撰文丨王聪 编辑丨王多鱼 排版丨水成文 T 细胞耗竭 （ T cell exhaustion ） 是一种功能减退状态，其特征为效应功能减弱以及抑制性受体表达增 加，这种状态由持续的抗原暴露和不利的微环境所导致。在癌症中观察到耗竭 T 细胞 （Tex） 无法清除恶 性细胞，这也是癌症患者对免疫疗法产生抗性的关键机制。 尽管 转录组学 分析为 T 细胞耗竭 （Tex） 细胞生物学提供了见解，但在不同生物体中，mRNA 丰度并不 总是蛋白质表达水平的可靠替代指标。之前的研究表明，无论功能状态如何，T 细胞中 mRNA 与蛋白质的 相关性都很差，并且转录后调控在 T 细胞分化和功能中具有重要意义。在此背景下，绘制 Tex 细胞的高分 辨率蛋白质组图谱将很有价值。 该耗竭程序产生异质性的 Tex 细胞群，其中 祖细胞耗竭 T 细胞 （Tprog） 细胞保留了干性和自我更新能 力，能够对免疫检查点阻断 （ICB） 疗法作出响应，并分化为具有细胞溶解能力的 中间耗竭 T 细胞 （Tint） 。相反， 终末耗竭 T 细胞 （Ttex） 细胞会随着时间的推移而累积，并且对免疫检查点阻断疗法 响应不佳。 此外，T 细胞耗竭还限制 ...

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].

撰文丨王聪 编辑丨王多鱼 排版丨水成文 异柠檬酸脱氢酶 （IDH） 突变型星形细胞瘤 是一种侵袭性强、具有可塑性的脑肿瘤，是 成人 弥漫性胶质瘤 的三种分子亚型之一，患者在接受标准治疗后几乎不 可避免地会出现复发。尽管分子诊断改善了患者的管理，但 IDH 突变型星形细胞瘤仍然致命，其治疗结局因肿瘤异质性和复杂的潜在分子机制而存在差异。 2025 年 9 月 11 日 ， 香港科技大学 王吉光 教授团队 与首都医科大学北京天坛医院 /北京神经外科研究所 江涛 院士团队合作，在 Cancer Cell 期刊发表了题 为： Protein-based classification reveals an immune-hot subtype in IDH-mutant astrocytoma with worse prognosi s 的研究论文。 该研究利用时空多组学数据，定义了 IDH 突变型星形细胞瘤的四种 分子亚型—— AFM、PPR 、 IME 和 NEU ，其中 IME 亚型属于预后不良的免疫热亚型，具 有丰富 的 肥胖细胞样分化 和淋巴细胞浸润的特征，该研究还开发了一款 AI 诊断工具—— GUIDE ...

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].

Summary of SEER (SEER) FY Conference Call - August 13, 2025 Company Overview - SEER has been public since December 2020 and focuses on enabling access to proteomic content at unprecedented scale, speed, and cost [2][3] - The company offers the Proteograph product suite, which includes an instrument, consumable kits, and software for analysis [5] Core Product Developments - The initial version of the Proteograph could process 16 samples in eight hours, while the Protograph XT increased capacity to 40 samples in the same timeframe, reducing mass spectrometry time by 150% [6] - The latest product, Protograph One, launched in June 2025, allows for large population-scale proteomics, with a 10,000-sample study announced in Q1 and a 20,000-sample study in Q2 [7][8] Market Potential and Predictions - The CEO predicts that 2025 will be a pivotal year for population-scale proteomics, with expectations for a 100,000-sample study by 2026 [8] - The proteomic market is expected to expand significantly as access to the proteome becomes more feasible, similar to the genomic market's evolution [10][11] Challenges and Innovations - Historical bottlenecks in proteomics included the scalability of mass spectrometry and the complexity of the proteome, which SEER aims to address with its technology [13][14] - SEER has invested heavily in data analysis capabilities to overcome data bottlenecks created by increased sample sizes [16] Competitive Landscape - SEER's unique approach allows for unbiased proteomic analysis, which is expected to create new markets and expand existing ones [11][20] - The company holds over 250 patents, indicating a strong position in the proteomics field despite emerging competitors [31] Revenue Model and Financial Outlook - SEER's revenue is currently derived from consumables (65%), the SEER Technology Access Center (25%), and instruments (10-15%) [40] - The company has approximately $260 million in cash with no debt, projecting a burn rate that allows for 6-7 years of operation without needing additional capital [52][53] - A stock buyback program has been initiated, reflecting confidence in the company's value proposition [53] Customer Engagement and Market Strategy - SEER aims to be a tools provider rather than a service business, focusing on partnerships with customers and CROs [33][41] - The SEER Technology Access Center and Strategic Instrument Placement programs have been crucial in driving customer engagement and facilitating data generation [37][39] Future Expectations - The academic and government sectors are expected to remain significant revenue sources, with biopharma showing potential for growth as customers recognize the value of SEER's offerings [46][48] - The company anticipates continued innovation and investment in its product line to maintain a competitive edge in the proteomics market [54][55]

Financial Data and Key Metrics Changes - Total revenue for Q2 2025 was $24.5 million, down 29% year over year due to temporary funding pauses and uncertainty in the U.S. academic and pharmaceutical end markets [15][16] - Gross profit was $11.3 million with a gross margin of 46.2%, while non-GAAP gross profit was $10.2 million with a non-GAAP gross margin of 41.8% [17][18] - Operating expenses increased to $48.4 million, up $15.2 million year over year, including significant costs related to acquisition and restructuring [19] - Adjusted EBITDA was a loss of $13.7 million compared to a loss of $4.1 million in the same quarter of the previous year [19] Business Line Data and Key Metrics Changes - Consumable revenue was $14.9 million, while instrument revenue was $2 million, with 10 instruments placed in the quarter compared to 22 in the previous year [16] - Accelerator lab revenue was $4 million, down 60%, driven by a decline in large multimillion-dollar projects from pharmaceutical customers [16] - Sales to diagnostics partners totaled $2.6 million, up from $0.7 million in the prior year period [16] Market Data and Key Metrics Changes - The customer mix was evenly split between pharma and academia, with academic sales declining 18% and pharma sales declining 38% [16] - The combined company expects to report $130 million to $135 million of revenue for 2025, with Simoa revenue expected to be $100 million to $105 million [21][22] Company Strategy and Development Direction - The company completed the transformative Equaya acquisition and is focused on sustainable double-digit revenue growth and margin improvement [6][7] - The strategic priorities include expanding the addressable market, accelerating the Simoa platform rollout, and building a foundation for an Alzheimer's diagnostic franchise [10][11][13] - The company aims to achieve approximately $85 million in synergy savings and cost reductions by 2026, with 75% of these expense reductions already implemented [7][23] Management's Comments on Operating Environment and Future Outlook - Management acknowledged temporary headwinds in academic funding and biopharma spending but expressed confidence in the long-term growth potential of proteomics [6][9] - The company is committed to achieving cash flow breakeven in 2026, even amidst challenging market conditions, and has already exceeded synergy expectations [24][25] Other Important Information - The company ended the quarter with $263.8 million in cash and equivalents, with adjusted cash usage improving by 49% year over year [20] - Akoya generated $18.2 million in Q2, contributing to the combined company's revenue outlook [21] Q&A Session Summary Question: Insights on Accelerator business and clinical trials - The Accelerator business grew approximately 40% year on year, with a net increase in customers, although project sizes are smaller than last year [29][30] Question: Academic funding outlook and customer confidence - There is strong resiliency in the consumables franchise, with approximately $100 million in consumables revenue, indicating potential positivity in academic funding [31][32] Question: Cost actions and long-term growth - The integration has focused on operating as one company, realizing significant synergies in operations and maintaining a focus on customer service while addressing cost structures [35][36]

Core Insights - The global neurodegenerative disease proteomics alliance (GNPC) has revealed biomarkers related to aging and neurodegenerative diseases, providing new insights into the biology of major neurodegenerative diseases like Alzheimer's and Parkinson's [1][2] - The research published in the journals Nature Medicine and Nature Aging highlights unique protein biomarkers that could lead to early detection and improved outcomes for neurodegenerative diseases [1][3] Group 1: Research Findings - The GNPC's flagship paper analyzed one of the world's largest proteomic datasets, comprising approximately 250 million unique protein measurements from 35,000 biological fluid samples, including plasma and cerebrospinal fluid [2] - The study identified specific proteins associated with Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis [2][3] - The research established disease-specific plasma biomarker profiles and identified common protein features among Alzheimer's, Parkinson's, and frontotemporal dementia [3] Group 2: Implications for Diagnosis and Treatment - The authors identified a cerebrospinal fluid and plasma protein feature associated with the APOEε4 allele, known to increase Alzheimer's disease risk, suggesting broader implications for other neurodegenerative diseases [3] - The study also revealed age-related changes in cognition-related proteins, providing new insights into how protein level changes in cerebrospinal fluid and plasma relate to cognitive health [3] - The importance of international collaboration, data sharing, and diverse datasets is emphasized for accelerating discoveries in neurodegenerative research, with future studies aimed at developing new diagnostic, preventive, and therapeutic approaches [3]

Core Insights - Illumina announced the acquisition of SomaLogic for $350 million in cash, aimed at enhancing its position in the growing proteomics market and accelerating its multi-omics strategy for 2024 [1][3] - The acquisition is based on a prior collaboration established in December 2021, focusing on integrating SomaLogic's protein detection technology into Illumina's NGS platform [3][4] - The global proteomics market is projected to grow from $33.6 billion in 2024 to $60.5 billion by 2029, with a compound annual growth rate (CAGR) of 12.4% [9] Company Strategy - Illumina's CEO stated that the acquisition will enhance the value of the NovaSeq X product and unlock greater potential for future advancements [3] - The integration of SomaLogic's technology with Illumina's scalable NGS platform and analysis software is expected to accelerate technological development in proteomics and reduce research time and costs [3] - The company aims to complete the acquisition by mid-2026, pending regulatory approvals, while both companies will continue to operate independently until then [4] Market Context - Illumina holds over 80% of the global gene sequencing market but has faced revenue declines and significant losses, particularly a projected loss of $1.223 billion in 2024 [6] - The company has been impacted by being placed on the "unreliable entity list" in China, affecting its business in the Greater China region [6] - The competitive landscape is intensifying, with rivals like Roche Diagnostics and BGI encroaching on Illumina's market share [6] Industry Trends - The proteomics field is seen as a critical area for future diagnostics and drug development, with the potential to discover new biomarkers and therapeutic targets [7] - Recent acquisitions in the proteomics space, such as Thermo Fisher's $3.1 billion purchase of Olink Holding AB, indicate a growing interest and investment in this sector [10] - Illumina's acquisition of SomaLogic is expected to strengthen its capabilities in the high-growth proteomics market, with profitability anticipated by 2027 [10]

Core Viewpoint - The article addresses misleading perceptions in the capital market regarding hyaluronic acid and recombinant collagen, emphasizing the need to correct these misconceptions to avoid resource misallocation and risks for companies like Huaxi Bio [1][2]. Industry Perspective - Recombinant collagen is a small branch of collagen research and industrial transformation, with the main advancements still held by life science research institutions and pharmaceutical companies [1]. - In 2024, China's hyaluronic acid exports reached 161 tons, with 11.8 tons being high-end pharmaceutical-grade, while recombinant collagen exports were less than 0.02 tons, indicating a lack of market support for the notion that recombinant collagen is replacing hyaluronic acid [2][3]. - The growth rate for hyaluronic acid in the domestic and international markets is over 10%, with Huaxi Bio's pharmaceutical-grade hyaluronic acid showing over 20% growth, contradicting claims of market pressure [3]. Company Performance - Huaxi Bio's performance decline is attributed to a drop in consumer goods business and one-time asset impairment losses, rather than competition from recombinant collagen [3]. - The company maintains a high profit margin of around 50% across its active ingredient and medical terminal businesses, with significant revenue contributions from hyaluronic acid [3]. Market Dynamics - Recent successful companies in the skincare sector are not solely due to the rise of recombinant collagen but are also driven by strong e-commerce capabilities and complex formulations [4]. - The article highlights the misuse of the term "recombinant collagen" by some companies, which may mislead consumers and investors, emphasizing the need for a credible market environment [5][8]. Regulatory and Scientific Standards - There is a lack of detection standards for recombinant collagen, leading to the misuse of the term and potential consumer deception [8]. - The company advocates for a collaborative approach among professionals, testing institutions, and media to enhance understanding and improve the industry ecosystem [7][9].