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The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex via the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.

Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associated with neuronal injury in the development of RION. Both the pharmacological inhibition of Cdk5 by roscovitine and the inhibition of Drp1 by mdivi-1 inhibited mitochondrial fission and the production of ROS associated with radiation-induced neuronal loss. Taken together, these findings may have clinical significance in preventing the development of RION.

Glaucoma is a leading cause of irreversible blindness, primarily driven by the progressive degeneration of retinal ganglion cells (RGCs). In this study, we report the novel application of bone marrow mesenchymal stem cells (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) in a glaucomatous ischemia/reperfusion (IR) model. ApoEVs exhibited remarkable anti-inflammatory properties, were efficiently internalized by retinal neurons, promoted RGC survival, and preserved visual function. Transcriptomic analysis revealed that ApoEV treatment significantly downregulated Irgm1, an inflammation-related gene. Notably, this study also established a new drug delivery strategy by successfully loading Berberine (Ber)—a natural compound with well-documented anti-inflammatory and neuroprotective effects—onto ApoEVs. The combination further enhanced their protective effects on RGCs, with synergistic suppression of inflammation and improved neuronal viability. Mechanistically, this enhancement was mediated through the coordinated inhibition of the MAPK signaling pathway via Irgm1, which is identified here for the first time as a potential therapeutic target in glaucoma. Collectively, our findings highlight the dual function of Berberine-loaded ApoEVs as a potent cell-free therapeutic strategy that integrates targeted anti-inflammatory and neuroprotective effects, offering a promising new avenue for the treatment of glaucomatous neurodegeneration. Graphical abstract

The human body is an intricate system, where diverse and complex signaling among different organs sustains physiological activities. The eye, as a primary organ for information acquisition, not only plays a crucial role in visual perception but also, as increasing evidence suggests, exerts a broad influence on the entire body through complex circuits upon receiving light signals which is called non-image-forming vision. However, the extent and mechanisms of light's impact on the body through the eyes remain insufficiently explored. There is also a dearth of comprehensive reviews elucidating the intricate interplay between light, the eye, and the systemic connections to the entire body. Herein, we propose the concept of the light-eye-body axis to systematically encapsulate the extensive non-image-forming effects of light signals received by the retina on the entire body. We reviewed the visual-neural structure basis of the light-eye-body axis, summarized the mechanism by which the eyes regulate the whole body and the current research status and challenges within the physiological and pathological processes involved in the light-eye-body axis. Future research should aim to expand the influence of the light-eye-body axis and explore its deeper mechanisms. Understanding and investigating the light-eye-body axis will contribute to improving lighting conditions to optimize health and guide the establishment of phototherapy standards in clinical practice.

Immune checkpoint molecules are promising anticancer targets, among which therapeutic antibodies targeting the PD-1/PD-L1 pathway have been widely applied to cancer treatment in clinical practice and have great potential. However, this treatment is greatly limited by its low response rates in certain cancers, lack of known biomarkers, immune-related toxicity, innate and acquired drug resistance, etc. Overcoming these limitations would significantly expand the anticancer applications of PD-1/PD-L1 blockade and improve the response rate and survival time of cancer patients. In the present review, we first illustrate the biological mechanisms of the PD-1/PD-L1 immune checkpoints and their role in the healthy immune system as well as in the tumor microenvironment (TME). The PD-1/PD-L1 pathway inhibits the anticancer effect of T cells in the TME, which in turn regulates the expression levels of PD-1 and PD-L1 through multiple mechanisms. Several strategies have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including combination therapy with other standard treatments, such as chemotherapy, radiotherapy, targeted therapy, anti-angiogenic therapy, other immunotherapies and even diet control. Downregulation of PD-L1 expression in the TME via pharmacological or gene regulation methods improves the efficacy of anti-PD-1/PD-L1 treatment. Surprisingly, recent preclinical studies have shown that upregulation of PD-L1 in the TME also improves the response and efficacy of immune checkpoint blockade. Immunotherapy is a promising anticancer strategy that provides novel insight into clinical applications. This review aims to guide the development of more effective and less toxic anti-PD-1/PD-L1 immunotherapies.

Lead halide perovskites have exhibited excellent performance in solar cells, LEDs and detectors. Thermal properties of perovskites, such as heat capacity and thermal conductivity, have rarely been studied and corresponding devices have barely been explored. Considering the high absorption coefficient (10 4 ~10 5  cm −1 ), low specific heat capacity (296–326 J kg −1 K −1 ) and small thermal diffusion coefficient (0.145 mm 2 s −1 ), herein we showcase the successful use of perovskite in optoacoustic transducers. The theoretically calculated phonon spectrum shows that the overlap of optical phonons and acoustic phonons leads to the up-conversion of acoustic phonons, and thus results in experimentally measured low thermal diffusion coefficient. The assembled device of PDMS/MAPbI 3 /PDMS simultaneously achieves broad bandwidths (−6 dB bandwidth: 40.8 MHz; central frequency: 29.2 MHz), and high conversion efficiency (2.97 × 10 −2 ), while all these parameters are the record values for optoacoustic transducers. We also fabricate miniatured devices by assembling perovskite film onto fibers, and clearly resolve the fine structure of fisheyes, which demonstrates the strong competitiveness of perovskite based optoacoustic transducers for ultrasound imaging. Lead halide perovskites are widely used e.g. in solar cells and LEDs, but devices based on thermal properties have received little attention. Here, the authors take advantage of the thermal properties to fabricate an optoacoustic transducer with both broad bandwidth and high conversion efficiency.

PurposeThe significance of physician-user interaction has been widely acknowledged in offline and online healthcare consultation. However, limited attempts have been made to explore the influence of physician-user interaction on users' perceived service quality (PSQ) in the mobile context. Based on the literature on physician-user interaction and media synchronicity theory, this study proposes a theoretical model where the interactive factors common across the offline, online and mobile context, i.e. physicians' informational support and emotional support, the interactive factors unique in the mobile context, i.e. physicians' response speed and voice service, and the interaction between the two categories of interactive factors predict users' PSQ in mobile consultation.Design/methodology/approachThis study collects consultation records between 25,225 users and 738 physicians from a leading Chinese mobile consultation application, and employs linear regression to verify the proposed theoretical model.FindingsPhysicians' informational, emotional support, response speed and voice service are found to have significant positive impacts on users' PSQ. Besides, physicians' response speed strengthens the positive impacts of physicians' informational and emotional support on users' PSQ, while physicians' voice service weakens the positive link between physicians' informational support on users' PSQ.Originality/valueThis study contributes to the antecedents for users' PSQ in mobile consultation by identifying unique interactive factors in the mobile context, and highlighting the individual and interaction effects of different physician-user interactive factors. Besides, this study employs novel methods, which leverages text classification and text pattern recognition to more accurately depict physicians' online behaviors based on objective communication records.

This research, which considers the rapid growth of urbanization and the concerns about energy security, analyzes the effect of urbanization on energy intensity by using the panel data of 72 countries between 2000 and 2014. The impact of institutional quality on the relationship between urbanization and energy intensity is also evaluated on the basis of a panel threshold model. Results suggest that the increase in urbanization leads to higher energy intensity. However, this positive effect of urbanization on energy intensity can be weakened by 0.033 when the institutional quality exceeds the threshold value. The positive mediating effect of institutional quality comprises approximately 31.37% of the total effect. Furthermore, the institutional threshold effect varies across country income and energy types, and it promotes more energy reduction and less energy consumption in OECD and non-OECD groups, respectively. The institutional threshold effect is only significant for fossil energy group but not for the renewable energy group.

This paper investigates the tracking consensus of nonlinear multi-agent systems under undirected topology, considering asynchronous switching caused by delays between communication topology switching and controller switching. First, by using the properties of undirected topology graphs, the controller design process is simplified. Then, to address asynchronous delays during topology switching, the system operation is divided into synchronized and delayed modes based on the status of the controller and topology. Every operating mode has a corresponding control strategy. To alleviate the burden of communication and computation, an event-triggered mechanism (ETM) is introduced to reduce the number of controller updates. By constructing an augmented Lyapunov function that incorporates both matching and mismatching periods, sufficient conditions ensuring system stability are established. The required controller based on the dynamic ETM is obtained by solving Linear Matrix Inequalities (LMIs). Finally, a simulation example is conducted to verify its effectiveness.

SARS-CoV-2 vaccination has been launched worldwide to build effective population-level immunity to curb the spread of this virus. The effectiveness and duration of protective immunity is a critical factor for public health. Here, we report the kinetics of the SARS-CoV-2 specific immune response in 204 individuals up to 1-year after recovery from COVID-19. RBD-IgG and full-length spike-IgG concentrations and serum neutralizing capacity decreases during the first 6-months, but is maintained stably up to 1-year after hospital discharge. Even individuals who had generated high IgG levels during early convalescent stages had IgG levels that had decreased to a similar level one year later. Notably, the RBD-IgG level positively correlates with serum neutralizing capacity, suggesting the representative role of RBD-IgG in predicting serum protection. Moreover, viral-specific cellular immune protection, including spike and nucleoprotein specific, persisted between 6 months and 12 months. Altogether, our study supports the persistence of viral-specific protective immunity over 1 year. The quality of immune response to SARS-CoV-2 is thought to wane over time, but it is unclear how long it can persist. Here the authors show persistent immune responses in a large number of patients over the course of a 1-year follow-up from the time of recovery from COVID-19.