African swine fever virus MGF505-6R attenuates type I interferon production by targeting STING for degradation.

African swine fever (ASF) is an acute hemorrhagic and devastating infectious disease affecting domestic pigs and wild boars. It is caused by the African swine fever virus (ASFV), which is characterized by genetic diversity and sophisticated immune evasion strategies. To facilitate infection, ASFV encodes multiple proteins to antagonize host innate immune responses, thereby contributing to viral virulence and pathogenicity. The molecular mechanisms employed by ASFV-encoded proteins to modulate host antiviral responses have not been comprehensively elucidated. In this study, it was observed that the ASFV MGF505-6R protein, a member of the multigene family 505 (MGF505), effectively suppressed the activation of the interferon-beta (IFN-ß) promoter, leading to reduced mRNA levels of antiviral genes. Additional evidence has revealed that MGF505-6R antagonizes the cGAS-STING signaling pathway by interacting with the stimulator of interferon genes (STING) for degradation in the autophagy-lysosomal pathway. The domain mapping revealed that the N-terminal region (1-260aa) of MGF505-6R is the primary domain responsible for interacting with STING, while the CTT domain of STING is crucial for its interaction with MGF505-6R. Furthermore, MGF505-6R also inhibits the activation of STING by reducing the K63-linked polyubiquitination of STING, leading to the disruption of STING oligomerization and TANK binding kinase 1 (TBK1) recruitment, thereby impairing the phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3). Collectively, our study elucidates a novel strategy developed by ASFV MGF505-6R to counteract host innate immune responses. This discovery may offer valuable insights for further exploration of ASFV immune evasion mechanisms and antiviral strategies.

Esketamine combined with sufentanil versus sufentanil in patient-controlled intravenous analgesia: a meta-analysis.

Objective: Patient-controlled intravenous analgesia (PCIA) can alleviate pain to some extent, and several randomized controlled trials (RCTs) have examined the efficacy of esketamine-assisted sufentanil in postoperative PCIA. In this research, we conducted a meta-analysis of relevant RCTs to compare the effect and safety of esketamine-sufentanil versus sufentanil alone for postoperative PCIA. Methods: We systematically searched the Cochrane Library, PubMed, Embase, Web of Science, CNKI, and other libraries up to December 2023 to screen out RCTs examining the use of esketamine combined with sufentanil for PCIA. We analysed analgesia scores, sedation scores, adverse drug reactions and postpartum depression scores as outcome indicators. Results: This meta-analysis included 32 RCTs. The results of the meta-analysis were as follows. 1) Visual Analog Scale: The VAS scores at 6, 12, 24, and 48 h were lower in the esketamine-sufentanil group than in the sufentanil alone group, and significant differences were found at all time points (p < 0.05). 2) Ramsay Sedation Scale: The sedation score of the esketamine-sufentanil group at 48 h after surgery was higher than that of the sufentanil group alone [mean difference (MD) = -0.09 points, confidence interval (CI): (-0.26, -0.07), p = 0.27], but this difference was not significant (p > 0.05). 3) Safety: Compared with sufentanil alone, the incidence rates of postoperative nausea-vomiting, dizziness-headache, skin pruritus and respiratory depression were significantly lower in the esketamine-sufentanil group. 4) Postartum depression: The reduction in postpartum depression scores were significantly greater in the esketamine-sufentanil group than in the sufentanil alone group at 3 days [MD = -1.35 points, CI: (-1.89, -0.81), p < 0.00001] and 7 days [MD = -1.29 points, CI: (-2.42, -0.16), p = 0.03]. Conclusion: The meta-analysis showed that the use of esketamine combined with sufentanil for postoperative PCIA could improve postoperative analgesia, alleviate postpartum depression and reduce the rate of postoperative adverse reactions, but there was no significant difference in sedation.

Simultaneous determination of 14 analgesics in postoperative analgesic solution by HPLC-DAD and LC-MS/MS.

A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The 14 mixtures were chromatographed via HPLC-DAD method which employed 0.05 mol/L potassium dihydrogen phosphate solution-acetonitrile as the mobile phase, the analytes were gradient elution on a SinoChrom ODS-BP C18 column with a total separation time of 35 min, and 14 mixtures showed a good linear relationship in the linear range. The Limit of Quantitation (LOQ) ranged from 0.10 to 20.0 µg/mL, the inter-day and intra-day precision of each analyte is within 1.1-2.0% and 0.4-1.3%, and the average absolute recovery of all compounds was above 98%. The LC-MS/MS method was used to successfully separate the 14 mixtures within 10 min which employed 0.1% formic acid-acetonitrile as the mobile phase, the analytes were gradient elution on a ACQUITY UPLC-BEH C18 column with a total separation time of 13 min, and 14 mixtures showed a good linear relationship in the linear range. The LOQ ranged from 0.005 to 0.2 ng/mL, the inter-day and intra-day precision of each analyte is within 1.2-4.1% and 0.6-3.3%, and the average absolute recovery of all compounds was above 93%. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines.

A self-assembled nanoparticle vaccine based on pseudorabies virus glycoprotein D induces potent protective immunity against pseudorabies virus infection.

Pseudorabies virus (PRV) mainly causes pseudorabies (PR) or Aujeszky's disease in pigs and can infect humans, raising public health concerns about zoonotic and interspecies transmission of PR. With the emergence of PRV variants in 2011, the classic attenuated PRV vaccine strains have failed to protect many swine herds against PR. Herein, we developed a self-assembled nanoparticle vaccine that induces potent protective immunity against PRV infection. PRV glycoprotein D (gD) was expressed using the baculovirus expression system and further presented on the lumazine synthase (LS) 60-meric protein scaffolds via the SpyTag003/SpyCatcher003 covalent coupling system. In mouse and piglet models, LSgD nanoparticles emulsified with the ISA 201VG adjuvant elicited robust humoral and cellular immune responses. Furthermore, LSgD nanoparticles provided effective protection against PRV infection and eliminated pathological symptoms in the brain and lungs. Collectively, the gD-based nanoparticle vaccine design appears to be a promising candidate for potent protection against PRV infection.

Nanoparticle vaccine based on the envelope protein domain III of Japanese encephalitis virus elicits robust protective immune responses in mice.

Aim: To develop a vaccine candidate for Japanese encephalitis virus (JEV), for which an effective and safe vaccine is urgently needed. Materials & methods: A vaccine candidate based on domain III of the JEV envelope protein and lumazine synthase (EDIII-LS) was prepared by coupling multivalent ED III to a self-assembling nanoparticle of LS through genetic fusion and self-assembly. Results: High enrichment of ED III was achieved based on the self-assembly of an EDIII-LS polymer. EDIII-LS strongly promoted dendritic cells' internalization and presentation compared with ED III monomer. The cellular and humoral immune responses provoked by EDIII-LS were remarkably higher than those caused by ED III in mice, and conferred complete protection against JEV challenge. Conclusion: The study of ED III-based nanoparticles suggests an effective approach against JEV.

Balance Analysis of Peripheral Neuropathy in Type 2 Diabetes Mellitus Based on Logistic Regression Equation.

This paper analyzes the factors of peripheral neuropathy in type 2 diabetes mellitus and puts forward a balanced analysis of peripheral neuropathy in type 2 diabetes mellitus based on logistic regression equation. A total of 1192 eligible patients were selected as the study subjects. All selected patients underwent 75 g oral glucose tolerance test to measure fasting blood glucose and insulin and 2-hour postprandial blood glucose and 2-hour postprandial insulin, as well as neuroelectrophysiological examination. The results showed that the OR values of age, course of disease, fingertip blood glucose immediately after admission, and 2-hour blood glucose were greater than 1, and the P values were all less than 0.05, which were the risk factors of diabetic peripheral neuropathy. OR value of ß cell function index (HBCI) is less than 1. P is less than 0.05, and it is a protective factor of diabetic peripheral neuropathy. Laboratory indicators are as follows: 75 g OGTT: 0-hour blood glucose, 2-hour blood glucose, and glycosylated hemoglobin; serum creatinine; glutamate transaminase; fibrinogen; ten items of hemoglobin; and indexes reflecting islet function: islet ß is thin, and there are significant differences in cell function index, insulin resistance index, and insulin secretion index between the non-DPN group and DPN group. Age, course of disease, fingertip blood glucose immediately after admission, and blood glucose within 2 hours after admission were the risk factors for diabetic peripheral neuropathy. Islet ß cell function index (HBCI) is a protective factor of diabetic peripheral neuropathy.