Jianjun Dai

A gastric-targeted oral microneedle is magnetically controlled to penetrate the gastric mucosa and release drugs in a pH-responsive manner. It carries diverse payloads from small molecules to biomacromolecules and shows in vivo efficacy.

EBV genomic variation has been shown to contribute to the development of certain EBV-associated cancers. While EBV genomic variation has been extensively studied at the nucleotide level, it remains unclear how synonymous codon usage contributes to viral adaptation across epithelial cancer contexts. Here, we analyzed 1148 EBV genomes with annotated tumor origins to investigate genome-wide genetic differentiation and codon usage patterns of 13 core genes across NPC- and GC-associated viruses and EBV types. SNP-based analyses revealed partial genetic separation between NPC-EBV and GC-EBV, characterized by both rare GC-associated risk variants and common protective haplotypes. Codon usage patterns, however, showed strong gene-specific structure: EBNA2 and EBNA3 clustered primarily by EBV type, whereas EBNA1 and LMP2A were more sensitive to tumor background. Codon bias analyses suggested heterogeneous contributions of mutational pressure and natural selection across genes and lineages, whereas lytic BALF genes displayed highly conserved codon usage despite cancer-associated variants. Collectively, this study demonstrates that codon usage patterns of specific EBV genes are associated with tumor background and are jointly shaped by gene function and viral lineage structure.

The increasing number of infections of mosquito-borne viruses, such as Chikungunya virus (CHIKV), highlight the urgent need for portable diagnostic tools in resource-limited areas, as traditional nucleic acid detection methods are unsuitable for on-site testing because of their reliance on bioenzymes and instruments. Bioenzyme-free nucleic acid amplification methods such as the catalytic hairpin assembly (CHA)-based lateral flow immunoassay (LFIA) have emerged as a promising strategy. However, the detection efficiency is constrained by the limited sites of the amplification products for bridging colorimetric probes to the test line. Herein, we report a multisite bridging mediated LFIA (mbLFIA) strategy, designing amplification products that have multiple sites for bridging colorimetric probes through dual mechanisms, thereby increasing the colorimetric signal by up to 10.8 times at low product concentrations. To further enhance the signal intensity, gold@platinum nanoparticles (Au@Pt NPs) featuring high peroxidase-like activity were used as colorimetric probes, as these can catalyze the oxidation and deposition of 3-amino-9-ethylcarbazole (AEC) on the test line, achieving a detection limit as low as 2 pmol·L⁻¹ for CHIKV. In a clinical evaluation using 36 suspected CHIKV mice serum samples, the method identified 16 positives, with 100% concordance to the reverse transcription polymerase chain reaction (RT-PCR) results, demonstrating high specificity and accuracy. This work provides a novel perspective for optimizing colorimetric signals in LFIA and presents a portable tool for the on-site nucleic acid detection of mosquito-borne viruses.

Merbecovirus, a subgenus of coronaviruses that includes the highly pathogenic Middle East respiratory syndrome coronavirus (MERSr-CoV), poses a significant zoonotic threat. To better understand its host adaptation and potential for cross-species transmission, we conducted a comprehensive analysis of codon usage patterns in 1967 Merbecovirus sequences. Phylogenetic analysis confirmed the division of Merbecoviruses into seven distinct clusters. Codon usage bias was found to be low and predominantly shaped by natural selection, with a consistent A/U-rich composition across the genome. Codon adaptation index (CAI) and relative codon deoptimization index (RCDI) analyses indicate that Merbecovirus exhibits potential host adaptation to Sus scrofa (pigs), Equus caballus (horses), and Oryctolagus cuniculus (rabbits), suggesting a risk of cross-species transmission. Strikingly, this genomic-level adaptation prediction is supported by emerging functional evidence: recent studies have demonstrated that key Merbecovirus lineages utilize diverse cell entry receptors (DPP4 or ACE2), a fundamental determinant of host tropism. For instance, the ability of the HKU5 lineage to utilize ACE2 receptors from mustelids like minks (Neogale vison) provides mechanistic support for the host adaptability trends inferred from our genomic analyses. By integrating existing receptor specificity data, this study provides the first systematic, large-scale analysis of codon usage across the Merbecovirus subgenus, elucidating key mechanisms of genomic adaptation and viral evolution. Our analytical framework provides a novel comparative perspective on host diversity and pinpoints specific surveillance priorities for mitigating future spillover risks.

Neonatal meningitis Escherichia coli (NMEC) breaching the blood-brain barrier (BBB) is a critical event in the development of E. coli meningitis. Brain microvascular endothelial cells (BMECs), the primary structural component of the BBB, play a central role in defending against pathogen invasion. In this study, we employ the NMEC strain RS218 (O18:K1:H7) to investigate the molecular mechanisms of cell death in BMECs and its pivotal contribution to BBB disruption. The study reveals that RS218 infection promotes assembly of the Ripoptosome complex. This leads to the coordinated activation of apoptosis, pyroptosis, and necroptosis. Notably, necroptosis can also occur through RIPK1-independent pathways. By generating Ripk1 ^D138N/D138N, Gsdmd ^-/-, and Casp8 ^-/- Ripk3 ^-/- mice, we demonstrate that the regulation of BMECs death was an important factor in BBB resistance to infection. Among these models, kinase-dead Ripk1 ^D138N/D138N mice exhibit the most effective BBB protection, independent of innate immune responses. Inhibition of RIPK1 kinase significantly preserves BBB integrity, and lowers RS218 invasion and neuroinflammation. Moreover, the combination of RIPK1 inhibition with antibiotics yields additive therapeutic effects. Our study advances the understanding of NMEC pathogenesis and supports the potential of RIPK1 as a therapeutic target for E. coli meningitis.

The study demonstrated that TB/QCS MNs disrupted the robust biofilm structure of T. mentagrophytes . Quaternary ammonium chitosan (QCS) as the needle tip matrix combined with loaded terbinafine (TB) exhibited synergistic antifungal effects.