An aerosol layer in the upper troposphere and lower stratosphere over the Asian summer monsoon (ASM) regions, namely, the Asian tropopause aerosol layer (ATAL), has been observed based on satellite ...remote sensing and in situ measurements; however, its source is still under debate. In August 2018, an experimental campaign over the Tibetan Plateau at Golmud (GLM, 36.48 °N, 94.93 °E) was performed, during which a balloon-borne Portable Optical Particle Counter was used to measure the aerosol particle profile. Backward-trajectory simulations were conducted with the Massive-Parallel Trajectory Calculations model to investigate the possible sources and transport pathways of the observed particles. The in situ measurements showed a robust ATAL around the tropopause, 16 km above sea level, with a maximum aerosol number density of 35 cm−3 and a maximum aerosol mass concentration of 0.15 g m−3 for particles with diameters between 0.14 and 3 m. The aerosol particles in the ATAL are mostly smaller than 0.25 m in diameter, accounting for 98% of all aerosol particles detected. The backward-trajectory analysis revealed that the air parcels arrived at the altitude of the ATAL through two separate pathways: (1) the uplift below the 360 K isentropic surface, where air parcels were first elevated to the upper troposphere and then joined the ASM anticyclonic circulation; and (2) the quasi-horizontal transport along the anticyclonic circulation, located approximately between the 360 and 420 K isentropic surfaces. The complex transport pathways may aggravate the challenge of analyzing the composition of the ATAL, and further observation campaigns are required to extend our knowledge.
Approximately 150 Tg of water vapor and 0.42 Tg of sulfur dioxide were injected directly into the stratosphere by the January 2022 Hunga volcanic eruption, which represents the largest water vapor ...injection in the satellite era. A comparison of numerical simulations to balloon‐borne and satellite observations of the water‐rich plume suggests that particle coagulation contributed to the Hunga aerosol's effective dry radius increase from 0.2 μm in February to around 0.4 μm in March. Our model suggests that the stratospheric aerosol effective radius is persistently perturbed for years by moderate and large‐magnitude volcanic events, whereas extreme wildfire events show limited impact on the stratospheric background particle size. Our analysis further suggests that both the particle optical efficiency and the aerosols' stratospheric lifetime explain Hunga's unusually large aerosol optical depth per unit of the SO2 injection, as compared with the Pinatubo eruption.
Plain Language Summary
The Hunga Tonga‐Hunga Ha'apai (HTHH) submarine volcano erupted in January 2022, injecting a modest amount of SO2 but a record amount of water vapor relative to other eruptions into the mid‐stratosphere observed in the satellite era. Our climate model simulations of the stratospheric aerosol suggest that the large water vapor injection caused the new particle formation of many new sulfuric acid solution particles with small radius, enhancing the collision efficiency. Rapid collision led to a peak radius of 0.2 μm by February and 0.4 μm by March of 2022. Our analysis finds that both particle optical properties and aerosol persistence collectively exert an influence on normalized anomaly aerosol optical depth, explaining the high aerosol optical depth per unit emission of SO2 by HTHH, relative to the 1991 Pinatubo eruption.
Key Points
Co‐injected water vapor triggered a sudden and large production of aerosols, followed by a fast particle growth via coagulation
Simulations and observations from La Réunion and Lauder suggest that the stratospheric aerosol size was elevated for 2 years
Both the high optical efficiency and long stratospheric lifetime of HTHH aerosol contribute to a higher AOD per unit emission than Pinatubo
Cadmium (Cd) has well-known central nervous system toxicity, and mitochondria are direct targets of Cd-induced neuronal toxicity. However, how Cd induces mitochondrial mass decrease in terms of its ...neurotoxic effects remains unknown. Puerarin, an isoflavone extracted from kudzu root, can cross the blood–brain barrier and exert protective effects in nervous system disease. The purpose of the study was to determine the mechanism of Cd-induced mitochondrial mass decrease and the protective role of puerarin in rat cortical neurons. The results indicated that Cd induced mitochondrial mass decrease by activating mitophagy mediated by the PTEN-induced putative kinase protein 1 (PINK1)–E3 ubiquitin ligase (Parkin) and Nip3-like protein X (Nix) pathways in rat cortical neurons. Puerarin improved the Cd-induced decrease in mitochondrial membrane potential (MMP) in vitro, and blocked PINK1–Parkin and Nix-mediated mitophagy, inhibiting Cd-induced mitochondrial mass decrease in rat cortical neurons in vitro and in vivo. In summary, our data clearly indicated that puerarin protects rat cortical neurons against Cd-induced neurotoxicity by ameliorating mitochondrial damage, inhibiting mitophagy-mediated mitochondrial mass decrease. Puerarin appears to have great potential as a neuroprotective agent.
•Cadmium exposure induces mitochondrial mass decrease in rat cortical neurons.•Cadmium activates mitophagy mediated by the PINK1–Parkin and Nix pathways.•Puerarin alleviates cadmium-induced mitochondrial mass decrease.•Puerarin blocks cadmium-activated PINK1–Parkin and Nix pathways.
Zearalenone (ZEA), one of the mycotoxins, exerts different mechanisms of toxicity in different cell types at different doses. It can not only stimulate cell proliferation but also inhibit cell ...viability, induce cell apoptosis, and cause cell death. Thus, the objective of this review is to summarize the available mechanisms and current evidence of what is known about the cell proliferation or cell death induced by ZEA. An increasing number of studies have suggested that ZEA promoted cell proliferation attributing to its estrogen-like effects and carcinogenic properties. What's more, many studies have indicated that ZEA caused cell death via affecting the distribution of the cell cycle, stimulating oxidative stress and inducing apoptosis. In addition, several studies have revealed that autophagy and some antioxidants can reverse the damage or cell death induced by ZEA. This review thoroughly summarized the metabolic process of ZEA and the molecular mechanisms of ZEA stimulating cell proliferation and cell death. It concluded that a low dose of ZEA can exert estrogen-like effects and carcinogenic properties, which can stimulate the proliferation of cells. While, in addition, a high dose of ZEA can cause cell death through inducing cell cycle arrest, oxidative stress, DNA damage, mitochondrial damage, and apoptosis.
Abstract
Mitochondrial transfer regulates intercellular communication, and mitochondria regulate cell metabolism and cell survival. However, the role and mechanism of mitochondrial transfer in ...Cd-induced nonalcoholic fatty liver disease (NAFLD) are unclear. The present study shows that mitochondria can be transferred between hepatocytes via microtubule-dependent tunneling nanotubes. After Cd treatment, mitochondria exhibit perinuclear aggregation in hepatocytes and blocked intercellular mitochondrial transfer. The different movement directions of mitochondria depend on their interaction with different motor proteins. The results show that Cd destroys the mitochondria-kinesin interaction, thus inhibiting mitochondrial transfer. Moreover, Cd increases the interaction of P62 with Dynactin1, promotes negative mitochondrial transport, and increases intracellular lipid accumulation. Mitochondria and hepatocyte co-culture significantly reduced Cd damage to hepatocytes and lipid accumulation. Thus, Cd blocks intercellular mitochondrial transfer by disrupting the microtubule system, inhibiting mitochondrial positive transport, and promoting their negative transport, thereby promoting the development of NAFLD.
Graphical Abstract
Cadmium (Cd) has been described as a potential inflammatory inducer, while increasing evidence shows that inappropriate inflammation is a contributing factor to kidney injury. Hence, research on ...Cd-triggered inflammatory response is of great significance for elucidating the mechanism of Cd-induced nephrotoxicity. Bromodomain-containing 4 (BRD4) is an important epigenetic regulator involved in the development of many inflammatory diseases, but its regulatory roles in Cd-triggered inflammatory response remain to be clarified. Here, we found that treatment with Cd in Sprague-Dawley rats (2 mg/kg bw, i.p., 5 consecutive days) and in rat kidney cell line (NRK-52E, 0–10 μM, 12 h) induced the transcription of inflammatory cytokines, which could be reduced by JQ1 (BRD4 inhibitor, 25 mg/kg bw, i.p., 3 consecutive days in vivo; 0.5 μM, 12 h in vitro) or BRD4 small interfering RNA (siRNA, in vitro), suggesting that BRD4 participates in Cd-triggered inflammatory response. Next, our study clarified the roles of BRD4 in Cd-triggered inflammatory response. The inhibition of BRD4 decreased Cd-promoted NF-κB nuclear translocation and activation in vivo and in vitro. Cd increased the acetylation level of RelA K310 and enhanced BRD4 binding to acetylated NF-κB RelA in vivo and in vitro, which were abrogated by inhibiting BRD4. In summary, our study suggests that BRD4 is involved in Cd-triggered transcription of inflammatory cytokines by mediating the activation of NF-κB signaling pathway and increasing itself binding to acetylated NF-κB RelA in rat kidney, therefore, BRD4 could be a potential therapeutic target for Cd-induced renal diseases.
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•Cd induces NF-κB–dependent transcription of pro-inflammatory cytokines in rat kidney.•The epigenetic regulator BRD4 participates in Cd-induced inflammatory response.•Cd ups RelA K310 acetylation levels instead of altering BRD4 expression levels.•Cd boosts BRD4–RelA K310ac binding to activate pro-inflammatory cytokine transcription.
Abstract
Hot extremes, ultraviolet (UV) radiation, and surface ozone all have prominent effects on human health and ecosystems. Here we show evidence that both hot extremes and high surface UV ...radiation at noon time occur concurrently in summer over the Yangtze Plain. Composite analysis suggests that hot extremes in summer are primarily caused by the westward extension of the Western Pacific Subtropical High, which leads to less clouds and consequently more downward solar radiation on the surface over the Yangtze Plain. It is found that surface UV radiation may be dominated by cloud variations, instead of stratospheric ozone during the hot extremes. Further analysis indicates that the hot extremes and high UV radiation, which play important roles in photochemistry in the troposphere, may result in more surface ozone. The concurrent hot extremes, strong UV radiation, and severe ozone pollutions over the Yangtze Plain in summer are likely to have dramatical influences on human health, which should be paid more attention.
The Fas/FasL signaling pathway is one of the primary apoptosis pathways, but the involvement and regulatory mechanism of this pathway by autophagy remain unclear. Here we demonstrated that cadmium ...(Cd) activated the Fas/FasL apoptosis pathway in rat proximal tubular (rPT) cells; this was accompanied by simultaneous activation of autophagy resulted in reduced apoptosis. In this model, we induced autophagy through RAPA and further demonstrated that autophagy protects against activation of Fas/FasL signaling and apoptosis. The antiapoptotic effect of autophagy was blocked by 3-MA, an autophagy inhibitor. The interactions between Beclin-1 and Fas, FasL, FADD, caspase-8 and BID/tBID were relatively weak, with the exception of cleaved caspase-8, indicated that minimal interactions between these proteins and Beclin-1 are involved in maintaining the balance of autophagy and apoptosis. Beclin-1 precipitated with cleaved caspase-8 in a dose-dependent mannter, and the expression was increased by siRNA against Beclin-1. These data suggested that Beclin-1-mediated autophagy impairs the expression and function of cleaved caspase-8 to protect against Cd-induced activation of apopotosis through Fas/FasL signaling pathway.
Autophagic dysfunction is one of the main mechanisms by which the environmental pollutant cadmium (Cd) induces cell injury. Puerarin (Pue, a monomeric Chinese herbal medicine extract) has been ...reported to alleviate Cd-induced cell injury by regulating autophagy pathways; however, its detailed mechanisms are unclear. In the present study, to investigate the detailed mechanisms by which Pue targets autophagy to alleviate Cd hepatotoxicity, alpha mouse liver 12 (AML12) cells were used to construct a model of Cd-induced hepatocyte injury
. First, the protective effect of Pue on Cd-induced cell injury was confirmed by changes in cell proliferation, cell morphology, and cell ultrastructure. Next, we found that Pue activated autophagy and mitigated Cd-induced autophagy blockade. In this process, the lysosome was further activated and the lysosomal degradation capacity was strengthened. We also found that Pue restored the autophagosome-lysosome fusion and the expression of Rab7 in Cd-exposed hepatocytes. However, the fusion of autophagosomes with lysosomes and autophagic flux were inhibited after knocking down
, and were further inhibited after combined treatment with Cd. In addition, after knocking down
, the protective effects of Pue on restoring autophagosome-lysosome fusion and alleviating autophagy blockade in Cd-exposed cells were inhibited. In conclusion, Pue-mediated alleviation of Cd-induced hepatocyte injury was related to the activation of autophagy and the alleviation of autophagy blockade. Pue also restored the fusion of autophagosomes and lysosomes by restoring the protein expression of Rab7, thereby alleviating Cd-induced autophagy blockade in hepatocytes.
The active form of vitamin D, 1α,25-(OH)2D3, not only promotes intestinal calcium absorption, but also regulates the formation of osteoclasts (OCs) and their capacity for bone mineral dissolution. ...Gal-3 is a newly discovered bone metabolic regulator involved in the proliferation, differentiation, and apoptosis of various cells. However, the role of galectin-3 (gal-3) in OC formation and the regulatory effects of 1α,25-(OH)2D3 have yet to be explored. To confirm whether gal-3 contributes to the regulatory effects of 1α,25-(OH)2D3 on osteoclastogenesis, osteoclast precursors (OCPs) were induced by macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). TRAP staining and bone resorption analyses were used to verify the formation and activation of OCs. qPCR, Western blotting, co-immunoprecipitation, and immunofluorescence assays were used to detect gene and protein expression. The regulatory effects of gal-3 in OC formation after treatment with 1α,25-(OH)2D3 were evaluated using gal-3 siRNA. The results showed that 1α,25-(OH)2D3 significantly increased gal-3 expression and inhibited OC formation and bone resorption. Expression levels of OC-related genes and proteins, matrix metalloproteinase 9 (MMP-9), nuclear factor of activated T cells 1 (NFATc1), and cathepsin K (Ctsk) were also inhibited by 1α,25-(OH)2D3. Gal-3 knockdown attenuated the inhibitory effects of 1α,25-(OH)2D3 on OC formation, activation, and gene and protein expression. In addition, gal-3 was co-localized with the vitamin D receptor (VDR). These data suggest that gal-3 contributes to the osteoclastogenesis inhibitory effect of lα,25-(OH)2D3, which is involved in bone and calcium homeostasis.
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