Microstructure and Mechanical Properties of a Novel Al-Mg-Sc-Ti Alloy Fabricated by Laser Powder Bed Fusion.

(TiH2 + ScH3)/Al-Mg composite powders with different Ti contents were produced by ball milling. These composite powders were fabricated to cube and cuboid shape samples via a laser powder bed fusion process with optimal processing parameters. The TiH2 and ScH3 particles underwent dehydrogenation during the laser powder bed fusion process, and these composite powders ultimately formed Al-Mg-Sc-Ti alloys. The relative density, printability, microstructure, hardness and tensile properties of these alloy samples were investigated. The results show that these Al-Mg-Sc-Ti alloys have lower hot-crack sensitivity, having fine equiaxed grains. An Al18Mg3(Ti,Sc)2 intermetallic phase and in situ L12-Al3(Sc,Ti) precipitations formed during the laser powder bed fusion process, which is beneficial for nucleation and dispersion strengthening. The ultimate tensile strength of the Al-Mg-0.7Sc-1.0Ti alloy was 313.6 MPa with an elongation of 6.6%. During the hot isostatic pressing treatment, most of the Mg element precipitated from the matrix and changed the Al3(Sc,Ti) into a Al18Mg3(Ti,Sc)2 precipitate completely. The Al-Mg-Sc-Ti alloys were nearly fully dense after the hot isostatic pressing treatment and exhibited better mechanical properties. The ultimate tensile strength of the Al-Mg-0.7Sc-1.0Ti was 475 MPa with an elongation of 8.5%.

MicroRNA-196a-5p facilitates the onset and progression via targeting ITM2B in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy affecting the digestive tract, with an increasing incidence rate worldwide. Recently, numerous studies revealed that microRNAs were associated with gene expression regulation, particularly their involvement in the regulation of tumor cells, garnering widespread attention. Here, we discovered that miR-196a-5p was significantly upregulated in both ESCC tissues and cells, which was correlated with an unfavorable prognosis. Series functional in vitro investigations have confirmed that silencing miR-196a-5p obviously restrained the ESCC cells malignant phenotypes and promoted apoptosis. Bioinformatics analysis and rescue experiments revealed that miR-196a-5p directly targeted ITM2B, exerting influence on the development of ESCC cells through negative regulation of ITM2B expression. Xenograft mouse models were established for conducting in vivo experiments, providing further confirmation of the regulatory mechanism and biological significance of the miR-196a-5p/ITM2B axis in ESCC. Our research demonstrated miR-196a-5p promoted ESCC malignant progression by interacting with ITM2B, thereby providing novel clues and potential targets for the new diagnosis and thereby of ESCC.

The development and validation of pathological sections based U-Net deep learning segmentation model for the detection of esophageal mucosa and squamous cell neoplasm.

Background: Deep learning methods have demonstrated great potential for processing high-resolution images. The U-Net model, in particular, has shown proficiency in the segmentation of biomedical images. However, limited research has examined the application of deep learning to esophageal squamous cell carcinoma (ESCC) segmentation. Therefore, this study aimed to develop deep learning segmentation systems specifically for ESCC. Methods: A Visual Geometry Group (VGG)-based U-Net neural network architecture was utilized to develop the segmentation models. A pathological image cohort of surgical specimens was used for model training and internal validation, with two additional endoscopic biopsy section cohort for external validation. Model efficacy was evaluated across several metrics including Intersection over Union (IOU), accuracy, positive predict value (PPV), true positive rate (TPR), specificity, dice similarity coefficient (DSC), area under the receiver operating characteristic curve (AUC), and F1-Score. Results: Surgical samples from ten patients were analyzed retrospectively, with each biopsy section cohort encompassing five patients. Transfer learning models based on U-Net weights yielded optimal results. For mucosa segmentation, the in internal validation achieved 93.81% IOU, with other parameters exceeding 96% (96.96% accuracy, 96.45% PPV, 96.65% TPR, 98.41% specificity, 96.81% DSC, 96.11% AUC, and 96.55% F1-Score). The tumor segmentation model attained an IOU of 91.95%, along with other parameters surpassing 95% (95.90% accuracy, 95.62% PPV, 95.71% TPR, 97.88% specificity, 95.81% DSC, 94.92% AUC, and 95.67% F1-Score). In the external validation for tumor segmentation model, IOU was 59.86% for validation database 1 (72.74% for accuracy, 76.03% for PPV, 77.17% for TPR, 83.80% for specificity, 74.89% for DSC, 71.83% for AUC, and 76.60% for F1-Score), and 50.88% for validation cohort 2 (68.03% for accuracy, 59.02% for PPV, 66.87% for TPR, 78.48% for specificity, 67.44% for DSC, 64.68% for AUC, and 62.70% for F1-Score). Conclusions: The models exhibited satisfactory results, paving the way for their potential deployment on standard computers and integration with other artificial intelligence models in clinical practice in the future. However, limited to the size of study, the generalizability of models is impaired in the external validation, larger pathological section cohort would be needed in future development to ensure robustness and generalization.

Neoadjuvant immunotherapy versus chemoimmunotherapy in non-small cell lung cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Worldwide, lung cancer is the most common cause of cancer morbidity and mortality. Non-small cell lung cancer (NSCLC) accounts for approximately 80 to 85% of all lung cancers. Recently, a few studies have reported the use of neoadjuvant immunotherapy or chemoimmunotherapy in NSCLC. However, no meta-analysis comparing neoadjuvant immunotherapy with chemoimmunotherapy has yet been reported. We perform a protocol for systematic review and meta-analysis to compare the efficacy and safety of neoadjuvant immunotherapy and chemoimmunotherapy in NSCLC. METHODS: The statement of preferred reporting items for systematic review and meta-analysis protocols will be used as guidelines for reporting the present review protocol. Original clinical randomized controlled trials assessing the beneficial effects and safety of neoadjuvant immunotherapy and chemoimmunotherapy in NSCLC will be included. Databases searched include China National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang Database, China Biological Medicine Database, PubMed, EMBASE Database, and Cochrane Central Register of Controlled Trials. Cochrane Collaboration's tool is used to assess the risk of bias in included randomized controlled trials. All calculations are carried out with Stata 11.0 (The Cochrane Collaboration, Oxford, UK). RESULTS: The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal. CONCLUSION: This evidence will be useful to practitioners, patients, and health policy-makers regarding the use of neoadjuvant chemoimmunotherapy in NSCLC.

CircHSPG2 absence weakens hypoxia-induced dysfunction in cardiomyocytes by targeting the miR-25-3p/PAWR axis.

Background: Circular RNAs (circRNAs) are important regulators in human cardiovascular diseases. Here, we investigated the role of circRNA heparan sulfate proteoglycan 2 (circHSPG2) in hypoxia-induced myocardial infarction (MI) and its associated mechanism. Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to examine RNA and protein expression. Cell viability was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. Cell proliferation was assessed by 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Flow cytometry (FCM) analysis was carried out to analyze the apoptosis of AC-16 cells. Lactate dehydrogenase (LDH) assay was implemented to assess cell death. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target relationship between microRNA-25-3p (miR-25-3p) and circHSPG2 or pro-apoptotic WT1 regulator (PAWR). Results: Hypoxia treatment up-regulated the expression of circHSPG2 in AC-16 cells. Hypoxia exposure reduced the viability, suppressed the proliferation and induced the apoptosis of AC-16 cells, and these effects were diminished by the silence of circHSPG2. CircHSPG2 acted as a molecular sponge for miR-25-3p. CircHSPG2 absence-mediated effects on hypoxia-induced AC-16 cells were largely reversed by anti-miR-25-3p. miR-25-3p bound to the 3' untranslated region (3'UTR) of PAWR. PAWR overexpression largely counteracted miR-25-3p-mediated effects on hypoxia-induced AC-16 cells. CircHSPG2 positively regulated the expression of PAWR by acting as miR-25-3p sponge in AC-16 cells. Conclusions: CircHSPG2 silencing protected AC-16 cells against hypoxia-induced dysfunction by targeting miR-25-3p/PAWR axis.

Multi-Object Detection in Security Screening Scene Based on Convolutional Neural Network.

The technique for target detection based on a convolutional neural network has been widely implemented in the industry. However, the detection accuracy of X-ray images in security screening scenarios still requires improvement. This paper proposes a coupled multi-scale feature extraction and multi-scale attention architecture. We integrate this architecture into the Single Shot MultiBox Detector (SSD) algorithm and find that it can significantly improve the effectiveness of target detection. Firstly, ResNet is used as the backbone network to replace the original VGG network to improve the feature extraction capability of the convolutional neural network for images. Secondly, a multi-scale feature extraction (MSE) structure is designed to enrich the information contained in the multi-stage prediction feature layer. Finally, the multi-scale attention architecture (MSA) is fused onto the prediction feature layer to eliminate the redundant features' interference and extract effective contextual information. In addition, a combination of Adaptive-NMS and Soft-NMS is used to output the final prediction anchor boxes when performing non-maximum suppression. The results of the experiments show that the improved method improves the mean average precision (mAP) value by 7.4% compared to the original approach. New modules make detection much more accurate while keeping the detection speed the same.

Circ_0000463 contributes to the progression and glutamine metabolism of non-small-cell lung cancer by targeting miR-924/SLC1A5 signaling.

BACKGROUND: Circular RNAs (circRNAs) have shown pivotal regulatory roles in the pathology of non-small cell lung cancer (NSCLC). However, the role of circ_0000463 in NSCLC progression and its associated molecular mechanism remain to be illustrated. METHODS: Cell proliferation ability was analyzed by colony formation assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell migration and invasion abilities were assessed by scratch test and transwell invasion assay. Flow cytometry was employed to analyze cell apoptotic rate. The interaction between microRNA-924 (miR-924) and circ_0000463 or solute carrier family 1 member 5 (SLC1A5) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The uptake of glutamine and the production of glutamate and α-ketoglutarate were analyzed using their corresponding kits. Xenograft model in vivo was established to analyze the role of circ_0000463 in tumor growth. RESULTS: Circ_0000463 expression was elevated in NSCLC tissues and cell lines. Circ_0000463 knockdown suppressed the proliferation, migration, and invasion and promoted the apoptosis of NSCLC cells. Circ_0000463 acted as a molecular sponge for miR-924, and circ_0000463 interference-mediated anti-tumor effects were largely reversed by the silence of miR-924 in NSCLC cells. miR-924 interacted with the 3' untranslated region (3'UTR) of SLC1A5, and SLC1A5 overexpression largely overturned miR-924 overexpression-mediated anti-tumor effects in NSCLC cells. Moreover, circ_0000463 absence suppressed the glutamine metabolism of NSCLC cells by targeting miR-924/SLC1A5 axis. Circ_0000463 knockdown suppressed xenograft tumor growth in vivo. CONCLUSION: Circ_0000463 absence suppressed the malignant behaviors and glutamine metabolism of NSCLC cells through mediating miR-924/SLC1A5 axis.

Thiol-functionalized reduced graphene oxide as self-assembled ion-to-electron transducer for durable solid-contact ion-selective electrodes.

Thiol-functionalized reduced graphene oxide (TRGO) as a novel ion-to-electron transducing layer is firstly employed to develop durable solid-contact ion-selective electrodes (SC-ISEs) in this work. The performance of the sensors is evaluated by determining K+ and NO3- as an example of cation and anion. The covalent linkage of TRGO at golden electrode surface generates a stable transducing layer. No water films are observed in the proposed TRGO-based potassium (K+-TRGO-ISEs) and nitrate (NO3--TRGO-ISEs) selective SC-ISEs. The resultant electrodes exhibit Nernstian responses (60.0 ±â€¯0.4 mV/decade for K+-TRGO-ISEs and -60.0 ±â€¯0.5 mV/decade for NO3--TRGO-ISEs), low detection limits (2.5 × 10-6 M for K+-TRGO-ISEs and 4.0 × 10-6 M for NO3--TRGO-ISEs) and good selectivity behavior. More importantly, the TRGO-based SC-ISEs display a much longer lifetime of 2 weeks than that of reduced graphene oxide-based SC-ISEs in continuous flowing solutions using a longer peristaltic pump. These improvements push TRGO a general and reliable transducer for the development of durable SC-ISEs.

Luteolin improves heart preservation through inhibiting hypoxia-dependent L-type calcium channels in cardiomyocytes.

The current study aimed to evaluate whether luteolin could improve long-term heart preservation; this was achieved by evaluating the heart following long-term storage in University of Wisconsin solution (the control group) and in solutions containing three luteolin concentrations. The effects of different preservation methods were evaluated with respect to cardiac function while hearts were in custom-made ex vivo Langendorff perfusion systems. Different preservation methods were evaluated with respect to the histology, ultrastructure and apoptosis rate of the hearts, and the function of cardiomyocytes. In the presence of luteolin, the rate pressure product of the left ventricle was increased within 60 min of reperfusion following a 12-h preservation, coronary flow was higher within 30 min of reperfusion, cardiac contractile function was higher throughout reperfusion following 12- and 18-h preservations, and the left ventricle peak systolic pressure was significantly higher compared with the control group (all P<0.05). The expression levels of apoptosis regulator Bax and apoptosis regulator Bcl-2 in the luteolin groups were significantly decreased and increased, respectively. Lactate dehydrogenase, creatine kinase and malondialdehyde enzymatic activity was increased following long-term storage, while the activity of superoxide dismutase was significantly decreased. Furthermore, luteolin inhibited L-type calcium currents in ventricular myocytes under hypoxia conditions. Thus, luteolin demonstrated protective effects during long-term heart preservation in what appeared to be a dose-dependent manner, which may be accomplished through inhibiting hypoxia-dependent L-type calcium channels.

Thread Structure Learning on Online Health Forums with Partially Labeled Data.

Thread structures, the reply relationships between posts, in online forums are very important for readers to understand the thread content, as well as for improving the effectiveness of automated forum information retrieval, expert findings, etc. However, most online forums only have partially labeled structures, which means that some reply relationships are known while the others are unknown. To address this problem, studies have been performed to learn and predict thread structures. However, existing work does not leverage the partially available thread structures to learn the complete thread structure. We have also observed that many online health forums are a type of person-centric forums, where persons are mentioned across posts, providing hints about the reply relationships between posts. In this paper, we first proposed to learn the complete thread structures by leveraging the partially known structures based on a statistical machine learning model: thread conditional random fields (threadCRF). Then we proposed to use person resolution, the process of identifying the same person mentioned in different contexts, together with threadCRF for thread structure learning. We have empirically verified the effectiveness of the proposed approaches.

Room temperature synthesis of pH-switchable polyaniline quantum dots as a turn-on fluorescent probe for acidic biotarget labeling.

The synthesis of well-defined light-element-derived quantum dots (LEQDs) with advanced optical properties under mild conditions is highly desirable yet challenging. Here, a polyaniline (PANI) structure is introduced into carbon-rich LEQDs to yield well-defined, fluorescent polyaniline quantum dots (PAQDs), PAQD24, through a one-pot room temperature reaction. The mild synthetic conditions effectively minimize the defects introduced during the conventional synthesis and endow PAQD24 with desirable optical properties, including a narrow emission band (full width at half maximum = 55 nm), an optimal quantum yield of 32.5% and two-photon fluorescence. Furthermore, the bandgap of PAQD24 is highly sensitive toward pH variations in the near-neutral region, due to the proton doping and dedoping of the PANI structure. Such unique properties together with its fine bio-compatibility enable the application of this material as a turn-on fluorescent probe for the labeling of acidic biotargets from sub-cellular to organ levels, providing potential applications in diagnosis and surgery guidance for certain diseases.

Effects of luteolin on regulatory proteins and enzymes for myocyte calcium circulation in hypothermic preserved rat heart.

Heart transplantation has been applied in the clinic as an optimal solution for patients with end stage cardiac failure for a number of years. However, hypothermic preservation of the heart remains limited to 4-6 h and calcium accumulation over time is an important factor resulting in cell death. To provide longer and safer storage for donor hearts, it was demonstrated in our previous study that luteolin, a traditional Chinese medicine used to treat cardiovascular diseases, inhibits cell death and L-type calcium currents during hypothermic preservation. In the current study, the protective role of luteolin in modulating cardiomyocyte calcium cycling was further investigated. Intracellular calcium overload has already been implicated in hypothermia-induced dysfunction of cardiomyocytes. University of Wisconsin (UW) solution supplemented with 7.5, 15 or 30 µmol/l luteolin was used to preserve fresh isolated cardiomyocytes at 4°C. The results demonstrated that all three doses of luteolin supplementation attenuated calcium overload over a 6 h preservation period. Luteolin also suppressed the accumulation of important regulatory proteins and enzymes for cardiomyocyte calcium circulation, mitochondria Ca2+ uniporter and calmodulin, which are normally induced by cold storage in UW solution. Protein Kinase A activity was also suppressed in cardiomyocytes preserved in luteolin supplemented UW solution, while Ca2+-Mg2+-ATPase activity was increased. The results demonstrated that luteolin confers a cardioprotective effect through inhibiting the changes of calcium regulators during cold storage and therefore ameliorates Ca2+ overload in rat cardiomyocytes.

Role of GPR30 in estrogen-induced prostate epithelial apoptosis and benign prostatic hyperplasia.

Several studies have implicated estrogen and the estrogen receptor (ER) in the pathogenesis of benign prostatic hyperplasia (BPH); however, the mechanism underlying this effect remains elusive. In the present study, we demonstrated that estrogen (17ß-estradiol, or E2)-induced activation of the G protein-coupled receptor 30 (GPR30) triggered Ca2+ release from the endoplasmic reticulum, increased the mitochondrial Ca2+ concentration, and thus induced prostate epithelial cell (PEC) apoptosis. Both E2 and the GPR30-specific agonist G1 induced a transient intracellular Ca2+ release in PECs via the phospholipase C (PLC)-inositol 1, 4, 5-triphosphate (IP3) pathway, and this was abolished by treatment with the GPR30 antagonist G15. The release of cytochrome c and activation of caspase-3 in response to GPR30 activation were observed. Data generated from the analysis of animal models and human clinical samples indicate that treatment with the GPR30 agonist relieves testosterone propionate (TP)-induced prostatic epithelial hyperplasia, and that the abundance of GPR30 is negatively associated with prostate volume. On the basis of these results, we propose a novel regulatory mechanism whereby estrogen induces the apoptosis of PECs via GPR30 activation. Inhibition of this activation is predicted to lead to abnormal PEC accumulation, and to thereby contribute to BPH pathogenesis.

[Effects of higeramine on hemodynamics and its tolerability and safety, an experimental study].

OBJECTIVE: To investigate the effects of higeramine (HG) on hemodynamics and its tolerability and safety so as to see if it can be used in cardiac loading test, and to compare the hemodynamic effects of HG and dobutamine (DB). METHODS: Six dogs were infused intrevenously with HG in escalating doses from l microgram/kg/min through 2 microgram/kg/min and to 4 microgram/kg/min, each dose being given for 5 minutes. Then the dogs were infused intravenously with DB at the escalating doses from 5 microgram/kg/min through 10 microgram/kg/min to 20 microgram/kg/min, each dose being given for 5 minutes. Heart rate (HR), blood pressure (BP), cardiac output (CO), myocardial oxygen consumption (MOC), and coronary blood flow (CBF) were measured at the beginning of test and by the end of each dose-infusion. Electrocardiography was conducted in the meantime. Left ventricular ejection fraction (LVEF) was measured with radionuclide equilibrium ventriculography. Another 8 dogs were given HG at the escalating doses from 1 microgram/kg/min up to 500 microgram/kg/min, each dose being infused for 3 minutes, to observe the tolerability and safety of HG, HR, BP, and ECG were monitored during the test. RESULTS: Intravenous administration of HG results in significant inotropic and chronotropic effects on the heart. HR, MOC, CO and CBF all increased in a dose-dependent manner in both HG and DB tests. HG did not cause significant change in systolic blood pressure (SBP), but a slight decrease in diastolic blood pressure (DBP) was found. HR increased steeply to the peak, and then remained at a plateau level. No significant ECG abnormality was seen except a few occasional premature ventricular beats. No dog died during the study. CONCLUSION: HG can be used in pharmacological stress test with remarkable tolerability and safety even at the dosage of 500 microgram/kg/min without serious adverse effect. It can be used as an alternative agent to DB under appropriate circumstances.