Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects.

BACKGROUND: SHEN26, an oral broad-spectrum antiviral drug, possesses potent preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a favorable safety profile. METHODS: We report safety, tolerability, and pharmacokinetic data from a randomized, double-blind, placebo-controlled phase I study of SHEN26. Eighty-six healthy subjects were enrolled in the three studies: a single ascending-dose study (SAD), a multiple ascending-dose study (MAD), and a food-effect study (FE). RESULTS: In the SAD trial, the maximum observed plasma concentration (Cmax) and area under the curve (AUC) of the SHEN26 rapid metabolite SHEN26-69-0 increased approximately dose-proportionally in the 50-400 mg fasting dose range. In the 800 mg dose group, standard meals increased the Cmax and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of Cmax and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (Tmax) and increased the Cmax and AUC of SHEN26-69-0 compared with fasting administration. Most treatment-related adverse events were mild and resolved without treatment. CONCLUSION: SHEN26 demonstrated satisfactory safety and tolerability in healthy subjects, which supports the continued study of SHEN26 against SARS-CoV-2. TRIAL REGISTRATION: The trial is registered in ClinicalTrials.gov (CT. gov identifier: NCT05504746).

Functions of Peroxiredoxins and Their Roles in Autoimmune Diseases.

Significance: Oxidative stress is a common feature of autoimmune diseases. Low levels of reactive oxygen species (ROS) generation are important for various biological processes. Redox homeostasis can be disrupted when there is an imbalance between the production of ROS and the detoxification effect of antioxidants. Peroxiredoxins (PRDXs) are essential regulators of cellular redox signaling. Recent Advances: PRDXs are widely expressed antioxidant enzymes, and their physiological role is mainly to remove excess ROS in cells and reduce oxidative stress. Recent studies have shown that almost all PRDX subtypes are involved in the development of autoimmune diseases. Critical Issues: The pathogenesis of autoimmune diseases is complex, and effective treatments are lacking. Therefore, there is an urgent need to find new therapeutic targets. In this review, we discuss the functions of PRDXs and their pathophysiological roles in several autoimmune diseases. PRDXs may serve as potential targets for the treatment of autoimmune diseases. Future Directions: PRDXs are important in oxidative stress-mediated pathological situations. Future in-depth exploration of the mechanisms involved in regulating PRDXs in autoimmune diseases is needed to develop strategies targeting PRDXs for the treatment of autoimmune diseases. Antioxid. Redox Signal. 40, 329-344.

Effects of background colour, polarity, and saturation on digital icon status recognition and visual search performance.

Visual design form is an important factor affecting users' cognition of icons, which plays an important role in visual search and the perception of the status shown by icons. In the graphical user interface, the icon colour is regularly used to indicate the running state of a function. The aim of this study was to investigate the effects of icon colour features on user perception and visual search performance under different background colours. There were three independent variables in the study, including background colour (white and black), icon polarity (positive and negative), and icon saturation (60, 80, and 100%). Thirty-one participants were recruited for the experiment. Task performance and eye movement results indicated that white background as well as positive polarity and 80% saturation icons brought the best performances. The findings of this study provide useful guidelines for designing more efficient and user-friendly icons and interfaces in the future.Practitioner summary: This study was to investigate the effects of icon colour features (polarity and saturation) on user perception and visual search performance under different colour backgrounds. Task performance and eye movement results indicated that white background as well as positive polarity and 80% saturation icons brought the best performances.

Targeting regulated chondrocyte death in osteoarthritis therapy.

In vivo articular cartilage degeneration is an essential hallmark of osteoarthritis (OA), involving chondrocyte senescence, extracellular matrix degradation, chondrocyte death, cartilage loss, and bone erosion. Among them, chondrocyte death is one of the major factors leading to cartilage degeneration. Many studies have reported that various cell death modes, including apoptosis, ferroptosis, and autophagy, play a key role in OA chondrocyte death. Currently, there is insufficient understanding of OA pathogenesis, and there remains a lack of treatment methods to prevent OA and inhibit its progression. Studies suggest that OA prevention and treatment are mainly directed to arrest premature or excessive chondrocyte death. In this review, we a) discuss the forms of death of chondrocytes and the associations between them, b) summarize the critical factors in chondrocyte death, c) discuss the vital role of chondrocyte death in OA, d) and, explore new approaches for targeting the regulation of chondrocyte death in OA treatment.

Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics.

Collagens serve essential mechanical functions throughout the body, particularly in the connective tissues. In articular cartilage, collagens provide most of the biomechanical properties of the extracellular matrix essential for its function. Collagen plays a very important role in maintaining the mechanical properties of articular cartilage and the stability of the ECM. Noteworthily, many pathogenic factors in the course of osteoarthritis and rheumatoid arthritis, such as mechanical injury, inflammation, and senescence, are involved in the irreversible degradation of collagen, leading to the progressive destruction of cartilage. The degradation of collagen can generate new biochemical markers with the ability to monitor disease progression and facilitate drug development. In addition, collagen can also be used as a biomaterial with excellent properties such as low immunogenicity, biodegradability, biocompatibility, and hydrophilicity. This review not only provides a systematic description of collagen and analyzes the structural characteristics of articular cartilage and the mechanisms of cartilage damage in disease states but also provides a detailed characterization of the biomarkers of collagen production and the role of collagen in cartilage repair, providing ideas and techniques for clinical diagnosis and treatment.

Study on Smart Home Interface Design Characteristics Considering the Influence of Age Difference: Focusing on Sliders.

Smart homes represent an effective approach to improve one's quality of life. Developing user interfaces that are both comfortable and understandable can assist users, particularly the elderly, embrace smart home technologies. It's critical to concentrate on the characteristics of smart home interface design and their impact on people of various ages. Since sliders are one of the most common components utilized in the smart home user interface, this article aimed to investigate the effects of slider design characteristics (e.g., button size, track color, and sliding orientation) on user performance and preference. Thirty-four participants were recruited for the experiment (16 for the young group, aged between 18 and 44 years; 18 for the middle-aged and elderly group, aged between 45 years and above). Our results revealed that both groups had shorter task completion time, less fixation time, and saccades on horizontal sliding orientation and larger buttons, which means better user performance. For the older group, the slider with color gradient track led to better user performance, while the track color only had less effect on the performance of the younger group. In terms of user preference, the results and performance of the older group were basically consistent, while the younger group had no significant difference in sliding orientation and track color.

The Effects of Smart Home Interface Touch Button Design Features on Performance among Young and Senior Users.

Touch technology-based smart homes have become increasingly prevalent, as they can help people with independent daily life, especially for the elderly. The aim of this study was to investigate the effects of button features (i.e., button size, graphics/text ratio, and icon style) in smart home interfaces on user performance across two age groups. Participants in the young group (n = 15) and senior group (n = 15) completed a clicking task. Button size ranged from 10 mm to 25 mm with 5 mm increments. The three levels of graphics/text ratio were 3:1, 1:1, and 1:3, while icon style was either flat or skeuomorphic. Results showed that button size and graphics/text ratio had significant effects on user performance in both groups, whereas icon style only had an effect in the senior group. It was observed that the elderly were fond of buttons with a larger size of 20 mm with larger texts and skeuomorphic icons, whereas the young preferred a button size of 15 mm with equal-sized graphics and text. These results may help to improve the accessibility and usability of smart home interface design.

MEMS inductor fabrication and emerging applications in power electronics and neurotechnologies.

MEMS inductors are used in a wide range of applications in micro- and nanotechnology, including RF MEMS, sensors, power electronics, and Bio-MEMS. Fabrication technologies set the boundary conditions for inductor design and their electrical and mechanical performance. This review provides a comprehensive overview of state-of-the-art MEMS technologies for inductor fabrication, presents recent advances in 3D additive fabrication technologies, and discusses the challenges and opportunities of MEMS inductors for two emerging applications, namely, integrated power electronics and neurotechnologies. Among the four top-down MEMS fabrication approaches, 3D surface micromachining and through-substrate-via (TSV) fabrication technology have been intensively studied to fabricate 3D inductors such as solenoid and toroid in-substrate TSV inductors. While 3D inductors are preferred for their high-quality factor, high power density, and low parasitic capacitance, in-substrate TSV inductors offer an additional unique advantage for 3D system integration and efficient thermal dissipation. These features make in-substrate TSV inductors promising to achieve the ultimate goal of monolithically integrated power converters. From another perspective, 3D bottom-up additive techniques such as ice lithography have great potential for fabricating inductors with geometries and specifications that are very challenging to achieve with established MEMS technologies. Finally, we discuss inspiring and emerging research opportunities for MEMS inductors.