Inhibition of Hmbox1 Promotes Cardiomyocyte Survival and Glucose Metabolism Through Gck Activation in Ischemia/Reperfusion Injury.

BACKGROUND: Exercise-induced physiological cardiac growth regulators may protect the heart from ischemia/reperfusion (I/R) injury. Homeobox-containing 1 (Hmbox1), a homeobox family member, has been identified as a putative transcriptional repressor and is downregulated in the exercised heart. However, its roles in exercise-induced physiological cardiac growth and its potential protective effects against cardiac I/R injury remain largely unexplored. METHODS: We studied the function of Hmbox1 in exercise-induced physiological cardiac growth in mice after 4 weeks of swimming exercise. Hmbox1 expression was then evaluated in human heart samples from deceased patients with myocardial infarction and in the animal cardiac I/R injury model. Its role in cardiac I/R injury was examined in mice with adeno-associated virus 9 (AAV9) vector-mediated Hmbox1 knockdown and in those with cardiac myocyte-specific Hmbox1 ablation. We performed RNA sequencing, promoter prediction, and binding assays and identified glucokinase (Gck) as a downstream effector of Hmbox1. The effects of Hmbox1 together with Gck were examined in cardiomyocytes to evaluate their cell size, proliferation, apoptosis, mitochondrial respiration, and glycolysis. The function of upstream regulator of Hmbox1, ETS1, was investigated through ETS1 overexpression in cardiac I/R mice in vivo. RESULTS: We demonstrated that Hmbox1 downregulation was required for exercise-induced physiological cardiac growth. Inhibition of Hmbox1 increased cardiomyocyte size in isolated neonatal rat cardiomyocytes and human embryonic stem cell-derived cardiomyocytes but did not affect cardiomyocyte proliferation. Under pathological conditions, Hmbox1 was upregulated in both human and animal postinfarct cardiac tissues. Furthermore, both cardiac myocyte-specific Hmbox1 knockout and AAV9-mediated Hmbox1 knockdown protected against cardiac I/R injury and heart failure. Therapeutic effects were observed when sh-Hmbox1 AAV9 was administered after I/R injury. Inhibition of Hmbox1 activated the Akt/mTOR/P70S6K pathway and transcriptionally upregulated Gck, leading to reduced apoptosis and improved mitochondrial respiration and glycolysis in cardiomyocytes. ETS1 functioned as an upstream negative regulator of Hmbox1 transcription, and its overexpression was protective against cardiac I/R injury. CONCLUSIONS: Our studies unravel a new role for the transcriptional repressor Hmbox1 in exercise-induced physiological cardiac growth. They also highlight the therapeutic potential of targeting Hmbox1 to improve myocardial survival and glucose metabolism after I/R injury.

Optofluidic tunable filters using ionic liquid electrolyte capacitors.

Tunable optical filter is a basic component for most optical systems. This study reports a unique design of Fabry-Pérot (FP) tunable filter by using an ionic liquid solution. The tunable filter consists of two neighboring regions: capacitor region and FP region. The former is in the form of electrolyte capacitor and the latter remains transparent as an FP cavity for light transmission. When the capacitor region is applied with a bias voltage, it attracts the ions from the FP region and thus reduces the ion concentration of the FP region, resulting in a change of the refractive index and eventually a shift of transmission peak of the FP cavity. Among four electrolyte solutions studied, 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM-PF6) exhibits the best overall performance, such as low insertion loss (3.2 dB), large side mode suppression ratio (23 dB) and high stability (drift <0.2 nm). Additionally, a wavelength tuning of 0.17 nm/V is achieved over 0-17 V, providing a tunable range of 3 nm. This device features low bias voltage, no mechanical movement, easy fabrication and seamless integration with microfluidics systems, and may find potential applications in spectral analyzers and lab-on-a-chip biosensing systems.

Evolution of Ozone Formation Sensitivity during a Persistent Regional Ozone Episode in Northeastern China and Its Implication for a Control Strategy.

In recent years, the magnitude and frequency of regional ozone (O3) episodes have increased in China. We combined ground-based measurements, observation-based model (OBM), and the Weather Research and Forecasting and Community Multiscale Air Quality (WRF-CMAQ) model to analyze a typical persistent O3 episode that occurred across 88 cities in northeastern China during June 19-30, 2021. The meteorological conditions, particularly the wind convergence centers, played crucial roles in the evolution of O3 pollution. Daily analysis of the O3 formation sensitivity showed that O3 formation was in the volatile organic compound (VOC)-limited or transitional regime at the onset of the pollution episode in 92% of the cities. Conversely, it tended to be or eventually became a NOx-limited regime as the episode progressed in the most polluted cities. Based on the emission-reduction scenario simulations, mitigation of the regional O3 pollution was found to be most effective through a phased control strategy, namely, reduction of a high ratio of VOCs to NOx at the onset of the pollution and lower ratio during evolution of the O3 episode. This study presents a new possibility for regional O3 pollution abatement in China based on a reasonable combination of OBM and the WRF-CMAQ model.

Double-Edged Role of VOCs Reduction in Nitrate Formation: Insights from Observations during the China International Import Expo 2018.

Aerosol nitrate (NO3-) constitutes a significant component of fine particles in China. Prioritizing the control of volatile organic compounds (VOCs) is a crucial step toward achieving clean air, yet its impact on NO3- pollution remains inadequately understood. Here, we examined the role of VOCs in NO3- formation by combining comprehensive field measurements conducted during the China International Import Expo (CIIE) in Shanghai (from 10 October to 22 November 2018) and multiphase chemical modeling. Despite a decline in primary pollutants during the CIIE, NO3- levels increased compared to pre-CIIE and post-CIIE─NO3- concentrations decreased in the daytime (by -10 and -26%) while increasing in the nighttime (by 8 and 30%). Analysis of the observations and backward trajectory indicates that the diurnal variation in NO3- was mainly attributed to local chemistry rather than meteorological conditions. Decreasing VOCs lowered the daytime NO3- production by reducing the hydroxyl radical level, whereas the greater VOCs reduction at night than that in the daytime increased the nitrate radical level, thereby promoting the nocturnal NO3- production. These results reveal the double-edged role of VOCs in NO3- formation, underscoring the need for transferring large VOC-emitting enterprises from the daytime to the nighttime, which should be considered in formulating corresponding policies.

miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection.

Exercise and its regulated molecules have myocardial protective effects against cardiac ischemia/reperfusion (I/R) injury. The muscle-enriched miR-486 was previously identified to be upregulated in the exercised heart, which prompted us to investigate the functional roles of miR-486 in cardiac I/R injury and to further explore its potential in contributing to exercise-induced protection against I/R injury. Our data showed that miR-486 was significantly downregulated in the heart upon cardiac I/R injury. Both preventive and therapeutic interventions of adeno-associated virus 9 (AAV9)-mediated miR-486 overexpression could reduce cardiac I/R injury. Using AAV9 expressing miR-486 with a cTnT promoter, we further demonstrated that cardiac muscle cell-targeted miR-486 overexpression was also sufficient to protect against cardiac I/R injury. Consistently, miR-486 was downregulated in oxygen-glucose deprivation/reperfusion (OGDR)-stressed cardiomyocytes, while upregulating miR-486 inhibited cardiomyocyte apoptosis through PTEN and FoxO1 inhibition and AKT/mTOR activation. Finally, we observed that miR-486 was necessary for exercise-induced protection against cardiac I/R injury. In conclusion, miR-486 is protective against cardiac I/R injury and myocardial apoptosis through targeting of PTEN and FoxO1 and activation of the AKT/mTOR pathway, and mediates the beneficial effect of exercise for myocardial protection. Increasing miR-486 might be a promising therapeutic strategy for myocardial protection.

Notch Signaling Pathway Promotes Th17 Cell Differentiation and Participates in Thyroid Autoimmune Injury in Experimental Autoimmune Thyroiditis Mice.

Purpose: To investigate whether the Notch signaling pathway participates in the occurrence and development of experimental autoimmune thyroiditis (EAT) by affecting the differentiation and function of Th17 cells. Materials and Methods: Experimental mice were randomly divided into a control group, an EAT-A group (porcine thyroid immunoglobulin- (pTg-) treated mice) and an EAT-B group (treated with the DAPT γ-secretase inhibitor before pTg). HE staining, IHC staining, flow cytometry, RT-qPCR, and ELISA were used to evaluate the degrees of thyroiditis, detect the percentage of Th17 cells and measure the expression of retinoic acid-related orphan receptor gamma t (RORγt), interleukin-17A (IL-17A), and the main components of the Notch signaling pathway. Results: The degrees of thyroiditis, the proportions of Th17 cells, and the expression of RORγt and IL-17A were significantly decreased in the EAT-B group after blocking the Notch signaling pathway by DAPT, and these parameters were significantly increased in the EAT-A group compared to the control group (all P < 0.05). Additionally, the Th17 cell percentages and IL-17A concentrations in spleen mononuclear cells (SMCs) from EAT-A mice decreased in a dose-dependent manner after DAPT treatment in vitro (all P < 0.01). Correlation analyses revealed that the Th17 cell percentages were positively correlated with the serum TgAb titers, Notch pathway-related mRNA expression levels, and IL-17A concentrations in EAT mice (all P < 0.05). Conclusions: The expression of Notch signaling pathway components was upregulated in EAT mice, but blockade of the Notch signaling pathway alleviated the degree of thyroiditis, decreased the Th17 cell proportions, and downregulated the IL-17A effector cytokine both in vivo and in vitro. These findings suggested that the Notch signaling pathway may be involved in the pathogenesis of thyroid autoimmune injury in EAT mice by promoting the differentiation of Th17 cells.

Extracellular Vesicles and Ischemic Cardiovascular Diseases.

Characterized by coronary artery obstruction or stenosis, ischemic cardiovascular diseases as advanced stages of coronary heart diseases commonly lead to left ventricular aneurysm, ventricular septal defect, and mitral insufficiency. Extracellular vesicles (EVs) secreted by diverse cells in the body exert roles in cell-cell interactions and intrinsic cellular regulations. With a lipid double-layer membrane and biological components such as DNA, protein, mRNA, microRNAs (miRNA), and siRNA inside, the EVs function as paracrine signaling for the pathophysiology of ischemic cardiovascular diseases and maintenance of the cardiac homeostasis. Unlike stem cell transplantation with the potential tumorigenicity and immunogenicity, the EV-based therapeutic strategy is proposed to satisfy the demand for cardiac repair and regeneration while the circulating EVs detected by a noninvasive approach can act as precious biomarkers. In this chapter, we extensively summarize the cardioprotective functions of native EVs and bioengineered EVs released from stem cells, cardiomyocytes, cardiac progenitor cells (CPCs), endothelial cells, fibroblast, smooth muscle cells, and immune cells. In addition, the potential of EVs as robust molecule biomarkers is discussed for clinical diagnosis of ischemic cardiovascular disease, attributed to the same pathology of EVs as that of their origin. Finally, we highlight EV-based therapy as a biocompatible alternative to direct cell-based therapy for ischemic cardiovascular diseases.

Integration of social status and trust through interpersonal brain synchronization.

Trust can be a dynamic social process, during which the social identity of the interacting agents (e.g., an investor and a trustee) can bias trust outcomes. Here, we investigated how social status modulates trust and the neural mechanisms underlying this process. An investor and a trustee performed a 10-round repeated trust game while their brain activity was being simultaneously recorded using functional near-infrared spectroscopy. The social status (either high or low) of both investors and trustees was manipulated via a math competition task. The behavioral results showed that in the initial round, individuals invested more in low-status partners. However, the investment ratio increased faster as the number of rounds increased during trust interaction when individuals were paired with a high-status partner. This increasing trend was particularly prominent in the low (investor)-high (trustee) status group. Moreover, the low-high group showed increased investor-trustee brain synchronization in the right temporoparietal junction as the number of rounds increased, while brain activation in the right dorsolateral prefrontal cortex of the investor decreased as the number of rounds increased. Both interpersonal brain synchronization and brain activation predicted investment performance at the early stage; furthermore, two-brain data provided earlier predictions than did single-brain data. These effects were detectable in the investment phase in the low-high group only; no comparable effects were observed in the repayment phase or other groups. Overall, this study demonstrated a multi-brain mechanism for the integration of social status and trust.

Molecular Dipole-Induced Photoredox Catalysis for Hydrogen Evolution over Self-Assembled Naphthalimide Nanoribbons.

D-π-A type 4-((9-phenylcarbazol-3-yl)ethynyl)-N-dodecyl-1,8-naphthalimide (CZNI) with a large dipole moment of 8.49 D and A-π-A type bis[(4,4'-1,8-naphthalimide)-N-dodecyl]ethyne (NINI) with a negligible dipole moment of 0.28 D, were smartly designed and synthesized to demonstrate the evidence of a molecular dipole as the dominant mechanism for controlling charge separation of organic semiconductors. In aqueous solution, these two novel naphthalimides can self-assemble to form nanoribbons (NRs) that present significantly different traces of exciton dissociation dynamics. Upon photoexcitation of NINI-NRs, no charge-separated excitons (CSEs) are formed due to the large exciton binding energy, accordingly there is no hydrogen evolution. On the contrary, in the photoexcited CZNI-NRs, the initial bound Frenkel excitons are dissociated to long-lived CSEs after undergoing ultrafast charge transfer within ca. 1.25 ps and charge separation within less than 5.0 ps. Finally, these free electrons were injected into Pt co-catalysts for reducing protons to H2 at a rate of ca. 417 µmol h-1 g-1 , correspondingly an apparent quantum efficiency of ca. 1.3 % can be achieved at 400 nm.

Electrically generated optical waveguide in a lithium-niobate thin film.

This paper reports an electrically generated optical waveguide for the transverse-magnetic wave. The waveguide is formed in a z-cut single-crystal lithium-niobate (LN) thin film by the electro-optic effect, where the extraordinary refractive index (RI) of the LN film is increased by a voltage applied to patterned electrodes that define the waveguide geometry. Such a waveguide can be made to exist or disappear by turning on or off the applied voltage. A straight waveguide and an S-bend waveguide with an RI contrast of ∼0.004 are generated at a voltage of 200 V. The propagation loss of the generated waveguide measured at the wavelength 532 nm is 1.8 dB/cm. Electrically generated optical waveguides could fulfill useful functions in photonic integrated circuits, such as reconfigurable cross connect and switching that require wavelength-independent and mode-independent operation.

Persistent sulfate formation from London Fog to Chinese haze.

Sulfate aerosols exert profound impacts on human and ecosystem health, weather, and climate, but their formation mechanism remains uncertain. Atmospheric models consistently underpredict sulfate levels under diverse environmental conditions. From atmospheric measurements in two Chinese megacities and complementary laboratory experiments, we show that the aqueous oxidation of SO2 by NO2 is key to efficient sulfate formation but is only feasible under two atmospheric conditions: on fine aerosols with high relative humidity and NH3 neutralization or under cloud conditions. Under polluted environments, this SO2 oxidation process leads to large sulfate production rates and promotes formation of nitrate and organic matter on aqueous particles, exacerbating severe haze development. Effective haze mitigation is achievable by intervening in the sulfate formation process with enforced NH3 and NO2 control measures. In addition to explaining the polluted episodes currently occurring in China and during the 1952 London Fog, this sulfate production mechanism is widespread, and our results suggest a way to tackle this growing problem in China and much of the developing world.

Dielectrophoresis-actuated in-plane optofluidic lens with tunability of focal length from negative to positive.

This paper reports a tunable in-plane optofluidic lens by continuously tuning a silicone oil-air interface from concave to convex using the dielectrophoresis (DEP) force. Two parallel glasses are bonded firmly on two sides by NOA 81(Norland Optical Adhesive 81) spacers, forming an open microfluidic channel. An ITO (indium tin oxide) strip and another unpatterned ITO layer are deposited on two glasses as the top and bottom electrodes. Initially, a capillary concave liquid-air interface is formed at the end of the open channel. Then the DEP force is enabled to continuously deform the interface (lens) from concave to convex. In the experiment, the focal length gradually decreases from about -1 mm to infinite and then from infinite to around + 1 mm when the driving voltage is increased from 0 V to 260 V. Particularly, the longitudinal spherical aberration (LSA) is effectively suppressed to have LSA < 0.04 when the lens is operated in the focusing state. This work is the first study of in-plane tunable lenses using the DEP force and possesses special merits as compared to the other reported tunable lenses that are formed by pumping different liquids or by temperature gradient, such as wide tunability, no need for continuous supply of liquids, low power consumption (~81 nJ per switching) due to the capacitor-type driving, and the use of only one type of liquid. Besides, its low aberration makes it favorable for light manipulation in microfluidic networks.

Noncoding RNAs in Cardiovascular Aging.

With a progressively growing elderly population, aging-associated cardiovascular diseases and other pathologies have brought great burden to the economy, society, and individuals. Therefore, identifying therapeutic targets and developing effective strategies to prevent from cardiovascular aging are highly needed. Accumulating evidences suggest that noncoding RNAs (ncRNAs) such as microRNAs and long noncoding RNAs (lncRNAs) play important roles in regulating gene expression, which contributes to many pathophysiological processes of cellular senescence, aging, and aging-related diseases in cardiovascular systems. Here we provided a general overview of ncRNAs as well as the underlying mechanisms involved in cardiovascular aging. Although the importance of ncRNAs in cardiovascular aging has been reported and commonly acknowledged, further studies are still necessary to elucidate the underlying molecular mechanisms.

Circular RNAs in Vascular Functions and Diseases.

Vascular disease is one of the top five causes of death and affects a variety of other diseases, such as heart, nervous system, and metabolic disorders. Vascular dysfunction is a hallmark of ischemia, cancer, and inflammatory diseases and can accelerate the progression of diseases. Circular RNAs (circRNAs) are a new type of noncoding RNAs with covalent bond ring structure, which have been reported to be abnormally expressed in many human diseases. circRNAs regulate gene expression through the sponging of microRNAs (miRNAs) and can also be used as disease biomarkers. Here we will summarize the functions of circRNAs in vascular diseases, including vascular dysfunction, atherosclerosis, diabetes mellitus-related retinal vascular dysfunction, chronic thromboembolic pulmonary hypertension, carotid atherosclerotic disease, hepatic vascular invasion in hepatocellular carcinoma, aortic aneurysm, coronary artery disease, and type 2 diabetes mellitus.

Comparison of daytime and nighttime new particle growth at the HKUST supersite in Hong Kong.

Particles larger than 50-100 nm in diameter have been considered to be effective cloud condensation nuclei (CCN) under typical atmospheric conditions. We studied the growth of newly formed particles (NPs) in the atmosphere and the conditions for these particles to grow beyond 50 nm at a suburban coastal site in Hong Kong. Altogether, 17 new particle formation events each lasting over 1 h were observed in 17 days during 8 Mar-28 Apr and 1 Nov-30 Dec 2011. In 12 events, single-stage growth of NPs was observed in daytime when the median mobility diameter of NPs (Dp) increased up to ∼40 nm but did not increase further. In three events, two-stage particle growth to 61-97 nm was observed at nighttime. The second stage growth was preceded by a first-stage growth in daytime when the Dp reached 43 ± 4 nm. In all these 15 events, organics and sulfuric acid were major contributors to the first-stage growth in daytime. Ammonium nitrate unlikely contributed to the growth in daytime, but it was correlated with the second-stage growth of ∼40 nm NPs to CCN sizes at nighttime. The remaining two events apparently showed second-stage growth in late afternoon but were confirmed to be due to mixing of NPs with pre-existing particles. We conclude that daytime NP growth cannot reach CCN sizes at our site, but nighttime NP growth driven by organics and NH4NO3 can.

Roles of SO2 oxidation in new particle formation events.

The oxidation of SO2 is commonly regarded as a major driver for new particle formation (NPF) in the atmosphere. In this study, we explored the connection between measured mixing ratio of SO2 and observed long-term (duration>3 hr) and short-term (duration<1.5 hr) NPF events at a semi-urban site in Toronto. Apparent NPF rates (J30) showed a moderate correlation with the concentration of sulfuric acid ([H2SO4]) calculated from the measured mixing ratio of SO2 in long-term NPF events and some short-term NPF events (Category I) (R2=0.66). The exponent in the fitting line of J30~[H2SO4]n in these events was 1.6. It was also found that SO2 mixing ratios varied a lot during long-term NPF events, leading to a significant variation of new particle counts. In the SO2-unexplained short-term NPF events (Category II), analysis showed that new particles were formed aloft and then mixed down to the ground level. Further calculation results showed that sulfuric acid oxidized from SO2 probably made a negligible contribution to the growth of >10 nm new particles.

Statistical analysis and environmental impact of pre-existing particle growth events in a Northern Chinese coastal megacity: A 725-day study in 2010-2018.

Pre-existing particles usually constitute the major fraction of atmospheric particles, except during some episodes in the presence of strong emissions and/or secondary generation of fresh particles. Previous case studies have investigated the growth of pre-existing particles and their potential environmental and climate impacts. However, there is limited knowledge about the statistical characteristics of these growth events and related effects. In this study, we examine pre-existing particle growth events using a large dataset (725 days from 2010 to 2018) collected at a coastal megacity in northern China. The occurrence frequency of pre-existing particle growth events was 12.4 % (90 out of 725 days). When these events were related to measured criteria air pollutants, no significant differences were found in PM2.5, SO2, NO2 and NO2 + O3 concentrations between periods with and without pre-existing particle growth events. These 90-day events can be further classified into two categories, i.e., Category 1, with 68 % of events representing the growth of pre-existing particles alone, and Category 2, with 32 % of events representing the simultaneous growth of pre-existing and newly formed particles. In Category 2, the growth rates of pre-existing particles and newly formed particles were close in 21 % of the cases, while pre-existing particles exhibited significantly larger growth rates in 69 % of the cases. Conversely, in 10 % of the cases, the growth rates of newly formed particles were larger. The different growth rate mechanisms were discussed in terms of the volatility of atmospheric condensation vapors. In addition, we present case studies on the impact of pre-existing particle growth on cloud condensation nuclei simultaneously measured, specifically considering the chemistry of condensation vapors and pre-existing particles.

Pharmacological Activation of AMPK Prevents Drp1-mediated Mitochondrial Fission and Alleviates Hepatic Steatosis In vitro.

BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Adenosine monophosphate-activated protein kinase (AMPK) activation is beneficial for NAFLD treatment. Recent studies show the excessive fission of mitochondria during NAFLD progression, so targeting mitochondria dynamics may be a possible target for NAFLD. Still, little is known about whether AMPK regulates mitochondrial dynamics in hepar. OBJECTIVE: This study investigated whether AMPK activation alleviates hepatic steatosis by regulating mitochondrial dynamics mediated by GTPase dynamin-related protein 1 (Drp1). METHODS: Human hepatocyte line L-02 cells were cultured and subjected to palmitic acid (PA) treatment for 24 h to establish a hepatic steatosis model in vitro, which was pre-treated with different tool drugs. Hepatocyte function, hepatocyte lipid content, mitochondrial reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were examined. The expression levels of genes and proteins associated with mitochondrial dynamics were assessed using reverse transcription-quantitative PCR and western blotting. RESULTS: The results indicated that 5-Aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an AMPK activator, improved hepatocyte function, as demonstrated by decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity (P＜0.05 or P＜0.01). In addition, AICAR decreased total cholesterol (TC) and triglyceride (TG) content and lipid deposition in hepatocytes (P＜0.01); decreased ROS production; improved MMP (P＜0.01); reduced fission-1 (Fis1) and mitochondrial fission factor (Mff) mRNA expression; and downregulated p-Drp1 (Ser 616) protein expression. In contrast, AICAR increased mitochondrial fusion factor mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2) mRNA expression and upregulated p-Drp1 (Ser 637) protein expression. Mdivi-1, a Drp-1 inhibitor, was used to confirm whether mitochondrial dynamics regulated by Drp1-mediated the role of AICAR. Similar to AICAR, Mdivi-1 improved hepatocyte function and MMP significantly, decreased ROS production and lipid deposition, downregulated Fis1 and Mff mRNA expression, downregulated p-Drp1 (Ser 616) protein expression, and enhanced Mfn1 and Mfn2 mRNA and p-Drp1 (Ser 637) protein expression. However, Compound C, an AMPKspecific inhibitor, had less impact on the protective effect of Mdivi-1. CONCLUSION: The results demonstrated that AMPK activation has a protective effect on hepatic steatosis in vitro, largely dependent on the inhibition of Drp1-mediated mitochondrial fission.

Key toxic components and sources affecting oxidative potential of atmospheric particulate matter using interpretable machine learning: Insights from fog episodes.

Fog significantly affects the air quality and human health. To investigate the health effects and mechanisms of atmospheric fine particulate matter (PM2.5) during fog episodes, PM2.5 samples were collected from the coastal suburb of Qingdao during different seasons from 2021 to 2022, with the major chemical composition in PM2.5 analyzed. The oxidative potential (OP) of PM2.5 was determined using the dithiothreitol (DTT) method. A positive matrix factorization model was adopted for PM2.5. Interpretable machine learning (IML) was used to reveal and quantify the key components and sources affecting OP. PM2.5 exhibited higher oxidative toxicity during fog episodes. Water-soluble organic carbon (WSOC), NH4+, K+, and water-soluble Fe positively affected the enhancement of DTTV (volume-based DTT activity) during fog episodes. The IML analysis demonstrated that WSOC and K+ contributed significantly to DTTV, with values of 0.31 ± 0.34 and 0.27 ± 0.22 nmol min-1 m-3, respectively. Regarding the sources, coal combustion and biomass burning contributed significantly to DTTV (0.40 ± 0.38 and 0.39 ± 0.36 nmol min-1 m-3, respectively), indicating the significant influence of combustion-related sources on OP. This study provides new insights into the effects of PM2.5 compositions and sources on OP by applying IML models.

Bio-Inspired Microreactors Continuously Synthesize Glucose Precursor from CO2 with an Energy Conversion Efficiency 3.3 Times of Rice.

Excessive CO2 and food shortage are two grand challenges of human society. Directly converting CO2 into food materials can simultaneously alleviate both, like what green crops do in nature. Nevertheless, natural photosynthesis has a limited energy efficiency due to low activity and specificity of key enzyme D-ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO). To enhance the efficiency, many prior studies focused on engineering the enzymes, but this study chooses to learn from the nature to design more efficient reactors. This work is original in mimicking the stacked structure of thylakoids in chloroplasts to immobilize RuBisCO in a microreactor using the layer-by-layer strategy, obtaining the continuous conversion of CO2 into glucose precursor at 1.9 nmol min-1 with enhanced activity (1.5 times), stability (≈8 times), and reusability (96% after 10 reuses) relative to the free RuBisCO. The microreactors are further scaled out from one to six in parallel and achieve the production at 15.8 nmol min-1 with an energy conversion efficiency of 3.3 times of rice, showing better performance of this artificial synthesis than NPS in terms of energy conversion efficiency. The exploration of the potential of mass production would benefit both food supply and carbon neutralization.