Innate lymphoid cells (ILCs) are key regulators of early immune responses and play a central role in mucosal immunity, where they contribute to host defense and tissue homoeostasis. This review synthesizes evidence that ILCs, including natural killer cells (NKs), ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells, directly sense pathogens via pattern recognition receptors (PRRs). Beyond their established role as cytokine responders, emerging data reveal that ILCs engage PRRs to initiate complementary, context-dependent signaling pathways. This direct recognition mechanism redefines the functional landscape of ILCs in early immune surveillance, moving beyond reliance on indirect stromal signals. Collectively, these insights reposition ILCs as active sentinels in host defense and highlight the ILC-PRR axis as a novel therapeutic avenue for modulating immune responses in infectious, inflammatory, and cancer-related diseases.

To investigate tissue damage and recovery after low-temperature plasma radiofrequency ablation in saline at 0 °C,4 °C, and 25 °C, and to determine optimal temperature parameters for plasma radiofrequency ablation. A total of 72 sides of oral and buccal mucosa from 36 New Zealand white rabbits were randomly divided into a long-term observation group and an immediate execution group. Subsequently, they were assigned to three temperature groups: 0 °C, 4 °C and 25 °C. In the long-term observation group, after ablation of the buccal mucosa on both sides of the rabbits, the damage area and the number of days required for healing at each postoperative time point were analyzed. Another group collected samples after the same treatment and performed pathological analysis to evaluate the depth of tissue damage, the extent of inflammatory cell infiltration and the proportion of collagen fibers at different temperatures. The complete healing time of the 0 °C group was shorter than that of the other two groups. On the third day after surgery, both the direct damage and the overall damage areas of the 0 °C group were larger than those of the 4 °C group and the 25 °C group. From the first to the third day after surgery, the recovery rate, whether for direct damage or overall damage, was better in the 4 °C and 25 °C groups compared to the 0 °C group. Additionally, from the seventh to the ninth day after surgery, the direct damage recovery rate in the 4 °C group was better than that in the 0 °C group. The postoperative tissue damage depth in the 0 °C group was shallower than in the 4 °C group. There were no significant differences among the three groups in inflammatory cell infiltration or the proportion of collagen fibers in the injured tissue. The initial injury area in the 0 °C group was larger, and the recovery rate was slower at certain time points during the recovery period. However, it achieved complete healing earlier than the 4 °C group and the 25 °C group. These results indicate that the temperature of the saline solution not only affects the extent of early injury but also influences the subsequent speed of tissue repair.Level of evidence: II.

Defining vaccine-induced protection in children with humoral immunodeficiency is essential to guide SARS-CoV-2 vaccination strategies in this high-risk population. We conducted a longitudinal analysis of SARS-CoV-2 immunity at 1, 6 and 12 months after a primary Pfizer-BioNTech mRNA vaccine series in 27 children aged 5-11 years with primary or secondary antibody deficiencies and 48 matched healthy controls. Functional T-cell responses were quantified by IFN-γ and IL-2 ELISpot, and SARS-CoV-2-specific B-cells and T-cells were assessed by spectral cytometry. Systemic and mucosal antibody responses were measured in serum and saliva, and neutralizing activity against ancestral and Omicron BA.5 strains was evaluated through microneutralization. Children with humoral immunodeficiency exhibited impaired systemic antibody responses after two mRNA doses, even after SARS-CoV-2 infection. A third dose improved humoral immunity in children with preserved B-cell compartments but did not rescue neutralizing antibody responses in those with severe B-cell lymphopenia. In contrast, preserved, polyfunctional SARS-CoV-2-specific T-cell responses were observed in children with humoral immunodeficiency, including those with severe B-cell lymphopenia, and were higher in asymptomatic immunocompromised children. These findings reveal a dissociation between humoral failure and preserved cellular immunity in B-cell-deficient children, supporting timely vaccination and integration of T-cell responses into vaccine-response assessment when neutralizing antibodies are absent.

Ulcerative colitis (UC) is defined as a chronic inflammatory disease with recurrent episodes, and current therapeutic strategies for this gastrointestinal disorder often fail to achieve satisfactory clinical outcomes. This clinical challenge underscores an urgent requirement to develop alternative treatment strategies. Patchouli alcohol (PA), a natural compound exhibiting anti-inflammatory and antioxidant properties, has shown potential; however, its precise mechanisms of action in UC remain to be fully elucidated. Our study shows that PA can effectively alleviate the symptoms of dextran sulfate sodium (DSS)-induced UC in mice. This therapeutic effect is achieved by reducing intestinal barrier impairment and inhibiting inflammatory reactions. In an LPS-induced inflammatory model using RAW264.7 cells, PA significantly downregulated the mRNA expression of il-1β and il-6. Mechanistically, protein disulfide isomerase (PDI) was identified as a direct target of PA. By inhibiting IRE1 activation via PDI, PA mitigates endoplasmic reticulum stress, thereby reducing intestinal epithelial injury and ultimately alleviating the severity of UC. In this research, it is determined that the ability of PA to protect the intestinal epithelial barrier is brought about by its specific targeting of PDI, which alleviates consequent endoplasmic reticulum stress and prevents cellular damage.

Oral ulcers, affecting 25% of the global population, cause significant pain and functional impairment due to lesions exacerbated by a dynamic oral environment. Current treatments fail to address the challenges of poor drug retention, excessive inflammation, inadequate angiogenesis, and persistent pain. Herein, we report a bioadhesive microneedle (MN) patch that enables sustained drug retention and synergistically achieves anti-inflammatory, pro-angiogenic, and analgesic functions by a spatiotemporally-ordered drug delivery mechanism. The MN tips, made of hyaluronic acid methacryloyl (HAMA), are loaded with triamcinolone acetonide (TA) and vascular endothelial growth factor (VEGF)-encapsulated silk fibroin nanoparticles (SFNP). By leveraging sustained drug retention and precise delivery, drug utilization is enhanced. This design enables rapid TA release to remodel the inflammatory microenvironment, followed by controlled and sustained VEGF release from the SFNP to promote vascular and tissue regeneration. A dopamine-modified silk fibroin (SFD) substrate provides robust mucosal adhesion, allowing prolonged attachment to ulcer sites and acting as a physical barrier for pain relief. Animal experiment results further demonstrate that the MN patch can significantly accelerate oral ulcer healing and improve therapeutic outcomes. Collectively, this multifunctional MN patch overcomes multiple limitations of existing treatments through spatiotemporally-ordered drug delivery, establishing a novel paradigm for mucosal disease management.

Neonatal calf health critically depends on successful passive transfer of immunity (PTI) via colostrum. Although PTI is routinely assessed by serum IgG concentration, associated systemic proteomic responses remain poorly defined. This study aimed to relate distinct PTI categories to neonatal calf serum proteomes and to evaluate colostrum proteomes to identify proteins influencing passive transfer success. Forty Holstein cow-calf pairs were enrolled. Calf serum was collected before colostrum feeding (0 h) and at 48 h. Serum IgG was quantified by ELISA, and calves were classified at 48 h as failed (FPTI, <1000 mg/dL, n = 11), adequate (APTI, 1000-2000 mg/dL, n = 11), or excellent (EPTI, >2000 mg/dL, n = 18). For proteomic analyses, five calves were purposefully selected in each group; serum samples were pooled by PTI group and time point, and colostrum samples by PTI group, then analyzed by LC-MS/MS in DIA mode. Proteomics identified 54 proteins in colostrum and 80 in serum, 27 of which were shared between matrices. Post-colostrum intake, 21 (FPTI), 5 (APTI), and 30 (EPTI) serum proteins changed significantly from 0 to 48 h. In EPTI calves, haptoglobin (Hp) (51.10-fold) and pigment epithelium-derived factor (PEDF) (27.24-fold) showed the strongest upregulation. At 48 h, lipopolysaccharide-binding protein (LBP) and haemoglobin subunit epsilon (Hb-ε) were lower in EPTI, whereas PEDF, polymeric immunoglobulin receptor (PIGR), and SERPINA3-6 were higher, consistent with coordinated activation of acute-phase, mucosal/transport, and protease-antiprotease pathways. These findings indicate that PTI involves coordinated proteomic changes beyond IgG alone and highlight candidate biomarkers of successful passive immunity in neonatal calves.