Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN

Neurocognitive Changes among Elderly Exposed to PCBs/PCDFs in Taiwan

BACKGROUND: In 1979 approximately 2,000 people were exposed to polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) due to ingestion of contaminated cooking oil in Taiwan. Although a previous study has shown delayed developmental milestones and poorer neurocognitive functioning in children born to exposed mothers, it is unclear whether neurocognitive functioning was impaired in people who were directly exposed to the PCBs and PDCFs. OBJECTIVE: The objective of this study was to compare neurocognitive functioning in people exposed to PCBs and PCDFs with that of unexposed sex- and age-matched neighbors. METHODS: We conducted a retrospective cohort study among exposed and unexposed subjects >= 60 years of age using prospective outcome measurements. We evaluated neurocognitive tests including cognition, memory modalities, learning, motor and sensory function, mood, and daily activity. RESULTS: In total, 162 (59%) exposed and 151 (55%) reference subjects completed this study. In exposed men, all test results were similar to the reference group; however, exposed women had reduced functioning in attention and digit span (ADS), visual memory span (VMS), and verbal memory recalls (VMR ), especially learning ability. We also found a borderline reduction in the Mini-Mental State Examination. The digit symbol, motor, sensory, depression ( determined by the Geriatric Depression Scale-Short Form), and activity of daily life were not different between the exposed and reference groups. A significant dose-response relationship was found for VMR, ADS, and VMS. CONCLUSION: Our study showed dose-dependent neurocognitive deficits in certain aspects of attention, visual memory, and learning ability in women previously exposed to PCBs and PCDFs, but not in exposed men

A universal programmable Gaussian Boson Sampler for drug discovery

Gaussian Boson Sampling (GBS) exhibits a unique ability to solve graph problems, such as finding cliques in complex graphs. It is noteworthy that many drug discovery tasks can be viewed as the clique-finding process, making them potentially suitable for quantum computation. However, to perform these tasks in their quantum-enhanced form, a large-scale quantum hardware with universal programmability is essential, which is yet to be achieved even with the most advanced GBS devices. Here, we construct a time-bin encoded GBS photonic quantum processor that is universal, programmable, and software-scalable. Our processor features freely adjustable squeezing parameters and can implement arbitrary unitary operations with a programmable interferometer. Using our processor, we have demonstrated the clique-finding task in a 32-node graph, where we found the maximum weighted clique with approximately twice the probability of success compared to classical sampling. Furthermore, a multifunctional quantum pharmaceutical platform is developed. This GBS processor is successfully used to execute two different drug discovery methods, namely molecular docking and RNA folding prediction. Our work achieves the state-of-the-art in GBS circuitry with its distinctive universal and programmable architecture which advances GBS towards real-world applications.Comment: 10 pages, 5 figure

Effectiveness of Simulation-Based Education on Childhood Fever Management by Taiwanese Parents

Childhood fever is a common symptom managed by parents at home. Most parents do not know the definition of fever, its effect, or its management. To establish simulation-based education for parents and evaluate its effectiveness for fever management at home are essential for nursing care. This study assesses the long-term effects of simulation-based education on information, motivation, behavioral skills, and behaviors related to parental fever management in Taiwan. Methods: Cluster random sampling was used to recruit parents having children aged from 3 months to 5 years who were attending kindergartens in Kaohsiung, Taiwan. A total of 160 parents were randomly assigned into experimental (EP) and control (CP) groups equally. Parents in the EP group received simulation-based education with fever education brochures, while the CP group received only the brochure. Data on parental fever information, motivation, behavioral skills, and management behaviors were collected before the 1st day, on the 1st day (except management behaviors), at the 6-month, and at the 12-month marks post-training with a self-developed instrument based on the information–motivation–behavioral skills model. Results: The results of a generalized estimating equation analysis indicated that the information, motivation, behavioral skills, and management behaviors of all participants had improved at the post-test assessment, with the EP group showing significantly better improvement than the CP group. This study supports that simulation-based education effectively enhances fever management of parents for a long period of time. Conclusion: Simulation-based education, compared to using the brochure, was a better strategy for improving parental information, motivation, behavioral skills, and behaviors regarding fever management. We suggest that providing community-based education on fever with scenario simulation is needed to increase parental competence for child care

Applicability of determination indexes for fatigue failure of modified asphalt

The malvern dynamic shear rheometer was used to conduct the time sweep fatigue tests on the 90# original binder, SBS modified asphalt, rock asphalt modified asphalt, crumb rubber modified asphalt, rock asphalt/SBS composite modified asphalt and rock asphalt/crumb rubber composite modified asphalt (RA/CRCMA) under the stress-controlled and strain-controlled modes. The corresponding fatigue life of modified asphalt was determined according to five fatigue failure definitions. The suitability of fatigue failure determination indexes of modified asphalt was evaluated by using the statistical analysis method. The fatigue performances of modified asphalts were compared and analyzed by using the recommended indexes. Research result shows that the index determined based on the normalized dynamic modulus is not affected by the load control mode and asphalt type. The indexes determined based on the phase angle and cumulative dissipative energy ratio are significantly affected by the asphalt type and load-controlled mode, and are not universal. The index determined based on the dissipated energy change rate is only suitable for the fatigue life judgment of stress-controlled mode. The index determined based on the reduced dissipated energy change rate is less affected by the asphalt type. It exhibits a preferable fatigue life evaluation effect on all asphalts in this study. The correlation coefficients of the indexes determined by the normalized dynamic modulus and the reduced dissipated energy change rate under the stress-controlled and strain-controlled modes are up to 0.94, and the mean absolute error is less than 20%, showing a good correlation and equivalent fatigue life ranking results. Due to the simple calculation and distinct definition, they are recommended to be used as the determination standard for testing the asphalt fatigue failure in time sweep fatigue test. According to the sequence of fatigue life of asphalts tested by the recommended indexes in this study, the RA/CRCMA with 18% crumb rubber and 5% rock asphalt shows the optimal fatigue resistance under the stress-controlled and strain-controlled modes

Isolation and Characterization of Eleven Polymorphic Microsatellite Loci for the Valuable Medicinal Plant Dendrobium huoshanense and Cross-Species Amplification

Abstract: Dendrobium huoshanense (Orchidaceae) is a perennial herb and a widely used medicinal plant in Traditional Chinese medicine (TCM) endemic to Huoshan County town in Anhui province in Southeast China. A microsatellite-enriched genomic DNA library of D. huoshanense was developed and screened to identify marker loci. Eleven polymorphic loci were isolated and analyzed by screening 25 individuals collected from a natural population. The number of alleles per locus ranged from 2 to 5. The observed and expected heterozygosities ranged from 0.227 to 0.818 and from 0.317 to 0.757, respectively. Two loci showed significant deviations from Hardy-Weinberg equilibrium and four of the pairwise comparisons of loci revealed linkage disequilibrium (p < 0.05). These microsatellite loci were cross-amplified for five congeneric species and seven loci can be amplified in all species. These simple sequence repeats (SSR) markers are useful in genetic studies of D. huoshanense and other related species and in conservatio

Prolonged persistence of IgM against dengue virus detected by commonly used commercial assays

Abstract Background Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. Methods We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. Results Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7–446.9) by SD ELISA, while at 175.7 days (95% CI 121.9–221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. Conclusion Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year