HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer

The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future

Pan-cancer analysis reveals that G6PD is a prognostic biomarker and therapeutic target for a variety of cancers

BackgroundDespite accumulating evidence revealing that Glucose-6-phosphate dehydrogenase (G6PD) is highly expressed in many tumor tissues and plays a remarkable role in cancer tumorigenesis and progression, there is still a lack of G6PD pan-cancer analysis. This study was designed to analyze the expression status and prognostic significance of G6PD in pan-cancer.MethodsG6PD expression data were obtained from multiple data resources including the Genotype-Tissue Expression, the Cancer Genome Atlas, and the Tumor Immunity Estimation Resource. These data were used to assess the G6PD expression, prognostic value, and clinical characteristics. The ESTIMATE algorithms were used to analyze the association between G6PD expression and immune-infiltrating cells and the tumor microenvironment. The functional enrichment analysis was also performed across pan-cancer. In addition, the GDSC1 database containing 403 drugs was utilized to explore the relationship between drug sensitivity and G6PD expression levels. Furthermore, we also performed clinical validation and in vitro experiments to further validate the role of G6PD in hepatocellular carcinoma (HCC) cells and its correlation with prognosis. The R software was used for statistical analysis and data visualization.ResultsG6PD expression was upregulated in most cancers compared to their normal counterparts. The study also revealed that G6PD expression was a prognostic indicator and high levels of G6PD expression were correlated with worse clinical prognosis including overall survival, disease-specific survival, and progression-free interval in multiple cancers. Furthermore, the G6PD level was also related to cancer immunity infiltration in most of the cancers, especially in KIRC, LGG, and LIHC. In addition to this, G6PD expression was positively related to pathological stages of KIRP, BRCA, KIRC, and LIHC. Functional analysis and protein-protein interactions network results revealed that G6PD was involved in metabolism-related activities, immune responses, proliferation, and apoptosis. Drug sensitivity analysis showed that IC50 values of most identified anti-cancer drugs were positively correlated with the G6PD expression. Notably, in vitro functional validation showed that G6PD knockdown attenuated the phenotypes of proliferation in HCC.ConclusionG6PD may serve as a potential prognostic biomarker for cancers and may be a potential therapeutic target gene for tumor therapy

Thermal Concentration on Thermoelectric Thin Film for Efficient Solar Energy Harvesting

Thermoelectric generators can directly harvest and convert ambient thermal energy into electricity, which makes it ideal for thermal energy conversion. However, the limited working temperature gradient developed by direct solar radiation severely restricts the performance and the application of solar thermoelectric generators. Here, we report a multilayer thin film integrating a solar selective absorbing coating and a thermoelectric layer, where an in-plane temperature gradient was established. The temperature gradient was relatively large since the absorbed solar energy could only flow through the restricted cross-section of the thin film, representing a high thermal concentration. The fabricated thin-film solar thermoelectric generators (100 mm × 15 mm) achieve an open-circuit voltage of about 300 mV, and an output power of 0.83 μW under AM 1.5G conditions. Our work opens up a promising new strategy to achieve the simple and cost-effective conversion of solar energy into electricity by thermal concentration

An Experimental Study on the Dynamic Mechanical Properties of Epoxy Polymer Concrete under Ultraviolet Aging

Epoxy polymer concrete (EPC) is widely applied in engineering for its excellent mechanical properties. The impact loads and severe climatic conditions such as ultraviolet radiation, temperature change and rain erosion are in general for its engineering practice, potentially degrading the performance of EPC. In this paper, a procedure of accelerated aging for EPC, imitating the aging effect of ultraviolet radiation and hygrothermal conditions based on the meteorological statistics of Guangzhou city, was designed. After various periods of accelerated aging, the dynamic behaviors of EPC were studied by using a Split Hopkinson Pressure Bar (SHPB). The verification of the experimental data was performed. The two-stage dynamic compression stress-strain curves were obtained: (a) linear growth stage following by strain hardening stage at impact velocity 12.2 m/s and 18.8 m/s, (b) linear growth stage and then a horizontal stage when impact velocity is 25.0 m/s, (c) linear growth stage following by strain softening stage at impact velocity 29.2 m/s. The experimental results show that the specimens after longer accelerated aging tend to be more easily broken, especially at impact velocity 12.2 m/s and 18.8 m/s, while the strain rate is the main factor affecting the compression strength and stiffness. Ultimately the influence of strain rate and equivalent aging time on dynamic increase factor was revealed by a fitting surface

High CD133 expression in proximal tubular cells in diabetic kidney disease: good or bad?

Abstract Background Proximal tubular cells (PTCs) play a critical role in the progression of diabetic kidney disease (DKD). As one of important progenitor markers, CD133 was reported to indicate the regeneration of dedifferentiated PTCs in acute kidney disease. However, its role in chronic DKD is unclear. Therefore, we aimed to investigate the expression patterns and elucidate its functional significance of CD133 in DKD. Methods Data mining was employed to illustrate the expression and molecular function of CD133 in PTCs in human DKD. Subsequently, rat models representing various stages of DKD progression were established. The expression of CD133 was confirmed in DKD rats, as well as in human PTCs (HK-2 cells) and rat PTCs (NRK-52E cells) exposed to high glucose. The immunofluorescence and flow cytometry techniques were utilized to determine the expression patterns of CD133, utilizing proliferative and injury indicators. After overexpression or knockdown of CD133 in HK-2 cells, the cell proliferation and apoptosis were detected by EdU assay, real-time cell analysis and flow analysis. Additionally, the evaluation of epithelial, progenitor cell, and apoptotic indices was performed through western blot and quantitative RT-PCR analyses. Results The expression of CD133 was notably elevated in both human and rat PTCs in DKD, and this expression increased as DKD progressed. CD133 was found to be co-expressed with CD24, KIM-1, SOX9, and PCNA, suggesting that CD133+ cells were damaged and associated with proliferation. In terms of functionality, the knockdown of CD133 resulted in a significant reduction in proliferation and an increase in apoptosis in HK-2 cells compared to the high glucose stimulus group. Conversely, the overexpression of CD133 significantly mitigated high glucose-induced cell apoptosis, but had no impact on cellular proliferation. Furthermore, the Nephroseq database provided additional evidence to support the correlation between CD133 expression and the progression of DKD. Analysis of single-cell RNA-sequencing data revealed that CD133+ PTCs potentially play a role in the advancement of DKD through multiple mechanisms, including heat damage, cell microtubule stabilization, cell growth inhibition and tumor necrosis factor-mediated signaling pathway. Conclusion Our study demonstrates that the upregulation of CD133 is linked to cellular proliferation and protects PTC from apoptosis in DKD and high glucose induced PTC injury. We propose that heightened CD133 expression may facilitate cellular self-protective responses during the initial stages of high glucose exposure. However, its sustained increase is associated with the pathological progression of DKD. In conclusion, CD133 exhibits dual roles in the advancement of DKD, necessitating further investigation

Inappropriate cessation of nucleos(t)ide analog associated with reduced liver transplant-free survival in patients with HBV-related acute on chronic liver failure

The inappropriate cessation of nucleos(t)ide analog (NA) therapy may lead to acute exacerbations of chronic hepatitis B virus (HBV) infection, acute-on-chronic liver failure (ACLF), and even death. This study aims to elucidate the association between inappropriate NA cessation and prognosis in patients with HBV-ACLF. A total of 901 patients with ACLF were enrolled and stratified into inappropriate NA cessation and non-NA cessation group. Clinical characteristics and prognosis between the two groups were compared. The association between inappropriate NA cessation and the prognosis of patients with HBV-ACLF was evaluated using Cox proportional hazard models after propensity score matching (PSM). NA cessation was identified in 132 patients (NA cessation group), while 769 patients were triggered by other factors (non-NA cessation group). The 28- and 90-day liver transplant-free survival rates were higher in patients with non-NA cessation than in those with NAs cessation (78.3 % vs. 62.1 %, P < 0.001; 62.8 % vs. 44.7 %, P < 0.001). The need for liver transplantation was significantly higher in the NA cessation group compared with the non-NAs cessation group (21.2 % vs. 7.0 %, P < 0.001). The Kaplan-Meier curve showed that inappropriate NA therapy discontinuation had reduced 28- and 90-day live transplant-free survival compared with other precipitating events prior to PSM (all P < 0.001). After matching, the 28- and 90-day transplantation-free survival was also significantly lower in the NA cessation group vs. the non-NA cessation group (P = 0.012 and P = 0.022). In conclusion, the inappropriate cessation of NA therapy is associated with reduced liver transplant-free survival in patients with HBV-related ACLF

Programmable microfluidics for dynamic multiband camouflage

Abstract Achieving multiband camouflage covering both visible and infrared regions is challenging due to the broad bandwidth and differentiated regulation demand in diverse regions. In this work, we propose a programmable microfluidic strategy that uses dye molecules in layered fluids to manipulate visible light- and infrared-semitransparent solvent to manipulate infrared light. With three primary fluid inputs, we achieve 64 chromaticity values and 8 emissivities from 0.42 to 0.90. In view of the wide tuning range, we demonstrate that the microfluidic film can dynamically change its surface reflectance to blend into varying backgrounds in both visible and infrared images. Moreover, we fabricate the microfluidic device in a textile form and demonstrate its ability to match exactly with the colors of natural leaves of different seasons in the full hyperspectrum range. Considering the broadband modulation and ease of operation, the programmable microfluidic strategy provides a feasible approach for smart optical surfaces in long-span optical spectra

Nightside Ionospheric Structure and Composition on Mars Driven by Energetic Electron Precipitation

Ionospheric chemistry plays an unexpectedly important role in the evolution of planetary habitability. This study is dedicated to a detailed modeling of the nightside Martian ionospheric structure and composition, a topic that has been poorly explored due to the absence of relevant measurements, but now becomes tractable owing to the unprecedented measurements made by the Mars Atmosphere and Volatile Evolution. Two-stream kinetic calculations and time-dependent fluid calculations are coupled to derive the nightside density profiles at 100–300 km for a large number of ion species, assuming solar wind electron precipitation as the only viable ionizing source in the ideal nonmagnetized atmosphere. Our calculations indicate the presence of a well-defined ionospheric peak at 146 km with a peak density of 8500 cm ^−3 , as driven by the strong atmospheric “absorption” of precipitating electrons at low altitudes. The distribution of nonterminal species is roughly under chemical equilibrium below 170 km, whereas for terminal species such as NO ^+ and HCO ^+ , diffusion is effective at essentially all altitudes, in direct contrast to the dayside behavior. In the more realistic magnetized atmosphere, the ionospheric peak seldom exists due to the patchiness of electron precipitation. In particular, our model results agree fairly well with the MAVEN measurements, especially in view of the coincidence between electron depletion and thermal plasma void seen along many MAVEN orbits. Compared to the dayside, the nightside ionospheric composition has a much higher proportion of NO ^+ and lower proportion of CO _2 ^+ , likely indicative of nightside enhancement of atmospheric O and N