Minimally Invasive Coronally Advanced Flap Techniques for Correction of Gingival Recession Defects: A Review.

For treatment of patients with isolated and/or multiple adjacent gingival recession defects, debate exists as to whether minimally invasive coronally advanced flap-based surgical techniques achieve improved root coverage compared with traditional evidence-based techniques. Correction of gingival recession defects requires mucogingival surgery utilizing tissue grafting and/or soft-tissue alternatives. Traditional mucogingival techniques for root coverage using autogenous tissue are associated with patient morbidity and discomfort. Considering the philosophical shift in daily practice from "patient-centered" to "person-centered," minimally invasive surgical procedures are warranted that provide esthetic results with reduced morbidity. This review article evaluates five minimally invasive mucogingival techniques: semilunar, tunneling, modified tunneling, vestibular incision subperiosteal tunnel access, and pinhole. These surgical procedures and their clinical application are compared and contrasted.

Bispecific Estrogen Receptor α Degraders Incorporating Novel Binders Identified Using DNA-Encoded Chemical Library Screening.

Bispecific degraders (PROTACs) of ERα are expected to be advantageous over current inhibitors of ERα signaling (aromatase inhibitors/SERMs/SERDs) used to treat ER+ breast cancer. Information from DNA-encoded chemical library (DECL) screening provides a method to identify novel PROTAC binding features as the linker positioning, and binding elements are determined directly from the screen. After screening ∼120 billion DNA-encoded molecules with ERα WT and 3 gain-of-function (GOF) mutants, with and without estradiol to identify features that enrich ERα competitively, the off-DNA synthesized small molecule exemplar 7 exhibited nanomolar ERα binding, antagonism, and degradation. Click chemistry synthesis on an alkyne E3 ligase engagers panel and an azide variant of 7 rapidly generated bispecific nanomolar degraders of ERα, with PROTACs 18 and 21 inhibiting ER+ MCF7 tumor growth in a mouse xenograft model of breast cancer. This study validates this approach toward identifying novel bispecific degrader leads from DECL screening with minimal optimization.