Pim-1, a carcinogenic threonine and serine kinase, inhibits apoptosis and advances the cell cycle. It is overexpressed in several human cancers. The proviral integration site of Moloney murine leukemia virus 1 is Pim-1. Previous studies have shown that the Pim-1 30-UTR regulates the stability of Pim-1 mRNA. Threonine and serine are identified as the proto-oncogene Pim-1 kinase. Pim-1 mediates numerous biological processes, including apoptosis, cell division, proliferation, and cancer. Pim-1-mediated anticancer activity has been reported in several analogs of thiazole/bis-thiazole, tetrazine, thiophenes, quinoline, pyrazolopyrimidine, 3-cyanopyridine, thiazolidine-2,4-dione, thieno[2,3-b]pyridine, triazolo[4,3-b]pyridazine, pyrazolo[1,5-a]pyrimidines, and pyrazolo[3,4-b]pyridine derivatives. Additionally, flavonoids and amino alcohol compounds that constitute Pim-1-mediated cancer therapy have also been identified thus far. Many compounds with Pim-1-mediated cytotoxicity have been discovered up to this point, and scientists are currently concentrating on bringing novel compounds with anticancer potential to the market.

Treatment of extensive multiregional hidradenitis suppurativa requires sequencing biologic therapy and surgery when active inflammation and irreversible structural disease coexist. A 58-year-old Japanese man with Hurley Stage III disease had inadequate overall control with adalimumab. At the assessment before medial-thigh surgery, the International Hidradenitis Suppurativa Severity Score System score was 48. Because he sought prompt relief from painful drainage and daily wound care, bilateral scarred and tunnel-bearing lesions were excised and reconstructed by staged split-thickness skin grafting while adalimumab was continued. Local control was achieved, but disease persisted elsewhere, prompting a switch to bimekizumab. Inflammatory lesion counts decreased, but Hidradenitis Suppurativa Clinical Response was not achieved at week 16 and extensive gluteal scars and draining tunnels remained. Bilateral gluteal excision and staged grafting were therefore performed during continued bimekizumab treatment, without postoperative infection, bleeding, or graft failure. Six months after reconstruction, the severity score was 9 and the clinical response criterion was met, reflecting both decreased inflammatory activity during bimekizumab treatment and surgical removal of structural lesions. Gluteal local control persisted through 15 months. This case illustrates sequencing biologic switching and regional surgery according to inflammatory activity, persistent structural disease, and the need for prompt symptom relief.

ATP-citrate lyase (ACLY) is a key enzyme in cellular metabolism that catalyses the cleavage of citrate to produce acetyl coenzyme A (acetyl-CoA), thereby bridging energy metabolism and epigenetic regulation. Acetyl-CoA serves as a common substrate for de novo lipogenesis (DNL) and histone acetylation. Aberrant ACLY activity is closely associated with various pathological conditions, including metabolic diseases, Immune-mediated inflammatory diseases (IMIDs), cancer, and neurodegenerative diseases, positioning ACLY as an important therapeutic target for these diseases. However, existing inhibitors face challenges such as insufficient selectivity and limited clinical efficacy and off-target effects. This review systematically summarises the molecular mechanisms and pathological significance of ACLY within the overarching framework of its dual metabolic-epigenetic functions, from three perspectives, namely its structure and function, disease relevance, and inhibitor development and optimisation strategies, aiming to provide a theoretical foundation for precision therapies targeting ACLY.

Why does performance pressure sometimes cause choking but sometimes elicit exceptional performance? We propose that pressure shifts the complexity of information-processing rules that guide action. Performance improves when shifts move processing toward task-matched complexity and deteriorates when they promote maladaptive simplification, overcomplexification, or the use of rules that exceed available processing resources.

Pt-based high-entropy alloy (Pt-HEA) catalysts show significant potential for the hydrogen evolution reaction (HER), yet their vast compositional space challenges conventional trial-and-error approaches. Here, we propose a large language model (LLM)-guided closed-loop framework for high-throughput discovery to accelerate the rational design and optimization of Pt-HEA catalysts. The framework first extracts structured knowledge from extensive literature and incorporates retrieval-augmented generation (RAG) to develop an LLM assistant tailored to HEA electrocatalysis research. The assistant transforms scattered literature knowledge, experimental constraints, and platform capabilities into experimentally feasible Pt-HEA candidate combinations and executable experimental protocols. High-throughput synthesis and screening enabled rapid evaluation of multiple Pt-HEA candidates, followed by Bayesian optimization to efficiently refine compositions within the representative Fe-Co-Ni-Cu-Pt system. This established a collaborative closed-loop workflow linking LLM-assisted candidate generation, high-throughput feedback, Bayesian optimization recommendations, density functional theory (DFT) mechanistic interpretation, and proton exchange membrane water electrolysis (PEMWE) device validation. Using this framework, we completed three iterative cycles involving 50 samples within 48 h, revealing how HER activity depends on atomic ratios in the Fe-Co-Ni-Cu-Pt system and identifying Fe30Co30Ni10Cu10Pt20 as the optimal composition. Theoretical calculations demonstrated that the multimetallic local coordination environment formed by Fe, Co, Ni, and Cu regulates the electronic structure of Pt active sites and fine-tunes the Pt-H interaction. Further PEMWE testing confirmed the catalyst's promising performance under device operating conditions. This work establishes a generalizable closed-loop paradigm integrating literature knowledge, experimental feedback, and model-driven decision-making, offering a viable route to the rational design and efficient optimization of complex multicomponent electrocatalytic materials.