hnRNPAB inhibits Influenza A virus infection by disturbing polymerase activity.

Influenza A virus (IAV) continuously poses a considerable threat to global health through seasonal epidemics and recurring pandemics. IAV RNA-dependent RNA polymerases (FluPol) mediate the transcription of RNA and replication of the viral genome. Searching for targets that inhibit viral polymerase activity helps us develop better antiviral drugs. Here, we identified heterogeneous nuclear ribonucleoprotein A/B (hnRNPAB) as an anti-influenza host factor. hnRNPAB interacts with NP of IAV to inhibit the interaction between PB1 and NP, which is dependent on the 5-amino-acid peptide of the hnRNPAB C-terminal domain (aa 318-322). We further found that the 5-amino-acid peptide blocks the interaction between PB1 and NP to destroy the FluPol activity. In vivo studies demonstrate that hnRNPAB-deficient mice display higher viral burdens, enhanced cytokine production, and increased mortality after influenza infection. These data demonstrate that hnRNPAB perturbs FluPol complex conformation to inhibit IAV infection, providing insights into anti-influenza defense mechanisms.

Periodontal Status and Saliva Metabolic Signature in Patients with Alzheimer's Disease.

BACKGROUND: Characterizing the periodontal status of patients with Alzheimer's disease (AD), investigating differences in salivary metabolism between patients with and without AD under the same periodontal conditions, and understanding how it is related to oral flora are critical. OBJECTIVE: We aimed to examine the periodontal condition of patients with AD and to screen salivary metabolic biomarkers from the saliva of individuals with and without AD with matched periodontal conditions. Furthermore, we aimed to explore the possible relationship between salivary metabolic changes and oral flora. METHODS: In total, 79 individuals were recruited into the experiment for periodontal analysis. Especially, 30 saliva samples from the AD group and 30 from healthy controls (HCs) with matched periodontal conditions were selected for metabolomic analysis. The random-forest algorithm was used to detect candidate biomarkers. Among these, 19 AD saliva and 19 HC samples were selected to investigate the microbiological factors influencing the alterations in saliva metabolism in patients with AD. RESULTS: The plaque index and bleeding on probing were considerably higher in the AD group. Further, Cis-3-(1-carboxy-ethyl)-3,5-cyclohexadiene-1,2-diol, dodecanoic acid, genipic acid, and N, N-dimethylthanolamine N-oxide were determined as candidate biomarkers, based on the area under the curve (AUC) value (AUC = 0.95). The results of oral-flora sequencing showed that dysbacteriosis may be a reason for the differences in AD saliva metabolism. CONCLUSION: Dysregulation of the proportion of specific bacterial flora in saliva plays a vital role in metabolic changes in AD. These results will contribute to further improving the AD saliva biomarker system.

Advances of Hydrogel Therapy in Periodontal Regeneration-A Materials Perspective Review.

Hydrogel, a functional polymer material, has emerged as a promising technology for therapies for periodontal diseases. It has the potential to mimic the extracellular matrix and provide suitable attachment sites and growth environments for periodontal cells, with high biocompatibility, water retention, and slow release. In this paper, we have summarized the main components of hydrogel in periodontal tissue regeneration and have discussed the primary construction strategies of hydrogels as a reference for future work. Hydrogels provide an ideal microenvironment for cells and play a significant role in periodontal tissue engineering. The development of intelligent and multifunctional hydrogels for periodontal tissue regeneration is essential for future research.

Pulmonary Infection Caused by Strongyloides stercoralis.

PURPOSE: Strongyloidiasis is mainly prevalent in developing countries with poor economic and sanitary conditions. The clinical manifestations of Strongyloides stercoralis infection are complex and diverse, lacking specificity, which can easily lead to misdiagnosis and delayed treatment. METHODS: An elderly male patient, repeated cough and expectoration for 4 years, with exacerbation and dyspnea for 10 days, was admitted to hospital. Sputum culture and smear were taken for examination. Nematode larvae were found under the microscope. Nematodes were also found in feces. RESULTS: Upon confirmation, the patient was diagnosed with a pulmonary infection caused by Strongyloides stercoralis. After treatment with albendazole, the symptoms improved, and the patient was discharged. CONCLUSION: In this case report, combination of microscopic examination of sputum and alveolar lavage fluid and CT scan were used to quickly identify the cause of the patient, it provides a diagnostic basis and method for clinical treatment.

Cocktail strategy based on a dual function nanoparticle and immune activator for effective tumor suppressive.

BACKGROUND: Immune checkpoint inhibitor-mediated immunotherapy cannot be carried out on a large scale clinically due to its low universality. In recent years, cyclic guanosine monophosphate synthase/interferon gene stimulating factor (cGAS/STING)-mediated innate immune signaling pathway-mediated immunotherapy has attracted more and more attention. In addition, metabolic inhibitors also show good effects on tumor treatment, but their application is often limited because of their large first pass effect or difficult administration. METHODS: The particle size and potential parameters were measured by DLS. In order to determine the optimal ratio of the two drugs, we calculated the CI value of different nanoparticles through MTT experiment, and simulated their synergistic effect through Gaussian software. Then the morphology and crystal form of the best proportion of drugs were studied by TEM and XRD. The anti-tumor mechanism of composite nanoparticles was confirmed by the determination of metabolic related indexes, Q-PCR and WB. The antitumor effect and immune activation effect were comprehensively evaluated by in vivo and in vitro experiments. RESULTS: Here, we found and synthesized BCP nanoparticles ((BPA + CPI) @ PLGA NPs) which can effectively reduce the metabolism of tumor cells and inhibit cell proliferation. At the same time, the release of mitochondrial DNA (mtDNA) caused by mitochondrial metabolism disorder further activated the cGAS/STING signal pathway in Hepa1-6 cells. We found that the drug-treated Hepa1-6 cells had obvious TBK1 phosphorylation and STING dimerization. Combined with STING agonist, it could effectively promote the activation of CD8 T cells and enhanced the therapeutic effect on liver cancer. CONCLUSION: Our results showed that PLGA nanocarrier can successfully improve the dosage forms of two metabolic inhibitors and show the effect of synergistic therapy. BCP nanoparticles can also activate the innate immunity of tumor cells and significantly enhance tumor inhibition after combined with STING agonists. This study has high reference and transformation value for the combined treatment of immunosuppression and metabolic inhibition.

Nucleobindin-2 Promotes the Growth and Invasion of Glioblastoma.

Background: Glioblastoma is one of the most malignant tumors in the brain with high mortality. In recent years, immunotherapy and targeted therapy show great prospects in the treatments for glioblastoma, whereas more effective therapeutic targets are still urgently needed to be developed. Nucleobindin-2 (NUCB2) is the precursor protein of nesfatin-1, which have a variety of metabolic functions, such as food intake and temperature regulation. In recent years, the potential link between NUCB2 and the development of multiple cancer was gradually revealed; however, the effects of NUCB2 on the progression of glioblastoma are still unclear. Methods: Immunohistochemical assays were performed to explore the NUCB2 expression levels in 94 samples of glioblastoma and corresponding nontumor tissues; patients were divided into NUCB2 high expression group and low expression group. Clinical analysis related to the clinical features, the potential link between NUCB2 expression levels, and clinical features were analyzed; the effects of NUCB2 on cell proliferation and invasion of glioblastoma were detected through colony formation and MTT assay, and transwell assay respectively. The possible effects of NUCB2 on tumor growth and metastasis were measured in mice. Results: In this study, we demonstrated that NUCB2 over-expression was correlated with the high degree of recurrence of patients with glioblastoma. Further, we also revealed that NUCB2 promoted cell proliferation and invasion of glioblastoma in vitro and promoted the growth and metastasis of glioblastoma in mice. Conclusion: This study provided evidence that NUCB2 might be a novel therapeutic target of glioblastoma.