Generalist foundation models (GFMs) are renowned for their exceptional capability and flexibility in diverse tasks. In the field of medicine, while GFMs exhibit superior generalizability, specialist models excel in precision because of their domain-specific knowledge. Here we show a cooperative framework, Generalist-Specialist Collaboration (GSCo), that synergistically combines a powerful generalist model with lightweight specialists. In this framework, specialists provide expert guidance, such as diagnostic predictions and visually similar clinical cases, as contextual information to the generalist, which then makes a final diagnosis. We developed MedDr, an open-source GFM tailored for medicine, as well as a suite of lightweight specialist models crafted for specific downstream tasks. A comprehensive evaluation on 32 datasets across diverse medical modalities shows that MedDr outperforms state-of-the-art GFMs on downstream datasets. Furthermore, GSCo exceeds GFMs and specialists in medical image diagnosis and report generation. This approach offers an effective and computationally efficient paradigm for deploying GFMs in clinical settings, enhancing scalability and enabling precise analysis across a wide range of scenarios.

Aneuploidy is common in cancer and has been implicated in promoting tumor progression, yet the underlying mechanisms remain poorly understood. By generating models of aneuploidy, we found that aneuploidy confers resistance to reactive oxygen species (ROS)-mediated cell death, independent of the specific chromosomes gained or lost. Mechanistically, poly(ADP-ribose) polymerase 1 (PARP1) is suppressed in aneuploid cells, which inhibits PARP1-mediated cell death (parthanatos). We validated aneuploidy-associated PARP1 suppression across 15 cell models and human tumors, with pronounced effects in metastatic tumors. Importantly, PARP1 downregulation promotes tumor metastasis while PARP1 upregulation suppresses it. Through a genome-wide CRISPR screen and functional validation, we identified the transcription factor CCAAT/enhancer-binding protein beta (CEBPB) as a mediator of PARP1 downregulation and ROS resistance in aneuploid cells. Lysosomal dysfunction serves as the upstream activator of CEBPB in aneuploid cells. We propose that aneuploidy-driven CEBPB activation suppresses PARP1, fostering ROS resistance and cancer progression.

Mustard gas (HD) causes ulcerative skin wounds; however, owing to its multiple mechanisms of action, no officially approved specific antidote has been developed to date. Moreover, current therapeutic materials for HD-induced skin injuries generally overlook the potential retention of residual HD at the wound site, which may adversely affect the healing process. Herein, a Janus membrane was rationally designed and successfully fabricated by electrospinning a blend of curcumin (denoted Cur)-loaded γ-cyclodextrin metal-organic framework (Cur@γ-CD-MOF) and polyacrylonitrile (PAN) onto a chitosan nonwoven fabric (CS-NWF) substrate, yielding a material with both pH-responsive drug release and HD detoxification capabilities. The resulting membrane was systematically characterized using IR, P-XRD, SEM, BET, TG and other techniques. The experimental results showed that the Cur@γ-CD-MOF@PAN side of the Janus membrane improved the aqueous solubility of Cur and enabled sustained, on-demand release. The skin-contacting CS-NWF side exhibited hemostatic capability, and Cur released from the membrane to the skin together with CS is thought to exert synergistic antioxidant effects. Moreover, the Janus membrane exhibited notable detoxification performance toward the HD simulant 2-chloroethyl ethyl sulfide and enabled real-time visual monitoring of the detoxification process through a steady color change of the system from red to yellow. Remarkably, in a guinea pig model of cutaneous HD intoxication, this Janus membrane showed a good therapeutic effect on HD-injured skin.

Immune checkpoint inhibitors, such as atezolizumab, have become integral to the treatment of various malignancies and have significantly improved clinical outcomes by enhancing host antitumor immune responses. However, with their expanding clinical use, immune-related adverse events (irAEs) have been increasingly recognized. These events may involve any organ system and pose new challenges in patient management. Most irAEs occur within the first few months following treatment initiation; however, they may also develop unexpectedly after prolonged periods of stable therapy. Late-onset irAEs are generally mild to moderate in severity, although a subset can progress to severe forms. Dermatological toxicities are the most frequently observed irAEs. Although most cutaneous reactions are mild and manageable, severe skin toxicities, although relatively uncommon, can substantially impair patients' quality of life and may necessitate treatment modification or discontinuation. Psoriasis is a recognized cutaneous irAE that may present either as a de novo disease in patients without a history of psoriasis or as an exacerbation of pre-existing psoriasis. This case report describes a rare presentation of severe psoriasis that developed following long-term atezolizumab therapy and improved following treatment with oral prednisolone in 61-year-old man with pulmonary large-cell neuroendocrine carcinoma.