The blockage of androgen receptors significantly impair bone repair in females through mechanisms that are different from those related to estrogen receptors.

α-Ag 2 WO 4 has attracted much attention in recent years due to its unique crystal and electronic structures, which are suitable for a wide range of applications. This work presents a more realistic study, based on first-principles calculations and experimental results, of the potential of α-Ag 2 WO 4 for antibacterial and photocatalytic activity. α-Ag 2 WO 4 material has been successfully synthesized by a coprecipitation method and subjected to microwave irradiation for different times. The as-synthesized microcrystals were structurally characterized by X-ray diffraction, while the morphological aspects were investigated by field emission scanning electron microscopy. The experimental studies and theoretical simulations of α-Ag 2 WO 4 , based on density functional theory calculations, have highlighted several key parameters (surface-dependent) that determine the antibacterial (against Staphylococcus aureus ) and photocatalytic activity (for the degradation of Rhodamine B), and provided some general principles for materials design. We believe that our results offer new insights regarding the local coordination of superficial Ag and W cations (i.e. clusters) on each exposed surface of the corresponding morphology, that dictate the antibacterial and photocatalytic activities of α-Ag 2 WO 4 , a field that has so far remained unexplored. Response to Reviewers:Manuscript ID: TCAC-D-20-00072 Response to reviewersWe acknowledge the Reviewers for their help in improving our manuscript. As can be seen in the revised text, these comments, remarks and suggestions were considered during our revision. Detailed responses, point-by-point, to the reviewers are summarized below and the changes were made along the revised version of the manuscript and were highlighted in red color.

Background: Sex hormone therapy has strict recommendations in the treatment of postmenopausal symptoms, in which testosterone (TES) replacement may play a potential role. However, it remains unclear whether TES affects the course of chronic inflammation and alveolar bone loss in females. Herein, we investigated the role of androgen receptor and TES on the inflammatory response and alveolar bone resorption associated with ligature-induced periodontal disease in female rats.Methods: Fifty female Holtzman rats were divided in five groups (n = 10/group):androgen receptor antagonist (flutamide); estrogen receptor antagonist (fulvestrant); TES supplementation; aromatase inhibitor (anastrozole); and TES plus anastrozole.Periodontitis was induced by ligatures around the lower first molars for 2 weeks. Twenty animals (n = 10/group) were used as untreated ligated or non-ligated controls.Bone loss and the number of osteoclasts were measured through radiographic and immunohistochemical analysis, respectively. Inflammatory cytokines, chemokines and bone markers were measured by multiplex immunoassay and ELISA in serum samples and periodontal tissues. Results:The blockage of androgen receptor significantly increased radiographic bone loss and tissue levels of IL-1 (P <0.05), IL-1 (P <0.001) and IL-10 (P <0.01) compared with the periodontitis group. Testosterone supplementation significantly increased EGF levels in tissue samples, whereas when combined with aromatase inhibitor anastrozole significantly increased both EGF and VEGF (P <0.05). None of the treatment conditions significantly impacted the number of osteoclasts compared with the periodontitis group. Conclusions:Androgen receptor activation is an important factor in the regulation of several inflammatory markers, and its blockage significantly increases bone loss. K E Y W O R D Salveolar bone loss, androgen receptor antagonists, aromatase inhibitors, estrogen antagonists, inflammation, testosterone J Periodontol. 2020;91:545-553.