Guanylate-binding protein 1 inhibits nuclear delivery of pseudorabies virus by disrupting structure of actin filaments.

The alphaherpesvirus pseudorabies virus (PRV) is the causative agent of pseudorabies, responsible for severe economic losses to the swine industry worldwide. The interferon-inducible GTPase guanylate-binding protein 1 (GBP1) exhibits antiviral immunity. Our findings show that there is a robust upregulation in the expression of porcine GBP1 during PRV infection. GBP1 knockout promotes PRV infection, while GBP1 overexpression restricts it. Importantly, we found that GBP1 impeded the normal structure of actin filaments in a GTPase-dependent manner, preventing PRV virions from reaching the nucleus. We also discovered that viral US3 protein bound GBP1 to interfere with its GTPase activity. Finally, the interaction between US3 and GBP1 requires US3 serine/threonine kinase activity sites and the GTPase domain (aa 1 to 308) of GBP1. Taken together, this study offers fresh perspectives on how PRV manipulates the host's antiviral immune system.

Taming Highly Unstable Radical Anions and 1,4-Organodilithiums by Flow Microreactors: Controlled Reductive Dimerization of Styrenes.

The reduction of styrenes with lithium arenide in a flow microreactor leads to the instantaneous generation of highly unstable radical anions that subsequently dimerize to yield the corresponding 1,4-organodilithiums. A flow reactor with fast mixing is essential for this reductive dimerization as the efficiency and selectivity are low under batch conditions. A series of styrenes undergo dimerization, and the resulting 1,4-organodilithiums are trapped with various electrophiles. Trapping with divalent electrophiles affords precursors for useful yet less accessible cyclic structures, for example, siloles from dichlorosilanes. Thus, we highlight the power of single-electron reduction of unsaturated compounds in flow microreactors for organic synthesis.

Competency model for dentists in China: Results of a Delphi study.

OBJECTIVE: With the increasing awareness of the importance of oral health, patients have an increasing need for integrated care from dentists. In China, the dentistry examination consists of two parts: a practical skills examination and a comprehensive medical examination; to date, no assessment methods that are based on specialized dentistry competencies, unlike the United States, Canada, and other countries, have been established. Therefore, the purpose of this study was to construct a competency model for dentists in China in order to guide the development, admission, training and assessment of dentists. METHODS: Using a literature review, focus group interviews and in-depth personal interviews, a dentist competency index was developed with an expert consultation questionnaire. A panel of 20 specialist experts was chosen from ten national medical universities to carry out two rounds of Delphi expert analysis, using the boundary value method to filter the indicators and the Analytic Hierarchy Process to calculate the weights of the primary indicators. RESULTS: Two rounds of Delphi results showed that the expert authority, enthusiasm, and coordination coefficients were high. Constructs of the competency model that included seven primary indicators and 62 secondary indicators determined the weight of each index. The seven primary indicators included the following: clinical skills and medical services, disease prevention and health promotion, interpersonal communication skills, core values and professionalism, medical knowledge and lifelong learning ability, teamwork ability and scientific research ability. CONCLUSION: In conclusion, the use of the Delphi method to construct an initial model of Chinese physician competency is scientific and feasible. The initial competency model conforms to the characteristics and quality requirements of dentists in China and has a strong scientific basis. The dentist competency model should be used in the National Dental Licensing Examination in China.

Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children.

Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited.