ZIP11 Regulates Nuclear Zinc Homeostasis in HeLa Cells and Is Required for Proliferation and Establishment of the Carcinogenic Phenotype.

Zinc (Zn) is an essential trace element that plays a key role in several biological processes, including transcription, signaling, and catalysis. A subcellular network of transporters ensures adequate distribution of Zn to facilitate homeostasis. Among these are a family of importers, the Zrt/Irt-like proteins (ZIP), which consists of 14 members (ZIP1-ZIP14) that mobilize Zn from the extracellular domain and organelles into the cytosol. Expression of these transporters varies among tissues and during developmental stages, and their distribution at various cellular locations is essential for defining the net cellular Zn transport. Normally, the ion is bound to proteins or sequestered in organelles and vesicles. However, though research has focused on Zn internalization in mammalian cells, little is known about Zn mobilization within organelles, including within the nuclei under both normal and pathological conditions. Analyses from stomach and colon tissues isolated from mouse suggested that ZIP11 is the only ZIP transporter localized to the nucleus of mammalian cells, yet no clear cellular role has been attributed to this protein. We hypothesized that ZIP11 is essential to maintaining nuclear Zn homeostasis in mammalian cells. To test this, we utilized HeLa cells, as research in humans correlated elevated expression of ZIP11 with poor prognosis in cervical cancer patients. We stably knocked down ZIP11 in HeLa cancer cells and investigated the effect of Zn dysregulation in vitro. Our data show that ZIP11 knockdown (KD) reduced HeLa cells proliferation due to nuclear accumulation of Zn. RNA-seq analyses revealed that genes related to angiogenesis, apoptosis, mRNA metabolism, and signaling pathways are dysregulated. Although the KD cells undergoing nuclear Zn stress can activate the homeostasis response by MTF1 and MT1, the RNA-seq analyses showed that only ZIP14 (an importer expressed on the plasma membrane and endocytic vesicles) is mildly induced, which may explain the sensitivity to elevated levels of extracellular Zn. Consequently, ZIP11 KD HeLa cells have impaired migration, invasive properties and decreased mitochondrial potential. Furthermore, KD of ZIP11 delayed cell cycle progression and rendered an enhanced senescent state in HeLa cells, pointing to a novel mechanism whereby maintenance of nuclear Zn homeostasis is essential for cancer progression.

Comparing physiological responses during cognitive tests in virtual environments vs. in identical real-world environments.

Immersive virtual environments (VEs) are increasingly used to evaluate human responses to design variables. VEs provide a tremendous capacity to isolate and readily adjust specific features of an architectural or product design. They also allow researchers to safely and effectively measure performance factors and physiological responses. However, the success of this form of design-testing depends on the generalizability of response measurements between VEs and real-world contexts. At the current time, there is very limited research evaluating the consistency of human response data across identical real and virtual environments. Rendering tools were used to precisely replicate a real-world classroom in virtual space. Participants were recruited and asked to complete a series of cognitive tests in the real classroom and in the virtual classroom. Physiological data were collected during these tests, including electroencephalography (EEG), electrocardiography (ECG), electrooculography (EOG), galvanic skin response (GSR), and head acceleration. Participants' accuracy on the cognitive tests did not significantly differ between the real classroom and the identical VE. However, the participants answered the tests more rapidly in the VE. No significant differences were found in eye blink rate and heart rate between the real and VR settings. Head acceleration and GSR variance were lower in the VE setting. Overall, EEG frequency band-power was not significantly altered between the real-world classroom and the VE. Analysis of EEG event-related potentials likewise indicated strong similarity between the real-world classroom and the VE, with a single exception related to executive functioning in a color-mismatch task.

Prenatal Exposure to Specific PM2.5 Chemical Constituents and Preterm Birth in China: A Nationwide Cohort Study.

Exposure to fine particulate matter (PM2.5) during pregnancy has been associated with preterm birth (PTB). However, the existing evidence is inconsistent, and the roles of specific PM2.5 chemical constituents remain unclear. Based on the China Labor and Delivery Survey, we included birth data from 89 hospitals in 25 provinces in mainland China, and conducted a national multicenter cohort study to examine the associations of PM2.5 and its chemical constituents with PTB risk in China. We applied satellite-based models to predict prenatal PM2.5 mass and six main component exposure. Multilevel logistic regression analysis was used to examine the associations, controlling for sociodemographic characteristics, seasonality, and spatial variation. We observe an increased PTB risk with an increase in PM2.5 mass and the most significant association is found during the third trimester when the adjusted odds ratio (OR) per interquartile range increases in PM2.5 total mass is 1.12 (95% confidence Interval, CI: 1.05-1.20). Infants conceived by assisted reproductive technology (ART) show greater PTB risk associated with PM2.5 exposure (OR = 1.33, 95% CI: 1.05-1.69) than those conceived naturally (OR = 1.11, 95% CI: 1.03-1.19). We also find black carbon, sulfate, ammonium and nitrate, often linked to fossil combustion, have comparable or larger estimates of the effect (OR = 1.07-1.14) than PM2.5. Our findings provide evidence that components mainly from fossil fuel combustion may have a perceptible influence on increased PTB risk associated with PM2.5 exposure in China. Additionally, compared to natural conception, conception through ART may be more susceptible to PM2.5 exposure.

Association between ambient temperature and daily emergency hospitalizations for acute coronary syndrome in Yancheng, China.

Acute coronary syndrome (ACS) is a major public health concern worldwide. Few studies have directly evaluated the associations between ambient temperature and ACS incidence. To explore the association between ambient temperature and ACS emergency hospitalizations in the area of subtropical monsoon climate, data on ACS emergency hospitalizations were collected from two highest-ranking hospitals in the central urban area of Yancheng, China, from January 1, 2013, to December 31, 2018. We applied the time-series method to investigate the potentially lagged and non-linear effects of ambient temperature on ACS using the generalized linear model combined with the distributed lag non-linear model after adjusting for time trend, day of the week, holiday, and relative humidity. We identified a total of 5303 cases of ACS emergency hospitalizations during the study period. The exposure-response curves between ambient temperature and ACS hospitalizations were inverse "J-shaped." The effects of extreme low temperature on ACS hospitalizations occurred on the present day and lasted for 3 days, followed by the harvesting effect. The effects of extreme high temperature occurred on the present day and lasted for 5 days. The cumulative relative risks of ACS were 2.14 [95% confident interval (CI): 1.32 to 3.47] for extremely low temperature and 1.66 (95% CI: 1.33 to 2.06) for extremely high temperature over the lag of 0-5 days, compared with the reference temperature (25.0 °C). Both low and high temperatures were significantly associated with higher risks of emergency hospital admissions for ACS in Yancheng, China.