Changes of Circulating Transforming Growth Factor-²1 Level During Radiation Therapy Are Correlated with the Prognosis of Locally Advanced Non-small Cell Lung Cancer

IntroductionWe hypothesized that plasma transforming growth factor-²1 (TGF-²1) level and its dynamic change are correlated with the prognosis of locally advanced non-small cell lung cancer (NSCLC) treated with radiation therapy (RT).MethodsPatients with stage IIIA or IIIB NSCLC treated with RT with or without chemotherapy were eligible for this study. Platelet poor plasma was collected from each patient within 1 week before RT (pre-RT) and at the 4th week during RT (during-RT). TGF-²1 level was measured with enzyme-linked immunosorbent assay. The primary end point was overall survival (OS) and the secondary end point was progression-free survival (PFS). Kaplan-Meier and Cox regression were used for risk factor evaluation.ResultsA total of 65 patients were eligible for the study. The median OS and PFS were 17.7 and 13.7 months, respectively. In univariate analysis, performance status, weight loss, radiation dose, and TGF-²1 ratio (during-RT/pre-RT TGF-²1 level) were all significantly correlated with OS. In the multivariate analysis, performance status, radiation dose, and TGF-²1 ratio were still significantly correlated with OS. The median OS was 30.7 months for patients with TGF-²1 ratio ≤1 versus 13.3 months for those with TGF-²1 ratio more than 1 (p = 0.0029); and the median PFS was 16.8 months versus 7.2 months, respectively (p = 0.010).ConclusionsIn locally advanced NSCLC, the decrease of TGF-²1 level during RT is correlated with favorable prognosis

Effects of Solution Treatment on Laser Welding of Ti–6Al–4V Alloy Plate Produced through Wire Arc Additive Manufacturing

Laser beam welding (LBW) had been successfully applied to the welding of Ti–6Al–4V plates by wire arc additive manufacturing. The effects of solution treatment on microstructure, tensile properties, and microhardness after LBW in different deposition directions were studied. When the wire speeding was 3 m/min and travel speed was 0.36 m/min, the difference in mechanical properties was related to the anisotropy of the microstructure. The long columnar grain along the building direction could provide an α path with a large aspect ratio and high elongation. More grain boundaries are present along the scanning direction than in others, showing high strength. The microstructure of the as-deposited condition mainly consists of coarse prior-β grains, partial basket-weave structure, and numerous martensite α′ phase. In LBW without solution treatment, the microstructure of the welds mainly consists of a large amount of martensite α′ and a small amount of basket-weave structure. The weld had high strength and hardness. The tensile strength was between 930 and 970 MPa. The hardness was between 415 and 456 HV. The elongation ranged from 5% to 7%. Afterwards, the temperature was maintained at 870 °C for 2 h, cooled to 600 °C in the furnace for 1 h, and finally air cooled to room temperature. The martensite α′ was almost completely transformed into platelet α. The microstructure of the welds mainly consists of partial β grains, thimbleful martensite α′, and a large of α path. The strength and hardness of the welds were reduced. The tensile strength is between 910 and 950 MPa. The hardness was between 398 and 445 HV. However, the elongation was significantly improved, and the elongation ranged from 10% to 12%

A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

Abstract Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-Seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Cyclization of 3 forms vibralactone (1) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate

Dynamics and characteristics of dry and moist heatwaves over East Asia

© 2022, The Author(s).The increasing frequency of heatwaves over East Asia (EA) is impacting agriculture, water management, and people’s livelihood. However, the effect of humidity on high-temperature events has not yet been fully explored. Using observations and future climate change projections conducted with the latest generation of Earth System models, we examine the mechanisms of dry and moist heatwaves over EA. In the dry heatwave region, anticyclonic circulation has been amplified after the onset of heatwaves under the influence of the convergence of anomalous wave activity flux over northern EA, resulting in surface warming via adiabatic processes. In contrast, the moist heatwaves are triggered by the locally generated anticyclonic anomalies, with the surface warming amplified by cloud and water vapor feedback. Model simulations from phase six of the Coupled Model Intercomparison Project projected display intensification of dry heatwaves and increased moist heatwave days in response to projected increases in greenhouse gas concentrations.11Nsciescopu

EBV antibody and gastric cancer risk: a population-based nested case-control study in southern China

Abstract Background We aim to clarify the controversial associations between EBV-related antibodies and gastric cancer risk. Methods We analysed the associations between serological Epstein-Barr nuclear antigen 1 immunoglobulin A (EBNA1-IgA) and viral capsid antigen immunoglobulin A (VCA-IgA) by enzyme-linked immunosorbent assay and the risk of gastric cancer in a nested case-control study originated from a population-based nasopharyngeal carcinoma (NPC) screening cohort in Zhongshan, a city of southern China, including 18 gastric cancer cases and 444 controls. Conditional logistic regression was used to calculate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results All the sera of cases were sampled before diagnosis and the median time interval was 3.04 (range: 0.04, 7.59) years. Both increased relative optical density (rOD) values of EBNA1-IgA and VCA-IgA were associated with higher risks of gastric cancer with age adjusted ORs of 1.99 (95%CI: 1.07, 3.70) and 2.64 (95%CI: 1.33, 5.23), respectively. Each participant was further classified as high or medium/low risk based on a combination of two anti-EBV antibody levels. Participants in the high-risk group had substantially higher odds of developing gastric cancer than that in the medium/low risk group with an age adjusted OR of 6.53 (95%CI: 1.69, 25.26). Conclusions Our research reveals positive associations between EBNA1-IgA and VCA-IgA and gastric cancer risk in southern China. We thus postulate that EBNA1-IgA and VCA-IgA might appear to be potential biomarkers for gastric cancer. More research to further validate the results among diverse populations and investigate its underlying biological mechanism is needed

Inflammatory Serum Proteins Are Severely Altered in Metastatic Gastric Adenocarcinoma Patients from the Chinese Population

<div><p>Background</p><p>Inflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.</p><p>Methods</p><p>Serum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.</p><p>Results</p><p>The serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.</p><p>Conclusions</p><p>These results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.</p></div

The utility of protein combinations to distinguish GA and associated distant metastasis.

<p>For multi-protein models, linear discriminate analysis was performed using 3 protein and 4 protein combinations. The diagnostic performance of each model was evaluated using leave one out cross validation method. The utility of serum proteins as cancer biomarkers was evaluated using the area-under-curve (AUC) of the ROC curves for different models. Several protein combinations possess excellent diagnostic value (AUC >0.9) in distinguishing both non-metastatic and metastatic samples from healthy controls.</p