Nanoplastics Shape Adaptive Anticancer Immunity in the Colon in Mice.

The impact of nanoplastics (NPs) on human health is still not well understood, and more research is needed to better understand the risks associated with these particles. In this study, we found that oral administration of polyethylene (PE) NPs in a mice model significantly disrupted the intestinal microenvironment, which shapes adaptive immune response and favors the established in situ colorectal tumor growth. Using single-cell RNA sequencing technology, we show that NPs triggered colon IL-1ß-producing macrophages by inducing lysosome damage, leading to colonic Treg and Th17 differentiation associated with T cell exhaustion, which creates a colon environment that favors the tumor initiation and progress. A similar effect is also observed in polystyrene NPs. Our result provides insight into the potential link between NPs ingestion and colon tumorigenesis, and the urgency of addressing plastic pollution worldwide.

Bone alteration and esthetics associated with implant-supported prostheses in the anterior maxilla under different implant placement timing: A retrospective clinical study of 1 to 3 years.

STATEMENT OF PROBLEM: Different factors influence alterations in facial bone thickness and esthetic outcomes after implant placement. Whether the timing of implant placement influences alterations in the bone dimensional and esthetic outcomes is unclear. PURPOSE: The purpose of this retrospective clinical study was to assess the influence of the timing of implant placement on alveolar bone alterations and esthetic outcome. MATERIAL AND METHODS: Data were collected from 40 patients who had received guided bone regeneration (GBR) performed simultaneously with immediate, early, or delayed single-tooth implant placement in the anterior maxilla. Facial and palatal horizontal bone thicknesses (FHBT, PHBT) and vertical bone level (FVBL, PVBL) immediately after surgery (T0), at 6 months after implant placement (T1), and at 1 to 3 years follow-up (T2) were measured, and the changes calculated. The pink esthetic score (PES) and white esthetic score (WES) were evaluated at the 1- to 3-year follow-up. The Kruskal-Wallis followed by the Dunn t test was applied to evaluate bone alteration among groups, and the Bonferroni method was used for adjusting multiple comparisons. The 1-way ANOVA test was used to determine any significance in the esthetic outcome in the 3 groups (α=.05). RESULTS: The reduction in the FHBT0 of the immediate, early, and delayed implant placement group (T2-T0) was -1.17 (-1.70, -0.61) mm, -1.53 (-1.69, -0.49) mm, and -1.47 (-2.30, -0.20) mm, respectively. The FHBT around the implant apices remained basically stable. No obvious changes in the PHBT around the implants of the immediate and delayed implant placement group were noted. The FVBL significantly decreased in each group during the follow-up period (-1.34 (01.88, -0.56) mm, immediate; -2.88 (-3.79, -1.07) mm, early; -1.26 (-2.52, -0.48) mm, delayed). The PVBL change in the early implant placement group (-2.18 (-3.26, -0.86) mm) was more significant than that in the immediate (-0.55 (-2.10, -0.17) mm) and delayed (-0.51 (-1.29, 0.02) mm) implantation groups (P =.013). The mean ±standard deviation PES/WES score of the immediate (15.6 ±1.84) and early (15.00 ±1.13) implant placement groups was higher than that of the delayed implant placement group (13.92 ±2.10) without significant difference. CONCLUSIONS: Similar bone changes and esthetic outcomes were found around implants of the immediate, early, and delayed implant placement groups.

Effects of extracellular DNA on dual-species biofilm formed by Streptococcus mutans and Candida albicans.

Streptococcus mutans is the most important acid-producing pathogen that causes dental caries, while Candida albicans is an opportunistic fungal pathogen that is frequently detected in conjunction with heavy infection by S. mutans. Their interactions in dental plaque biofilms remain unclear. Extracellular DNA (eDNA) is found in oral biofilms, but its effects have not been thoroughly defined. In this study, the role of eDNA in dual-species biofilms formed by S. mutans and C. albicans was investigated. With eDNA removal, the growth of both strains was not affected, but the formation of dual-species biofilms obviously decreased. In addition, the removal of eDNA spatially disrupted the structure of the dual-species biofilm. It was also shown that eDNA mainly affected the initial attachment and development stages of the dual-species biofilms but not the well-developed biofilms. A similar phenomenon was also observed in the cell viability of dual-species biofilms after DNase I treatment. To further exploration, we analyzed the expression of genes associated with biofilm formation in both S. mutans and C. albicans. We determined that the co-cultivation of S. mutans and C. albicans promotes the expression of genes related to extracellular polysaccharide production (e.g., gtfC), adhesion (e.g., spaP, epa1), mycelial transformation (e.g., hwp1), and drug resistance (e.g., cdr2). However, these genes were significantly downregulated when the eDNA of the dual-species biofilm was removed by adding DNase I compared to those untreated groups. Altogether, eDNA removal, such as that by DNase I treatment, could be considered a promising strategy to control oral biofilms and biofilm-associated oral diseases.

Small-Sized Microplastics Negatively Affect Rotifers: Changes in the Key Life-History Traits and Rotifer-Phaeocystis Population Dynamics.

Most coastal waters are at risk from microplastics, which vary in concentration and size. Rotifers, as important primary consumers linking primary producers and higher trophic consumers, usually coexist with the harmful alga Phaeocystis and microplastics in coastal waters; this coexistence may interfere with rotifer life-history traits and ingestion of Phaeocystis. To evaluate the effects of microplastics on rotifers, we designed a series of experiments concerning rotifer Brachionus plicatilis life-history traits and rotifer-Phaeocystis (predator-prey) population dynamics under different concentrations and sizes of microplastics. The results showed that small-sized microplastics (0.07 µm) at high levels (≥5 µg mL-1) decreased rotifer survival and reproduction, prolonged the time to maturation, and reduced the body size at maturation, whereas large-sized microplastics (0.7 and 7 µm) had no effect on rotifer life-history traits. For rotifer-Phaeocystis population levels, small-sized microplastics (0.07 µm) significantly delayed the elimination of Phaeocystis by rotifers; this is the first study to test the effects of microplastics on predator-prey dynamics. The results of rotifer-Phaeocystis population dynamics are consistent with the changes in the life-history traits of rotifers and further confirm the negative effects of small-sized microplastics (0.07 µm) on rotifers. These findings help to reveal the effect of pollutants on predator-prey population dynamics.

Genetic associations between circulating immune cells and periodontitis highlight the prospect of systemic immunoregulation in periodontal care.

Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues to be an attractive approach in periodontal care, particularly within the context of 'predictive, preventive, and personalized' periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells and periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable MR, subgroup analysis, reverse MR, and Bayesian model averaging (MR-BMA) were utilized to investigate the causal relationships. Furthermore, transcriptome-wide association study and colocalization analysis were deployed to pinpoint the underlying genes. Consequently, the MR study indicated a causal association between circulating neutrophils, natural killer T cells, plasmacytoid dendritic cells, and an elevated risk of periodontitis. MR-BMA analysis revealed that neutrophils were the primary contributors to periodontitis. The high-confidence genes S100A9 and S100A12, located on 1q21.3, could potentially serve as immunomodulatory targets for neutrophil-mediated periodontitis. These findings hold promise for early diagnosis, risk assessment, targeted prevention, and personalized treatment of periodontitis. Considering the marginal association observed in our study, further research is required to comprehend the biological underpinnings and ascertain the clinical relevance thoroughly.

Blood Clot Scaffold Loaded with Liposome Vaccine and siRNAs Targeting PD-L1 and TIM-3 for Effective DC Activation and Cancer Immunotherapy.

Tumor vaccines have been showing a relatively weak response rate in cancer patients, while deficiencies in delivery efficiency to dendritic cells (DCs), as well as DC-intrinsic immunosuppressive signals, contribute to a great extent. In this work, we report an implantable blood clot loaded with liposomes-protamine-hyaluronic acid nanoparticles (LPH NPs) containing vaccine (LPH-vaccine) and LPH NPs containing siRNA (LPH-siRNA) for synergistic DC recruitment and activation. The subcutaneously implanted blood clot scaffold can recruit abundant immune cells, particularly DCs, to form a DC-rich environment in vivo. Within the scaffold, LPH-vaccine effectively delivers antigens and adjuvants to the recruited DCs and induces the maturation of DCs. More importantly, LPH-siRNA that targets programmed death-ligand 1 (PD-L1) and T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) can reduce immunosuppressive signals in mature DCs and prevent the DCs from expressing a regulatory program in the scaffold. The activated DCs correlate with an improved magnitude and efficacy of T cell priming, resulting in the production of tumor antigen-specific T cells in multiple mouse models. Our strategy can also be used for patient-tailored therapy by change of tumor neoantigens, suggesting a promising strategy for cancer therapy in the clinic.

Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine.

Nanoplastics (NPs) as contaminants in food and water have drawn increasing public attention. However, little is known about how NPs shape the gut immune landscape after injection. In this study, we fabricate NPs (∼500 nm) and microplastics (MPs) (∼2 µm) and evaluate their in vivo effects by feeding them to mice. The results suggest that NPs show a better ability to induce gut macrophage activation than MPs. In addition, NPs trigger gut interleukin-1 (IL-1)-producing macrophage reprogramming via inducing lysosomal damage. More importantly, IL-1 signaling from the intestine can affect brain immunity, leading to microglial activation and Th17 differentiation, all of which correlates with a decline in cognitive and short-term memory in NP-fed mice. Thus, this study provides insight into the mechanism of action of the gut-brain axis, delineates the way NPs reduce brain function, and highlights the importance of fixing the plastic pollution problem worldwide.

Electrochemical deposition of lithium coating on titanium implant with enhanced early stage osseointegration.

Recently, a large number of studies have reported that lithium (Li) displayed a positive effect on osteogenesis. However, only a few studies have investigated the Li-incorporated surfaces through electrochemical deposition. In this study, electrochemical deposition was conducted on a CHI600E electrochemical workstation. The characterization of electrochemical deposition (ECD) and ECD-Li surfaces were detected by field-emission scanning electron microscopy with energy-dispersive spectrometer. rBMSCs were cultured on two surfaces for subsequent adhesion, proliferation and live/dead assay. To evaluate the effects of Li-incorporated implants by electrochemical deposition on osseointegration in vivo, teeth extraction of two premolars and one first molar in bilateral mandible were performed on six male beagle dogs. After 3 months, ZDI and ZDI-Li implants were inserted into the bilateral mandible of each beagle dog. Micro Computed Tomography (Micro-CT) and hard tissue sectioning analysis were carried out to evaluate the osseointegration at 4- and 8-weeks post-implantation. Results showed that ECD-Li surface promoted adhesion and proliferation of BMSCs in the early stage. More importantly, through micro-CT analysis, the values of bone volume/total volume (BV/TV) (0.374 ± 0.015), bone-implant contact (BIC) (0.831 ± 0.025), and Tb.Th (0.412 ± 0.007) in ZDI-Li group was significantly higher than those of ZDI group (0.302 ± 0.009, 0.700 ± 0.023, 0.353 ± 0.001, p < .01) at 4 weeks. Similarly, ZDI-Li group manifested more bone contact with the implant surfaces at 4 weeks based on hard tissue sectioning analysis, whereas no significant difference was detected between two groups at 8 weeks. Therefore, incorporating Li into implant surface through ECD could enhance early osseointegration in vivo.

3D Printing Scaffold Vaccine for Antitumor Immunity.

Cancer vaccine platform has attracted great interest in the field of cancer immunotherapy. Here, 3D printed scaffolds loaded with immunoregulators are developed for enhanced cancer immunotherapy. The rapid manufacturing and precise molding based on 3D printing can realize the mass manufacturing of cancer vaccines and personalized design. Meanwhile, compared to the traditional hydrogel, the 3D-scaffold with porous structure endows its similar functions compared with real lymphoid organs by recruitment of a great number of immune cells, leading to the formation of "artificial tertiary lymphoid structures," where there is a promising site to enhance both humoral and cellular immune responses. Efficient anticancer immunity is induced when combined with immune checkpoint blockade to inhibit the tumor growth. Personalized antitumor scaffold vaccines are further demonstrated for filling of tumor site after surgery to prevent cancer metastasis. Taken together, these results promise the 3D printing scaffold vaccine as the potential strategy for cancer vaccine therapy in the future.