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The infiltration and deposition of cholesterol in the arterial wall play an important role in the initiation and development of atherosclerosis. Smooth muscle cells (SMCs) are the major cell type in the intima. Upon exposure to cholesterol, SMCs may undergo a phenotype switching into foam cells. Meanwhile, the pathological processes of the blood vessel such as cholesterol deposition and calcification induce the changes in the substrate stiffness around SMCs. However, whether substrate stiffness affects the cholesterol accumulation in SMCs and the formation of foam cells is not well-understood. In this study, SMCs were cultured on the substrates with different stiffnesses ranging from 1 to 100 kPa and treated with cholesterol. We found that cholesterol accumulation in SMCs was higher on 1 and 100 kPa substrates than that on intermediate stiffness at 40 kPa; consistently, total cholesterol (TC) content on 1 and 100 kPa substrates was also higher. As a result, the accumulation of cholesterol increased the expression of macrophage marker CD68 and downregulated SMC contractile marker smooth muscle α-actin (ACTA2). Furthermore, the mRNA and protein expression level of cholesterol efflux gene ATP-binding cassette transporter A1 (ABCA1) was much higher on 40 kPa substrate. With the treatment of a liver X receptor (LXR) agonist GW3965, the expression of ABCA1 increased and cholesterol loading decreased, showing an additive effect with substrate stiffness. In contrast, inhibition of LXR decreased ABCA1 gene expression and increased cholesterol accumulation in SMCs. Consistently, when ABCA1 gene was knockdown, the cholesterol accumulation was increased in SMCs on all substrates with different stiffness. These results revealed that substrate stiffness played an important role on SMCs cholesterol accumulation by regulating the ABCA1 expression. Our findings on the effects of substrate stiffness on cholesterol efflux unravel a new mechanism of biophysical regulation of cholesterol metabolism and SMC phenotype, and provide a rational basis for the development of novel therapies.

Vascular inflammation plays an important role in the pathogenesis and the development of cardiovascular diseases such as arteriosclerosis and restenosis, and the dysfunction of endothelial cells (ECs) may result in the activation of monocytes and other inflammatory cells. ECs exhibit an elongated morphology in the straight part of arteries but a cobblestone shape near the pro-atherogenic region such as branch bifurcation. Although the effects of hemodynamic forces on ECs have been widely studied, it is not clear whether the EC morphology affects its own function and thus the inflammatory response of monocytes. Here we showed that elongated ECs cultured on poly-(dimethyl siloxane) membrane surface with microgrooves significantly suppressed the activation of the monocytes in co-culture, in comparison to ECs with a cobblestone shape. The transfer of EC-conditioned medium to monocytes had the same effect, suggesting that soluble factors were involved in EC-monocyte communication. Further investigation demonstrated that elongated ECs upregulated the expression of anti-inflammatory microRNAs, especially miR-10a. Moreover, miR-10a was found in the extracellular vesicles (EVs) released by ECs and transferred to monocytes, and the inhibition of EV secretion from ECs repressed the upregulation of miR-10a. Consistently, the inhibition of miR-10a expression in ECs reduced their anti-inflammatory effect on monocytes. These results reveal that the EC morphology can regulate inflammatory response through EVs, which provides a basis for the design and the optimization of biomaterials for vascular tissue engineering.

As a stable, low-cost, environment-friendly, and gas-sensitive material, semiconductor metal oxides have been widely used for gas sensing. In the past few years, single-atom catalysts (SACs) have gained increasing attention in the field of gas sensing with the advantages of maximized atomic utilization and unique electronic and chemical properties and have successfully been applied to enhance the detection sensitivity and selectivity of metal oxide gas sensors. However, the application of SACs in gas sensors is still in its infancy. Herein, we critically review the recent advances and current status of single-atom catalysts in metal oxide gas sensors, providing some suggestions for the development of this field. The synthesis methods and characterization techniques of SAC-modified metal oxides are summarized. The interactions between SACs and metal oxides are crucial for the stable loading of single-atom catalysts and for improving gas-sensitive performance. Then, the current application progress of various SACs (Au, Pt, Cu, Ni, etc.) in metal oxide gas sensors is introduced. Finally, the challenges and perspectives of SACs in metal oxide gas sensors are presented. [ABSTRACT FROM AUTHOR]

BACKGROUND Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments. OBJECTIVE AND RATIONALE The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment. SEARCH METHODS PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed. OUTCOMES A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment. WIDER IMPLICATIONS The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1) , actin-like7A (ACTL7A) , actin-like 9 (ACTL9) , and IQ motif-containing N (IQCN) , ICSI may also fail to fertilize. We can consider artificial oocyte activation technology with ICSI to improve fertilization rate and reduce monetary and time costs. In the future, fertility is expected to be improved or restored by interfering with or supplementing the relevant genes. [ABSTRACT FROM AUTHOR]

Explosives can be analyzed for their content by detecting the photolytic gaseous byproducts. However, to prevent electrostatic sparking, explosives are frequently preserved in conditions with low temperatures and high humidity, impeding the performance of gas detection. Thus, it has become a research priority to develop gas sensors that operate at ambient temperature and high humidity levels in the realm of explosive breakdown gas-phase detection. In this work, 3-aminopropyltriethoxysilane (APTES) self-assembled monolayer-functionalized tin diselenide (APTES-SnSe 2 ) nanosheets were synthesized via a facile solution stirring strategy, resulting in a room-temperature NO 2 sensor with improved sensitivity and humidity tolerance. The APTES-SnSe 2 sensor with moderate functionalization time outperforms the pure SnSe 2 sensor in terms of the response value (317.51 vs 110.98%) and response deviation (3.11 vs 24.13%) under humidity interference to 500 ppb NO 2 . According to density functional theory simulations, the stronger adsorption of terminal amino groups of the APTES molecules to NO 2 molecules and stable adsorption energy in the presence of H 2 O are the causes of the improved sensing capabilities. Practically, the APTES-SnSe 2 sensor achieves accurate detection of photolysis gases from trace nitro explosives octogen, pentaerythritol tetranitrate, and trinitrotoluene at room temperature and various humidity levels. This study provides a potential strategy for the construction of gas sensors with high responsiveness and antihumidity capabilities to identify explosive content in harsh environments.

The success of the two mRNA vaccines developed by Moderna and BioNTech during the COVID-19 pandemic increased research interest into the application of mRNA technologies. Compared with the canonical linear mRNA used in these vaccines, circular mRNA has been found to mediate more potent and durable protein expression and demands a simpler manufacturing procedure. However, the application of circular mRNA is still at the initiation stage, and proof of concept for its use as a future medicine or vaccine is required. In the current study, we established a novel type of circular mRNA, termed cmRNA, based on the echovirus 29-derived internal ribosome entry site element and newly designed homology arms and RNA spacers. Our results demonstrated that this type of circular mRNA could mediate strong and durable expression of various types of proteins, compared with typical linear mRNA. Moreover, for the first time, our study demonstrated that direct intratumoral administration of cmRNA encoding a mixture of cytokines achieved successful modulation of intratumoral and systematic anti-tumor immune responses and enhanced anti-programmed cell death protein 1 (PD-1) antibody-induced tumor repression in a syngeneic mouse model. This novel circular mRNA platform is thereby suitable for direct intratumoral administration for cancer therapy., Competing Interests: One patent has been filed to protect cmRNA as well as its application (inventors Z.S., C.Z., and J.Z.), one patent has been filed to protect the use of circular mRNA administrated intratumorally as anti-tumor therapy (inventors C.Z., J.Y., and Y.T.), and one patent has been filed to protect the use of Ringer’s solution for circular mRNA intratumoral administration (inventors J.Y., Y.T., and J.Z.)., (© 2022 The Authors.)

Metal-oxide-based chemiresistive hydrogen sensors exhibit high sensitivity, long-term stability, and low cost and have been extensively applied in safety monitoring of H 2 . However, the sensing performances are dramatically affected by the water vapor, resulting in reduced response value and increased response/recovery time. To improve the anti-humidity property of sensors, coating the breathable and hydrophobic membrane on the surface of the sensing film is an effective strategy. In this work, the poly[4,5-difluoro-2,2-bis(trifluoromethyl)-1,3-dioxole- co -tetrafluoroethylene] (Teflon AF-2400) was dip-coated on the surface of SnO 2 in a commercial hydrogen sensor (TGS2615) as a breathable and hydrophobic membrane. For safety, He instead of H 2 was used to test the gas permeability of membranes. The Teflon membrane shows a high He permeability of up to 40,700 Barrer and an excellent He/H 2 O selectivity of 99. Moreover, Teflon shows high processability to form a defect-free coating on the rough surface of the sensing film and high chemical stability under the operando condition of the sensor. Thus, the Teflon-modified sensor possesses excellent selectivity with a value of 5, and the resistance is stable at 10,554 ± 3% Ω for 20 days in 80% RH. The modified sensor shows an improved anti-humidity property with a 75% response to 200 ppm H 2 at 80% RH and has a low coefficient of variation value of 7.23% that shows advances than other reported sensors modified by coatings. The commercially available Teflon and the simple coating technology make the strategy easily scale up and show promising applications.