dp53 Restrains Ectopic Neural Stem Cell Formation in the Drosophila Brain in a Non-Apoptotic Mechanism Involving Archipelago and Cyclin E

Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs) possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs) called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53) was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E). Overexpression of Cyc E was able to abrogate dp53′s ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago), a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has important clinical implications

Particulate matter deposited on leaf of five evergreen species in Beijing, China:source identification and size distribution

Airborne particulate matter (PM) has become a serious problem, and urban plants can play important roles in reducing PM concentrations in the air. The morphology, size, and elemental composition of PM on tree leaves (five evergreen species) from Beijing, China, were obtained, together with number density of PM size fraction, by using scanning electron microscopy (SEM) and energy dispersive X-rays (EDX). The rinse and weigh method was used to characterize PM in three size categories (0.2–2.5 μm, 2.5–10 μm, and 10–100 μm). The results showed that PM up to 2 μm can get into the stomatal cavity, and the most furrowed areas of the leaf surfaces were sites of maximum PM deposition. The leaf-deposited PM mainly comprised C, O, Si, and Fe. The number of particles per leaf per cm2 was 1.95 × 107, and 96% of the particles were less than 2.5 μm. The mass concentration was 148.44 μg/cm2, and PM2.5 comprised only 2.09% by weight while PM larger than 10 μm comprised 79%. Juniperus formosana was most effective at mitigating airborne PM on the leaf scale. Pinus bungeana accumulated the most PM on the tree scale. The results showed that urban plants can play important roles in mitigating urban airborne PM

The spatial-temporal characteristics and health impacts of ambient fine particulate matter in China

Airborne particulate matter presents a serious health threat to human beings, but in China there have until now been few epidemiological studies, especially regarding the impact of ambient fine particulate matter (PM2.5). This study explored first the temporal and spatial characteristics of ambient airborne PM2.5 in China, 2013. Mortality, respiratory diseases, cardiovascular diseases, and chronic bronchitis were then evaluated as four health endpoints attributed to PM2.5. The results showed that the average annual PM2.5 concentration was 72.71 μg/m3; the PM2.5 concentration was below 35 μg/m3 for only 6% of the time, for the whole year. In terms of the PM2.5 concentration, January (133.10 μg/m3) and December (120.19 μg/m3) were the most polluted months, whereas July (38.76 μg/m3) and August (41.31 μg/m3) were the least polluted months. The most highly polluted areas were concentrated in North China. In terms of the health endpoints attributable to PM2.5, there were 763,595 mortality, 149,754 cardiovascular diseases, 446,035 respiratory diseases, and 2,389,035 chronic bronchitis cases. Results were very important to clarify the current PM2.5 pollution situation and the health impact of PM2.5 in China. And also provided a reference for the assessing damage caused by PM2.5 pollution

Reprint of:The spatial-temporal characteristics and health impacts of ambient fine particulate matter in China

Airborne particulate matter presents a serious health threat to human beings, but in China there have until now been few epidemiological studies, especially regarding the impact of ambient fine particulate matter (PM2.5). This study explored first the temporal and spatial characteristics of ambient airborne PM2.5 in China, 2013. Mortality, respiratory diseases, cardiovascular diseases, and chronic bronchitis were then evaluated as four health endpoints attributed to PM2.5. The results showed that the average annual PM2.5 concentration was 72.71 μg/m3; the PM2.5 concentration was below 35 μg/m3 for only 6% of the time, for the whole year. In terms of the PM2.5 concentration, January (133.10 μg/m3) and December (120.19 μg/m3) were the most polluted months, whereas July (38.76 μg/m3) and August (41.31 μg/m3) were the least polluted months. The most highly polluted areas were concentrated in North China. In terms of the health endpoints attributable to PM2.5, there were 763,595 mortality, 149,754 cardiovascular diseases, 446,035 respiratory diseases, and 2,389,035 chronic bronchitis cases. Results were very important to clarify the current PM2.5 pollution situation and the health impact of PM2.5 in China. And also provided a reference for the assessing damage caused by PM2.5 pollution

1-O-Acetylgeopyxin A, a derivative of a fungal metabolite, blocks tetrodotoxin-sensitive voltage-gated sodium, calcium channels and neuronal excitability which correlates with inhibition of neuropathic pain

Chronic pain can be the result of an underlying disease or condition, medical treatment, inflammation, or injury. The number of persons experiencing this type of pain is substantial, affecting upwards of 50 million adults in the United States. Pharmacotherapy of most of the severe chronic pain patients includes drugs such as gabapentinoids, re-uptake blockers and opioids. Unfortunately, gabapentinoids are not effective in up to two-thirds of this population and although opioids can be initially effective, their long-term use is associated with multiple side effects. Therefore, there is a great need to develop novel non-opioid alternative therapies to relieve chronic pain. For this purpose, we screened a small library of natural products and their derivatives in the search for pharmacological inhibitors of voltage-gated calcium and sodium channels, which are outstanding molecular targets due to their important roles in nociceptive pathways. We discovered that the acetylated derivative of the ent-kaurane diterpenoid, geopyxin A, 1-O-acetylgeopyxin A, blocks voltage-gated calcium and tetrodotoxin-sensitive voltage-gated sodium channels but not tetrodotoxin-resistant sodium channels in dorsal root ganglion (DRG) neurons. Consistent with inhibition of voltage-gated sodium and calcium channels, 1-O-acetylgeopyxin A reduced reduce action potential firing frequency and increased firing threshold (rheobase) in DRG neurons. Finally, we identified the potential of 1-O-acetylgeopyxin A to reverse mechanical allodynia in a preclinical rat model of HIV-induced sensory neuropathy. Dual targeting of both sodium and calcium channels may permit block of nociceptor excitability and of release of pro-nociceptive transmitters. Future studies will harness the core structure of geopyxins for the generation of antinociceptive drugs.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

N<i>x</i>C‑Induced Switching of Methane and Ethylene Products’ Selectivity from CO₂ Electroreduction over Cu Catalyst

Regulating the electronic properties or morphology feature of CO2 electroreduction catalysts can maintain selectivity toward certain reduction products. Here we report a nitrogen doped carbon (NxC) modification strategy that can switch CH4 and CH2CH2 product selectivity during CO2 electrolysis over the Cu catalyst. The fabricated core–shell Cu@NxC catalyst exhibited good performance in suppressing HER and promoting CO2RR. About 90% FEs was achieved over the Cu@NxC-350 °C (10:4) catalyst, of which the CH2CH2 FEs was 54% at −1.4 V vs RHE. However, the C1 product was the majority over the Cu@NxC-400 °C (10:4) catalyst, and 63% FEs of CH4 was achieved at the same applied potential. The in-depth characterization revealed that the remarkable selectivity switching of CH4 and CH2CH2 products originated from the NxC shell, rather than the change in the electronic feature of the Cu core. The more pyrrolic N contained in the Cu@NxC catalyst tended to form bridge-bonded *CO, leading to a dominant CH4 product, while the more pyridinic N contained in the Cu@NxC catalyst tended to form linearly bonded *CO, which was favorable for C–C coupling to form the CH2CH2 product. Our results provided insights into the role of the chemical environment on CO2 electroreduction processes

Boosting Photocatalytic Hydrogen Evolution Activity by Accelerating Water Dissociation over Rh/Zn(OH)₂ Catalyst in Alkaline Solution

In the present work, we report that a Rh/Zn(OH)2 catalyst, prepared by an in situ photodeposition strategy, can enhance water dissociation kinetics to boost the photocatalytic hydrogen evolution reaction (HER) in the mild alkaline environment. In comparison to a Rh NP catalyst, the Rh/Zn(OH)2 catalyst exhibited a 3-fold increase in the rate of H2 evolution. In-depth characterization manifests that the impressive photocatalytic performance was ascribed to multiple factors. First, the strong interaction between Rh nanoparticles (NPs) and Zn(OH)2, coupled with the 3D network structure of amorphous Zn(OH)2 for Eosin Y (EY) molecule adsorption, ensured the rapid transfer of photogenerated carrier pairs. Second, the kinetics of water dissociation over the Rh/Zn(OH)2 catalyst was accelerated in the mild alkaline solution. As a result, the Rh/Zn(OH)2 catalyst achieved a high HER rate of 60.9 mmol·g–1·h–1, and the apparent quantum efficiency (AQE) reached 79.5% at 430 nm. Overall, our work will expand the candidate materials to design high-performance catalysts for photocatalytic H2 evolution in alkaline solutions