Hunan Cancer Hospital

Hydrogen sulfide (H2S) has emerged as a key neuromodulator in the central nervous system, yet its accurate quantification in the brain system remains challenging due to strong interference from endogenous thiols and other sulfur-containing species. Here, we report an excited-state intramolecular proton transfer (ESIPT)-based fluorescent probe designed for selective and sensitive detection of H2S. The probe incorporates a cyano-substituted carbamate unit that suppresses ESIPT, producing a distinct turn-on fluorescence response at 594 nm upon H2S-induced cleavage. The probe exhibits a strong linear fluorescence enhancement in the range of 2-50 μM (R2 = 0.997) with a low detection limit of 0.206 μM. The reaction product shows excellent fluorescence stability over several hours, minimal sensitivity to pH variations under physiological conditions, and outstanding selectivity against biologically abundant ions, reactive species, thiols, and amino acids. Importantly, the probe enabled reliable quantification of endogenous H2S in hippocampal microdialysates from normal and Parkinson's disease (PD) mice. These findings demonstrate the potential of the probe as a robust analytical tool for studying H2S dynamics in neurochemical processes.

IntroductionThis study aims to systematically map the intellectual landscape and emerging trends in lipid metabolism research within hepatocellular carcinoma from 2014 to 2024.MethodsA total of 607 peer-reviewed publications were retrieved from the Web of Science Core Collection and PubMed. Bibliometric and visualization tools, including VOSviewer and CiteSpace, were employed to perform data analysis, including keyword co-occurrence and cluster analysis.ResultsWe identified a significant surge in research activity, with 53.05% of the total literature published in the last three years. China and the USA emerged as the leading contributors, with the University of California System and the journal Cancers being the most prolific institution and publication outlet, respectively. Current research hotspots are centered on the mechanisms by which oxidative stress drives the transformation of non-alcoholic fatty liver disease into hepatocellular carcinoma. Furthermore, three critical frontiers for future investigation were identified: (1) the regulatory role of PPARγ in lipid metabolic reprogramming and its therapeutic implications; (2) the molecular mechanisms of the farnesoid X receptor in modulating bile acid metabolism during hepatocarcinogenesis; and (3) the NF-κB signaling pathways that mediate metabolic shifts and confer chemoresistance in liver cancer.DiscussionThese findings provide a comprehensive reference for prioritizing research directions and therapeutic target discovery in the metabolic-related oncology domain.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

Acquired drug resistance continues to plague targeted therapies for colorectal cancer (CRC), with low chemosensitivity severely limiting treatment effectiveness. Our research reveals a key player in this challenge-POU2F1, a transcription factor known to drive tumor progression. We found this oncogene is markedly overexpressed in chemotherapy-resistant CRC, where it undermines treatment by suppressing MDR2 protein degradation. Mechanistically, we discovered POU2F1 stimulates MCT4 expression, which in turn triggers the cytosolic lactate export, where decreases the level of PPP1R11 lactylation, a negative regulator of MDR2. Further experiments unveil that lactylation of PPP1R11, a critical post-translational modification that normally stabilizes PPP1R11 and boosts its E3 ligase activity, promotes MDR2 ubiquitination and degradation, sensitizing cells to chemotherapy. Overall, our findings highlight the ability of POU2F1 in chemoresistance and regulating protein lactylation. Moreover, our work links lactylation to the exquisite regulation of the chemotherapy resistance by POU2F1, thus broadening the current knowledge of POU2F1 biological functions and the mechanism underlying target gene regulation.