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The softening of the heat affected zone (HAZ) remains a significant challenge in fusion welding of novel Al–Mg–Si–Cu alloy, and the underlying mechanisms vary across different aging states. However, limited research has been conducted on this topic. Therefore, this study investigates the influence of various aging states on the microstructure and mechanical properties within the HAZ of welded joints by selecting extrusions treated with T4, T5, and T6 heat treatments. The results indicate that the increase in hardness of HAZ I is attributed to solid solution strengthening. In the HAZ I, the precipitated phases are mostly dissolved into the matrix under the influence of a peak temperature of 464.6 °C, and no residual precipitated phase is detected in T4 and T5 alloy joints, while some undissolved Q phase is observed in T6 alloy joint. The decrease in hardness of HAZ Ⅱ is attributed to the limited precipitation of coarse β'' and Q' phases for the T4 alloy welded joints, which weakens the solid solution strengthening. However, the softening mechanisms in the HAZ Ⅱ of the T5 and T6 alloy joints are ascribed to the dissolution of β'' and subsequent precipitation of Q' and Q phases. HAZ Ⅲ, close to the base metal, exhibits a lesser degree of influence and thus experiences a gradual recovery in hardness. This study can provide theoretical guidance for the exploration of high-strength, heat-resistant aluminum alloys.

Objective To screen the distribution frequency of Mur blood group among voluntary blood donors in Hezhou, Guangxi, and further analyze the molecular basis of of Mur antigen positive samples. Methods The Mur phenotype of voluntary blood donors in Hezhou was serologically screened using microplate method, and the distribution frequency of Mur antigens in different ethnic groups was analyzed. Genetic typing was performed on these positive samples with PCR-SSP method to verify the accuracy of the serological method, and the genetic background was sequenced and analyzed. Results Among 3 298 samples from voluntary blood donors in Hezhou, 432(13.10%, 432/3 298) were screened positive for Mur antigen, and PCR-SSP genotyping validation showed that all 432 samples were electrophoretic positive. Among them, the proportion of Han blood donors with positive Mur antigen was 12.79%(331/2 587), Yao ethnic group was 13.25%(64/483), Zhuang ethnic group was 16.51%(36/218), and no statistically significant difference was found in the three groups(P>0.05). Further sequencing results showed that 428 samples were GYP(B-A-B) Mur, also known as GYP. Mur type(12.98%, 428/3 298), the other 4 samples were GYP(B-A-B) Bun, also known as GYP. Bun type(0.12%, 4/3 298). Conclusion The Mur blood type frequency is high in the voluntary blood donors in Hezhou, Guangxi, and is predominant characterized by GYP. Mur genotype. Due to ethnic integration, no significant difference was noticed in the frequency of Mur blood type distribution between Han, Zhuang and Yao population. Therefore, conducting extensive Mur blood group antigen and antibody testing in Hezhou is of great significance for ensuring clinical blood transfusion safety.

ObjectiveTo examine the association of overweight/obesity and serum vitamin C (serum VC) with serum uric acid (SUA) and to assess causality using Mendelian randomization (MR).Methods4,772 participants from the National Health and Nutrition Examination Survey (NHANES), 2017–2018 were included in this study. Multivariate linear regression, variance inflation factor and quantile regression were used to analyze the relationships between overweight/obesity and serum VC and SUA levels. Secondly, Mendelian randomization (MR) was utilized to mitigate bias and prevent reverse causality in the observational study. Genetic variants associated with obesity (N = 13,848), vitamin C levels (N = 64,979) and serum uric acid levels (N = 343,836) were sourced from the most extensive genome-wide association studies (GWAS). The primary analytical method employed was inverse variance weighted (IVW).ResultsBased on the observational study, BMI was positively associated with SUA (β = 0.06, 95% CI: 0.05 to 0.07, p =25), the negative effects of serum VC on SUA enhanced with increasing serum VC. High serum VC level (Q4 level, above 1.19 mg/dL) reduced SUA (β = −0.30, 95% CI: −0.47 to −0.14, p

A fractal structure featuring symmetric/asymmetric airfoil fins is embedded within the smooth channels of the printed circuit heat exchanger (PCHE), significantly enhancing its heat transfer performance. In this study, a horizontally installed two-layer channel configuration is examined, with hot CO2 flowing through the upper channel and cold CO2 through the lower channel. Two distinct airfoil fin designs, namely NACA 0021 symmetric and NACA 4822 asymmetric, are tested for their channel reinforcement effect. The numerical analysis reveals that channels equipped with these fins exhibit substantially improved heat transfer compared to smooth channels. Notably, the comprehensive evaluation index for the asymmetric airfoil fin channel is enhanced by a factor ranging from 1.05 to 3.76. Moreover, despite a modest increase in pressure drop, indicated by a dimensionless friction factor of 0.67–1.31, the heat transfer performance remains superior. Crucially, optimal heat transfer does not rely solely on high fluid flow rates but instead demands an apt flow matching between the hot and cold fluid channels.

Abstract Background The aim of this study was to investigate the pathogenicity of vancomycin-resistant Enterococcus faecalis (VREs) to human colon cells in vitro. Methods Three E. faecalis isolates (2 VREs and E. faecalis ATCC 29212) were cocultured with NCM460, HT-29 and HCT116 cells. Changes in cell morphology and bacterial adhesion were assessed at different time points. Interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGFA) expression were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell migration and human umbilical vein endothelial cells (HUVECs) tube formation assays were used for angiogenesis studies. The activity of PI3K/AKT/mTOR signaling pathway was measured by Western blotting. Results The growth and adhesion of E. faecalis at a multiplicity of infection (MOI) of 1:1 were greater than those at a MOI of 100:1(p

Abstract Cancer immunotherapy is an attractive strategy because it stimulates immune cells to target malignant cells by regulating the intrinsic activity of the immune system. However, due to lacking many immunologic markers, it remains difficult to treat glioma, a representative “cold” tumor. Herein, to wake the “hot” tumor immunity of glioma, Porphyromonas gingivalis (Pg) is customized with a coating to create an immunogenic tumor microenvironment and further prove the effect in combination with the immune checkpoint agent anti‐PD‐1, exhibiting elevated therapeutic efficacy. This is accomplished not by enhancing the delivery of PD‐1 blockade to enhance the effect of immunotherapy, but by introducing bacterial photothermal therapy to promote greater involvement of M1 cells in the immune response. After reaching glioma, the bacteria further target glioma cells and M2 phenotype macrophages selectively, enabling precise photothermal conversion for lysing tumor cells and M2 phenotype macrophages, which thereby enhances the positive feedback loop of cancer cells‐M1 macrophages‐T cells. Collectively, the bacteria synergized with PD‐1 blockade strategy may be the key to overcoming the immunosuppressive glioma microenvironment and improving the outcome of immunotherapy toward glioma.

To tackle the intricate challenges associated with the low detection accuracy of images taken by unmanned aerial vehicles (UAVs), arising from the diverse sizes and types of objects coupled with limited feature information, we present the SRE-YOLOv8 as an advanced method. Our method enhances the YOLOv8 object detection algorithm by leveraging the Swin Transformer and a lightweight residual feature pyramid network (RE-FPN) structure. Firstly, we introduce an optimized Swin Transformer module into the backbone network to preserve ample global contextual information during feature extraction and to extract a broader spectrum of features using self-attention mechanisms. Subsequently, we integrate a Residual Feature Augmentation (RFA) module and a lightweight attention mechanism named ECA, thereby transforming the original FPN structure to RE-FPN, intensifying the network’s emphasis on critical features. Additionally, an SOD (small object detection) layer is incorporated to enhance the network’s ability to recognize the spatial information of the model, thus augmenting accuracy in detecting small objects. Finally, we employ a Dynamic Head equipped with multiple attention mechanisms in the object detection head to enhance its performance in identifying low-resolution targets amidst complex backgrounds. Experimental evaluation conducted on the VisDrone2021 dataset reveals a significant advancement, showcasing an impressive 9.2% enhancement over the original YOLOv8 algorithm.

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients’ prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs).Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was evaluated.Results: Among the patients taking immunosuppressive medication, PI was observed in 548 (6.9%). The median time of PI occurrence after immunosuppressive therapy was 123.0 (interquartile range: 63.0, 436.0) days. Thirteen statistically significant independent predictors (sex, age, hypertension, DM, malignant tumour, use of biologics, use of CNIs, use of methylprednisolone at 500 mg, use of methylprednisolone at 40 mg, use of methylprednisolone at 40 mg total dose, use of oral glucocorticoids, albumin level, and haemoglobin level) were screened using the LASSO algorithm and multivariate COX regression analysis. The PIP model built on these features performed reasonably well, with the developing C-index of 0.87 (sensitivity: 85.4%; specificity: 81.0%) and validation C-indices of 0.837, 0.829, 0.832 and 0.830 for predicting 90-, 180-, 270- and 360-day PI probability, respectively. The decision curve analysis (DCA) and calibration curves displayed excellent clinical utility and calibration performance of the nomogram.Conclusion: The PIP model presented herein could aid in the prediction of PI risk in individual patients who receive immunosuppressive treatment and help personalise clinical decision-making.

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to Crizotinib. Furthermore, molecular dynamic disclosed that introducing the spiro group could reduce the steric hindrance with bulky side chain (Arginine) in solvent region of ROS1G2032R, which explained the sensitivity of C01 to drug-resistant mutant. These results indicated a path forward for the generation of anti Crizotinib-resistant ROS1/ALK dual inhibitors.

BackgroundThere has been a surge in academic and business interest in software as a medical device (SaMD). SaMD enables medical professionals to streamline existing medical practices and make innovative medical processes such as digital therapeutics a reality. Furthermore, SaMD is a billion-dollar market. However, SaMD is not clearly understood as a technological change and emerging industry. ObjectiveThis study aims to review the landscape of SaMD in response to increasing interest in SaMD within health systems and regulation. The objectives of the study are to (1) clarify the innovation process of SaMD, (2) identify the prevailing typology of such innovation, and (3) elucidate the underlying mechanisms driving the SaMD innovation process. MethodsWe collected product information on 581 US Food and Drug Administration–approved SaMDs from the OpenFDA website and 268 company profiles of the corresponding manufacturers from Crunchbase, Bloomberg, PichBook.com, and other company websites. In addition to assessing the metadata of SaMD, we used correspondence and business process analysis to assess the distribution of intended use and how SaMDs interact with other devices in the medical process. ResultsThe current SaMD industry is highly concentrated in medical image processing and radiological analysis. Incumbents in the medical device industry currently lead the market and focus on incremental innovation, whereas new entrants, particularly startups, produce more disruptive innovation. We found that hardware medical device functions as a complementary asset for SaMD, whereas how SaMD interacts with the complementary asset differs according to its intended use. Based on these findings, we propose a regime map that illustrates the SaMD innovation process. ConclusionsSaMD, as an industry, is nascent and dominated by incremental innovation. The innovation process of the present SaMD industry is shaped by data accessibility, which is key to building disruptive innovation.

Abstract Background Enterococcus faecalis (Efa) has been shown to be a “driver bacteria” in the occurrence and development of colorectal cancer (CRC). This study aims to explore the effect of specific metabolites of Efa on CRC. Methods The pro-tumor effects of Efa were assessed in colonic epithelial cells. The tumor-stimulating molecule produced by Efa was identified using liquid chromatography mass spectrometry (LC-MS). The proliferative effect of metabolites on CRC cells in vitro was assayed as well. The concentration of vascular endothelial growth factor A (VEGFA) and interleukin-8 (IL-8) was determined using enzyme-linked immunosorbent assay (ELISA). Tubular formation assay of human umbilical vein endothelial cells (HUVEC) and cell migration assay were applied to study angiogenesis. Additionally, western blot analysis was used to investigate key regulatory proteins involved in the angiogenesis pathway. Tumor growth was assessed using mouse models with two CRC cells and human colon cancer organoid. Results Co-incubation with the conditioned medium of Efa increased the proliferation of cultured CRC cells. Biliverdin (BV) was determined as the key metabolite produced by Efa using LC-MS screening. BV promoted colony formation and cell proliferation and inhibited cell cycle arrest of cultured CRC cells. BV significantly increased the expression level of IL-8 and VEGFA by regulating the PI3K/AKT/mTOR signaling pathway, leading to the acceleration of angiogenesis in CRC. The up-regulation of proliferation and angiogenesis by BV were also confirmed in mice. Conclusion In conclusion, BV, as the tumor-stimulating metabolite of Efa, generates proliferative and angiogenic effects on CRC, which is mainly mediated by the activation of PI3K/AKT/mTOR.

In recent years, the frequency of strokes has been on the rise year by year and has become the second leading cause of death around the world, which is characterized by a high mortality rate, high recurrence rate, and high disability rate. Ischemic strokes account for a large percentage of strokes. A reperfusion injury in ischemic strokes is a complex cascade of oxidative stress, neuroinflammation, immune infiltration, and mitochondrial damage. Conventional treatments are ineffective, and the presence of the blood–brain barrier (BBB) leads to inefficient drug delivery utilization, so researchers are turning their attention to nano-drug delivery systems. Functionalized nano-drug delivery systems have been widely studied and applied to the study of cerebral ischemic diseases due to their favorable biocompatibility, high efficiency, strong specificity, and specific targeting ability. In this paper, we briefly describe the pathological process of reperfusion injuries in strokes and focus on the therapeutic research progress of nano-drug delivery systems in ischemic strokes, aiming to provide certain references to understand the progress of research on nano-drug delivery systems (NDDSs).

Epidermal growth factor receptor (EGFR) inhibitors have been used in clinical for the treatment of non-small-cell lung cancer for years. However, the emergence of drug resistance continues to be a major problem. To identify potential inhibitors, molecular docking-based virtual screening was conducted on ChemDiv and Enamine commercial databases using the Glide program. After multi-step VS and visual inspection, a total of 23 compounds with novel and varied structures were selected, and the predicted ADMET properties were within the satisfactory range. Further molecular dynamics simulations revealed that the reprehensive compound ZINC49691377 formed a stable complex with the allosteric pocket of EGFR and exhibited conserved hydrogen bond interactions with Lys 745 and Asp855 of EGFR over the course of simulation. All compounds were further tested in experiments. Among them, the most promising hit ZINC49691377 demonstrated excellent anti-proliferation activity against H1975 and PC-9 cells, while showing no significant anti-proliferation activity against A549 cells. Meanwhile, apoptosis analysis indicated that the compound ZINC49691377 can effectively induce apoptosis of H1975 and PC-9 cells in a dose-dependent manner, while having no significant effect on the apoptosis of A549 cells. The results indicate that ZINC49691377 exhibits good selectivity. Based on virtual screening and bioassays, ZINC4961377 can be considered as an excellent starting point for the development of new EGFR inhibitors.

The heat transfers on the single and array jet impingement with microcapsule phase change material (MEPCM) suspension are numerically investigated. The equivalent heat capacity method and DPM model are employed to treat the latent heat absorption and motion of the MEPCM particles in suspension, respectively, as well as the VOF method for tracking the free surface from suspension to air. The results show that the latent heat absorption and disturbance effect of the MEPCM particles can significantly improve the heat transfer of the suspension compared to the water. There exists an optimal jet distance at ΔL/D = 4.2 and an optimal suspension concentration at ηp = 5% to achieve the optimal heat transfer. The jet inlet temperature has a favourable range for the heat transfer enhancement, −0.83 < θj

Objectives: Caffeine has been shown to reduce the incidence of bronchopulmonary dysplasia (BPD). To investigate the protective mechanism of caffeine in a hyperoxia-based cell model of BPD in vitro.Methods: Type II alveolar epithelial cells (AECs II) were isolated and randomly divided into 6 groups: the normal, hyperoxia, caffeine (50 μM caffeine), antagonist (5 μM ZM241385), agonist (5 μM CGS21680), and DMSO groups. Transfection with siRNA against adenosine A2A receptor (siA2AR) was performed in AECs II.Results: Caffeine alone or in combination with adenosine A2A receptor (A2AR) antagonist inhibited apoptosis, promoted proliferation and reduced oxidative stress (OS). The cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) mRNA, A2AR mRNA and the protein levels of A2AR, phospho-Src, phospho-ERK1/2, phospho-P38 and cleaved caspase-3 were decreased in the caffeine and antagonist groups compared with that in the hyperoxia group. However, the effects of caffeine above were weakened by the A2AR agonist. Knockdown of A2AR showed similar results to caffeine.Discussion: Caffeine can reduce apoptosis, promote proliferation, and alleviate OS in hyperoxia-induced AECs II injury by inhibiting the A2AR/cAMP/PKA/Src/ERK1/2/p38MAPK signaling pathway. A2AR may serve as a promising therapeutic target for BPD in prematurity.

The fractional advection-reaction-diffusion equation plays a key role in describing the processes of multiple species transported by a fluid. Different numerical methods have been proposed for the case of fixed-order derivatives, while there are no such methods for the generalization of variable-order cases. In this paper, a numerical treatment is given to solve a variable-order model with time fractional derivative defined in the Atangana-Baleanu-Caputo sense. By using shifted Gegenbauer cardinal function, this approach is based on the application of spectral collocation method and operator matrices. Then the desired problem is transformed into solving a nonlinear system, which can greatly simplifies the solution process. Numerical experiments are presented to illustrate the effectiveness and accuracy of the proposed method.

Purpose: The underlying mechanism for radiation as a potentiator of immune checkpoint inhibition (ICI) is unclear. We developed a novel murine model to investigate the effects of post-irradiation intratumoral heterogeneity (ITH) on response to ICI. Experimental design: Parental mouse melanoma B16F10 cells were irradiated in vitro (5Gy x 3 fractions), then an a priori determined number of resulting colonies were implanted in C57BL/6J immunocompetent mice creating syngeneic models of unirradiated (parental) and irradiated tumors with low (irradiated-L) and high (irradiated-H) ITH. Mice were treated with placebo, α-PD-L1, α-CTLA-4 or dual ICI. Murine tumors underwent whole exome sequencing (WES). Clinically correlated paired pre- and post-irradiation patient rectal adenocarcinoma samples underwent WES. Results: Irradiated-L tumors showed increased tumor mutational burden (TMB) and a sustained decrease in ITH. Irradiated-L tumors were predicted to express five neoantigens with high variant allele frequency/clonal distribution. Mice with irradiated-L and irradiated-H versus parental B16F10 tumors demonstrated longer overall survival with dual ICI. Only mice with irradiated-L tumors experienced an overall survival benefit with single agent ICI. Clinically correlated rectal adenocarcinoma samples showed similarly increased TMB and decreased ITH following irradiation. Conclusions: Post-irradiation ITH modulates ICI response in a murine melanoma model. Irradiation may offer a mechanism to widen the therapeutic window of ICI.

Abstract Aims The purpose of this study was to perform an assessment of circulating microRNAs (miRNAs) as promising biomarker for hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) through a meta-analysis. Methods A comprehensive literatures search extended up to March 1, 2020 in PubMed, Cochrane library, Embase, Web of Science, Scopus and Ovid databases. The collected data were analyzed by random-effects model, the pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were used to explore the diagnostic performance of circulating miRNAs. Meta-regression and subgroup analysis were further carried out to explore the heterogeneity. Results A total of 16 articles including 3606 HCV-HCC patients and 3387 HCV patients without HCC were collected. The pooled estimates indicated miRNAs could distinguish HCC patients from chronic hepatitis C (CHC) and HCV-associated liver cirrhosis (HCV-LC), with a SEN of 0.83 (95% CI, 0.79–0.87), a SPE of 0.77 (95% CI, 0.71–0.82), a DOR of 17 (95% CI, 12–28), and an AUC of 0.87 (95% CI, 0.84–0.90). The combination of miRNAs and AFP showed a better diagnostic accuracy than each alone. Subgroup analysis demonstrated that diagnostic accuracy of miRNAs was better for plasma types, up-regulated miRNAs, and miRNA clusters. There was no evidence of publication bias in Deeks’ funnel plot. Conclusions Circulating miRNAs, especially for miRNA clusters, have a relatively high diagnostic value for HCV-HCC from CHC and HCV-LC.

Heat shock protein 90 (Hsp90) has been an important therapeutic target for cancer therapy for decades. Unexpectedly, the monotherapy of N-terminal Hsp90 inhibitor STA9090 related clinical trials halted in phase III, and metastases were reported in animal models with the treatment of N-terminal Hsp90 inhibitors. Vacuolar protein sorting-associated protein 35 (VPS35) plays a vital role in endosome-derived EV (extracellular vesicle) traffic in neurodegeneration diseases, but no vps35 related EV were reported in tumors till now. Since tumor derived EVs contributes to metastasis and VPS35 is recently found to be involved in the invasion and metastasis of hepatocellular carcinoma (HCC), whether N-terminal Hsp90 inhibitor STA9090 induced EVs generation and the role of VPS35 in it were explored in this study. We found that N-terminal Hsp90 inhibitor STA9090 upregulated Bclaf1 and VPS35 levels, increased the secretion of EVs, and STA9090-induced-EVs promoted the invasion of HepG2 cells. As the clinical data suggested that the increased Bclaf1 and VPS35 levels correlated with increased metastasis and poorer prognosis in HCC, we focused on the Bclaf1-VPS35-EVs axis to further explore the mechanism of VPS35-related metastasis. The results demonstrated that Bclaf1 facilitated the transcription of VPS35 via bZIP domain, and knockdown of Bclaf1 or VPS35 alleviated pro-metastatic capability of STA9090-induced-EVs. All the results revealed the role of Bclaf1-VPS35-EVs axis on metastasis of HCC, and VPS35 knockdown decreased Hsp90 Inhibitor STA9090 induced extracellular vesicle release and metastasis, which provided a new combination therapeutic strategy to inhibit the metastasis of HCC caused by N-terminal Hsp90 inhibitor induced extracellular vesicles.

In the context of global countries’ pursuit of sustainable development and “dual carbon” goals of China, this paper combines the Tapio decoupling model, Kaya’s equation and LMDI decomposition method to analyze the relationship between carbon emissions and economic growth and the driving factors of carbon emissions in the Yellow River Basin (YRB) of China from 2001 to 2019. It is found that the decoupling state of CO2 and economic growth in the Yellow River Basin shows a trend of expansion negative decoupling - expansion connection - weak decoupling - strong decoupling, but different regions shows some heterogeneity. The economic intensity effect and population size effect generally play a positive role in driving carbon emissions, while carbon emission intensity, industrial structure and energy structure effect play a negative role in driving carbon emissions in most years. From the regional perspective, the energy consumption structure in the middle reaches is the most important factor to promote carbon emissions. In terms of time period, the industrial structure effect is the driving factor of carbon emissions in the decoupling state overall as expansionary linkage, while it is the inhibitor of carbon emissions in the decoupling state overall as weak decoupling. This study also puts forward countermeasures such as optimize the energy structure and upgrade the industrial structure to achieve green and high-quality economic development in the YRB.

Based on the shear stress transfer (SST) k-ω model, Ffowcs-Williams and Hawkings (FW–H) equation, and Lilley sound source equation, the flow and sound field of high-temperature and high-pressure steam ejectors are simulated. The entrainment performance, near-field sound source, and far-field noise of the steam ejector are discussed. The influences of working parameters including the primary steam pressure, the secondary steam pressure, and the back pressure are analyzed. The results show that under the design conditions, the steam ejector has two shock waves and three sound source regions. A shear layer at the boundary of the first shock wave generates the Sound source-I, and the flow separation at the boundary of the second shock wave causes the Sound source-III. The Sound source-II is located near the mixing chamber wall and the sound pressure levels around the ejector depend on the distances from the Sound source-II. In terms of the entrainment performance, with the increasing primary pressure or the decreasing secondary pressure, as the driving pressure difference of the secondary steam decreases, so does the entrainment ratio. As the back pressure increases, the entrainment ratio firstly remains constant, and then rapidly decreases when the back pressure exceeds the critical value at pb = 5.5 MPa. In terms of the noise characteristics, the sound pressure level and the intensity of the second shock wave have a positive correlation. When the primary or secondary pressure increases, the sound pressure level increases. Moreover, with the increasing back pressure, the sound pressure level firstly decreases, reaches the minimum of 98.2 dB at the critical back pressure, and then slowly increases.

Targeting the epidermal growth factor receptor (EGFR) is one of the potential ways to treat glioblastoma (GBM). In this study, we investigate the anti-GBM tumor effects of the EGFR inhibitor SMUZ106 in both in vitro and in vivo conditions. The effects of SMUZ106 on the growth and proliferation of GBM cells were explored through MTT and clone formation experiments. Additionally, flow cytometry experiments were conducted to study the effects of SMUZ106 on the cell cycle and apoptosis of GBM cells. The inhibitory activity and selectivity of SMUZ106 to the EGFR protein were proved by Western blotting, molecular docking, and kinase spectrum screening methods. We also conducted a pharmacokinetic analysis of SMUZ106 hydrochloride following i.v. or p.o. administration to mice and assessed the acute toxicity level of SMUZ106 hydrochloride following p.o. administration to mice. Subcutaneous and orthotopic xenograft models of U87MG-EGFRvIII cells were established to assess the antitumor activity of SMUZ106 hydrochloride in vivo. SMUZ106 could inhibit the growth and proliferation of GBM cells, especially for the U87MG-EGFRvIII cells with a mean IC50 value of 4.36 μM. Western blotting analyses showed that compound SMUZ106 inhibits the level of EGFR phosphorylation in GBM cells. It was also shown that SMUZ106 targets EGFR and presents high selectivity. In vivo, the absolute bioavailability of SMUZ106 hydrochloride was 51.97%, and its LD50 exceeded 5000 mg/kg. SMUZ106 hydrochloride significantly inhibited GBM growth in vivo. Furthermore, SMUZ106 inhibited the activity of U87MG-resistant cells induced by temozolomide (TMZ) (IC50: 7.86 μM). These results suggest that SMUZ106 hydrochloride has the potential to be used as a treatment method for GBM as an EGFR inhibitor.

BackgroundDistant metastasis is the leading risk factor of death in breast cancer patients, with lung and liver being commonly involved sites of distant seeding. Ongoing clinical trials are studying the benefit from additional local treatment to these metastatic sites with radiation therapy. However, little is known about the tissue-specific microenvironment and the modulating response to treatments due to limitations of traditional in vitro systems. By using biomatrix scaffolds (BMSs) to recreate the complex composition of extracellular matrices in normal organs, we chose to study the radiotherapy response with engineered breast cancer “metastases” in liver and lung organ-specific tissues.MethodsLiver and lung BMSs were prepared for tissue culture. Human breast cancer cell lines were passaged on normal tissue culture plates or tissue culture plates coated with Matrigel, liver BMSs, and lung BMSs. Clonogenic assays were performed to measure cell survival with varying doses of radiation. Reactive Oxygen Species (ROS) detection assay was used to measure ROS levels after 6 Gy irradiation to cancer cells.ResultsThe response of breast cell lines to varying doses of radiotherapy is affected by their in vitro acellular microenvironment. Breast cancer cells grown in liver BMSs were more radiosensitive than when grown in lung BMSs. ROS levels for breast cancer cells cultured in lung and liver BMSs were higher than that in plastic or in Matrigel plate cells, before and after radiotherapy, highlighting the interaction with surrounding tissue-specific growth factors and cytokines. ROSs in both lung and liver BMSs were significantly increased after radiotherapy delivery, suggesting these sites create prime environments for radiation-induced cell death.ConclusionsThe therapeutic response of breast cancer metastases is dependent on the organ-specific microenvironment. The interaction between tissue microenvironment in these organs may identify sensitivity of therapeutic drug targets and radiation delivery for future studies.

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumour in the central nervous system (CNS). As the ideal targets for GBM treatment, Src family kinases (SFKs) have attracted much attention. Herein, a new series of imidazo[4,5-c]pyridin-2-one derivatives were designed and synthesised as SFK inhibitors. Compounds 1d, 1e, 1q, 1s exhibited potential Src and Fyn kinase inhibition in the submicromolar range, of which were next tested for their antiproliferative potency on four GBM cell lines. Compound 1s showed effective activity against U87, U251, T98G, and U87-EGFRvIII GBM cell lines, comparable to that of lead compound PP2. Molecular dynamics (MDs) simulation revealed the possible binding patterns of the most active compound 1s in ATP binding site of SFKs. ADME prediction suggested that 1s accord with the criteria of CNS drugs. These results led us to identify a novel SFK inhibitor as candidate for GBM treatment.

Abstract Applying machine learning to healthcare sheds light on evidence-based decision making and has shown promises to improve healthcare by combining clinical knowledge and biomedical data. However, medicine and data science are not synchronized. Oftentimes, researchers with a strong data science background do not understand the clinical challenges, while on the other hand, physicians do not know the capacity and limitation of state-of-the-art machine learning methods. The difficulty boils down to the lack of a common interface between two highly intelligent communities due to the privacy concerns and the disciplinary gap. The School of Biomedical Informatics (SBMI) at UTHealth is a pilot in connecting both worlds to promote interdisciplinary research. Recently, the Center for Secure Artificial Intelligence For hEalthcare (SAFE) at SBMI is organizing a series of machine learning healthcare hackathons for real-world clinical challenges. We hosted our first Hackathon themed centered around Sudden Unexpected Death in Epilepsy and finding ways to recognize the warning signs. This community effort demonstrated that interdisciplinary discussion and productive competition has significantly increased the accuracy of warning sign detection compared to the previous work, and ultimately showing a potential of this hackathon as a platform to connect the two communities of data science and medicine.

Abstract Objectives The aim of this study was to systematically assess the accuracy of circulating microRNAs (miRNAs) as a promising biomarker for sepsis via a meta-analysis. Methods PubMed, Cochrane Library, Embase, Web of Science, Scopus, and Ovid databases were searched up to April 3, 2020. The Quality in Prognostic Studies (QUADAS-2) tool was used to assess methodological quality. The pooled sensitivity (Sen), specificity (Spe), positive or negative likelihood ratios (PLR or NLR), diagnostic odds ratio (DOR), curve, and area under the curve (AUC) were calculated with 95% confidence interval (95% CI). The overall accuracy (OA) of miRNAs, procalcitonin (PCT), and C-reactive protein (CRP) was analyzed by the chi-square test. Results A total of 22 records were eligible for systematic review, including 2210 sepsis, 426 systemic inflammatory response syndrome (SIRS), and 1076 healthy controls (HC). The pooled Sen, Spe, and DOR of miRNAs were 0.80 (95% CI 0.75–0.83), 0.85 (95% CI 0.80–0.89), and 22 (15–32), respectively. The DOR of PCT and CRP were 17 (95% CI 4–68) and 7 (95% CI 1–48), respectively. The OA value of miRNAs (79.02%) and PCT (76.95%) were higher than CRP (61.22%) (P < 0.000). The subgroup analysis indicated that miRNAs in adults, serum type, downregulation of miRNA expression, criteria of Sepsis-3, internal reference of non-U6, and dysregulation expression of miR-223 had superior diagnostic accuracy. In addition, there was no significant publication bias among the included studies. Fagan’s nomogram showed valuable clinical utility. Conclusions Our meta-analysis indicated that the level of circulating miRNAs, particularly the miR-223, could be used as an indicator for sepsis.

Synechococcus is one group of main primary producers and plays a key role in oceanic carbon fixation and transformation. To explore how the temperature rise affects the bioavailability of Synechococcus-derived dissolved organic matter (SOM) and whether this effect would be altered by the involvement of heterotrophic bacteria, we compared the optical and molecular properties of the SOM of axenic Synechococcus sp. PCC7002 culture (Syn) to that with associated heterotrophic bacteria (SynB) under 15, 18, and 21°C growth temperatures at exponential and decay growth phases. Our results showed that the temperature rise increased the bioavailability of the SOM of both Syn and SynB cultures by lowering the proportion of the hydrogen-poor and double-bond structure-rich humus-like components and highly unsaturated substances, as indicated by the increase of spectral slope ratio (SR) and biological index (BIX) and decrease of humification index (HIX). Moreover, the involvement of heterotrophic bacteria modified the Synechococcus-derived SOM, together with its intracellular dissolved organic matter (DOM) excludes, lowering the SOM bioavailability. Our results indicated that the warming in climate change scenario may enhance the bioavailability of the Synechococcus-derived SOM although it may be tempered by the involvement of heterotrophic bacteria, providing an insight for preservation of the organic carbon pool in global oceans.

The purpose of this study was to investigate the effect of percutaneous nephrolithotripsy guided by B-ultrasound in the treatment of complex renal calculi. A total of 82 patients with complex renal calculi were selected, who underwent percutaneous nephrolithotripsy guided by B-ultrasound. The average operation time was 101.52 ±8.35 minutes, the average intraoperative bleeding volume was 132.86 ±7.22 ml, the average hospital stay was 10.47 (±1.68) days, the primary calculi clearance rate was 85.37% (70 cases), and the secondary calculi clearance rate was 95.12% (78 cases). Postoperative complications occurred in 18 (21.95%) cases, including fever in 13 (15.85%), residual stone in 4 (4.88%), and delayed bleeding in 1 (1.22%) case. The findings show that percutaneous nephrolithotripsy guided by B-ultrasound is safe and effective in the treatment of complex renal calculi and is suitable for popularisation and application in primary hospitals. Key words: B-ultrasound; complex renal calculi; percutaneous nephrolithotomy

Abstract Introduction Enterococcus faecalis is a significant cause of nosocomial infections and is difficult to treat because of intrinsic and acquired resistance to many antibiotics. In addition, the emergence of linezolid-resistant E. faecalis (LZR-Efa) is reducing the choices available for anti-infective therapy. The aim of this study was to examine the in vitro antibacterial effects of fosfomycin (FM), vancomycin (VAN) and daptomycin (DAP), alone and in combination, against LZR-Efa. Methods Five LZR-Efa strains and E. faecalis ATCC 29212 were studied. The antibacterial effects of FM, and of FM, VAN and DAP, were assessed using the time–kill assay. Biofilm formation and elimination were evaluated by crystal violet staining. Results When used at concentrations greater than 0.5 × MIC, FM did not produce dose-dependent effects against LZR-Efa isolates. The use of DAP (47.1 mg/L) alone, and FM (83 mg/L) combined with DAP (20.6 mg/L), produced a persistent inhibitory effect against both planktonic LZR-Efa isolates and those forming biofilms. In addition, FM and VAN combined with glucose-6-phosphate produced visible eradication effects against biofilms grown for 24 h, while DAP alone or combined with FM resulted in the best eradication activity against biofilms grown for 72 h prior to exposure. Conclusion The use of FM combined with DAP provided the best potential therapeutic option for treating LZR-Efa infections out of those tested. In addition, the optimum treatment for biofilm elimination depended on the stage of biofilm formation.

Abstract Background Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at

Background Infantile pneumonia (IP) seriously affects the health of children. This article mainly discussed the protective effect of long non-coding RNA NKILA (lnc NKILA) on IP by detecting cell viability, apoptosis and inflammatory response of MRC5 cells.Methods Cell counting kit-8 (CCK-8) was used to detect cell viability, while flow cytometry was used to detect cell apoptosis. The expression of apoptosis-associated factors (Bcl-2, Bax, PARP and Cleaved-PARP) and NF-κB and JNK pathway-related factors (t-IκBα, p-IκBα, t-p65, p-p65, β-actin, t-JNK and p-JNK) were tested by western blot. Otherwise, productions of inflammatory factors interleukin (IL)-1β and IL-6 were tested by enzyme-linked immunosorbent assay (ELISA) and western blot. Furthermore, RNA levels were respectively tested and changed by RT-qPCR and cell transfection.Results Tumour necrosis factor-α (TNF-α) treatment reduced cell viability, induced cell apoptosis and promoted inflammatory factors expression. NKILA overexpression remitted TNF-α-induced injury. Moreover, NKILA positively regulated miR-21. miR-21 inhibition could weaken the functions of NKILA overexpression on TNF-α-induced injury. At last, NKILA and miR-21 were involved in the regulation of JNK and NF-κB pathways.Conclusions NKILA overexpression remitted TNF-α-induced MRC5 cell injury by up-regulation of miR-21 and via inactivation of JNK and NF-κB signaling pathways.

The 2014 Research Excellence Framework (REF) assessed the quality of university research in the UK. 20% of the assessment was allocated according to peer review of the impact of research, reflecting the growing importance of impact in UK government policy. Beyond academia, impact is defined as a change or benefit to the economy, society, culture, public policy or services, health, the environment, or quality of life. Each institution submitted a set of four-page impact case studies. These are predominantly free-form descriptions and evidences of the impact of study. Numerous analyses of these case studies have been conducted, but they have utilised either qualitative methods or primary forms of text searching. These approaches have limitations, including the time required to manually analyse the data and the frequently inferior quality of the answers provided by applying computational analysis to unstructured, context-less free text data. This paper describes a new system to address these problems. At its core is a structured, queryable representation of the case study data. We describe the ontology design used to structure the information and how semantic web related technologies are used to store and query the data. Experiments show that this gives two significant advantages over existing techniques: improved accuracy in question answering and the capability to answer a broader range of questions, by integrating data from external sources. Then we investigate whether machine learning can predict each case study’s grade using this structured representation. The results provide accurate predictions for computer science impact case studies.

Combined with wavelet threshold denoising and Ensemble Empirical Mode Decomposition (EEMD) decomposition, an identification method based on Manta Ray Foraging Optimization-BP (MRFO-BP) neural network for vibration signals of residual pressure utilization hydraulic units is proposed to distinguish the vibration signal of each unit. The feature vectors of vibration signals are extracted by wavelet denoising and EEMD decomposition. The weights and thresholds in BP neural network are optimized by the MRFO algorithm. The feature vectors are input into the optimized BP neural network to realize the identification and classification of vibration signals. Compared with Particle Swarm Optimization-BP (PSO-BP) neural network, Bat Algorithm-BP (BA-BP) neural network, and BP neural network, the results show that the identification rate of each measuring point from the MRFO-BP neural network is greatly improved. The average identification rate of other measuring points is 98.514%, except the identification rate of the generator, which is 85.389%. Therefore, the MRFO-BP neural network has better stability and higher identification accuracy and can identify and classify vibration signals more accurately. The conclusions can provide theoretical basis for vibration signals identification of residual pressure utilization hydraulic unit. When the vibration signal of each unit cannot be clearly distinguished, the vibration signals of the units are identified by the method proposed in this paper. According to the obtained results, a feasible classification method can be provided for the vibration signals belonging to different units.

Aim: It is difficult to identify neonatal sepsis early due to the lack of specific markers. The aim of the present study was to explore whether miR-26a expression in peripheral blood mononuclear cells (PBMCs) could be used as a diagnostic marker of the disease and whether phosphatase and tensin homolog (PTEN) was involved in suppressing miR-26a expression.Methods: A total of 51 early-onset septic newborns and 102 healthy newborns were included. Blood specimens were collected from septic newborns at the time of clinical diagnosis (baseline) and again between 72 and 96 h after birth. Blood specimens were collected from healthy newborns on admission. The expressions of miR-26a and PTEN in PBMCs were measured using real-time quantitative PCR (RT-qPCR). Other data, including hemoculture, were collected from medical records.Results: In septic newborns with and without a positive hemoculture, a lower baseline level of miR-26a in PBMCs was associated with a higher risk of disease. Additionally, at baseline, there was a certain linear relationship between the levels of miR-26a and two serological inflammatory markers (i.e., white blood cell count and C-reactive protein level) in septic newborns. In addition, the baseline expressions of miR-26a and PTEN showed a reverse linear relationship. Compared with those at baseline, the expression of miR-26a was higher and the expression of PTEN was lower in septic newborns starting at 72 h after birth.Conclusion: A lower baseline miR-26a expression in PBMCs indicated the occurrence of early-onset neonatal sepsis, and a reduced miR-26a expression might be partly related to the inflammatory process and PTEN upregulation.

Glioblastoma multiforme (GBM) is the most common brain malignancy and major cause of high mortality in patients with GBM, and its high recurrence rate is its most prominent feature. However, the pathobiological mechanisms involved in recurrent GBM remain largely unknown. Here, whole-transcriptome sequencing (RNA-sequencing, RNA-Seq) was used in characterizing the expression profile of recurrent GBM, and the aim was to identify crucial biomarkers that contribute to GBM relapse. Differentially expressed RNAs in three recurrent GBM tissues compared with three primary GBM tissues were identified through RNA-Seq. The function and mechanism of a candidate long noncoding RNA (lncRNA) in the progression and recurrence of GBM were elucidated by performing comprehensive bioinformatics analyses, such as functional enrichment analysis, protein–protein interaction prediction, and lncRNA–miRNA–mRNA regulatory network construction, and a series of in vitro assays. As the most significantly upregulated gene identified in recurrent GBM, HSPA1A is mainly related to antigen presentation and the MAPK signaling pathway, as indicated by functional enrichment analysis. HSPA1A was predicted as the target gene of the lncRNA NONHSAT079852.2. qRT-PCR revealed that NONHSAT079852.2 was significantly elevated in recurrent GBM relative to that in primary GBM, and high NONHSAT079852.2 expression was associated with the poor overall survival rates of patients with GBM. The knockdown of NONHSAT079852.2 successfully induced tumor cell apoptosis, inhibited the proliferation, migration, invasion and the expression level of HSPA1A in glioma cells. NONHSAT079852.2 was identified to be a sponge for hsa-miR-10401-3p through luciferase reporter assay. Moreover, HSPA1A was targeted and regulated by hsa-miR-10401-3p. Collectively, the results suggested that NONHSAT079852.2 acts as a sponge of hsa-mir-10401-3p and thereby enhances HSPA1A expression, promotes tumor cell proliferation and invasion, and leads to the progression and recurrence of GBM. This study will provide new insight into the regulatory mechanisms of NONHSAT079852.2-mediated competing endogenous RNA in the pathogenesis of recurrent GBM and evidence of the potential of lncRNAs as diagnostic biomarkers or potential therapeutic targets.

Electronic health records are valuable for clinical and translational research. Institutions must protect patient privacy and comply with applicable regulations while allowing appropriate access to clinical data for research. The processes that investigators must follow to access clinical data can be substantially different at different institutions. In this paper, we describe the process developed at our institution that has been active for 5 years and was used to satisfy over 200 requests for access to identified clinical data, usually within 1 day for internal requests and 3 days for visiting researchers.

Abstract Background Due to the intact structure of lignocellulosic biomass, pretreatment was a prerequisite to improve the enzymatic hydrolysis by disrupting the recalcitrant lignocellulose and increasing the accessibility of cellulose to enzyme. In this study, an alkaline hydrogen peroxide (AHP) pretreatment of sugarcane bagasse with various loadings of H2O2 (1.25–6.25 wt%) at temperatures of 60–160 °C was proposed to degrade hemicellulose/lignin and improve the enzymatic digestibility. Results It was found that increasing H2O2 loadings during pretreatment lead to the enhancement of substrate digestibility, whereas the alkali (only NaOH)-pretreated solid generated higher glucose yield than that pretreated under AHP pretreatment with lower loading of H2O2. This enhancement of enzymatic digestibility was due to the degradation of hemicellulose and lignin. Furthermore, Tween 80 was added to promote enzymatic digestibility, however, the increased yields were different with various substrates and hydrolysis time. The highest glucose yield of 77.6% was obtained after pretreatment at 160 °C for 60 min with 6.25% H2O2 and the addition of Tween 80, representing 89.1% of glucose in pretreated substrate. Conclusions This study demonstrated that the AHP pretreatment could greatly enhance the enzymatic saccharification. The addition of Tween 80 played remarkable performances in promoting the glucose yield during enzymatic hydrolysis by stabilizing and protecting the enzyme activity. This study provided an economical feasible and gradual process for the generation of glucose, which will be subsequently converted to bioethanol and bio-chemicals.

Abstract Background The recalcitrant structure of lignocellulosic biomass made it challenging for their bioconversion into biofuels and biochemicals. Pretreatment was required to deconstruct the intact structure by the removal of hemicellulose/lignin, improving the cellulose accessibility of enzyme. Combinatorial pretreatments with liquid hot water/H2SO4 and ethanol/NaOH of sugarcane bagasse were developed to improve enzymatic hydrolysis under mild conditions. Results After one-step 60% ethanol containing 0.5% NaOH pretreatment with solid to liquid ratio of 1/10, the glucose yield after hydrolysis for 72 h with enzyme dosage of 20 FPU/g substrate was enhanced by 41% and 205% compared to that of NaOH or 60% ethanol pretreated solids, respectively. This improvement was correlated with the removal of hemicellulose and lignin. However, using combinatorial pretreatments with 1% H2SO4 followed by 60% ethanol containing 0.5% NaOH, the highest glucose yield with Tween 80 reached 76%, representing 84.5% of theoretical glucose in pretreated substrate. While retaining similar glucose yield, the addition of Tween 80 capacitated either a reduction of enzyme loading by 50% or shortening hydrolysis time to 24 h. However, the enhancement with the addition of Tween 80 decreased as hydrolysis time was extended. Conclusions This study demonstrated that a combinatorial pretreatment with 1% H2SO4 followed by 60% ethanol containing 0.5% NaOH had significant effects on improving the enzymatic hydrolysis of sugarcane bagasse. The addition of Tween 80 enabled reducing the enzyme loading or shortening the hydrolysis time. This study provided an economically feasible and mild process for the generation of glucose, which will be subsequently converted to bioethanol and biochemicals.

ABSTRACT Eutrophication and deoxygenation possibly occur in coastal waters due to excessive nutrients from agricultural and aquacultural activities, leading to sulfide accumulation. Cyanobacteria, as photosynthetic prokaryotes, play significant roles in carbon fixation in the ocean. Although some cyanobacteria can use sulfide as the electron donor for photosynthesis under anaerobic conditions, little is known on how they interact with sulfide under aerobic conditions. In this study, we report that Synechococcus sp. strain PCC7002 (PCC7002), harboring an sqr gene encoding sulfide:quinone oxidoreductase (SQR), oxidized self-produced sulfide to S0, present as persulfide and polysulfide in the cell. The Δsqr mutant contained less cellular S0 and had increased expression of key genes involved in photosynthesis, but it was less competitive than the wild type in cocultures. Further, PCC7002 with SQR and persulfide dioxygenase (PDO) oxidized exogenous sulfide to tolerate high sulfide levels. Thus, SQR offers some benefits to cyanobacteria even under aerobic conditions, explaining the common presence of SQR in cyanobacteria. IMPORTANCE Cyanobacteria are a major force for primary production via oxygenic photosynthesis in the ocean. A marine cyanobacterium, PCC7002, is actively involved in sulfide metabolism. It uses SQR to detoxify exogenous sulfide, enabling it to survive better than its Δsqr mutant in sulfide-rich environments. PCC7002 also uses SQR to oxidize endogenously generated sulfide to S0, which is required for the proper expression of key genes involved in photosynthesis. Thus, SQR has at least two physiological functions in PCC7002. The observation provides a new perspective for the interplays of C and S cycles.

Recent studies have illuminated that blocking Ca2+ influx into effector cells is an attractive therapeutic strategy for lung injury. We hypothesize that T-type calcium channel may be a potential therapeutic target for acute lung injury (ALI). In this study, the pharmacological activity of mibefradil (a classical T-type calcium channel inhibitor) was assessed in a mouse model of lipopolysaccharide- (LPS-) induced ALI. In LPS challenged mice, mibefradil (20 and 40 mg/kg) dramatically decreased the total cell number, as well as the productions of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF). Mibefradil also suppressed total protein concentration in BALF, attenuated Evans blue extravasation, MPO activity, and NF-κB activation in lung tissue. Furthermore, flunarizine, a widely prescripted antimigraine agent with potent inhibition on T-type channel, was also found to protect mice against lung injury. These data demonstrated that T-type calcium channel inhibitors may be beneficial for treating acute lung injury. The important role of T-type calcium channel in the acute lung injury is encouraged to be further investigated.

Phosphatidylcholine (PC) has been demonstrated as anti-inflammatory and antioxidant/pro-oxidant molecules. In this study, we investigated the protective effects of PC on inflammatory bowel disease (IBD) caused by lipopolysaccharide (LPS)-induced injury in intestinal epithelia cells. The IEC-6 cells (intestinal epithelia cells) were stimulated with LPS (1 μg/mL) for 24 h with or without PC pretreatment, in the next steps: (1) the level of the inflammatory cytokine tumor necrosis factor (TNF)-α was measured with ELISA; (2) the nuclear translocation and phosphorylation of NF-κB was investigated with Western blot, EMSA, immunofluorence assay; (3) the protein phosporylation levels in MAPK signaling pathway were detected with Western blot method. The results showed: (1) compared with the normal group, 10 and 20 μg/mL of PC significantly inhibited the production and activation of TNF-α, (P

Glioma is the most common and aggressive tumor of the central nervous system. The uncontrolled proliferation, cellular heterogeneity, and diffusive capacity of glioma cells contribute to a very poor prognosis of patients with high grade glioma. Compared to normal cells, cancer cells exhibit a higher rate of glucose uptake, which is accompanied with the metabolic switch from oxidative phosphorylation to aerobic glycolysis. The metabolic reprogramming of cancer cell supports excessive cell proliferation, which are frequently mediated by the activation of oncogenes or the perturbations of tumor suppressor genes. Recently, a growing body of evidence has started to reveal that long noncoding RNAs (lncRNAs) are implicated in a wide spectrum of biological processes in glioma, including malignant phenotypes and aerobic glycolysis. However, the mechanisms of diverse lncRNAs in the initiation and progression of gliomas remain to be fully unveiled. In this review, we summarized the diverse roles of lncRNAs in shaping the biological features and aerobic glycolysis of glioma. The thorough understanding of lncRNAs in glioma biology provides opportunities for developing diagnostic biomarkers and novel therapeutic strategies targeting gliomas.

Abstract In this editorial, we first summarize the 2016 International Conference on Intelligent Biology and Medicine (ICIBM 2016) that was held on December 8–10, 2016 in Houston, Texas, USA, and then briefly introduce the ten research articles included in this supplement issue. ICIBM 2016 included four workshops or tutorials, four keynote lectures, four conference invited talks, eight concurrent scientific sessions and a poster session for 53 accepted abstracts, covering current topics in bioinformatics, systems biology, intelligent computing, and biomedical informatics. Through our call for papers, a total of 77 original manuscripts were submitted to ICIBM 2016. After peer review, 11 articles were selected in this special issue, covering topics such as single cell RNA-seq analysis method, genome sequence and variation analysis, bioinformatics method for vaccine development, and cancer genomics.

Objective. Phosphatidylcholine (PC) is the major surface-active phospholipid and creates a hydrophobic nature to the surface. It has been reported to reverse the progression of liver fibrosis and to improve liver function. The aim of the present study was to evaluate the effects of orally administered PC on intestinal barrier function (IBF) in rats with drug-induced liver injury. Method. Rats with carbon tetrachloride- (CCl4-) induced liver injury were treated with 100 mg/kg PC once daily for 21 days. The effects of PC therapy on (i) liver function and portal pressure, (ii) intestinal and hepatic histology, and (iii) plasma endotoxin, diamine oxidase (DAO), and tumour necrosis factor- (TNF-) α levels were investigated. Results. PC therapy reduced portal pressure and improved the liver function in CCl4-induced liver injury. In PC-treated liver injury rats, collagen fibres were gradually decreased, while the disordered arrangement of hepatocytes and disorganized hepatic lobules were partially repaired, and inflammatory cell infiltration was decreased in the fibrous tissue. Lower inflammatory cell infiltration in the ileum improved intestinal histology, and reduced serum DAO levels were observed in PC-treated cirrhotic rats. These changes were associated with reduced inflammatory activity, as indicated by decreased serum TNF-α levels and plasma endotoxin levels. Conclusions. These results suggest that PC therapy is hepatoprotective and is able to restore IBF and reduce endotoxaemia in rats with drug-induced liver injury.

Background As the world’s second-largest economy, China has launched health reforms for the second time and invested significant funding in medical informatics (MI) since 2010; however, few studies have been conducted on the outcomes of this ambitious cause. Objective This study analyzed the features of major MI meetings held in China and compared them with similar MI conferences in the United States, aiming at informing researchers on the outcomes of MI in China and the US from the professional conference perspective and encouraging greater international cooperation for the advancement of the field of medical informatics in China and, ultimately, the promotion of China’s health reform. Methods Qualitative and quantitative analyses of four MI meetings in China (i.e., CMIAAS, CHINC, CHITEC, and CPMI) and two in the US (i.e., AMIA and HIMSS) were conducted. Furthermore, the size, constituent parts and regional allocation of participants, topics, and fields of research for each meeting were determined and compared. Results From 1985 to 2016, approximately 45,000 individuals attended the CMIAAS and CPMI (academic), CHINC and CHITEC (industry), resulting in 5,085 documented articles. In contrast, in 2015, 38,000 and 3,700 individuals, respectively, attended the American HIMSS (industry) and AMIA (academic) conferences and published 1,926 papers in the latter. Compared to those of HIMSS in 2015, the meeting duration of Chinese industry CHITEC was 3 vs. 5 days, the number of vendors was 100 vs. 1,500+, the number of sub-forums was 10 vs. 250; while compared to those of AMIA, the meeting duration of Chinese CMIAAS was 2 vs. 8 days, the number of vendors was 5 vs. 65+, the number of sub-forums was 4 vs. 26. HIMSS and AMIA were more open, international, and comprehensive in comparison to the aforementioned Chinese conferences. Conclusions The current MI in China can be characterized as “hot in industry application, and cold in academic research.” Taking into consideration the economic scale together with the huge investment in MI, conference yield and attendee diversity are still low in China. This study demonstrates an urgent necessity to elevate the medical informatics discipline in China and to expand research fields in order to maintain pace with the development of medical informatics in the US and other countries.

At least 15 cases of human beings infected with H5N6 have been reported since 2014, of which at least nine were fatal. The highly pathogenic avian H5N6 influenza virus may pose a serious threat to both public health and the poultry industry. However, the molecular features promoting the adaptation of avian H5N6 influenza viruses to mammalian hosts is not well understood. Here, we sequentially passaged an avian H5N6 influenza A virus (A/Northern Shoveler/Ningxia/488-53/2015) 10 times in mice to identify the adaptive amino acid substitutions that confer enhanced virulence to H5N6 in mammals. The 1st and 10th passages of the mouse-adapted H5N6 viruses were named P1 and P10, respectively. P1 and P10 displayed higher pathogenicity in mice than their parent strain. P10 showed significantly higher replication capability in vivo and could be detected in the brains of mice, whereas P1 displayed higher replication efficiency in their lungs but was not detectable in the brain. Similar to its parent strain, P10 remained no transmissible between guinea pigs. Using genome sequencing and alignment, multiple amino acid substitutions, including PB2 E627K, PB2 T23I, PA T97I, and HA R239H, were found in the adaptation of H5N6 to mice. In summary, we identified amino acid changes that are associated with H5N6 adaptation to mice.

Janus kinase 2 (JAK2) is an intracellular nonreceptor tyrosine kinase that belongs to the JAK family of kinases, which play an important role in survival, proliferation, and differentiation of a variety of cells. JAK2 inhibitors are potential drugs for the treatment of myeloproliferative neoplasms. The three dimensional quantitative structure-activity relationships have been studied on a series of JAK2 inhibitors by comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA). The CoMFA model had a cross-validated coefficient q2 of 0.633, and the relation non-cross-validated coefficient r2 of 0.976. The F value is 225.030. The contributions of steric and electrostatic fields to the activity are 55.2% and 44.8%, respectively. For the CoMSIA study, the q2, r2, and F values of the model are 0.614, 0.929, and 88.771, respectively. The contributions of steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond donor fields to the activity are 27.3%, 23.9%, 16.4%, 21.7%, and 10.7%, respectively. The CoMFA and CoMSIA models showed strong predictive ability, and the 3D contour plots give the basis on the structure modification of JAK2 inhibitors.

Tie-2, a kind of endothelial cell tyrosine kinase receptor, is required for embryonic blood vessel development and tumor angiogenesis. Several compounds that showed potent activity toward this attractive anticancer drug target in the assay have been reported. In order to investigate the structure-activity correlation of indolocarbazole series compounds and modify them to improve their selectivity and activity, 3D-QSAR models were built using CoMFA and CoMSIA methods and molecular docking was used to check the results. Based on the common sketch align, two good QSAR models with high predictabilities (CoMFA model: q2 = 0.823, r2 = 0.979; CoMSIA model: q2 = 0.804, r2 = 0.967) were obtained and the contour maps obtained from both models were applied to identify the influence on the biological activity. Molecular docking was then used to confirm the results. Combined with the molecular docking results, the detail binding mode between the ligands and Tie-2 was elucidated, which enabled us to interpret the structure-activity relationship. These satisfactory results not only offered help to comprehend the action mechanism of indolocarbazole series compounds, but also provide new information for the design of new potent inhibitors.

Objective To develop and test a statistical model which correctly predicts the approval of outpatient referrals when reviewed by a specialty service based on nine discriminating variables. Design Retrospective cross-sectional study. Setting Large public county hospital system in a southern US city. Participants Written documents and associated data from 500 random adult referrals made by primary care providers to various specialty services during the course of one month. Main outcome measures The resulting correct prediction rates obtained by the model. Results The model correctly predicted 78.6% of approved referrals using all nine discriminating variables, 75.3% of approved referrals using all variables in a stepwise manner and 74.7% of approved referrals using only the referral total word count as a single discriminating variable. Conclusions Three iterations of the model correctly predicted at least 75% of the approved referrals in the validation set. A correct prediction of whether or not a referral will be approved can be made in three out of four cases.