Construction of V2O5@MXene Cathodes toward a High Specific Capacity Aqueous Aluminum-Ion Battery.

Aqueous aluminum-ion batteries (AAIBs) are considered a strong candidate for the new generation of energy storage devices. The lack of suitable cathode materials has been a bottleneck factor hindering the future development of AAIBs. In this work, we design and construct a highly effective cathode with dual morphologies. Two-dimensional (2D) layered MXene materials possessed good conductivity and hydrophilicity, which are used as the substrates to deposit rod-shaped vanadium oxides (V2O5) to form a three-dimensional (3D) cathode. The cathode design provides a strong boost for the rapid electrochemical activities of rod-shaped V2O5 by embedding/extracting both protons (H+) and aluminum-ion (Al3+). As a result, the V2O5@MXene cathode based AAIB delivers an ultrahigh initial specific capacity of 626 mAh/g at 0.1 A/g with a stable cycle performance up to 100 cycles. This work is a breakthrough for the development of cathode materials for AAIBs.

Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.

Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites. Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N3) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency. The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.

Age effects on prosodic boundary perception.

The redundancy hypothesis proposes that older listeners need a larger array of acoustic cues than younger listeners for effective speech perception. This research investigated this hypothesis by examining the aging effects on the use of prosodic cues in speech segmentation in Mandarin Chinese. We examined how younger and older listeners perceived prosodic boundaries using three main prosodic cues (pause, final lengthening, and pitch change) across eight conditions involving different cue combinations. The stimuli consisted of syntactically ambiguous phrase pairs, each containing two or three objects. Participants (22 younger listeners and 22 older listeners) performed a speech recognition task to judge the number of objects they heard. Both groups primarily relied on the pause cue for identifying prosodic boundaries, using final lengthening and pitch change as secondary cues. However, older listeners showed reduced sensitivity to these cues, compensating by integrating the primary cue pause with the secondary cue pitch change for more precise segmentation. The present study reveals older listeners' integration strategy in using prosodic cues for speech segmentation, supporting the redundancy hypothesis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Aging affects auditory contributions to focus perception in Jianghuai Mandarina).

Speakers can place their prosodic prominence on any locations within a sentence, generating focus prosody for listeners to perceive new information. This study aimed to investigate age-related changes in the bottom-up processing of focus perception in Jianghuai Mandarin by clarifying the perceptual cues and the auditory processing abilities involved in the identification of focus locations. Young, middle-aged, and older speakers of Jianghuai Mandarin completed a focus identification task and an auditory perception task. The results showed that increasing age led to a decrease in listeners' accuracy rate in identifying focus locations, with all participants performing the worst when dynamic pitch cues were inaccessible. Auditory processing abilities did not predict focus perception performance in young and middle-aged listeners but accounted significantly for the variance in older adults' performance. These findings suggest that age-related deteriorations in focus perception can be largely attributed to declined auditory processing of perceptual cues. Poor ability to extract frequency modulation cues may be the most important underlying psychoacoustic factor for older adults' difficulties in perceiving focus prosody in Jianghuai Mandarin. The results contribute to our understanding of the bottom-up mechanisms involved in linguistic prosody processing in aging adults, particularly in tonal languages.

α-MnO2 Cathode with Oxygen Vacancies Accelerated Affinity Electrolyte for Dual-Ion Co-Encapsulated Aqueous Aluminum Ion Batteries.

Aluminum batteries (ABs) are identified as one of the most promising candidates for the next generation of large-scale energy storage elements because of their efficient three-electron reaction. Compared to ionic electrolytes, aqueous aluminum-ion batteries (AAIBs) are considered safer, less costly, and more environmentally friendly. However, considerable cycling performance is a key issue limiting the development of AAIBs. Stable, efficient, and electrolyte-friendly cathodes are most desirable for AAIBs. Herein, a rod-shaped defect-rich α-MnO2 is designed as a cathode, which is capable to deliver high performance with stable cycling for 180 cycles at 500 mA g-1 and maintains a discharge specific capacity of ≈100 mAh g-1. In addition, the infiltrability simulation is effectively utilized to corroborate the rapid electrochemical reaction brought about by the defective mechanism. With the formation of oxygen vacancies, the dual embedding of protons and metal ions is activated. This work provides a brand-new design for the development and characterization of cathodes for AAIBs.

Analysis of the impact of temperature on the spectral shift in ultraviolet hyperspectral imaging spectrometers.

The imaging spectrometer's high performance in practical applications may be compromised by environmental factors, particularly temperature variations, posing a challenge to its stability. Temperature fluctuations can induce spectral shift, directly impacting the accuracy of spectral measurements, subsequently influencing the precision of radiometric measurements. To address this issue, this study investigates a dual-channel UV imaging spectrometer. This instrument boasts a wavelength calibration accuracy of 0.01 nm. This paper conducts an in-depth analysis of the various mechanisms through which temperature changes influence the spectral line offset in the imaging spectrometer, integrating actual orbital temperature data to discuss the instrument's temperature load settings. The impact of temperature on spectral shift is examined using finite element analysis and optical design software. Estimations of spectral shift were made based on temperature variations. Simulation results indicated that the maximum deviation of spectral shift is estimated at 0.018 nm under a temperature condition of 16 ± 1°C. Under a more controlled orbital temperature condition (16 ± 0.3°C), the maximum deviation of spectral shift decreased to 0.01 nm. Experimental data revealed that at 16 ± 1°C, the maximum deviation of spectral shift did not exceed 0.01 nm. This effectively corroborates our theoretical analysis. The relationship between temperature and spectral shift offers a crucial theoretical foundation for calibrating spectral measurements and managing the thermal conditions of the instrument.

Functional analysis of a wheat class III peroxidase gene, TaPer12-3A, in seed dormancy and germination.

BACKGROUND: Class III peroxidases (PODs) perform crucial functions in various developmental processes and responses to biotic and abiotic stresses. However, their roles in wheat seed dormancy (SD) and germination remain elusive. RESULTS: Here, we identified a wheat class III POD gene, named TaPer12-3A, based on transcriptome data and expression analysis. TaPer12-3A showed decreasing and increasing expression trends with SD acquisition and release, respectively. It was highly expressed in wheat seeds and localized in the endoplasmic reticulum and cytoplasm. Germination tests were performed using the transgenic Arabidopsis and rice lines as well as wheat mutant mutagenized with ethyl methane sulfonate (EMS) in Jing 411 (J411) background. These results indicated that TaPer12-3A negatively regulated SD and positively mediated germination. Further studies showed that TaPer12-3A maintained H2O2 homeostasis by scavenging excess H2O2 and participated in the biosynthesis and catabolism pathways of gibberellic acid and abscisic acid to regulate SD and germination. CONCLUSION: These findings not only provide new insights for future functional analysis of TaPer12-3A in regulating wheat SD and germination but also provide a target gene for breeding wheat varieties with high pre-harvest sprouting resistance by gene editing technology.

Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Natural killer (NK) cell-based adoptive immunotherapy has demonstrated encouraging therapeutic effects in clinical trials for hematological cancers. However, the effectiveness of treatment for solid tumors remains a challenge due to insufficient recruitment and infiltration of NK cells into tumor tissues. Herein, a programmed nanoremodeler (DAS@P/H/pp) is designed to remodel dense physical stromal barriers and for dysregulation of the chemokine of the tumor environment to enhance the recruitment and infiltration of NK cells in tumors. The DAS@P/H/pp is triggered by the acidic tumor environment, resulting in charge reversal and subsequent hyaluronidase (HAase) release. HAase effectively degrades the extracellular matrix, promoting the delivery of immunoregulatory molecules and chemotherapy drugs into deep tumor tissues. In mouse models of pancreatic cancer, this nanomediated strategy for the programmed remodeling of the tumor microenvironment significantly boosts the recruitment of NK92 cells and their tumor cell-killing capabilities under the supervision of multiplexed near-infrared-II fluorescence.

Danhong formula alleviates endothelial dysfunction and reduces blood pressure in hypertension by regulating MicroRNA 24 - Phosphatidylinositol 3-Kinase-Serine/Threonine Kinase- Endothelial Nitric Oxide Synthase axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Essential hypertension (EH) is one of the important risk factors of cardio-cerebrovascular diseases, and it can significantly increase the incidence and mortality of acute myocardial infarction, cerebral infarction and hemorrhage. Danhong Formula (DHF) was consisting of Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese) (Plant names have been checked with http://www.the plant list.org on June 28th, 2023) was approved by State Food and Drug Administration of China, that has been used for thousands of years in the treatment of cardiovascular diseases in China with proven safety and efficacy. Though our previous studies have found that DHF improved endothelial dysfunction (ED) and decreased high blood pressure (BP), the underlying mechanisms of its antihypertensive effect still remain unclear. AIM OF THE STUDY: This study investigated whether DHF regulated MicroRNA 24- Phosphatidylinositol 3-Kinase-Serine/Threonine Kinase- Endothelial Nitric Oxide Synthase (miR-24 - PI3K/AKT/eNOS) axis to produce antihypertensive effect and improve endothelial dysfunction. MATERIALS AND METHODS: Firstly, the chemical components of DHF were analyzed by UHPLC-MS. After that, BP was continuously monitored within the 1st, 3rd, and 4th week in SHR to evaluate the antihypertensive effect of DHF intraperitoneal injection. In addition, not only the contents of serum nitric oxide (NO), prostacyclin (PGI2), and angiotensin II (Ang II) were detected, but also the isolated aorta ring experiment was conducted to evaluate the vasomotoricity to evaluate of DHF on improving endothelial dysfunction. Key proteins or mRNA expression associated with miR-24 - PI3K/AKT/eNOS axis in aorta were detected by capillary Western blot, immunohistochemistry or RT-PCR to explore the underlying mechanisms. Index of NO, Ang II PGI2 and key proteins or mRNA expression were also conducted in miR-24-3p over-expression HUVECs model. RESULTS: Compared with SHR control group, DHF (4 mL/kg/day, 2 mL/kg/day, 1 mL/kg/day) treatment significantly reduced high BP in SHR and selectively increased acetylcholine (Ach) induced vasodilation, but not sodium nitroprusside (SNP) in a manner of concentration dependency in isolated aorta ring. DHF (4 mL/kg/day, 1 mL/kg/day) treatment was accompanying an increment of NO and PGI2, and lowering AngII in SHR. Moreover, DHF treatment significantly up-regulated expression of p-PI3K, p-AKT, mTOR, eNOS and p-eNOS, but down-regulated miR-24-3p expression in aorta. Compared with miR-24-3p over-expression HUVECs model group, DHF treatment inhibited miR- 24-3p expression and up-regulated p-PI3K, p-AKT, mTOR and eNOS mRNA expression. Similarly, DHF treatment increased PI3K, AKT, mTOR and eNOS protein expression in HUVECs by Western blot. CONCLUSIONS: These findings suggest that DHF alleviates endothelial dysfunction and reduces high BP in SHR mediated by down-regulating miR-24 via ultimately facilitating up-regulation of PI3K/AKT/eNOS axis. This current study firstly demonstrates a potential direction for antihypertensive mechanism of DHF from microRNA aspect and will promote its clinical applications.

Suppression of endoplasmic reticulum stress by 4-PBA enhanced atherosclerotic plaque stability via up-regulating CLOCK expression.

Endoplasmic reticulum (ER) stress refers to a condition where the normal functioning of the ER is disrupted due to a variety of cellular stress factors. As a result, there is an accumulation of unfolded and misfolded proteins within the ER. Numerous studies have shown that ER stress can exacerbate inflammatory reactions and contribute to the development of various inflammatory diseases. However, the role of ER stress in the stability of atherosclerotic plaques remains poorly understood. In this study, we aimed to explore the potential impact of a specific ER stress inhibitor known as 4-phenyl butyric acid (4-PBA) on atherosclerosis in mice. The mice were fed a high-fat diet, and treatment with 4-PBA significantly improved the stability of the atherosclerotic plaques. This was evidenced by a reduction in oxidative stress and an increase in circadian locomotor output cycles kaput (CLOCK) protein and mRNA expression within the plaques. Additionally, 4-PBA reduced the expression of ER stress-related proteins and decreased apoptosis in the atherosclerotic plaques. In vitro investigation, we observed the effect of 4-PBA on vascular smooth muscle cells (VSMCs) that were exposed to oxidized low-density lipoprotein (ox-LDL), a significant contributor to the development of atherosclerosis. 4-PBA reduced reactive oxygen species (ROS) production and attenuated apoptosis, GRP78 and CHOP protein expression in ox-LDL-Induced VSMCs via up-regulating CLOCK expression. However, when the short hairpin RNA against CLOCK (sh-CLOCK) was introduced to the VSMCs, the protective effect of 4-PBA was abolished. This suggests that the up-regulation of CLOCK expression is crucial for the beneficial effects of 4-PBA on atherosclerotic plaque stability. This finding suggests that targeting ER stress and modulating CLOCK protein levels might be a promising way to enhance the stability of atherosclerotic plaques.

Oxygen Vacancies Boosted Proton Intercalation Kinetics for Aqueous Aluminum-Manganese Batteries.

Aluminum-ion batteries have garnered an extensive amount of attention due to their superior electrochemical performance, low cost, and high safety. To address the limitation of battery performance, exploring new cathode materials and understanding the reaction mechanism for these batteries are of great significance. Among numerous candidates, multiple structures and valence states make manganese-based oxides the best choice for aqueous aluminum-ion batteries (AAIBs). In this work, a new cathode consists of γ-MnO2 with abundant oxygen vacancies. As a result, the electrode shows a high discharge capacity of 481.9 mAh g-1 at 0.2 A g-1 and a sustained reversible capacity of 128.6 mAh g-1 after 200 cycles at 0.4 A g-1. In particular, through density functional theory calculation and experimental comparison, the role of oxygen vacancies in accelerating the reaction kinetics of H+ has been verified. This study provides insights into the application of manganese dioxide materials in aqueous AAIBs.

Effects of porous carbon materials on heat storage performance of CaCl2 hydrate for low-grade thermal energy.

Thermochemical energy storage (TES) is a promising technology to overcome supply-demand mismatch in the recycling of low-grade industrial waste heat. A novel sorbent is developed for low-grade TES system by employing an ordered mesoporous carbon, CMK-3, as the matrix of CaCl2 hydrates. Expanded graphite (EG) and activated carbon (AC) as matrixes are also discussed for a comparative study. All the composites show quick kinetic within 120 °C. Salt upload ability and heat storage capacity of the composites follow the order of CMK-3/CaCl2 (2037.2 kJ kg-1, 50.4 wt%) > EG/CaCl2 (1637.6 kJ kg-1, 48.1 wt%) > AC/CaCl2 (1221.8 kJ kg-1, 46.3 wt%). CMK-3/CaCl2 show the best heat storage performance due to the ordered tubular mesostructure, which limits the deliquescence at a proper level and provided good accommodation for salt solution. The inner solution absorption presents positive thermal effect that add to total heat storage capacity, making actual heat sorption of CMK-3/CaCl2 much higher than pure chemical reaction heat. A 25-cycle sorption-desorption experiment shows excellent cycling stability of CMK-3/CaCl2. This study proves CMK-3/CaCl2 to be a promising composite for low-grade TES system below 120 °C, and provides new insights for improving energy density of the heat storage materials.

Energy-saving optimization of the parallel chillers system based on a multi-strategy improved sparrow search algorithm.

The energy usage of parallel chillers systems accounts for 25-40 % of the total energy cost of a building. In light of global warming concerns and the need for energy conservation, it is essential to distribute the load of the parallel chillers systems effectively to achieve energy savings in buildings. Accordingly, this study presents a multi-strategy improved sparrow search algorithm (MSSA) to address optimization of the optimal chillers loading (OCL) problem. The proposed algorithm augments the basic sparrow search algorithm (SSA) by introducing the Sine chaotic map, Levy flight method, and Cauchy variation to enhance diversity, avoid local optima, and increase global and local search capacities. We use 9 benchmark functions to check the performance of the proposed MSSA algorithm, and the results are better than the selected algorithms such as particle swarm algorithm (PSO), harris hawks optimization (HHO), artificial rabbit optimization (ARO) and sparrow search algorithm (SSA). In addition, MSSA is applied to two typical cases to demonstrate its performance to optimal chillers loading and the results indicate that the MSSA outperforms similar algorithms. This study validates that MSSA can provide a promising solution to resolve the OCL problem.

Refinement and predicting formaldehyde concentrations of indoor fabric: Effects of temperature and humidity.

Indoor air pollution resulting from volatile organic compounds (VOCs) is a significant health concern, especially formaldehyde. Therefore, predicting indoor formaldehyde concentration is essential for environmental control. In this research, the authors develop a thermal and wet coupling calculation model of porous fabric that considers the influence of different phases of wet components and the coupling effect of heat and humidity on formaldehyde migration. We propose a modified calculation method of the formaldehyde mass transfer characteristic parameters of fabric to obtain the diffusion coefficient D and partition coefficient K. The heat and humidity coupling model and formaldehyde mass transfer model of fabric are simultaneously solved, and the authors analyze the influence mechanism of fabric loading rate, fabric type, temperature, and humidity on indoor formaldehyde mass transfer characteristics. We study the variation trend of fabric formaldehyde mass transfer characteristics coefficient and the temporal and spatial distribution of indoor formaldehyde concentration. The theoretical model is applied to practical problems by pre-evaluating the indoor formaldehyde concentration of decorated residential buildings in typical climate areas of China before occupancy. The authors obtain the variation rule of indoor formaldehyde concentration of residential buildings under typical hot and humid climate conditions, building materials, furniture, and fabrics. To provide theoretical support for indoor environmental control and human health protection.

Performance investigation of LiCl·H2O-γ-Al2O3 composite materials for low-grade heat storage.

In this study, the influences of nano γ-Al2O3 on the thermal storage performance of LiCl were experimentally investigated. The XRD results show that a complex of lithium aluminium oxychloride (LiAlOCl2) was formed through the LiCl·H2O and γ-Al2O3 composites preparation process. The in situ diffuse reflectance infrared Fourier transform spectroscopy measurement reveals that the addition of γ-Al2O3 accelerated the hydration rate of LiCl composites, concentrated the spectrum utilization range, and promoted the desorption rate of physical adsorbed H2O and low-frequency structural -OH in the materials. The highest specific surface area of the composite is 34.5 times higher than that of pure LiCl. The addition of γ-Al2O3 can increase the conversion rate of LiCl·H2O to approximately 100% at the hydration time of 1 h and the addition content of γ-Al2O3 at 15 wt%. A maximum heat storage density (HSD) for the LiCl·H2O-γ-Al2O3 composite can reach 714.7 kJ kgLiCl·H2O-1 in 1 h when the addition content of γ-Al2O3 was 15%wt and its water uptake can reach 0.26 g g-1 in 1 h. It also can be found that the addition of Al2O3 in LiCl resulted in a decrease of the activation energy from 90.89 kJ mol-1 to 79.76 kJ mol-1. However, the thermal conductivity of the LiCl·H2O-γ-Al2O3 composite slightly decreased with the increase of nano γ-Al2O3 content.

Co-Administration of nalbuphine to improve morphine tolerance in mice with bone cancer pain.

BACKGROUND: Kappa-opioid receptor (KOR) agonists are known for having opposite and/or different effects compared with Mu-opioid receptor (MOR) agonists. This study is aimed at clarifying the analgesic effect and tolerance of nalbuphine combined with morphine, and quantifying the mRNA and protein expression of spinal MOR and KOR in a mouse bone cancer pain (BCP) model treated with nalbuphine and morphine. METHOD: BCP model was prepared in C3H/HeNCrlVr Mice by implanting the sarcoma cells into the intramedullary space of the femur. The paw withdrawal thermal latency (PWL) measured by thermal radiometer was used to assess thermal hyperalgesia. PWL testing was performed after implantation and drug administration according to the protocol. Hematoxylin-eosin staining in the spinal cord and x-ray in the femoral intramedullary canal was detected. Real-time PCR and western blot analysis played a role in detecting spinal MOR and KOR expression changes. RESULTS: In tumor-implanted mice, the spinal MOR and KOR protein and mRNA expression was down-regulated when compared to that in sham-implanted mice (p < 0.05). Morphine therapy can lead to a decrease in spinal µ receptor expression. Similarly, the nalbuphine therapy can lead to a decrease in the expression of κ receptor protein and mRNA at the spinal cord level (p < 0.05). Morphine, nalbuphine, or nalbuphine co-administration with morphine all can extend the paw withdrawal thermal latency (PWL) to radiant thermal stimulation in tumor-implanted mice (p < 0.05). Compared with the morphine treatment group, nalbuphine co-administration with morphine delayed the reduction of PWL value again (p < 0.05). DISCUSSION: BCP itself may induce down-regulation of the spinal MOR and KOR expression. A low dose of nalbuphine co-administration with morphine led to the delayed emergence of morphine tolerance. The part of the mechanism may be due to the regulation of spinal opioid receptors expression.

Dendroclimatic response of Pinus tabuliformis Carr. along an altitudinal gradient in the warm temperate region of China.

Introduction: Global climate change can affect the sensitivity of tree radial growth to climate factors, but the specific responses of tree radial growth to microclimate along the altitudinal gradient in the long term are still unclear. Methods: In this study, the tree-ring width chronologies of Pinus tabuliformis Carr. in Shanxi Province of China were studied at three altitude gradients (1200-1300 m (low altitude), 1300-1400 m (medium altitude) and 1400-1500 m (high altitude)) during 1958-2017. Results: The results showed that (1) the climate background could be divided into two periods based on the Mann-Kendall test analysis: 1958-1996 was a stable period (mean annual temperature (MAT)=10.25°C, mean annual precipitation (MAP)=614.39 mm), and 1997-2017 was a rapid change period (MAT=10.91°C, MAP=564.70 mm), indicating a warming and drying trend in the study region. (2) The radial growth of P. tabuliformis at different altitudes showed inconsistent variation patterns. The tree radial growth at low and medium altitudes (CV=27.01% for low altitude and CV=24.69% for medium altitude) showed larger variation amplitudes during the rapid change period than that in the stable period (CV=12.40% for low altitude and CV=18.42% for medium altitude). In contrast to the increasing trend, the tree radial growth rates at the high altitude showed a decreasing trend across years. (3) In the stable period, the radial growth of P. tabuliformis at the low altitude showed a significantly negative response to temperature and a positive response to precipitation in May and June. The tree radial growth at the medium altitude was positively related to precipitation in June and minimum temperature in February. The tree growth at the high altitude was mainly positively correlated with the temperature in May and August. In the rapid change period, the radial growth of P. tabuliformis at the low altitude was affected by more meteorological factors than that in the stable period. Medium-altitude trees were positively influenced by precipitation in June and minimum temperature in January, whereas high-altitude trees responded positively to wind speed in February. (4) Along altitudinal gradients, tree radial growth was more related to temperature than precipitation in the stable period. The tree radial growth at the high altitude during the rapid change period was only affected by wind speed in February, whereas the tree radial growth at low and medium altitudes was mainly affected by temperature to a similar extent during the two periods. Discussion: The study indicated that tree growth-climate response models could help deeply understand the impact of climate change on tree growth adaptation and would be beneficial for developing sustainable management policies for forest ecosystems in the transition zone from warm-temperate to subtropical climates.

METTL14/YTHDF1 axis-modified UCHL5 aggravates atherosclerosis by activating the NLRP3 inflammasome.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to VSMC proliferation and migration in atherosclerosis (AS). Nevertheless, the regulatory mechanism of VSMC phenotypic switching during AS progression is unclear. Here, the role and regulatory mechanism of UCHL5 in VSMC phenotypic switching during AS progression were investigated. METHODS: ApoE-/- mice were fed with high fat diet to establish AS model in vivo. VSMCs stimulated by ox-LDL were used as AS cellular model. VSMC proliferation and migration were examined by CCK8 assay and transwell assay, respectively. The levels of pro-inflammatory cytokines were assessed using ELISA. The interactions between METTL14/YTHDF1, UCHL5 and NLRP3 were analyzed using RIP and/or dual-luciferase reporter gene and/or Co-IP assays. NLRP3 ubiquitination was analyzed by ubiquitination analysis. RESULTS: UCHL5 was significantly upregulated in AS patients and ox-LDL-treated VSMCs. UCHL5 silencing ameliorated plaque formation and vascular remodeling in vivo and suppressed ox-LDL-induced VSMC proliferation, migration, inflammation and phenotypic switching in vitro. Moreover, METTL14 could increase UCHL5 mRNA m6A level and promoted UCHL5 expression by recruiting YTHDF1. Moreover, UCHL5 overexpression enhanced protein stability by deubiquitinating NLRP3. Rescue studies revealed that NLRP3 overexpression abrogated UCHL5 silencing-mediated biological effects in ox-LDL-treated VSMCs. CONCLUSION: UCHL5 modified by METTL14/YTHDF1 axis could facilitate the inflammation and vascular remodeling in atherosclerosis by activating the NLRP3 inflammasome.

Circadian gene CLOCK accelerates atherosclerosis by promoting endothelial autophagy.

Atherosclerosis (AS) is a chronic inflammatory disease which gives rise to life-threatening complications like ischemic stroke. Rupture of carotid atherosclerotic plaque is the main cause of ischemic stroke. Emerging evidence has demonstrated that disturbed circadian rhythms could accelerate the progression of atherosclerosis by regulating endothelial function. Moreover, our previous study implicated the circadian gene circadian locomotor output cycles kaput (CLOCK) in the pathogenesis of unstable plaques. In this study, we explored the underlying mechanism that CLOCK mediates endothelial cell autophagy involved in the progression of AS. Circadian and autophagy gene expression was analyzed in the GSE41571 dataset and human carotid atherosclerotic plaque samples. Then we used ox-LDL to treat HUVECs, and analyzed CLOCK and autophagy gene in endothelial cells. Besides that, we comprehensively analyzed in vivo experiments to explore the function of CLOCK in autophagy and atherosclerosis using different staining including HE, MT and IF staining. In the dataset and patient samples, CLOCK expression and autophagy were decreased in the unstable plaque group compared with the stable group. Decreased Beclin1, ATG5, LC3, and CLOCK were also observed in HUVECs under oxidative stress condition which also enhances cell proliferation. In vivo, we also found decreasing level of CLOCK, Beclin1, LC3 and ATG5 in ApoE-/- mice compared with WT mice. Silencing of CLOCK in ApoE-/- mice may further aggravate atherosclerosis including decreased cap thickness and collagens. Our findings implicated that downregulation CLOCK would impair endothelial cell autophagy and accelerate atherosclerotic plaque, which provides a novel strategy for treatment of progression in AS.

Are lay abstracts published in Autism readable enough for the general public? A short report.

LAY ABSTRACT: Research papers are sometimes hard to follow. Lay abstracts give a short account of research papers. However, it is unclear whether lay abstracts are readable to the lay people. This study examined the readability of 570 abstracts and lay abstracts published between 2020 and 2022 in the journal Autism. We found that that lay abstracts are easier to read than abstracts but are harder to read than news reports. The findings suggest that lay abstracts, on average, are hard to read for the lay people. We propose that the journal and its authors may invite reviewers from outside the research community to test whether a lay abstract is readable.