Oral inflammatory diseases affect nearly half of all humans, yet mechanisms underlying rapidly-destructive inflammation remain poorly understood. We compared peri-implantitis with moderate- and high-grade periodontitis using integrated microbial and single-cell sequencing (>967,169-cells; single-cell RNA-seq, spatial proteotranscriptomics). Laser capture microdissection with compartmental microbiome analysis revealed reduced bacterial load and diversity in peri-implantitis. Expansion of the Human Periodontal Atlas with peri-implantitis single-cell RNA-seq data (36-samples; 121,395 cells) identified CD34⁺ vascular endothelial cell (VEC) rarefaction and oxidative stress, hypoxia, and NAD⁺ metabolism-associated transcriptional programs enriched in a TNFRSF6B⁺/ICAM1⁺ post-capillary venule (PC-VEC) subpopulation. NAD⁺-consuming ectoenzyme CD38 was selectively enriched and orthogonally confirmed by spatial transcriptomics (6-samples; 283,377-cells) and proteomics (23-samples; 562,397-cells). Spatial neighborhood analyses demonstrated CD38⁺-high PC-VEC expansion, closer proximity, and higher IL16–CD4 T cell signaling in peri-implantitis. Matched high-grade periodontitis biopsies confirmed spatially restricted CD38⁺-VECs despite similar microbial burden, identifying endothelial vasculopathy underlying rapidly advancing oral inflammation and a potential therapeutic axis.

The DNA damage response (DDR) mechanisms that allow cells to tolerate DNA replication stress are critically important for genome stability and cell viability. Using an unbiased genetic screen, we identify a role for the RING finger E3 ubiquitin ligase RNF25 in promoting DNA replication stress tolerance. In response to DNA replication stress, RNF25-deficient cells generate aberrantly high levels of single-stranded DNA (ssDNA), accumulate in S-phase and show reduced mitotic entry. Using single-molecule DNA fiber analysis, we show that RNF25 protects reversed DNA replication forks generated by the fork remodeler HLTF from nucleolytic degradation by MRE11 and CtIP. Mechanistically, RNF25 interacts with the replication fork protection factor REV7 and recruits REV7 to nascent DNA after replication stress. The role of RNF25 in protecting replication forks is fully separable from its canonical functions in ubiquitin conjugation. This work reveals the RNF25-REV7 signaling axis as an important protective mechanism in cells experiencing replication stress.

Oral inflammatory diseases affect nearly half of the global population. Among them, newly defined peri-implantitis and high-grade periodontitis represent rapidly advancing inflammatory disease types, marked by relatively rapid tissue destruction. Despite their prevalence, the cell mechanisms and spatial architecture driving this severity remain poorly understood. Focusing first on peri-implantitis versus low- and moderate-grade periodontitis, we applied microbial profiling, single-cell RNA sequencing (scRNA-seq), and spatial proteomics (sp-proteomics) to uncover shared pathogenic programs linked to accelerated niche breakdown. Furthermore, to preserve spatial fidelity, each tissue was anatomically orientated along the tooth- or implant-epithelial interface, analogous sites of disease origination. Laser capture microdissection followed by microbiome analysis of unique tissue compartments revealed reduced bacterial load and diversity in peri-implantitis stroma. We then expanded our version-1 Human Periodontal Atlas by integrating newly generated peri-implantitis scRNAseq data (36-total samples; 121395-cells), revealing widespread transcriptional alterations, including oxidative stress, hypoxic, and NAD+ metabolism-associated signatures, primarily in a subpopulation of TNFRSF6B+/ICAM1+ post-capillary venules. We then performed high-resolution sp-proteomics (15-total samples; 337260-cells) and analyzed VEC states and associated neighborhoods via AstroSuite using newly developed tri-wise spatial analysis. This revealed CD34+-VEC loss and CD38+-VEC expansion almost exclusively in peri-implantitis. We extended this analysis to high-grade periodontitis. Mucosal biopsies from four lesion-affected and four unaffected sites within the same individuals (1:1 matched; 8 samples; 225137-cells) again demonstrated spatially restricted CD38+-VEC remodeling exclusively in affected tissues, with similar vasculopathy front patterning. The findings nominate spatially distinct vasculopathy patterning as a hallmark of rapidly advancing oral inflammation and a targetable therapeutic axis.

Background: The influenza pandemic is a wide-ranging threat to people’s health and property all over the world. Developing effective strategies for predicting the influenza outbreak which may prevent or at least get ready for a new influenza pandemic is now a top global public health priority.Methods: Owing to the complexity of influenza outbreaks that are usually involved with spatial and temporal characteristics of both biological and social systems, however, it is a challenging task to achieve the real-time monitoring of influenza outbreaks. In this study, by exploring the rich dynamical information of the city network during influenza outbreaks, we developed a computational method, the minimum-spanning-tree-based dynamical network marker (MST-DNM), to identify the tipping point or critical stage prior to the influenza outbreak.Results: With historical records of influenza outpatients between 2009 and 2018, the MST-DNM strategy has been validated by accurate predictions of the influenza outbreaks in three Japanese cities/regions respectively, i.e., Tokyo, Osaka, Hokkaido. These successful applications show that the early-warning signal was detected 4 weeks on average ahead of each influenza outbreak.Conclusion: The results show that our method is of considerable potential in the practice of public health surveillance.

Patients with severe Dentofacial Disharmony such as Class III underbites have a twentyfold increased prevalence of speech disorders. To understand the longitudinal effects of corrective jaw surgery on speech, a prospective observational cohort study was conducted of Class III patients (n = 67, Ages 15-36, without clefts). Class I proportional controls (n = 54) and Class III patients were recorded 1-2 months pre-surgery, 2-6 months post-surgery (short-term) and 9-14 months post-surgery (long-term). Speech recordings were evaluated through distortion ratings and measurement of spectral changes in consonant production. ANOVAs and linear mixed-effects models were used to assess changes in speech and cephalometric measures. Here we show that spectral features, distortion, self-reported speech outcomes, and cephalometric measures significantly improve post-operatively. Patients with severe distortions improve the most after surgery. Consonant production requires properly positioned articulatory structures, and surgery provides longitudinal speech improvement for patients with jaw disproportions. Data indicate functional benefit of jaw surgery on speech.