Financial Data and Key Metrics Changes - Revenue for Q3 2025 was $552,000, impacted by capital sales headwinds in the market [4][16] - Gross profit was $194,000, with a gross margin of 35% [16] - For the nine months ended September 30, 2025, revenue was $2.0 million, and gross profit was $1.0 million, with a gross margin of 52% [16][18] - Total operating expenses for Q3 2025 were $40 million, compared to $28.5 million in Q3 2024 [18] - Adjusted operating expenses for Q3 2025 were $21.4 million, down from $26.0 million in Q3 2024 [18] Business Line Data and Key Metrics Changes - The company launched an expanded set of instrument acquisition options, resulting in 12 new customers implementing the platform [5] - More than half of the new customers are in academic labs, a segment previously difficult to access due to NIH funding challenges [5] Market Data and Key Metrics Changes - The company experienced year-over-year revenue impacts due to capital market headwinds and NIH funding uncertainties [17] - The placements program has allowed access to key academic centers, with over half of placements going into academic labs [34] Company Strategy and Development Direction - The company aims to accelerate commercial adoption, deliver on its innovation roadmap, and preserve financial strength [4] - The Proteus platform is a key focus, with successful sequencing runs completed on prototype systems [9] - The company is exploring partnership opportunities to enhance development activities and expand market participation [8] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about early traction with the placement program despite ongoing capital market challenges [13] - The company anticipates modest improvement in Q4 2025, but not a significant upswing compared to historical trends [40] - There is uncertainty regarding NIH funding due to the government shutdown, but proposals indicate a potential retention of funding levels [41][42] Other Important Information - The company has a strong balance sheet with $230.5 million in cash and investments as of September 30, 2025 [20] - A Form S-3 shelf registration statement for $300 million was filed to support business initiatives [22] - Management and board collectively hold approximately 18% of the total outstanding stock, indicating strong investment in the company's success [24] Q&A Session Summary Question: Updates on the investor day and Proteus sequencer development - The investor day on November 19 will provide updates on Proteus, including early sequencing data and key milestones for 2026 [28][29] Question: Involvement in DARPA's PRESS program - The company is aware of the PRESS program but does not align perfectly with its microsystem strategy [31] Question: Breakdown of placements by market segment - More than half of the placements went into academic labs, with the remainder split between pharma, biotech, and agricultural testing [34] Question: Seasonal trends from Q3 to Q4 - A modest improvement is expected in Q4 2025, but not as significant as in typical years due to various challenges [40] Question: Key hurdles to market launch of Proteus - Key hurdles include scaling from prototypes to fully integrated systems and optimizing the platform for manufacturing [44][46]

Core Viewpoint - The article discusses a groundbreaking study on protein restriction (PR) and its potential anti-aging effects, highlighting the importance of dietary interventions in extending lifespan and improving health [1][2][12]. Group 1: Research Findings - The study systematically mapped the proteomic landscape of aging across 41 organs/tissues in male mice, revealing significant protein expression heterogeneity during aging [4]. - Protein restriction was found to significantly alleviate age-related protein expression abnormalities in various tissues [6]. - The research indicated that protein restriction reduces age-related DNA methylation accumulation and reverses abnormal protein phosphorylation patterns in aging tissues [6]. Group 2: Health Implications - The study confirmed that protein restriction has cross-species cardiovascular protective effects, supported by analyses of plasma samples from both mice and humans [7]. - It was noted that lower protein intake is associated with enhanced cardiovascular health and reduced inflammation risk in humans [11]. Group 3: Timing and Gender Differences - The effects of protein restriction vary by gender and timing, with middle age identified as the optimal period for dietary intervention [8][11].

Summary of the Conference Call for 诺禾致源 (Nuohe Zhiyuan) Company Overview - **Company**: 诺禾致源 (Nuohe Zhiyuan) - **Period**: January to September 2025 Key Financial Metrics - **Total Revenue**: 15.81 billion CNY, up 4.05% year-on-year [2][3] - **Q3 Revenue**: 5.41 billion CNY, up 3.47% year-on-year [3] - **Overseas Revenue**: 7.92 billion CNY, up 4.1% year-on-year, accounting for 50.09% of total revenue [2][3] - **Q3 Overseas Revenue**: 2.58 billion CNY, down 0.48% year-on-year [3] - **Domestic Revenue**: 7.89 billion CNY, up 4% year-on-year [2] - **Q3 Domestic Revenue**: 2.82 billion CNY, up 7.37% year-on-year, and up 8.61% quarter-on-quarter [5] - **Gross Margin**: 41.9%, down 0.7 percentage points year-on-year [10] - **Net Profit**: 1.16 billion CNY, down 10.17% year-on-year, with a net profit margin of 7.31% [11] - **R&D Investment**: 56.1 million CNY in Q3, focusing on emerging fields [12] Revenue Breakdown by Market - **Americas**: Q3 revenue down 12% due to changes in research funding and policy impacts [4] - **EMEA**: Q3 revenue down 12%, affected by project completion and funding transitions [4] - **Europe**: Q3 revenue up 19%, indicating strong performance [4] - **Customer Segmentation**: 70% of revenue from universities and research institutions, 30% from hospitals and enterprises [6] Product and Service Performance - **Life Sciences Research Services**: Revenue of 5.52 billion CNY, up 6.21% year-on-year [7] - **Monitoring and Sequencing Platform Services**: Revenue of 7.7 billion CNY, up 3.23% year-on-year, but Q3 revenue down 3.42% [7] - **Emerging Business Contributions**: Approximately 32% of total revenue, up 4 percentage points year-on-year, with a growth of about 20% [8] R&D and Innovation - **R&D Focus Areas**: Single-cell genomics, spatial genomics, proteomics, metabolomics, epigenetics, and long-read sequencing [12][18] - **AI Integration**: Progress in AI applications, particularly in omics data analysis and virtual cell modeling [20][28] Market Challenges and Strategies - **Domestic Market Competition**: Increased competition leading to a 30% price drop; company aims to reduce competition through mergers and acquisitions [16][23] - **Geopolitical Impact**: U.S. market affected by geopolitical tensions, but the company maintains strong relationships in key regions [21] - **Cash Flow Management**: Operating cash flow was negative 87 million CNY for the first nine months, but turned positive in Q3 at 77 million CNY [14] Future Outlook - **Expansion Plans**: Continued investment in overseas markets, including new laboratories in Singapore and Europe [30] - **Focus on NGS and AI**: Anticipated growth in NGS applications and AI integration to enhance research capabilities [24][28] Additional Insights - **Customer Base Growth**: Stable customer structure with a slight increase in contributions from universities and research institutions [6] - **Cash Flow Volatility**: Short-term fluctuations in cash flow due to proactive risk management strategies [14] - **Regulatory Environment**: Ongoing adjustments to align with changing policies in the domestic and international markets [26][27]

Core Insights - The π-HuB Park industrial park has been established in Guangzhou as a key component of the international scientific initiative π-HuB, marking a new phase of industrial collaboration and ecological development in the field of proteomics [1][4][9] - The π-HuB initiative aims to create a comprehensive "real-time panorama" of the proteome, facilitating advancements in biomedicine, clinical diagnostics, and agricultural biotechnology [2][3] - The establishment of the industrial park is expected to enhance Guangzhou's competitiveness in the global biomedicine sector and help capture opportunities in the trillion-dollar precision medicine market [9][10] Industry Overview - The global proteomics market is projected to grow at a compound annual growth rate (CAGR) of 12.4% from 2024 to 2029, indicating significant investment and interest from major international players [3] - The π-HuB initiative has garnered support from over 114 top scientific teams across more than 20 countries and regions, highlighting its international collaboration and significance [2] Strategic Collaborations - The industrial park has formed strategic partnerships with leading companies such as Danaher, Thermo Fisher Scientific, and Dary Biotech, which will facilitate the development and commercialization of innovative technologies and products [1][9] - π-HuB will collaborate with Danaher to establish a joint innovation center aimed at nurturing and investing in high-potential early-stage projects [8] Regional Advantages - Guangzhou's strong medical and industrial foundation, including over 7,000 healthcare institutions and nearly 7,000 biopharmaceutical companies, positions it as a key player in the proteomics field [6] - The local government is providing comprehensive support in terms of platform development, talent acquisition, clinical resources, and financial backing to facilitate the growth of the π-HuB initiative [6] Future Prospects - The establishment of the π-HuB Park is expected to attract more scientists and entrepreneurs to Guangzhou, fostering the growth of leading companies in the proteomics industry and transforming technological advantages into industrial strengths [10]

Core Insights - The proteomics research service industry in China is experiencing significant growth, with the market size projected to increase from 437 million yuan in 2019 to 1.822 billion yuan in 2024, and expected to reach 2.26 billion yuan by 2025, indicating a robust expansion trend [1][4][12] Industry Definition and Process - Proteomics is a biological science that studies the composition and changes of proteins in cells, tissues, or organisms. The main processes of proteomics analysis include protein extraction and purification, enzymatic digestion into smaller peptides, identification and quantification using mass spectrometry, and bioinformatics analysis [2][4] Industry Development Status - The application potential of proteomics technology spans basic scientific research, clinical translation, clinical diagnosis, and new drug development. The rapid growth in national investment in life sciences, basic medicine, and agricultural sciences has led to an increase in the types of technologies, customer types, and the number of customers in the proteomics research service sector [4][12] Industry Value Chain - The proteomics market has developed a complete value chain that includes upstream suppliers of mass spectrometry instruments and reagents, midstream proteomics service companies, and downstream end customers such as research institutions, universities, and hospitals [6][12] Competitive Landscape - The market share in China's proteomics research service industry is relatively concentrated, with the top five companies (CR5) holding 58.8% of the market. The leading companies include Jingjie Biotechnology, Zhongke New Life, BGI, Novogene, and Ouyi Biomedical, with respective market shares of 25.0%, 13.9%, 11.2%, 5.1%, and 3.6% [7][8] Key Companies - BGI focuses on providing research services and precision medicine solutions through multi-omics big data technologies, including gene testing and mass spectrometry analysis. Their DIA protein quantification analysis employs data-independent acquisition methods [8][10] - Jingjie Biotechnology specializes in proteomics technology services and antibody reagent products, serving clients in life sciences research, drug development, and clinical diagnostics. In 2022, they reported 836 clients and revenue of 195 million yuan [10][11] Industry Development Trends - The proteomics research service sector is expected to continue its rapid growth, driven by advancements in mass spectrometry and bioinformatics. The market is still in a relatively early stage compared to Europe and the US, with increasing applications in life sciences and medicine [12] - The trend in proteomics analysis is moving towards requiring less sample volume and achieving faster identification of a greater variety of proteins, with high-depth, high-throughput, and high-sensitivity analyses being key goals [12]

Core Insights - The article discusses T cell exhaustion as a critical mechanism in cancer immunotherapy resistance, highlighting the role of a specific stress response called Tex-PSR [3][4][10] Group 1: T Cell Exhaustion Mechanism - T cell exhaustion (Tex) is characterized by reduced effector function and increased expression of inhibitory receptors, driven by persistent antigen exposure and adverse microenvironments [3] - The study identifies a unique stress response, Tex-PSR, which is triggered by the accumulation of misfolded proteins, leading to T cell exhaustion and immune evasion [4][9] Group 2: Research Findings - The research provides a comprehensive protein landscape of Tex cells under various conditions, revealing inconsistencies between mRNA transcription levels and protein expression [7][8] - Tex-PSR is marked by increased global protein synthesis, unlike the classical unfolded protein response (UPR), which typically inhibits protein synthesis [8][13] Group 3: Clinical Implications - The findings suggest that targeting the Tex-PSR pathway could represent a new direction for cancer immunotherapy, potentially improving T cell vitality and reversing exhaustion [10][12] - The study indicates that the Tex-PSR characteristics are also present in exhausted T cells from human cancer patients, correlating with poor clinical responses to immunotherapy [9][10]

Core Viewpoint - The research highlights that Alzheimer's disease (AD) is not solely characterized by the accumulation of amyloid-beta (Aβ) plaques and tau tangles, but also involves a disruption in communication between neurons and glial cells, particularly astrocytes and microglia, which is crucial for disease progression [2][3][5]. Group 1: Research Findings - The study published in Cell provides a comprehensive view of how brain cells interact in Alzheimer's patients, revealing that the disruption of information exchange between neurons and glial cells is closely related to the development of AD [3][5]. - A protein named AHNAK has been identified as a key driver protein in the disrupted protein networks associated with Alzheimer's disease, suggesting a new avenue for innovative treatment strategies [3][9]. - The research team conducted deep proteomic analysis on the parahippocampal gyrus (PHG) of 198 deceased Alzheimer's patients, mild cognitive impairment (MCI) patients, and normal controls to understand molecular dysregulation in AD [6][7]. Group 2: Key Protein Networks - The analysis revealed over 300 key driver proteins (KDPs) that play significant roles in triggering or accelerating Alzheimer's disease, with AHNAK being one of the most prominent proteins found in astrocytes [8][11]. - The study indicates that in Alzheimer's disease, the balance between neurons and glial cells is disrupted, leading to hyperactivity of glial cells and diminished neuronal function, which correlates with increased inflammation [8][11]. - Different biological factors, such as sex and genetic background, can influence the expression of these protein networks, with carriers of the APOE4 gene showing distinct patterns of protein network disruption compared to non-carriers [11].

Core Insights - The article discusses the research on IDH-mutant astrocytoma, highlighting its aggressive nature and poor prognosis despite advancements in molecular diagnostics [2][9] - A new classification system based on protein profiling has been developed, identifying four molecular subtypes of IDH-mutant astrocytoma, with a focus on the immune-hot subtype (IME) that is associated with worse outcomes [3][10] Molecular Subtypes - The study defines four molecular subtypes of IDH-mutant astrocytoma: AFM, PPR, IME, and NEU, with IME being characterized by significant immune infiltration and poor prognosis [3][7] - The IME subtype accounts for approximately 13% of IDH-mutant astrocytomas and shows a tendency to evolve during tumor recurrence [7][10] Prognostic Factors - The research indicates that the presence of CDKN2A/B gene homozygous deletions is a diagnostic criterion for WHO grade 4 IDH-mutant astrocytoma, while MYC gene amplification suggests aggressive tumor progression [5][10] - The study emphasizes the importance of protein-based classification in predicting survival outcomes and treatment responses, which is more effective than transcriptomic approaches [6][10] AI Diagnostic Tool - An AI-driven diagnostic tool named GUIDE has been developed, which integrates multimodal data including histopathological images, transcriptomics, proteomics, and DNA methylation data for accurate patient stratification [8][10] - This tool supports both single-modal and multi-modal inputs, enhancing the precision of patient classification [8][10]

Core Viewpoint - The study presents a novel method for real-time diagnosis of cholangiocarcinoma (CCA) by combining optical fiber biosensors based on bile clusterin with digestive endoscopy, addressing the urgent need for improved diagnostic techniques for this aggressive cancer type [2][10]. Summary by Sections Diagnosis Challenges - Cholangiocarcinoma is a highly malignant tumor with a poor prognosis, characterized by late diagnosis due to non-specific early symptoms, resulting in a 5-year survival rate of only 7%-20% [2]. Research Findings - The research team identified clusterin (CLU) as a promising biomarker for CCA through proteomic analysis of bile and cell supernatants, highlighting its overexpression in various cancers [5]. - The optical fiber biosensor technology, particularly surface plasmon resonance (SPR), was utilized for its high sensitivity and stability in detecting biological markers [5]. Methodology - The study involved 583 subjects and two rounds of proteomic analysis to screen and validate biomarkers for CCA, leading to the development of an SPR-based optical fiber biosensor [6]. - The biosensor demonstrated a high correlation coefficient of 0.989 and could accurately detect varying concentrations of CLU, with a detection time of 2 seconds and an area under the curve (AUC) of 0.854 [7]. Clinical Application - The CLU optical fiber biosensor was successfully integrated with digestive endoscopy, allowing for real-time in vivo diagnosis of CCA, with results aligning with postoperative pathology findings in patients [8][10].

Core Viewpoint - The article highlights the advancements in proteomics, emphasizing the technological innovations and research developments that have significantly impacted the field over the past three decades [2][3]. Group 1: Technological Breakthroughs - Key innovations include new methods for ligand-target protein identification (PELSA), peptide preparation techniques (OPPRAD), and advancements in high-throughput sequencing platforms like DEEP-SEQ [3]. - The integration of cutting-edge technologies such as spatial proteomics and single-cell proteomics is also noted, showcasing the evolution of proteomics methodologies [3]. Group 2: Research Progress - The article discusses the latest developments in proteomics related to precision medicine, spatial proteomics, and post-translational modification proteomics [3]. - It mentions the participation of experts from prestigious institutions like Shanghai Jiao Tong University and Fudan University, who will share their latest research findings [3]. Group 3: Event Details - The "Seventh Proteomics New Technologies and Methods" online seminar is scheduled for August 28, 2025, organized by Instrument Information Network [5]. - The agenda includes various presentations from leading researchers and industry experts, covering topics such as automated high-throughput quality control in proteomics and the application of advanced mass spectrometry techniques [6].