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关键词： Papillary thyroid carcinoma (PTC)   thyroidectomy   lobectomy   extrathyroidal extension (ETE)   strap muscle invasion  

摘要： Background: The optimal extent of thyroidectomy for papillary thyroid carcinoma (PTC) measuring >1 cm and <= 4 cm remains a subject of debate. This study aimed to determine the optimal surgical extent for clinically node-negative (cN0) unilateral PTC measuring >1 cm and <= 4 cm and to identify factors associated with recurrence risk. Methods: We conducted a retrospective analysis of 403 patients with unilateral cN0 PTC measuring 11-40 mm. Propensity score-matched (PSM) analysis was performed using five covariates including age, sex, tumor size, central neck dissection, and follow-up duration. Patients were stratified by tumor size (11-20 vs. 21-40 mm), degree of extrathyroidal extension (ETE) (none, minimal, and invasion into the strap muscle), and surgical extent (lobectomy vs. total thyroidectomy). Recurrence and survival outcomes were compared. Results: In the baseline cohorts, among the 403 patients, 304 had 11-20 mm tumors, and 99 had 21-40 mm PTC. Total thyroidectomy was performed in 65.3% of cases. Rates of minimal ETE and strap muscle invasion were 41.4% and 8.2%, respectively. Recurrence rates did not differ significantly by tumor size, ETE status (except strap muscle invasion), or surgical extent. Strap muscle invasion independently predicted recurrence [hazard ratio (HR) =6.380, P=0.01] and was associated with poorer disease-free survival. After PSM, 88 pairs of patients were generated in the lobectomy and total thyroidectomy groups. In the PSM cohort, the recurrence rate did not differ between the two groups. However, the overall complication rate was significantly higher in the total thyroidectomy group (49.5% vs. 24.8%, P=0.009), largely driven by a higher rate of transient hypoparathyroidism (39.1% vs. 7.6%, P<0.001). Conclusions: In patients with unilateral cN0 PTC measuring 11-40 mm, lobectomy may serve as an appropriate primary surgical option, providing disease control comparable to total thyroidectomy while reducing procedure-related complication

摘要： Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a master regulator of luminal lineage in urothelial carcinoma. FX-909 is a first-in-class oral small-molecule PPAR gamma inverse agonist. Here we report the first part of FX-909-CLINPRO-1, a phase 1A 3 + 3 dose-escalation study of FX-909, that enrolled 56 patients with advanced solid tumors, including 46 with urothelial carcinoma. The primary end point was safety and tolerability;secondary end points included recommended phase 2 dose determination, pharmacokinetics and preliminary antitumor activity. FX-909 exhibited an acceptable safety and tolerability profile. Grade >= 3 adverse events included anemia (26.8%), thrombocytopenia (21.4%), fatigue (10.7%) and hyperglycemia (7.1%). Doses of 30 mg and 50 mg daily were selected for recommended phase 2 dose optimization. Objective responses were observed in 17.5% of patients with urothelial carcinoma across all dose levels. Exploratory analyses revealed that tumor responses were enriched in patients with high PPAR gamma expression. FX-909 demonstrated acceptable safety and tolerability with preliminary antitumor activity, supporting further clinical development in urothelial cancer. *** identifier: NCT05929235.

关键词： Anode material   Carbon-based 2D material   First-principles calculations   Potassium-ion battery   Sodium-ion battery  

摘要： The rapid demand for sustainable energy storage highlights the importance of developing advanced anode materials for sodium- and potassium-ion batteries. However, conventional carbon materials, such as graphite, suffer from limited ion adsorption and low capacity, which hinder their practical application. To address these limitations, we investigate the electrochemical performance of T-carbon [1 1 0] (TC) monolayer using first-principles calculations. Structural, electronic, and stability analyses confirm that TC possesses robust dynamical, mechanical, and thermal stability, along with metallic conductivity. Adsorption studies show that Na and K ions preferentially occupy H₁ and H₂ sites with strong binding and ∼0.9 |e| charge transfer. CI-NEB and Arrhenius analysis reveal low diffusion barriers, with K ions showing an ultralow barrier of 0.026 eV and a diffusion coefficient of 3.44 × 10⁻³ cm² s⁻¹ at 300 K. Importantly, the maximum configurations, C₂₄Na₁₈ and C₂₄K₁₀, correspond to ultrahigh theoretical capacities of 1674 and 930 mAh g⁻¹. These results highlight TC as a promising anode for high-performance Na/K-ion batteries.

摘要： The development of high-performance organic photothermal conversion agents (PTCAs) with strong near-infrared (NIR) absorption, high photothermal conversion efficiency (PCE), and excellent biocompatibility remains a critical challenge in photothermal therapy (PTT). In this study, we designed and synthesized a series of novel donor-acceptor-donor (D-A-D) small molecules based on a benzo[1,2-b:4,3-b']dithiophene-4,5-dione (BDTD-4,5-dione) core as a strong electron-accepting unit, symmetrically functionalized with triphenylamine (TPA) derivatives as tunable electron donors. By focusing on the strong electron-donating N,N-dimethylaniline (NPA) unit-contrasted with a methoxy-substituted analog-we achieved effective modulation of the HOMO energy, bandgap, and supramolecular aggregation, underscoring the advantage of enhanced donor strength for photothermal applications. Spectroscopic and electrochemical analyses revealed that electron-rich substituents significantly redshifted the intramolecular charge transfer (ICT) absorption into the NIR region (650-900 nm) and enhanced molar extinction coefficients. Among the derivatives, the dimethylamino-functionalized compound (BDQ-NPA) exhibited the most redshifted absorption, a narrow bandgap (2.0 eV), and an outstanding PCE of 35.05% under 808 nm laser irradiation. Theoretical calculations confirmed strong D-A interactions and efficient charge separation in the excited state. BDQ-NPA self-assembled into stable nanoparticles with excellent photostability and biocompatibility, facilitating efficient cellular uptake and NIR-triggered photothermal ablation of cancer cells in vitro. In vivo studies demonstrated significant tumor growth inhibition in a murine model following a single dose of BDQ-NPA and 808 nm irradiation, with no observable systemic toxicity. This work establishes BDTD-4,5-dione as a promising acceptor core for NIR-absorbing organic PTCAs and highlights the efficacy of substituent engineering in optimizing phototherma

关键词： milt   peptide   anti-fatigue   identification   energy metabolism  

摘要： Objectives: While several physiological functions of milt peptides have been discovered, the structural characteristics of Theragra chalcogramma milt peptides (TMP) and their anti-fatigue mechanisms remain unclear. Methods: TMP was obtained by hydrolysis via flavor enzyme and alkaline protease, and its structural characteristics were analyzed. A mice model of exercise-induced fatigue was established. The anti-fatigue effect of TMP was evaluated by determining the main biochemical indices in the serum, liver, and skeletal muscle of mice. Additionally, qPCR analysis was conducted to investigate its regulatory effects on relevant energy metabolism pathways. Results: TMP contained 18.2% branched-chain amino acids, with those with molecular weights below 1000 Da accounting for 91.6%. A total of 154 characteristic peptides, such as VPFPR and LPPGR, were identified from TMP, among which 64% of the peptides contained glutamic acid, arginine, or aspartic acid. Molecular docking of potential bioactive peptides to AMP-activated protein kinase (AMPK) revealed binding energies from -9.1 to -5.5 kcal/mol. The exhaustive swimming test showed that oral administration of TMP prolonged the swimming duration. In the fatigue murine model, TMP reduced blood urea nitrogen and blood lactic acid levels while enhancing the content of muscle glycogen. Meanwhile, TMP significantly increased the activity of glutathione peroxidase and superoxide dismutase and reduced the accumulation of malondialdehyde, demonstrating antioxidant properties. Additionally, TMP significantly decreased creatine kinase and lactate dehydrogenase extravasation, thereby protecting muscle tissue, as corroborated by immunohistochemical analyses. Mechanistically, TMP upregulated AMPK and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) expression, promoting mitochondrial biogenesis via the AMPK/PGC-1 alpha pathway. Conclusions: These findings suggest TMP has potential as a dietary supplem

关键词： B-position modulation   m-cresol   Metal loading   Perovskite catalyst   Photo-Fenton  

摘要： As one of the core advanced oxidation processes, UV photo-Fenton technology demonstrates unique advantages in treating refractory organic wastewater. This study focuses on strontium zirconate-based catalysts with a perovskite structure. To address the high recombination rate of electron-hole pairs and weak visible-light response in conventional photocatalysts, an innovative iron-doped modification system was developed. A series of SrFe_xZr_1-xO_3-δ catalysts with gradient variations in Fe/Zr molar ratios were synthesized via a co-precipitation method, and their performance in the UV-H₂O₂ synergistic catalytic oxidation system for m-cresol wastewater treatment was investigated. Experimental results demonstrated that SrFe_0.25Zr_0.75O₃ exhibited optimal catalytic performance when x = 0.25. Subsequently, noble metals: Ag, Co, Pd were loaded onto the optimized catalyst surface using a sodium borohydride reduction method. XPS characterization confirmed that the metal loading effectively facilitated the directional migration of photogenerated electrons to the metal sites. Among the modified catalysts, Pd-SrFe_0.25Zr_0.75O₃ displayed superior catalytic activity, with its apparent rate constant increasing by 43 % compared to the pristine material. This enhancement is attributed to the greater electronegativity of the metal element, which promotes the transfer of electrons from the metal to the catalyst, thus effectively decreasing the compounding rate of the electron-hole pairs and improving the photocatalytic effect of the catalysts. These findings not only provide novel insights into photocatalytic wastewater treatment but also offer valuable references for the modification of perovskite-type catalysts.

关键词： Cadonilimab   programmed cell death-1 inhibitor (PD-1 inhibitor)   chemotherapy   gastric/ gastroesophageal junction cancer (G/GEJ cancer)   programmed cell death-ligand 1 combined positive score <5 (PD-L1 CPS <5  

摘要： Background: Cadonilimab (AK104) is a first-in-class bispecific antibody targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). This study evaluated the effectiveness and safety of cadonilimab plus chemotherapy vs. PD-1 inhibitor plus chemotherapy as first-line treatment for advanced gastric/gastroesophageal junction (G/GEJ) cancer with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) <5. Methods: Between August 2022 and August 2024, patients with PD-L1 CPS <5 G/GEJ cancer who received first-line cadonilimab plus chemotherapy (cadonilimab group) or PD-1 inhibitor plus chemotherapy (PD-1 inhibitor group) were included. After propensity score matching (PSM), the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety were analyzed. Results: Fifty-two patients were analyzed after PSM (26 per group). At data cutoff (February 28, 2025), median follow-up was 11.0 months [95% confidence interval (CI): 8.3-15.3]. Compared with the PD-1 inhibitor group, cadonilimab group exhibited a numerically higher ORR (73.3% vs. 57.1%, P=0.45). In addition, the median PFS [9.3 vs. 5.8 months;hazard ratio (HR) =0.43;95% CI: 0.23-0.80;P=0.006] and OS (14.3 vs. 10.3 months;HR =0.49;95% CI: 0.26-0.93;P=0.03) were significantly longer in the cadonilimab group than in the PD-1 inhibitor group. The incidence of treatment-related adverse events (AEs) was comparable between the two groups, occurring in 92.3% of patients receiving cadonilimab plus chemotherapy and 100.0% of those receiving PD-1 inhibitor plus chemotherapy. Immune-related AEs occurred in 8 patients (30.8%) in the cadonilimab group and 6 patients (23.1%) in the PD-1 inhibitor group. Conclusions: Compared to PD-1 inhibitor plus chemotherapy, cadonilimab plus chemotherapy significantly improved PFS and OS with a manageable safety profile in the first-line treatment of advanced G/GEJ cancer with PD-L1 CPS

关键词： Campanumoea javanica polysaccharide   Macrophage polarization   SIRT1   TGF-β1/Smad3 pathway   Wound healing  

摘要： Abnormal wound healing, including delayed and excessive healing, is a significant clinical challenge requiring multidisciplinary interventions. Campanumoea javanica Bl., traditionally used postoperatively for hemostasis, immune enhancement, and postsurgical repair in minority ethnic regions, has shown potential in promoting wound healing. However, the underlying mechanisms remain unclear.

关键词： Isocitrate dehydrogenase 1-mutated   Ivosidenib   Matching-adjusted indirect comparison   Olutasidenib   Relapsed/refractory acute myeloid leukemia  

摘要： IntroductionOlutasidenib and ivosidenib are isocitrate dehydrogenase 1 (IDH1) inhibitors approved for relapsed/refractory (R/R) IDH1 mutant (IDH1m) acute myeloid leukemia (AML).MethodsA matching-adjusted indirect comparison estimated relative treatment effects using registrational Phase I/II data for olutasidenib (Study 2102-HEM-101;individual patient data) and ivosidenib (Study AG120-C-001;study-level data) since a head-to-head trial is unlikely. Weights were estimated using a logistic propensity score model adjusted for pre-defined covariates identified from a literature review, validated by clinical experts. Eight covariates were determined to be the most important prognostic factors/effect modifiers for the target population as reported in the Food and Drug Administration labels: number of prior systemic therapies, age, prior hematopoietic stem cell transplantation, AML type, relapse type, cytogenetic risk, Eastern Cooperative Oncology Group performance status, and IDH1 *** versus ivosidenib adjusted rates of complete remission (CR;odds ratio [OR] 1.12, 95% confidence interval [CI] 0.61-2.08), CR plus CR with partial hematologic recovery (CR + CRh;OR 0.83, 95% CI 0.46-1.50), and median CR duration (difference in medians 11.18 months, 95% CI - 4.30 to 22.72) were not significantly different. Median CR + CRh duration was significantly longer for olutasidenib (difference in medians 9.84 months, 95% CI 3.24-22.28), accompanied by a numerical non-significant trend in overall survival that should be considered exploratory (hazard ratio 0.75, 95% CI 0.53-1.07).ConclusionWhile not confirmatory, these findings may be clinically relevant in the context of this difficult-to-treat R/R IDH1m AML population.