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Dysregulated proline metabolism contributes to retinal fibrosis in neovascular AMD: Therapeutic potential of prolyl-4-hydroxylase inhibition

Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (AMD). This study shows that proline metabolism, particularly P4HA1-mediated proline hydroxylation, is activated in JR5558 mice and human AMD tissues. Diethyl pythiDC reduced collagen turnover and fibrovascular lesion expansion, with potential added benefit when combined with aflibercept.
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KernelGenBench: Can LLMs and Agents Write Efficient Kernels Across Operator Sources and Hardware Platforms?

arXiv:2607.27231v3 Announce Type: replace Abstract: Modern AI systems depend on specialized accelerator kernels, whose development is complicated by increasingly diverse operators and hardware. LLMs and agentic systems promise to automate this work, but existing evaluations do not show whether their performance transfers across operator sources and hardware platforms, or what such transfer costs. We present KernelGenBench, the first unified multi-source and multi-chip infrastructure for evaluating LLM- and agent-generated Triton kernels. With a common Triton target spanning six hardware platforms, it provides the broadest cross-vendor hardware coverage among existing kernel-generation benchmarks. We report two controlled analytical views: KernelGenBench-MS (Multi-Source) covers 210 operators from PyTorch ATen, production vLLM operators, and proprietary cuBLAS routines, while KernelGenBench-MC (Multi-Chip) evaluates a semantically stable 110-operator subset across six hardware platforms. Our evaluation consumed over 15 billion tokens. Agentic execution improved correctness, but no method dominated across sources and platforms: vLLM posed the strongest correctness challenge, cuBLAS set the highest performance ceiling, and AutoKernel accuracy fell from 87% on NVIDIA to 25% on Iluvatar CoreX. These improvements were costly: specialized agents averaged 4.99 million tokens per successful operator, rising to 6.25 million for CUDA Optimized Skill. The results establish operator source, hardware platform, and agentic scaffold as distinct dimensions of kernel-generation capability, and show that success in a familiar source-hardware setting is not a reliable proxy for deployment readiness.
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Hepatotoxicity Prediction and Multi-omics Reveal Mitochondrial and Lipid Metabolic Dysregulation in PM<sub>2.5</sub>-Induced Liver Fibrosis

Environ Health (Wash). 2025 Nov 14;4(3):513-521. doi: 10.1021/envhealth.5c00401. eCollection 2026 Mar 20.

ABSTRACT

Prolonged exposure to fine particulate matter (PM2.5) has been linked to chronic liver injury and cancer. However, an alternative risk assessment method to prospective longitudinal studies of exposome-metabolome interactions for liver inflammation-associated hepatocellular carcinoma (HCC) is lacking. This study investigates the risk of long-term real-world PM2.5 exposure in hepatocarcinogenesis through machine learning techniques. Shotgun mass spectrometry (MS) imaging data were acquired from mouse models across a continuum of fibrosis, cirrhosis, and HCC for training a multiclass classification model to identify "No Risk", "Cancer Risk", and "Cancer". Direct infusion-MS data from PM2.5-exposed mouse livers were analyzed to classify risk. By integrating data-driven and knowledge-based approaches, 14 disease progression biomarkers were identified for modeling. Our results suggest that chronic real-world PM2.5 exposure can induce liver fibrosis, presenting cancer risk. Incorporating metabolomics, lipidomics, and transcriptomics, we propose PM2.5 exposure induces mitochondrial dysfunction, activates AMPK signaling, and increases ceramide accumulation, potentially mediating insulin resistance that contributes to nonalcoholic fatty liver disease and HCC progression. This work represents a significant advancement in assessing hepatotoxicity of environmental toxicants by reducing reliance on traditional animal testing methods. It also underscores the potential of emerging technologies in transforming our understanding of PM2.5 exposure, paving the way for targeted interventions.

PMID:41883379 | PMC:PMC13010293 | DOI:10.1021/envhealth.5c00401

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