In-cell Catalysis by Tethered Organo-Osmium Complexes Generates Selectivity for Breast Cancer Cells.

Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple-negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin-bound in the extracellular medium, while cellular accumulation studies identified an energy-dependent, protein-mediated Os accumulation pathway, consistent with albumin-mediated uptake. Importantly, the tethered Os complex was active for in-cell transfer hydrogenation catalysis, initiated by co-administration of a non-toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non-tumorigenic cells.

Associations of ambient temperature and total cloud cover during pregnancy with newborn vitamin D status.

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.

[Analysis of epidemiological characteristics of respiratory pathogens in children with influenza-like illnesses in a children's hospital in Beijing from 2022 to 2023].

To investigate the status and epidemiological characteristics of respiratory pathogens infections in children with influenza-like illnesses (ILI) in Beijing Children's Hospital from 2022 to 2023. A dual amplification technique was used to detect nucleic acids of seven common respiratory pathogens, including influenza A virus (Flu A), influenza B virus (Flu B), mycoplasma pneumoniae (MP), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), and Chlamydia pneumoniae (CP), in outpatient and inpatient children (aged 0-18 years) with influenza-like symptoms who sought medical care at Beijing Children's Hospital, from January 2022 to March 2023. A total of 43 663 children were included in the study, of which 27 903 tested positive for respiratory pathogens with a total detection rate of 63.91%. Flu A had the highest detection rate of 69.93% (27 332/39 084), followed by MP about 13.22% (380/2 875). The total detection rate of RSV, PIV and ADV was 7.69% (131/1 704). Flu B had a detection rate of 0.16% (64/39 084). No CP was detected in this study. A total of 7 cases of dual infections were detected, with a detection rate of 0.41% (7/1 704). The Chi-square test was used to analyze the differences in detection rates of pathogens among different genders, age groups, and different seasons. Among the seven pathogens, only Flu A had statistically significant differences in gender (χ2=16.712, P<0.001). The detection rates of Flu A and MP showed an increasing trend with age (both P trend<0.001), while the detection rates of RSV and PIV showed a decreasing trend with age (both P trend<0.001). Flu A had its epidemic peak in winter and spring, with detection rates of 61.30% (3 907/6 374) and 77.47% (23 207/29 958) respectively; MP and PIV had higher detection rates in autumn (25.14% and 7.64% respectively); RSV showed a relatively higher detection rate in winter (8.69%); Flu B and ADV had lower detection rates throughout the study period (0.16% and 1.17% respectively). In conclusion, children with ILI in 2022-2023 were mainly infected with a single respiratory pathogen, and occasionally dual pathogen infections were observed. Among them, the detection rate of Flu A was the highest, and only Flu A showed a gender difference in detection rate. As the age of the children patients increased, the detection rate of Flu A and MP showed an increasing trend, while RSV and PIV showed a decreasing trend. The prevalence of Flu A, Flu B, MP, PIV, and RSV were seasonal.

[Construction of natural population cohort on telephone follow-up management quality control system and discussion regarding critical issues by REDCap system].

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.