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Abstract Mucopolysaccharidosis (MPS) type II is caused by a deficiency of iduronate-2-sulfatase and is characterized by the accumulation of glycosaminoglycans (GAGs). Without effective therapy, the severe form of MPS II causes progressive neurodegeneration and death. This study generated multiple clones of induced pluripotent stem cells (iPSCs) and their isogenic controls (ISO) from four patients with MPS II neurodegeneration. MPS II-iPSCs were successfully differentiated into cortical neurons with characteristic biochemical and cellular phenotypes, including axonal beadings positive for phosphorylated tau, and unique electrophysiological abnormalities, which were mostly rescued in ISO-iPSC-derived neurons. RNA sequencing analysis uncovered dysregulation in three major signaling pathways, including Wnt/β-catenin, p38 MAP kinase, and calcium pathways, in mature MPS II neurons. Further mechanistic characterization indicated that the dysregulation in calcium signaling led to an elevated intracellular calcium level, which might be linked to compromised survival of neurons. Based on these dysregulated pathways, several related chemicals and drugs were tested using this mature MPS II neuron-based platform and a small-molecule glycogen synthase kinase-3β inhibitor was found to significantly rescue neuronal survival, neurite morphology, and electrophysiological abnormalities in MPS II neurons. Our results underscore that the MPS II-iPSC-based platform significantly contributes to unraveling the mechanisms underlying the degeneration and death of MPS II neurons and assessing potential drug candidates. Furthermore, the study revealed that targeting the specific dysregulation of signaling pathways downstream of GAG accumulation in MPS II neurons with a well-characterized drug could potentially ameliorate neuronal degeneration.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Abstract Because of the cancer incidence increase and population aging in Taiwan, we aimed to assess the cancer prevalence, to summarize the comorbidities of older patients with the five most common cancers (i.e., breast, colorectal, liver, lung, and oral), and to develop a Taiwan cancer comorbidity index (TCCI) for studying their actual prognosis. The linkage of the Taiwan Cancer Registry, Cause of Death Database, and National Health Insurance Research Database was used. We followed the standard statistical learning steps to obtain a survival model with good discriminatory accuracy in predicting death due to noncancer causes, from which we obtained the TCCI and defined comorbidity levels. We reported the actual prognosis by age, stage, and comorbidity level. In Taiwan, cancer prevalence nearly doubled in 2004–2014, and comorbidities were common among older patients. Stage was the major predictor of patients' actual prognoses. For localized and regional breast, colorectal, and oral cancers, comorbidities correlated with noncancer-related deaths. Compared with the US, the chances of dying from comorbidities in Taiwan were lower and the chances of dying from cancer were higher for breast, colorectal, and male lung cancers. These actual prognoses could help clinicians and patients in treatment decision-making and help policymakers in resource planning.

While canonical oxygen-rebound pathway has been utilized by several Fe/2OG enzymes, insights into the desaturation process remain to be elucidated. Here, the authors suggest that a carbocation might be deployed to enable chemically divergent desaturations through decarboxylation and deprotonation.

Sb- and Nb-doped Zr and Sn-umbites have been prepared using hydrothermal synthesis with both high purity and yield. All four materials display excellent removal of Cs+ cations from acidic, neutral, and basic solutions, abating at least 80% of the Cs present. This performance is retained in the presence of competing Na+ cations as well as across the pH range. The most sustained selectivity is observed in acidic media, with evidence of a minor reduction in selectivity under basic conditions. The umbites have successfully been shaped into pellets, introducing macroporosity and retaining the selective uptake of Cs in the presence of excess Na. Through thermal treatment, samples of partially Cs-exchanged umbite can be converted into dense silicate phases where radioactive Cs can be immobilized in a potential wasteform for long term storage. These findings present doped umbites as prospective materials for industrial use with selective abatement properties and capabilities for deployment followed by end of life geological disposal.

Bacterial cellulose (BC) is a microbial cellulose that presents various characteristics such as high mechanical strength, high water content, and great biocompatibility and biodegradability. Therefore, it provides great potential to be applied in functional packaging applications. In this study, formic acid (80 µg/mL) was found to promote BC production (a 23% increase in yield from 5.18 to 6.38 g/L) utilizing quorum sensing-related gene (ginI) induction within 5 days of cultivation. The enhancement in BC relied on the addition of FA in static culture, and there was no need to shift to another production system, thus providing an economical approach for industrial production. The characteristic analysis showed that the induced BC still retained its high water-holding capacity (98.4%) with no other structure, morphology, or property changes including chemical groups, crystallinity (80.4%), and thermostability (with Tmax at 360 °C). Analysis of the produced BC showed that it is a suitable, ecofriendly biomaterial for food packaging, and its further evaluation will be accomplished in future studies.

The Taiwan Lantern Festival (TLF) is a specific cultural tradition that has evolved over many years. It is a large-scale festival as determined by the large number of installations and visitors—that is, 20 million visitors in a period of two weeks. The aim of this study is to combine the TLF-related physical dynamics of land use and lantern installations with the augmented dynamics of lantern installations at reallocated sites. We compared five cities in Taiwan with regard to land alterations between 2016 and 2020. The TLF land assessment identified 34 cross-referred types of land use between aerial imagery and GIS surveys in a small area of 2 km × 2 km, in total. The change in land use by year varied between 2% and 499%, up to three times. The complexity of physical dynamics was re-experienced by a more sustainable dynamic of augmented reality (AR) using a scan-to-AR approach to reactivate the installations and fabrics at redeployed sites. The installations of the 2016 TLF were applied. We found that the land use, 3D scan, and AR reshaped the spatio-temporal festivalscape by both types of dynamics. The simulation demonstrated that the fabric retrieved by heterogeneous technologies had equal importance in assessing the host city and in enabling a reactivation for more diversified scales and characters, even with a smartphone AR.

Hyperuricemia is a disease caused by a high level of uric acid in the blood. It is an important factor for gout and may be linked to renal and hepatic failure. The objective of this study was to investigate the hypouricemic effects of submerged culture of Ganoderma lucidum. The lyophilized powder of mycelium (GM) and extracellular polysaccharides (GP) of the G. lucidum submerged culture were prepared. The contents of hypouricemic components, including phenolics and flavonoids, in GM (34.33 ± 0.41 mg/g and 0.32 ± 0.01 mg/g) were higher than that in GP (20.52 ± 1.49 mg/g and not detected). The hypouricemic effect of GM and GP was evaluated in potassium oxonate (PO)-injected rats. The average food intake (23.3 ± 1.2 g/day) and body weight (355.7 ± 28.0 g) were decreased, and the serum level of uric acid (5.56 ± 0.41 mg/dL) was increased in PO-injected rats. However, allopurinol (10 mg/kg b.w.) or GM treatment (200 or 400 mg/kg b.w) improved food intake (26.3 ± 2.7 g/day) and reduced the level of uric acid (4.45 ± 0.46 mg/dL). In parallel, the activity of hepatic xanthine oxidase (XOD) was downregulated from 841.29 ± 299.58 μU/mg protein to 540.80 ± 199.20 μU/mg protein. Moreover, GM and GP (200 or 400 mg/kg b.w) alleviated the level of blood urea nitrogen (BUN) from 30.49 ± 4.71 to 21.16 ± 4.25 mg/dL. GP treatment also diminished the level of alanine transaminase (ALT) from 52.63 ± 18.82 to 27.35 ±6.82 U/L. These results clearly demonstrated the hypouricemic effect of submerged G. lucidum culture and their potential against hyperuricemia-associated renal and hepatic damage. GM was more potent to alleviate hyperuricemia, and GP was more potent to improve renal and hepatic function.