zPoseScore model for accurate and robust protein-ligand docking pose scoring in CASP15.

We introduce a deep learning-based ligand pose scoring model called zPoseScore for predicting protein-ligand complexes in the 15th Critical Assessment of Protein Structure Prediction (CASP15). Our contributions are threefold: first, we generate six training and evaluation data sets by employing advanced data augmentation and sampling methods. Second, we redesign the "zFormer" module, inspired by AlphaFold2's Evoformer, to efficiently describe protein-ligand interactions. This module enables the extraction of protein-ligand paired features that lead to accurate predictions. Finally, we develop the zPoseScore framework with zFormer for scoring and ranking ligand poses, allowing for atomic-level protein-ligand feature encoding and fusion to output refined ligand poses and ligand per-atom deviations. Our results demonstrate excellent performance on various testing data sets, achieving Pearson's correlation R = 0.783 and 0.659 for ranking docking decoys generated based on experimental and predicted protein structures of CASF-2016 protein-ligand complexes. Additionally, we obtain an averaged local distance difference test (lDDT pli = 0.558) of AIchemy LIG2 in CASP15 for de novo protein-ligand complex structure predictions. Detailed analysis shows that accurate ligand binding site prediction and side-chain orientation are crucial for achieving better prediction performance. Our proposed model is one of the most accurate protein-ligand pose prediction models and could serve as a valuable tool in small molecule drug discovery.

Photoelectrons Sequentially Regulate Antibacterial Activity and Osseointegration of Titanium Implants.

Titanium implants are widely used ; however, implantation occasionally fails due to infections during the surgery or poor osseointegration after the surgery. To solve the problem, an intelligent functional surface on titanium implant that can sequentially eradicate bacteria biofilm at the initial period and promote osseointegration at the late period of post-surgery time is designed. Such surfaces can be excited by near infrared light (NIR), with rare earth nanoparticles to upconvert the NIR light to visible range and adsorb by Au nanoparticles, supported by titanium oxide porous film on titanium implants. Under NIR irradiation, the implant converts the energy of phonon to hot electrons and lattice vibrations, while the former flows directly to the contact substance or partially reacts with the surrounding to generate reactive oxygen species, and the latter leads to the local temperature increase. The biofilm or microbes on the implant surface can be eradicated by NIR treatment in vitro and in vivo. Additionally, the surface exhibits superior biocompatibility for cell survival, adhesion, proliferation, and osteogenic differentiation, which provides the foundation for osseointegration. In vivo implantation experiments demonstrate osseointegration is also promoted. This work thus demonstrates NIR-generated electrons can sequentially eradicate biofilms and regulate the osteogenic process, providing new solutions to fabricate efficient implant surfaces.

Regulation of the upconversion effect to promote the removal of biofilms on a titanium surface via photoelectrons.

Biofilms on public devices and medical instruments are harmful. Hence, it is of great importance to fabricate antibacterial surfaces. In this work, we target the preparation of an antibacterial surface excited by near-infrared light via the coating of rare earth nanoparticles (RE NPs) on a titanium surface. The upconverted luminescence is absorbed by gold nanoparticles (Au NPs, absorber) to produce hot electrons and reactive oxygen species to eliminate the biofilms. The key parameters in tuning the upconversion effect to eliminate the biofilms are systematically investigated, which include the ratios of the sensitizer, activator, and matrix in the RE NPs, or the absorber Au NPs. The regulated RE NPs exhibit an upconversion quantum yield of 3.5%. Under illumination, photogenerated electrons flow through the surface to bacteria, such as E. coli, which disrupt the breath chain and eventually lead to the death of bacteria. The mild increase of the local temperature has an impact on the elimination of biofilms on the surface to a certain degree as well. Such a configuration on the surface of titanium exhibits a high reproducibility on the removal of biofilms and is functional after the penetration of light using soft tissue. This work thus provides a novel direction in the application of upconversion materials to be used in the fabrication of antibacterial surfaces.

Ion-incorporated titanium implants for staged regulation of antibacterial activity and immunoregulation-mediated osteogenesis.

Antibacterial properties and osteogenic activity are considered as two crucial factors for the initial healing and long-term survivability of orthopedic implants. For decades, various drug-loaded implants to enhance biological activities have been investigated extensively. More importantly, to control the drug release timing is equally significant due to the sequential biological processes after implantation. Hence, developing a staged regulation system on the titanium surface is practically significant. Here, we prepared TiO2 nanotubes (TiO2 NTs) on the titanium surface by anodization, followed by the incorporation of zinc (Zn) and strontium (Sr) sequentially through a hydrothermal process. Surface characterization confirmed the successful fabrication of Zn and Sr-incorporated TiO2 NTs (Zn-Sr/TiO2) on the titanium surface. The ion release results exhibited the differential release characteristic of Zn and Sr, which meant the early-stage release of Zn and the long-term release of Sr. It was exactly in accord with  the biological process after implantation, laying the basis of staged regulation after implantation. Zn-Sr/TiO2 showed favorable anti-early infection properties both in vitro and in vivo. Its inhibition effect on bacterial biofilm formation was attributed to the resistance against bacteria's initial adhesion and the killing effect on planktonic bacteria. Additionally, the release of Sr could alleviate infection-induced damage via immunoregulation. The biocompatibility and osteogenic activity mediated by M2 macrophage activation were confirmed with in vitro and in vivo studies. Therefore, it exhibited great potential in staged regulation for antibacterial activity in the early stage and the M2 activation-mediated osteogenic activity in the late stage. The staged regulation process was based on the differential release of Zn and Sr to achieve the early antibacterial effect and the long-term immune-induced osteogenic activity, to prevent implant-related infection and achieve better osseointegration. These two kinds of ions played their roles synergistically and complement mutually. This work is expected to provide an innovative idea for realizing sequential regulation after implantation.

A novel Electro-Fenton process characterized by aeration from inside a graphite felt electrode with enhanced electrogeneration of H2O2 and cycle of Fe3+/Fe2.

A novel Electro-Fenton process characterized by aeration from inside a graphite felt electrode with enhanced generation of H2O2 and cycle of Fe3+/Fe2+ was proposed. The new type of Electro-Fenton process was used to degrade organic pollutants via graphite felt electrode aeration (GF-EA). The H2O2 concentration by GF-EA could reach 152-169 mg/L in a wide pH range (3-10), which was much higher than that achieved by graphite felt using solution aeration (GF-SA, 37-113 mg/L). For the degradation of nitrobenzene (NB), benzoic acid (BA), bisphenol A (BPA), and sulfamethoxazole (SMX) at pH 5.5, the percentage degradation by GF-EA could reach 55%, 56%, 80%, and 60% higher than those obtained by GF-SA, respectively. The solution TOC removal by GF-EA were enhanced by 29-51% relative to GF-SA. Mechanism analysis showed both OH and ferryl species were involved in the reaction system, and the amounts of OH and dissolved iron species in GF-EA group were 7.7 times and 4-8 times higher than those in GF-SA group, respectively. Besides, the mass transfer rate of GF-EA system was 5.4 times higher than that of GF-SA system. High amounts of H2O2, dissolved iron species and OH were attributed to the enhanced mass transfer of O2 and the solution.