Human cytomegalovirus uracil DNA glycosylase associates with ppUL44 and accelerates the accumulation of viral DNA

BACKGROUND: Human cytomegalovirus UL114 encodes a uracil-DNA glycosylase homolog that is highly conserved in all characterized herpesviruses that infect mammals. Previous studies demonstrated that the deletion of this nonessential gene delays significantly the onset of viral DNA synthesis and results in a prolonged replication cycle. The gene product, pUL114, also appears to be important in late phase DNA synthesis presumably by introducing single stranded breaks. RESULTS: A series of experiments was performed to formally assign the observed phenotype to pUL114 and to characterize the function of the protein in viral replication. A cell line expressing pUL114 complemented the observed phenotype of a UL114 deletion virus in trans, confirming that the observed defects were the result of a deficiency in this gene product. Stocks of recombinant viruses without elevated levels of uracil were produced in the complementing cells; however they retained the phenotype of poor growth in normal fibroblasts suggesting that poor replication was unrelated to uracil content of input genomes. Recombinant viruses expressing epitope tagged versions of this gene demonstrated that pUL114 was expressed at early times and that it localized to viral replication compartments. This protein also coprecipitated with the DNA polymerase processivity factor, ppUL44 suggesting that these proteins associate in infected cells. This apparent interaction did not appear to require other viral proteins since ppUL44 could recruit pUL114 to the nucleus in uninfected cells. An analysis of DNA replication kinetics revealed that the initial rate of DNA synthesis and the accumulation of progeny viral genomes were significantly reduced compared to the parent virus. CONCLUSION: These data suggest that pUL114 associates with ppUL44 and that it functions as part of the viral DNA replication complex to increase the efficiency of both early and late phase viral DNA synthesis

Sodium butyrate ameliorates gut dysfunction and motor deficits in a mouse model of Parkinson’s disease by regulating gut microbiota

BackgroundA growing body of evidence showed that gut microbiota dysbiosis might be associated with the pathogenesis of Parkinson’s disease (PD). Microbiota-targeted interventions could play a protective role in PD by regulating the gut microbiota-gut-brain axis. Sodium butyrate (NaB) could improve gut microbiota dysbiosis in PD and other neuropsychiatric disorders. However, the potential mechanism associated with the complex interaction between NaB and gut microbiota-gut-brain communication in PD needs further investigation.MethodsC57BL/6 mice were subjected to a rotenone-induced PD model and were treated intragastrically with NaB for 4 weeks. The gut function and motor function were evaluated. The α-synuclein expression in colon and substantia nigra were detected by western blotting. Tyrosine hydroxylase (TH)-positive neurons in substantia nigra were measured by immunofluorescence. Moreover, gut microbiota composition was analyzed by 16S rRNA sequencing. Fecal short chain fatty acids (SCFAs) levels were determined by liquid chromatography tandem mass spectrometry (LC–MS). The levels of glucagon like peptide-1 (GLP-1) in tissues and serum were evaluated using enzyme-linked immunosorbent assay (ELISA).ResultsNaB ameliorated gut dysfunction and motor deficits in rotenone-induced mice. Meanwhile, NaB protected against rotenone-induced α-synuclein expression in colon and substantia nigra, and prevented the loss of TH-positive neurons. In addition, NaB could remodel gut microbiota composition, and regulate gut SCFAs metabolism, and restore GLP-1 levels in colon, serum, and substantia nigra in PD mice.ConclusionNaB could ameliorate gut dysfunction and motor deficits in rotenone-induced PD mice, and the mechanism might be associated with the regulation of gut microbiota dysbiosis

Daily Peer Relationships and Academic Achievement among College Students: A Social Network Analysis Based on Behavioral Big Data

This study aimed to detect college students’ daily peer networks through a behavioral big-data-driven social network analysis and to explore the relationship between college students’ daily peer relationships and academic achievement. We collected data on the class attendance, eating, and bathing records of 4738 undergraduate students who entered a university in 2018 to infer the daily peer relationship networks of students. The Louvain algorithm and some network indicators such as density and average clustering coefficient were used to investigate social network characteristics of peer relationship networks. The findings show that initially, students in the same dormitory tended to form daily peer relationships, gradually shifting toward relationships centered on classmates as time progressed. These peer networks often aligned with geographical location and living areas. Moreover, the peers of college students who received high-level scholarships were more likely to receive scholarships. The number of peers was positively correlated with the likelihood of receiving a scholarship. The research findings contribute to the application of information technology to promote the sustainable development of higher education and individual students

Low-voltage multicolor electroluminescence from all-inorganic carbon dots/Si-heterostructured light-emitting diodes

Low-voltage and multicolor electroluminescent light-emitting diodes (LEDs) based upon carbon dots (CDs) are demonstrated by using simple all-inorganic CDs/Si heterostructures. Electroluminescence (EL) originations of the CDs/Si LEDs are investigated clearly without the interference of commonly used organic semiconductors. Three distinct peaks at 438, 540, and 600nm are achieved in the EL spectra of the CDs/Si LEDs, and they are found to only originate from the CDs. Addition of a PMMA polymer does not influence the EL originations, but improves the flatness of the CD active layer, thereby enhancing the EL performance of the CDs/Si LEDs. Most strikingly, the emission threshold voltage of such all-inorganic CDs/Si LEDs is as low as 3.4V, which is the lowest onset voltage among the CDs-based LEDs by using fluorescent CDs as the active emitter. The ultra-low driving voltage proves the feasibility of the all-inorganic CDs/Si LEDs in the future multicolor solid-state lighting applications

Guideline for the management of pediatric off-label use of drugs in China (2021)

Abstract Background The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. Methods We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk–benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). Results We developed the first guideline for the management of pediatric off-label use of drugs in China. Conclusions The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future