Proteolysis-targeting chimeras (PROTACs) are engineered techniques for targeted protein degradation. A bifunctional PROTAC molecule with two covalently-linked ligands recruits target protein and E3 ubiquitin ligase together to trigger proteasomal degradation of target protein by the ubiquitin-proteasome system. PROTAC has emerged as a promising approach for targeted therapy in various diseases, particularly in cancers. In this review, we introduce the principle and development of PROTAC technology, as well as the advantages of PROTACs over traditional anti-cancer therapies. Moreover, we summarize the application of PROTACs in targeting critical oncoproteins, provide the guidelines for the molecular design of PROTACs and discuss the challenges in the targeted degradation by PROTACs.

In 1.0 M KOH, Co–P@NC/CC, prepared by electrodeposition of cobalt–phosphorus nanoparticles on a polyimide derived N-doped carbon nanosheet array supported on carbon cloth, shows outstanding catalytic activity with the demand of an overpotential of 75 mV to drive 10 mA cm ⁻² .

Chronic pain surrounding the temporomandibular joints and masticatory muscles is often the primary chief complaint of patients with temporomandibular disorders (TMD) seeking treatment. Yet, the neuro-pathophysiological basis underlying it remains to be clarified. Neuroimaging techniques have provided a deeper understanding of what happens to brain structure and function in TMD patients with chronic pain. Therefore, we performed a systematic review of magnetic resonance imaging (MRI) studies investigating structural and functional brain alterations in TMD patients to further unravel the neurobiological underpinnings of TMD-related pain. Online databases (PubMed, EMBASE, and Web of Science) were searched up to August 3, 2019, as complemented by a hand search in reference lists. A total of 622 papers were initially identified after duplicates removed and 25 studies met inclusion criteria for this review. Notably, the variations of MRI techniques used and study design among included studies preclude a meta-analysis and we discussed the findings qualitatively according to the specific neural system or network the brain regions were involved in. Brain changes were found in pathways responsible for abnormal pain perception, including the classic trigemino-thalamo-cortical system and the lateral and medial pain systems. Dysfunction and maladaptive changes were also identified in the default mode network, the top-down antinociceptive periaqueductal gray-raphe magnus pathway, as well as the motor system. TMD patients displayed altered brain activations in response to both innocuous and painful stimuli compared with healthy controls. Additionally, evidence indicates that splint therapy can alleviate TMD-related symptoms by inducing functional brain changes. In summary, MRI research provides important novel insights into the altered neural manifestations underlying chronic pain in TMD.

The role and underlying mechanism of exosomes derived from human periodontal ligament stem cells (PDLSC) in osteogenesis are unclear. In the present study, we identified the exosomes derived from PDLSCs and found that osteogenic induction can enhance the osteogenic ability of PDLSC-derived exosomes in promoting the osteogenic differentiation of rat bone marrow stem cells (BMSCs). To investigate the underlying mechanism, we analyzed the exosomal miRNA expression profiles of undifferentiated and osteogenic differentiated PDLSCs by RNA sequencing. The results showed that seventy-two miRNAs were upregulated and thirty-five miRNAs were downregulated after osteogenic induction. The results of Gene Ontology analysis and pathway analysis demonstrated that the target genes of differentially expressed exosomal miRNAs participate in the regulation of a variety of biological processes, such as catalytic activity, protein binding, metabolic processes, cell development, and differentiation, and are enriched in osteogenic differentiation-related pathways, such as MAPK signaling, AMPK signaling, and insulin signaling pathways. Our results reveal for the first time that the exosomal miRNAs derived from osteogenic differentiated PDLSCs may promote the osteogenic differentiation of BMSCs, which provides a basis for further research on the regulatory function of exosomal miRNA of PDLSCs during osteogenesis.

Objective: To evaluate the effect of the multiloop edgewise arch wire (MEAW) technique with maxillary mini-implants in the camouflage treatment of skeletal Class III malocclusion. Materials and Methods: Twenty patients were treated with the MEAW technique and modified Class III elastics from the maxillary mini-implants. Twenty-four patients were treated with MEAW and long Class III elastics from the upper second molars as control. Lateral cephalometric radiographs were obtained and analyzed before and after treatment, and 1 year after retention. Results: Satisfactory occlusion was established in both groups. Through principal component analysis, it could be concluded the anterior-posterior dental position, skeletal sagittal and vertical position, and upper molar vertical position changed within groups and between groups; vertical lower teeth position and Wits distance changed in the experimental group and between groups. In the experimental group, the lower incisors tipped lingually 2.7 mm and extruded 2.4 mm. The lingual inclination of the lower incisors increased 3.5°. The mandibular first molars tipped distally 9.1° and intruded 0.4 mm. Their cusps moved 3.4 mm distally. In the control group, the upper incisors proclined 3°, and the upper first molar extruded 2 mm. SN-MP increased 1.6° and S-Go/N-ME decreased 1. Conclusions: The MEAW technique combined with modified Class III elastics by maxillary mini-implants can effectively tip the mandibular molars distally without any extrusion and tip the lower incisors lingually with extrusion to camouflage skeletal Class III malocclusions. Clockwise rotation of the mandible and further proclination of upper incisors can be avoided. The MEAW technique and modified Class III elastics provided an appropriate treatment strategy especially for patients with high angle and open bite tendency.