N⁶-methyladenosine (m⁶A) modification plays a critical role in cell cycle regulation, while the mechanism of m⁶A in regulating mitosis remains underexplored. Here, we found that the total m⁶A modification level in cells increased during mitosis by the liquid chromatography-mass spectrometry/mass spectrometry and m⁶A dot blot assays. Silencing methyltransferase-like 3 (METTL3) or METTL14 results in delayed mitosis, abnormal spindle assembly, and chromosome segregation defects by the immunofluorescence. By analyzing transcriptome-wide m⁶A targets in HeLa cells, we identified polo-like kinase 1 (PLK1) as a key gene modified by m⁶A in regulating mitosis. Specifically, through immunoblotting and RNA pulldown, m⁶A modification inhibits PLK1 translation via YTH N⁶-methyladenosine RNA binding protein 1, thus mediating cell cycle homeostasis. Demethylation of PLK1 mRNA leads to significant mitotic abnormalities. These findings highlight the critical role of m⁶A in regulating mitosis and the potential of m⁶A as a therapeutic target in proliferative diseases such as cancer.
Humans ; Polo-Like Kinase 1 ; Cell Cycle Proteins/metabolism* ; Proto-Oncogene Proteins/metabolism* ; Protein Serine-Threonine Kinases/metabolism* ; Mitosis/physiology* ; HeLa Cells ; Adenosine/genetics* ; Methyltransferases/metabolism* ; RNA, Messenger/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.

Objective To investigate the efficacy and safety of conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery in the treatment of recurrent anterior shoulder dislocation(RASD)with scapula glenoid bone defect>15%and meshing Hill-Sachs lesion.Methods The clinical data of 65 patients with RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion admitted to our hospital from January 2022 to December 2024 were retrospectively analyzed.They were divided into group A,group B,and group C according to different surgical methods.Among them,group A underwent conventional open Latarjet surgery(n=18),group B underwent arthroscopic Latarjet surgery(n=21),and group C underwent arthroscopic Bankart repair combined with Remplissage surgery(n=26).The surgical conditions,preoperative and postoperative scores of related scales[visual analogue scale(VAS),Constant-Murley shoulder score,the University of California Los Angeles(UCLA)shoulder score],shoulder range of motion,postoperative complications and recurrence were compared among the three groups.Results Operation time:group B was longer than group A and group C(P<0.05),and group A was longer than group C(P<0.05).Intraoperative blood loss and hospital stay:group A was more or longer than group B and group C(P<0.05),group B was more or longer than group C(P<0.05).The VAS scores of the three groups at 1,6 and 12 months after operation were lower than those before operation(P<0.05).Pain VAS score at 1 and 6 months after operation:group A was higher than group B and group C(P<0.05).Pain VAS score at 1 month after operation:group B was higher than group C.Pain VAS score at 12 months after operation:there was no significant difference among the three groups(P>0.05).The UCLA shoulder scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).UCLA score at 1 month after operation:group A0.05).The Constant-Murley scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).Constant-Murley score at 1 month after operation:group A was lower than group B and group C(P<0.05).Constant-Murley score at 6 and 12 months after operation:three groups were equivalent(P>0.05).Forward flexion and lifting range of motion in the three groups:at 12 months after operation>before operation(P<0.05).Forward flexion and lifting range of motion was evaluated at 12 months after operation:there was no significant difference among the three groups(P>0.05).The range of motion of external rotation at body side and external rotation at 90° abduction before operation and at 12 months after operation:there was no significant difference between group A and group B(P>0.05).External rotation at body side and external rotation at 90° abduction of group C:at 12 months after operation of it was less than that before operation(P<0.05).The range of motion of external rotation at body side and external rotation at 90° abduction was obtained at 12 months after operation:group A and group B were greater than group C(P<0.05).Postoperative complication rate and recurrence rate:three groups were equivalent(P>0.05).Conclusion Conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery can effectively improve shoulder joint function and relieve pain in the treatment of RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion.However,the two shoulder arthroscopic procedures are less traumatic and have faster postoperative recovery.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

Objective To investigate the efficacy and safety of conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery in the treatment of recurrent anterior shoulder dislocation(RASD)with scapula glenoid bone defect>15%and meshing Hill-Sachs lesion.Methods The clinical data of 65 patients with RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion admitted to our hospital from January 2022 to December 2024 were retrospectively analyzed.They were divided into group A,group B,and group C according to different surgical methods.Among them,group A underwent conventional open Latarjet surgery(n=18),group B underwent arthroscopic Latarjet surgery(n=21),and group C underwent arthroscopic Bankart repair combined with Remplissage surgery(n=26).The surgical conditions,preoperative and postoperative scores of related scales[visual analogue scale(VAS),Constant-Murley shoulder score,the University of California Los Angeles(UCLA)shoulder score],shoulder range of motion,postoperative complications and recurrence were compared among the three groups.Results Operation time:group B was longer than group A and group C(P<0.05),and group A was longer than group C(P<0.05).Intraoperative blood loss and hospital stay:group A was more or longer than group B and group C(P<0.05),group B was more or longer than group C(P<0.05).The VAS scores of the three groups at 1,6 and 12 months after operation were lower than those before operation(P<0.05).Pain VAS score at 1 and 6 months after operation:group A was higher than group B and group C(P<0.05).Pain VAS score at 1 month after operation:group B was higher than group C.Pain VAS score at 12 months after operation:there was no significant difference among the three groups(P>0.05).The UCLA shoulder scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).UCLA score at 1 month after operation:group A0.05).The Constant-Murley scores of group A at 6 and 12 months after operation and group B and group C at 1,6 and 12 months after operation were higher than those before operation(P<0.05).Constant-Murley score at 1 month after operation:group A was lower than group B and group C(P<0.05).Constant-Murley score at 6 and 12 months after operation:three groups were equivalent(P>0.05).Forward flexion and lifting range of motion in the three groups:at 12 months after operation>before operation(P<0.05).Forward flexion and lifting range of motion was evaluated at 12 months after operation:there was no significant difference among the three groups(P>0.05).The range of motion of external rotation at body side and external rotation at 90° abduction before operation and at 12 months after operation:there was no significant difference between group A and group B(P>0.05).External rotation at body side and external rotation at 90° abduction of group C:at 12 months after operation of it was less than that before operation(P<0.05).The range of motion of external rotation at body side and external rotation at 90° abduction was obtained at 12 months after operation:group A and group B were greater than group C(P<0.05).Postoperative complication rate and recurrence rate:three groups were equivalent(P>0.05).Conclusion Conventional open Latarjet surgery,arthroscopic Latarjet surgery,arthroscopic Bankart repair combined with Remplissage surgery can effectively improve shoulder joint function and relieve pain in the treatment of RASD with 15%～25%scapula glenoid bone defect and meshing Hill-Sachs lesion.However,the two shoulder arthroscopic procedures are less traumatic and have faster postoperative recovery.

This study was aimed at investigating the effectiveness of various host nucleic acid removal and non-specific amplifica-tion techniques in animal tissue samples,to increase the accuracy of pathogen identification in tissue samples.Simulated samples were prepared with a mixture of mouse lung tissue homogenates and Klebsiella pneumoniae fluids,and processed with six host nucleic acid removal kits and three non-specific amplification techniques.The effectiveness of each method in removing host DNA and enriching nucleic acids of pathogenic microorganisms was evaluated through real-time fluorescence quantitative PCR and high-throughput se-quencing.For host nucleic acid removal techniques,the method of selective cleavage and quantitative degradation of host DNA(Com-plete5 kit)effectively decreased the host nucleic acid content in tissue samples and increased the relative abundance of pathogen nucleic acids.In contrast,the magnetic bead method for host DNA removal(Next microbiome DNA enrichment Kit kit)was less effec-tive.At lower pathogen concentrations(77 CFU/mL),the Vazyme kit was more effective than the other kits in removing host nucleic acids.Non-specific amplification techniques(MALBAC whole genome amplification,MDA isothermal amplification,and random primer amplification)were not applicable to tissue samples and were not effective in increasing the relative abundance of pathogen nucleic acids.Selective lysis and quantitative degradation of host DNA were suitable for processing tissue samples with high host back-ground and low pathogenic microorganism levels,whereas non-specific amplification methods were not applicable to tissue samples for pre-processing of macro-genome high-throughput sequencing.

Objective:To compare the value of different imaging modalities in evaluating early efficacy of 90Y-selective internal radiation therapy (SIRT) for liver malignant tumors. Methods:From September 2021 to December 2023, a retrospective analysis was conducted on 43 patients (32 males, 11 females; age (55.8±14.7) years) with liver malignant tumors who received 90Y-SIRT at Hainan Cancer Hospital and Boao Super Hospital. The injection dosage of 90Y was 1.5(1.2, 2.4)GBq. Clinical and imaging data of patients before and after treatment for multimodal evaluation were collected, including MRI plain and enhanced scans, as well as diffusion weighted imaging (DWI). Plain scan images were evaluated for the treatment efficacy by response evaluation criteria in solid tumors (RECIST) 1.1 version, while enhanced MRI was scored into 1-5 based on changes in the target area, including increased low-density range, necrotic features, and decreased enhancement. The minimum apparent diffusion coefficient (ADC min) of DWI increased by 20% compared to baseline was determined to be responsive. Wilcoxon signed rank test was used to analyze data, and ROC curve analysis was used to analyze the diagnostic efficacy of different imaging modalities (Delong test). Results:All patients had baseline MRI data, 39 underwent MRI at 1-month after treatment, and 22 underwent MRI at 3-month after treatment. Based on MRI plain scan images, the target lesions showed partial remission (PR) in 10.26%(4/39) of patients, progressive disease (PD) in 5.13%(2/39) of patients, and stable disease (SD) in 84.61%(33/39) of patients at 1-month after treatment; while there were 40.91%(9/22) PR, 9.09%(2/22) PD and 50.00%(11/22) SD at 3-month after treatment. Based on DWI images, 35.90%(14/39) and 68.18%(15/22) of patients were considered responsive at 1-month and 3-month after treatment, respectively. Compared with baseline, the differences of tumor sizes, enhancement degree of target lesions and ADC min at 1-month and 3-month after treatment were statistically significant ( Z values: from -3.88 to -2.39, all P<0.05). Compared with the tumor size and enhancement degree, the AUCs of ADC min were the highest at 1-month (0.701) and 3-month (0.953) after treatment ( Z values: 0.40-2.29, all P<0.05). Conclusions:MRI plain scan, MRI enhancement and DWI are effective in the evaluation the efficacy of 90Y-SIRT for liver malignant tumors at 1-month and 3-month after treatment. ADC min is superior to tumor size and enhancement degree in diagnostic efficacy.

Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Objective:To compare the differences of actual absorbed doses of liver malignant tumors after 90Y-selective internal radiation therapy (SIRT) evaluated by 90Y PET/CT and 90Y bremsstrahlung (BRS) SPECT/CT imaging, and to compare the image quality of the 2 imaging methods. Methods:Twenty-one patients (15 males and 6 females; age: (52.4±15.4) years) with liver malignant tumors (15 cases of primary liver cancer, 6 cases of liver metastases; 39 lesions) between September 2021 and August 2022 were retrospectively analyzed. All patients underwent both 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging in the Department of Nuclear Medicine, Hainan Cancer Hospital. The ratios of the actual absorbed doses based on 90Y PET/CT imaging and 90Y BRS SPECT/CT imaging to the lowest standard absorbed dose(100 Gy) for tumor response were calculated. The image contrast and distinguishability of the two imaging methods were scored. Wilcoxon signed rank test and Wilcoxon rank sum test were used for data analysis. Results:The tumor absorbed doses evaluated by 90Y PET/CT and 90Y BRS SPECT/CT were 143.94(55.91, 233.48) Gy and 107.82(53.59, 157.53) Gy respectively. The doses evaluated by 90Y PET/CT were higher than the standard threshold in 24 lesions, while 19 lesions showed higher evaluated doses by 90Y BRS SPECT/CT than the standard threshold. Compared with 90Y PET/CT, 90Y BRS SPECT/CT underestimated the tumor absorbed dose of -24.25%(-32.32%, -12.14%). The ratio of dose evaluated by 90Y PET/CT to the lowest standard threshold was 1.33(0.56, 1.91), which was higher than that of dose evaluated by 90Y BRS SPECT/CT to the lowest standard threshold (0.97(0.47, 1.25); z=0.04, P<0.001). PET/CT image contrast was scored 0, 1, 2, 3 in 2, 2, 12, 23 lesions respectively, and SPECT/CT image contrast was scored 0, 1, 2, 3 in 2, 3, 16, 18 lesions respectively ( z=-1.29, P=0.199). The distinguishability scores of 0, 1, 2 based on PET/CT images were found in 3, 15, 21 lesions, while those based on SPECT/CT images were found in 4, 32, 3 lesions respectively ( z=-2.79, P=0.005). Conclusion:90Y PET/CT imaging is superior to 90Y BRS SPECT/CT imaging in radiation dose evaluation and tumor focus differentiation in patients with liver malignant tumors after 90Y-SIRT.