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Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners. Methods Twenty patients receiving Invisalign were recruited. The relative intrusion values in the ClinCheck software were recorded as the preset intrusion. The achieved intrusion values were measured through the digital model superimposition. Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values, and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency. Results For the mandibular anterior teeth, the mean intrusion efficiency was 62.2%, with the highest in the central incisors and the lowest in the canines. The intrusion amounts, incisors labial inclinations, and canine attachment types affected the intrusion efficiency. The differences between the preset and achieved values were significant, and the linear relationship existed. The formula of the intrusion overcorrection for the mandibular anterior teeth is “Z=(W-0.110)/0.533-W”. Z represents the overcorrection and W represents the ideal intrusion. Conclusion The preset intrusion values in the treatment protocol could not be fully achieved. Moreover, correction should be designed in cases of mandibular canine intrusion, large amountsof intrusion, orlingually inclined incisors. Compared to the optimized attachments, the vertical rectangular attachments on the mandibular canines could improve the efficiency.

Nanomedicine, as an interdisciplinary discipline involving the development and application of nanoscale materials and technologies, is rapidly developing under the impetus of bionanotechnology and has attracted a great deal of attention from researchers. Especially, with the global outbreak of COVID-19, the in-depth investigation of the infection mechanism of the viruses has made the study of virus-mimicking nanosystems (VMNs) a popular research topic. In this review, we initiate with a brief historical perspective on the emergence and development of VMNs for providing a comprehensive view of the field. Next, we present emerging design principles and functionalization strategies for fabricating VMNs in light of viral infection mechanisms. Then, we describe recent advances in VMNs in biology, with a major emphasis on representative examples. Finally, we summarize the opportunities and challenges that exist in this field, hoping to provide new insights and inspiration to develop VMNs for disease diagnosis and treatment and to attract the interest of more researchers from different fields. [ABSTRACT FROM AUTHOR]

The common gating of CLC-1 has been shown to be inhibited by intracellular adenosine triphosphate (ATP) in acidic pH conditions. Such modulation is thought to be mediated by direct binding of ATP to the cystathionine β-synthase (CBS) domains at the C-terminal cytoplasmic region of CLC-1. Guided by the crystal structure of the C-terminal domain of CLC-5, we constructed a homology model of CLC-1's C terminus and mutated critical amino acid residues lining the potential ATP-binding site. The CLC-1 mutations V634A and E865A completely abolished the ATP inhibition of CLC-1, consistent with the loss of ATP binding seen with the corresponding mutations in CLC-5. Mutating two other residues, V613 and V860, also disrupted the ATP modulation of CLC-1. However, placing aromatic amino acids at position 634 increases the apparent ATP affinity. Mutant cycle analyses showed that the modulation effects of ATP and cytidine triphosphate on wild-type CLC-1 and the V634F mutant were nonadditive, suggesting that the side chain of amino acid at position 634 interacts with the base moiety of the nucleotide. The mutation effects of V634F and V613A on the ATP modulation were also nonadditive, which is consistent with the assertion suggested from the homology model that these two residues may both interact with the bound nucleotide. These results provide evidence for a direct ATP binding for modulating the function of CLC-1 and suggest an overall conserved architecture of the ATP-binding sites in CLC-1 and CLC-5. This study also demonstrates that CLC-1 is a convenient experimental model for studying the interaction of nucleotides/nucleosides with the CBS domain.

Amino groups are common in both natural and synthetic compounds and offer a very attractive class of endogenous handles for bioconjugation. However, the ability to differentiate two types of amino groups and join them with high hetero‐selectivity and efficiency in a complex setting remains elusive. Herein, we report a new method for bioconjugation via one‐pot chemoselective clamping of two different amine nucleophiles using a simple ortho‐phthalaldehyde (OPA) reagent. Various α‐amino acids, aryl amines, and secondary amines can be crosslinked to the ϵ‐amino side chain of lysine on peptides or proteins with high efficiency and hetero‐selectivity. This method offers a simple and powerful means to crosslink small molecule drugs, imaging probes, peptides, proteins, carbohydrates, and even virus particles without any pre‐functionalization. [ABSTRACT FROM AUTHOR]

Cystic fibrosis transmembrane conductance regulator (CFTR), a member of the ABC (ATP binding cassette) transporter family, is a chloride channel whose activity is controlled by protein kinase--dependent phosphorylation. Opening and closing (gating) of the phosphorylated CFTR is coupled to ATP binding and hydrolysis at CFTR's two nucleotide binding domains (NBD1 and NBD2). Recent studies present evidence that the open channel conformation reflects a head-to-tail dimerization of CFTR's two NBDs as seen in the NBDs of other ABC transporters (Vergani et al., 2005). Whether these two ATP binding sites play an equivalent role in the dynamics of NBD dimerization, and thus in gating CFTR channels, remains unsettled. Based on the crystal structures of NBDs, sequence alignment, and homology modeling, we have identified two critical aromatic amino acids (W401 in NBD1 and Y1219 in NBD2) that coordinate the adenine ring of the bound ATR Conversion of the W401 residue to glycine (W401G) has little effect on the sensitivity of the opening rate to [ATP], but the same mutation at the Y1219 residue dramatically lowers the apparent affinity for ATP by >50-fold, suggesting distinct roles of these two ATP binding sites in channel opening. The W401G mutation, however, shortens the open time constant. Energetic analysis of our data suggests that the free energy of ATP binding at NBD1, but not at NBD2, contributes significantly to the energetics of the open state. This kinetic and energetic asymmetry of CFTR's two NBDs suggests an asymmetric motion of the NBDs during channel gating. Opening of the channel is initiated by ATP binding at the NBD2 site, whereas separation of the NBD dimer at the NBD1 site constitutes the rate-limiting step in channel closing.

The kinetic study of Disperse Blue 56 inhibition of phosphomannomutase/phosphoglucomutase (PMM/PGM) is reported as the first detailed kinetic characterization of an aggregating inhibitor. The results help to identify certain characteristics that may facilitate recognition of aggregating inhibitors.

A practical method for the synthesis of selenylsubstituted indolo[2,1‐a]isoquinolin‐6(5H)‐ones through Fe(OTf)3‐promoted tandem selenylation/cyclization of 2‐arylindoles was developed. In this transformation, new C−Se bond and C−C bond were constructed simultaneously under mild conditions. [ABSTRACT FROM AUTHOR]

A metal‐free and efficient visible‐light‐induced spirocyclization of indolyl‐ynones with diselenides at room temperature under air atmosphere to prepare 3‐selenospiroindolenines in moderate to good yields has been developed. The resulting products were tested for in vitro anticancer activity by MTT assay, and compounds 3 c and 3 e showed potent cancer cell‐growth inhibition activities. [ABSTRACT FROM AUTHOR]