Serum cystatin C and chemerin levels in diabetic retinopathy

Peer reviewedPublisher PD

Predicting bacterial transport through saturated porous media using an automated machine learning model

Escherichia coli, as an indicator of fecal contamination, can move from manure-amended soil to groundwater under rainfall or irrigation events. Predicting its vertical transport in the subsurface is essential for the development of engineering solutions to reduce the risk of microbiological contamination. In this study, we collected 377 datasets from 61 published papers addressing E. coli transport through saturated porous media and trained six types of machine learning algorithms to predict bacterial transport. Eight variables, including bacterial concentration, porous medium type, median grain size, ionic strength, pore water velocity, column length, saturated hydraulic conductivity, and organic matter content were used as input variables while the first-order attachment coefficient and spatial removal rate were set as target variables. The eight input variables have low correlations with the target variables, namely, they cannot predict target variables independently. However, using the predictive models, input variables can effectively predict the target variables. For scenarios with higher bacterial retention, such as smaller median grain size, the predictive models showed better performance. Among six types of machine learning algorithms, Gradient Boosting Machine and Extreme Gradient Boosting outperformed other algorithms. In most predictive models, pore water velocity, ionic strength, median grain size, and column length showed higher importance than other input variables. This study provided a valuable tool to evaluate the transport risk of E.coli in the subsurface under saturated water flow conditions. It also proved the feasibility of data-driven methods that could be used for predicting other contaminants’ transport in the environment

The development of a novel in vitro model of human liver for the study of disease pathogenesis

The development of systems for the long term in vitro culture of functional liver tissue is a major research goal. The central limitation of experimental systems to date has been the early de-differentiation of primary hepatocytes in cultures. Several factors including cell-cell interaction, cell-matrix interaction, soluble factors and 3D structures have been identified as the keys to overcome this limitation. The first aim of this project is to compare the established 3D model, co-culture of hepatocytes and hepatic stellate cells (HSCs) on PDLLA coated surfaces, to other best available systems using collagen and Matrigel. The hypothesis is that hepatocytes functionalities, established by cell-cell interaction, 3D structures and soluble factors, can be further enhanced by introduction of cell-matrix interaction. In order to test the hypothesis, rat hepatocytes were cultured in five different systems, including monoculture of hepatocytes on collagen gel, in collagen-Matrigel sandwich, co-culture of hepatocytes and HSCs on collagen gel, in collagen-Matrigel sandwich and on PDLLA coated surface. Hepatocyte specific function assays, namely albumin secretion, urea secretion, testosterone metabolism by HPLC and CYP activities by LC-MS-MS, were used to analyze cell functionalities. Homo-spheroids were only formed in monoculture on collagen gel, but hetero-spheroids were developed in all the co-culture systems. The results of function assays showed hepatocytes in collagen-Matrigel sandwich configuration had the best secretion of albumin and urea and best CYP activities during the culture period. These data demonstrated the hypothesis that hepatocyte functions of the established model can be further improved by introduction of cell-matrix interaction. In addition to establishment of rat hepatocyte culture systems, hetero-spheroids of primary human hepatocytes and primary human HSCs on PDLLA coated plates were developed successfully, due to the great improvements of isolation and culture of primary human HSCs. However, hepatocyte function assays have not been applied yet. Hepatic cell lines have several advantages that are not applicable to primary cultured human hepatocytes, namely unlimited lifespan and stable phenotype. The immortalized Fa2N-4 cell lines have recently been assessed as replacements of primary human hepatocytes in CYP induction studies. The second aim of this study was to simultaneously characterize CYP1A2, CYP2C9, CYP3A4 and CYP2B6 induction in Fa2N-4 cells through assessment of mRNA, protein and activity endpoints for a range of prototypical compounds (previously assessed in human hepatocytes) with known positive and negative induction potential. LC-MS-MS and RT-PCR were used for assessment of activity and mRNA endpoints respectively. As a result, it is considered that Fa2N-4 cells offer a substitute for primary human hepatocytes for CYP1A2 and CYP3A4 induction but not for CYP2B6 due to lack of cytosolic CAR expression

An Aquaporin 3-Notch1 Axis in Keratinocyte Differentiation and Inflammation

Aquaporin 3 (AQP3) is an aquaglyceroporin which transports water, glycerol and small solutes across the plasma membrane. Its functions are not limited to fluid transport but also involve the regulation of cell proliferation, migration, skin hydration, wound healing and tumorigenesis. While AQP3 has been reported to play an important role in keratinocyte proliferation, its role in differentiation remains controversial. Our study demonstrated that the expression of AQP3 was regulated during differentiation and that it participated in keratinocyte differentiation control. We further revealed that AQP3 was a transcriptional target of Notch signaling, a critical pathway regulating keratinocyte differentiation and tumor suppression, and it regulated differentiation through a reciprocal negative feedback loop with Notch1. When the expression level of AQP3 was elevated, impaired barrier integrity and increased pro-inflammatory cytokine production ensued, mimicking the pathological conditions in Notch deficient mice and in atopic dermatitis. Dysregulation of AQP3 and Notch receptors has been reported in several skin diseases, including skin cancer. Our discovery of the novel AQP3-Notch1 axis may provide insight into epidermal homeostasis control and possible translational applications, including its potential use as a biomarker for molecular diagnosis in environmental studies

Sex inequality driven by dispersal

Inequality between the sexes is pervasive both outside and inside the home. One contributing factor could be the dispersal of one sex at marriage that sets up sex-specific differences in relatedness to the group. Here we exploit the ecological diversity and different social structures found in southwest China to investigate the role of sex-biased dispersal on inequality in the sexual division of labor. We use a wearable fitness tracker and validated readings by confirming that participants' daily "steps" were positively correlated with time spent in high-energy activities, such as agriculture and animal husbandry work, and negatively correlated with low-energy activities, such as leisure and relaxation. We applied multilevel comparative approaches to examine the relative workload pattern between the sexes under different dispersal states. Our results reveal two characteristics that lead to an unfavorable division of workload: being female and dispersing at marriage. This is consistent with the hypothesis that males have increased bargaining power when remaining in their natal home, leading to inequality in workload

Gender inequality in workloads explained by operational sex ratio

Ecological differences between human populations can affect the relative strength of sexual selection, and hence drive gender inequality. Here, we exploit the cultural diversity of southwestern China, where some village sex ratios are female-biased, in part due to a proportion of males entering monastic celibacy, to evaluate the role of sex ratio on the sexual division of labor. We used a detachable activity tracker to measure workload by step counts in both sexes among 561 individuals in 55 villages in six different areas. We show that a lower sex ratio and a higher prevalence of monasticism are associated with higher women’s workloads and reduced men’s workloads in the non-celibate population. As the operational sex ratio increases, gender inequality diminishes. This study offers valuable insights into the origins of gender disparities by examining the role of sex ratio on the sexual division of labor

Expert consensus on the management of adverse events in patients receiving targeted agents for advanced thyroid cancer (2023 edition)

Recently, targeted therapy has become the standard of care for advanced thyroid cancer. Although expert consensus on the management of adverse events in patients receiving targeted agents for radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) was formulated by Thyroid Cancer Committee of Chinese Society of Clinical Oncology in 2018, the tumor types which are eligible for targeted therapy have been extended to medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), and targeted agents have been approved from multikinase inhibitors (MKIs) to BRAF inhibitors, MEK inhibitors, RET inhibitors and TRK inhibitors. Along with the widely used targeted agents with different mechanism, the management of adverse events for targeted agents needs to be standardized and improved, especially considering the specialties of the physicians who are involved in the targeted therapy for thyroid cancer are variable. Therefore, Thyroid Cancer Committee of Chinese Society of Clinical Oncology convened an expert task force charged with developing consensus to serves as a guidance to standardize utilization of targeted agents and to optimize clinical practice