Jialiu Xie

Background/Objectives: Omega-3 polyunsaturated fatty acids (PUFAs) influence lipid-mediated inflammatory pathways implicated in migraine, yet randomized trial data evaluating biologic effects of omega-3 supplementation in youth with migraine remain limited. This pilot quasi-randomized clinical trial aimed to determine whether 12 weeks of omega-3 PUFA supplementation produces measurable changes in whole-blood EPA and DHA levels in children and adolescents with migraine, and to characterize changes in patient-reported measures of pain, migraine-related disability, and psychological distress. Methods: We conducted a parallel-group, quasi-randomized, double-blind, placebo-controlled trial in children and adolescents (ages 10–17) with migraine diagnosed per International Classification of Headache Disorders, 3rd edition criteria, recruited from pediatric neurology clinics at two academic medical centers. Of 57 participants allocated 1:1 to daily omega-3 PUFA supplementation (340 mg EPA + 510 mg DHA) or coconut oil placebo for 12 weeks, 44 completed the study and were analyzed. The primary outcome was change in whole-blood omega-3 PUFA index. Secondary outcomes included patient-reported measures of pain intensity, pain interference, migraine-related disability, and psychological distress. Exploratory outcomes included changes in omega-6/omega-3 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratios. Between-group differences were evaluated using ANCOVA adjusting for baseline values. Results: Omega-3 supplementation significantly altered lipid biomarker profiles. Compared with placebo, the intervention group demonstrated greater increases in omega-3 PUFA index (adjusted mean difference 1.64; 95% CI 0.94–2.35; p < 0.001) and greater reductions in omega-6/omega-3 ratio (−2.57; 95% CI −4.25 to −0.90; p = 0.003) and AA/EPA ratio (−13.52; 95% CI −21.55 to −5.49; p = 0.002), consistent with the increase in whole-blood omega-3 levels. No significant between-group differences were observed in patient-reported outcomes. Conclusions: Omega-3 PUFA supplementation significantly altered lipid biomarker profiles in youth with migraine over 12 weeks, supporting a measurable whole-blood EPA + DHA response in this proof-of-concept trial. Future larger-scale trials with longer duration are needed to evaluate clinical effects.

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.

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.

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.

The DNA repair protein RAD18 activates ‘Y-family’ Trans-Lesion Synthesis (TLS) DNA polymerases that are DNA damage-tolerant and potentially error-prone. RAD18 is also frequently overexpressed and pathologically activated in cancer cells. However, the extent to which RAD18 shapes cancer genomes and impacts tumorigenesis is unclear. Therefore, we tested the effect of Rad18 status on chemically-induced and oncogene-driven tumorigenesis. In a chemically-induced oral carcinogenesis model, acute (2-16 days) 4NQO-treatment induces expression of Rad18 and TLS polymerase mRNAs in mouse oral epithelial cells prior to emergence of oral squamous cell carcinomas (OSCCs). Chronic (8 week) 4NQO-treatment leads to onset of oral tumors that is accelerated in Rad18 ^-/- mice when compared with Rad18 ^+/+ animals. Analysis of OSCC exomes reveals increased levels of G(C)>T(A) transversions in Rad18 ^-/- tumors when compared with Rad18 ^+/+ . Therefore, Rad18 promotes error-free bypass of 4NQO-induced DNA lesions and suppresses 4NQO-induced oral carcinogenesis. In a Kras ^G12D -induced lung carcinogenesis model, Rad18 -deficiency did not affect rates or incidence of oncogene-induced lung tumors or mutations. Taken together, we demonstrate that Rad18 has context-specific tumor-suppressive activity. Given the prevalence of 4NQO-like environmental exposures, RAD18 is highly likely to shape human cancer genomes and perhaps influence other aspects of the tumorigenic process.

Respiratory viral infections pose a global health burden, yet the cellular immune responses driving protection or pathology remain unclear. Natural infection cohorts often lack pre-exposure baseline data and structured temporal sampling. In contrast, inoculation and vaccination trials generate insightful longitudinal transcriptomic data. However, the scattering of these datasets across platforms, along with inconsistent metadata and preprocessing procedure, hinders AI-driven discovery. To address these challenges, we developed the Human Respiratory Viral Immunization LongitudinAl Gene Expression (HR-VILAGE-3K3M) repository: an AI-ready, rigorously curated dataset that integrates 14,136 RNA-seq profiles from 3,178 subjects across 66 studies encompassing over 2.56 million cells. Spanning vaccination, inoculation, and mixed exposures, the dataset includes microarray, bulk RNA-seq, and single-cell RNA-seq from whole blood, PBMCs, and nasal swabs, sourced from GEO, ImmPort, and ArrayExpress. We harmonized subject-level metadata, standardized outcome measures, applied unified preprocessing pipelines with rigorous quality control, and aligned all data to official gene symbols. To demonstrate the utility of HR-VILAGE-3K3M, we performed predictive modeling of vaccine responders and evaluated batch-effect correction methods. Beyond these initial demonstrations, it supports diverse systems immunology applications and benchmarking of feature selection and transfer learning algorithms. Its scale and heterogeneity also make it ideal for pretraining foundation models of the human immune response and for advancing multimodal learning frameworks. As the largest longitudinal transcriptomic resource for human respiratory viral immunization, it provides an accessible platform for reproducible AI-driven research, accelerating systems immunology and vaccine development against emerging viral threats.

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.