Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Objective To analyze the difference in ground reaction force (GRF) between male and female runners and between left and right limbs using the one-dimensional statistical parametric mapping (SPM). Methods Thirty male and female runners participated the running test on force treadmill at the speed of 12 km/h. GRF of consecutive five steps were recorded. The independent-sample t test and paired-sample t test in the SPM package were used to check the male vs female and right limb vs left limb differences. Results Male and female runners showed inter-limb asymmetry in vertical average loading rate (VALR), and the VALR of male runners was significantly higher than that of female runners in the left limb, while no significant differences were found in the right limb. Male and female runners showed significant differences in the right vertical GRF during push-off and medial-lateral GRF during landing, while left medial-lateral GRF presented significant differences during landing and mid stance. Male runners showed right limb vs left limb significance in the anterior-posterior GRF during push-off, vertical GRF during landing and push-off and medial-lateral GRF during landing, while female runners exhibited right limb vs left limb significance in vertical GRF during landing and push-off. Conclusions This study introduced the application of SPM in statistical analysis of GRF, elaborated the procedures and theory, compared the test of time-series data in SPM and discrete value with traditional statistics, and discussed the difference and features in SPM and SnPM, thus providing references for the application in data analysis of sports biomechanics. Comparison in the male vs female and right limb vs left limb revealed the genders and inter-limb symmetrical differences in the landing, mid-stance and push-off phases during stance. The research findings laid the foundation for future investigation of mechanism in running related injuries and strategy of prevention and treatment.

OpenSim musculoskeletal modelling has developed rapidly and been widely utilized due to its open-source. Apart from calculation of the basic kinematic and kinetic data, subject-specific OpenSim model could reveal information of neuromuscular control, muscle forces and geometry, and contact forces. Image-based model-ling of the neuromuscular control in pathological gait and ergonomic evaluation of the prostheses confirmed the reliability and feasibility, but limitations in time-consumption and foot-ankle modelling also existed. The subject-specific modelling of pathological gait could improve the accuracy and diversity of clinical biomechanics and medical engineering research. It could also reveal the pathological features, and provide scientific evidence to design specific and accurate protocols of motor function diagnosis and rehabilitation, health monitoring and evaluation, and ergonomic customization and assessment of devices, as well as future directions and implications in the research field.

Objective: To assess the knowledge, attitudes, and practices (KAP) on Zika virus infection among pregnant women in Brunei Darussalam by a cross-sectional survey. Methods: Between February and June 2017, we recruited 234 pregnant women from all government healthcare centres at Brunei-Muara district, using a modified systematic sampling approach. A pre-tested and self-administered questionnaire was used and data analysis was conducted using descriptive statistics and multiple logistic regression analyses. Results: The study participants were mainly Malay (87.2%) and their mean age was 28.0 years. The median knowledge score was 13, out of a possible score of 28. Most participants (92.7%) knew that Zika virus was transmitted by mosquito bites whereas some (34.6%) knew that sexual transmission was also possible. Media (radio, television or newspapers) was the preferred source of updated information on Zika virus, followed by healthcare workers (44.0%), government announcements (43.2%), and social media (38.0%). Pregnant women who were 25 years old or older [Adj. OR=3.62 (95% CI: 1.57, 9.51)], not Malays [Adj. OR=3.32 (95% CI: 1.35, 8.55)], and had an average monthly household income of more than BND $3 000 [Adj. OR=4.06 (95% CI: 1.81, 19.44)] were more likely to score higher for knowledge on Zika virus. The median prevention practice score was 23, out of a possible score of 36. Most participants reported wearing covering clothes (98.3%) and kept their living surroundings clean (99.6%). Most participants (88.0%) agreed that Zika is an important issue in their community. Conclusion: We found a lack of knowledge on Zika virus infection among pregnant women attending government maternal and child healthcare centres in Brunei Darussalam, in particular that Zika virus can be sexually transmitted. Such information could be well disseminated at the healthcare centre level. Health literacy studies should be conducted to understand the facilitators and barriers of KAP on Zika virus infection among pregnant women.

A large number of women will pass through menopause each year. Women in menopausal transition experience a variety of menopausal symptoms. Although hormonal therapy remains the most effective treatment, side effects have been reported by several large studies. An increased number of women seek the use of complementary and alternative medicine (CAM) for treating menopausal symptoms. This review analyzes the evidence from systematic reviews, randomized controlled trials and epidemiological studies of using herbal medicine (Black cohosh, Dong quai, St John's wart, Hops, Wild yam, Ginseng, and evening primrose oil) and acupuncture for the treatment of menopausal symptoms. Evidence supporting the efficacy and safety of most CAM for relief of menopausal symptoms are limited. Future larger and better controlled studies testing the effectiveness of these treatments are needed.
Complementary Therapies ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Menopause ; drug effects ; physiology ; Mind-Body Therapies

Dental caries (tooth decay) is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineral in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound (Glycyrrhizol A), from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to produce these specific herbal extracts in large quantities, and then used these extracts to develop a sugar-free lollipop that effectively kills cariogenic bacteria like Streptococcus mutans. Further studies showed that these sugar-free lollipops are safe and their antimicrobial activity is stable. Two pilot human studies indicate that a brief application of these lollipops (twice a day for ten days) led to a marked reduction of cariogenic bacteria in oral cavity among most human subjects tested. This herbal lollipop could be a novel tool to promote oral health through functional foods.
Aged ; Animals ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; toxicity ; Candy ; analysis ; Child ; Dental Caries ; prevention & control ; Glycyrrhiza ; Humans ; Jurkat Cells ; drug effects ; Lactobacillus casei ; drug effects ; Mice ; Microbial Sensitivity Tests ; Mutagenicity Tests ; Phytotherapy ; Pilot Projects ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; Pterocarpans ; pharmacology ; therapeutic use ; toxicity ; Safety ; Saliva ; microbiology ; Streptococcus mutans ; drug effects ; Streptococcus sobrinus ; drug effects ; Sweetening Agents

Tyrosine aminotransferase (TAT) catalyzes the transamination of tyrosine and other aromatic amino acids. The enzyme is thought to play a role in tyrosinemia type II, hepatitis and hepatic carcinoma recovery. The objective of this study is to investigate its biochemical and structural characteristics and substrate specificity in order to provide insight regarding its involvement in these diseases. Mouse TAT (mTAT) was cloned from a mouse cDNA library, and its recombinant protein was produced using Escherichia coli cells and purified using various chromatographic techniques. The recombinant mTAT is able to catalyze the transamination of tyrosine using α-ketoglutaric acid as an amino group acceptor at neutral pH. The enzyme also can use glutamate and phenylalanine as amino group donors and p-hydroxy-phenylpyruvate, phenylpyruvate and alpha-ketocaproic acid as amino group acceptors. Through macromolecular crystallography we have determined the mTAT crystal structure at 2.9 Å resolution. The crystal structure revealed the interaction between the pyridoxal-5'-phosphate cofactor and the enzyme, as well as the formation of a disulphide bond. The detection of disulphide bond provides some rational explanation regarding previously observed TAT inactivation under oxidative conditions and reactivation of the inactive TAT in the presence of a reducing agent. Molecular dynamics simulations using the crystal structures of Trypanosoma cruzi TAT and human TAT provided further insight regarding the substrate-enzyme interactions and substrate specificity. The biochemical and structural properties of TAT and the binding of its cofactor and the substrate may help in elucidation of the mechanism of TAT inhibition and activation.
Animals ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Mice ; Molecular Dynamics Simulation ; Tyrosine Transaminase ; chemistry

Pandemic influenza has posed an increasing threat to public health worldwide in the last decade. In the 20th century, three human pandemic influenza outbreaks occurred in 1918, 1957 and 1968, causing significant mortality. A number of hypotheses have been proposed for the emergence and development of pandemic viruses, including direct introduction into humans from an avian origin and reassortment between avian and previously circulating human viruses, either directly in humans or via an intermediate mammalian host. However, the evolutionary history of the pandemic viruses has been controversial, largely due to the lack of background genetic information and rigorous phylogenetic analyses. The pandemic that emerged in early April 2009 in North America provides a unique opportunity to investigate its emergence and development both in human and animal aspects. Recent genetic analyses of data accumulated through long-term influenza surveillance provided insights into the emergence of this novel pandemic virus. In this review, we summarise the recent literature that describes the evolutionary pathway of the pandemic viruses. We also discuss the implications of these findings on the early detection and control of future pandemics.
Animals ; Birds ; virology ; Communicable Diseases, Emerging ; epidemiology ; history ; virology ; Evolution, Molecular ; History, 20th Century ; History, 21st Century ; Humans ; Influenza A Virus, H1N1 Subtype ; genetics ; Influenza A Virus, H3N2 Subtype ; genetics ; Influenza in Birds ; epidemiology ; history ; virology ; Influenza, Human ; epidemiology ; history ; virology ; Pandemics ; history