Multiplex Imaging Reveals Novel Subcellular, Microenvironmental, and Racial Patterns of MRTFA/B Activation in Invasive Breast Cancers and Metastases.

Breast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin related transcription factors A and B (MRTFA/B) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we used a combination of multiplexed immunofluorescence and bioinformatics analyses to show that MRTFA/B are concurrently activated in tumor cells, but they show distinct patterns of expression across different histological subtypes and in the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen presenting cells (APCs) and its expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR). These results provide unique insights into how MRTFA and MRTFB can promote metastasis in human cancer, into the racial disparities of their expression patterns, and their function within the complex breast cancer TME.

Novel calcium oxide activated peroxymonosulfate system for methylene blue removal: Identification of key influencing factors, transformation pathway and toxicity assessment.

The activation of peroxymonosulfate (PMS) has gained significant interest in the removal of organic pollutants. However, traditional methods usually suffer from drawbacks such as secondary contamination and high energy requirements. In this study, we propose a green and cost-effective approach utilizing calcium oxide (CaO) to activate PMS, aiming to construct a simple and reliable PMS based advanced oxidation processes (AOPs). The proposed CaO/PMS system achieved fast degradation of methylene blue (MB), where the degradation rate of CaO/PMS system (0.24 min-1) was nearly 2.67 times that of PMS alone (0.09 min-1). Under the optimized condition, CaO/PMS system exhibited remarkable durability against pH changes, co-exists ions or organic matters. Furthermore, singlet oxygen (1O2) was identified as the dominant reactive oxygen species by electron paramagnetic resonance (EPR) and quenching tests. Accordingly, the degradation pathways of MB are proposed by combing the results of LC/MS analysis and density functional theory (DFT) calculations, and the predicted ecotoxicity of the generated byproducts evaluated by EOCSAR could provide systematic insights into the fates and environmental risks of MB. Overall, the study provides an eco-friendly and effective strategy for treating dyeing wastewater, which should shed light on the application of PMS based AOPs.

Inhalation bioaccessibility and risk assessment for PM-bound organic components: Co-effects of component physicochemical properties, PM properties, and sources.

Inhalation bioaccessibility and deposition in respiratory tracts of organic components in atmospheric particulate matter (PM) are key factors for accurately estimating health risks and understanding human exposures. This study evaluated the in-vitro inhalation bioaccessibility of polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives, phthalic acid esters (PAEs), polychlorinated biphenyls (PCBs), and organophosphate flame retardants (OPFRs) in size-resolved PM from a Chinese megacity. The bioaccessibility ranged from 0.2% to 77.8% in the heating period (HP), and from 0.7% to 94.2% in the non-heating period (NHP). Result suggests that less hydrophobic organics might be more bioaccessible. Bioaccessibility of medium logKow organics in sizes > 0.65 µm was significantly inhibited by high carbon fractions, indicating the co-effects. Then, this is the first study to explore effects of sources on inhalation bioaccessibility of organics. Coal and biomass combustion in HP and traffic emission in NHP negatively correlated with bioaccessibility. Secondary particles also negatively correlated with bioaccessibility of medium logKow organics. Incremental lifetime cancer risk (ILCR) and non-cancer risk (HQ) for all measured components in PM10 were estimated after considering the bioaccessibility and deposition efficiencies and the HQ and ILCR were within the acceptable range. BaP and DEHP were strong contributors to HQ and ILCR, respectively.

Trends in economic burden of type 2 diabetes in China: Based on longitudinal claim data.

Objective: Diabetes is a major health issue in China that has a significant economic burden on society. Understanding the economic impact of diabetes can help policymakers make informed decisions about healthcare spending and priorities. This study aims to estimate the economic burden of patients with diabetes in an urban setting in China and to identify the impact of hospitalization and complications on health care costs for people with diabetes. Methods: The study was conducted in a sample city located in eastern China. All patients diagnosed with diabetes before January 2015 were identified from the official health management information system, and their social demographics and records of their health care uses and costs were extracted from the claim database from 2014 to 2019. Six groups of complications were identified according to ICD-10 codes. The diabetes-related direct medical cost (DM cost) was described for patients in stratified groups. A multiple linear regression model was applied to identify the effect of hospitalization and complications on the DM cost of diabetic patients. Results: Our research included 44,994 patients with diabetes, the average annual DM costs for diabetic patients increased from 1,292.72 USD in 2014 to 2,092.87 USD in 2019. The costs of diabetes are closely related to hospitalizations and the type and number of complications. The average annual DM cost of patients who were hospitalized was 2.23 times that of those without hospitalization, and it rose as the number of complications increased. Cardiovascular complications and nephropathic complications were the complications that had the greatest impact on patients' DM costs, increasing by an average of 65 and 54%, respectively. Conclusion: The economic burden of diabetes in urban China has increased significantly. Hospitalization and the type and number of complications have significant impacts on the economic burden of patients with diabetes. Efforts should be made to prevent the development of long-term complications in the population with diabetes.

Robust and Efficient Assessment of Potency (REAP) as a quantitative tool for dose-response curve estimation.

The median-effect equation has been widely used to describe the dose-response relationship and identify compounds that activate or inhibit specific disease targets in contemporary drug discovery. However, the experimental data often contain extreme responses, which may significantly impair the estimation accuracy and impede valid quantitative assessment in the standard estimation procedure. To improve the quantitative estimation of the dose-response relationship, we introduce a novel approach based on robust beta regression. Substantive simulation studies under various scenarios demonstrate solid evidence that the proposed approach consistently provides robust estimation for the median-effect equation, particularly when there are extreme outcome observations. Moreover, simulation studies illustrate that the proposed approach also provides a narrower confidence interval, suggesting a higher power in statistical testing. Finally, to efficiently and conveniently perform common lab data analyses, we develop a freely accessible web-based analytic tool to facilitate the quantitative implementation of the proposed approach for the scientific community.

Finding a new drug which is both safe and efficient is an expensive and time-consuming endeavour. In particular, establishing the 'dose-effect relationship' ­ how beneficial a drug is at different dosages ­ can be challenging. Predicting this curve requires gathering experimental data by exposing and recording how cells respond to various levels of the drug. However, extreme values are often observed at low and high dosages, potentially introducing errors that are hard to correct in the prediction process. Yet, these extreme observations are sometimes genuine so researchers cannot just ignore them. To improve dose-effect estimation, Zhou, Liu, Fang et al. developed a new general-purpose approach. It uses advanced statistical modelling to account for extremes in lab data. This strategy outperformed other methods when dealing with these observations while also providing higher efficiency in data analysis with more uniform data in experiments. To facilitate implementation, Zhou, Liu, Fang et al. set up a user-friendly tool baptized 'REAP'; this free online resource allows scientists without advanced statistical experience to harness the new approach and to perform dose-effect analysis more easily and accurately. This could boost research across many different disciplines that examine the effects of chemicals on cells.

Gender Bias and the Lack of Equity in Pandemic Nursing in China: A Qualitative Study.

There has long been a gender bias in medicine. This qualitative study aims to identify the experience of sexism among frontline female nurses and further explore their expectations and possible strategies to get rid of gender bias. This is a descriptive phenomenological study of 23 female nurses with 11 ± 3.98 years of experience who spent 36 ± 6.50 days at the frontline during the initial COVID-19 outbreak. We employed Colaizzi's phenomenological analysis method to understand the subjective experiences, revealing the following themes: (a) materialization of gender identity; (b) incoordinate relationships; (c) future voice of female nurses. The gender bias experienced by female frontline nurses further challenges their emotional identity and self-identity. Therefore, it is important to require extensive consciousness-raising and policy support to defend female nurses' rights.

The prehistoric roots of Chinese cuisines: Mapping staple food systems of China, 6000 BC-220 AD.

We conducted a meta-analysis of published carbon and nitrogen isotope data from archaeological human skeletal remains (n = 2448) from 128 sites cross China in order to investigate broad spatial and temporal patterns in the formation of staple cuisines. Between 6000-5000 cal BC we found evidence for an already distinct north versus south divide in the use of main crop staples (namely millet vs. a broad spectrum of C3 plant based diet including rice) that became more pronounced between 5000-2000 cal BC. We infer that this pattern can be understood as a difference in the spectrum of subsistence activities employed in the Loess Plateau and the Yangtze-Huai regions, which can be partly explained by differences in environmental conditions. We argue that regional differentiation in dietary tradition are not driven by differences in the conventional "stages" of shifting modes of subsistence (hunting-foraging-pastoralism-farming), but rather by myriad subsistence choices that combined and discarded modes in a number of innovative ways over thousands of years. The introduction of wheat and barley from southwestern Asia after 2000 cal BC resulted in the development of an additional east to west gradient in the degree of incorporation of the different staple products into human diets. Wheat and barley were rapidly adopted as staple foods in the Continental Interior contra the very gradual pace of adoption of these western crops in the Loess Plateau. While environmental and social factors likely contributed to their slow adoption, we explored local cooking practice as a third explanation; wheat and barley may have been more readily folded into grinding-and-baking cooking traditions than into steaming-and-boiling traditions. Changes in these culinary practices may have begun in the female sector of society.

A Low-Cost Resource Re-Allocation Scheme for Increasing the Number of Guaranteed Services in Resource-Limited Vehicular Networks.

Vehicular networks are becoming increasingly dense due to expanding wireless services and platooning has been regarded as a promising technology to improve road capacity and on-road safety. Constrained by limited resources, not all communication links in platoons can be allocated to the resources without suffering interference. To guarantee the quality of service, it is required to determine the set of served services at which the scale of demand exceeds the capability of the network. To increase the number of guaranteed services, the resource allocation has to be adjusted to adapt to the dynamic environment of the vehicular network. However, resource re-allocation results in additional costs, including signal overhead and latency. To increase the number of guaranteed services at a low-cost in a resource-limited vehicular network, we propose a time dynamic optimization method that constrains the network re-allocation rate. To decrease the computational complexity, the time dynamic optimization problem is converted into a deterministic optimization problem using the Lyapunov optimization theory. The simulation indicates that the analytical results do approximate the reality, and that the proposed scheme results in a higher number of guaranteed services as compared to the results of a similar algorithm.

Comprehensive assessment showed no associations of variants at the SLC10A1 locus with susceptibility to persistent HBV infection among Southern Chinese.

The sodium taurocholate cotransporting polypeptide (NTCP) encoded by SLC10A1 was recently demonstrated to be a functional receptor for hepatitis B virus (HBV). The role of SLC10A1 polymorphisms, particularly the Ser267Phe variant (rs2296651) in exon 4, has been frequently investigated in regard to risk of persistent HBV infection. However, these investigations have generated conflicting results. To examine whether common genetic variation at the SLC10A1 locus is associated with risk of persistent HBV infection, haplotype-tagging and imputed single nucleotide polymorphisms (SNPs) were assessed in two case-control sample sets, totally including 2,550 cases (persistently HBV infected subjects, PIs) and 2,124 controls (spontaneously recovered subjects, SRs) of Southern Chinese ancestry. To test whether rare or subpolymorphic SLC10A1 variants are associated with disease risk, the gene's exons in 244 cases were sequenced. Overall, we found neither SNPs nor haplotypes of SLC10A1 showed significant association in the two sample sets. Furthermore, no significant associations of rare variants or copy number variation covering SLC10A1 were observed. Finally, expression quantitative trait locus analyses revealed that SNPs potentially affecting SLC10A1 expression also showed no significant associations. We conclude that genetic variation at the SLC10A1 locus is not likely a major risk factor of persistent HBV infection among Southern Chinese.