88.5% and 72.1% respectively (P<0.05). Statistical analysis was not performed due to the small number of metastatic lesions of <10mm. The specificity of (99m)Tc-RGD-BBN SPET/CT and of US was not different, no matter the size of the axilla lymph nodes that had no metastases (P>0.05). Technetium-99m-RGD-BBN SPET/CT had higher sensitivity and NPV than US in detecting primary breast tumors and axilla lymph nodes and it also showed an advantage in distance metastatic lesions detection. On the contrary, specificity and PPV of the two methods were not different. CONCLUSION: Technetium-99m-RGD-BBN SPET/CT cannot totally replace US in the detection of primary breast cancer and axillary lymph nodes metastases. It can be used as an additional imaging tool of eliminating the necessity of surgical biopsy and histopathologic examination because of its high NPV.

(99)mTc-3PRGD2 scintimammography in palpable and nonpalpable breast lesions.

The aim of this study was to explore the diagnostic performance of 99mTc-3(poly-(ethylene glycol),PEG)4-RGD2 (99mTc-3PRGD2) scintimammography (SMM) in patients with either palpable or nonpalpable breast lesions and compare SMM to mammography to assess the possible incremental value of SMM in breast cancer detection. We also investigated the αvß3 expression in malignant and benign breast lesions. Ninety-four patients with 110 lesions were included in this study. Mammograms were evaluated according to the Breast Imaging Reporting and Data System (BI-RADS) by a specialized imaging radiologist. Prone SMM was performed 1 hour after injection of 99mTc-3PRGD2. Scintigraphic images were interpreted independently by two experienced nuclear medicine physicians using a three-point system, and the kappa value was calculated to determine the interreader agreement. The McNemar test was used to compare SMM and mammography with respect to sensitivity, specificity, and accuracy. Diagnostic values for breast cancer detection were evaluated for each lesion. Immunohistochemistry was performed to evaluate integrin αvß3 expression. Histopathology revealed 46 malignant lesions and 64 benign lesions. The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SMM were 83%, 73%, 77%, 69%, and 85%, respectively. The kappa value between the two reviewers was 0.63. The diagnostic values of SMM were higher than those of mammography in evaluating overall breast lesions. A sensitivity of 91% was achieved when SMM and mammography results were combined with 60% of all false-negative mammography findings classified as true-positive results by SMM. Integrin αvß3 expression was positively identified using SMM imaging. SMM is a promising tool to avoid unnecessary biopsies when used in addition to mammography and can be used to image αvß3 expression in breast cancer with good image quality.

Silencing ANLN hinders the proliferation, migration, invasion, and angiogenesis of oral squamous cell carcinoma.

BACKGROUND: The actin-binding protein anillin (ANLN) functions as an oncogene in various cancers but has not been fully studied in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression of ANLN in OSCC tissues and cell lines, to better understand its role in mediating proliferative, angiogenic, invasive, and metastatic capabilities in this type of cancer. METHODS: ANLN mRNA and protein levels were assessed using qPCR and western immunoblotting. The expression intensity of ANLN was evaluated using immunohistochemical (IHC) staining. Biological functional assays were employed to characterize the behavior of OSCC cells influenced by ANLN. Additionally, comprehensive bioinformatics analysis, including GO analysis and KEGG enrichment analysis, was performed on differentially expressed genes in ANLN-mediated pathways. RESULTS: OSCC tumors and cell lines exhibited higher ANLN expression. Silencing of ANLN significantly suppressed OSCC cell proliferation, as evidenced by a significant reduction in the Ki-67 index both in vitro and in vivo. The migration and invasive ability of OSCC cells were markedly diminished, coinciding with a decrease in epithelial-mesenchymal transition activity. ANLN was also found to promote angiogenic activity in OSCC cells, partly through synergistic effects mediated by vascular endothelial growth factor A (VEGFA). Downregulation of ANLN expression led to decreased VEGFA levels, resulting in reduced angiogenesis characterized by fewer vascular branches. CONCLUSIONS: Our findings highlight the promising role of ANLN as a biomarker for both diagnostic and prognostic in OSCC. Targeting ANLN with inhibitory strategies could impede the oncogenesis processes at the core of OSCC development, presenting significant opportunities for advancing therapeutic interventions.

Computational study of transcatheter aortic valve replacement based on patient-specific models-rapid surgical planning for self-expanding valves.

Transcatheter aortic valve replacement (TAVR) is a minimally invasive interventional solution for treating aortic stenosis. The complex post-TAVR complications are associated with the type of valve implanted and the position of the implantation. The study aimed to establish a rapid numerical research method for TAVR to assess the performance differences of self-expanding valves released at various positions. It also aimed to calculate the risks of postoperative paravalvular leak and atrioventricular conduction block, comparing these risks to clinical outcomes to verify the method's effectiveness and accuracy. Based on medical images, six cases were established, including the aortic wall, native valve and calcification; one with a bicuspid aortic valve and five with tricuspid aortic valves. The parameters for the stent materials used by the patients were customized. High strain in the contact area between the stent and the valve annulus may lead to atrioventricular conduction block. Postoperatively, the self-expanding valve maintained a circular cross-section, reducing the risk of paravalvular leak and demonstrating favorable hemodynamic characteristics, consistent with clinical observations. The outcomes of the six simulations showed no significant difference in valve frame morphology or paravalvular leak risk compared to clinical results, thereby validating the numerical simulation process proposed for quickly selecting valve models and optimal release positions, aiding in TAVR preoperative planning based on patients'geometric characteristics.

The research on borehole stability in depleted reservoir and caprock: using the geophysics logging data.

Long-term oil and gas exploitation in reservoir will lead to pore pressure depletion. The pore pressure depletion will result in changes of horizontal in-situ stresses both in reservoirs and caprock formations. Using the geophysics logging data, the magnitude and orientation changes of horizontal stresses in caprock and reservoir are studied. Furthermore, the borehole stability can be affected by in-situ stresses changes. To address this issue, the dehydration from caprock to reservoir and roof effect of caprock are performed. Based on that, the influence scope and magnitude of horizontal stresses reduction in caprock above the depleted reservoirs are estimated. The effects of development on borehole stability in both reservoir and caprock are studied step by step with the above geomechanical model.

Experimental study on a new radioactive probe for the treatment of lacrimal duct stenosis.

Our aim was to study the treatment effect of a radioactive probe on lacrimal duct stenosis. We applied experimentally in 30 inbred white rabbits a lacrimal duct stenosis model and the rabbits were randomly divided into 3 groups: the stenosis group, the surgery group and the radioactive probe group. We also separated a blank control group of 5 rabbits. Rabbits in the surgery group and the radioactive probe group were examined by digital subtraction angiography (DSA) 10 min and 30 d after treatment before being sacrificed. Rabbits in the stenosis group and the control group were examined by DSA 60 min before they were sacrificed. Specimens of the lacrimal ducts at the stenosis site were collected immediately after the rabbits were sacrificed. Morphological changes were observed through haematoxyline-eosin staining, while lumen areas of lacrimal duct were observed through computer based photo analysis. For the surgery and the radioactive probe group, stenosis cure rates were 100% 10 min after treatment. Thirty days after treatment, the rates of stenosis were 40% and 5% for the above groups, respectively. Morphological observations showed that each layer of the lacrimal duct wall in the stenosis group became thicker with higher proliferation of cells. Each layer of the lacrimal duct wall in the surgery group was thinner than in the stenosis group; however, the extent of cell profileration was similar. In the radiation treatment group, the interstitial layers of the lacrimal duct epithelium, elastin and collagen fibers and other connective tissue components were thinner than in the surgery group. Cells proliferation was significantly weakened in the radiation treatment than in the stenosis and in the surgery groups. The average areas of lacrimal duct in the control, stenosis, surgery and the radioactive probe groups of the examined sites, were: 0.84±0.28 mm2, 0.26±0.13 mm2, 0.55±0.31 mm2 and 0.80±0.36 mm2, respectively. In conclusion, the radioactive lacrimal duct probe showed distinct therapeutic effects in curing lacrimal duct stenosis and in preventing restenosis after the operation.

[Surface-enhanced Raman spectroscopy of thiuram pesticide].

In the present paper, two SERS-active substrates (silver mirror and HNO3 etched Ag foil) were prepared for thiuram detecting and studying. SERS can provide the molecular vibrational model and structure information of thiuram at low concentration, thus providing very valuable information regarding the structure of the adsorbed molecules. This technique also allows for the in situ study of this molecule when adsorbed on a silver surface and the identification of the chemical state when they are adsorbed on the surface of silver substrate. The SERS study of thiuram was carried out at several adsorbtion concentrations, revealing that two different coordination complexes having different geometries (monodentate and bidentate) are possible adsorbed on the silver surface. These results have a significant importance regarding the understanding of the potential environmental impact of these molecules.