Objective:To assess intrafractional errors of the deformation of clinical target volumes (CTVs) during online adaptive radiotherapy (OART) for prostate cancer patients, aiming to provide a basis for online plan optimization.Methods:A retrospective analysis was conducted for 13 prostate cancer patients who received 1.5 T magnetic resonance imaging (MRI)-guided OART (8 Gy × 5 fractions, totaling 65 fractions) at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences. The MRI images were collected at the beginning and end of various treatment fractions. Then, the CTVs and organs at risk (OARs) were delineated by the same radiation oncologist. After rigid registration and triangle mesh generation, the surface vertices were extracted. The deformable registration for the CTV surfaces was performed using the thin-plate spline robust point matching (TPS-RPM) algorithm, yielding vertex correspondences. Last, both systematic and random intrafractional errors of CTV deformation were calculated.Results:The average Hausdorff distance (HD) for deformable registration of treatment fractions was (1.68 ± 0.28) mm. The intrafractional systematic errors of CTV deformation were (0.25 ± 3.18) mm (anterior-posterior direction; A-P), (0.89 ± 3.85) mm (left-right direction, L-R), and (-1.98 ± 6.69) mm (superior-inferior direction, S-I). The intrafractional random errors of CTV deformation were determined at (-0.26 ± 1.89) mm (A-P), (-0.08 ± 0.88) mm (L-R), and (-0.04 ± 1.86) mm (S-I).Conclusions:During OART, CTV deformations primarily occur in the S-I direction. Therefore, it is necessary to consider the expanded size of margins in this direction during OART for prostate cancer.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:To assess intrafractional errors of the deformation of clinical target volumes (CTVs) during online adaptive radiotherapy (OART) for prostate cancer patients, aiming to provide a basis for online plan optimization.Methods:A retrospective analysis was conducted for 13 prostate cancer patients who received 1.5 T magnetic resonance imaging (MRI)-guided OART (8 Gy × 5 fractions, totaling 65 fractions) at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences. The MRI images were collected at the beginning and end of various treatment fractions. Then, the CTVs and organs at risk (OARs) were delineated by the same radiation oncologist. After rigid registration and triangle mesh generation, the surface vertices were extracted. The deformable registration for the CTV surfaces was performed using the thin-plate spline robust point matching (TPS-RPM) algorithm, yielding vertex correspondences. Last, both systematic and random intrafractional errors of CTV deformation were calculated.Results:The average Hausdorff distance (HD) for deformable registration of treatment fractions was (1.68 ± 0.28) mm. The intrafractional systematic errors of CTV deformation were (0.25 ± 3.18) mm (anterior-posterior direction; A-P), (0.89 ± 3.85) mm (left-right direction, L-R), and (-1.98 ± 6.69) mm (superior-inferior direction, S-I). The intrafractional random errors of CTV deformation were determined at (-0.26 ± 1.89) mm (A-P), (-0.08 ± 0.88) mm (L-R), and (-0.04 ± 1.86) mm (S-I).Conclusions:During OART, CTV deformations primarily occur in the S-I direction. Therefore, it is necessary to consider the expanded size of margins in this direction during OART for prostate cancer.

Due to good biocompatibility and mechanical properties similar to those of natural biological tissues,hydrogels have been widely used in biomedical fields.With the development of biomechanics,more and more researches have found that the viscoelastic tunable composite hydrogels based on dynamic covalent bonds can better simulate the viscoelastic mechanical properties of biological tissues and natural extracellular matrix over time due to their superior biomechanical properties and stimulus responsiveness.This review summarizes in detail the applications of viscoelastic tunable composite hydrogels based on different types of dynamic covalent bonds(imide bonds,disulfide bonds,borate ester bonds,etc.)in the fields of regulating cell function,affecting tissue regeneration and repair,as well as drug delivery.The challenges and opportunities for future research are also proposed.

Due to good biocompatibility and mechanical properties similar to those of natural biological tissues,hydrogels have been widely used in biomedical fields.With the development of biomechanics,more and more researches have found that the viscoelastic tunable composite hydrogels based on dynamic covalent bonds can better simulate the viscoelastic mechanical properties of biological tissues and natural extracellular matrix over time due to their superior biomechanical properties and stimulus responsiveness.This review summarizes in detail the applications of viscoelastic tunable composite hydrogels based on different types of dynamic covalent bonds(imide bonds,disulfide bonds,borate ester bonds,etc.)in the fields of regulating cell function,affecting tissue regeneration and repair,as well as drug delivery.The challenges and opportunities for future research are also proposed.

Objective: To explore the occurrence of cognitive impairment in Chinese heart failure (HF) patients and it's impact on prognosis. Methods: In this prospective observational study, a total of 990 HF patients were enrolled from 24 hospitals in China during December 2012 to November 2014. All patients were administrated with the interview-format Montreal Cognitive Assessment (MoCA), according to which they were divided into MoCA<26 (with cognitive impairment) group and MoCA≥26 (without cognitive impairment) group. Baseline data were collected and a 1-year follow up was carried out. Univariate and multivariate logistic or Cox regression were performed for 1-year outcomes. Results: Cognitive impairment was evidenced in 628 patients (63.4%) and they were more likely to be older, female, and with higher proportion of New York Heart Association(NYHA) class Ⅲ-Ⅳ, chronic obstructive pulmonary disease (COPD), ischemic heart disease, while body mass index (BMI), education level, and medical insurance rate were lower (all P<0.05) as compared to patients in MoCA≥26 group. The rate of percutaneous intervention, device implantation, cardiac surgery and evidence-based medications were significantly lower in MoCA<26 group than in MoCA≥26 group (all P<0.05). During the 1-year follow up, patients in the MoCA<26 group had higher all-cause mortality (10.2%(64/628) vs. 2.2%(8/362), P<0.01), cardiovascular mortality (5.9%(37/628) vs. 0.8%(3/362), P<0.01) and major adverse cardiac and cerebrovascular events (MACCE) (9.6%(60/628) vs. 2.5%(8/362), P<0.01) than patients in the MoCA≥26 group. In univariate regression, MoCA<26 was associated with increased all-cause mortality (HR(95%CI):4.739(2.272-9.885), P<0.01), cardiovascular mortality (HR(95%CI):7.258(2.237-23.548), P=0.001) and MACCE (OR(95%CI):4.143(2.031-8.453), P<0.01). After adjustment by multivariate regression, MoCA<26 was indicated as an independent risk factor for all-cause mortality (HR(95%CI): 6.387(2.533-16.104), P<0.01), cardiovascular mortality (HR(95%CI): 10.848(2.586-45.506), P=0.001) and MACCE (OR(95%CI): 4.081(1.299-12.816), P=0.016), while not for re-hospitalization for HF (OR(95%CI):1.010(0.700-1.457), P=0.957). Conclusions Cognitive impairment is common in HF patients,and it is an independent prognostic factor for 1-year outcomes. Routine cognitive function assessment and active intervention are thus recommended for HF patients.

Adenomatous Polyposis Coli Protein ; chemistry ; metabolism ; Amino Acid Sequence ; Chromatography, High Pressure Liquid ; HeLa Cells ; Humans ; Kinesin ; chemistry ; metabolism ; Microtubule-Associated Proteins ; chemistry ; metabolism ; Microtubules ; metabolism ; Molecular Sequence Data ; Phosphopeptides ; analysis ; Phosphorylation ; Protein Multimerization ; Tandem Mass Spectrometry