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In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells.

Designing high-performance thermal catalysts with stable catalytic sites is an important challenge. Conventional wisdom holds that strong metal-support interactions can benefit the catalyst performance, but there is a knowledge gap in generalizing this effect across different metals. Here, we have successfully developed a generalizable strong metal-support interaction strategy guided by Tammann temperatures of materials, enabling functional oxide encapsulation of transition metal nanocatalysts. As an illustrative example, Co@BaAl 2 O 4 core@shell is synthesized and tracked in real-time through in-situ microscopy and spectroscopy, revealing an unconventional strong metal-support interaction encapsulation mechanism. Notably, Co@BaAl 2 O 4 exhibits exceptional activity relative to previously reported core@shell catalysts, displaying excellent long-term stability during high-temperature chemical reactions and overcoming the durability and reusability limitations of conventional supported catalysts. This pioneering design and widely applicable approach has been validated to guide the encapsulation of various transition metal nanoparticles for environmental tolerance functionalities, offering great potential to advance energy, catalysis, and environmental fields. The authors report a synthetic strategy to create core@shell catalysts using strong metal-support interactions and low-Tammann-temperature compounds. The resulting materials are highly stable and may be useful in industrial applications.

In order to study the effect of thermal barrier coating deposition inside the film holes of turbine guide vanes on film cooling performance, film effectiveness on the suction side is measured by infrared thermal imaging technology. Film effectiveness is obtained at blockage ratios of 0, 0.2, 0.5, and 0.8, and blowing ratios of 0.7, 1.05, and 1.4. Film effectiveness decreases and the spanwise inhomogeneity becomes evident with an increase of the blockage ratio. When blowing ratios increase from 0.7 to 1.4, the surface averaged film effectiveness decreases by 55–60% at a large blockage ratio of 0.8, 21–27% at the middle blockage ratio of 0.5 and by no more than 11% at a small blockage ratio of 0.2. The rounded corners formed by blockage enhance the adhesion of the film at the small blockage ratio of 0.2, thereby improving the film cooling performance near the hole exit. There is a maximum increase of 0.2 in film effectiveness within four hole diameters.

Background Biopsies are essential in differentiating benign from malignant lesions in routine gastroscopy. Nevertheless, redundant biopsies increase patients’ expenses and pathologists’ workload. Probe-based confocal laser endomicroscopy (pCLE) enables real-time in vivo histological evaluation for gastric neoplasms and precancerous conditions. However, endoscopists vary widely in skill, and the use of pCLE requires histopathology expertise, which limits its application in nonacademic settings. This study aimed to develop a pCLE computer-aided diagnosis system (CCADS) for real-time whole-chain diagnosis of Correa cascade of gastric cancer and evaluate it in a real clinical setting. Methods Gastric pCLE images and videos from 5771 examinations were retrospectively collected. CCADS was constructed using deep learning networks. It was developed using 47,462 pCLE images and 461 video segments and evaluated via multistep validation. A total of 11,439 images and 667 videos were identified for offline validation. Consecutive patients from October 2019 to September 2021 were enrolled in a prospective diagnostic study for real-time validation, which included 951 patients in the statistics. Blinded expert endoscopists and CCADS independently performed real-time pCLE diagnosis of gastric mucosal lesions in routine examinations, with double-read histopathology as the gold standard. The real-time diagnostic performance of CCADS was evaluated and compared with that of experts. Results CCADS achieved high diagnostic performance in image test, video test, and a prospective diagnostic study with a large sample size. Overall, 1254 lesions from 951 patients were included in the prospective test. The real-time diagnostic accuracies of CCADS for inflammation, atrophy, gastric intestinal metaplasia (GIM), low-grade intraepithelial neoplasia (LGIN), and high-grade intraepithelial neoplasia and gastric cancer (HGIN/CA) were 91.71%–97.13%. CCADS achieved high sensitivity (98.44%) and specificity (97.06%) for HGIN/CA. Compared with experts, CCADS achieved similar accuracies in diagnosing atrophy, GIM, and LGIN and similar sensitivities in all five categories. Further, CCADS showed a significantly higher sensitivity (96.70% vs. 89.01%, p  = 0.044) for gastric neoplasms (LGIN + HGIN/CA) and reduced the misdiagnosis of neoplasms. Conclusions CCADS achieved expert-level whole-chain diagnosis of Correa cascade. It could assist endoscopists in improved surveillance of gastric neoplasms and precancerous conditions, promote the application of pCLE, and reduce biopsies. Trial registration ClinicalTrials.gov Identifier: NCT03784209.

Precisely quantifying the spatiotemporal variation patterns of ecosystem water use efficiency (WUE) (i.e., WUE and WUE ) and carbon use efficiency (CUE) across diverse regions, as well as identifying the spatial heterogeneity of their principal influencing factors, are crucial for elucidating the complex underlying mechanisms governing carbon and water cycles in the Yellow River Basin (YRB). In this study, we utilized multi-source remote sensing data, and employed Ensemble Empirical Mode Decomposition (EEMD) to explore the nonlinear spatiotemporal trends and patterns of WUE , WUE , and CUE within the YRB ecosystem. Additionally, we applied the optimally parameterized XGBoost and SHAP models to discern the spatial heterogeneity of the key factors driving their spatiotemporal variations. The results showed that: (1) The WUE , WUE , and CUE of the YRB ecosystem exhibited a spatial distribution pattern characterized by higher values in the southeast and lower values in the northwest, with these metrics were predominantly concentrated at elevations ranging from 1000 to 1500 meters. (2) The interannual change rates of the yearly average values of WUE , WUE and CUE in the YRB ecosystem were 0.008 , 0.005 , and 0.001, respectively. The predominant change patterns for WUE and WUE were monotonic increases, covering approximately 42.44% and 41.97% of the watershed area, respectively. In contrast, the change pattern for CUE was primarily a decrease followed by an increase, observed across 42.51% of the watershed area. (3) In the YRB ecosystem, the leaf area index (LAI) emerged as the primary determinant of WUE and WUE . Specifically, WUE and WUE both showed an upward trend in tandem with the increase in LAI. Furthermore, temperature was identified as the key driving factor for CUE within the YRB ecosystem. (4) In the YRB ecosystem, LAI exhibited the highest importance index for both WUE and WUE . It played a dominant role in approximately 42.80% and 45.35% of the study areas for WUE and WUE , respectively. Conversely, temperature was a crucial factor influencing the spatial variability of CUE in the YRB ecosystem, exerting a predominant influence in 38.88% of the study areas.

The acquisition of high-accuracy reflectance in mid-infrared channels is of great significance for the on-orbit cross-calibration of other bands using the mid-infrared band. However, due to the phenomenon that some sensors have a wide range of wavelengths covered by adjacent channels in the mid-infrared band, the traditional method of estimating the mid-infrared reflectivity assumes that the sea surface reflectivity in different mid-infrared bands is equal, which will lead to a large error during calculation. To solve this problem, this study proposes a nonlinear split-window algorithm involving ocean sun glint data to retrieve reflectivity of FY-3D/MERSI-2 channels 20. The results show that the variation range of sea surface reflectivity of channel 20 in the glint area is 10~25%, the mean value of the reflectivity difference obtained by the nonlinear split-window algorithm is 0.27%, and the RMSE is 0.0066. Among the main influencing factors, the atmospheric conditions have the greatest impact, and the effects of the uncertainties in the water vapor content and aerosol optical thickness on the calculation results are 1.16% and 0.34%, respectively. The initial value limits of the mid-infrared sea surface reflectivity also contribute approximately 0.84%, and their contribution to the uncertainty represents one of the main components. This work shows that the nonlinear split-window algorithm can calculate the infrared sea surface reflectivity with high accuracy and can be used as a reference for in-orbit cross-calibration between different bands.

The double-wall structure is one of the most effective cooling techniques used in many engineering applications, such as turbine vane/blade, heat exchangers, etc. Heat transfer on the internal surfaces of a double-wall structure was studied at impinging Reynolds numbers ranging from 1 × 104 to 6 × 104 using the transient thermochromic liquid crystal (TLC) technique. The two-dimensional distributions of Nusselt numbers and their averaged values were obtained on the impingement surface, target surface and the pin fin surface. The Nusselt number correlations on the surfaces mentioned above were determined as a function of Reynolds number. The results show that the second peak values of the Nusselt number distribution appear on the target surface at all Reynolds numbers studied in this paper for a short distance of the target surface to impingement surface. This phenomenon becomes significant with the further increase of the Reynolds number. The difference between the Nusselt number at the second peak and the stagnation point decreases with the increasing Reynolds number. The maximal Nusselt number regions on the impingement surface appear at the left and right sides of the pin fins between the two impingement holes. The Nusselt numbers of the pin fin surfaces are highly dependent on their various locations in the double-wall structures. The contributions of the impingement surface, pin fin surface and target surface to the overall heat transfer rate are analyzed. The target surface contributed the largest amount of heat transfer rate with a value of about 62%. The heat transfer contribution is from 18% to 21% for the impingement surface and 16% to 18% for the pin fin surfaces within the studied Reynolds numbers.

Nirmatrelvir-ritonavir (Paxlovid) has received emergency use authorization from the US Food and Drug Administration owing to its effectiveness and safety. However, data on the effectiveness and safety of Paxlovid use in COVID-19 patients with onset of more than 5 days are lacking. A real-world retrospective study was performed during the outbreak involving the SARS-CoV-2 BA.5.2 subvariant. Hospitalized COVID-19 patients (including mild, moderate, severe and critical cases) were divided into three groups: Paxlovid treatment within (Group A) or more than (Group B) 5 days of COVID-19 onset and no Paxlovid treatment during more than 5 days of COVID-19 onset with only basic symptomatic treatment (Group C). Endpoints were all-cause 28-day mortality, improvement in clinical classification, and a composite endpoint of disease progression, viral load and virus elimination time. Safety was assessed by comparing adverse events reported during treatment in each group. During the period, 248 hospitalized COVID-19 patients, including 55 in Group A, 170 in Group B, and 23 in Group C, were enrolled. There were no significant differences in the clinical classification improvement rate [80.0% (16/20) vs. 81.3% (52/64), = 1.000; 60.0% (21/35) vs. 55.7% (59/106), = 0.653, respectively] or all-cause 28-day mortality [0% (0/20) vs. 1.6% (1/64), = 1.000; 11.4% (4/35) vs. 6.6% (7/106), = 0.576, respectively] between Groups A and B for nonsevere and severe cases. However, the clinical classification improvement rate in Group B was markedly higher than that in Group C [81.3% (52/64) vs. 50.0% (6/12), = 0.049] among nonsevere cases. Cycle threshold values of the N and ORF genes in Group B were significantly increased after Paxlovid treatment [31.14 (IQR 26.81-33.93) vs. 38.14 (IQR 36.92-40.00), < 0.001; 31.33 (IQR 26.00-33.47) vs. 38.62 (IQR 35.62-40.00), < 0.001, respectively]. No significant differences in reported adverse events of neurological disease ( = 0.571), liver injury ( = 0.960) or kidney injury ( = 0.193) between Group A and Group B were found. Paxlovid treatment within 10 days of onset can shorten the disease course of COVID-19 by reducing the viral load. Paxlovid is effective and safe in treating COVID-19 with onset of more than five or even 10 days when patients have a high viral load.

Xylene exposure is known to induce toxicity in hematopoietic stem and progenitor cells (HSPCs), leading to bone marrow suppression and potential leukemogenesis. However, research on the gene expression profiles associated with xylene-induced toxicity in HSPCs, and effective therapeutic interventions, remains scarce. In our study, we employed single-cell RNA sequencing to capture the transcriptomic shifts within bone marrow HSPCs both prior to and following treatment with coniferyl ferulate (CF) in a mouse model of xylene-induced hematotoxicity. Subsequently, we pinpointed CF as a targeted agent using SPR-LC/MS analysis. This enabled us to confirm the link between the gene Mgst2 and specific cellular subtypes. Our data revealed that CF significantly countered the reduction of both monocyte and neutrophil progenitor cells, which are commonly affected by xylene toxicity. Through targeted analysis, we identified Mgst2 as a direct molecular target of CF. Notably, Mgst2 is preferentially expressed in neutrophil progenitor cells and is implicated in mitochondrial metabolic processes. By selectively inhibiting Mgst2 in bone marrow, we observed amelioration of xylene-induced hematotoxic effects. In summary, our findings suggest that coniferyl ferulate can mitigate the detrimental impact of xylene on hematopoietic stem and progenitor cells by targeting Mgst2, particularly within subpopulations of neutrophil progenitors. This discovery not only advances our comprehension of the cellular response of HSPCs to xenobiotic stressors like xylene but also identifies CF and Mgst2 as potential therapeutic targets for alleviating xylene-induced hematotoxicity.

In order to alleviate membrane fouling and improve removal efficiency, a series of pretreatment technologies were applied to the ultrafiltration process. In this study, ClO2 was used as a pre-oxidation strategy for the ultrafiltration (UF) process. Humic acid (HA), sodium alginate (SA), and bovine serum albumin (BSA) were used as three typical organic model foulants, and the mixture of the three substances was used as a representation of simulated natural water. The dosages of ClO2 were 0.5, 1, 2, 4, and 8 mg/L, with 90 min pre-oxidation. The results showed that ClO2 pre-oxidation at low doses (1–2 mg/L) could alleviate the membrane flux decline caused by humus, polysaccharides, and simulated natural water, but had a limited alleviating effect on the irreversible resistance of the membrane. The interfacial free energy analysis showed that the interaction force between the membrane and the simulated natural water was also repulsive after the pre-oxidation, indicating that ClO2 pre-oxidation was an effective way to alleviate cake layer fouling by reducing the interaction between the foulant and the membrane. In addition, ClO2 oxidation activated the hidden functional groups in the raw water, resulting in an increase in the fluorescence value of humic analogs, but had a good removal effect on the fluorescence intensity of BSA. Furthermore, the membrane fouling fitting model showed that ClO2, at a low dose (1 mg/L), could change the mechanism of membrane fouling induced by simulated natural water from standard blocking and cake layer blocking to critical blocking. Overall, ClO2 pre-oxidation was an efficient pretreatment strategy for UF membrane fouling alleviation, especially for the fouling control of HA and SA at low dosages.