Engineered neutrophils, modified via advanced biotechnological tools, are emerging as pivotal agents in translational medicine. By integrating gene editing (e.g., CRISPR-Cas9), nanotechnology, and artificial intelligence (AI), these cells are redefining precision diagnostics and therapeutics. Gene editing enables precise reprogramming to enhance tumor-targeting, antimicrobial activity, and immune modulation. Nanotechnology facilitates neutrophil-bound drug delivery, improving targeting to inflamed or tumor sites while reducing off-target effects. Simultaneously, AI-driven platforms analyze multi-omics data to optimize engineering strategies and personalize treatments. These innovations demonstrate significant promise across clinical domains: in oncology, they deliver cytotoxic payloads and remodel the tumor microenvironment; in infectious diseases, they enhance pathogen clearance; and in autoimmune disorders, they dampen aberrant inflammatory responses. Despite this progress, challenges including off-target edits, short in vivo persistence, and immune rejection persist. The convergence of microfluidics and high-throughput screening, coupled with AI-driven monitoring, is essential to accelerate clinical translation. As interdisciplinary collaboration deepens, engineered neutrophils stand at the forefront of next-generation medicine, offering versatile, patient-tailored strategies to bridge the gap between bioengineering breakthroughs and clinical reality.

Microbes can respond to stress in ways that benefit plants under stress, a phenomenon called microbe-mediated acclimation. However, microbe-mediated acclimation has been tested under a limited number of stressors, and it remains unclear whether plant benefits are stress-specific or whether microbial stress responses provide cross-tolerance to multiple stressors. We inoculated Chamaecrista fasciculata plants with microbial communities from the rhizosphere of field plants that experienced salt, herbicide, or herbivory stress, non-stressful conditions, or a sterile inoculant and grew them under these same four environments in the greenhouse. We did not observe microbe-mediated acclimation to any stressor, nor did microbes respond to stress in ways that provided cross-tolerance to multiple stressors. Instead, inoculation with a live microbial community (absent exposure to stress) exacerbated the fitness effects of herbicide and herbivory stress, and microbial responses to herbicide consistently reduced plant survival across all contemporary environments. Our results suggest that microbial communities do not always respond to stress in ways that promote plant stress tolerance, despite the many cases reported in the literature, and illustrate the need for future research identifying which stressors and environmental contexts are most likely to result in microbe-mediated acclimation versus persistent negative microbial legacy effects of stress.

Microbiomes that enhance the performance of host plants are likely to be co-introduced with their host during colonization because of their intimate association. Yet, it is unclear how co-introduced microbes will impact host colonization, as both the microbiome and its effects could vary upon introduction into a new habitat. Using the duckweed Lemna japonica - a cosmopolitan, freshwater angiosperm - and its microbiome, we tracked the colonization of both plants and microbes during an experimental co-introduction in the wild. We tested how plant performance varied during colonization when plants were co-introduced with microbes from their home habitat or with microbes local to the introduced habitat. We found that plant performance was substantially reduced when plants were co-introduced with microbes from their home habitat (i.e. with microbes that are non-local to the introduced habitat), relative to hosts with a local microbiome. Moreover, negative impacts from the initial, non-local microbiome persisted for multiple host generations despite a rapid turnover in microbiome composition. Our results suggest that the initial microbiome plants are co-introduced and can leave lasting impacts on plant performance during colonization. Considering the identity of the co-introduced microbiome will therefore be critical to predicting plant colonization dynamics in an era of global change.

Minor histocompatibility antigen (mHAg)-specific alloreactive donor T cells cause graft vs. host disease (GVHD) in matched related donor allogeneic hematopoietic cell transplantation (HCT). In a phase I trial, we expanded and infused (on day -2) mHAg-specific donor regulatory T cells (Treg) together with sirolimus-based pharmacologic prophylaxis to examine safety and preliminary efficacy of this GVHD prevention approach. We employed a 3+3 phase I design escalating Treg dose in 4 levels: 0.5 x 105/kg, 1 x 105/kg, 2 x 105/kg, and 4 x 105/kg. Dose-limiting toxicity (DLT) included grade 4-5 related infusion reaction, grade 4-5 unexpected organ toxicity, grade III-IV acute GVHD, or treatment-related death. Secondary and exploratory measures examined acute and chronic GVHD, survival outcomes, and Treg clone (TCR-Seq) expansion in culture, and in-vivo longevity and expansion post-HCT. 15 subjects were included (N=3 each per dose levels 1-3, and N=6 in dose level 4). No DLT were observed, and 4 x 105/kg Treg was identified as MTD. Median follow up for survivors was 41.7 months (range 14.5-72.8). The day 100 cumulative incidence of grade II-IV acute GVHD was 13% (95% CI 2-35%). NIH moderate/severe chronic GVHD by 1 year was 6.7% (95% CI 0.36-27%) and by 3 years was 20% (95%CI 4.4-44%). Overall survival was 73% (95% CI 54-100%). Treg clones expanded in culture, and demonstrated post-HCT lineage fidelity, persistence, and in-vivo expansion. This translational trial supports mHAg-specific expanded donor Treg as a novel GVHD prevention strategy, and demonstrates expanded donor Treg clones can persist and expand through one-year post-HCT. NCT01795573.

Getah virus (GETV) has reemerged as an important mosquito-borne pathogen affecting livestock health in East and Southeast Asia. To quantify its epidemiological patterns, we conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant meta-analysis of literature published between 2000 and September 2025. Analysis of 24 observational studies covering swine, equine, bovine, caprine, and wildlife populations using a random-effects model revealed a pooled mammalian seroprevalence of 26% (95% confidence interval [CI]: 0.17-0.38) and a pooled nucleic acid positivity rate of 2% (95% CI: 0.01-0.05), consistent with broad past exposure but limited detection of active viremia in cross-sectional surveys. Swine were identified as the main amplifying hosts, particularly in intensive farming regions of eastern and southern China, where herd seropositivity exceeded 60%. Results indicate a significant prevalence increase over the past 25 years. The established mosquito-swine-mosquito transmission cycle confirms GETV has transformed from a sporadic pathogen into a persistent threat within intensive farming environments.

While family income and neighborhood disadvantage have been associated with adolescent mental health, less is known about their independent associations with distinct, group-based patterns of change. Moreover, little is known about how school environments are associated with such mental health trajectory patterns, and if they serve as independent promotive factors or are protective factors that mitigate risk. Data come from the Adolescent Brain Cognitive Development Study[SM](ABCD study[®]; n = 9769; baseline through year 2; ages 9-13). Internalizing and externalizing behaviors were measured with the Child Behavior Checklist. Growth mixture modeling was utilized to identify subgroups with distinct mental health trajectories, and logistic regression was used to examine the association between family income, neighborhood environment and trajectory group membership, and moderation by baseline school and school district characteristics, controlling for age, sex, race/ethnicity, and parental education. Two trajectory classes were identified for internalizing (91%; low-decreasing, 9%; high-increasing) and externalizing behaviors (92%; low-decreasing, 8%; high-stable). Lower family income was associated with a high-increasing trajectory pattern of internalizing and a high-stable pattern of externalizing behaviors. A more positive school climate predicted belonging to the low-decreasing trajectory group for internalizing and externalizing behaviors, though there was no evidence of moderation. Low family income, but not neighborhood disadvantage, was a risk factor for trajectories of internalizing and externalizing behavior elevated within a clinical range that persisted from age 9 through early adolescence. However, a positive school climate was a promotive, rather than a protective, factor for internalizing and externalizing trajectories. Supporting families with resources and enhancing the school context may improve adolescent mental health.

The truncated constitutive active form of protein kinase C (PKC) called protein kinase M (PKM) plays a role in long-term memory maintenance in vertebrate and invertebrate models. Previously we have shown that the Aplysia Kidney/Brain protein (KIBRA) stabilizes the atypical PKM Apl III, but not the classical PKM Apl I in Aplysia neurons. Expression of Aplysia KIBRA with changes in the proposed atypical PKM binding site does not stabilize PKM Apl III and erases forms of plasticity supported by PKM Apl III. Here, we have examined biomolecular fluorescence complementation (BIFC) between KIBRA variants and PKM Apl III in Aplysia neurons. These KIBRA variants include: the KIBRA with changes in the proposed atypical binding site noted above; a splicing variant that stabilizes PKM Apl I, but not PKM Apl III; and several mutations identified in mammalian WW and C2 domain containing protein 3 (WWC3, a member of the chordate-specific expansion of the KIBRA family) associated with cancer or neurodevelopmental disorders. Surprisingly, we find that some KIBRA variants show BIFC with PKM Apl III but do not stabilize PKM Apl III. We used models of protein-protein interactions (AlphaFold 3) to gain insights into the discrepancy between BIFC and stabilization of PKMs by KIBRA and KIBRA variants and suggest a model where stabilization is linked to stable inhibition of PKMs by KIBRA.