Background Accumulating evidence supports that lysine-specific demethylase 5 (KDM5) family members act as oncogenic drivers. This study was performed to elucidate the potential effects of KDM5A on ...prostate cancer (PCa) progression via the miR-495/YTHDF2/m6A-MOB3B axis. Methods The expression of KDM5A, miR-495, YTHDF2 and MOB3B was validated in human PCa tissues and cell lines. Ectopic expression and knockdown experiments were developed in PCa cells to evaluate their effects on PCa cell proliferation, migration, invasion and apoptosis. Mechanistic insights into the interaction among KDM5A, miR-495, YTHDF2 and MOB3B were obtained after dual luciferase reporter, ChIP, and PAR-CLIP assays. Me-RIP assay was used to determine m6A modification level of MOB3B mRNA in PCa cells. Mouse xenograft models of PCa cells were also established to monitor the tumor growth. Results KDM5A was highly expressed in human PCa tissues and cell lines. Upregulated KDM5A stimulated PCa cell proliferation, migration and invasion, but reduced cell apoptosis. Mechanistically, KDM5A, as a H3K4me3 demethylase, bound to the miR-495 promoter, which led to inhibition of its transcription and expression. As a target of miR-495, YTHDF2 could inhibit MOB3B expression by recognizing m6A modification of MOB3B mRNA and inducing mRNA degradation. Furthermore, KDM5A was found to downregulate MOB3B expression, consequently augmenting PCa cell proliferation, migration and invasion in vitro and promoting tumor growth in vivo via the miR-495/YTHDF2 axis. Conclusion In summary, our study highlights the potential of histone demethylase KDM5A activity in enhancing PCa progression, and suggests KDM5A as a promising target for PCa treatment. Keywords: KDM5A, microRNA-145, YTHDF2, MOB3B, m6A modification, Prostate cancer, Migration, Invasion
While ambient formaldehyde (HCHO) concentrations are increasing worldwide, there was limited research on its health effects.
To assess the association of long-term exposure to ambient HCHO with the ...risk of respiratory (RESP) mortality and the associated mortality burden in China.
Annual and seasonal RESP death and tropospheric HCHO vertical columns data were collected in 466 counties/districts across China during 2013–2016. A difference-in-differences approach combined with a generalized linear mixed-effects regression model was employed to assess the exposure-response association between long-term ambient HCHO exposure and RESP mortality risk. Additionally, we computed the attributable fraction (AF) to gauge the proportion of RESP mortality attributable to HCHO exposure.
This analysis encompassed 560,929 RESP deaths. The annual mean ambient HCHO concentration across selected counties/districts was 8.02×1015 ± 2.22×1015 molec.cm−2 during 2013–2016. Each 1.00×1015 molec.cm−2 increase in ambient HCHO was associated with a 1.61 % increase excess risk (ER), 95 % confidence interval (CI): 1.20 %, 2.03 % in the RESP mortality risk. The AF of RESP mortality attributable to HCHO was 12.16 % (95 %CI:9.33 %, 14.88 %), resulting in an annual average of 125,422 (95 %CI:96,404, 153,410) attributable deaths in China. Stratified analyses suggested stronger associations in individuals aged ≥65 years old (ER=1.87 %, 95 %CI:1.43 %, 2.32 %), in cold seasons (ER=1.00 %, 95 %CI:0.56 %, 1.44 %), in urban areas (ER=1.65 %, 95 %CI:1.15 %, 2.16 %), and in chronic obstructive pulmonary disease patients (ER=1.95 %, 95 %CI:1.42 %, 2.48 %).
This study suggested that long-term HCHO exposure may significantly increase the risk of RESP mortality, leading to a substantial mortality burden. Targeted measures should be implemented to control ambient HCHO pollution promptly.
•First study to find the effect of long-term ambient HCHO exposure on respiratory death•The respiratory death burden from ambient HCHO exposure varies widely by region•Measures should be taken to protect the populations vulnerable to HCHO exposure
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•This is a national cohort study focusing on PM2.5 and hyphenation across China.•Long-term exposure to PM2.5 may increase blood pressure and risk of hypertension.•We found different ...effects of PM2.5 components on blood pressure and hypertension.•BC and OM have greater effects on SBP in patients with hypertensive than others.•These effects were modified by sex, urbanicity, smoking status, and cooking fuel type.
Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 μm) and its specific components with hypertension and blood pressure is limited.
We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007–2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively.
Each interquartile range (IQR = 16.80 μg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR μg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42−, NO3−, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure.
These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.
Polymer-derived silicon carbide/silicon nitride (PDC–SiC/Si3N4) composites were prepared by additive manufacturing and infiltration technology. The composite green bodies were prepared using ...selective laser sintering (SLS) three-dimensional (3D) printing technology. Carbon-rich PDC–SiC was generated via precursor infiltration and pyrolysis (PIP) to increase the dielectric constant and enhance the electromagnetic wave (EMW) attenuation ability of the composites. Low-dielectric materials, including Al2O3, TiO2, and AlPO4, were introduced by sol infiltration to improve the impedance-matching characteristics of the composites. The results showed that the EMW absorption ability of the PDC–SiC/Si3N4 composites enhanced after two and four PIP cycles, whereas it degraded with further increasing the PIP cycle number. Among all the samples, the PDC–SiC/Si3N4 composite after four PIP cycles displayed an excellent EMW absorption ability with the minimal reflection loss of −46.79 dB, whereas its effective absorption bandwidth was narrow. Comparing to the sample without infiltration, the effective absorption bandwidth of the samples after the infiltration treatment with TiO2 or Al(H2PO4)3 sol increased from 1.44 GHz to 4.08 GHz and 3.52 GHz, respectively. These results demonstrate that the PIP process and infiltration with TiO2 or Al(H2PO4)3 sol resulted in a 3D-printed PDC–SiC/Si3N4 ceramic that is a promising EMW absorption material suitable for high-temperature environments.
Although studies have estimated the associations of PM2.5 with total mortality or cardiopulmonary mortality, few have comprehensively examined cause-specific mortality risk and burden caused by ...ambient PM2.5. Thus, this study investigated the association of short-term exposure to PM2.5 with cause-specific mortality using a death-spectrum wide association study (DWAS). Individual information of 5,450,764 deaths during 2013–2018 were collected from six provinces in China. Daily PM2.5 concentration in the case and control days were estimated by a random forest model. A time-stratified case-crossover study design was applied to estimate the associations (access risk, ER) of PM2.5 with cause-specific mortality, which was then used to calculate the population-attributable fraction (PAF) of mortality and the corresponding mortality burden caused by PM2.5. Each 10 μg/m3 increase in PM2.5 concentration (lag03) was associated with a 0.80 % 95 % confidence interval (CI): 0.73 %, 0.86 % rise in total mortality. We found greater mortality effect at PM2.5 concentrations < 50 μg/m3. Stratified analyses showed greater ERs in females (1.01 %, 95 %CI: 0.91 %, 1.11 %), children ≤ 5 years (2.17 %, 95 %CI: 0.85 %, 3.51 %), and old people ≥ 70 years. We identified 33 specific causes (level 2) of death which had significant associations with PM2.5, including 16 circulatory diseases, 9 respiratory diseases, and 8 other causes. The PAF estimated based on the overall association between PM2.5 and total mortality was 3.16 % (95 %CI: 2.89 %, 3.40 %). However, the PAF was reduced to 2.88 % (95 %CI: 1.88 %, 3.81 %) using the associations of PM2.5 with 33 level 2 causes of death, based on which 250.15 (95 %CI: 163.29, 330.93) thousand deaths were attributable to short-term PM2.5 exposure across China in 2019. Overall, this study provided a comprehensive picture on the death-spectrum wide association between PM2.5 and morality in China. We observed robust positive cause-specific associations of PM2.5 with mortality risk, which may provide more precise basis in assessing the mortality burden of air pollution.
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•We estimate association of short-term exposure to PM2.5 with cause-specific mortality.•A time-stratified case-crossover study design was used in 5.4 million deaths in China.•Short-term exposure to PM2.5 is associated with mortality from 33 specific causes.•Mortality burden of PM2.5 using associations with total mortality was overestimated.•The results provide more precise basis in assessing mortality burden of air pollution.
Abstract
Rice false smut, caused by
Ustilaginoidea virens
, is one of the most important diseases in rice. The disease not only causes significant yield losses in China and worldwide but also ...produces multiple types of mycotoxins that pose a serious threat to the health of humans and animals. To effectively prevent and control the disease, the pathogenicity mechanisms of
U. virens
have been studied preliminarily, and some control strategies have been developed. This review focuses on recent progress in understanding the molecular mechanisms of
U. virens
pathogenicity, including virulence-related genes, transcriptional regulation of virulence genes, and effector-mediated interactions between rice and
U. virens
. Based on the molecular mechanisms underlying the rice-
U. virens
interactions, the possibilities of the pathogenicity genes in
U. virens
and host immune-related genes as potential targets for biological agents, host-induced gene silencing, and molecular design breeding are also discussed.
The development of stimuli-responsive controlled release formulations is a potential method of improving pesticide utilization efficiency and alleviating current pesticide-related environmental ...pollution. In this study, a self-destruction redox-responsive pesticide delivery system using biodegradable disulfide-bond-bridged mesoporous organosilica (DMON) nanoparticles as the porous carriers and coordination complexes of gallic acid (GA) and Fe(III) ions as the capping agents were established for controlling prochloraz (PRO) release. The GA-Fe(III) complexes deposited onto the surface of DMON nanoparticles could effectively improve the light stability of prochloraz. Due to the decomposition of GA-Fe(III) complexes, the nano-vehicles had excellent redox-responsive performance under the reducing environments generated by the fungus. The spreadability of PRO@DMON-GA-Fe(III) nanoparticles on the rice leaves was increased due to the hydrogen bonds between GA and rice leaves. Compared with prochloraz emulsifiable concentrate, PRO@DMON-GA-Fe(III) nanoparticles showed better fungicidal activity against
with a longer duration under the same concentration of prochloraz. More importantly, DMON-GA-Fe(III) nanocarriers did not observe obvious toxicity to the growth of rice seedlings. Considering non-toxic organic solvents and excellent antifungal activity, redox-responsive pesticide controlled release systems with self-destruction properties have great application prospects in the field of plant disease management.
The first 1000 days of life, encompassing pregnancy and the first 2 years after birth, represent a critical period for human health development. Despite this significance, there has been limited ...research into the associations between mixed exposure to air pollutants during this period and the development of asthma/wheezing in children. Furthermore, the finer sensitivity window of exposure during this crucial developmental phase remains unclear.
This study aims to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (particulate matter 2.5 PM
, carbon monoxide CO, sulfur dioxide SO
, nitrogen dioxide NO
, and ozone O
) and the incidence of childhood asthma/wheezing. In addition, we aimed to pinpoint the potential sensitivity window during which air pollution exerts its effects.
We conducted a prospective birth cohort study wherein pregnant women were recruited during early pregnancy and followed up along with their children. Information regarding maternal and child characteristics was collected through questionnaires during each round of investigation. Diagnosis of asthma/wheezing was obtained from children's medical records. In addition, maternal and child exposures to air pollutants (PM
CO, SO
, NO
, and O
) were evaluated using a spatiotemporal land use regression model. To estimate the mutual associations of exposure to mixed air pollutants with the risk of asthma/wheezing in children, we used the quantile g-computation model.
In our study cohort of 3725 children, 392 (10.52%) were diagnosed with asthma/wheezing. After the follow-up period, the mean age of the children was 3.2 (SD 0.8) years, and a total of 14,982 person-years were successfully followed up for all study participants. We found that each quartile increase in exposure to mixed air pollutants (PM
, CO, SO
, NO
, and O
) during the second trimester of pregnancy was associated with an adjusted hazard ratio (HR) of 1.24 (95% CI 1.04-1.47). Notably, CO made the largest positive contribution (64.28%) to the mutual effect. After categorizing the exposure according to the embryonic respiratory development stages, we observed that each additional quartile of mixed exposure to air pollutants during the pseudoglandular and canalicular stages was associated with HRs of 1.24 (95% CI 1.03-1.51) and 1.23 (95% CI 1.01-1.51), respectively. Moreover, for the first year and first 2 years after birth, each quartile increment of exposure to mixed air pollutants was associated with HRs of 1.65 (95% CI 1.30-2.10) and 2.53 (95% CI 2.16-2.97), respectively. Notably, SO
made the largest positive contribution in both phases, accounting for 50.30% and 74.70% of the association, respectively.
Exposure to elevated levels of mixed air pollutants during the first 1000 days of life appears to elevate the risk of childhood asthma/wheezing. Specifically, the second trimester, especially during the pseudoglandular and canalicular stages, and the initial 2 years after birth emerge as crucial susceptibility windows.
Chinese Clinical Trial Registry ChiCTR-ROC-17013496; https://tinyurl.com/2ctufw8n.
Multimodal antimicrobial technology is regarded as a promising strategy for controlling plant diseases because it enhances antimicrobial efficacy by blocking multiple pesticide-resistance pathways. ...In this work, a pH-responsive multimodal antimicrobial system was constructed based on ZIF-90 for the controlled release of kasugamycin (KSM). A series of physicochemical characterizations confirmed the successful fabrication of ZIF-90-KSM. The results indicated that the loading capacity of ZIF-90-KSM for KSM was approximately 6.7% and that the ZIF-90 nanocarriers could protect KSM against photodegradation effectively. The acid pH at the site of disease not only decompose the Schiff base bonds between KSM and ZIF-90, but also completely dissolved the nanocarriers. The simultaneous release of KSM and Zn2+ ions was able to achieve multimodal antimicrobial functions during disease occurs. A bioactivity survey indicated that ZIF-90-KSM had superior fungicidal activity and longer duration against Magnaporthe oryzae than KSM aqueous solution. In addition, the phytotoxicity assessment of ZIF-90-KSM on rice plants did not reveal any adverse effects. Therefore, ZIF-90-KSM prepared by Schiff base reaction has great potential for achieving synergistic antifungal functions and provides an eco-friendly approach to manage rice diseases.
Although the health impacts of ambient ozone (O3) have been widely assessed, studies simultaneously investigating the acute and chronic effects of O3 on mortality from respiratory diseases (RESP) are ...scarce.
We extracted personal information of all recorded deaths from RESP throughout 2013–2018 in six provinces in China. The daily, seasonal, and annual mean air pollutant concentrations at the township/subdistrict level were estimated by a random forest model. The acute association between the maximum daily average 8h ozone (MDA8 O3) and RESP mortality was examined by a time-stratified case-crossover study design, and the chronic association was estimated by a difference-in-differences (DID) analysis approach. We also calculated the attributable fraction (AF) of RESP mortality attributable to MDA8 O3.
There were 1,034,226 RESP deaths included in this study. The excess risks (ERs) of overall RESP mortality for each 10 μg/m3 increase in short-term (lag03 days) and long-term (one-year average) exposure to MDA8 O3 were 0.38 % (95%CI: 0.26 %, 0.50 %) and 4.37 % (3.91 %, 4.84 %), respectively. The AFs of overall RESP mortality ascribed to short- and long-term MDA8 O3 exposures were 3.00 % (2.03 %, 3.95 %) and 29.45 % (26.86 %, 31.95 %), respectively. The average annual number of RESP deaths attributable to short-term MDA8 O3 exposure was 30,790 and 302,254 were attributable to long-term MDA8 O3 exposure across China during 2013–2018.
Both short- and long-term exposure to ambient MDA8 O3 were positively associated with RESP mortality, and long-term exposure to MDA8 O3 may lead to a greater RESP mortality burden than short-term exposure to MDA8 O3.
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