❌

Normal view

Received — 10 September 2026 ⏭

A complement C5-targeted GalNAc-conjugated siRNA with sustained efficacy in a non-human primate model of IgA nephropathy

✇Molecular Therapy
By: Xueyan Zhang · Xue Zhang · Qiuyu Yang · Bin Kang · Mo Dan · Chunlei Li · Yan Chen · Jianhua Gan · Xiaoye Su
13 August 2026 at 08:00
This study characterizes a GalNAc-C5 small interfering RNA with potent in vitro and in vivo activity. Single subcutaneous dosing sustains long-term C5 suppression in cynomolgus monkeys with IgA nephropathy, outperforming Nefecon in blocking glomerular complement deposition, supporting its standalone or combinational clinical application.

Protein glycosylation profiling in lung adenocarcinoma and precursor lesions: analysis of FFPE tissue sections

✇Pulmonary nodule
By: Jinggang Cui · Yan Chen · Shuang Yue · Jianbo Deng · Wenqi Zhang · Shengye Wen · Lingbo Zhao · Rumeng Zhang · Shuang Yang · Junhong Jiang
27 July 2026 at 18:00

Anal Bioanal Chem. 2026 Jul 27. doi: 10.1007/s00216-026-06702-z. Online ahead of print.

ABSTRACT

Protein glycosylation is a major post-translational modification that regulates tumor initiation and progression; however, its dynamic modeling during multistep evolution of lung adenocarcinoma (LUAD) remains poorly understood, particularly in clinically archived tissues. Here, we established an integrated multi-omics workflow combining global proteomes, N-glycans, and site-specific intact N-glycopeptides to comprehensively characterize glycosylation in formalin-fixed paraffin-embedded (FFPE) specimens spanning four pathological stages of LUAD progression: inflammatory nodules (IN), atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), and invasive adenocarcinoma (IAC). Using optimized protein extraction, hydrophilic interaction liquid chromatography (HILIC)-based glycopeptide enrichment, and high-resolution LC-MS/MS, we achieved large-scale identification of proteins, N-glycans, and intact glycopeptides from archival clinical samples. Integrated analyses revealed progressive remodeling of site-specific N-glycosylation during malignant transformation, characterized by increased glycan branching, fucosylation, and sialylation during the transition from premalignant lesions to invasive cancer. Sialylated glycans reached their highest abundance in the premalignant AAH stage, whereas highly branched and fucosylated complex N-glycans predominated in invasive adenocarcinoma, indicating stage-dependent glycan remodeling throughout disease progression. Functional enrichment analyses linked these glycosylation alterations to extracellular matrix organization, neutrophil degranulation, and immune-associated pathways, while representative glycoproteins, including CEACAM6 and FGB, exhibited coordinated changes in protein abundance and site-specific glycoform micro-heterogeneity across pathological stages. Collectively, this study demonstrates the feasibility of deep glycoproteomic profiling using archived FFPE tissues and provides a comprehensive molecular atlas of glycosylation remodeling during LUAD progression. These findings establish a valuable resource for elucidating disease mechanisms and identifying stage-specific glycosylation biomarkers and potential glycan-targeted therapeutic candidates for early lung adenocarcinoma.

PMID:42509285 | DOI:10.1007/s00216-026-06702-z

Received — 27 May 2026 ⏭

AI in the Enterprise: How People Use M365 Copilot Chat

✇cs.AI, q-bio.NC updates on arXiv.org
By: Scott Counts · Yan Chen · Jing Dong · Himanshu Sharma · Andrey Zaikin · Rui Hu · Alperen Kok · Gorkem Ozer Yilmaz · Siddharth Suri · Kiran Tomlinson · Sonia Jaffe · Will Wang
26 May 2026 at 12:00
arXiv:2605.23958v1 Announce Type: cross Abstract: M365 Copilot is used every week by millions of people across more than a million companies around the world as part of their workflows. Uniquely positioned in the AI landscape given its near-exclusive use for work purposes, M365 Copilot can offer a clear picture of how people use AI for work and where that usage may expand next. This paper characterizes that usage through direct classification of user interactions with M365 Copilot Chat. Based on an anonymized and privacy-preserving analysis of a sample of approximately 5.5 million sessions, we combine a learned classification of user intent with a classification of O*NET work activities done with M365 Copilot Chat. We find that M365 Copilot is emerging as an everyday assistant for knowledge work: writing dominates, but users also rely on it for information retrieval, analysis, decision making and strategizing, and evaluating and diagnosing programs and systems, among others. Information seeking tasks remain common, but time trends suggest a relative shift away from ``chat as search'' and toward content and communication-related work. Comparisons across occupational groupings and to work done in the labor market further show that usage is broad but uneven, where the relative share of work done with M365 Copilot Chat cuts across jobs in some cases and is occupation-specific in others. Areas of relative underrepresentation in the labor market suggest the next frontier for enterprise AI adoption.

All Leaks Count, Some Count More: Interpretable Temporal Contamination Detection and Mitigation in LLM Backtesting

✇cs.AI, q-bio.NC updates on arXiv.org
By: Zeyu Zhang · Ryan Chen · Bradly C. Stadie
26 May 2026 at 12:00
arXiv:2602.17234v2 Announce Type: replace Abstract: Backtesting LLMs on resolved events assumes models reason only from pre-cutoff knowledge, yet pretrained models inevitably leak post-cutoff knowledge. We introduce a claim-level evaluation framework that decomposes prediction rationales into atomic claims and applies Shapley values to quantify each claim's decision impact, yielding \textbf{Shapley-DCLR} (\textbf{Shapley}-weighted \textbf{D}ecision-\textbf{C}ritical \textbf{L}eakage \textbf{R}ate) -- an interpretable metric measuring what fraction of decision-driving reasoning is contaminated. We further propose \textbf{TimeSPEC} (\textbf{Time}-\textbf{S}upervised \textbf{P}rediction with \textbf{E}xtracted \textbf{C}laims), an inference-time architecture that interleaves temporally-filtered retrieval with claim-level supervision, producing predictions grounded entirely in pre-cutoff evidence. Across three LLMs, the ablation experiments confirm retrieval and supervision are jointly necessary; and a three-task probe further illstrates that the performance cost of temporal enforcement scales with each task's reliance on post-cutoff information.
Received — 8 April 2026 ⏭

SoSBench: Benchmarking Safety Alignment on Six Scientific Domains

✇cs.AI, q-bio.NC updates on arXiv.org
By: Fengqing Jiang · Fengbo Ma · Zhangchen Xu · Yuetai Li · Zixin Rao · Bhaskar Ramasubramanian · Luyao Niu · Bo Li · Xianyan Chen · Zhen Xiang · Radha Poovendran
7 April 2026 at 12:00
arXiv:2505.21605v3 Announce Type: replace-cross Abstract: Large language models (LLMs) exhibit advancing capabilities in complex tasks, such as reasoning and graduate-level question answering, yet their resilience against misuse, particularly involving scientifically sophisticated risks, remains underexplored. Existing safety benchmarks typically focus either on instructions requiring minimal knowledge comprehension (e.g., ``tell me how to build a bomb") or utilize prompts that are relatively low-risk (e.g., multiple-choice or classification tasks about hazardous content). Consequently, they fail to adequately assess model safety when handling knowledge-intensive, hazardous scenarios. To address this critical gap, we introduce SoSBench, a regulation-grounded, hazard-focused benchmark encompassing six high-risk scientific domains: chemistry, biology, medicine, pharmacology, physics, and psychology. The benchmark comprises 3,000 prompts derived from real-world regulations and laws, systematically expanded via an LLM-assisted evolutionary pipeline that introduces diverse, realistic misuse scenarios (e.g., detailed explosive synthesis instructions involving advanced chemical formulas). We evaluate frontier models within a unified evaluation framework using our SoSBench. Despite their alignment claims, advanced models consistently disclose policy-violating content across all domains, demonstrating alarmingly high rates of harmful responses (e.g., 84.9% for Deepseek-R1 and 50.3% for GPT-4.1). These results highlight significant safety alignment deficiencies and underscore urgent concerns regarding the responsible deployment of powerful LLMs.
Received — 4 April 2026 ⏭

GenOM: Ontology Matching with Description Generation and Large Language Model

✇cs.AI, q-bio.NC updates on arXiv.org
By: Yiping Song · Jiaoyan Chen · Renate A. Schmidt
3 April 2026 at 12:00
arXiv:2508.10703v3 Announce Type: replace Abstract: Ontology matching (OM) plays an essential role in enabling semantic interoperability and integration across heterogeneous knowledge sources, particularly in the biomedical domain which contains numerous complex concepts related to diseases and pharmaceuticals. This paper introduces GenOM, a large language model (LLM)-based ontology alignment framework, which enriches the semantic representations of ontology concepts via generating textual definitions, retrieves alignment candidates with an embedding model, and incorporates exact matching-based tools to improve precision. Extensive experiments conducted on the OAEI Bio-ML track demonstrate that GenOM can often achieve competitive performance, surpassing many baselines including traditional OM systems and recent LLM-based methods. Further ablation studies confirm the effectiveness of semantic enrichment and few-shot prompting, highlighting the framework's robustness and adaptability.
Received — 2 April 2026 ⏭

Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy

✇MRD
By: Chen Zhao · Lei Qiu · Ning An · Yong Ju · Jacqueline Ziqian Yang · Hyoyong Kim · Ryan Y Zhang · Junseok Lee · Jingjing He · Liang-Yan Chen · Yaya Xu · Yue Ma · Emily Ren · Sophie Pan · Pranay Sashikanth · Jina Kim · Di Wang · Peiling Zhang · Jianlin Hu · Yang Gao · Yuhan Bao · Yanhua Tu · Li Wang · Zhili Wang · Zhicheng Zhang · Renjun Pei · Edwin M Posadas · Sungyong You · Wanxing Chai-Ho · Tasha L Lin · Sarah M Larson · Dinesh S Rao · Hsian-Rong Tseng · Na Sun · Chunrui Li · Yazhen Zhu
27 March 2026 at 18:00

Res Sq [Preprint]. 2026 Mar 18:rs.3.rs-8913641. doi: 10.21203/rs.3.rs-8913641/v1.

ABSTRACT

Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.

PMID:41890853 | PMC:PMC13015583 | DOI:10.21203/rs.3.rs-8913641/v1

Received — 14 March 2026 ⏭

Profiling of the mycobiome and metabolome: a comparative study of benign pulmonary nodules and lung adenocarcinoma

✇Pulmonary nodule
By: Weiyi Zhang · Yuan Dong · Fangyan Chen · Fang Wang · Jiahui Li · Chunxi Liu · Tianyi Liu · Li Han · Xiaodong Jia
11 March 2026 at 18:00

Front Cell Infect Microbiol. 2026 Feb 23;16:1732958. doi: 10.3389/fcimb.2026.1732958. eCollection 2026.

ABSTRACT

INTRODUCTION: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer, is a form of malignant pulmonary nodule that requires clinical differentiation from benign pulmonary nodules (BPN). The mechanisms underlying the development of LUAD are complex, and effective non-invasive methods for differentiating BPN from LUAD are lacking. This study aimed not only to distinguish BPN from LUAD using gut fungi and serum metabolites, but also to establish an integrated network of gut fungi-metabolite-cytokine interactions.

METHODS: Fecal and serum samples from individuals with BPN and patients with LUAD were subjected to internal transcribed spacer sequencing, ultra-performance liquid chromatography-tandem mass spectrometry, and multiplex Luminex assays to quantify gut fungi, metabolites, and cytokines, respectively.

RESULTS: A significant difference in gut fungal communities was observed between the BPN and LUAD groups. Multiple genera and species were more abundant in LUAD than in BPN. Docosapentaenoic acid n-6 (DPAn-6), indole-3-propionic acid (IPA), and interferon-γ-induced protein 10 (IP-10) were significantly elevated in the LUAD group. The integrated model established using a combination of gut fungi and metabolites demonstrated excellent performance in distinguishing BPN from LUAD. A network of interactions was established among differentially abundant gut fungi, serum metabolites, and cytokines.

CONCLUSION: Our study identifies a novel panel of fungal and metabolite biomarkers for differentiating between BPN and LUAD, and constructs a multi-omics network that provides new insights into investigating the mechanistic role of gut mycobiota dysbiosis in LUAD.

PMID:41809995 | PMC:PMC12968269 | DOI:10.3389/fcimb.2026.1732958

Received — 5 March 2026 ⏭

Local Shapley: Model-Induced Locality and Optimal Reuse in Data Valuation

✇cs.AI, q-bio.NC updates on arXiv.org
By: Xuan Yang · Hsi-Wen Chen · Ming-Syan Chen · Jian Pei
5 March 2026 at 13:00
arXiv:2603.03672v1 Announce Type: cross Abstract: The Shapley value provides a principled foundation for data valuation, but exact computation is #P-hard due to the exponential coalition space. Existing accelerations remain global and ignore a structural property of modern predictors: for a given test instance, only a small subset of training points influences the prediction. We formalize this model-induced locality through support sets defined by the model's computational pathway (e.g., neighbors in KNN, leaves in trees, receptive fields in GNNs), showing that Shapley computation can be projected onto these supports without loss when locality is exact. This reframes Shapley evaluation as a structured data processing problem over overlapping support-induced subset families rather than exhaustive coalition enumeration. We prove that the intrinsic complexity of Local Shapley is governed by the number of distinct influential subsets, establishing an information-theoretic lower bound on retraining operations. Guided by this result, we propose LSMR (Local Shapley via Model Reuse), an optimal subset-centric algorithm that trains each influential subset exactly once via support mapping and pivot scheduling. For larger supports, we develop LSMR-A, a reuse-aware Monte Carlo estimator that remains unbiased with exponential concentration, with runtime determined by the number of distinct sampled subsets rather than total draws. Experiments across multiple model families demonstrate substantial retraining reductions and speedups while preserving high valuation fidelity.
Received — 25 February 2026 ⏭

Unifying Evolutionary Prompt Search and Reinforcement Learning for LLM Self-Improvement

✇cs.AI, q-bio.NC updates on arXiv.org
By: Lunjun Zhang · Ryan Chen · Bradly C. Stadie
24 February 2026 at 13:00
arXiv:2602.14697v2 Announce Type: replace Abstract: Building agentic systems that can autonomously self-improve from experience is a longstanding goal of AI. Large language models (LLMs) today primarily self-improve via two mechanisms: self-reflection for context updates, and reinforcement learning (RL) for weight updates. In this work, we propose Evolutionary System Prompt Learning (E-SPL), a method for jointly improving model contexts and model weights. In each RL iteration, E-SPL samples trajectories under multiple system prompts in parallel. It applies RL updates to LLM weights conditioned on system prompts, and evolutionary updates to system prompts via mutation and crossover, two genetic operators based on LLM self-reflection. Each system prompt is assigned a TrueSkill rating for evolutionary selection, updated from relative performance within each RL iteration. E-SPL encourages a natural division between declarative knowledge encoded in prompts and procedural knowledge encoded in weights, resulting in improved performance across reasoning and agentic tasks. For instance, in an easy-to-hard (AIME $\rightarrow$ BeyondAIME) generalization setting, E-SPL improves RL success rate from 38.8% $\rightarrow$ 45.1% while also outperforming reflective prompt evolution (40.0%). Overall, our results demonstrate that RL and evolutionary prompt search are deeply synergistic, and unifying the two yields consistent gains in sample efficiency and generalization. Code: https://github.com/LunjunZhang/E-SPL
There are no more articles
❌