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Abstract Background This retrospective study aimed to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and albumin for 30-day mortality in patients with postoperative acute pulmonary embolism (PAPE). Methods We retrospectively reviewed the medical records of 101 patients with PAPE admitted from September 1, 2012, to March 31, 2019. The characteristics, surgical information, admission examination data and mortality within 30 days after PAPE were obtained from our electronic medical recording system and follow-up. The associations between the NLR, PLR, and other predictors and 30-day mortality were analyzed with univariate and multivariate analyses. Then, the nomogram including the independent predictors was established and evaluated. Results Twenty-four patients died within 30 days, corresponding to a 30-day mortality rate of 23.8%. The results of the multivariate analysis indicated that both the NLR and albumin were independent predictors for 30-day mortality in patients with PAPE. The probability of death increased by approximately 17.1% (OR = 1.171, 95% CI: 1.073–1.277, P = 0.000) with a one-unit increase in the NLR, and the probability of death decreased by approximately 15.4% (OR = 0.846, 95% CI: 0.762c–0.939, P = 0.002) with a one-unit increase in albumin. The area under the curve of the nomogram was 0.888 (95% CI: 0.812–0.964). Conclusion Our findings showed that an elevated NLR and decreased albumin were related to poor prognosis in patients with PAPE. The NLR and albumin were independent prognostic factors for PAPE.

Abstract Background Alternative splicing (AS) may cause structural and functional variations in the protein to promote the proliferation of tumor cells. However, there is no comprehensive analysis of the clinical significance of AS in Helicobacter pylori-negative gastric cancer (HP − GC). Methods The clinical, gene expression profile data and AS events of 138 HP − GC patients were obtained from the database named the cancer genome atlas. Differently expressed AS (DEAS) events were determined by a comparison of the PSI values between HP − GC samples and adjacent normal samples. Unsupervised clustering analysis, proportional regression and Kaplan–Meier analysis were used to explore the association between clinical data and immune features and to establish two nomograms about the prognosis of HP − GC. Finally, splicing networks were constructed using Cytoscape. Results A total of 48141 AS events and 1041 DEAS events were found in HP − GC. Various functions and pathways of DEAS events parent genes were enriched, such as cell-substrate junction, cell leading edge, focal adhension, and AMPK signaling. Seven overall survival (OS)-related and seven disease-free survival (DFS)-related AS events were used to construct the prognostic signatures. Based on the independent prognostic factors, two nomograms were established and showed excellent performance. Then, splicing regulatory networks among the correlations suggested that splicing factors were significantly associated with prognostic DEASs. Finally, the unsupervised clustering analysis revealed that DEAS-based clusters were associated with clinical characteristics, tumor microenvironment, tumor mutation burden, and immune features. Conclusion Seven OS-related and seven DFS-related AS events have been found to be correlated with the prognosis of HP − GC and can be used as prognostic factors to establish an effective nomogram.

Abstract Background Bone metastasis (BM) is one of the common sites of hepatocellular carcinoma (HCC), and the prognosis of BM patients is worse than patients without it. Our study aimed to identify predictors and prognostic factors of BM in HCC patients and develop two nomograms to quantify the risk of BM and the prognosis of HCC patients with BM. Methods We retrospectively reviewed the data of patients who were diagnosed as HCC between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Independent predictors for BM from HCC patients were determined by the univariate and multivariate logistic regression analysis. Independent prognostic factors for HCC patients with BM were identified by univariate and multivariate Cox regression analysis. Two nomograms were established and evaluated by calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results Nine thousand and forty-seven patients were included. The independent risk factors of BM in newly diagnosed HCC patients are sex, grade, T stage, and N stage. The independent prognostic factors for HCC patients with BM are radiotherapy, chemotherapy, and lung metastasis. The AUC of diagnostic nomogram were 0.726 in the training set and 0.629 in the testing set. For the prognostic nomogram, the AUCs of 6-, 9-, and 12-months were 0.753, 0.799, and 0.732 in the training set and 0.698, 0.770, and 0.823 in the validation set. The calibration curve and DCA indicated the good performance of the nomogram. Conclusions Two nomograms were established to predict the incidence of BM in HCC patients and the prognosis of HCC patients with BM, respectively. Both nomograms have satisfactory accuracy, and clinical utility may benefit for clinical decision-making.

Abstract Background The need for a transfusion is one of the adverse events following total knee arthroplasty (TKA), and accurately predicting this need remains challenging for arthroplasty surgeons. The purpose of the present research is to study the preoperative predictors of transfusion risk in patients following TKA and develop a nomogram. Methods The nomogram was developed based on a training set of 5402 patients who underwent TKA at the Affiliated Hospital of Qingdao University between September 2013 and November 2018. The independent predictors of transfusion were identified by univariate, LASSO, and binary logistic regression analyses. Then, a nomogram was established based on these independent predictors. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were selected to evaluate the nomogram. The results were validated using an independent set of 1116 patients who underwent TKA between December 2018 and September 2019. In addition, we also carried out subgroup analyses in the training and testing sets based on the independent predictors. Results Five independent predictors were identified by multivariate analysis and were used to establish the nomogram. The AUCs of the nomogram were 0.884 (95% CI: 0.865–0.903) and 0.839 (95% CI, 0.773–0.905) in the training and testing sets, respectively. In both the training and testing sets, the calibration curve indicated that the prediction by the nomogram was highly consistent with the actual observation, and the DCA indicated that the nomogram had a favorable level of clinical usefulness. In addition, the AUC of the nomogram was significantly higher than the AUC of any independent predictor for predicting transfusion risk following TKA, and the subgroup analysis showed good performance in 20 subgroups. Conclusion Lower preoperative Hb levels, simultaneous bilateral TKA, lower BMI, older age, and coronary heart disease were identified as independent predictors of postoperative transfusion in patients following TKA. A nomogram incorporating the above five predictors could accurately predict the transfusion risk.

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

Eutectic structures in Ag-based brazing filler metals play an important role in improving the properties of alloys and brazed joints. The typical microstructures and morphological evolution of Ag-Cu eutectic structures in Ag-based brazing filler metals solidified at various cooling rates and with the addition of different Sn contents were investigated. The formation mechanisms of anomalous eutectic structure (AES) and the morphological transition from lamellar eutectic structure (LES) to AES were elucidated. The microstructures in alloys solidified at a slow cooling rate and with low Sn content consisted of the full AES, which was attributed to the remelting of the LES during recalescence. Increasing the Sn content and cooling rate promoted the formation of developed Ag dendrite, eutectic dendrite with branches, and AES with large dimensions. The AES in rapidly solidified filler metals with a high Sn content was ascribed to the decomposition of the Ag-rich dendrite skeleton and the growth of Cu-rich between the ternary dendrite arms.

The smelting slag obtained through iron collection from waste automobile three-way catalysts was used as a raw material to prepare microcrystalline glass through a one-step crystallization heat treatment. The phase composition and microstructure of the prepared glass were analyzed through X-ray diffraction and scanning electron microscopy–energy dispersive X-ray spectroscopy, respectively. Single-factor experiments were conducted to investigate the effects of crystallization temperature from 900 to 950 °C and crystallization time from 0.5 to 4 h on the physical and chemical properties of the microcrystalline glass. The results indicated that the optimum crystallization temperature and time for preparing microcrystalline glass with glass smelting slag through the proposed one-step crystallization heat treatment process were 950 °C and 3 h, respectively. Under these experimental conditions, the number of crystalline phases of the microcrystalline glass was high, the grains were mainly spherical and columnar particles, the sample structure was dense, and the best results were obtained: the density was 2.72 g/cm3, the water absorption was 1.55%, the porosity was 4.2%, the Vickers hardness was 618 HV, the acid resistance was 2.6%, and the alkali resistance was 0.04%. In addition, the results of the toxicity characteristic leaching procedure indicated that the leaching concentrations of heavy metals such as Zn, Cr, and Pb in the microcrystalline glass were lower than those in the base glass and were considerably lower than the acceptable limits. The microcrystalline glass obtained from final smelting slag through heat treatment can enhance the stabilization of harmful elements. The findings of this study can be applied to the treatment of bulk solid waste.

Local chronicles are a kind of historical record in China that are written in detail and play an important role in the transmission of local history and culture. Due to the single-text-carrier form of local chronicles, people have limited access to information on urban characteristics and culture; therefore, based on the cultural gene theory and Hofstede model, also known as the cultural onion model, this paper develops a “Spirit–Sign” content framework with the themes of urban characteristics and culture. Based on this framework, we map the urban characteristics and culture (visualization strategy and map design) of local chronicles. Taking the historic city of Dengfeng in the Central Plains as an example, the spatial information of the four historical city characteristics of Dengfeng was mined for the map design using the content framework of the city characteristics proposed in this study. The results of the study found that (1) there is a certain overlap in the spatial distribution of the four characteristic cultures of Dengfeng, indicating that the spiritual (traditional customs and famous people and events) and material (famous buildings and products) are complementary and mutually reinforcing to a certain extent; and (2) with the iterative development of Chinese dynasties, the material characteristic cultures of Dengfeng show strong temporal and spatial differences, which laterally reflect the changes in human activities and urban changes of each dynasty and also reflect the very important historical position occupied by Dengfeng in China. Compared with the traditional text-carrier form of local chronicles, the content construction and map visualization of the city’s historical and cultural information proposed in this study can effectively explore more potential cultural characteristics, as well as spatial and temporal connections of Dengfeng and thus help people better understand the historical characteristics of the city.

Background: Acute high-altitude (HA) exposure results in blood pressure (BP) and cardiac function variations in most subjects, some of whom suffer from acute mountain sickness (AMS). Several previous studies have found that cardiovascular function indicators are potentially correlated with AMS.Objectives: This study aims to examine HA-induced cardiovascular adaptations in AMS patients and compare them with healthy subjects. It also aims to investigate the relationship between cardiovascular function indicators and AMS, as well as to provide some insightful information about the prevention and treatment of AMS.Methods: Seventy-two subjects were enrolled in this cohort study. All the subjects ascended Litang (4,100 m above sea level). They were monitored by a 24-h ambulatory blood pressure (ABP) device and underwent echocardiography examination within 24 h of altitude exposure. The 2018 Lake Louise questionnaire was used to evaluate AMS.Results: Acute mountain sickness group consisted of more women (17 [60.7%] vs. 10 [22.7%], p = 0.001) and fewer smokers (5 [17.9%] vs. 23 [52.3%], p = 0.003). Compared with subjects without AMS, subjects with AMS had lower pulse pressure (PP) (daytime PP, 45.23 ± 7.88 vs. 52.14 ± 4.75, p < 0.001; nighttime PP, 42.81 ± 5.92 vs. 49.39 ± 7.67, p < 0.001) and lower effective arterial elastance (Ea) (1.53 ± 0.24 vs. 1.73 ± 0.39, p = 0.023). Multivariate regression indicated that female sex (OR = 0.23, p = 0.024), lower daytime PP (OR = 0.86, p = 0.004), and lower Ea (OR = 0.03, p = 0.015) at low altitude (LA) were independent risk factors for AMS. Combined daytime PP and Ea at LA had a high predictive value for AMS (AUC = 0.873; 95% CI: 0.789–0.956). Correlation analysis showed that AMS-induced headache correlated with daytime PP (R = −0.401, p < 0.001) and nighttime PP at LA (R = −0.401, p < 0.001).Conclusion: Our study demonstrated that AMS patients had a lower PP and Ea at LA. These baseline indicators of vasodilation at LA were closely associated with AMS, which may explain the higher headache severity in subjects with higher PP at LA.

Ribulose 5-phosphate (Ru5P) and guanosine 5′-triphosphate (GTP) are two key precursors of riboflavin, whereby Ru5P is also a precursor of GTP. Ribulose 5-phosphate 3-epimerase (Rpe) catalyzes the conversion of ribulose 5-phosphate into xylulose 5-phosphate. Inactivation of Rpe can reduce the consumption of Ru5P, enhancing the carbon flux toward riboflavin biosynthesis. Here we investigated the effect of mutation of rpe and other related genes on riboflavin production, physiological and metabolic phenotypes in Bacillus subtilis LY (BSLY). Introducing single nucleotide deletion (generated BSR) or nonsense mutation (generated BSRN) on the genomic copy of rpe, resulting in more than fivefold increase of riboflavin production over the parental strain. BSR process 62% Rpe activity, while BSRN lost the entire Rpe activity and had a growth defect compared with the parent strain. BSR and BSRN exhibited increases of the inosine and guanine titers, in addition, BSRN exhibited an increase of inosine 5′-monophosphate titer in fermentation. The transcription levels of most oxidative pentose phosphate pathway and purine synthesis genes were unchanged in BSR, except for the levels of zwf and ndk, which were higher than in BSLY. The production of riboflavin was increased to 479.90 ± 33.21 mg/L when ribA was overexpressed in BSR. The overexpression of zwf, gntZ, prs, and purF also enhanced the riboflavin production. Finally, overexpression of the rib operon by the pMX45 plasmid and mutant gnd by pHP03 plasmid in BSR led to a 3.05-fold increase of the riboflavin production (977.29 ± 63.44 mg/L), showing the potential for further engineering of this strain.

In recent years, climate change and the intervention of anthropogenic activities have altered the seasonal features of Asian dust storms. This may also cause seasonal variations (including dust occurrence frequency and optical/microphysical properties) in dust aerosols transported to downstream regions. The Jianghan Plain is dramatically influenced by multiple dust sources due to its geographical location in central China. In this study, we focused on the climatology of dust aerosols over the Jianghan Plain based on the 15-year (2006–2021) continuous space-borne observations of the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) as well as Modern-Era Retrospective Analysis for Research and Applications version 2 (MERRA-2) reanalysis data. A typical dust event that intrudes the Jianghan Plain was studied in detail. According to the statistical results, dust aerosols frequently intrude into the Jianghan Plain in spring and winter, with occurrence frequencies (under cloud free condition hereafter) exceeding 0.70 and higher altitudes of 4–6 km. The dust occurrence frequency declined to approximately 0.40 in autumn and nearly zero in summer, while the dust plumes were generally located at lower altitudes of 1–3 km. The dust plumes observed in the Jianghan Plain were simultaneously linked to the Taklimakan Desert and Gobi Desert in spring and mainly originated from the Taklimakan Desert in winter and autumn. The dust particles were mainly distributed below 4-km altitude, with the largest dust extinction coefficients and dust mass concentrations in spring. In all seasons, the particle depolarization ratios are 0.1–0.2 below 4-km altitude, suggesting a possible mix with local anthropogenic aerosols. The mean dust column mass concentrations in spring showed an evident declining trend from 210 µg m−2 in 2006 to 100 µg m−2 in 2021 in the Jianghan Plain, attributed to the reduced dust activity in the source regions of Asian dust.

BackgroundIncreasing evidence indicates that alternative polyadenylation (APA) is associated with the prognosis of cancers.MethodsWe obtained gene expression and APA profiles of 259 sarcoma patients from the TCGA dataportal and TC3A database, respectively. The prognostic signatures, clinical nomograms, and regulatory networks were studied by integrated bioinformatics analyses. Then, the immune cell infiltration profile was obtained from the ImmuCellAI. The association between APA-based signature and immune cells was studied.ResultsA total of 61 and 38 APA events were identified as overall survival (OS)- and progress free-survival (PFS)-related biomarkers, respectively. Two signatures were generated. The area under the curves (AUC) values of OS signature were 0.900, 0.928, and 0.963 over 2-, 4-, and 6-years, respectively. And the AUC values of PFS signature at 2-, 4-, and 6-years were 0.826, 0.840, and 0.847, respectively. Overall and subgroup analyses indicated that high-risk patients had a worse prognosis than low-risk patients (all p-values < 0.05). In addition, immunomics analyses indicated that there are different patterns of immune cell infiltration between low- and high-risk patients. Furthermore, two clinical-APA nomograms were established and the C-indexes were 0.813 and 0.809 for OS nomogram and PFS nomogram, respectively. Finally, two APA regulatory networks were constructed. FIP1L1-VPS26B was identified as a key regulating relationship and validated in the pan-cancer analyses.ConclusionIn this study, we identified prognostic predictors based on APA events with high accuracy for risk stratification in sarcoma patients and uncovered interesting regulatory networks in sarcoma that could be underlying mechanisms. This study not only provides novel potential prognostic biomarkers but promote precision medicine and provide potential novel research interests for immunotherapy.

Neuromorphic computing using multilevel nonvolatile memories as synapses offers opportunities for future energy‐ and area‐efficient artificial intelligence. Among these memories, artificial synapses based on current‐induced magnetization switching driven by spin–orbit torques (SOTs) have attracted great attention recently. Herein, the gradient descent algorithm, a primary learning algorithm, implemented on a 2 × 1 SOT synaptic array is reported. Successful pattern classifications are experimentally realized through the tuning of cycle‐to‐cycle variation, linearity range, and linearity deviation of the multilevel SOT synapse. Also, a larger m × n SOT synaptic array with m controlling transistors is proposed and it is found that the classification accuracies can be improved dramatically by decreasing the cycle‐to‐cycle variation. A way for the application of spin–orbit device arrays in neuromorphic computing is paved and the crucial importance of the cycle‐to‐cycle variation for a multilevel SOT synapse is suggested.

Background and Aims: The dietary inflammatory index (DII) is associated with non-communicable disease. We conducted an umbrella review to systematically evaluate meta-analyses of observational studies on DII and diverse health outcomes.Methods: We comprehensively searched the PubMed, Web of Science, and Embase databases to identify related systematic reviews and meta-analyses of observational studies. Those investigating the association between DII and a wide range of health outcomes in humans were eligible for inclusion. For each meta-analysis, we estimated the summary effect size by using fixed and random effects models, the 95% confidence interval, and the 95% prediction interval. We assessed heterogeneity, evidence of small-study effects, and excess significance bias.Results: The umbrella review identified 35 meta-analyses assessing associations between DII and various health outcomes: cancer (n = 24), mortality (n = 4), metabolic (n = 4), and other (n = 3). The methodological quality was high or moderate. Of the 35 meta-analyses, we observed highly suggestive evidence for harmful associations between digestive tract cancer, colorectal cancer, overall cancer, pharyngeal cancer, UADT cancer, and CVD mortality. Moreover, 11 harmful associations showed suggestive evidence: hormone-dependent cancer, rectal cancer, colon cancer, breast and prostate cancer, gynecological cancer, breast cancer, ovarian cancer, colorectal cancer, prostate cancer, all-cause mortality, and depression.Conclusion: DII is likely to be associated with harmful effects in multiple health outcomes. Robust randomized controlled trials are warranted to understand whether the observed results are causal.Systematic Review Registration: CRD42021218361

IntroductionPulmonary artery pressure (PAP) is increased and right ventricular (RV) function is well preserved in healthy subjects upon exposure to high altitude (HA). An increase in PAP may trigger notching of the right ventricular outflow tract Doppler flow velocity envelope (RVOT notch), which is associated with impaired RV function in patients with pulmonary hypertension. However, whether HA exposure can induce RVOT notch formation and the subsequent impact on cardiac function in healthy subjects remains unclear.MethodsA total of 99 subjects (69 males and 30 females) with a median age of 25 years were enrolled in this study; they traveled from 500 to 4100 m by bus over a 2-day period. All subjects underwent a comprehensive physiological and echocardiographic examination 1 day before ascension at low altitude and 15 ± 3 h after arrival at HA. The RVOT notch was determined by the presence of a notched shape in the RVOT Doppler flow velocity envelope. The systolic PAP (SPAP) was calculated as Bernoulli equation SPAP = 4 × (maximum tricuspid regurgitation velocity)2+5 and mean PAP (mPAP) = 0.61 × SPAP+2. Cardiac output was calculated as stroke volume × heart rate. Pulmonary capillary wedge pressure (PCWP) was calculated as 1.9+1.24 × mitral E/e’. Pulmonary vascular resistance (PVR) was calculated as (mPAP-PCWP)/CO.ResultsAfter HA exposure, 20 (20.2%) subjects had an RVOT notch [notch (+)], and 79 (79.8%) subjects did not have an RVOT notch [notch (−)]. In the multivariate logistic regression analysis, the SPAP, right ventricular global longitude strain (RV GLS), and tricuspid E/A were independently associated with the RVOT notch. The SPAP, mPAP, PVR, standard deviations of the times to peak systolic strain in the four mid-basal RV segments (RVSD4), peak velocity of the isovolumic contraction period (ICV), and the peak systolic velocity (s’) at the mitral/tricuspid annulus were increased in all subjects. Conversely, the pulse oxygen saturation (SpO2), RV GLS, and tricuspid annulus plane systolic excursion (TAPSE)/SPAP were decreased. However, the increases of SPAP, mPAP, PVR, and RVSD4 and the decreases of SpO2, RV GLS, and TAPSE/SPAP were more pronounced in the notch (+) group than in the notch (−) group. Additionally, increased tricuspid ICV and mitral/tricuspid s’ were found only in the notch (−) group.ConclusionHA exposure-induced RVOT notch formation is associated with impaired RV function, including no increase in the tricuspid ICV or s’, reduction of RV deformation, deterioration in RV-pulmonary artery coupling, and RV intraventricular synchrony.

Background: The expression of long non-coding RNA (lncRNA) is associated with the epithelial-mesenchymal transition (EMT) in tumorigenicity, but the role of EMT-related lncRNA in colorectal cancer (CRC) remains unclear.Methods: The clinical data and gene expression profile of CRC patients were obtained from The Cancer Genome Atlas database. Differential expression analysis, Cox regression model, and Kaplan-Meier analysis were used to study the relationship between EMT-related lncRNAs and the prognosis of CRC. Functional analysis and unsupervised clustering analysis were performed to explore the influence of certain lncRNAs on CRC. Finally, Cytoscape was used to construct mRNA-lncRNA networks.Results: Two signatures incorporating six and ten EMT-related lncRNAs were constructed for predicting the overall survival (OS) and disease-free survival (DFS), respectively. Kaplan-Meier survival curves indicated that patients in the high-risk group had a poorer prognosis than those in the low-risk group. The results of the functional analysis suggested that the P53 and ECM-receptor pathways affect the prognosis of CRC, and AL591178.1 is a key prognostic EMT-related lncRNA, which is negatively related to immune cells, P53 pathway, and ECM-receptor pathway.Conclusion: Six OS-related and ten DFS-related EMT-related lncRNAs were correlated with the prognosis of CRC by potentially affecting the immune microenvironment, and AL591178.1 plays a key role as a prognostic factor.

BackgroundEndometrial cancer (EC) is one of the most common female malignant tumors. The immunity is believed to be associated with EC patients’ survival, and growing studies have shown that aberrant alternative splicing (AS) might contribute to the progression of cancers.MethodsWe downloaded the clinical information and mRNA expression profiles of 542 tumor tissues and 23 normal tissues from The Cancer Genome Atlas (TCGA) database. ESTIMATE algorithm was carried out on each EC sample, and the OS-related different expressed AS (DEAS) events were identified by comparing the high and low stromal/immune scores groups. Next, we constructed a risk score model to predict the prognosis of EC patients. Finally, we used unsupervised cluster analysis to compare the relationship between prognosis and tumor immune microenvironment.ResultsThe prognostic risk score model was constructed based on 16 OS-related DEAS events finally identified, and then we found that compared with high-risk group the OS in the low-risk group was notably better. Furthermore, according to the results of unsupervised cluster analysis, we found that the better the prognosis, the higher the patient’s ESTIMATE score and the higher the infiltration of immune cells.ConclusionsWe used bioinformatics to construct a gene signature to predict the prognosis of patients with EC. The gene signature was combined with tumor microenvironment (TME) and AS events, which allowed a deeper understanding of the immune status of EC patients, and also provided new insights for clinical patients with EC.

Objective: To evaluate the efficacy and safety of balloon occlusion of the abdominal aorta for the treatment of pernicious placenta previa with placenta accreta. Methods: The clinical data of 623 patients with pernicious placenta previa combined with placenta accrete, who were admitted to our hospital from January 2013 to January 2019 were retrospectively analyzed. All patients underwent abdominal aortic balloon occlusion combined with cesarean section, and 78 patients underwent sequential bilateral uterine artery embolization. We analyzed the operation time, intraoperative blood loss, blood transfusion volume, intraoperative and postoperative complications, fetal radiation exposure time and dose, and the Apgar score of the newborns. We also performed other evaluations to ascertain the efficacy and safety of abdominal aortic balloon occlusion treatment for dangerous placenta previa with placenta accrete. Results: Of the 623 patients, 545 underwent only abdominal aortic balloon occlusion, and 78 underwent uterine artery embolization due to intraoperative or postoperative bleeding. The uterus was successfully preserved in all patients. Except for five cases of right lower extremity arterial thrombosis, the remaining patients did not have postoperative lower extremity arteriovenous thrombosis, renal insufficiency, late postpartum hemorrhage, ectopic embolism, spinal cord or peripheral nerve damage, pelvic infection, or other serious complications. The mean operative time was 65.3 (±14.5) min. The mean intraoperative blood loss was620 (±570) ml. Ninety-six patients (15.4%, 96/623) were treated with blood transfusion, and the average amount of blood transfused was 750 (±400) ml. The average number of hospitalization days was 6.8 (±3.4) days, the average time of fetal ray exposure was 5.2 (±1.6) s, and the average radiation dose was 4.1 (±2.7) mGy. The neonatal Apgar score, was 8.4 (±0.6) points at 1 ​min, and 9.6 (±0.4) points at 5 ​min. In the follow-up to May 31, 2019, 29 patients were lost to follow-up, 96 were lactating, and 498 were menstruating. Except for the cases lost to follow-up, the remaining 596 surviving newborns (including 2 twins) showed no abnormalities at the 42-day postnatal outpatient follow-up examination. Conclusion: Balloon occlusion of the abdominal aorta is a safe and effective method for the treatment of pernicious placenta previa with placenta accreta. Keywords: Abdominal aortic balloon, Placenta accrete, Placenta previa, Safety

The mobility of pristine amorphous indium gallium zinc oxide (a-IGZO) thin-film transistors (TFTs) is insufficient to meet the requirement of the future ultra-high-definition displays. Reported herein is the fabrication of hydrogenated long-channel IGZO TFTs exhibiting a transconductance and an on/off ratio that are orders of magnitude superior to those of the regular devices. The gate bias stability of the treated IGZO TFTs was greatly enhanced, with the threshold voltage shifting by less than 1 V after 1 h stress. Experimentally, the hydrogenation of the active layer was achieved via the deposition of a SiNx/SiOx bilayer on top of the IGZO via plasma-enhanced chemical vapor deposition followed by post-annealing under optimized conditions. The elemental depth profiles indicated that this enhanced performance originated from the hydrogen doping of the IGZO film. Furthermore, a dual-gate structure was fabricated to alleviate the deterioration of the subthreshold properties induced by the excess hydrogen doping.

Abstract Background Recent studies have revealed that numerous oncogenic long non-coding RNAs (lncRNAs) play pivotal roles in pancreatic ductal adenocarcinoma (PDAC) progression, but little is known about tumor-suppressive lncRNAs in PDAC. This study was conducted to evaluate the function of tumor-suppressive LINC01197 in PDAC progression and investigate the detailed mechanisms. Methods LncRNA microarray was used to identify differentially expressed lncRNAs in FOXO1-overexpressing PANC1 cells. LINC01197 expression was evaluated by quantitative PCR, Northern blotting, and fluorescence in situ hybridization. The Cancer Genome Atlas database was used to analyze the prognostic role of LNC01197 in PDAC. A luciferase reporter assay was performed to confirm the interaction between LNC01197 and FOXO1. The biological function of LINC01197 was evaluated by colony formation assay in vitro and in an animal subcutaneous tumorigenesis experiment and Ki67 staining in vivo. RNA-pulldown, western blotting, RNA immunoprecipitation assay, and co-immunoprecipitation were further performed to determine the molecular mechanism of LNC01197 and β-catenin in the Wnt pathway. Results We found that a FOXO1-related lncRNA, LINC01197, was significantly decreased in PDAC malignant tissues and that its low expression predicted poor prognosis. Moreover, LINC01197 was mainly localized in the nucleus and inhibited PDAC cell proliferation both in vitro and in vivo. Mechanistically, LINC01197 was found to bind to β-catenin and inhibit Wnt/β-catenin signaling activity by disrupting β-catenin binding to TCF4 in PDAC cells. Conclusions The novel FOXO1/LINC01197/β-catenin axis was dysregulated during PDAC progression. Our study provides insight into the mechanisms of LINC01197 in PDAC and reveal a potential target for PDAC clinical therapy and prognostic prediction.

Abstract Background Nasopharyngeal carcinoma (NPC), a highly invasive tumor, exhibits a distinctive racial and geographic distribution. As options of agents for effective combination chemoradiotherapy for advanced NPC are limited, novel therapeutic approaches are desperately needed. Here the potential of silencing NFBD1 in combination with PARP inhibition as a novel therapeutic strategy for NPC was investigated. Methods To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines via lentivirus mediated shRNA, and the colony formation, MTS assay, comet assay and apoptosis analysis were used to evaluate the sensitivity of NFBD1 knockdown on PARP inhibition. The signaling change was assessed by western blot, Immunofluorescence and flow cytometry. Furthermore, Xenografts model was used to evaluate the role of silencing NFBD1 in combination with PARP inhibition. Results We find that silencing NFBD1 in combination with PARP inhibition significantly inhibits the cell proliferation and cell cycle checkpoint activity, and increases the apoptosis and DNA damage. Mechanistic studies reveal that NFBD1 loss blocks olaparib-induced homologous recombination repair by decreasing the formation of BRCA1, BRCA2 and RAD51 foci. Furthermore, the xenograft tumor model demonstrated significantly increases sensitivity towards PARP inhibition under NFBD1 deficiency. Conclusions We show that NFBD1 depletion may possess sensitizing effects of PARP inhibitor, and consequently offers novel therapeutic options for a significant subset of patients.

Nanoporous gold (NPG) plays an important role in high-performance electronic devices, including sensors, electrocatalysis, and energy storage systems. However, the traditional fabricating methods of NPG, dealloying technique or electrochemical reduction technique, usually require complex experimental procedures and sophisticated equipment. In this work, we reported a unique and simple method to prepare the NPG through a low-temperature solution process. More importantly, the structure of the NPG-based electrode can be further controlled by using the post-treatment process, such as thermal treatment and plasma treatment. Additionally, we also demonstrate the application of the resulting NPG electrodes in flexible photodetectors, which performs a higher sensitivity than common planar photodetectors. We believe that our work opens a possibility for the nanoporous metal in future electronics that is flexible, large scale, with facile fabrication, and low cost.

Clinically significant portal hypertension (CSPH) is associated with an incremental risk of esophageal varices and overt clinical decompensations. However, hepatic venous pressure gradient (HVPG) measurement, the gold standard for defining CSPH (HVPG≥10 mm Hg) is invasive and therefore not suitable for routine clinical practice. This study aims to develop and validate a radiomics-based model as a noninvasive method for accurate detection of CSPH in cirrhosis.The prospective multicenter diagnostic trial (CHESS1701, ClinicalTrials.gov identifier: NCT03138915) involved 385 patients with cirrhosis from five liver centers in China between August 2016 and September 2017. Patients who had both HVPG measurement and contrast-enhanced CT within 14 days prior to the catheterization were collected. The noninvasive radiomics model, termed rHVPG for CSPH was developed based on CT images in a training cohort consisted of 222 consecutive patients and the diagnostic performance was prospectively assessed in 163 consecutive patients in four external validation cohorts.rHVPG showed a good performance in detection of CSPH with a C-index of 0·849 (95%CI: 0·786–0·911). Application of rHVPG in four external prospective validation cohorts still gave excellent performance with the C-index of 0·889 (95%CI: 0·752–1·000, 0·800 (95%CI: 0·614–0·986), 0·917 (95%CI: 0·772–1·000), and 0·827 (95%CI: 0·618–1·000), respectively. Intraclass correlation coefficients for inter- and intra-observer agreement were 0·92–0·99 and 0·97–0·99, respectively.A radiomics signature was developed and prospectively validated as an accurate method for noninvasive detection of CSPH in cirrhosis. The tool of rHVPG assessment can facilitate the identification of CSPH rapidly when invasive transjugular procedure is not available. Keywords: Portal hypertension, Liver cirrhosis, Hepatic venous pressure gradient, Radiomics, Noninvasive

Over the past two decades, scholars developed various unmanned sailboat platforms, but most of them have specialized designs and controllers. Whereas these robotic sailboats have good performance with open-source designs, it is actually hard for interested researchers or fans to follow and make their own sailboats with these open-source designs. Thus, in this paper, a generic and flexible unmanned sailboat platform with easy access to the hardware and software architectures is designed and tested. The commonly used 1-m class RC racing sailboat was employed to install Pixhawk V2.4.8, Arduino Mega 2,560, GPS module M8N, custom-designed wind direction sensor, and wireless 433 Mhz telegram. The widely used open-source hardware modules were selected to keep reliable and low-cost hardware setup to emphasize the generality and feasibility of the unmanned sailboat platform. In software architecture, the Pixhawk V2.4.8 provided reliable states’ feedback. The Arduino Mega 2,560 received estimated states from Pixhawk V2.4.8 and the wind vane sensor, and then controlled servo actuators of rudder and sail using simplified algorithms. Due to the complexity of introducing robot operating system and its packages, we designed a generic but real-time software architecture just using Arduino Mega 2,560. A suitable line-of-sight guidance strategy and PID-based controllers were used to let the autonomous sailboat sail at user-defined waypoints. Field tests validated the sailing performance in facing WRSC challenges. Results of fleet race, station keeping, and area scanning proved that our design and algorithms could control the 1-m class RC sailboat with acceptable accuracy. The proposed design and algorithms contributed to developing educational, low-cost, micro class autonomous sailboats with accessible, generic, and flexible hardware and software. Besides, our sailboat platform also facilitates readers to develop similar sailboats with more focus on their missions.

BackgroundAcute high altitude (HA) exposure elicits blood pressure (BP) responses in most subjects, and some of them suffer from acute mountain sickness (AMS). However, a 24-h ambulatory BP (ABP) change and the correlation with the occurrence of AMS in different sexes are still unclear.ObjectivesThis prospective study aimed to investigate HA induced BP responses in males and females and the relationship between AMS and 24-h ABP.MethodsForty-six subjects were matched according to demographic parameters by propensity score matching with a ratio of 1:1. All the subjects were monitored by a 24-h ABP device; the measurement was one period of 24 h BP. 2018 Lake Louise questionnaire was used to evaluate AMS.ResultsBoth the incidence of AMS (14 [60.9%] vs. 5 [21.7%], P = 0.007) and headache (18 [78.3%] vs. 8 [34.8%], P = 0.003) were higher in females than in males. All subjects showed an elevated BP in the early morning [morning systolic BP (SBP), 114.72 ± 13.57 vs. 120.67 ± 11.10, P = 0.013]. The elevation of morning SBP variation was more significant in females than in males (11.95 ± 13.19 vs. −0.05 ± 14.49, P = 0.005), and a higher morning BP surge increase (4.69 ± 18.09 vs. −9.66 ± 16.96, P = 0.005) was observed after acute HA exposure in the female group. The increase of morning SBP was associated with AMS occurrence (R = 0.662, P < 0.001) and AMS score (R = 0.664, P = 0.001). Among the AMS symptoms, we further revealed that the incidence (R = 0.786, P < 0.001) and the severity of headache (R = 0.864, P < 0.001) are closely correlated to morning SBP.ConclusionsOur study demonstrates that females are more likely to suffer from AMS than males. AMS is closely associated with elevated BP in the early morning period, which may be correlated to higher headache incidence in subjects with higher morning SBP.

Skin aging caused by UV radiation is called photoaging is characterized by skin roughness and dryness accompanied by a significant reduction of dermal collagen. Rapamycin is a macrolide immunosuppressant which has been shown to exhibit “anti-aging” effects in cells and organisms, however, its roles in the skin photoaging remains unclear. Here, we investigate the role of rapamycin and HSP27, which we have previously identified as an inhibitor of UV-induced apoptosis and senescence in HaCat cells, in a UVA-induced photoaging model of primary human dermal fibroblasts (HDFs). Results from senescence-associated beta-galactosidase (SA-β-gal) staining revealed that rapamycin significantly reduced senescence in UVA-treated HDFs. In addition, treatment with rapamycin significantly increased cell autophagy levels, decreased the expression of p53 and phosphorylated HSP27, and reduced genotoxic and oxidative cellular stress levels in UVA-induced HDFs. Knockdown of HSP27 resulted in a significant increase of MMP-1 and MMP-3 as well as a decrease in type I collagen expression. Rapamycin mitigated these effects by activation of the classical TGF-β/Smad signaling pathway and increasing the transcriptional activity of MAPK/AP-1. Taken together, these results suggest that rapamycin may potentially serve as a preventive and therapeutic agent for UVA-induced photoaging of the skin.

Male novel coronavirus disease (COVID-19) patients tend to have poorer clinical outcomes than female patients, while the myocardial injury is strongly associated with COVID-19-related adverse events. Owing to a lack of corresponding data, we aimed to investigate the sex differences in the incidence of myocardial injury in COVID-19 patients and to identify the potential underlying mechanisms, which may partly account for the sex bias in the incidence of adverse events. This retrospective study included 1,157 COVID-19 patients who were hospitalized in Huoshenshan Hospital from 12 March 2020 to 11 April 2020. Data on the patients’ demographic characteristics, initial symptoms, comorbidities and laboratory tests were collected. Totally, 571 (49.4%) female and 586 (50.6%) male COVID-19 patients were enrolled. The incidence of myocardial injury was higher among men than women (9.2 vs. 4.9%, p = 0.004). In the logistic regression analysis, age, and chronic kidney disease were associated with myocardial injury in both sexes. However, hypertension [odds ratio (OR) = 2.25, 95% confidence interval (CI) 1.20–4.22], coronary artery disease (OR = 2.46, 95% CI 1.14–5.34), leucocyte counts (OR = 3.13, 95% CI 1.24–7.86), hs-CRP (OR = 4.45, 95% CI 1.33–14.83), and D-dimer [OR = 3.93 (1.27–12.19), 95% CI 1.27–12.19] were independent risk factors only in the men. The correlations of hs-CRP and D-dimer with hs-cTnI and BNP were stronger in the men. The incidence of myocardial injury in COVID-19 patients is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders in men. Our findings can be used to improve the quality of clinical management in such settings.

BackgroundAmong colon cancer patients, liver metastasis is a commonly deadly phenomenon, but there are few prognostic models for these patients.MethodsThe clinicopathologic data of colon cancer with liver metastasis (CCLM) patients were downloaded from the Surveillance, Epidemiology and End Results (SEER) database. All patients were randomly divided into training and internal validation sets based on the ratio of 7:3. A prognostic nomogram was established with Cox analysis in the training set, which was validated by two independent validation sets.ResultsA total of 5,700 CCLM patients were included. Age, race, tumor size, tumor site, histological type, grade, AJCC N status, carcinoembryonic antigen (CEA), lung metastasis, bone metastasis, surgery, and chemotherapy were independently associated with the overall survival (OS) of CCLM in the training set, which were used to establish a nomogram. The AUCs of 1-, 2- and 3-year were higher than or equal to 0.700 in the training, internal validation, and external validation sets, indicating the favorable effects of our nomogram. Besides, whether in overall or subgroup analysis, the risk score calculated by this nomogram can divide CCLM patients into high-, middle- and low-risk groups, which suggested that the nomogram can significantly determine patients with different prognosis and is suitable for different patients.ConclusionHigher age, the race of black, larger tumor size, higher grade, histological type of mucinous adenocarcinoma and signet ring cell carcinoma, higher N stage, RCC, lung metastasis, bone metastasis, without surgery, without chemotherapy, and elevated CEA were independently associated with poor prognosis of CCLM patients. A nomogram incorporating the above variables could accurately predict the prognosis of CCLM.

Background: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients’ satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference. Methods: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience. Findings: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83–0•95), 92% (95% CI: 78–98%), 88% (95% CI: 78–95%), 80% (95% CI: 70–92%), 95% (95% CI: 90–100%), 7•91 (95% CI: 4•10–15•30), and 0•09 (95% CI: 0•03–0•30), respectively. The kappa score of 0•78 (95% CI: 0•65–0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD (p < 0•0001, d = 1•15 [95%CI: 0•88–1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred. Interpretation: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction. Funding: A full list of funding can be found in the Funding Support section.

Among all fatal gynecological malignant tumors, ovarian cancer has the highest mortality rate. The purpose of this study was to develop a stable and personalized glycometabolism-related prognostic signature to predict the overall survival of ovarian cancer patients. The gene expression profiles and clinical information of ovarian cancer patients were derived from four public GEO datasets, which were divided into training and testing cohorts. Glycometabolism-related genes significantly associated with prognosis were selected. A risk score model was established and validated to evaluate its predictive value. We found 5 genes significantly related to prognosis and established a five-mRNA signature. The five-mRNA signature significantly divided patients into a low-risk group and a high-risk group in the training set and validation set. Survival analysis showed that high risk scores obtained by the model were significantly correlated with adverse survival outcomes and could be regarded as an independent predictor for patients with ovarian cancer. In addition, the five-mRNA signature can predict the overall survival of ovarian cancer patients in different subgroups. In summary, we successfully constructed a model that can predict the prognosis of patients with ovarian cancer, which provides new insights into postoperative treatment strategies, promotes individualized therapy, and provides potential new targets for immunotherapy.

Co-treatment for two kinds of hazardous solid waste is an effective method to reduce cost and increase recycle efficiency of value resource. This work developed an integrated process based on capture of red mud (RM) and a one-step heat-treatment process to efficiently recover PGMs from spent auto-catalysts (SAC) and reuse RM simultaneously. Firstly, the iron oxide in RM was reduced to metallic iron to capture PGMs by the reduction process, without the addition of an extra reducing agent, since SAC contained abundant organic volatiles. Then, the mixed waste of SAC and RM was melted under high temperature with additives of CaO and H3BO3. More than 99% of PGMs can be extracted under the optimal conditions of 40–50 wt% of RM addition, 14 wt% of H3BO3 addition, 0.7–0.8 of basicity, 1500 °C of temperature, and 40 min of holding time. In addition, PGM content in obtained glassy slag was less than 1 g/t. The mechanism of iron trapping PGMs was also discussed in detailed, which mainly contained two stages: migration of PGMs and separation of PGM-bearing alloy and slag phases. Besides, the obtained glassy slag was further prepared into glass-ceramic by a one-step heat-treatment process. It was found that the prepared glass-ceramic has good thermostability and an excellent stabilizing effect on heavy metals. Overall, the results indicated that the developed integrated smelting–collection process is an efficient and promising method for the reutilization of SAC and RM.

The aims of this study were to explore the effect of high-altitude (HA) exposure on the incidence, determinants, and impacts of right ventricular dyssynchrony (RVD). In our study, 108 healthy young men were enrolled, and physiological and echocardiographic variables were recorded at both sea level and 4,100 m. By using two-dimensional speckle-tracking echocardiography, RVD was evaluated by calculating the R–R interval-corrected standard deviation of the time-to-peak systolic strain for the four mid-basal RV segments (RVSD4) and defined by RVSD4 > 18.7 ms. After HA exposure, RVSD4 was significantly increased, and the incidence of RVD was approximately 32.4%. Subjects with RVD showed lower oxygen saturation (SaO2) and RV global longitudinal strain and higher systolic pulmonary artery pressure than those without RVD. Moreover, myocardial acceleration during isovolumic contraction was increased in all subjects and those without RVD, but not in those with RVD. Multivariate logistic regression revealed that SaO2 is an independent determinant of RVD at HA (odds ratio: 0.72, 95% CI: 0.56–0.92; P = 0.009). However, the mean pulmonary artery pressure was linearly correlated with the magnitude of RVD in the presence of Notch. No changes were found in RV fractional area change, tricuspid annular motion, or tricuspid s’ velocity between subjects with and without RVD. Collectively, we demonstrated for the first time that HA exposure could induce RVD in healthy subjects, which may be mainly attributed to the decline in SaO2 as well as RV overload; the incidence of RVD was associated with reduced RV regional function and blunted myocardial acceleration.

Introduction Gastro-oesophageal variceal bleeding is one of the most common and severe complications with high mortality in cirrhotic patients who developed portal hypertension. Hepatic venous pressure gradient (HVPG) is a globally recommended golden standard for the portal pressure assessment and an HVPG ≥16 mm Hg indicates a higher risk of death and rebleeding. This study aims to compare the effectiveness and safety of splenectomy and pericardial devascularisation (laparoscopic therapy) plus propranolol and endoscopic therapy plus propranolol for variceal rebleeding in cirrhotic patients with HVPG between 16 and 20 mm Hg.Methods and analysis This is a multicenter, randomised, controlled clinical trial. Participants will be 1:1 assigned randomly into either laparoscopic or endoscopic groups. Forty participants whose transjugular HVPG lies between 16 and 20 mm Hg with a history of gastro-oesophageal variceal bleeding will be recruited from three sites in China. Participants will receive either endoscopic therapy plus propranolol or laparoscopic therapy plus propranolol. The primary outcome measure will be the occurrence of gastro-oesophageal variceal rebleeding. Secondary outcome measures will include overall survival, occurrence of hepatocellular carcinoma, the occurrence of venous thrombosis, the occurrence of adverse events, quality of life and tolerability of treatment. Outcome measures will be evaluated at baseline, 12 weeks, 24 weeks, 36 weeks, 48 weeks and 60 weeks. Multivariate COX regression model will be introduced for analyses of occurrence data and Kaplan-Meier analysis with the log-rank test for intergroup comparison.Ethics and dissemination Ethical approval was obtained from all three participating sites. Primary and secondary outcome data will be submitted for publication in peer-reviewed journals and widely disseminated.Trial registration number NCT03783065; Pre-results.Trial status Recruitment for this study started in December 2018 while the first participant was randomised in January 2019. Recruitment is estimated to stop in October 2019.

Abstract Write‐once‐read‐many (WORM) memory behavior is often observed in polymer electret memory (PEM) devices, greatly limiting their overall performance. This paper systematically investigates the device physics of PEM devices with poly(α‐methylstyrene) as a charge trapping layer and pentacene as a semiconductor channel. The combined experiments on transistors, capacitances, and optical spectroscopy reveal that both the WORM memory behavior after negative and positive pulses and the gradual formation of memory after the continuous scanning are the results of the deficiency in minority (electrons) transport and trapping. Corresponding quantitative models are established and well explain the two‐stage, gradual trapping processes to form memory. By reducing the structural disorder and lateral channel length, ambipolar, bistable memory and much faster formation of memory window is obtained based on the same PEM device. The insights into device physics of PEM devices are expected to facilitate the design of organic, nonvolatile memory devices with high programming and erasing efficiencies.

Summary: Rationally designing drugs that last longer in the face of biological evolution is a critical objective of drug discovery. However, this goal is thwarted by the diversity and stochasticity of evolutionary trajectories that drive uncertainty in the clinic. Although biophysical models can qualitatively predict whether a mutation causes resistance, they cannot quantitatively predict the relative abundance of resistance mutations in patient populations. We present stochastic, first-principle models that are parameterized on a large in vitro dataset and that accurately predict the epidemiological abundance of resistance mutations across multiple leukemia clinical trials. The ability to forecast resistance variants requires an understanding of their underlying mutation biases. Beyond leukemia, a meta-analysis across prostate cancer, breast cancer, and gastrointestinal stromal tumors suggests that resistance evolution in the adjuvant setting is influenced by mutational bias. Our analysis establishes a principle for rational drug design: when evolution favors the most probable mutant, so should drug design. : Drug resistance is often addressed through next-generation drug design, but evolutionary diversity complicates these efforts. Here, Leighow et al. demonstrate that multi-scale models can quantitatively predict mutant frequency. We find that when heterogeneity is limited, analysis requires an understanding of substitution likelihood. We show that these models can inform evolutionarily optimized drug design. Keywords: drug resistance, predictive evolution, stochastic dynamics

Background. Approximately 20–40% of recipients of cardiac resynchronization therapy (CRT) do not respond to it based on the current patient selection criteria. The purpose of this study was to identify baseline parameters that can predict CRT response and to evaluate the effect of those predictive parameters on long-term prognosis. Methods. This was a retrospective, nonrandomized, noncontrolled cohort study. Patients who received CRT in our centre were divided into responders and nonresponders by the definition of CRT response (an increase in left ventricular ejection fraction (LVEF) of ≥5% and improvement of ≥1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up). Results. Of the 101 patients, 68 were responders and 33 were nonresponders. Left ventricular end-diastolic diameter (LVEDD; OR: 0.88, 95% CI: 0.81–0.95, P=0.001) and QRS duration (OR: 1.07, 95% CI: 1.04–1.10, P

Background and Aims. Gastroesophageal variceal bleeding is a serious complication of portal hypertension in cirrhotic patients and could be predicted by hepatic venous pressure gradient (HVPG). However, whether the presence of ascites affects the prognostic value of HVPG for patients with acute variceal bleeding is still unknown. This retrospective study is aimed at investigating the influence of ascites on predictive performance of HVPG for early rebleeding in cirrhotic patients with acute variceal bleeding. Methods. In this retrospective study, a total of 148 patients with cirrhosis hospitalized for acute variceal bleeding who underwent HVPG measurement and endoscopic variceal ligation (EVL) for the prevention of rebleeding were included. The receiver operating characteristic curve (ROC) and logistical regression method were employed to analyze the predictive performance of HVPG for early rebleeding. The locally weighted scatterplot smoothing approach was adopted to assess the monotonicity between bleeding risk and HVPG. Results. A significantly higher HVPG level was observed in patients with early rebleeding compared to patients without rebleeding in the nonascites cohort. When using HVPG to predict early rebleeding, there was a lower area under curve in the ascites cohort compared to the nonascites cohort. HVPG was recognized as a risk factor for early rebleeding by a logistic regression model only in the nonascites cohort. An overall monotonicity in the trend of change in HVPG and risk for early rebleeding was observed in the nonascites cohort solely. Conclusion. The predictive value of HVPG for early rebleeding in patients with cirrhosis that developed acute variceal bleeding is hindered by the presence of ascites.

Abstract Heterostructures based on two-dimensional (2D) materials have sparked wide interests in both fundamental physics and applied devices. Recently, Dirac/Weyl semimetals are emerging as capable functional materials for optoelectronic devices. However, thus far the interfacial coupling of an all-semimetal 2D heterostructure has not been investigated, and its effects on optoelectronic properties remain less well understood. Here, a heterostructure comprising of all semi-metallic constituents, namely graphene and WTe2, is fabricated. Standard photocurrent measurements on a graphene/WTe2 phototransistor reveal a pronounced photocurrent enhancement (a photoresponsivity ~8.7 A/W under 650 nm laser illumination). Transport and photocurrent mapping suggest that both photovoltaic and photothermoelectric effects contribute to the enhanced photoresponse of the hybrid system. Our results help to enrich the understanding of new and emerging device concepts based on 2D layered materials.

Background/Aims: Interleukin-1β (IL-1β) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPβ regulates the production of IL-1β are unclear. In this study, we aimed to explore the role of C/EBPβ in regulating IL-1β production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. Methods: RAW264.7 macrophages were treated with 0, 25, 50 or 100 μg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1β secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1β was tested by dual-luciferase reporter assay. Results: Ox-LDL increased IL-1β production, accompanied with increasing C/EBPβ and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPβ deficiency in macrophages blocked ox-LDL-induced increases in IL-1β expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1β production, but not C/EBPβ expression. Dual-luciferase reporter results showed that overexpression of C/EBPβ significantly enhanced binding activity of p65 to IL-1β promoter. In addition, C/EBP 1β deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1β, IL-6, p65 and caspase-1. Conclusions: Our results demonstrate that C/EBPβ acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1β production in macrophages and may regulate IL-1β maturation by promoting caspase-1. C/EBPβ may be a promising candidate for the prevention and treatment of atherosclerosis.

Purpose: The BTF3 is involved in oncogenesis, while the biological roles in HSCC remain unclear. The aim of this study was to explore the impact of BTF3 knockdown on biological phenotypes of human HSCC in vivo and in vitro. Methods: The expression of BTF3 was assessed in HSCC and normal tissues. In vitro experiments were performed to explore impact of BTF3 knockdown on biological phenotypes of human HSCC cell line, including proliferation, cell cycle, and apoptosis. Moreover, nude mice were used to evaluate growth of xenograft tumors. Finally, gene chip was used to explore the potential signaling pathways of BTF3, with confirmation of potential BTF3-related genes. Results: Our results showed elevated expression of BTF3 was observed in HSCC tumors compared to paired adjacent normal tissues in 68 patients, and positively associated with lymph node metastasis and survival of this HSCC patient cohort. In addition, in vitro experiments showed that BTF3 knockdown significantly impaired regulation of proliferation, cell cycle, and apoptosis, potentially via ATM signaling pathway. Finally, in vivo experiments demonstrated that BTF3 functioned as an oncogene by promoting the development and progression of HSCC tumors, indicating its oncogenic role in HSCC. Conclusions: This study for the first time demonstrated that expression of BTF3 is upregulated in HSCC tumors and this upregulation is positively correlated with lymph node metastasis of this malignancy. The oncogenic role of BTF3 is further validated for tumor promotion and progression of HSCC in vivo, indicating that BTF3 is a potential therapeutic target and prognostic biomarker for HSCC.

Abstract Background Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype–phenotype correlations. Methods A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (

Nanowire-microfluidic strain sensors: a stretchable multi-scale sensing solution By combining metal nanowires and conductive polymers, high-performance stretchable nanowire-microfluidic strain sensors are realized. A team lead by Chuan Liu from the School of Electronics and Information Technology at Sun Yat-Sen University developed a hybrid strain sensor consisting of brittle metal nanowires and conductive polymers. These robust nanowire-microfluidic strain sensors are sensitive to multiscale strains––from 4% to over 400%––and show record-high gauge factor, a figure-of-merit that quantifies the level of sensitivity. The hybrid strain sensor’s high performance is made possible by the electric percolation pathways formed between the parallel nanowire network and the microfluidic channels. The combination of high stretchability and high sensitivity over a large strain range enables the device to be suitable for multiscale sensing. Liu and coworkers demonstrate the applicability of their nanowire-microfluidic strain sensors to human motion detection and human–machine interactive systems.

Recent studies on organic thin-film transistors (OTFTs) have reported high mobility values, but many of them showed non-ideal current–voltage characteristics that could lead to the overestimation of the mobility values. In this study, the non-ideal transistor behavior was briefly investigated by considering the effect of charge injection, and a method of overcoming the effect was developed. Correspondingly, various charge injection layers were developed, and their effects on the modification of metal contacts, including work function tuning and interfacial doping, were studied. The materials that had been coated formed a good metal-semiconductor interface through fine manipulation in the wetting and dewetting of the selected liquid. With such electrodes, the OTFTs were fabricated at room temperature and exhibited almost ideal transistor behavior in terms of the current–voltage characteristics, featuring high (over 10 cm2/Vs) field-effect mobility.

Background/Aims: In the process of bone development and remodeling, the vasculature is regarded as the communicative network between the bone and neighboring tissues. Recently, it has been reported that the processes of angiogenesis and osteogenesis are coupled temporally and spatially. However, few studies reported the relationship and relevant mechanism between osteoclastogenesis and vasculogenesis. Methods: Arraystar Mouse lncRNA microarray V3.0 was firstly used to analyze the differentially expressed lncRNA genes in osteoclast different stages during osteoclastogenesis. Cell counting kit 8 (CCK-8) analysis, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, migration and tube formation assays were used to detect impact of osteoclast different stages on the proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs), respectively. Finally, transfection of AK131850 shRNA, miR-93-5p mimic and miR-93-5p inhibitor, qRT-PCR, western blotting, enzyme-linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH) and luciferase reporter assay were carried out to dissect molecular mechanisms. Results: In this study, we found that newborn OCs (N-OC) and mature OCs (M-OC) during osteoclastogenesis significantly promoted proliferation, differentiation, migration and tube formation of endothelial progenitor cells (EPCs). Through lncRNA microarray and GO&pathway analysis, we found that AK131850 and co-expressed gene, vascular endothelial growth factor a (VEGFa), were significantly up-regulated in N-OC and M-OC. After inhibition of AK131850 the promoting effect of N-OC and M-OC on EPCs was reversed. Furthermore, we found that AK131850 directly competed miR-93-5p in N-OC and M-OC through sponge, thereby increasing VEGFa transcription, expression and secretion through derepressing of miR-93-5p on VEGFa. Conclusion: Our results provided the first finding that lncRNA-AK131850 sponged miR-93-5p in N-OC and M-OC during osteoclastogenesis to enhance the secretion of VEGFa, thus promoting vasculogenesis of EPCs.

Abstract Background Smoking is a leading cause of numerous human disorders including lung cancer, chronic obstructive pulmonary disease, and atherosclerotic cardiovascular disease. The development of modified risk tobacco products (MRTPs) has been suggested as a possible way to reduce the risks of tobacco smoking by reducing exposure to cigarette smoke toxicants. This study is designed to investigate whether biomarkers of such exposure are reduced when smokers switch from smoking commercial cigarettes to using either a novel or a commercially-available tobacco heating product (THP). Design and Methods This study will assess biomarkers of exposure in current smokers who either remain smoking, switch to THP use, or quit all tobacco use completely, for 5 days. The study is an in-clinic (confinement) two-centre, randomised controlled clinical study with a forced-switching design. Subjects of either gender will be aged 23–55 years (minimum legal smoking age plus 3 years), of Japanese origin and with a verified smoking status (assessed by exhaled breath carbon monoxide and urinary cotinine levels). Subjects will have a usual brand cigarette within the International Organisation for Standardisation (ISO) tar band of 6-8 mg and will be judged to be healthy by medical history, physical examination, vital signs, electrocardiography (ECG), clinical biochemistry and lung function tests. The primary objective of this study is to assess changes within groups in selected biomarkers of exposure (BoE) and of biological effect (BoBE) after a forced switch from a commercial control cigarette to either a menthol or a non-menthol THP. Secondary objectives are to assess between-group differences, to determine nicotine pharmacokinetics for cigarettes and THPs, to assess subject’s satisfaction with the study products, and to monitor additional endpoints related to safety and product use. Discussion Data from this study will advance our scientific understanding of the changes in exposure to cigarette smoke toxicants in smokers who switch to using a THP. Trial registrations UMIN000024988 (25th November 2016); ISRCTN14301360 (14th December 2016)