This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.

Objective:To explore the diagnostic value of combining Ki67, molecular subtyping, and ultrasonographic parameters in predicting axillary lymph node metastasis in breast cancer.Methods:200 breast cancer patients who were admitted to Meizhou People’s Hospital from Jan. 2020 to Dec. 2022 were collected. Based on the presence or absence of axillary lymph node metastasis in breast cancer, the patients were divided into an axillary lymph node metastasis group and a non-axillary lymph node metastasis group. Age, clinical stage, tumor location, tumor size, degree of differentiation, boundary, blood flow, echo, calcification, morphology, vascular invasion, Ki67, molecular typing, resistance index (RI) , shear wave velocity were collected. Multivariate Logistic regression analysis was used to screen the risk factors for axillary lymph node metastasis of breast cancer, and receiver operating characteristic curve (ROC) was used to evaluate the clinical value of ki67, molecular typing combined with ultrasound parameters in the diagnosis of axillary lymph node metastasis of breast cancer.Results:There were no statistically significant differences in age, clinical stage, tumor location, tumor size, differentiation degree, boundary, blood flow, echo or calcification between the axillary lymph node metastasis group and the non-axillary lymph node metastasis group ( t=0.80, χ20.13, χ2=0.14, χ2=0.90, χ2=0.64, χ2=1.03, χ2=0.04, χ2=0.34, χ2=1.2, P>0.05) , while there were statistically significant differences in morphology, vascular invasion, Ki67, molecular classification, RI and shear wave velocity between the two groups ( χ2=12.01, χ2=8.75, χ2=11.36, χ2=11.43, t=6.34, t=7.25, P<0.05) . Multivariate Logistic regression analysis showed that vascular invasion, Ki67 high expression, triple negative breast cancer, RI and shear wave velocity were all risk factors for axillary lymph node metastasis ( OR=5.572,4.026,3.632,107.639,1.936, P<0.05) . ROC curve analysis results showed that the AUC of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was 0.620, 0.594, 0.744 and 0.792, respectively, and the AUC of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was 0.846. The AUC of the combination of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was higher than that of Ki67, molecular typing, RI and shear wave velocity alone ( Z=5.55,7.10,3.44,2.45, P<0.05) . Conclusions:High Ki67 expression, triple-negative breast cancer, lymphovascular invasion,RI, and shear wave velocity are all risk factors for axillary lymph node metastasis in breast cancer. The combined use of Ki67, molecular subtype, RI, and shear wave velocity can improve the diagnostic accuracy for axillary lymph node metastasis in breast cancer.

Objective To evaluate the recognition capability of AI-enabled Cellsee CS-BM1 automatic cell morphology analyzer for pe-ripheral blood smears and its roles in assisting manual classification,and explore the application value of AI system in the diagnosis network of tiered primary medical units.Methods The blood samples which triggered the re-examination rules were collected from six primary medical units,including the Laboratory Department of Shanghai Jiahui International Hospital,and so on,from March to No-vember 2023.The smears of peripheral blood were prepared and AI analyzer was used for pre-classification to evaluate its recognition performance in identifying the samples with abnormal WBC and RBC.The sensitivity,specificity,and accuracy of WBC classification by six junior and intermediate technicians,both with and without AI assistance,were analyzed.Additionally,the roles of the AI system in tiered diagnosis of primary medical units were also evaluated.Results The sensitivity,specificity,and accuracy of AI system in recognizing malignant primitive cells were 92.86％,95.16％,and 95.10％,respectively.The sensitivities of AI system in recognizing immature granulocytes,reactive lymphocytes,and nucleated RBCs were all greater than 90％.The sensitivity of AI system in identif-ying abnormal morphology of RBCs reached 99.59％,along with rapid quantitative analysis for various anomalous types of RBCs.In AI-assisted mode,the sensitivity of recognition for all cell types was improved to varying degrees by junior and intermediate technicians,and the sensitivity for recognizing malignant primitive cells,reactive lymphocytes,and immature granulocytes increased to 58.24％,53.39％,and 62.37％for junior technicians,and to 92.06％,83.24％,and 83.12％for intermediate technicians,respectively.The improvements for junior technicians were particularly significant,with increases of 12.46％,10.61％,and 3.71％for each cell type,respectively.Both groups achieved higher specificity and accuracy.Through AI pre-classification and manual review,a variety of pe-ripheral blood cell-related diseases were accurately diagnosed in the tiered healthcare practice of primary medical units,including 339 cases(11.13％)of red blood cell diseases,5 cases(0.16％)of platelet diseases,2 343 cases(76.90％)of infection-related disea-ses,and 28 cases(0.92％)of malignant hematological diseases.In addition,332 cases(10.90％)which lacked an obvious related cause or required further examinations were identified as well.Conclusion AI pre-classification has demonstrated strong cell recogni-tion capabilities and may assist technicians in improving the sensitivity,specificity,and accuracy of blood cell classification.AI could en-hance the disease-screening capabilities in the tiered diagnosis network of primary medical units,presenting a broad application prospect.

To summarize rescuing and nursing experience of 3 ectopic pregnancy patients,suffering from severe toxicity caused by low-dose methotrexate(MTX)treatment.The key points include:constantly monitoring of patients for at least a week after MTX administration,and identifying MTX toxicity related symptoms as soon as possible;promptly establishing a multidisciplinary medical team to establish individualized rescue plans;quickly initiating the rescue therapy and implementing targeted fluid management to accelerate MTX excretion;intensifying protective isolation caring to prevent and control infection;applying refined safety management to prevent spontaneous bleeding;providing intensive caring of skin and mucosal toxicity symptoms to promote healing process;supplying individualized psychological counseling and support in time;strengthening the protection of the damaged organ.After emergent rescuing and intensive nursing,all 3 patients successfully recovered and were discharged from the hospital.

Objective To explore the role and potential mechanisms of plasma-activated solution(PAS)in alleviating dextran sulfate sodium salt(DSS)-induced ulcerative colitis.Methods We constructed a DSS-induced ulcerative colitis mouse model and evaluated the effect of PAS in vivo by observing mouse weight,calculating disease activity indexes,detecting inflammatory factors and oxidative stress indicators through ELISA.We also evaluated the effect of PAS on colon cell proliferation and migration ability through clone formation experiments,scratch experiments,and used Western blotting to determine the expression levels of proliferation-related proteins.Results PAS significantly reversed DSS-induced weight loss and increased disease activity indexes in mice(P＜0.05).The serum inflammatory cytokine levels(TNF-α,IL-6 and IL-1β)in PAS group were significantly reduced compared to those in DSS group(P＜0.05).PAS treatment could improve the imbalance of colonic redox homeostasis including changes of malondialdehyde,catalase and superoxide dismutase caused by DSS(P＜0.05).After the use of endothelial nitric oxide synthase inhibitors,changes in various indicators caused by in vivo PAS disappeared(P＜0.001).The clone formation ability of colon cells was stronger in the group treated with PAS,and the expression of proliferation-related proteins increased.Cell scratch experiments suggested that intervention with PAS could reverse the decrease in cell migration ability caused by lipopolysaccharide(P＜0.001).After the application of endothelial nitric oxide synthase inhibitors,the pro-proliferative and migratory effects of PAS disappeared(P＜0.05).Conclusion PAS alleviate DSS-induced colitis in mice and promote colonic epithelial cell repair through the eNOS pathway.

Objective To explore the application of plasma-activated solution(PAS)in the treatment of peritoneal metastasis in mice.Methods A mice model of peritoneal tumor transplantation was established,and PAS was prepared for intervention in the mice.The growth of the peritoneally transplanted tumor was assessed using in vivo imaging technology,while the apoptosis level was evaluated through flow cytometry,immunofluorescence,and Western blotting.Results At the in vitro level,there was no significant impact on tumor cell apoptosis level under adherent conditions observed when utilizing PAS(P＞0.05).Under non-adherent condition,PAS significantly augmented tumor cell apoptosis level(P＜0.05),substantially increased the proportion of deceased cells(P＜0.05),and markedly elevated intracellular total and mitochondrial reactive oxygen species levels(P＜0.05).In vivo level,using PAS following peritoneal transplanted tumor formation exhibited no noteworthy influence on peritoneal transplanted tumor growth(P＞0.05),while immediate utilization of PAS during model conducting effectively reduced abdominal tumor spread(P＜0.05).Conclusion PAS inhibits tumor peritoneal dissemination in mice by promoting tumor cell anoikis.

The gastrin-releasing peptide receptor(GRPR)is highly expressed in various malignant tumors(e.g.,glioblastoma,prostate cancer,and breast cancer)and has emerged as an important molecular target for precision cancer diagnosis and therapy.In recent years,the combined application of radionuclide-la-beled GRPR ligands with positron emission tomography/computed tomography(PET/CT)has achieved ground-breaking progress in noninvasive diagnosis,accurate staging,and therapeutic monitoring of GRPR-positive tumors.Meanwhile,GRPR-targeted radionuclide therapeutics have demonstrated significant therapeutic potential and promising clinical applications in trials.This GRPR-based theranostic strategy pioneers a novel ap-proach for precision medicine in GRPR-overexpressing tumors.

Objective:To analyze the genomic characteristics and antibiotic resistance of Listeria monocytogenes isolated from food sources in Beijing City in 2022. Methods:A total of 83 strains of Listeria monocytogenes were isolated from three major categories of food, namely raw poultry, raw livestock meat and ready-to-eat foods, in Beijing′s food safety risk monitoring in 2022. Whole-genome sequencing (WGS) was performed to determine serogroups, multilocus sequence typing (ST) and core genome multilocus sequence typing (cgMLST). Virulence genes and antibiotic resistance genes were identified using the VFDB and ResFinder 3.0 databases. Antimicrobial susceptibility to eight antibiotics was tested via the broth microdilution method. Results:The predominant serogroup was 1/2a, 3a (61.2%). All the isolates were divided into 14 STs, with ST121 (21.7%), ST8 (20.5%), ST9 (13.3%), and ST87 (13.3%) as the dominant types. All 83 isolates were classified into 75 cgMLST types, with six clusters showing identical profiles, indicating potential clonal transmission. Comparative genomic analysis revealed that strains of the same ST clustered together regardless of geographic origin, and some Beijing isolates differed by fewer than 10 alleles from strains isolated in other countries. All the isolates in the study carried virulence islands 1(LIPI-1) and LIPI-2. LIPI-3 was detected in ST1, ST11 and ST3 isolates, while LIPI-4 was found in ST87 isolates. About 42 isolates (50.6%, including ST1, ST11, ST5, ST307, ST8, ST9, ST155, and ST3) harbored SSI-1, and 18 ST121 isolates carried SSI-2. Only 3.61% (three strains) and 4.82% (four strains) of isolates exhibited resistance to tetracycline and erythromycin, respectively. No resistance to other tested antibiotics was observed.Conclusion:Foodborne Listeria monocytogenes in Beijing exhibits high genomic diversity but is dominated by specific STs, some of which are associated with hypervirulence. Some Beijing isolates have homology with food-derived isolates from other countries.

Objective:To explore the diagnostic value of combining Ki67, molecular subtyping, and ultrasonographic parameters in predicting axillary lymph node metastasis in breast cancer.Methods:200 breast cancer patients who were admitted to Meizhou People’s Hospital from Jan. 2020 to Dec. 2022 were collected. Based on the presence or absence of axillary lymph node metastasis in breast cancer, the patients were divided into an axillary lymph node metastasis group and a non-axillary lymph node metastasis group. Age, clinical stage, tumor location, tumor size, degree of differentiation, boundary, blood flow, echo, calcification, morphology, vascular invasion, Ki67, molecular typing, resistance index (RI) , shear wave velocity were collected. Multivariate Logistic regression analysis was used to screen the risk factors for axillary lymph node metastasis of breast cancer, and receiver operating characteristic curve (ROC) was used to evaluate the clinical value of ki67, molecular typing combined with ultrasound parameters in the diagnosis of axillary lymph node metastasis of breast cancer.Results:There were no statistically significant differences in age, clinical stage, tumor location, tumor size, differentiation degree, boundary, blood flow, echo or calcification between the axillary lymph node metastasis group and the non-axillary lymph node metastasis group ( t=0.80, χ20.13, χ2=0.14, χ2=0.90, χ2=0.64, χ2=1.03, χ2=0.04, χ2=0.34, χ2=1.2, P>0.05) , while there were statistically significant differences in morphology, vascular invasion, Ki67, molecular classification, RI and shear wave velocity between the two groups ( χ2=12.01, χ2=8.75, χ2=11.36, χ2=11.43, t=6.34, t=7.25, P<0.05) . Multivariate Logistic regression analysis showed that vascular invasion, Ki67 high expression, triple negative breast cancer, RI and shear wave velocity were all risk factors for axillary lymph node metastasis ( OR=5.572,4.026,3.632,107.639,1.936, P<0.05) . ROC curve analysis results showed that the AUC of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was 0.620, 0.594, 0.744 and 0.792, respectively, and the AUC of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was 0.846. The AUC of the combination of Ki67, molecular typing, RI and shear wave velocity in the diagnosis of axillary lymph node metastasis of breast cancer was higher than that of Ki67, molecular typing, RI and shear wave velocity alone ( Z=5.55,7.10,3.44,2.45, P<0.05) . Conclusions:High Ki67 expression, triple-negative breast cancer, lymphovascular invasion,RI, and shear wave velocity are all risk factors for axillary lymph node metastasis in breast cancer. The combined use of Ki67, molecular subtype, RI, and shear wave velocity can improve the diagnostic accuracy for axillary lymph node metastasis in breast cancer.