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Epithelial-mesenchymal transition (EMT) is an important characteristic in the remodeling of chronic rhinosinusitis with nasal polyps (CRSwNP). IL-36γ and fibroblast activation protein (FAP) may exacerbate remodeling in CRS. Here, we aimed to determine whether IL-36γ and FAP expression are associated with EMT and may be a predictor for CRSwNP prognosis.52 non-Eos CRSwNP patients and 12 control patients were obtained and were followed up for more than 1 year after surgery. IL-36γ, FAP and EMT markers expression were evaluated by real-time polymerase chain reaction and western-blot. Masson trichrome staining was adopted to assess tissue fibrotic changes. Furthermore, the soluble form of IL-36γ and FAP in nasal secretions were detect by ELISA.While basal expression of E-cadherin decreased, the expression of IL-36γ, vimentin and FAP increased in nasal polyps. In well prognosis patients, the expression of IL-36γ, vimentin and FAP were significantly decreased than in poor prognosis patients, while the protein expression of E-cadherin was increased. The protein expression of IL-36γ was notably increased in recurrent nasal polyps than in preoperation specimens. A positive relationship between IL-36γ and FAP expression, a negative relationship between IL-36γ and E-cad expression was noted. The soluble form of IL-36γ and FAP increased during the development of non-Eos CRSwNP, with the highest level in poor prognosis patients after surgery.Non-Eos CRSwNP have partially undergone EMT under baseline conditions. IL-36γ and FAP expression were related with EMT, the soluble form of IL-36γ and FAP in nasal-secretions may predict the prognosis of patients.

Phthalate esters (PAEs) and bisphenol A (BPA) are endocrine-disrupting chemicals (EDCs), which are widely used in the production of food plastic packaging and easily migrate to food.

Some patients with acute large vessel occlusion (LVO) presented imaging mismatch, low Alberta Stroke Program Early CT Score (ASPECTS) with small ischemic core, or high ASPECTS with large ischemic core. The study was designed to explore whether patients with imaging mismatch could benefit from endovascular treatment (EVT).We retrospectively reviewed patients with LVO treated with EVT in our center from March 2018 to Jul 2020. Patients were divided into three groups, imaging mismatch, small ischemic core, and large ischemic core groups. Pooled analyses based on stroke onset to treatment time were done. Multivariate regression analysis was performed to explore the factors for good outcomes.Sixty-eight of 419 patients with LVO presented with imaging mismatch, and 35 of those (51%) achieved good outcomes after EVT at 90-day. No significant differences were noted in good outcomes and symptomatic intracranial hemorrhage (sICH) between patients with imaging mismatch and small ischemic core. Compared with large ischemic core, patients with imaging mismatch presented lower risk of sICH (95% confidence interval (CI) 0.04-0.75, p = 0.011) within 6 h and higher proportion of good outcomes (95% CI 0.37-0.82, p = 0.002) at 6 to 24 h. Baseline NIHSS (odds ratio (OR) = 0.91, 95% CI 0.88-0.95)), ASPECTS (OR = 1.14, 95% CI 1.01-1.29), ischemic core (OR = 0.99, 95% CI 0.98-1.00), and sICH (OR = 61.61, 95% CI 8.09-461.32) were associated with good outcomes.Patients with imaging mismatch treated within 24 h could benefit from EVT and without increasing the risk of sICH.• Patients with imaging mismatch between ASPECTS and ischemic core could achieve good outcomes after endovascular treatment. • Compared with large ischemic core, patients with imaging mismatch presented lower risk of symptomatic hemorrhage within 6 h and higher proportion of good outcomes within 6-24 h. • Baseline NIHSS score, ASPECTS, ischemic core, and symptomatic intracranial hemorrhage were associated with good outcomes.

Physicochemical properties of nanoparticles are important in regulating nanoparticle toxicity; however, the contribution of nanoparticle charge remains unclear. The objective of this study was to investigate the pulmonary effects of inhalation of charged soot nanoparticles. We established a stably charged nanoparticle generation system for whole-body exposure in BALB/c mice, which produced positively charged, negatively charged, and neutral soot nanoparticles in a wide range of concentrations. After a 7-day exposure, pulmonary toxicity was assessed, together with proteomics analysis. The charged soot nanoparticles on average carried 1.17-1.35 electric charges, and the sizes for nanoparticles under different charging conditions were all fixed at 69 ~ 72 nm. We observed that charged soot nanoparticles induced cytotoxic LDH and increased lung permeability, with the release of 8-isoprostane and caspase-3 and systemic IL-6 in mice, especially for positively charged soot nanoparticles. Next, we observed that positive-charged soot nanoparticles upregulated Eif2, Eif4, sirtuin, mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR), and HIPPO-related signaling pathways in the lungs compared with negatively charged soot nanoparticles. HIF1α, sirt1, E-cadherin, and Yap were increased in mice's lungs by positively charged soot nanoparticle exposure. In conclusion, carbonaceous nanoparticles carrying electric ions, especially positive-charged, are particularly toxic when inhaled and should be of concern in terms of pulmonary health protection.

Mitophagy, as one of the most important cellular processes to ensure quality control of mitochondria, aims at transporting damaged, aging, dysfunctional or excess mitochondria to vacuoles (plants and fungi) or lysosomes (mammals) for degradation and recycling. The normal functioning of mitophagy is critical for cellular homeostasis from yeasts to humans. Although the role of mitophagy has been well studied in mammalian cells and in certain model organisms, especially the budding yeast

Coronal mass ejections (CMEs) are one of the most violent solar eruptions, which can burst out large amounts of magnetized plasma with speeds up to thousands of kilometers per second. When it reaches the Earth, a CME can cause geomagnetic storm, affecting aviation safety, satellite operations, communications systems and power facilities. Therefore, fast and accurate prediction of CME arrival time is crucial for avoiding severe damaging effects and reducing economic losses. The initial morphology and kinematics of a CME in the corona can be observed by the coronagraphs equipped on the Solar and Heliospheric Observatory (SOHO), so that the coronagraphs should be useful to predict the CME arrival times. In this study, convolutional neural network (CNN) is used to obtain the features of SOHO/LASCO coronagraph pictures related to the CME transit time, and establish a model capable of predicting the CME arrival time. The influence of different hyperparameters of CNN on the prediction results is studied. Further, we add a physical information constraint of the initial velocities of CME to the basic CNN outputs, and found that smaller prediction errors can be obtained.

Three-dimensional (3-d) magnetohydrodynamics (MHD) modeling is a key method for studying the interplanetary solar wind. In this article, In this paper, we introduce a new 3-d MHD solar wind model driven by the self-consistent boundary condition obtained from multiple observations and Artificial Neural Network (ANN) machine learning technique. At the inner boundary, the magnetic field is derived using the magnetogram and potential field source surface extrapolation; the electron density is derived from the polarized brightness (pB) observations, the velocity can be deduced by an ANN using both the magnetogram and pB observations, and the temperature is derived from the magnetic field and electron density by a self-consistent method. Then, the 3-d interplanetary solar wind from CR2057 to CR2062 are modeled by the new model with the self-consistent boundary conditions. The modeling results present various observational characteristics at different latitudes, and are in good agreement with both the OMNI and Ulysses observations.

The growing interest in the use of lentiviral vectors (LVs) for various applications has created a strong demand for large quantities of vectors. To meet the increased demand, we developed a high cell density culture process for production of LV using stable producer clones generated from HEK293 cells, and improved volumetric LV productivity by up to fivefold, reaching a high titer of 8.2 × 107 TU/mL. However, culture media selection and feeding strategy development were not straightforward. The stable producer clone either did not grow or grow to lower cell density in majority of six commercial HEK293 media selected from four manufacturers, although its parental cell line, HEK293 cell, grows robustly in these media. In addition, the LV productivity was only improved up to 53% by increasing cell density from 1 × 106 and 3.8 × 106 cells/mL at induction in batch cultures using two identified top performance media, even these two media supported the clone growth to 5.7 × 106 and 8.1 × 106 cells/mL, respectively. A combination of media and feed from different companies was required to provide diverse nutrients and generate synergetic effect, which supported the clone growing to a higher cell density of 11 × 106 cells/mL and also increasing LV productivity by up to fivefold. This study illustrates that culture media selection and feeding strategy development for a new clone or cell line can be a complex process, due to variable nutritional requirements of a new clone. A combination of diversified culture media and feed provides a broader nutrients and could be used as one fast approach to dramatically improve process performance.

Objective. To investigate the effect and mechanism of osimertinib combined with bevacizumab on lung cancer through cell and transplanted tumor animal experiments and to provide theoretical basis for further clinical trials. Methods. Immunohistochemistry was used to detect the expression of PD-L1 in tumor vessels of nonmetastatic lung adenocarcinoma and metastatic lung adenocarcinoma. At the same time, the expression of CD8 and FoxP3 in tumor tissue was detected. qRT-PCR was used to detect the effect of osimertinib on PD-L1 expression in HUVECs. The expression levels of p-Akt and p-ERK in HUVECs treated with osimertinib were analyzed by Western blot. AKT was blocked by AKT specific inhibitor Ly294002 to analyze the expression of PD-L1 in HUVECs. An animal model of transplanted tumor was constructed to analyze whether osimertinib could enhance the antitumor effect of bevacizumab. Results. PD-L1 was highly expressed in vascular endothelial cells of metastatic lung cancer. FoxP3 was highly expressed in metastatic lung adenocarcinoma, while CD8 expression was low. Osimertinib inhibits PD-L1 expression in endothelial cells. Mechanism studies have shown that osimertinib inhibits PD-L1 expression in endothelial cells through the AKT/ERK pathway. Osimertinib inhibited endothelial cell PD-L1 expression, increased CD8+T cell infiltration, inhibited tumor growth, and enhanced the tumor effect of bevacizumab. Conclusion. Osimertinib can significantly increase the killing ability of bevacizumab against tumor. Osimertinib can improve the tumor microenvironment and enhance the antitumor effect of bevacizumab by reducing the expression of PD-L1 in tumor blood vessels.

PurposeThe COVID-19 pandemic has accelerated the process of teleworking and teleworking is expected to be a central feature of workplaces of the future. The present study examines the effect of leader-member exchange (LMX) and perception of loneliness on the relationship between proactive coping and the work productivity of teleworkers during the COVID-19 crisis time.Design/methodology/approachUsing structural equation modeling (SEM), this study the study is based on a survey of 572 teleworkers in Taiwan drawn from a variety of industry sectors.FindingsThrough the application of a hypothesized moderated mediation model, the indirect effects of proactive coping on work productivity via LMX are stronger for employees who experience a higher level of perceived loneliness.Research limitations/implicationsThe results have contributed to current understanding on the success of telework at the individual level and extends research framework of teleworking. Using self-report questionnaire is one of the limitations; however, this was feasible data collection method during COVID-19.Practical implicationsOrganizations need to provide further training aimed at enhancing proactive coping and dealing with future work challenges in the complex and dynamic workplace.Originality/valueThis study is the first among its type to examine proactive coping and job productivity from a LMX during COVID-19.

The etiology for a considerable proportion of patients with congenital radioulnar synostosis (RUS) remains unclear. This study aimed to investigate the genetic cause of RUS without a known cause.Patients with RUS were investigated. Exome sequencing and/or Sanger sequencing was performed. Bioinformatics analysis was also performed. Pathogenicity was evaluated for variants of interest.We identified unique missense variants in MECOM (encodes EVI1) associated with RUS in 8 families. Of them, 6 families had variants in residue R781, including 3 families with R781C (c.2341CT), 2 families with R781H (c.2342GA), and 1 family with R781L (c.2342GT). Another 2 variants included I783T (c.2348TC) in 1 family and Q777E (c.2329CG) in 1 family. All these variants were clustered within the ninth zinc finger motif of EVI1. Phenotype evaluation identified that most of these patients with RUS harboring mutant MECOM had finger malformations, but none of them had identifiable hematological abnormalities. Functional experiments showed that MECOM R781C led to alterations in TGF-β-mediated transcriptional responses.This study examined MECOM variants by focusing on RUS instead of hematological abnormalities. The R781 residue in EVI1 is a hotspot for human RUS variants. Mutant MECOM is the second most common cause for familial RUS.

Hypoxic resistance is the main obstacle to radiotherapy for laryngeal carcinoma. Our previous study indicated that hypoxia-inducible factor 1α (HIF-1α) and glucose transporter 1 (Glut-1) double knockout reduced tumour biological behaviour in laryngeal carcinoma cells. However, their radioresistance mechanism remains unclear. In this study, cell viability was determined by CCK8 assay. Glucose uptake capability was evaluated by measurement of

Venous thromboembolism (VTE) is a major cause of unexpected and perioperative in-hospital deaths. It is characterized by high morbidity, high mortality, high misdiagnosis rate, and high missed diagnosis rates. VTE is a common postoperative complication in cancer patients. VTE is preventable, and early identification of risk factors leading to VTE and appropriate early preventive actions can reduce its occurrence and mortality. Presently, there is no uniform standard for the prevention and control of VTE in clinical practice, and hospitals in China lack mature and effective protocols for the assessment, prevention, and treatment of VTE.To explore whether an early warning program could influence the occurrence of deep vein thrombosis (DVT) postoperatively.This is a comparative retrospective cohort study, which enrolled patients who underwent laparotomic or laparoscopic gastrointestinal tumor resection for gastrointestinal cancer between January 2016 and December 2019. Patients were divided into a control group and an early warning group depending on whether or not the early warning program was implemented. A venous thromboembolism prevention and control team was established. The outcomes included the occurrence of DVT, the correct rate of VTE assessment, the coagulation indicators, and the mastery of VTE knowledge by the nurses.A total of 264 patients were included in this study, with 128 patients in the control group and 136 patients in the early warning group. The occurrence rate of DVT in the early warning group was 6.6% (9/136), compared with 14.1% (18/128) in the control group (The early warning strategy was independently associated with the decreasing occurrence of VTE, and it might be suitable for protection from VTE in patients undergoing gastrointestinal cancer surgery.

This study aims to explore the effects of aquatic strength training on the postural balance and walking function of stroke patients.A total of 56 chronic stroke patients more than 6 months post-stroke with walking and balance impairments were included in this study. After baseline evaluations, patients were randomly assigned to either the experiment group (n = 29) or control group (n = 27). Patients in the control group underwent conventional hydrotherapy, whereas patients in the experiment group received conventional hydrotherapy combined with aquatic lower extremity strength training. After six weeks of rehabilitation, all patients were evaluated by a blinded assessor, and the functional assessments including: Berg Balance Scale (BBS); Timed Up and Go Test (TUG and mTUG); 2 Minute Walk Test (2MWMT); and Gait analysis.There were no significant differences (P .05) between the two groups in all evaluation indexes before rehabilitation. Six weeks after treatments, the results from both groups showed significant improvements compared with those in the baseline evaluations (P .05). Notably, compared with the control group, BBS, TUG and mTUG, 2MWMT, and Gait analysis including stride length in the non-hemiplegic side, stride length, as well as walking speed and stride frequency in the hemiplegic side in experiment group were markedly improved (P .05).Aquatic strength training can improve postural balance and lower extremity motor functions in chronic stroke patients.

Jasmonic acid (JA) is involved in phosphorus (P) stress in plants, but its underlying molecular mechanisms are still elusive. In this study, we found root endogenous JA content in rice increased under P deficiency (-P), suggesting that JA might participate in P homeostasis in plants. This hypothesis was further confirmed through the addition of exogenous JA (+JA), as this could increase both the root and shoot soluble P content through regulating root cell wall P reutilization. In addition, –P+JA treatment significantly induced the expression of P transporter gene OsPT2, together with increased xylem P content, implying that JA is also important for P translocation from the root to the shoot in P-deficient rice. Furthermore, the accumulation of the molecular signal nitric oxide (NO) was enhanced under –P+JA treatment when compared with –P treatment alone, while the addition of c-PTIO, a scavenger of NO, could reverse the P-deficient phenotype alleviated by JA. Taken together, our results reveal a JA-NO-cell wall P reutilization pathway under P deficiency in rice.

BackgroundStroke etiology might influence the clinical outcomes in patients with large vessel occlusion receiving endovascular treatment (EVT) with or without thrombolysis.ObjectiveTo examine whether stroke etiology resulted in different efficacy and safety in patients treated with EVT-alone or EVT preceded by intravenous alteplase (combined therapy).MethodsWe assessed the efficacy and safety of treatment strategy based on prespecified stroke etiology, cardioembolism (CE), large-artery atherosclerosis (LAA), and undetermined cause (UC) for patients enrolled in the DIRECT-MT trial. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Multivariate ordinal logistic regression analysis was used to calculate the adjusted common OR for a shift of better mRS score for EVT-alone versus combined therapy. A term was entered to test for interaction.ResultsIn this study, 656 patients were grouped into three prespecified stroke etiologic subgroups. The adjusted common ORs for improvement in the 90-day ordinal mRS score with EVT-alone were 1.2 (95% CI 0.8 to 1.8) for CE, 1.6 (95% CI 0.8 to 3.3) for LAA, and 0.8 (95% CI 0.5 to 1.3) for UC. Compared with CE, EVT-alone was more likely to result in an mRS score of 0–1 (pinteraction=0.047) and extended Thrombolysis in Cerebral Infarction ≥2b (pinteraction=0.041) in the LAA group. The differences in mortality and symptomatic intracranial hemorrhage within 90 days were not significant between the subgroups (p＞0.05).ConclusionsThe results did not support the hypothesis that a specific treatment strategy based on stroke etiology should be used for patients with large vessel occlusion (NCT03469206).

Project schedule management is an important part of prefabricated construction project management. General contracting is an effective way to promote the development of prefabricated construction. However, at present, from the perspective of general contracting, the risk factors affecting the project progress of prefabricated buildings are not clear, and the relationship between risks is not known. The purpose of this study is to study the composition, hierarchical structure and transmission path of schedule risk factors of prefabricated construction in general contracting mode, so as to help the general contractor formulate effective schedule risk avoidance measures. This study uses grounded theory to obtain 22 risk factors that affect the progress of assembly building projects, and the data are from expert interviews. Using Delphi method and interpretative structural modeling (ISM), these factors are divided into seven levels, and the ISM model of schedule risk factors is constructed. The research shows that there are 60 progress risk transmission paths, and four progress risk transfer chains are obtained. This paper also further analyzes and puts forward suggestions to avoid risks for each level. Doi: 10.28991/CEJ-2022-08-01-010 Full Text: PDF

A three-in-one carbon protective layer is introduced on a Zn anode (3D-NC@Zn) for high-quality Zn deposition. The 3D-NC@Zn electrode exhibits long-term stability over 1300 h at both high rate (10 mA cm−2, 1 mA h cm−2) and high capacity (1 mA cm−2, 10 mA h cm−2).

Purpose: Hepatocellular carcinoma (HCC), a common cancer worldwide, has a dismal outcome partly due to the poor identification of early-stage HCC. Currently, one third of HCC patients present with low serum α-fetoprotein (AFP) levels, the only clinically available diagnostic marker for HCC. The aim of this study was to identify new diagnostic molecular markers for HCC, especially for individuals with low serum AFP.Experimental Design: We used the microarray technique to determine the expression profiles of 218 HCC specimens from patients with either high or low serum AFP. From the microarray study, we selected five candidate genes (i.e., GPC3, PEG10, MDK, SERPINI1, and QP-C), which were overexpressed in HCCs. Using quantitative real-time PCR analyses, we validated the expression of these five genes in 50 AFP-normal and 8 AFP-positive HCC specimens and 36 cirrhotic noncancerous hepatic specimens, which include 52 independent specimens not used in microarray analysis.Results: A significant increase in the expression of the five candidate genes could be detected in most of the HCC samples, including those with normal serum AFP and small tumors. GPC3, MDK, and SERPINI1 encode known serum proteins. Consistently, a significant increase in serum midkine, encoded by MDK, was associated with HCC patients, including those with normal serum AFP. Using prediction analysis of microarray, we showed that a combined score of these five genes can accurately classify noncancerous hepatic tissues (100%) and HCC (71%).Conclusions: We suggest that a diagnostic signature approach using a combined score of these five biomarkers rather than a single marker may improve the prediction accuracy of HCC patients, including those with normal serum AFP and smaller-sized tumors.

Antiproliferative effect of RAF709 compared to dabrafenib, trametinib, RAF265 and sorafenib across a tumor cell panel

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