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Ginsenoside Rg5 is a rare ginsenoside showing promising tumor-suppressive effects. This study aimed to explore its radio-sensitizing effects and the underlying mechanisms. Human lung adenocarcinoma cell lines A549 and Calu-3 were used for in vitro and in vivo analysis. Bioinformatic molecular docking prediction and following validation by surface plasmon resonance (SPR) technology, cellular thermal shift assay (CETSA), and isothermal titration calorimetry (ITC) were conducted to explore the binding between ginsenoside Rg5 and 90 kD heat shock protein alpha (HSP90α). The effects of ginsenoside Rg5 on HSP90-cell division cycle 37 (CDC37) interaction, the client protein stability, and the downstream regulations were further explored. Results showed that ginsenoside Rg5 could induce cell-cycle arrest at the G1 phase and enhance irradiation-induced cell apoptosis. It could bind to HSP90α with a high affinity, but the affinity was drastically decreased by HSP90α Y61A mutation. Co-immunoprecipitation (Co-IP) and ITC assays confirmed that ginsenoside Rg5 disrupts the HSP90-CDC37 interaction in a dose-dependent manner. It reduced irradiation-induced upregulation of the HSP90-CDC37 client proteins, including SRC, CDK4, RAF1, and ULK1 in A549 cell-derived xenograft (CDX) tumors. Ginsenoside Rg5 or MRT67307 (an IKKε/TBK1 inhibitor) pretreatment suppressed irradiation-induced elevation of the LC3-II/β ratio and restored irradiation-induced downregulation of p62 expression. In A549 CDX tumors, ginsenoside Rg5 treatment suppressed LC3 expression and enhanced irradiation-induced DNA damage. In conclusion, ginsenoside Rg5 may be a potential radiosensitizer for lung adenocarcinoma. It interacts with HSP90α and reduces the binding between HSP90 and CDC37, thereby increasing the ubiquitin-mediated proteasomal degradation of the HSP90-CDC37 client proteins.

ObjectivesIt remains controversial whether sarcopenia has any significant impact on the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC). Therefore, in this study, we aimed to assess the association between sarcopenia and clinical outcomes in patients with advanced NSCLC receiving EGFR-TKIs or ICIs as a first-line therapy.MethodsWe retrospectively enrolled 131 patients with advanced NSCLC treated with first-line EGFR-TKIs or ICIs between 1 March 2019 and 31 March 2021. To estimate sarcopenia, we calculated skeletal muscle index (SMI) as the ratio of skeletal muscle area (cm2) to height squared (m2). Associations between sarcopenia and overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method and log-rank tests, respectively. A Cox proportional hazards regression model was used to assess the factors associated with OS and PFS. The Student’s t-test or Mann–Whitney U test was used to compare the SMI between patients with or without objective response and disease control. The chi-squared test was used to compare adverse events (AEs) between patients with and without sarcopenia.ResultsAmong the 131 patients, 35 (26.7%) were diagnosed with sarcopenia. Sarcopenia was an independent predictor of poor OS and PFS (p < 0.05) overall and in the EGFR-TKI- and ICI-treated cohorts. Among all patients, those with sarcopenia showed significantly shorter OS and PFS than those without sarcopenia (median OS and PFS: 13.0 vs. 26.0 months and 6.4 vs. 15.1 months; both p < 0.001). These associations were consistent across the subtypes of most clinical characteristics. Statistically significant differences between the objective response (OR) and non-OR groups were also observed in the mean SMI (OR group, 43.89 ± 7.55 vs. non-OR group, 38.84 ± 7.11 cm2/m2; p < 0.001). In addition, we observed similar results with disease control (DC) and non-DC groups (DC group, 42.46 ± 7.64 vs. non-DCR group, 33.74 ± 4.31 cm2/m2; p < 0.001). The AEs did not differ significantly between the sarcopenia and non-sarcopenia groups.ConclusionSarcopenia before treatment might be a significant predictor of poor clinical outcomes (shorter OS and PFS, fewer ORs, less DC) in patients with advanced NSCLC treated with EGFR-TKIs or ICIs as the first-line therapy.

In recent years, oil and gas exploration of the Baikouquan Formation in the northwestern margin of the Junggar Basin has seen major breakthroughs have been made in oil and gas exploration. Sandstone and conglomerate reservoirs are developed in the Baikouquan Formation in this area, but the factors affecting the differences in petro physical properties of these two types of reservoirs are still unclear. In this paper, taking the Baikouquan Formation in the Hongcheguai area on the northwestern margin of the Junggar Basin as an example, a large number of core observations, thin sections, scanning electron microscopy, and petro physical property test data were used to evaluate the petro logical characteristics, reservoir space types, digenesis and pore evolution of the sandstone and conglomerate reservoirs. The results show that the sandstone and conglomerate rocks of the Baikouquan Formation in the study area have a large content of tuffaceous components. The sandstone reservoirs are dominated by primary intergranular pores, and the conglomerate reservoirs are dominated by secondary dissolved pores. In addition, the porosity is negatively correlated with rock permeability for the conglomerate rocks of the Baikouquan Formation. However, the porosity is positively correlated with rock permeability of the sandstone reservoirs. According to the analysis of the digenetic process, the compaction and cementation can lead to a significant decrease in the petro physical properties of the reservoir. While dissolution can improve the petro physical properties of the sandstone reservoirs to a small extent, and can improve that of the conglomerate reservoirs to a greater extent. Moreover, local fractures are important factors affecting the petro physical properties of the conglomerate reservoirs. The existence of abnormal high pressure has a certain effect on the preservation of primary pores. On the whole, the controlling factors of the petro physical properties of the conglomerate reservoirs in the Baikouquan Formation include sedimentation, diagenesis, and tectonic actives, while that of the sandstone reservoirs mainly include sedimentation and diagenesis.

ObjectivesAlthough lipids have been assessed for their possible roles in cancer survival prediction, studies on the association between serum triglyceride (TG) levels and the prognosis of esophageal squamous cell carcinoma (ESCC) patients are limited. This study aimed to evaluate whether serum TG is associated with outcomes in patients with ESCC and investigate any interaction between serum TG and clinical parameters, especially body fat mass.Materials and methodsWe conducted a prospective case study on patients diagnosed with ESCC between March 2012 and November 2018. We measured patients’ serum TG levels before and after treatment. The association between serum TG and overall survival (OS) was evaluated using hazard ratios. We sought to determine a threshold point using optimal stratification. Survival analysis was performed using Kaplan–Meier curves and a Cox proportional hazards model.ResultsOf the 257 participants diagnosed with ESCC, 200 (77.8%) were men. Median follow-up time was 22.4 months (range 3.3–92.4 months). Using univariate Cox proportional hazard analysis and subsequent multivariate analysis, post-TG levels, Karnofsky performance scores, T stages, and chemotherapy cycles were shown to be independent prognostic factors for OS (p < 0.05). The post-TG cut-off point to best classify patients with respect to time to mortality was 1.47 mmol/L. A post-TG level of ≥ 1.47 mmol/L could independently predict a better OS (hazard ratio: 0.55, 95% confidence interval: 0.37–0.79). The associations were consistent across the subtypes of clinical parameters. Furthermore, the post-body mass index, post-subcutaneous adipose tissue area, post-visceral adipose tissue area, post-total adiposity tissue area, and post-total adipose density exhibited a strong positive association with post-TG levels.ConclusionPost-TG levels were found to be a significant positive prognostic biomarker for body fat mass and OS in ESCC patients.

Abstract Although targeting cancer metabolism is a promising therapeutic strategy, clinical success depends on accurate molecular and metabolic subtyping. Here, this study reports two metabolism‐based molecular subtypes associated with the ketogenic treatment of colon cancer: glycolytic (glycolysis+/ketolysis−) and ketolytic (glycolysis+/ketolysis+), which are manifested by distinct profiles of metabolic enzymes and mitochondrial dysfunction, and by different responses to ketone‐containing interventions in vitro and in vivo. Notably, the glycolytic subtype is able to be transformed into the ketolytic subtype in p53‐mutated tumors upon glucose limitation, rendering resistance to ketogenic therapy associated with upregulation of ketolytic enzymes, such as OXCT1 by mutant p53. The allosteric activator of mutant p53 effectively blocks the rewired molecular expression and the reprogrammed metabolism, leading to the suppression of tumor growth. The findings highlight the utility of metabolic subtyping to guide ketogenic therapy in colon cancer and identify mutant p53 as a synthetic lethality target for ketogenic treatment.

The carbonate successions from the Chihsia Formation play an important role for hydrocarbon exploration in the South China. However, the dolomites occurring in the upper section of the Chihsia Formation have been enigmatic, which confined further understanding of the depositional and/or diagenetic fluids and hydrocarbon prediction. In this study, the Pingdingshan section was investigated as a typical outcrop of Chihsian carbonates. On the basis of lithofacies/mineralogic observation of hand specimens and thin-sections, three types of dolomites were classified according to their crystal sizes, that is, micritic dolomite, sucrosic dolomite, and saddle dolomite. Comprehensive, micro-area geochemical proxies, including homogenization temperatures of fluid-inclusions, carbon and oxygen isotopes, and trace and rare-earth elements, were analyzed on different types of dolomites and matrix calcites. The results revealed that the selected samples were representative of temporal seawater and were not contaminated by terrestrial input. The temperatures and salinities of fluid-inclusions, combined with carbon and oxygen isotopic values, revealed that sucrosic dolomites originated from penecontemporaneous micritic dolomites, which had been crystallized and altered into fine- to medium-sized dolomite clusters during the later-stage burying process. In contrast, the saddle dolomites occurring in carbonate matrix or fractures were formed in a hydrothermal environment with a dolomitizing fluid temperature higher than 170°C. This inference is consistent with evidence from rare-earth elements and carbon and oxygen isotopes. Our findings provide new clues for the origin elucidation of dolomitizing fluids in the Chihsia Formation, South China.

Lumen segmentation in intravascular optical coherence tomography (IVOCT) images is a fundamental work for more advanced plaque analysis, stent recognition, fractional flow reserve (FFR) assessment, and so on. However, the catheter, guide-wire, inadequate blood clearance, and other factors will impact on the accuracy of lumen segmentation. We present a simple and effective method for automatic lumen segmentation method in IVOCT based on morphological features. We use image enhancement, median filtering, image binarization, and morphological closing operation to reduce speckle noise, minimize the effect of blood artifacts and fill in small holes inside vascular walls. We extract the orientation and area-size of connected regions as morphological features in images and remove the catheter and guide-wire completely by morphological corrosion operation, small area-size region removal, and orientation morphological feature comparison, and then the contour of the lumen can be discriminated. The evaluation metrics of this method, the Dice index, Hausdorff distance, Jaccard index, and accuracy of 99.32%, 0.06 mm, 99.4%, and 99.66%, respectively, are obtained from comparing with expert annotations on 268 IVOCT images. Compared with the other morphology-based lumen segmentation methods, the presented method can remove the catheter and guide-wire completely, even if the catheter and guide-wire cling to the lumen or the shape of the catheter is irregular. Since only morphological operations are used to complete all processes, the calculation burden is reduced greatly.

We present an optimized attenuation compensation and contrast enhancement algorithm to improve the quality of the intravascular optical coherence tomography (IVOCT) images and overcome the drawbacks of the previous algorithms, including pseudocharacteristics such as the variation of the tissue attenuation and the artifact shadows. We first analyze the variation of the tissue attenuation caused by the effect of the compensation and enhancement in theory. We compare the values of the estimated tissue attenuation in the baseline and enhanced IVOCT images with calcium, lipid, or fibrous plaques, respectively, to find an optimal enhancement coefficient preserving the attenuation characteristics. Then, we make a comparison of the IVOCT images with different values of the enhancement coefficient to evaluate the effects of each algorithm based on the improvement of visibility in depth, the contrast enhancement, and the preservation of characteristics. We point out that the optimizing attenuation coefficient for attenuation compensation and contrast enhancement algorithm could achieve the quality improvement of IVOCT images, as well as avoiding the pseudocharacteristics.

Materials with zero thermal expansion (ZTE) or precisely tailored thermal expansion are in urgent demand of modern industries. However, the overwhelming majority of materials show positive thermal expansion. To develop ZTE or negative thermal expansion (NTE) materials as compensators has become an important challenge. Here, we present the evidence for the realization of ultra-low thermal expansion in Mn–Co–Ge–In particles. The bulk with the Ni2In-type hexagonal structure undergoes giant NTE owing to a martensitic magnetostructural transition. The major finding is that the thermal expansion behavior can be totally controlled by modulating the crystallinity degree and phase transition from atomic scale. Self-compensation effect leads to ultra-low thermal expansion with a linear expansion coefficient as small as +0.68 × 10−6/K over a wide temperature range around room temperature. The present study opens an avenue to reach ZTE particularly from the large class of giant NTE materials based on phase transition.

The electric field dependent high-temperature small-polaron hopping conduction was investigated in patterned Pr0.7(Ca0.6Sr0.4)0.3MnO3 strips. The small-polaronic activation energy EA and the carrier localization were found to decrease with the reduction of the strip size. Meanwhile, a similar dependence on the strip size was also obtained for the calculated small-polaron coupling constants, which could be related to the strain relaxation in strips. These results indicate that the spatial confinement prefers to delocalize the carrier and reduce the electron-phonon interaction. Furthermore, opposite variation trends of EA under negative and positive electric field were found in the strips with small size, which could be attributed to the enhancement of polarization effect induced by the reduction of strip size.

This study designed a digital teaching game named Kitties' Magic Journey (KMJ). The principle of leveraging in the course of natural technology and life was used as the teaching subject. The game combined design items included animation, narrative story, fun and usability, which integrated ARCS learning motivation theory. The experimental group used KMJ, whereas the control group used traditional teaching. The two groups were administered pre- and post-tests, the ARCS learning motivation scale, and a semi-open questionnaire. In addition, the experimental group was administered a digital game design scale. The results showed that both KMJ and traditional teaching improved learning effectiveness. Although the learning effectiveness of the experimental group was higher than that of the control group, the difference was not statistically significant. Furthermore, the learning motivation of the experimental group was significantly higher than that of the control group. A canonical correlation analysis of the game design items dimensions and the learning motivation dimensions showed significant correlations, and animation dimension showed the strongest correlation with relevance dimension. The results of this study can provide future reference and guidance in game teaching design and help design a game-based learning system that can attract students.

This study developed four AR games and investigated their influence on learning in a Grade 5 English course by integrating theories of digital game-based learning, the attention relevance confidence-satisfaction (ARCS) model, and different types of digital games. Moreover, the elements between AR game design and the ARCS model were examined. 147 fifth grade students were selected as the participants in the experiment. The experimental group used AR game, while the control group used traditional learning. A pre-test and post-test, ARCS Learning Motivation questionnaire, AR game design elements questionnaire and Semi-open questionnaires were conducted with both groups. Results showed that students who received AR game learning exhibited significantly higher learning motivation than students who underwent traditional learning; however, no significant differences were observed in their learning effectiveness. A canonical correlation analysis of the AR game design elements dimensions and the learning motivation dimensions showed significant correlations, and 3D graphics dimension showed the strongest correlation with the satisfaction dimension. The finding of this study is that 3D graphics is the most important element in AR game designs, and the most popular type of AR game is role-playing. Based on the research results, high-quality 3D graphics in the design of AR games is needed to be satisfied with the other amusing storylines and interesting characters of the role-playing game is also the key of designing AR games.

Two cases of complicated pain exist: posterior screw fixation and myofascial pain. Intramuscular pulsed radiofrequency (PRF) may be an alternative treatment for such patients. This is a two-stage animal study. In the first stage, two muscle groups and two nerve groups were subdivided into a high-temperature group with PRF at 58 °C and a regular temperature with PRF at 42 °C in rats. In the second stage, two nerve injury groups were subdivided into nerve injury with PRF 42 °C on the sciatic nerve and muscle. Blood and spinal cord samples were collected. In the first stage, the immunohistochemical analysis showed that PRF upregulated brain-derived neurotrophic factor (BDNF) in the spinal cord in both groups of rats. In the second stage, the immunohistochemical analysis showed significant BDNF and tropomyosin receptor kinase B (TrkB) expression within the spinal cord after PRF in muscles and nerves after nerve injury. The blood biomarkers showed a significant increase in BDNF levels. PRF in the muscle in rats could upregulate BDNF-TrkB in the spinal cord, similar to PRF on the sciatica nerve for pain relief in rats. PRF could be considered clinically for patients with complicated pain and this study also demonstrated the role of BDNF in pain modulation. The optimal temperature for PRF was 42 °C. [ABSTRACT FROM AUTHOR]