Abstract. Post-treatment soil-transmitted helminth re-infection patterns were studied as part of a randomized controlled trial among school-aged children from an ethnic minority group in Yunnan province, People's Republic of China. Children with a soil-transmitted helminth infection (N = 194) were randomly assigned to triple-dose albendazole or placebo and their infection status monitored over a 6-month period using the Kato-Katz and Baermann techniques. Baseline prevalence of Trichuris trichiura, Ascaris lumbricoides, hookworm, and Strongyloides stercoralis were 94.5%, 93.3%, 61.3%, and 3.1%, respectively, with more than half of the participants harboring triple-species infections. For the intervention group (N = 99), the 1-month post-treatment cure rates were 96.7%, 91.5%, and 19.6% for hookworm, A. lumbricoides, and T. trichiura, respectively. Egg reduction rates were above 88% for all three species. Rapid re-infection with A. lumbricoides was observed: the prevalence 4 and 6 months post-treatment was 75.8% and 83.8%, respectively. Re-infection with hookworm and T. trichiura was considerably slower.

N 6-Methyladenosine (m6A) is the most abundant modification within diverse RNAs including mRNAs and lncRNAs and is regulated by a reversible process with important biological functions. Human YTH domain family 2 (YTHDF2) selectively recognized m6A-RNAs to regulate degradation. However, the possible regulation of YTHDF2 by protein post-translational modification remains unknown. Here, we show that YTHDF2 is SUMOylated in vivo and in vitro at the major site of K571, which can be induced by hypoxia while reduced by oxidative stress and SUMOylation inhibitors. SUMOylation of YTHDF2 has little impact on its ubiquitination and localization, but significantly increases its binding affinity of m6A-modified mRNAs and subsequently results in deregulated gene expressions which accounts for cancer progression. Moreover, Disease-free survival analysis of patients with lung adenocarcinoma derived from TCGA dataset reveals that higher expression of YTHDF2 together with higher expression of SUMO1 predicts poor prognosis. Our works uncover a new regulatory mechanism for YTHDF2 recognition of m6A-RNAs and highlight the importance of YTHDF2 SUMOylation in post-transcriptional gene expression regulation and cancer progression.

BackgroundChronic soil-transmitted helminth (STH) infections have been associated with reduced physical fitness, but available evidence is limited. The aim of this cross-sectional survey was to assess the feasibility of measuring children's physical fitness and to relate it to STH infections. Our study was carried out among school-aged children of the Bulang ethnic group in rural southwest People's Republic of China (P.R. China). Standardized, quality-controlled methods were employed to determine STH infections (Kato-Katz technique), haemoglobin levels, anthropometry (body weight and height) and physical fitness (20-m shuttle run test).ResultsA compliance of 87% suggested good acceptance of the methods used. Among 69 children with complete data records, infection prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm were 81%, 44% and 6%, respectively. The maximum volume of oxygen that can be utilized within 1 min during exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.94 ml kg-1 min-1 lower than that of their non-infected counterparts (P = 0.005). Until exhaustion, T. trichiura-infected children had completed 6.14 20-m laps less (P = 0.004). Additionally, the mean VO2 max estimate of stunted children was lowered by 1.63 ml kg-1 min-1 (P = 0.002) and they completed 5.32 20-m laps less (P = 0.001) compared to children of normal stature. No significant association between stunting and infection with any STH species could be established.ConclusionsImplementation of physical fitness tests in rural, resource-constraint settings is feasible. The physical fitness of children who are stunted or infected with STHs, particularly T. trichiura, is significantly impaired. We have launched a larger study and will determine the dynamics of school-aged children's physical fitness over a 7-month period after administration of anthelminthic drugs.

Argonaute2 (AGO2) is an effector of small RNA mediated gene silencing. Increasing evidence show that post-translational modifications of AGO2 can change miRNA activity at specific or global levels. Among the six mature miRNAs that are encoded by miR-17-92, miR-19b1 is the most powerful to exert the oncogenic properties of the entire cluster. Here we identify that AGO2 can be acetylated by P300/CBP and deacetylated by HDAC7, and that acetylation occurs at three sites K720, K493, and K355. Mutation of K493R/K720R, but not K355R at AGO2, inhibits miR-19b biogenesis. We demonstrate that acetylation of AGO2 specifically increases its recruiting pre-miR-19b1 to form the miPDC (miRNA precursor deposit complex), thereby to enhance miR-19b maturation. The motif UGUGUG in the terminal-loop of pre-miR-19b1, as a specific processing feature that is recognized and bound by acetylated AGO2, is essential for the assembly of miRISC (miRNA-induced silencing complex) loading complex. Analyses on public clinical data, xenograft mouse models, and IHC and ISH staining of lung cancer tissues, further confirm that the high levels of both AGO2 acetylation and miR-19b correlate with poor prognosis in lung cancer patients. Our finding reveals a novel function of AGO2 acetylation in increasing oncogenic miR-19b biogenesis and suggests that modulation of AGO2 acetylation has potential clinical implications.

Transforming growth factor beta (TGFβ) signaling in breast cancer is selectively associated with pulmonary metastasis. However, the underlying mechanisms remain unclear. Here we show that Bcl-3, a member of the IκB family, serves as a critical regulator in TGFβ signaling to modulate breast cancer pulmonary metastasis. Bcl-3 expression was significantly associated with metastasis-free survival in breast cancer patients. Bcl-3 deletion inhibited the migration and invasion of breast cancer cells in vitro, as well as breast cancer lung metastasis in vivo. Bcl-3 was required for the expression of downstream TGFβ signaling genes that are involved in breast cancer lung metastasis. Bcl-3 knockdown enhanced the degradation of Smad3 but not Smad2 following TGFβ treatment. Bcl-3 could bind to Smad3 and prevent the ubiquitination and degradation of Smad3 protein. These results indicate that Bcl-3 serves as a promising target to prevent breast tumor lung metastasis.

Here we report the experimental analysis on the low-n (mostly n  =  1, sometimes n  =  2) magnetic coherent mode (MCM) at a characteristic frequency 20–, which has been frequently observed in various H-mode discharges on EAST. This mode can be easily identified in the magnetic fluctuations measured by the fast Mirnov coils mounted on the vacuum vessel wall, but is detected by the local measurements of edge electrostatic fluctuations only when the mode is sufficiently strong. The apperance of the MCM is summarized covering broad ranges of discharge parameters, in particular, the different heating schemes including pure neutral beams injected in either co- or counter-current direction as well as pure ratio-frequency waves. This may rule out the possibility of fast particle driven modes. Radial distribution and poloidal propagation of the MCM are investigated using the Doppler backscattering system and Langmuir probes inserted at the outer midplane, respectively. Temporal evolution of MCM amplitude during large ELM crashes is evaluated in detail, may suggesting the mode is closely correlated with pedestal buildup. Dedicated experiments reveal the possible correlations of MCM’s frequencies with edge line-averaged density and edge safety factor q95. We also present the observation of multi MCMs at relatively high q95, which are speculated locating at different rational surfaces in the pedestal via analyzing their mode structures and nonlinear interactions. Finally, effect of the MCM on edge particle transport is explored via surveying the correlation between the intermittent events of the mode and the particle fluxes deposited on the divertor target plates, utilizing the conditional analysis method. Corresponding results suggest that the MCM seems to primarily result in a notable poloidal redistribution of the divertor particle flux, rather than a considerable net increase of the total flux.

Isotactic polypropylene (iPP) samples with different molecular weights were used to investigate the relationship between cavitation processes triggered at small- and large-strain regimes. The cavitation triggered at large strains was observed in all deformation cases regardless of the occurrence of cavitation activated at small strain. The initiation of the large-strain-cavitation process required a critical stress, which was mainly determined by the molecular weight of iPP, because it was a result of the disentanglement of the highly oriented amorphous network initiated by the breakage of interfibrillar load-bearing tie chains. In general, iPP with higher molecular weight required a higher critical stress to trigger this cavitation and presented more intensive whitening. However, the intensity of cavitation activated at small strains decreased with increasing iPP molecular weight. The cavities generated at small strain are therefore supposed to have no contribution to the cavitation initiated at large strain.

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