Abstract: Persistent diarrhea in children under 24 months old has been a global public health concern, including in Vietnam. Therefore, the authors conducted a randomised, double-blind, placebo-controlled clinical trial to evaluate the effectiveness of two Bacillus spore probiotic suspensions, namely LiveSpo CLAUSY containing B. clausii at 2 billion CFU/5 ml ampoule; and LiveSpo DIA30 containing B. subtilis, B. clausii, and B. coagulans at 5 billion CFU/5 ml ampoule, as a supportive treatment for children with persistent diarrhea. Children were randomly allocated into the control (using RO water) and two experimental groups, Clausy (using LiveSpo CLAUSY) and Dia30 (using LiveSpo DIA30), n=30/group. All three groups were treated following the standard protocol at the hospital, supplemented with either placebo or high-dose probiotics up to 4-6 ampoules/day. The results showed that Bacillus spore probiotics helped to shorten the treatment duration by approximately 1-3 days and enhanced treatment effectiveness by 1.3-2.4 folds compared to the control group in reducing the typical diarrhea symptoms, including bowel movements ≥3 times/day, presence of mucus, and diaper stool. Notably, LiveSpo DIA30 exhibited a better efficacy of 10-50% compared to LiveSpo CLAUSY. This is the world’s first clinical study demonstrating the effectiveness of high-dose Bacillus spore probiotics in supporting the treatment of diarrhea symptoms in children with persistent diarrhea.

Abstract: Two Permian-Triassic boundary (PTB) successions, Lung Cam in Vietnam, and Lukač in Slovenia, have been sampled for high-resolution magnetic susceptibility, stable isotope and elemental chemistry, and biostratigraphic analyses. These successions are located on the eastern (Lung Cam section) and western margins (Lukač section) of the Paleo-Tethys Ocean during PTB time. Lung Cam, lying along the eastern margin of the Paleo-Tethys Ocean provides an excellent proxy for correlation back to the GSSP and out to other Paleo-Tethyan successions. This proxy is tested herein by correlating the Lung Cam section in Vietnam to the Lukač section in Slovenia, which was deposited along the western margin of the Paleo-Tethys Ocean during the PTB interval. It is shown herein that both the Lung Cam and Lukač sections can be correlated and exhibit similar characteristics through the PTB interval. 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Abstract: Mutations in the orphan transporter MFSD7c (also known as Flvcr2 ), are linked to Fowler syndrome. Here, we used Mfsd7c knockout ( Mfsd7c –/– ) mice and cell-based assays to reveal that MFSD7c is a choline transporter at the blood–brain barrier (BBB). We performed comprehensive metabolomics analysis and detected differential changes of metabolites in the brains and livers of Mfsd7c –/– embryos. Particularly, we found that choline-related metabolites were altered in the brains but not in the livers of Mfsd7c –/– embryos. Thus, we hypothesized that MFSD7c regulates the level of choline in the brain. Indeed, expression of human MFSD7c in cells significantly increased choline uptake. Interestingly, we showed that choline uptake by MFSD7c is greatly increased by choline-metabolizing enzymes, leading us to demonstrate that MFSD7c is a facilitative transporter of choline. Furthermore, single-cell patch clamp analysis showed that the import of choline by MFSD7c is electrogenic. Choline transport function of MFSD7c was shown to be conserved in vertebrates, but not in yeasts. We demonstrated that human MFSD7c is a functional ortholog of HNM1, the yeast choline importer. We also showed that several missense mutations identified in patients exhibiting Fowler syndrome had abolished or reduced choline transport activity. Mice lacking Mfsd7c in endothelial cells of the central nervous system suppressed the import of exogenous choline from blood but unexpectedly had increased choline levels in the brain. Stable-isotope tracing study revealed that MFSD7c was required for exporting choline derived from lysophosphatidylcholine in the brain. Collectively, our work identifies MFSD7c as a choline exporter at the BBB and provides a foundation for future work to reveal the disease mechanisms of Fowler syndrome.