Spatial proteomics measures tens of proteins in every cell of a tissue section, but its cost confines it to small research cohorts, whereas hematoxylin and eosin (H\&E) slides exist for nearly every patient. Inferring single-cell spatial proteomics from H\&E would bring its analyses to routine pathology, and a growing number of virtual staining models pursue this goal. Each is evaluated on its own cohort, panel and pixel-level metric, and released models transfer poorly to new cohorts, leaving open which approach to build on and which proteins H\&E can reveal. We introduce CellPlex, a benchmark that poses the task at the level of the cell: seven cohorts with same-section H\&E and multiplexed immunofluorescence, from colorectal and breast cancer to lymph-node metastases, bone marrow and glioma, with 717 samples, 44.8 million cells and 149 proteins, processed by one pipeline into per-cell targets. Pathology foundation models (PFMs) are adapted with one cell-level protocol, specialist models are fine-tuned under a matched budget, and all are scored on the same cells. Adapted PFMs are the most accurate models on every cohort, ahead of the specialists even after fine-tuning, but keep less than half of their accuracy on cohorts they were not trained on. Which proteins can be predicted depends on the tissue, not on how many cells were measured for them. By fixing the cells, targets and splits on which predictions are judged, CellPlex sets a common standard for inferring costly molecular measurements from routine H\&E and shows how far H\&E can stand in for spatial proteomics. We will release the data, splits, evaluation code and baselines as a testbed for developing and comparing future pathology foundation models and virtual staining methods.
Large language models (LLMs) have shown promise in medical question answering and clinical reasoning, yet their improvement remains constrained by static parametric knowledge and costly expert supervision. Self-evolving agents offer a promising alternative by enabling models to improve through iterative task generation and problem-solving. However, most existing self-evolving methods are designed for easily verifiable domains such as mathematics and coding, where solutions can be checked by exact answers or executable programs. Medical reasoning is fundamentally different: it is open-ended, knowledge-intensive, and often only partially verifiable. We present MedZERO, a self-evolving framework for open-ended medical reasoning. MedZERO couples an Examiner that generates frontier medical question-option pairs with a Reasoner that solves them through evidence-grounded multi-turn reasoning with external knowledge tools. To support reliable, continual improvement, MedZERO adopts controlled knowledge accumulation, which maintains temporary exploratory knowledge and curated persistent knowledge in reasoning. We evaluate MedZERO on five public medical reasoning benchmarks using 4B- and 8B-scale base models under open-ended evaluation. At both model scales, MedZERO achieves the highest average accuracy among the evaluated methods. Code available at https://github.com/IcecreamArtist/MedZERO.