[Temporal Evolution and Source Appointment of Black Carbon Aerosol in Ordos During Summer and Autumn 2019].

In this study, black carbon (BC) aerosols were continuously observed using a seven-channel aethalometer (AE-33) in Ordos from August 12 to October 4, 2019; using this data combined with article matter (PM), pollutant gas, and meteorological element data; a HYSPLIT model; and potential source contribution function (PSCF) and concentration-weighted trajectory (CWT) models, we analyzed the temporal evolution and potential source appointment and main influence areas of BC. The results showed that the average of ρ(BC) was 882 ng·m-3, accounting for 6.08% of PM2.5. The ρ(BC) was mainly concentrated at 200-1000 ng·m-3, accounting for 55.9% of the total samples. In different BC mass concentration ranges, BCliquid was the mainstay, with an average proportion of 86%. The diurnal variations in BC and PM2.5 showed unimodal distributions, with peaks at 08:00 and 10:00, respectively, and peak concentrations increased by 24.3% and 47.2%, respectively. The diurnal variation in BCsolid showed a bimodal distribution, with peaks at 08:00 and 20:00, respectively. The diurnal variation in the BCliquid showed a unimodal distribution with a peak at 08:00. The strong correlation between BC and NO2 indicated a greater impact of vehicle emissions on BC concentration, whereas the weak correlation between BC and SO2 indicated a lower impact of industrial emissions on BC concentration. The dominant air masses affecting the Ordos could be divided into four categories. The southern air masses (35.6%) had the highest mass concentration of atmospheric pollutants, followed by the local air masses (26.9%) and the northwest air masses (18.8%), and the northeast air masses (18.7%) had the lowest mass concentration of pollutants. The influence of the Ordos on the downstream areas was mainly divided into the northeast air masses (40.9%), the northwest air masses (30.4%), and the southeast air masses (28.7%). High CWT value areas of BC were mainly located in the southern Yan'an-Tongchuan-Baoji-Hanzhong areas and Lvliang-Linfen-Sanmenxia-Nanyang areas. They were two long and narrow transmission belts with a weight mass concentration exceeding 1400 ng·m-3. High CWT value areas of BC had the greatest impact on the Wuhai-Bayannaoer-Baotou-Hohhot regions, with a weight concentration exceeding 900 ng·m-3. The long-range transportation of BC could reach the Yulin-Yan'an-Tongchuan-Baoji areas in the south, the Shuozhou-Datong-Beijing areas in the east, and the Xilin Gol League-Xing'an League-Hulunbuir areas in the northeast.

[Factors Influencing New Atmospheric Particle Formation in Ordos During Summer and Autumn 2019].

In this study, the aerosol number size distribution in the range of 10 nm-10 µm was collected from August 16 to October 04, 2019 at Ordos using a wide-range particle spectrometer (WPS). Combined with PM (PM2.5 and PM10), pollution gases, meteorological data, and the HYSPLIT model, the characteristics and impact factors of new particle formation (NPF) were discussed. The results indicated that there were 19 NPF events during the observation period, which have different effects on diurnal variation in aerosol number concentration in different modes. The NPF events caused a sharp increase in the number concentration of nucleation and Aitken mode aerosols, but had little effect on the number concentration of accumulation and coarse mode aerosols. The temperature, wind speed, and total solar radiation during NPF days were usually higher than those in non-NPF days, and the RH during NPF days was lower. On NPF days, the mass concentrations of PM2.5, PM10, CO, and NO2 were lower than those on non-NPF days, while the mass concentrations of O3 and SO2 were higher. NPF events were observed in 40.0% of northern air masses and 29.6% of southern air masses. There were significant differences in meteorological elements in different NPF event air mass types. The southern NPF event air mass type had the lowest wind speed and the highest RH, with averages of (2.4±1.5) m·s-1 and (48.8±10.8)%, respectively. The northern NPF event air mass type had the highest wind speed and total solar radiation, with averages of (4.2±1.9) m·s-1 and (664.5±255.6) W·m-2, respectively. The western air mass type of NPF event had the lowest RH, with an average of (29.8±12.7)%. The formation rates of new particles in the different air mass types of NPF events were similar, ranging from 1.5 to 1.8 cm-3·s-1. The largest growth rate was (12.7±13.6) nm·h-1 in the southern NPF event air mass type, which was 1.2 times and 1.4 times higher than the NPF events of northern air masses and western air masses.

Squamosamide derivative FLZ protected dopaminergic neuron by activating Akt signaling pathway in 6-OHDA-induced in vivo and in vitro Parkinson's disease models.

Parkinson's disease (PD) is a neurodegenerative disease affecting up to 80% of dopaminergic neurons in the nigrostriatal pathway. FLZ, a novel synthetic squamosamide derivative from a Chinese herb, has been shown to have neuroprotective effects in experimental PD models. In this study, we carried out a set of in vitro and in vivo experiments to address the neuroprotective effect of FLZ and related mechanism. The results showed that FLZ significantly improved motor dysfunction and dopaminergic neuronal loss of rats injured by 6-hydroxydopamine (6-OHDA). The beneficial effects of FLZ attributed to the elevation of dopaminergic neuron number, dopamine level and tyrosine hydroxylase (TH) activity. Mechanistic study showed that FLZ protected TH activity and dopaminergic neurons through decreasing α-synuclein (α-Syn) expression and the interaction between α-Syn and TH. Further studies indicated the involvement of phosphoinositide 3-kinases (PI3K)/Akt signaling pathway in the protective effect of FLZ since it showed that blocking PI3K/Akt signaling pathway prevented the expression of α-Syn and attenuated the neuroprotection of FLZ. In addition, FLZ treatment reduced the expression of RTP801, an important protein involved in the pathogenesis of PD. Taken together, these results revealed that FLZ suppressed α-Syn expression and elevated TH activity in dopaminergic neuron through activating Akt survival pathway in 6-OHDA-induced PD models. The data also provided evidence that FLZ had potent neuroprotecive effects and might become a new promising agent for PD treatment.

FLZ alleviates the memory deficits in transgenic mouse model of Alzheimer's disease via decreasing beta-amyloid production and tau hyperphosphorylation.

Alzheimer's disease (AD) is the most common cause of dementia worldwide and mainly characterized by the aggregated ß-amyloid (Aß) and hyperphosphorylated tau. FLZ is a novel synthetic derivative of natural squamosamide and has been proved to improve memory deficits in dementia animal models. In this study, we aimed to investigate the mechanisms of FLZ's neuroprotective effect in APP/PS1 double transgenic mice and SH-SY5Y (APPwt/swe) cells. The results showed that treatment with FLZ significantly improved the memory deficits of APP/PS1 transgenic mice and decreased apoptosis of SH-SY5Y (APPwt/swe) cells. FLZ markedly attenuated Aß accumulation and tau phosphorylation both in vivo and in vitro. Mechanistic study showed that FLZ interfered APP processing, i.e., FLZ decreased ß-amyloid precursor protein (APP) phosphorylation, APP-carboxy-terminal fragment (APP-CTF) production and ß-amyloid precursor protein cleaving enzyme 1 (BACE1) expression. These results indicated that FLZ reduced Aß production through inhibiting amyloidogenic pathway. The mechanistic study about FLZ's inhibitory effect on tau phosphorylation revealed t the involvement of Akt/glycogen synthase kinase 3ß (GSK3ß) pathway. FLZ treatment increased Akt activity and inhibited GSK3ß activity both in vivo and in vitro. The inhibitory effect of FLZ on GSK3ß activity and tau phosphorylation was suppressed by inhibiting Akt activity, indicating that Akt/GSK3ß pathway might be the possible mechanism involved in the inhibitory effect of FLZ on tau hyperphosphorylation. These results suggested FLZ might be a potential anti-AD drug as it not only reduced Aß production via inhibition amyloidogenic APP processing pathway, but also attenuated tau hyperphosphoylation mediated by Akt/GSK3ß.

FLZ, a novel HSP27 and HSP70 inducer, protects SH-SY5Y cells from apoptosis caused by MPP(+).

Heat shock proteins (HSPs) play an essential role in various neurodegenerative diseases. Manipulation of upregulation of HSPs in cells has been demonstrated to provide a therapeutic strategy to counteract the misfolding and aggregation of proteins that resulted in neurodegenerative disease. Our previous studies have shown that FLZ, a synthetic novel derivative of squamosamide from a Chinese herb, had potent neuroprotective effect against several experimental Parkinson's disease (PD) models. However, the mechanism of its neuroprotective effect is still not clarified. The present study demonstrated that FLZ induced HSP27 and HSP70 proteins and mRNA expression in a time- and dose-dependent manner in SH-SY5Y cells. Further studies showed that FLZ treatment stimulated the activation of heat shock factor 1 (HSF1) and its regulatory kinase Akt. Inactivation of Akt pathway by the PI3K inhibitor LY294002 blocked the expression of HSP27 and HSP70 induced by FLZ. Moreover, the inducing effects of FLZ on HSP27, HSP70, and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/HSP70 induced by FLZ against MPP(+) was assessed in SH-SY5Y cells. The pretreatment of FLZ significantly induced the accumulations of HSP27/HSP70 and suppressed the apoptosis caused by MPP(+) in SH-SY5Y cells. However, the protective effects of FLZ against MPP(+) were significantly blocked by quercetin, which indicated that the cytoprotective action of FLZ against MPP(+)-induced apoptosis is at least partially mediated by its induction of HSP27/HSP70. These results provide new evidence for elucidating the mechanism of the neuroprotective effect of FLZ against PD.

[Neurodegenerative conformational disease and heat shock proteins].

Many major neurodegenerative diseases are associated with proteins misfolding and aggregation, which are also called "neurodegenerative conformational disease". The interaction of gene mutation and environmental factors are probably primary events resulting in oligomer and aggregate formations of proteins. Moreover, the dysfunctions of protein control systems, i.e. the ubiquitin-proteasome system and autophagy-lysosomal system, also contribute to the neurodegenerative process. The present review mainly summarizes protein misfolding and aggregation in the development of neurodegenerative conformational disease and the underling mechanisms, as well as upregulation of heatshock proteins as a promising treatment method for this kind of disease.