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The binding of dicationic Hoechst 33258 (ligand) to DNA was characterized by means of the fluorescence spectra, fluorescence intensity titration, time-resolved fluorescence decay, light scattering, circular dichroism, and fluorescence thermal denaturation measurements, and two binding modes were distinguished by the experimental results. Type 1 binding has the stoichiometry of one ligand to more than 12 base pairs, and it is defined as quasi-minor groove binding which has the typical prolonged fluorescence lifetime of about 4.4 ns. In type 1 binding, planar conformation of the ligand is favorable. Type 2 binding with phosphate to ligand ratio (P/L) < 2.5 has the stoichiometry of one ligand to two phosphates. It is defined as a highly dense and orderly stacked binding with DNA backbone as the template. Electrostatic interactions between doubly protonated ligands and negatively charged DNA backbone play a predominant role in the type 2 binding mode. The characteristics of this type of binding result in a twisted conformation of the ligand that has a fluorescence lifetime of less than 1 ns. The results also indicate that the binding is in a cooperative manner primarily by stacking of the aromatic rings of the neighboring ligands. Type 1 binding is only observed for double-stranded DNA (dsDNA) with affinity constant of 1.83 x 10(7) M-1. In the type 2 binding mode, the binding affinity constants are 4.9 x 10(6) and 4.3 x 10(6) M-1 for dsDNA and single-stranded DNA (ssDNA), respectively. The type 2 binding is base pair independent while the type 1 binding is base pair related. The experiments described in this paper revealed that the dication bindings are different from the monocation bindings reported by previous study. The dication binding leads to stronger aggregation at low ligand concentration and results in orderly arrangements of the ligands along DNA chains. Furthermore the dication binding is demonstrated to be beneficial for enhancing the DNA's stability.

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BackgroundPeer-delivered services potentially provide broad, multifaceted benefits for persons suffering severe mental illness. Most studies to date have been conducted in countries with well-developed outpatient mental health systems. The objective of this study was to examine the feasibility for developing a community-based peer service in China.MethodsThirteen peer service providers and 54 consumers were recruited from four communities in Beijing. We initiated the program in two communities, followed by another two in order to verify and add to our understanding of potential scalable feasibility. Semi-structured face-to-face interviews were conducted 12 month after initiation at each site to measure satisfaction and perceived benefits from perspectives of peer service providers, and consumers and their caregivers.ResultsKey stakeholders reported that peer support services were satisfying and beneficial. Eleven of 13 peer service providers were willing to continue in their roles. Ten, 8, and 7 of them perceived improvements in working skills, social communication skills, and mood, respectively. Among consumers, 39 of 54 were satisfied with peer services. Improvements in mood, social communication skills, illness knowledge, and illness stability were detected among 23, 18, 13, and 13 consumers, respectively. For caregivers, 31 of 32 expressed a positive view regarding peer services. Caregivers reported improvement in their own mood, confidence in recovery of their family members, and reduction in caretaker burdens.ConclusionsThe findings highlight that peer-delivered services have promise in China for benefiting persons with severe mental illness and their family caregivers, as well as the peer service providers themselves.

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