Objective:The objective of this study was to search for targeted small molecule inhibitors of Sortase A(SrtA)of Streptococcus mutans(S.mutans),and to provide an experimental basis for the exploration of novel and effective anti-caries drugs.Methods:Using the crystal structure of SrtA enzyme of S.mutans UA159(PDB code:4TQX)as the receptor and amino acid Cys205 as the covalent binding site,we screened potential small molecule compounds from the natural small molecule drug-like molecule libraries of the compounds using molecular covalent docking technology and ADMET drug-forming filtration.The study screened small molecule compounds that inhibit adhesion without antibacterial effect,as determined by the minimum inhibitory concentration(MIC)and bacterial adhesion experiments.The binding modes and stabilities of the small molecule compounds were verified through molecular dynamics simulation.Results:A total of 20 small molecule compounds were selected by molecular co-valent docking technology and ADMET druggability filtration,among which AK-968/40369373 and AK-968/40385877 inhibited the adhesion of S.mutans better than trans-chalcone,and the difference was statistically significant(P＜0.05).Molecular dynam-ics simulations confirmed that AK-968/40369373 and AK-968/40385877 could form stable covalent binding to SrtA.Conclusion:Virtual screening and validation are effective methods for selecting potential targeting inhibitors of SrtA.The small-molecule com-pounds AK-968/40369373 and AK-968/40385877 obtained in this study are expected to be used as small-molecule inhibitors tar-geting S.mutans SrtA.

Objective:The objective of this study was to search for targeted small molecule inhibitors of Sortase A(SrtA)of Streptococcus mutans(S.mutans),and to provide an experimental basis for the exploration of novel and effective anti-caries drugs.Methods:Using the crystal structure of SrtA enzyme of S.mutans UA159(PDB code:4TQX)as the receptor and amino acid Cys205 as the covalent binding site,we screened potential small molecule compounds from the natural small molecule drug-like molecule libraries of the compounds using molecular covalent docking technology and ADMET drug-forming filtration.The study screened small molecule compounds that inhibit adhesion without antibacterial effect,as determined by the minimum inhibitory concentration(MIC)and bacterial adhesion experiments.The binding modes and stabilities of the small molecule compounds were verified through molecular dynamics simulation.Results:A total of 20 small molecule compounds were selected by molecular co-valent docking technology and ADMET druggability filtration,among which AK-968/40369373 and AK-968/40385877 inhibited the adhesion of S.mutans better than trans-chalcone,and the difference was statistically significant(P＜0.05).Molecular dynam-ics simulations confirmed that AK-968/40369373 and AK-968/40385877 could form stable covalent binding to SrtA.Conclusion:Virtual screening and validation are effective methods for selecting potential targeting inhibitors of SrtA.The small-molecule com-pounds AK-968/40369373 and AK-968/40385877 obtained in this study are expected to be used as small-molecule inhibitors tar-geting S.mutans SrtA.

Pathological dry skin is a disturbing and intractable healthcare burden,characterized by epithelial hy-perplasia and severe itch.Atopic dermatitis(AD)and psoriasis models with complications of dry skin have been studied using single-cell RNA sequencing(scRNA-seq).However,scRNA-seq analysis of the dry skin mouse model(acetone/ether/water(AEW)-treated model)is still lacking.Here,we used scRNA-seq and in situ hybridization to identify a novel proliferative basal cell(PBC)state that exclusively expresses transcription factor CUT-like homeobox 1(Cux1).Further in vitro study demonstrated that Cux1 is vital for keratinocyte proliferation by regulating a series of cyclin-dependent kinases(CDKs)and cyclins.Clinically,Cux1+PBCs were increased in patients with psoriasis,suggesting that Cux1+ PBCs play an important part in epidermal hyperplasia.This study presents a systematic knowledge of the tran-scriptomic changes in a chronic dry skin mouse model,as well as a potential therapeutic target against dry skin-related dermatoses.

Objective: To investigate the physical properties of Ti-6Al-4V clasps generated by selective laser melting (SLM) with different construction directions and to compare these clasps with cast clasps, which could provide a basis for fabricating SLM clasps with high precision and excellent mechanical properties. Methods: Ti-6Al-4V clasps were fabricated by SLM at 0 degrees (SLM0 group), 45 degrees (SLM45 group) and 90 degrees (SLM90 group) (n = 12). Twelve clasps were cast by the casting method as the control group. Meanwhile, four metal abutments were cast randomly as the abutments of the four groups. X-ray was used to detect cracks in the clasps of each group. The roughness of the clasps was measured by confocal microscopy, the fitness tests between clasps and abutment were processed by stereomicroscopy, and the microstructure of clasps in each group was observed under a metallographic microscope to evaluate the physical properties. Results : There were 0-8 visible cracks in the casting group but no obvious defects in the SLM groups. The maximum surface roughness was observed in the cast group (18.102 ± 3.762) μm, while the minimum roughness was observed in the SLM90 group (5.942 ± 1.486) μm (P < 0.05). There was no statistically significant difference in surface roughness between the SLM0 group [(8.711 ± 2.378) μm] and the SLM45 group [(8.513 ± 1.161) μm]. Fitness was worst in the casting group [(68.445 ± 14.876) μm] and best in the SLM90 group [(33.417 ± 5.880) μm] (P < 0.05). There was no statistically significant difference in fitness between the SLM0 group [(52.917 ± 12.102) μm] and the SLM45 group [(50.889 ± 7.011) μm]. In addition, the growth direction of the β grains was roughly parallel to the build direction, and acicular α grains were present between β grains. SLM was composed of fine grains, while the cast group had large grains. Conclusions Specimens generated by SLM had finer grains than cast specimens. In addition, SLM90 clasps had the highest fitness and the lowest surface roughness.