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Abstract Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1‐catalyzed RNA N7‐methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non‐ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac‐specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC‐ or Mettl1‐induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

Ferroptosis is a nonapoptotic form of regulated cell death that has been reported to play a central role in cardiac ischemia‒reperfusion (I/R) injury. N-acetyltransferase 10 (NAT10) contributes to cardiomyocyte apoptosis by functioning as an RNA ac4c acetyltransferase, but its role in cardiomyocyte ferroptosis during I/R injury has not been determined. This study aimed to elucidate the role of NAT10 in cardiac ferroptosis as well as the underlying mechanism. The mRNA and protein levels of NAT10 were increased in mouse hearts after I/R and in cardiomyocytes that were exposed to hypoxia/reoxygenation. P53 acted as an endogenous activator of NAT10 during I/R in a transcription-dependent manner. Cardiac overexpression of NAT10 caused cardiomyocyte ferroptosis to exacerbate I/R injury, while cardiomyocyte-specific knockout of NAT10 or pharmacological inhibition of NAT10 with Remodelin had the opposite effects. The inhibition of cardiomyocyte ferroptosis by Fer-1 exerted superior cardioprotective effects against the NAT10-induced exacerbation of post-I/R cardiac damage than the inhibition of apoptosis by emricasan. Mechanistically, NAT10 induced the ac4C modification of Mybbp1a, increasing its stability, which in turn activated p53 and subsequently repressed the transcription of the anti-ferroptotic gene SLC7A11. Moreover, knockdown of Mybbp1a partially abolished the detrimental effects of NAT10 overexpression on cardiomyocyte ferroptosis and cardiac I/R injury. Collectively, our study revealed that p53 and NAT10 interdependently cooperate to form a positive feedback loop that promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury, suggesting that targeting the NAT10/Mybbp1a/p53 axis may be a novel approach for treating cardiac I/R.

Abstract Heart failure (HF) patients in general have a higher risk of developing cancer. Several animal studies have indicated that cardiac remodeling and HF remarkably accelerate tumor progression, highlighting a cause-and-effect relationship between these two disease entities. Targeting ferroptosis, a prevailing form of non-apoptotic cell death, has been considered a promising therapeutic strategy for human cancers. Exosomes critically contribute to proximal and distant organ-organ communications and play crucial roles in regulating diseases in a paracrine manner. However, whether exosomes control the sensitivity of cancer to ferroptosis via regulating the cardiomyocyte-tumor cell crosstalk in ischemic HF has not yet been explored. Here, we demonstrate that myocardial infarction (MI) decreased the sensitivity of cancer cells to the canonical ferroptosis activator erastin or imidazole ketone erastin in a mouse model of xenograft tumor. Post-MI plasma exosomes potently blunted the sensitivity of tumor cells to ferroptosis inducers both in vitro in mouse Lewis lung carcinoma cell line LLC and osteosarcoma cell line K7M2 and in vivo with xenograft tumorigenesis model. The expression of miR-22-3p in cardiomyocytes and plasma-exosomes was significantly upregulated in the failing hearts of mice with chronic MI and of HF patients as well. Incubation of tumor cells with the exosomes isolated from post-MI mouse plasma or overexpression of miR-22-3p alone abrogated erastin-induced ferroptotic cell death in vitro. Cardiomyocyte-enriched miR-22-3p was packaged in exosomes and transferred into tumor cells. Inhibition of cardiomyocyte-specific miR-22-3p by AAV9 sponge increased the sensitivity of cancer cells to ferroptosis. ACSL4, a pro-ferroptotic gene, was experimentally established as a target of miR-22-3p in tumor cells. Taken together, our findings uncovered for the first time that MI suppresses erastin-induced ferroptosis through releasing miR-22-3p-enriched exosomes derived from cardiomyocytes. Therefore, targeting exosome-mediated cardiomyocyte/tumor pathological communication may offer a novel approach for the ferroptosis-based antitumor therapy.

Chemo-photothermal/photodynamic synergistic therapy is a new effective cancer treatment method to overcome the limitations of single chemotherapy. However, the limited low photothermal conversion efficiency, the hypoxic tumor microenvironment, and premature leakage of the drug constrain their clinical applications. To address these challenges, an all-in-one biodegradable polydopamine-coated UiO-66 framework nanomedicine (DUPM) was developed to co-deliver the drug doxorubicin hydrochloride (DOX) and the excellent photothermal material MoOx nanoparticles (NPs). The results showed that DUPM exhibited good physicochemical stability and efficiently accumulated tumor tissues under pH-, glutathione-, and NIR-triggered drug release behaviour. Of note, the synthesized MoOx NPs endowed DUPM with self-supporting oxygen production and generated more reactive oxygen species (1O2 and·OH), besides, it induces Mo-mediated redox reaction to deplete excessive glutathione thus relieving tumor hypoxia to enhance PDT, further improving synergistic therapy. Meanwhile, DUPM showed strong absorption in the near-infrared range and high photothermal conversion efficiency at 808 nm (51.50%) to realize photoacoustic imaging-guided diagnosis and treatment of cancer. Compared with monotherapy, the in vivo anti-tumor efficacy results showed that DUMP exerted satisfactory tumor growth inhibition effects (94.43%) with good biocompatibility. This study provides a facile strategy to develop intelligent multifunctional nanoparticles with tumor hypoxia relief for improving synergistic therapy and diagnosis against breast cancer.

With the increasing number of electric vehicles (EVs), the disordered charging of a large number of EVs will have a large influence on the power grid. The problems of charging and discharging optimization management for EVs are studied in this paper. The distribution of characteristic quantities of charging behaviour such as the starting time and charging duration are analysed. The results show that charging distribution is in line with a logarithmic normal distribution. An EV charging behaviour model is established, and error calibration is carried out. The result shows that the error is within its permitted scope. The daily EV charge load is obtained by using the Latin hypercube Monte Carlo statistical method. Genetic particle swarm optimization (PSO) is proposed to optimize the proportion of AC 1, AC 2 and DC charging equipment, and the optimal solution can not only meet the needs of users but also reduce equipment investment and the EV peak valley difference, so the effectiveness of the method is verified.

N6-methyladenosine (m6A) methylation in RNA is a dynamic and reversible modification regulated by methyltransferases and demethylases, which has been reported to participate in many pathological processes of various diseases, including cardiac disorders. This study was designed to investigate an m6A writer Mettl14 on cardiac ischemia–reperfusion (I/R) injury and uncover the underlying mechanism. The m6A and Mettl14 protein levels were increased in I/R hearts and neonatal mouse cardiomyocytes upon oxidative stress. Mettl14 knockout (Mettl14+/−) mice showed pronounced increases in cardiac infarct size and LDH release and aggravation in cardiac dysfunction post-I/R. Conversely, adenovirus-mediated overexpression of Mettl14 markedly reduced infarct size and apoptosis and improved cardiac function during I/R injury. Silencing of Mettl14 alone significantly caused a decrease in cell viability and an increase in LDH release and further exacerbated these effects in the presence of H2O2, while overexpression of Mettl14 ameliorated cardiomyocyte injury in vitro. Mettl14 resulted in enhanced levels of Wnt1 m6A modification and Wnt1 protein but not its transcript level. Furthermore, Mettl14 overexpression blocked I/R-induced downregulation of Wnt1 and β-catenin proteins, whereas Mettl14+/− hearts exhibited the opposite results. Knockdown of Wnt1 abrogated Mettl14-mediated upregulation of β-catenin and protection against injury upon H2O2. Our study demonstrates that Mettl14 attenuates cardiac I/R injury by activating Wnt/β-catenin in an m6A-dependent manner, providing a novel therapeutic target for ischemic heart disease.

The contents of potentially toxic elements (V, Cr, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb) and emission characteristics of PM2.5 in soil fugitive dust (SFD) in six Yunnan cities (Baoshan, Kunming, Wenshan, Honghe, Yuxi, and Zhaotong) were investigated in this research. The results showed that the contents of Zn and Pb in PM2.5 of SFD were the highest around Honghe and Yuxi, respectively, while the contents of Mn were the highest in PM2.5 of SFD around the other four cities. The enrichment factor and correlation indicated that the potentially toxic elements’ pollution degrees of PM2.5 of SFD around Kunming, Yuxi, and Honghe were higher than those around the other three cities and that potentially toxic elements were generally affected by metal smelting activities, and in Zhaotong, were affected by coal burning activities, while in Wenshan and Baoshan were less affected by human activities. The total emission of PM2.5 of SFD in the six cities was 7705.49 t in 2018. The total emission factor of PM2.5 of SFD reached the highest level from January to May and the lowest level from July to October. The health risk assessment showed that the potentially toxic elements in PM2.5 of SFD for children in the six cities and for adults in Baoshan, Kunming, Honghe, and Zhaotong had non-carcinogenic risk (non-carcinogenic risk thresholds were greater than 1), and As contributes most to non-carcinogenic risk. The carcinogenic risk value of Cr in PM2.5 of SFD in Kunming and Zhaotong was between 1 × 10−6 and 1 × 10−4, which had a certain carcinogenic risk. More attention should be paid to alleviate health risks posed by particle-bound potentially toxic elements through SFD.

In order to investigate the seasonal variation in chemical characteristics of VOCs in the urban and suburban areas of southwest China, we used SUMMA canister sampling in Jinghong city from October 2016 to June 2017. Forty-eight VOC species concentrations were analyzed using atmospheric preconcentration gas chromatography–mass spectrometry (GC–MS), Then, regional VOC pollution characteristics, ozone formation potentials (OFP), source identity, and health risk assessments were studied. The results showed that the average concentration of total mass was 144.34 μg·m−3 in the urban area and 47.81 μg·m−3 in the suburban area. Alkanes accounted for the highest proportion of VOC groups at 38.11%, followed by olefins (36.60%) and aromatic hydrocarbons (25.28%). Propane and isoprene were the species with the highest mass concentrations in urban and suburban sampling sites. The calculation of OFP showed that the contributions of olefins and aromatic hydrocarbons were higher than those of alkanes. Through the ratio of specific species, the VOCs were mainly affected by motor vehicle exhaust emissions, fuel volatilization, vegetation emissions, and biomass combustion. Combined with the analysis of the backward trajectory model, biomass burning activities in Myanmar influenced the concentration of VOCs in Jinghong. Health risk assessments have shown that the noncarcinogenic risk and hazard index of atmospheric VOCs in Jinghong were low (less than 1). However, the value of the benzene cancer risk to the human body was higher than the safety threshold of 1 × 10−6, showing that benzene has carcinogenic risk. This study provides effective support for local governments formulating air pollution control policies.

The root is in direct contact with soil. Modulation of root growth in response to alterations in soil conditions is pivotal for plant adaptation. Extensive research has been conducted concerning the adjustment of root elongation and architecture in response to environmental factors. However, little is known about the modulation of the root growth trajectory, as well as its hormonal mechanism. Here we report that abscisic acid (ABA) participated in controlling root growth trajectory. The roots upon ABA treatment or from ABA-accumulation double mutant cyp707a1,3 exhibit agravitropism-like growth pattern (wavy growth trajectory). The agravitropism-like phenotype is mainly ascribed to the compromised shootward transportation of auxin since we detected a reduced fluorescence intensity of auxin reporter DR5:VENUS in the root epidermis upon exogenous ABA application or in the endogenous ABA-accumulation double mutant cyp707a1,3. We then tried to decipher the mechanism by which ABA suppressed shootward auxin transport. The membrane abundance of PIN2, a facilitator of shootward auxin transport, was significantly reduced following ABA treatment and in cyp707a1,3. Finally, we revealed that ABA reduced the membrane PIN2 intensity through suppressing the PIN2 expression rather than accelerating PIN2 degradation. Ultimately, our results suggest a pivotal role for ABA in the root growth trajectory and the hormonal interactions orchestrating this process.

This paper studied the chemical characteristics and seasonal changes of PM2.5 in plateau cities on the southwest border of China. Urban air was sampled in Baoshan City during the rainy and dry seasons. Finally, 174 PM2.5 filters were collected (including 87 quartz and 87 Teflon samples for PM2.5). The mass concentrations, water-soluble inorganic ions, organic and inorganic carbon concentrations, and inorganic elements constituting PM2.5 were determined. Positive definite matrix factorization was used to identify potential sources of PM2.5, and the backward trajectory model was used to calculate the contribution of the long-distance transmission of air particles to the Baoshan area. It was found that in the wet season, most of the air masses come from the Indian Ocean and Myanmar. In the dry season, the air mass mainly comes from the China and Myanmar border area. The average concentration of PM2.5 in the wet and dry seasons was 23.17 ± 12.23 μg/m3. The daily mean value of OC/EC indicated that the measured SOC content was generated by the photochemical processes active during the sampling days. However, elements from anthropogenic sources (Na, Mg, Al, Si, P, K, Ca, Ti, Fe, Cu, Zn, Sb, Ba, and Pb) accounted for 99.51% and 99.40% of the total inorganic elements in the wet season and dry season, respectively. Finally, source apportionment showed that SIA, dust, industry, biomass burning, motor vehicle emissions, and copper smelting emissions constituted the major contributions of PM2.5 in Baoshan. Using combined data from three measurement sites provides a focus on the common sources affecting all locations.