Single-cell RNA Sequencing Identifies Natural Kill Cell-Related Transcription Factors Associated With Age-Related Macular Degeneration.

Background: Age-related Macular Degeneration (AMD) poses a growing global health concern as the leading cause of central vision loss in elderly people. Objection: This study focuses on unraveling the intricate involvement of Natural Killer (NK) cells in AMD, shedding light on their immune responses and cytokine regulatory roles. Methods: Transcriptomic data from the Gene Expression Omnibus database were utilized, employing single-cell RNA-seq analysis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and single-cell regulatory network inference and clustering (SCENIC) analysis were applied to reveal the regulatory mechanisms of NK cells in early-stage AMD patients. Machine learning models, such as random forests and decision trees, were employed to screen hub genes and key transcription factors (TFs) associated with AMD. Results: Distinct cell clusters were identified in the present study, especially the T/NK cluster, with a notable increase in NK cell abundance observed in AMD. Cell-cell communication analyses revealed altered interactions, particularly in NK cells, indicating their potential role in AMD pathogenesis. HdWGCNA highlighted the turquoise module, enriched in inflammation-related pathways, as significantly associated with AMD in NK cells. The SCENIC analysis identified key TFs in NK cell regulatory networks. The integration of hub genes and TFs identified CREM, FOXP1, IRF1, NFKB2, and USF2 as potential predictors for AMD through machine learning. Conclusion: This comprehensive approach enhances our understanding of NK cell dynamics, signaling alterations, and potential predictive models for AMD. The identified TFs provide new avenues for molecular interventions and highlight the intricate relationship between NK cells and AMD pathogenesis. Overall, this study contributes valuable insights for advancing our understanding and management of AMD.

Towards digital healthy ageing: the case of Agatha and priorities moving forward.

Digital tools have an important role to play in meeting the health demands of ageing societies. However, current technological design paradigms often marginalize older people. We adopted a lean, user-centred approach to prototype the Avatar for Global Access to Technology for Healthy Ageing (Agatha), an interactive one-stop shop for healthy ageing promotion. Building on this experience, we present a vision for an integrated approach to "digital healthy ageing". Older people consulted predominantly associated "healthy ageing" with disease avoidance. Digital healthy ageing should take a more holistic approach, covering self-care, prevention, and active ageing. It should also consider social determinants of health in old age, including access to information and digital health literacy, as they interact with poverty, education, access to health services and other structural factors. We use this framework to map out key areas of innovation and explore policy priorities and opportunities for innovation practitioners.

Systematic scoping review of the implementation, adoption, use, and effectiveness of digital contact tracing interventions for COVID-19 in the Western Pacific Region.

A systematic scoping review of digital contact tracing (DCT) interventions for COVID-19 was conducted to describe the implementation, adoption, use and effectiveness of DCT interventions implemented as part of the COVID-19 response in the Western Pacific Region (WPR). A systematic search identified 341 studies and 128 grey literature sources, of which 18 studies and 41 grey literature sources were included. 17 (46%) WPR countries and areas implemented DCT interventions. Adoption ranged from 14.6% to 92.7% in different adult populations and epidemiological contexts. Trust in authorities, and privacy concerns and beliefs, were the most frequent determinants of adoption and use. Only two studies analysed DCT effectiveness, which showed limited to no effectiveness of DCT interventions in low transmission settings. Overall, there is limited evidence available to evaluate the contribution of DCT to mitigating COVID-19 in the WPR. Preparedness for future health emergencies should include developing robust frameworks for DCT effectiveness evaluations.

Use of ß­blockers and risk of age­related macular degeneration among hypertensive patients: An insight from The National Health and Nutrition Examination Survey.

Although age-related macular degeneration (AMD) is the leading cause of legal blindness, the treatment methods for AMD are limited. The aim of the present study was to examine the association between oral ß-blockers (BBs) and the risk of developing AMD among hypertensive patients. For this purpose, a total of 3,311 hypertensive patients from the National Health and Nutrition Examination Survey were included in the study. The use of BBs and treatment duration data were collected using a self-reported questionnaire. AMD was diagnosed by gradable retinal images. Multivariate-adjusted survey-weighted univariate logistic regression was used to confirm the association between the use of BBs and the risk of developing AMD. The results revealed that the use of BBs exerted a beneficial effect (odds ratio (OR), 0.34; 95% confidence interval (95% CI, 0.13-0.92; P=0.04) in late-stage AMD in the multivariate adjusted model. When the BBs were classified into non-selective BBs and selective BBs, the protective effect in late-stage AMD was still observed in the non-selective BBs (OR, 0.20; 95% CI, 0.07-0.61; P<0.001). After accounting for treatment duration, long-term treatment with BBs (>6 years) was also found to reduce the risk of late-stage AMD (OR, 0.13; 95% CI, 0.03-0.63; P=0.01). In late-stage AMD, the long-term use of BBs was beneficial for geographic atrophy (OR, 0.07; 95% CI, 0.02-0.28; P<0.001). On the whole, the present study demonstrates that the use of non-selective BBs exerted a beneficial effect against the risk of late-stage AMD among hypertensive patients. Long-term treatment with BBs was also associated with lower risk of developing AMD. These findings may provide novel strategies for the management and treatment of AMD.

Giant photon momentum locked THz emission in a centrosymmetric Dirac semimetal.

Strong second-order optical nonlinearities often require broken material centrosymmetry, thereby limiting the type and quality of materials used for nonlinear optical devices. Here, we report a giant and highly tunable terahertz (THz) emission from thin polycrystalline films of the centrosymmetric Dirac semimetal PtSe2. Our PtSe2 THz emission is turned on at oblique incidence and locked to the photon momentum of the incident pump beam. Notably, we find an emitted THz efficiency that is giant: It is two orders of magnitude larger than the standard THz-generating nonlinear crystal ZnTe and has values approaching that of the noncentrosymmetric topological material TaAs. Further, PtSe2 THz emission displays THz sign and amplitude that is controlled by the incident pump polarization and helicity state even as optical absorption is only weakly polarization dependent and helicity independent. Our work demonstrates how photon drag can activate pronounced optical nonlinearities that are available even in centrosymmetric Dirac materials.

Digital health interventions for COVID-19 in China: a retrospective analysis.

BACKGROUND: The use of digital health technologies was an integral part to China's early response to coronavirus disease 2019 (COVID-19). Existing literatures have analyzed and discussed implemented digital health innovations from the perspective of technologies, whereas how policy mechanisms contributed to the formulation of the digital health landscape for COVID-19 was overlooked. This study aimed to examine the contexts and key mechanisms in China's rapid mobilization of digital health interventions in response to COVID-19, and to document and share lessons learned. METHODS: Policy documents were identified and retrieved from government portals and recognized media outlets. Data on digital health interventions were collected through three consecutive surveys administered between 23 January 2020 and 31 March 2020 by China Academy of Information and Communication Technology (CAICT) affiliated to the Ministry of Industry and Information Technology (MIIT). Participants were member companies of the Internet Health alliance established by MIIT and the National Health Commission (NHC) in June 2016. Self-report digital interventions focusing on social and economic recovery were excluded. Two hundred and sixty-six unique digital health interventions meeting our criteria were extracted from 175 narratives on digital health interventions submitted by 116 participating companies. Thematic analysis was conducted to describe the scope and priority of policies advocating for the use of digital health technologies and the implementation pattern of digital health interventions. Data limitations precluded an evaluation of the impact of digital health interventions over a longer time frame. RESULTS: Between January and March 2020, national policy directives promoting the use of digital technologies for the containment of COVID-19 collectively advocated for use cases in emergency planning and preparedness, public health response, and clinical services. Interventions to strengthen clinical services were mentioned more than the other two themes (n = 15, 62.5% (15/24)). Using digital technologies for public health response was mentioned much less than clinical services (n = 5, 20.8% (5/24)). Emergency planning and preparedness was least mentioned (n = 4, 16.7% (4/24)). Interventions in support of clinical services disproportionately favored healthcare facilities in less resource-constraint settings. Digital health interventions shared the same pattern of distribution. More digital health technologies were implemented in clinical services (n = 103, 38.7% (103/266)) than that in public health response (n = 91, 34.2% (91/266)). Emergency planning and preparedness had the least self-reported digital health interventions (n = 72, 27.1% (72/266)). We further identified case studies under each theme in which the wide use of digital health technologies highlighted contextual factors and key enabling mechanisms. CONCLUSIONS: The contextual factors and key enabling mechanisms through the use of policy instruments to promote digital health interventions for COVID-19 in China include pathway of policy directives influencing the private sector using a decentralized system, the booming digital health landscape before COVID-19, agility of the public sector in introducing regulatory flexibilities and incentives to mobilize the private sector.

Progress in Research on the Role of FGF in the Formation and Treatment of Corneal Neovascularization.

Corneal neovascularization (CNV) is a sight-threatening disease usually associated with inflammatory, infectious, degenerative, and traumatic disorders of the ocular surface. Fibroblast growth factor (FGF) family members play an important role in angiogenesis to induce corneal neovascularization, which significantly affects the differentiation, proliferation, metastasis, and chemotaxis of vascular endothelial cells. Both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) demonstrate positive staining in capillaries and induce corneal stromal cells. The anabolism of endothelial cells is induced by bFGF in corneal neovascularization. FGFs exert their effects via specific binding to cell surface-expressed specific receptors. We believe that both anti-FGF antibodies and anti-FGF receptor antibodies represent new directions for the treatment of CNV. Similar to anti-vascular endothelial growth factor antibodies, subconjunctival injection and eye drops can be considered effective forms of drug delivery.

Fibroblast Growth Factor 22 Inhibits ER Stress-Induced Apoptosis and Improves Recovery of Spinal Cord Injury.

Currently, inhibiting or reducing neuronal cell death is the main strategy to improve recovery of spinal cord injury (SCI). Therapies using nerve growth factors to treat SCI mainly focused on reducing the area damaged by postinjury degeneration to promote functional recovery. In this report, we investigated the mechanism of ER (endoplasmic reticulum) stress-induced apoptosis and the protective action of fibroblast growth factor 22 (FGF22) in vivo. Our results demonstrated that ER stress-induced apoptosis plays a significant role in injury of SCI model rats. FGF22 administration promoted recovery and increased neuron survival in the spinal cord lesions of model mice. The protective effect of FGF22 is related to decreased expression of CHOP (C/EBP-homologous protein), GRP78 (glucose-regulated protein 78), caspase-12, X-box binding protein 1 (XBP1), eukaryotic initiation factor 2α (Eif-2α) and Bad which are ER stress-induced apoptosis response proteins. Moreover, FGF22 administration also increased the number of neurons and the expression of growth-associated protein 43 (GAP43) which was related to axon regeneration. We also demonstrated that the protective effect of FGF22 effectively reduces neuronal apoptosis and promotes axonal regeneration. Our study first illustrated that the function of FGF22 is related to the inhibition of ER stress-induced cell death in SCI recovery via activation of downstream signals. This study also suggested a new tendency of FGF22 therapy development in central neural system injuries, which involved chronic ER stress-induced apoptosis.

Anisotropic Picosecond Spin-Photocurrent from Weyl Semimetal WTe2.

The generation and detection of ultrafast spin current, preferably reaching a frequency up to terahertz, is the core of spintronics. Studies have shown that the Weyl semimetal WTe2 is of great potential in generating spin currents. However, the prior studies have been limited to the static measurements with the in-plane spin orientation. In this work, we demonstrate a picosecond spin-photocurrent in a Td-WTe2 thin film via a terahertz time domain spectroscopy with a circularly polarized laser excitation. The anisotropic dependence of the circular photogalvanic effect (CPGE) in the terahertz emission reveals that the picosecond spin-photocurrent is generated along the rotational asymmetry a-axis. Notably, the generated spins are aligned along the out-of-plane direction under the light normally incident to the film surface, which provides an efficient means to manipulate magnetic devices with perpendicular magnetic anisotropy. A spin-splitting band induced by intrinsic inversion symmetry breaking enables the manipulation of a spin current by modulating the helicity of the laser excitation. Moreover, CPGE nearly vanishes at a transition temperature of ∼175 K due to the carrier compensation. Our work provides an insight into the dynamic behavior of the anisotropic spin-photocurrent of Td-WTe2 in terahertz frequencies and shows a great potential for the future development of terahertz-spintronic devices with Weyl semimetals.

Sub-Picosecond Carrier Dynamics Induced by Efficient Charge Transfer in MoTe2/WTe2 van der Waals Heterostructures.

Demonstration of van der Waals (vdW) semiconductor/metal heterostructures (SMHs) based on transition metal dichalcogenides has been a central approach in high-speed electronics by introducing ultrafast carrier dynamics. In this regard, a Weyl semimetal WTe2 is of great interest due to its vdW layered nature, low work function, and superior electrical properties. However, little is still known about its heterostructures, and a few picoseconds photocarrier lifetimes hinder its applications in high-speed electronics. Here, we propose a SMH: semimetallic Td phase WTe2 with its sister compound of semiconducting 2H phase MoTe2. Time-resolved terahertz (THz) spectroscopy demonstrated that WTe2 exhibited the significantly shorter carrier lifetimes of sub-picosecond when forming a junction with MoTe2. We provided explicit characteristic signatures, revealing charge transfer across the interface and the subsequent interlayer exciton decay. This work not only offers the extension of the THz detection scope of ultrafast phenomena from atomically thin materials but also provides a building block of vertical SMHs for high-speed electronic devices with sub-picosecond photocarrier lifetimes.

Electric-field control of spin accumulation direction for spin-orbit torques.

Electric field is an energy-efficient tool that can be leveraged to control spin-orbit torques (SOTs). Although the amount of current-induced spin accumulation in a heavy metal (HM)/ferromagnet (FM) heterostructure can be regulated to a certain degree using an electric field in various materials, the control of its direction has remained elusive so far. Here, we report that both the direction and amount of current-induced spin accumulation at the HM/FM interface can be dynamically controlled using an electric field in an oxide capped SOT device. The applied electric field transports oxygen ions and modulates the HM/FM interfacial chemistry resulting in an interplay between the spin Hall and the interfacial torques which in turn facilitates a non-volatile and reversible control over the direction and magnitude of SOTs. Our electric-field controlled spin-orbitronics device can be programmed to behave either like the SOT systems with a positive spin Hall angle or a negative spin Hall angle.

[Progress on neurogenesis mechanisms of endogenous adult neural stem cells].

Endogenous adult neural stem cells are closely related to the normal physiological functions of the brain and many neurodegenerative diseases. Neurons are affected by factors such as extracellular microenvironment and intracellular signaling. In recent years, some specific signaling pathways have been found that affect the occurrence of neural stem cells in adult neural networks, including proliferation, differentiation, maturation, migration, and integration with host functions. In this paper, we summarize the signals and their molecular mechanisms, including the related signaling pathways, neurotrophic factors, neurotransmitters, intracellular transcription factors and epigenetic regulation of neuronal differentiation from both the extracellular and intracellular aspects, providing basic theoretical support for the treatment of central nervous system diseases through neural stem cells approach.

Ultrafast Spin-to-Charge Conversion at the Surface of Topological Insulator Thin Films.

Strong spin-orbit coupling, resulting in the formation of spin-momentum-locked surface states, endows topological insulators with superior spin-to-charge conversion characteristics, though the dynamics that govern it have remained elusive. Here, an all-optical method is presented, which enables unprecedented tracking of the ultrafast dynamics of spin-to-charge conversion in a prototypical topological insulator Bi2 Se3 /ferromagnetic Co heterostructure, down to the sub-picosecond timescale. Compared to pure Bi2 Se3 or Co, a giant terahertz emission is observed in the heterostructure that originates from spin-to-charge conversion, in which the topological surface states play a crucial role. A 0.12 ps timescale is identified that sets a technological speed limit of spin-to-charge conversion processes in topological insulators. In addition, it is shown that the spin-to-charge conversion efficiency is temperature independent in Bi2 Se3 as expected from the nature of the surface states, paving the way for designing next-generation high-speed optospintronic devices based on topological insulators at room temperature.

Direct visualization of current-induced spin accumulation in topological insulators.

Charge-to-spin conversion in various materials is the key for the fundamental understanding of spin-orbitronics and efficient magnetization manipulation. Here we report the direct spatial imaging of current-induced spin accumulation at the channel edges of Bi2Se3 and BiSbTeSe2 topological insulators as well as Pt by a scanning photovoltage microscope at room temperature. The spin polarization is along the out-of-plane direction with opposite signs for the two channel edges. The accumulated spin direction reverses sign upon changing the current direction and the detected spin signal shows a linear dependence on the magnitude of currents, indicating that our observed phenomena are current-induced effects. The spin Hall angle of Bi2Se3, BiSbTeSe2, and Pt is determined to be 0.0085, 0.0616, and 0.0085, respectively. Our results open up the possibility of optically detecting the current-induced spin accumulations, and thus point towards a better understanding of the interaction between spins and circularly polarized light.

High-Performance THz Emitters Based on Ferromagnetic/Nonmagnetic Heterostructures.

A low-cost, intense, broadband, noise resistive, magnetic field controllable, flexible, and low power driven THz emitter based on thin nonmagnetic/ferromagnetic metallic heterostructures is demonstrated. The THz emission origins from the inverse spin Hall Effect. The proposed devices are not only promising for a wide range of THz equipment, but also offer an alternative approach to characterize the spin-orbit interaction in nonmagnetic/ferromagnetic bilayers.