Recent advances in differential expression analysis for single-cell RNA-seq and spatially resolved transcriptomic studies.

Differential expression (DE) analysis is a necessary step in the analysis of single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) data. Unlike traditional bulk RNA-seq, DE analysis for scRNA-seq or SRT data has unique characteristics that may contribute to the difficulty of detecting DE genes. However, the plethora of DE tools that work with various assumptions makes it difficult to choose an appropriate one. Furthermore, a comprehensive review on detecting DE genes for scRNA-seq data or SRT data from multi-condition, multi-sample experimental designs is lacking. To bridge such a gap, here, we first focus on the challenges of DE detection, then highlight potential opportunities that facilitate further progress in scRNA-seq or SRT analysis, and finally provide insights and guidance in selecting appropriate DE tools or developing new computational DE methods.

A Combination of EGFR Inhibitors and AE-PDT Could Synergistically Suppress Breast Cancer Progression.

BACKGROUND: Breast cancer is the most frequently diagnosed malignancy and the leading cause of cancerrelated deaths in women. Activation of EGFR by EC-secreted EGFR ligands promotes breast cancer progression. Current treatments provide limited benefits in triple-negative breast cancer (TNBC). Photodynamic therapy (PDT) has been proven effective for the treatment of TNBC through the EGFR pathway, but the underlying mechanism is still unclear. PURPOSE: The purpose of this study was to determine the role of the EGFR pathway in the treatment of PDT on TNBC in a co-culture system. METHODS: MB-231 and HUVEC were co-cultured for experiments (HU-231). Cell viability and ROS production were detected after AE-PDT, a combination of EGFR inhibitors (AEE788)with PDT to test angiogenesis, apoptosis, and pyroptosis. WB detects expression of EGFR. EGFR, P-EGFR, VEGF, caspase-1, capase-3, and GSDMD . RESULTS: AE-PDT inhibited HU-231 cell proliferation and tumor angiogenesis, and induced cell apoptosis and pyroptosis by promoting ROS production. AEE788, an inhibitor of the EGFR, enhanced HU-231 cell killing after AE-PDT. CONCLUSION: Our study suggested that the combination of EGFR inhibitors and AE-PDT could synergistically suppress breast cancer progression, providing a new treatment strategy.

Dynamic Crushing Behavior of Ethylene Vinyl Acetate Copolymer Foam Based on Energy Method.

This paper aimed to experimentally clarify the dynamic crushing mechanism and performance of ethylene vinyl acetate copolymer (EVA) and analyze the influence of density and thickness on its mechanical behavior and energy absorption properties under dynamic impact loadings. Hence, a series of dynamic compression tests were carried out on EVA foams with different densities and thicknesses. When the impact energy is 66.64 J, for foam with a density of 150 kg/m3, the maximum contact force, maximum displacement, maximum strain, absorbed energy, and specific energy absorption (SEA) increased by 20 ± 2%, -38.5 ± 2%, -38.5 ± 2%, 4 ± 2%, and 105 ± 2%, respectively, compared to foam with a density of 70 kg/m3. The ratios of absorbed energy to impact energy for different thickness specimens are almost equal. The specimen density has no effect on the efficiency of energy absorption and has a greater effect on the SEA. Meanwhile, when the impact energy-to-thickness ratio is 1680 J/m, compared to foam with a thickness of 30 mm, the maximum contact force, maximum displacement, maximum strain, absorbed energy, and SEA for foam with a thickness of 60 mm increased by 28.5 ± 2%, 211.3 ± 2%, 56.6 ± 2%, 100.8 ± 2%, and 0.4 ± 0.5%, respectively. When the impact energy is 66.64 J, compared to foam with a thickness of 30 mm, the maximum contact force, maximum displacement, maximum stain, absorbed energy, and SEA for foam with a thickness of 60 mm increased by -42.5 ± 2%, 163.5 ± 2%, 31.7 ± 2%, 4.1 ± 2%, and 4.1 ± 2%, respectively. The SEA of two different-thickness EVA specimens is almost equal, about 2.8 J/g. The ratios of absorbed energy to impact energy for different thickness specimens are almost equal, both at 72%. The specimen thickness has no effect on the efficiency of energy absorption and has a greater effect on the maximum contact force. In the range of impact energy, thickness, and density studied, the absorbed energy and SEA are not affected by the thickness of EVA specimens and are determined by the impact energy. The density has no significant effect on the absorbed energy but has a greater effect on the SEA. However, for EVA foams, the greater the density, the greater the mass, and the higher the cost. Taking into account lightweight and cost factors, when optimizing cushioning design within a safe range, we can choose EVA foams with a smaller density and thickness.

The ALK1­Smad1/5­ID1 pathway participates in tumour angiogenesis induced by low­dose photodynamic therapy.

Photodynamic therapy (PDT) is an effective and low­invasive tumour therapy. However, it can induce tumour angiogenesis, which is a main factor leading to tumour recurrence and metastasis. Activin receptor­like kinase­1 (ALK1) is a key factor regulating angiogenesis. However, it remains unclear whether ALK1 plays an unusual role in low­dose PDT­induced tumour angiogenesis. In the present study, human umbilical vein endothelial cells (HUVECs) co­cultured with breast cancer MDA­MB­231 cells (termed HU­231 cells) were used to construct an experimental model of tumour angiogenesis induced by low­dose PDT. The viability, and the proliferative, invasive, migratory, as well as the tube­forming ability of the HU­231 cells were evaluated following low­dose PDT. In particular, ALK1 inhibitor and and an adenovirus against ALK1 were used to further verify the role of ALK1 in low­dose PDT­induced tumour angiogenesis. Moreover, the expression of ALK1, inhibitor of DNA binding 1 (ID1), Smad 1, p­Smad1/5, AKT and PI3K were detected in order to verify the underlying mechanisms. The findings indicated that low­dose PDT enhanced the proliferative ability of the HU­231 cells and reinforced their migratory, invasive and tube formation capacity. However, these effects were reversed with the addition of an ALK1 inhibitor or by the knockdown of ALK1 using adenovirus. These results indicated that ALK1 was involved and played a critical role in tumour angiogenesis induced by low­dose PDT. Furthermore, ALK1 was found to participate in PDT­induced tumour angiogenesis by activating the Smad1/5­ID1 pathway, as opposed to the PI3K/AKT pathway. On the whole, the present study, for the first time, to the best of our knowledge, demonstrates that ALK1 is involved in PDT­induced tumour angiogenesis. The inhibition of ALK1 can suppress PDT­induced tumour angiogenesis, which can enhance the effects of PDT and may thus provide a novel treatment strategy for PDT.

The lag effect of exposure to PM2.5 on esophageal cancer in urban-rural areas across China.

Exposure to PM2.5 pollution is a significant health concern and increases risks for cancers in China. However, the studies regarding the effect of PM2.5 and esophageal cancer incidence (ECI) among urban-rural areas are limited. In this study, we examined the sex- and area-specific association between exposure to PM2.5 and ECI, as well as explored the corresponding lag effects on ECI using a geographical weighted Poisson regression. We found significantly positive effect on ECI for males and females in different models, with the greatest increase of 1.44% (95% CI: 1.30%, 1.59%) and 2.42% (95% CI: 2.17%, 2.66%) in per 10 ug/m3 increase of PM2.5 for males and females at single year lag7 and lag4 after all covariates controlled, respectively. We also found that the long-term effect of PM2.5 on ECI was relatively stable at all moving average year lags. Moreover, rural areas had higher ECI risks for males (0.17%) and females (0.64%) with longer lag period than urban areas. In addition, higher risks for both sexes appeared in north, northwestern, and east China. The findings indicated that long-term exposure to PM2.5 was significantly associated with increased risks for ECI, which reinforce a comprehensive understanding for ECI related to PM2.5.

The associations of air pollution and socioeconomic factors with esophageal cancer in China based on a spatiotemporal analysis.

Rapid urbanization and industrialization in China have incurred serious air pollution and consequent health concerns. In this study, we examined the modifying effects of urbanization and socioeconomic factors on the association between PM2.5 and incidence of esophageal cancer (EC) in 2000-2015 using spatiotemporal techniques and a quasi-Poisson generalized linear model. The results showed a downward trend of EC and high-risk areas aggregated in North China and Huai River Basin. In addition, a stronger association between PM2.5 and incidence was observed in low urbanization group, and the association was stronger for females than males. When exposure time-windows were adjusted as 0, 5, 10, 15 years, the incidence risk increased by 2.48% (95% CI: 2.23%, 2.73%), 2.20% (95% CI: 1.91%, 2.49%), 2.18% (95% CI%: 1.92%, 2.43%), 1.87% (95% CI%:1.64, 2.10%) for males, respectively and 4.03% (95% CI: 3.63%, 4.43%), 2.20% (95% CI: 1.91%, 2.49%), 3.97% (95% CI: 3.54%, 4.41%), 3.06% (95% CI: 2.71%, 3.41%) for females, respectively. The findings indicated people in low urbanization group faced with a stronger EC risk caused by PM2.5, which contributes to a more comprehensive understanding of combating EC challenges related to PM2.5 pollution.

Spatial-temporal characteristics of nitrogen degradation in typical Rivers of Taihu Lake Basin, China.

In this study, we focus on the measurement of different nitrogen (N) forms and investigate the spatial-temporal variability of degradation coefficient in river channels. We aim to provide a new approach of deriving in-situ degradation coefficients of different N forms, and highlight factors that determine the spatial-temporal variability of degradation coefficients. Our results are based on a two-year field survey in 34 channels around the Taihu Lake Basin, eastern China. The derived degradation coefficients of different N forms based our newly-developed experimental device are: degradation coefficients of TN, NH4+-N and NO3-N range from 0.006-0.449 d-1, 0.022-1.175 d-1 and -0.096-2.402 d-1, respectively. The degradation coefficients of N show strong dependence on N concentration and water temperature. The seasonal difference of water temperature and N concentration leads to spatial-temporal variability of degradation coefficients. The derived degradation coefficients of N are further verified through one-dimensional water quality model simulations. The degradation coefficient obtained in this study and the influencing factors of its spatial-temporal variability provide invaluable reference for studies in aquatic environment.

[Distribution and Pollution Assessment of Nutrients in the Surface Sediments of a Macrophyte-Dominated Zone in Lake Taihu].

To clarify the spatial distribution and pollution status of nutrients in the surface sediments from a macrophyte-dominated zone in Lake Taihu, total nitrogen (TN), total phosphorus (TP), alkali nitrogen (AN), available phosphorus (AP), and organic matter (OM) were measured at 60 sampling sites in Xukou Bay. A pollution evaluation and source apportionment analysis of these nutrients was also carried out. The average contents of TN, TP, AN, AP, and OM in the surface sediments of Xukou Bay were 1027.5, 423.2, 46.4, 15.3, and 17096.6 mg·kg-1, respectively, with the OM content being significantly higher in the northeast zone than in other areas of the bay. The average value of STN and STP was 1.75 and 0.91, respectively, indicating that TN and TP represent moderate and mild levels of pollution, respectively. The average comprehensive pollution index (FF) was 1.57, indicated that the surface sediment was moderately polluted. The observed organic pollution index indicated that the surface sediments in Xukou Bay were generally clean. Based on C/N values, organic matter in the surface sediments is derived from the bio-deposition of non-fibrous plants and phytoplankton. Based on correlation analysis, OM and TN in the surface sediments of Xukou Bay are derived from the same source, while TP is derived from an alternative source.

[Spatial Distribution and Pollution Assessment of Heavy Metals in River Sediments from Lake Taihu Basin].

To clarify the pollution characteristics of heavy metals in the surface sediments of rivers in economically developed areas, analysis of the contents of eight heavy metals, assessment of ecological risks, and identification of the source of heavy metals in surface sediments from typical rivers of Lake Taihu Basin were carried out in this study. The results showed that the average contents of Zn, Cr, Ni, Cu, Pb, As, Cd, and Hg in the surface sediments of Lake Taihu Basin were 163.62, 102.46, 45.50, 44.71, 37.00, 13.34, 0.479, and 0.109 mg·kg-1, respectively. Except for Hg, the average contents of other 7 heavy metals were higher than their background values. The geo-accumulation index indicated that Pb, Ni, Zn, Cu, and Cd amount to a low pollution state. According to the pollution load index, Pb, Ni, Zn, and Cu represent a moderately polluted state, while Cd, Cr, and As a low degree pollution state. Based on the potential ecological risk index, Cd and Hg represent moderate potential ecological risk, and the others low potential ecological risk. Source identification of heavy metals by multivariate statistical analysis showed that Pb was largely from non-point pollutions; Cr, Ni, and Zn stemmed from electroplating, alloy manufacturing industries, and nature; Cu and As were mainly from pesticides and discharge of industrial wastewater; Cd was dominantly from smelting industry; and Hg was mainly derived from fossil fuel combustion and petroleum products.

Spatio-Temporal Differences in Nitrogen Reduction Rates under Biotic and Abiotic Processes in River Water of the Taihu Basin, China.

Understanding spatio-temporal differences in nitrogen (N) transformation, transport and reduction rates in water bodies is critical to achieve effective mitigation of river eutrophication. We performed culture experiments in six rivers in the Taihu Basin using a custom made in-situ experimental apparatus. We investigated spatio-temporal differences in reduce processes and rates of different N forms and assessed the contribution of biological processes to dissolved inorganic N (DIN) reduce. Results showed that biological processes played a major role in N reduction in summer, while non-microbial processes were dominant in winter. We observed significant spatial and temporal differences in the studied mechanisms, with reduction rates of different N compounds being significantly higher in summer and autumn than spring and winter. Reduction rates ranged from 105.4 ± 25.3 to 1458.8 ± 98.4 mg·(m³·d)-1 for total N, 33.1 ± 12.3 to 440.9 ± 33.1 mg·(m³·d)-1 for ammonium, 56.3 ± 22.7 to 332.1 ± 61.9 mg·(m³·d)-1 for nitrate and 0.4 ± 0.3 to 31.8 ± 9.0 mg·(m³·d)-1 for nitrite across four seasons. Mean DIN reduction rates with and without microbial activity were 96.0 ± 46.4 mg·(m³·d)-1 and 288.1 ± 67.8 mg·(m³·d)-1, respectively, with microbial activity rates accounting for 29.7% of the DIN load and 2.2% of the N load. Results of correlation and principal component analysis showed that the main factors influencing N processing were the concentrations of different N forms and multiple environmental factors in spring, N concentrations, DO and pH in summer, N concentrations and water velocity in autumn and N concentrations in winter.