Degradation of saccharides is relevant to the design of catalytic therapeutics, the production of biofuels, inhibition of biofilms, as well as other applications in chemical biology. Herein, we report the design of multinuclear Cu complexes that enable cleavage of saccharides under physiological conditions. Reactivity studies with para-nitrophenyl (pNP)-conjugated carbohydrates show that dinuclear Cu complexes exhibit a synergistic effect and promote faster and more robust cleavage of saccharide substrates, relative to the mononuclear Cu complex, while no further enhancement is observed for the tetranuclear Cu complex. The use of scavengers for reactive oxygen species confirms that saccharide cleavage is promoted by the formation of superoxide and hydroxyl radicals through CuII/I redox chemistry, similar to that observed for native copper-containing lytic polysaccharide monooxygenases (LMPOs). Differences in selectivity for di- and tetranuclear Cu complexes are modest. However, these are the first reported small multinuclear Cu complexes that show selectivity and reactivity against mono- and disaccharide substrates and form a basis for further development of metalloglycosidases for applications in chemical biology.
Telomere length determines the replicative capacity of mammalian cells. Successive telomere reduction to a critically short length can lead to cellular senescence that irreversibly prevents cells from further cell division. A series of Cu complexes has been designed as selective artificial nucleases that degrade G-quadruplex telomeric DNA and exhibit selective DNA binding affinity and cleavage reactivity toward G-quadruplex telomeric DNA over duplex DNA. In contrast to proteinbased nucleases that usually lack membrane permeability, significant cellular uptake and nuclear localization of these Cu complexes was observed. Rapid telomere reduction of cancer cells was also observed after only 1 day incubation, while the absence of DNA fragmentation indicates a low level of nonselective DNA cleavage. Robust telomere reduction by the designed Cu complexes is an S-phasespecific event that is associated with increased formation of the G-quadruplex structure during DNA replication.
Spontaneous spinal epidural hematomas (SSEHs) are neurological emergencies complicated by a wide array of presentations. In this study, we report a case of a patient who presented with neck pain and was diagnosed with an SSEH with computed tomography (CT) angiography with subsequent confirmation by magnetic resonance imaging (MRI). The high-risk location and size of the lesion guided management and surgical intervention. In a stable patient presenting to the emergency department without focal neurological deficits, clinical suspicion and assessment of risk factors are integral in the evaluation of patient risk and subsequent imaging and intervention.
Objective Vaccine hesitancy among healthcare providers can compromise public confidence in vaccination during the ongoing COVID-19 global epidemic and increase susceptibility to life-threatening disease. We sought to investigate predictors of openness to vaccination among healthcare workers who choose not to be vaccinated against COVID-19 in order to explore potential solutions. Methods Physicians, physician assistants, and nurses who chose not to be vaccinated were surveyed to decipher reasons for vaccine refusal and personal loss due to the virus along with demographic variables. Multivariate logistic regression analysis evaluated whether provider role, parenthood, and death of family or friends were associated with strong versus relative vaccine refusal. Results The predominant reasons for vaccine hesitancy in this cohort of health care workers who had access to, but chose not to be vaccinated (n=500) were a concern for vaccine side effects (69.6%) and the belief that the vaccines are inadequately studied (61.6%). Being a physician, a parent, and having no experience of death in the family or friends had 2.64 times (95% CI: 1.65-4.23, p < 0.001), 1.72 times (95% CI: 1.05-2.81, p = 0.032), and 1.70 times (95% CI: 1.06-2.72, p = 0.028) the odds of strong vaccine refusal, respectively. Older age (35 and up) respondents were 1.83 times (95% CI: 1.24-2.68, p = 0.002) more likely to be open to vaccination.
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