Identification of a novel fusion gene, RARA::ANKRD34C, in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia that is distinguished by the chromosomal translocation t(15;17)(q24;q21), which leads to the fusion of the promyelocytic leukemia (PML) gene with the retinoic acid receptor alpha (RARA). Recently, we identified a novel fusion gene in APL, RARA::ankyrin repeat domain 34C (ANKRD34C), identified its functions by morphological, cytogenetic, molecular biological and multiplex fluorescence in situ hybridization analyses, and demonstrated the potential therapeutic effect clinically and experimentally of all-trans retinoic acid (ATRA); the findings have important implications for the diagnosis and treatment of atypical APL.

Evaluation of Neurotoxicity in BALB/c Mice following Chronic Exposure to Polystyrene Microplastics.

BACKGROUND: The toxicity of microplastics (MPs) has attracted wide attention from researchers. Previous studies have indicated that MPs produce toxic effects on a variety of organs in aquatic organisms and mammals. However, the exact neurotoxicity of MPs in mammals is still unclear. OBJECTIVES: We aimed to confirm the neurotoxicity of chronic exposure to polystyrene MPs (PS-MPs) at environmental pollution concentrations. METHODS: In the present study, mice were provided drinking water containing 100µg/L and 1,000µg/L PS-MPs with diameters of 0.5, 4, and 10µm for 180 consecutive days. After the exposure period, the mice were anesthetized to gain brain tissues. The accumulation of PS-MPs in brain tissues, integrity of the blood-brain barrier, inflammation, and spine density were detected. We evaluated learning and memory ability by the Morris water maze and novel object recognition tests. RESULTS: We observed the accumulation of PS-MPs with various particle diameters (0.5, 4, and 10µm) in the brains of exposed mice. Meanwhile, exposed mice also exhibited disruption of the blood-brain barrier, higher level of dendritic spine density, and an inflammatory response in the hippocampus. In addition, exposed mice exhibited cognitive and memory deficits compared with control mice as determined using the Morris water maze and novel object recognition tests, respectively. There was a concentration-dependent trend, but no particle size-dependent differences were seen in the neurotoxicity of MPs. CONCLUSIONS: Collectively, our results suggested that PS-MPs exposure can lead to learning and memory dysfunctions and induce neurotoxic effects in mice, findings which have wide-ranging implications for the public regarding the potential risks of MPs. https://doi.org/10.1289/EHP10255.

Chronic exposure to polystyrene microplastics induced male reproductive toxicity and decreased testosterone levels via the LH-mediated LHR/cAMP/PKA/StAR pathway.

BACKGROUND: Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear. RESULTS: In vivo, mice were given drinking water containing 100 µg/L and 1000 µg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 µm, 4 µm, and 10 µm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs. CONCLUSIONS: PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

Inequities in consistent condom use among sexually experienced undergraduates in mainland China: implications for planning interventions.

BACKGROUND: Since pre-exposure prophylaxis (PrEP) is mainly prescribed to high-risk uninfected individuals, consistent condom use (CCU) continues to be recommended as an inexpensive, feasible, practical and acceptable way to prevent the general population from acquiring and transmitting HIV through sexual intercourse. The objective of this cross-sectional study was to compare the relative importance of various determinants of CCU among sexually experienced undergraduates in mainland China so as to assess and subsequently to suggest ways to eliminate inequities in its use. METHOD: From September 10, 2018, to January 9, 2019, an anonymous self-administered online questionnaire was voluntarily completed by 12,750 participants distributed across 30 provinces in mainland China (except for Tibet). The present analysis was restricted to 2054 sexually experienced undergraduates. Pearson's chi-square test and Logistic regression models were chosen to analyze the factors associated with CCU. RESULTS: The overall rate of CCU was 61.3% [95% confidence interval (CI) = 59.2-63.4%]. CCU was inequitably distributed since enabling factors exerted greater effects than predisposing and need variables. Compared with heterosexual men, heterosexual women [adjusted odds ratio (AOR) = 0.78, 95% confidence interval (CI):0.64-0.96)], non-heterosexuals men (AOR = 0.64, 95% CI:0.45-0.92) and women (AOR = 0.68, 95% CI:0.47-0.99) were less prone to using condoms consistently. Those with more resources [i.e., higher levels of self- efficacy for condom use (AOR = 2.86, 95% CI:2.35-3.49) and being knowledgeable of the national AIDS policy (AOR = 1.50, 95% CI:1.23-1.82)], and those with lower need for condoms [i.e., late initiation of sexual activity (AOR = 1.34, 95% CI:1.09-1.64) and single sexual partner (AOR = 1.68,95% CI:1.21-2.33)] were more likely to be consistent condom users. CONCLUSIONS: In order to increase consistency of condom use and simultaneously reduce the remaining inequities, a comprehensive intervention measure should be taken to target heterosexual women, non-heterosexual men and women, and those with higher need for condoms, improve their condom use self- efficacy and raise their awareness of the national AIDS policy.