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Abstract Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

In the global pursuit of energy conservation, reduction in consumption and emissions, as well as lightweighting, 5xxx-series aluminum alloys have emerged as a promising lightweight and high-strength material with a wide range of applications in aerospace, transportation, building structures, medical devices, and more. However, it is worth noting that 5XXX-series aluminum alloys belong to a category of non-heat-treatable reinforced aluminum alloys with limited means of enhancing their properties through heat treatment. Consequently, the development of high-performance 5XXX-series aluminum alloys poses a significant challenge. This paper provides an overview of the research progress on 5xxx-series aluminum alloys while discussing the current state of research regarding the influence of microalloying elements on their microstructure and properties. Furthermore, it elucidates the emerging trends in synergistic regulation between deformation processes and heat treatment processes for enhancing organizational refinement and improving alloy properties. Additionally, this study analyzes the reinforcement mechanism responsible for the exceptional properties exhibited by 5xxx-series aluminum alloys. Lastly, it discusses the exceptional properties exhibited by 5xxx-series alloys along with their primary areas of application. The findings presented herein can serve as a valuable reference for future advancements in advanced high-performance 5xxx-series aluminum alloys.

Rock breaking has always been a challenging problem that must be solved in projects such as excavating mountains, drilling wells, and constructing railways. Among the rock-breaking cutter steels, AISI H13 steel and wear-resistant high manganese steel have become the best choices. From the characteristics and failure modes of the two, rock-breaking cutter steels should simultaneously have high strength, high toughness and high wear resistance to avoid short-term fracture/damage and cost increase. Analyzing the problems existing in the molding process of rock-breaking cutter steels such as die casting, forging, and hot stamping, traditional strengthening technologies such as alloying optimization, heat treatment, and surface treatment can achieve certain performance enhancement. After reaching the limits of traditional strengthening technologies, a series of nanoparticle strengthening technologies came into being. The selection, addition amount, and addition method of nanoparticles all affect the microstructure, mechanical properties and wear. To this end, this article summarizes the research progress and challenges of rock-breaking cutter steels, and discusses traditional strengthening technologies and mainstream nanoparticle strengthening technologies. It provides a reference for the future development of high-quality and high-performance rock-breaking cutter steels, with aim to simultaneously expand their application potentials to other fields.

The explosive growth of wireless communications and electronic devices has brought electromagnetic radiation's harmfulness and hidden trouble to light, which has a major impact on electrical equipment's ability to function normally. MXene, a material with favorable features like conductivity, a unique two-dimensional multiple-layer structure and abundant surface functional groups, has made it a viable contender for high-performance microwave-absorbers. This article introduces the synthesis strategy of MXene/MXene-based materials and their parent phase MAX, comprehensively summarizes and analyzes the current progress in the study on the microwave-absorbing properties of MXene/MXene-based materials, analyzes the main problems and bottlenecks. Future research directions for MXene microwave-absorbing are discussed in detail.

Objective The existing theoretical calculation method of earth pressure does not take into account the discrete characteristics of pebble stratum such as large porosity and loose structure, and the calculated results are different from the actual earth pressure. Therefore, it is necessary to study the earth pressure calculation method suitable for pebble stratum in Chengdu area. Method Based on Chengdu Rail Transit Line 7, the differences between the earth pressure in deep foundation pit of pebble stratum and the theoretical Rankine value are analyzed, and an earth pressure calculation method for deep foundation pit excavation is established. Using discrete element numerical simulation and statistical data analysis, the distribution characteristics of static earth pressure, passive earth pressure and active earth pressure under the three basic displacement modes of the enclosure structure translation, rotation around the wall top and rotation around wall bottom are obtained. By comparing with the calculation results from Rankine earth pressure theory, the correction coefficient of the earth pressure under three different displacement modes are obtained, and the calculation method of earth pressure correction for deep foundation pit is established. The proposed earth pressure calculation method is verified by further comparison with the on-site measured data. Result & Conclusion The distribution of active earth pressure and passive earth pressure shows strong nonlinearity, which can be described by double fold lines, and the intersection points are located at the buried depth of 8m and 9m respectively. The static earth pressure correction coefficient is distributed between 0.91 and 0.96, not need for correction in use. The active earth pressure correction coefficient is distributed between 0.33 and 0.78, and the passive earth pressure correction coefficient is between 0.52 and 0.91, should be corrected in use. The calculated results of earth pressure in deep foundation pit of pebble stratum are in good agreement with the on-site measured results, providing a reference for similar rail transit projects.

BackgroundWhile prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron.MethodsWe conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms.ResultsWe enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P < .001), cough (50.9%, 63.3%, 66.7%; P < .001), and runny noses (48.9%, 71.3%, 72.9%; P < .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P < .001), shortness of breath (42.7%, 29.5%, 27.5%; P < .001), loss of taste (47.1%, 61.8%, 19.2%; P < .001), and loss of smell (47.5%, 55.6%, 20.0%; P < .001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28).ConclusionsParticipants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste.Trial registrationNCT04610515.

BackgroundThe prevalence, incidence, and interrelationships of persistent symptoms after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vary. There are limited data on specific phenotypes of persistent symptoms. Using latent class analysis (LCA) modeling, we sought to identify whether specific phenotypes of COVID-19 were present 3 months and 6 months post-infection.MethodsThis was a multicenter study of symptomatic adults tested for SARS-CoV-2 with prospectively collected data on general symptoms and fatigue-related symptoms up to 6 months postdiagnosis. Using LCA, we identified symptomatically homogenous groups among COVID-positive and COVID-negative participants at each time period for both general and fatigue-related symptoms.ResultsAmong 5963 baseline participants (4504 COVID-positive and 1459 COVID-negative), 4056 had 3-month and 2856 had 6-month data at the time of analysis. We identified 4 distinct phenotypes of post-COVID conditions (PCCs) at 3 and 6 months for both general and fatigue-related symptoms; minimal-symptom groups represented 70% of participants at 3 and 6 months. When compared with the COVID-negative cohort, COVID-positive participants had higher occurrence of loss of taste/smell and cognition problems. There was substantial class-switching over time; those in 1 symptom class at 3 months were equally likely to remain or enter a new phenotype at 6 months.ConclusionsWe identified distinct classes of PCC phenotypes for general and fatigue-related symptoms. Most participants had minimal or no symptoms at 3 and 6 months of follow-up. Significant proportions of participants changed symptom groups over time, suggesting that symptoms present during the acute illness may differ from prolonged symptoms and that PCCs may have a more dynamic nature than previously recognized. Clinical Trials Registration. NCT04610515.