Fluorescence Enhancement of Unconstrained GFP Chromophore Analogues Based on the Push-Pull Substituent Effect.

Unlike the high fluorescence quantum yield of the naturally occurring green fluorescence protein (GFP, Φf ∼ 0.8), the GFP chromophore, a benzylidenedimethylimidazolinone (BDI) dye, is nearly nonfluorescent (Φf < 0.001) in common solutions at room temperature. While many efforts have been devoted into the BDI chromophore engineering for fluorescence recovery, limited success has been achieved for structurally unconstrained GFP chromophore analogues (uGFPc). Herein we report a rational design of uGFPc toward an unprecedentedly high fluorescence quantum efficiency of 0.60 in hexane. This is achieved by a combined ortho-CN and meta-dimethylamino substituent electronic effect that largely suppresses the Z → E photoisomerization (the τ torsion) reaction, which is the major nonradiative decay channel of uGFPc. The structural design relied on the assumptions that the τ torsion of the meta-amino-substituted BDI systems leads to a zwitterionic twisted intermediate state (1p*) and that destabilizing the 1p* state by an electron-withdrawing CN substituent at the ortho or para position could slow down the τ torsion. The observed CN position effect conforms to the design concept. The push-pull substitution of BDI also leads to sensitive fluorescence-quenching responses to electron donors such as trimethylamine and to H-bond donors such as methanol.

Investigating the effectiveness of adjuvant therapy for patients with hormone receptor-positive ductal carcinoma in situ.

BACKGROUND: This study compared the recurrence risk of single versus dual adjuvant radiotherapy (RT) and hormonal therapy (HT) following breast-conserving surgery (BCS) in patients with hormone receptor-positive ductal carcinoma in situ (DCIS). METHODS: This retrospective cohort study used the Taiwan Cancer Registry database linking to the Taiwan National Health Insurance data from 2011 to 2016. We compared the recurrence risk between BCS-based regimens in Cox regressions and presented as adjusted hazard ratio (HR) and 95% confidence interval (95%CI). RESULTS: The 1,836 study cohort with a low-to-intermediate risk of recurrence was grouped into BCS alone (6.1%), BCS+RT (6.2%), BCS+HT (23.4%) and BCS+HT+RT (64.3%) according to the initial treatments. During the follow-up (median: 3.3 years), the highest 5-year recurrence-free survival rate was in BCS+RT (94.1%) group and followed by BCS+HT+RT (92.8%), BCS+HT (87.4%) and BCS alone (84.9%). Of the single adjuvant therapies, RT was more effective than HT. Both BCS+HT (HR: 1.52, 95%CI: 0.99-2.35) and BCS+RT (HR: 1.10, 95%CI: 0.50-2.41) did not significantly increase recurrence risk comparing against the BCS+HT+RT group. CONCLUSION: Single adjuvant demonstrated a similar subsequent recurrence risk with dual adjuvant. This study supports the proposition to de-escalate adjuvant treatments in patients with low-to-intermediate risk of DCIS recurrence.

Probing Molecular-Scale Oxidative Generation of Quinone Methides and Their Transformation Using Tip-Enhanced Raman Spectroscopy.

Quinone methides (QMs) are very important intermediates in chemistry. These species are most often generated in situ with metal oxidants and transition metal complexes. Here, tip-enhanced Raman spectroscopy (TERS) has been implemented to investigate the in situ oxidative generation of a QM species from alkylphenols facilitated by a transition metal complex. Using TERS, the metal oxidant-mediated transformation of a phenol species has been observed. The subsequent oxidative addition reaction of QM has also been identified based on distinct vibrational features, which have been assigned based on density functional theory (DFT). This study may establish TERS as a chemical detection tool for various QM-mediated reactions.

Photoinduced Enhanced Raman Probe for Use in Highly Specific and Sensitive Imaging for Tyrosine Dimerization in Inflammatory Cells.

A background-free photoinduced enhanced Raman (PIER) probe for highly sensitive detection of tyrosine dimerization process due to oxidative reaction in inflammatory cells is presented. The PIER probe could monitor oxidative reaction in real time by producing time-resolved spectral with discrete changes in Raman intensity. To the best of our knowledge, this is the first report on C≡C probes with PIER and vastly improved Raman activity. These results will contribute to the cutting edge of development of stable and highly sensitive chemical imaging technology.