The normal microflora of the skin includes staphylococcal species that will induce inflammation when present below the dermis but are tolerated on the epidermal surface without initiating inflammation. Here we reveal a previously unknown mechanism by which a product of staphylococci inhibits skin inflammation. This inhibition is mediated by staphylococcal lipoteichoic acid (LTA), and acts selectively on keratinocytes triggered through Toll-like receptor (TLR) 3. The significance of this is seen by observations that TLR3 activation is required for normal inflammation after injury, and that keratinocytes require TLR3 to respond to RNA from damaged cells with the release of inflammatory cytokines. Staphylococcal LTA inhibits both inflammatory cytokine release from keratinocytes and inflammation triggered by injury through a TLR2-dependent mechanism. These findings show for the first time that the skin epithelium requires TLR3 for normal inflammation after wounding and that the microflora can modulate specific cutaneous inflammatory responses.

Background Microplastic pollution has become a serious global environmental threat. The abundance of microplastics in the air is an order of magnitude higher than that in other media, which means that all living animals breathing with lungs (including humans) cannot escape the fate of inhaling microplastics. However, there is no direct evidence to demonstrate what type and abundance of microplastics exist in lung tissue. In addition, whether the retention of microplastics and the long-term friction between microplastics and lung tissue are related to some respiratory diseases is largely unknown. Ground glass nodules (GGNs) are areas of lesions of homogeneous density and with hazy increase in density in the lung field that do not obscure the bronchovascular structure, which have been increasingly identified in past decades. Although their etiology is broad, the correlation of microplastics with GGNs remains elusive. Results In this study, we identified the presence of 65 microfibers, including 24 microplastics (> 20 μm) in 100 human lung tissues with μ-FTIR. The detection rate of microfibers in tumor was 58%, higher than that in normal tissue (46%), and 2/3 of microplastics were found in tumor. Microfibers seemed to be embedded in lung tissues, which was suggested by the in situ observation via LDIR. Additionally, sub-micron-sized plastic particles were also detected in some lung tissues with Raman. The abundance of microfibers in lung tissue gradually accumulated with the increase of age. Moreover, the detection rate in tumor of patients with higher microfiber exposure risk history was significantly higher than those with a relatively lower one, implying microfiber inhalation could be related to the formation of GGN. Further, serious weared surface of microfibers isolated from lung tissue emphasized a possible link of surface roughness to the disease progression. Conclusions Collectively, the existence of microplastics in human lung tissues was validated, and their correlation with GGN formation was preliminarily explored, which laid a foundation for future research on microplastic exposure in the etiology of lung cancer and other related respiratory diseases. Graphical Abstract

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier‐free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH‐responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor‐associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier‐free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.

Objective Obesity is a complex chronic disease of high prevalence worldwide. Multiple factors play integral roles in obesity development, with rising interest focusing on the contribution of environmental pollutants frequent in modern society. Silver nanoparticles (AgNPs) are widely used for bactericidal purpose in various applications in daily life. However, their potential toxicity and contribution to the obesity epidemic are not clear. Methods Beige adipocytes are newly discovered adipocytes characterized by high thermogenic and energy dissipating capacity upon activation and the “browning” process. In the present study, we assess the impact of AgNPs exposure on beige adipocytes differentiation and functionality both in vitro and in vivo . We also systematically investigate the influence of AgNPs on adiposity and metabolic performance in mice, as well as the possible underlying molecular mechanism. Results The results showed that, independent of particle size, AgNPs inhibit the adipogenic, mitochondrial, and thermogenic gene programs of beige adipocytes, thus suppressing their differentiation ability, mitochondrial activity, and thermogenic response. Importantly, exposure to AgNPs in mice suppresses browning gene programs in subcutaneous fat, leading to decreased energy expenditure and increased adiposity in mice. Mechanistically, we found that AgNPs increase reactive oxidative species (ROS) levels and specifically activate MAPK-ERK signaling in beige adipocytes. The negative impacts of AgNPs on beige adipocytes can be ameliorated by antioxidant or ERK inhibitor FR180204 treatment. Conclusions Taken together, these results revealed an unexpected role of AgNPs in promoting adiposity through the inhibition of beige adipocyte differentiation and functionality, possibly by disrupting ROS homeostasis and ERK phosphorylation. Future assessments on the health risk of AgNPs applications and their safe dosages are warranted.

No abstract