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Sialidase has an important role in the pathogenesis of periodontitis and Porphyromonas gingivalisis a sialidase‐producing organism implicated in periodontitis development. The aim of this study was to evaluate the anti‐virulence and anti‐inflammatory properties of the sialidase inhibitor, 2‐deoxy‐2,3‐didehydro‐N‐acetylneuraminic acid (DANA), in vitro and in vivo. The effects of DANA on P. gingivalissialidase and cell viability were determined, and the effects of DANA on P. gingivalisvirulence were evaluated by assessment of growth curves, cell morphology, biofilm formation, fimbriae gene expression, and gingipains and lipopolysaccharide (LPS) activity. Anti‐inflammatory effects of DANA on LPS‐induced macrophages were assessed by measurement of tumor necrosis factor‐alpha (TNF‐α), interleukin (IL‐1β), inducible nitric oxide synthase (iNOS) secretions. The effect of DANA on P. gingivalis–induced periodontitis in rats was analyzed by radiography, stereoscopic microscopy, histopathology, and immunohistochemistry. Sialidase inhibition rate of 1mM DANA was 72.01%. Compared with untreated controls, treatment with DANA inhibited P. gingivalisgrowth and biofilm formation, and significantly decreased expression of the fimA, fimR, and fimSgenes, as well as gingipains activity. DANA did not influence macrophage viability, but significantly inhibited TNF‐α, IL‐1β, and iNOS production in LPS‐stimulated macrophages. In the periodontitis rat model, DANA prevented alveolar bone absorption and inhibited TNF‐α and IL‐1β production. DANA can reduce the growth, the biofilm formation and the virulence of P. gingivalisand exhibits anti‐inflammatory effects, as well as effects against rat periodontitis, suggesting that DANA should be considered for development as a new adjunctive treatment for periodontitis.

Two-dimensional floating gate van der Waals heterostructures present an appealing opportunity to combine optoelectronic sensing and memory functionality in atomically thin layers, which, as optoelectronic memory, can find applications in high-throughput image sensors, artificial photonic neuromorphic hardware, etc.However, existing optoelectronic memory generally suffers from overshoot characteristics after optical stimulation due to the inherent and persistent recombination loss of photogenerated electron–hole pairs. Here, we demonstrate multibit floating gate optoelectronic memory free from such transient dynamics, based on a new van der Waals heterostructure of PtS2/h-BN/graphene. The large electron affinity of PtS2creates highly asymmetric tunneling barriers for hot electrons and holes across h-BN, therefore enabling the efficient separation of photogenerated electron–hole pairs during the optical programming of memory. Ladder-type optical programming involving up to 74 discriminable states (>6 bits) is thus achieved, with linear conductance during the update of memory, using sequentially applied light pulses. The present two-dimensional heterostructure with asymmetric charge tunneling barriers may inspire the future exploration of practical multibit optoelectronic memory viaattentive band engineering in two-dimensional van der Waals heterostructures.

Introduction: It is crucial to investigate the distinct proteins that contribute to the advancement of lung cancer. Material and Methods: We analyzed the expression levels of 92 immuno-oncology-related proteins in 96 pairs of lung adenocarcinoma tissue samples using Olink proteomics. The differentially expressed proteins (DEPs) were successively screened in tumor and paraneoplastic groups, early and intermediate-late groups by a nonparametric rank sum test, and the distribution and expression levels of DEPs were determined by volcano and heat maps, etc., and the area under the curve was calculated. Results: A total of 24 DEPs were identified in comparisons between tumor and paracancerous tissues. Among them, interleukin-8 (IL8) and chemokine (C–C motif) ligand 20 (CCL20) as potential markers for distinguishing tumor tissues. Through further screening, it was found that interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) may be able to lead to tumor progression through the JaK-STAT signaling pathway, Toll-like receptor signaling pathway and PI3K/AKT signaling pathway. Interestingly, our study revealed a down-regulation of IL6 and VEGFA in tumor tissues compared to paracancerous tissues. Conclusions: IL8 + CCL20 (AUC: 0.7056) have the potential to differentiate tumor tissue from paracancerous tissue; IL6 + VEGFA (AUC: 0.7531) are important protein markers potentially responsible for tumor progression.

Personalized in situtumor vaccination is a promising immunotherapeutic modality. Currently, seeking immunogenic cell death (ICD) to generate in situtumor vaccines is still mired by insufficient immunogenicity and an entrenched immunosuppressive tumor microenvironment (TME). Herein, a series of tetrazine-functionalized ruthenium(II) sonosensitizers have been designed and screened for establishing a bioorthogonal-activated in situtumor vaccine via oncolytic pyroptosis induction. Based on nanodelivery-augmented bioorthogonal metabolic glycoengineering, the original tumor is selectively remolded to introduce artificial target bicycle [6.1.0] nonyne (BCN) into cell membrane. Through specific bioorthogonal ligation with intratumoral BCN receptors, sonosensitizers can realize precise membrane-anchoring and synchronous click-activation in desired tumor sites. Upon ultrasound (US) irradiation, the activated sonosensitizers can intensively disrupt the cell membrane with dual type I/II reactive oxygen species (ROS) generation for a high-efficiency sonodynamic therapy (SDT). More importantly, the severe membrane damage can eminently evoke oncolytic pyroptosis to maximize tumor immunogenicity and reverse immunosuppressive TME, ultimately eliciting powerful and durable systemic antitumor immunity. The US-triggered pyroptosis is certified to effectively inhibit the growths of primary and distant tumors, and suppress tumor metastasis and recurrence in “cold” tumor models. This bioorthogonal-driven tumor-specific pyroptosis induction strategy has great potential for the development of robust in situtumor vaccines.