Core Viewpoint - The research highlights the development of a genetically engineered optoenergetic rhodopsin (mt-EcGAPR) that utilizes ambient light to power mitochondria, potentially alleviating retinal neurodegeneration, particularly in glaucoma [3][10]. Group 1: Mitochondrial Function and Disease - Mitochondria are essential for energy production, ion homeostasis, and cell survival, with their proton motive force playing a critical role in ATP synthesis and calcium balance [2]. - Dysregulation of mitochondrial proton motive force is linked to various pathological conditions, including neurodegenerative diseases, metabolic disorders, and aging [2]. Group 2: Research Development - The study introduces mt-EcGAPR, a mitochondrial-targeted proton pump that can harness environmental light to generate energy for mitochondria, thereby mitigating retinal neurodegeneration [3][8]. - The research demonstrates that mt-EcGAPR significantly increases ATP production and reduces reactive oxygen species (ROS) accumulation in a mouse model of glaucoma [8]. Group 3: Mechanism and Implications - Mechanistically, mt-EcGAPR protects retinal ganglion cells by inhibiting endoplasmic reticulum stress-mediated cell death pathways, ultimately improving vision in glaucoma models [8][10]. - This study positions mt-EcGAPR as a promising therapeutic strategy for glaucoma and potentially other neurodegenerative diseases associated with mitochondrial dysfunction [10].

Core Insights - The Chinese optogenetics industry has made significant progress, transitioning from a technology follower to a leader, with a market size projected at approximately 5.276 billion yuan in 2024, reflecting a year-on-year growth of 9.10% [1][11] - Domestic research teams have achieved breakthroughs in the development of photosensitive proteins, gene delivery systems, and optical equipment, enhancing the efficiency and precision of optogenetics applications [1][11] - Despite advancements, existing optogenetic tools still face limitations, such as large control modules, poor tissue penetration, off-target effects, and optical toxicity, necessitating ongoing optimization [1][11] Industry Overview - Optogenetics combines optical and genetic techniques to control cell activity by expressing light-sensitive ion channels, pumps, or enzymes in target cells [2] - The basic principle involves inserting opsin genes into target neurons, allowing them to respond to specific wavelengths of light, thereby regulating ionic flow and neuronal activity [2] Industry Development History - The Chinese optogenetics industry has evolved through three main phases: early exploration and technology foundation (2004-2010), technological breakthroughs and clinical application exploration (2011-2020), and accelerated clinical translation and industrialization (2021-present) [4] - Key milestones include the first successful retinal treatment in 2016 and the development of the REDMAP system in 2023 [4] Industry Value Chain - The upstream of the optogenetics industry includes photosensitive proteins, gene delivery systems, raw materials, hardware systems, and auxiliary technologies [6] - The midstream focuses on optogenetics technology services, product research and development, while the downstream applications span neuroscience, cross-disciplinary fields, ophthalmology, neurology, cardiac diseases, and metabolic disorders [6] Market Size - The optogenetics market in China is expected to reach approximately 5.276 billion yuan in 2024, with a growth rate of 9.10% year-on-year [11] - Technological advancements, such as the REDMAP light switch developed by East China Normal University, have contributed to this market expansion [11] Industry Trends 1. **Innovative Technological Breakthroughs**: The industry is driven by technological innovation, facilitating rapid translation from laboratory to clinical applications, exemplified by the REDMAP light switch and ZM-02 gene therapy [14][16] 2. **Policy Support and Capital Acceleration**: National policies supporting innovative drugs and dynamic adjustments to medical insurance directories are stimulating the commercialization of optogenetic therapies [16] 3. **Cross-Disciplinary Applications**: Optogenetics is expanding beyond neuroscience into fields like tumor treatment, metabolic diseases, and mental health, fostering multi-disciplinary integration [17]

Group 1 - The Nobel Prize in Physiology or Medicine will be announced on October 6, 2025, with a focus on significant discoveries in the field [2] - The article predicts five major candidates for this year's award, with GLP-1 discovery and related drug development being a prominent contender [3][4] - GLP-1 drugs, such as semaglutide, have shown effectiveness in managing diabetes, obesity, and other health conditions, marking a significant advancement in weight management [4][9] Group 2 - CAR-T cell therapy, a groundbreaking cancer treatment utilizing genetically modified T cells, has gained FDA approval for multiple therapies since 2017 [10][11] - Key figures in CAR-T research, including Carl June, Michel Sadelain, and Steven Rosenberg, are likely candidates for the Nobel Prize due to their contributions to the field [12] Group 3 - The cGAS-STING pathway, discovered by Chinese scientist Zhijian James Chen, has been recognized with multiple prestigious awards, making him a strong candidate for the Nobel Prize [14][15][20] - Chen's work elucidates how DNA triggers immune responses, which is crucial for understanding various diseases [16][18] Group 4 - Optogenetics, a technique developed by Karl Deisseroth, allows precise control of neuronal activity using light, revolutionizing neuroscience research [21][26] - Deisseroth, along with other contributors like Peter Hegemann and Gero Miesenböck, is a likely recipient of the Nobel Prize for their foundational work in this area [23][29] Group 5 - The phenomenon of phase separation in biological molecules is gaining attention, with recent awards recognizing its significance in cellular organization and function [30][32] - Key researchers in this field, including Anthony Hyman and Clifford Brangwynne, have made substantial contributions that could lead to a Nobel Prize recognition [30][34]

Core Viewpoint - The article discusses a revolutionary approach to neuromodulation using reversible photothermal-gated DNA nanochannels, which offers a universal solution for treating various neurological diseases related to ion transport disorders, such as paralysis, epilepsy, and congenital pain insensitivity [3][8]. Group 1: Current Challenges in Neuromodulation - Existing clinical treatments for neurological diseases often rely on stimulating biological ion channels, but small molecule drugs lack subtype specificity and have rapid metabolism, limiting treatment precision and effectiveness [2] - Invasive methods like intracortical stimulation (ICS) and deep brain stimulation (DBS) carry risks of infection and postoperative complications, while non-invasive methods such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) lack channel-level targeting, leading to unclear mechanisms and limited treatment scope [2] Group 2: Innovative Research Findings - The research team developed a reversible photothermal-gated DNA nanochannel (NC-JNP) that achieves nanoscale spatial resolution and second-level temporal precision for neuromodulation [5] - The system combines thermoresponsive DNA nanochannels with gold-iron oxide Janus nanoparticles, which serve as local near-infrared (NIR) photothermal converters, achieving a 98.4% cell membrane insertion efficiency [5][6] - Under 808 nm wavelength laser irradiation, the nanochannels exhibit a cyclic gate effect for ion transport, enhancing the excitability of dorsal root ganglion neurons within seconds [5][6] Group 3: Implications for Treatment - The NC-JNP strategy successfully restored pain perception in NaV 1.7 gene knockout mice after one minute of laser irradiation, demonstrating its potential for precise neuromodulation [5][6] - This innovative approach overcomes the limitations of traditional tools in achieving high spatiotemporal resolution without the need for genetic editing, providing a promising avenue for treating neurological and neuromuscular diseases [8]

Core Viewpoint - The article discusses a groundbreaking study that utilizes optogenetics to discover compounds that can selectively modulate the Integrated Stress Response (ISR), which has therapeutic potential for various diseases including viral infections, cancer, and neurodegenerative disorders [2][4]. Group 1: Research Overview - The research was published in the journal Cell by a team from the Broad Institute, led by Professor James Collins, and included Felix Wong and Maxwell Wilson [3]. - The study developed an optogenetics platform for drug discovery, enabling the identification of compounds that can selectively eliminate cells with high ISR under various stress conditions [4][14]. Group 2: Methodology and Findings - The research team utilized double-stranded RNA-dependent protein kinase R (PKR) as a key sensor for ISR activation, simulating natural activation during viral infections [7]. - A high-throughput screening of 370,830 compounds was conducted, identifying those that enhance cell death without cytotoxicity across different cell types and stressors [7][14]. - The identified compounds were shown to upregulate Activating Transcription Factor 4 (ATF4), increasing cellular sensitivity to stress and apoptosis, with GCN2 identified as a molecular target [8]. Group 3: Antiviral Activity - The compounds demonstrated broad-spectrum antiviral activity, with one compound significantly reducing viral load in a mouse model of herpes simplex virus infection [9][14]. - Structure-activity relationship and toxicology studies highlighted opportunities for optimizing therapeutic effects [9]. Group 4: Significance of the Study - The study showcases a novel optogenetics approach for drug discovery and introduces ISR enhancers with potential therapeutic applications [10].

Core Viewpoint - The study indicates that optogenetic vagal nerve stimulation (VNS) can alleviate heart failure (HF) by limiting the generation of monocyte-derived inflammatory CCRL2+ macrophages [2][3][4]. Summary by Sections Mechanism of Action - The research demonstrates that VNS reduces the proportion of CCRL2+ macrophages, which are derived from myeloid monocytes and exhibit unique tumor necrosis factor alpha (TNF-α) cytokine responses, hypertrophic, and fibrotic characteristics [4]. - The elimination of CCRL2+ macrophages can prevent cardiac remodeling and heart failure [4]. Key Findings - The study confirms a positive correlation between CCRL2+ macrophages and TNF-α responsive proteins in the human heart with cardiac remodeling and dysfunction [5]. - Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) plays a crucial role in the cardiac protective effects mediated by VNS, as it inhibits the response of CCRL2+ macrophages to TNF-α by increasing the expression of the transcription factor NRF2 [4][5]. Therapeutic Implications - Overall, the results suggest that the vagus nerve-immune axis can regulate heart failure and represents a promising therapeutic target [6].