Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in sleep in which the airways narrow or collapse during sleep, causing obstructive sleep apnea. The prevalence of OSAS continues to rise worldwide, particularly in middle-aged and elderly individuals. The mechanism of upper airway collapse is incompletely understood but is associated with several factors, including obesity, craniofacial changes, altered muscle function in the upper airway, pharyngeal neuropathy, and fluid shifts to the neck. The main characteristics of OSAS are recurrent pauses in respiration, which lead to intermittent hypoxia (IH) and hypercapnia, accompanied by blood oxygen desaturation and arousal during sleep, which sharply increases the risk of several diseases. This paper first briefly describes the epidemiology, incidence, and pathophysiological mechanisms of OSAS. Next, the alterations in relevant signaling pathways induced by IH are systematically reviewed and discussed. For example, IH can induce gut microbiota (GM) dysbiosis, impair the intestinal barrier, and alter intestinal metabolites. These mechanisms ultimately lead to secondary oxidative stress, systemic inflammation, and sympathetic activation. We then summarize the effects of IH on disease pathogenesis, including cardiocerebrovascular disorders, neurological disorders, metabolic diseases, cancer, reproductive disorders, and COVID-19. Finally, different therapeutic strategies for OSAS caused by different causes are proposed. Multidisciplinary approaches and shared decision-making are necessary for the successful treatment of OSAS in the future, but more randomized controlled trials are needed for further evaluation to define what treatments are best for specific OSAS patients.

A trimeric spike-based COVID-19 vaccine candidate induces broad neutralization against SARS-CoV-2 variants.

COVID-19 pandemic caused by SARS-CoV-2 infection has an impact on global public health and social economy. The emerging immune escape of SARS-CoV-2 variants pose great challenges to the development of vaccines based on original strains. The development of second-generation COVID-19 vaccines to induce immune responses with broad-spectrum protective effects is a matter of great urgency. Here, a prefusion-stabilized spike (S) trimer protein based on B.1.351 variant was expressed and prepared with CpG7909/aluminum hydroxide dual adjuvant to investigate the immunogenicity in mice. The results showed that the candidate vaccine could induce a significant receptor binding domain-specific antibody response and a substantial interferon-γ-mediated immune response. Furthermore, the candidate vaccine also elicited robust cross-neutralization against the pseudoviruses of the original strain, Beta variant, Delta variant and Omicron variant. The vaccine strategy of S-trimer protein formulated with CpG7909/aluminum hydroxide dual adjuvant may be considered a means to increase vaccine effectiveness against future variants.

Customized High-Sensitivity Plasmonic Metasensing Towards Immunodetection of Single Bio-Nanoparticles

Plasmonic metasurface biosensing has shown great potential in label-free detection of bio-nanoparticles with various sizes, such as cancer antigens, exosomes and SARS-CoV-2 virus. It typically relies on the immunoassay, but current studies usually neglect the perfect size matching between each target bio-nanoparticle and the surface near-field domain, which should be very critical for the enhancement of detection performance. In order to maximize the immunodetection capability for each bio-nanoparticle, we propose a plasmonic meta-biosensor based on the field-customized mechanism. Our design overcomes the serious interference of biofunctionalization and accomplishes a sensitivity of 27 times higher than the conventional nanoplasmonic counterpart. Our method also builds the important basis of single bio-nanoparticle immunodetection by a plasmonic metasurface. The customized plasmonic metasensing study implies a promising way towards ultra-low concentration biosensing or even single bio-nanoparticle detection for high-performance point-of-care-testing in the near future.

Affinity Exploration of SARS-CoV-2 RBD Variants to mAb-Functionalized Plasmonic Metasurfaces for Label-Free Immunoassay Boosting.

Plasmonic metasurfaces (PMs) functionalized with the monoclonal antibody (mAb) are promising biophotonic sensors for biomolecular interaction analysis and convenient immunoassay of various biomarkers, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Previous PM biosensing suffers from the slow affinity detection rate and lack of sufficient immunoassay studies on various SARS-CoV-2 variants. Here, we develop a high-efficiency affinity testing method based on label-free PM sensors with mAbs and demonstrate their binding characteristics to 12 spike receptor binding domain (RBD) variants of SARS-CoV-2. In addition to the research of plasmonic near-field influence on surface biomolecule sensing, we provide a comprehensive report about the Langmuir binding equilibrium of molecular kinetics between 12 SARS-CoV-2 RBD variants and mAb-functionalized PMs, which plays a crucial role in label-free immunosensing. A high-affinity mAb can be combined with the highly sensitive propagating plasmonic mode to boost the detection of SARS-CoV-2 variants. Owing to a better understanding of molecular dynamics on PMs, we develop an ultrasensitive biosensor of the SARS-CoV-2 Omicron variant. The experiments show great distinguishment of P < 0.0001 from respiratory diseases induced by other viruses, and the limit of detection is 2 orders smaller than the commercial colloidal gold immunoassay. Our study shows the label-free biosensing by low-cost wafer-scale PMs, which will provide essential information on biomolecular interaction and facilitate high-precision point-of-care testing for emerging SARS-CoV-2 variants in the future.

Plasmonic Metasurfaces for Medical Diagnosis Applications: A Review.

Plasmonic metasurfaces have been widely used in biosensing to improve the interaction between light and biomolecules through the effects of near-field confinement. When paired with biofunctionalization, plasmonic metasurface sensing is considered as a viable strategy for improving biomarker detection technologies. In this review, we enumerate the fundamental mechanism of plasmonic metasurfaces sensing and present their detection in human tumors and COVID-19. The advantages of rapid sampling, streamlined processes, high sensitivity, and easy accessibility are highlighted compared with traditional detection techniques. This review is looking forward to assisting scientists in advancing research and developing a new generation of multifunctional biosensors.

Hawkes process modeling of COVID-19 with mobility leading indicators and spatial covariates.

Hawkes processes are used in statistical modeling for event clustering and causal inference, while they also can be viewed as stochastic versions of popular compartmental models used in epidemiology. Here we show how to develop accurate models of COVID-19 transmission using Hawkes processes with spatial-temporal covariates. We model the conditional intensity of new COVID-19 cases and deaths in the U.S. at the county level, estimating the dynamic reproduction number of the virus within an EM algorithm through a regression on Google mobility indices and demographic covariates in the maximization step. We validate the approach on both short-term and long-term forecasting tasks, showing that the Hawkes process outperforms several models currently used to track the pandemic, including an ensemble approach and an SEIR-variant. We also investigate which covariates and mobility indices are most important for building forecasts of COVID-19 in the U.S.

The Relationship Among Organizational Identity, Psychological Resilience and Work Engagement of the First-Line Nurses in the Prevention and Control of COVID-19 Based on Structural Equation Model.

PURPOSE: To explore how the organizational identity and psychological resilience affect work engagement of the front-line nurses in the prevention and control of coronavirus disease 2019 (COVID-19) and to establish the relationship model based on these factors. MATERIAL AND METHODS: Convenience sampling was applied to collect questionnaire samples from 216 nurses (from 12 cities in 6 provinces). General information questionnaires, organizational identity scale (OIQ), psychological resilience scale (CD-RISC), and Utrecht Work Engagement Scale (UWES) were used as tools for data collection. RESULTS: Both organizational identification and psychological resilience had a positive impact on work engagement (r=0.457~0.669). The structural equation model indicated that psychological resilience had a significant partial mediating effect on the relationship between organizational identity and work engagement; the mediating effect value was 0.25, the overall effect value of work engagement was 0.73, and the mediating effect accounted for 34.2%. CONCLUSION: Our results revealed that organizational identity could directly affect nursing. It can also indirectly affect nurses' work engagement through the intermediary role of psychological resilience. In face of the COVID-19 epidemic, hospitals and nursing managers could improve the level of nurses' job involvement by improving organizational identity, which in turn may have a positive effect on psychological resilience.