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Abstract Background The necessity of early treatment for lysosomal storage diseases (LSDs) has triggered the development of newborn screening for LSDs in recent years. Here we report the first 70,000 newborns screened for Mucopolysaccharidosis (MPS) type 4A (Morquio syndrome) and other LSDs by an 8-plex assay including the original 4-plex LSD screening tandem mass spectrometry (MS/MS) assay for Pompe disease, Fabry disease, Gaucher disease, and MPS I disease. Methods The additional reaction for MPS II, MPS 3B, MPS 4A, and MPS 6 enzymes was performed separately from the 4-plex reaction. The two reactions were quenched and extracted, then combined before carrying out a single 2-min UPLC-MS/MS analysis. Results From Mar. 2018 to Apr. 2019, 73,743 newborns were screened with the 8-plex LSD screening assay. The 8-plex assay revealed a better analytical precision than the previous 4-plex assay possibly because the 8-plex was carried out using UPLC-MS/MS. Six newborns were found to have low MPS-4A enzyme (N-acetylgalactosamine-6-sulfatase) activity and biallelic GALNS pathogenic mutations in trans; these patients are presumably affected with MPS4A, making an incidence of one in 12,291 (95% confident interval (CI): 5633-26,817). One mutation, c.857C > T (p.T286 M) of the GALNS gene, accounted 5 of the 12 mutated alleles. These newborns had immature vertebral bodies at 1 month of age, and one case was treated with elosulfase alfa 2 mg/kg/week starting from 4 months of age. Among other MPSs screened, one case of MPS I, 3 cases of MPS II, and 3 cases of MPS 3B were detected. One case of mucolipidosis type III was also diagnosed. In conjunction with another 9 patients of Pompe disease, Gaucher disease, and classical Fabry disease, making an incidence of LSDs as one in 3206 newborns (95% CI: 2137 - 4811). The one with infantile-onset Pompe disease and the one with Gaucher disease were treated since the age of 8 days and 41 days respectively. Conclusions Routine newborn screening of MPS 4A and other LSDs were made possible by the 8-plex LSD screening assay. However, detailed phenotype prediction and the time to start treatment will need further elucidation.

Abstract Background The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p

Abstract During COVID-19 pandemic, cases of postvaccination infections and restored SARS-CoV-2 virus have increased after full vaccination, which might be contributed to by immune surveillance escape or virus rebound. Here, artificial linear 9-mer human leucocyte antigen (HLA)-restricted UC peptides were designed based on the well-conserved S2 region of the SARS-CoV-2 spike protein regardless of rapid mutation and glycosylation hindrance. The UC peptides were characterized for its effect on immune molecules and cells by HLA-tetramer refolding assay for HLA-binding ability, by HLA-tetramer specific T cell assay for engaged cytotoxic T lymphocytes (CTLs) involvement, by HLA-dextramer T cell assay for B cell activation, by intracellular cytokine release assay for polarization of immune response, Th1 or Th2. The specific lysis activity assay of T cells was performed for direct activation of cytotoxic T lymphocytes by UC peptides. Mice were immunized for immunogenicity of UC peptides in vivo and immunized sera was assay for complement cytotoxicity assay. Results appeared that through the engagement of UC peptides and immune molecules, HLA-I and II, that CTLs elicited cytotoxic activity by recognizing SARS-CoV-2 spike-bearing cells and preferably secreting Th1 cytokines. The UC peptides also showed immunogenicity and generated a specific antibody in mice by both intramuscular injection and oral delivery without adjuvant formulation. In conclusion, a T-cell vaccine could provide long-lasting protection against SARS-CoV-2 either during reinfection or during SARS-CoV-2 rebound. Due to its ability to eradicate SARS-CoV-2 virus-infected cells, a COVID-19 T-cell vaccine might provide a solution to lower COVID-19 severity and long COVID-19.

Abstract Background While surgery remains the primary treatment for oral squamous cell carcinoma (OCSCC), induction chemotherapy (IC) can be used as a bridging or neoadjuvant therapy. This nationwide study in Taiwan examines the survival outcomes of OCSCC patients who received IC before surgery. Methods We analyzed data from 29,891 patients with OCSCC. Of these, 29,058 initially underwent surgery (OP group), whereas 833 received IC before surgery (IC + OP group). A propensity score (PS)‐matched analysis (4, 1 ratio, 3260 vs. 815 patients) was performed considering tumor subsite, sex, age, Charlson comorbidity index, clinical T1–T4b tumors, clinical N0–3 disease, and clinical stage I–IV. Results In the PS‐matched cohort, the 5‐year disease‐specific survival (DSS) and overall survival (OS) rates were 65% and 57%, respectively. When comparing the OP and IC + OP groups, the 5‐year DSS rates were 66% and 62%, respectively (p = 0.1162). Additionally, the 5‐year OS rates were 57% and 56%, respectively (p = 0.9917). No significant intergroup differences in survival were observed for specific subgroups with cT4a tumors, cT4b tumors, cN3 disease, pT4b tumors, and pN3 disease. However, for patients with pT4a tumors, the OP group demonstrated superior 5‐year outcomes compared to the IC + OP group, with a DSS of 62% versus 52% (p = 0.0006) and an OS of 53% versus 44% (p = 0.0060). Notably, patients with cT2–3, cN1, and c‐Stage II disease in the IC + OP group were significantly more likely to achieve pT0–1 status (p

The variations in the water area and water level of Cheonji, the caldera lake of Baekdu Mountain, serve as reliable indicators of volcanic precursors. However, the geographical and spatial features of Baekdusan make it impossible to directly observe the water area and water level. Therefore, it is crucial to rely on remote sensing data for monitoring purposes. Optical satellite imagery employs different spectral bands to accurately delineate the boundaries between water bodies and non-water bodies. Conventional methods for classifying water bodies using optical satellite images are significantly influenced by the surrounding environment, including factors like terrain and shadows. As a result, these methods often misclassify the boundaries. To address these limitations, deep learning techniques have been employed in recent times. Hence, this study aimed to create an AI dataset using Landsat-5/-7/-8 and Sentinel-2 optical satellite images to accurately detect the water body area and water level of Cheonji lake. By utilizing deep learning methods on the dataset, it is reasonable to consistently observe the area and level of water in Cheonji lake. Furthermore, by integrating additional volcanic precursor monitoring factors, a more accurate volcano monitoring system can be established.

This document provides statistical data and analyses on the relationship between temporomandibular disorders (TMDs) and various symptoms. The data includes scores for TMDs, orofacial pain, and psychological distress, as well as correlations between these variables. The document also includes the results of multivariate logistic regression analyses, indicating the odds ratios for the presence of painful and "any" TMDs. The findings suggest that there is a significant association between TMDs and symptoms such as tinnitus, dizziness, ear pruritus, hearing loss, headache, eye pain, neck pain, and back pain. Further research is needed to better understand these relationships. [Extracted from the article]

Abstract Background Elective tracheotomy is commonly performed in resected oral squamous cell carcinoma (OCSCC) to maintain airway patency. However, the indications for this procedure vary among surgeons. This nationwide study evaluated the impact of tracheotomy on both the duration of in‐hospital stay and long‐term survival outcomes in patients with OCSCC. Methods A total of 18,416 patients with OCSCC were included in the analysis, comprising 7981 patients who underwent elective tracheotomy and 10,435 who did not. The primary outcomes assessed were 5‐year disease‐specific survival (DSS) and overall survival (OS). To minimize potential confounding factors, a propensity score (PS)‐matched analysis was performed on 4301 patients from each group. The duration of hospital stay was not included as a variable in the PS‐matched analysis. Results Prior to PS matching, patients with tracheotomy had significantly lower 5‐year DSS and OS rates compared to those without (71% vs. 82%, p

Abstract Background To compare the clinical outcomes of two treatment modalities, initial surgery and primary definitive radiotherapy (RT), in Taiwanese patients diagnosed with cT1−2N0M0 oral cavity squamous cell carcinoma (OCSCC). Methods Between 2011 and 2019, we analyzed data for 13,542 cT1−2N0M0 patients who underwent initial surgery (n = 13,542) or definitive RT with a dosage of at least 6600 cGy (n = 145) for the treatment of OCSCC. To account for baseline differences, we employed propensity score (PS) matching, resulting in two well‐balanced study groups (initial surgery, n = 580; definitive RT, n = 145). Results Before PS matching, the 5‐year disease‐specific survival (DSS) rates were 88% for the surgery group and 58% for the RT group. After PS matching, the 5‐year DSS rates of the two groups were 86% and 58%, respectively. Similarly, the 5‐year overall survival (OS) rates before PS matching were 80% for the surgery group and 36% for the RT group, whereas after PS matching, they were 73% and 36%, respectively. All these differences were statistically significant (p

The fluctuations in the area and level of Cheonji in Baekdu Mountain have been employed as significant indicators of volcanic activity. Monitoring these changes directly in the field is challenging because of the geographical and spatial features of Baekdu Mountain. Therefore, remote sensing technology is crucial. Synthetic aperture radar utilizes high-transmittance microwaves to directly emit and detect the backscattering from objects. This weatherproof approach allows monitoring in every climate. Additionally, it can accurately differentiate between water bodies and land based on their distinct roughness and permittivity characteristics. Therefore, satellite radar is highly suitable for monitoring the water area of Cheonji. The existing algorithms for classifying water bodies using satellite radar images are significantly impacted by speckle noise and shadows, resulting in frequent misclassification. Deep learning techniques are being utilized in algorithms to accurately compute the area and boundary of interest in an image, surpassing the capabilities of previous algorithms. This study involved the creation of an AI dataset specifically designed for detecting water bodies in Cheonji. The dataset was constructed using satellite radar images from TerraSAR-X, Sentinel-1, and ALOS-2 PALSAR-2. The primary objective was to accurately detect the area and level of water bodies. Applying the dataset of this study to deep learning techniques for ongoing monitoring of the water bodies and water levels of Cheonji is anticipated to significantly contribute to a systematic method for monitoring and forecasting volcanic activity in Baekdu Mountain.

Background: Radical prostatectomy has become the gold standard for treating localized prostate cancer. Improvement in the single-site technique and surgeon's skill reduces not only the hospital duration but also the number of wounds. Realizing the learning curve for a new procedure can prevent unnecessary mistakes. Objective: To analyze the learning curve of extraperitoneal laparoendoscopic single-site robot-assisted radical prostatectomy (LESS-RaRP). Methods: We retrospectively evaluated 160 patients diagnosed with prostate cancer during June 2016 to December 2020 who underwent extraperitoneal LESS-RaRP. Calculated cumulative sum analysis (CUSUM) was used to evaluate the learning curves for the extraperitoneal setting time, robotic console time, total operation time, and blood loss. The operative and functional outcomes were also assessed. Results: The learning curve of the total operation time was observed in 79 cases. For the extraperitoneal setting and robotic console times, the learning curve was observed in 87 and 76 cases, respectively. The learning curve for blood loss was observed in 36 cases. No in-hospital mortality or respiratory failure was observed. Conclusion: Extraperitoneal LESS-RaRP using the da Vinci Si system is safe and feasible. Approximately 80 patients are required to achieve a stable and consistent operative time. A learning curve for blood loss was observed after 36 cases.

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.

Abstract Background The current NCCN guidelines recommend considering elective neck dissection (END) for early‐stage oral cavity squamous cell carcinoma (OCSCC) with a depth of invasion (DOI) exceeding 3 mm. However, this DOI threshold, determined by evaluating the occult lymph node metastatic rate, lacks robust supporting evidence regarding its impact on patient outcomes. In this nationwide study, we sought to explore the specific indications for END in patients diagnosed with OCSCC at stage cT2N0M0, as defined by the AJCC Eighth Edition staging criteria. Methods We examined 4723 patients with cT2N0M0 OCSCC, of which 3744 underwent END and 979 were monitored through neck observation (NO). Results Patients who underwent END had better 5‐year outcomes compared to those in the NO group. The END group had higher rates of neck control (95% vs. 84%, p

Abstract The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1. Mechanistically, USP5 interacts with PD-1, leading to deubiquitination and stabilization of PD-1. Moreover, extracellular signal-regulated kinase (ERK) phosphorylates PD-1 at Thr234 and promotes PD-1 interaction with USP5. Conditional knockout of Usp5 in T cells increases the production of effector cytokines and retards tumor growth in mice. USP5 inhibition in combination with Trametinib or anti-CTLA-4 has an additive effect on suppressing tumor growth in mice. Together, this study describes a molecular mechanism of ERK/USP5-mediated regulation of PD-1 and identifies potential combinatorial therapeutic strategies for enhancing anti-tumor efficacy.

Background: Reinforcement of the immune-regulatory pathway is a feasible strategy for prevention and therapy of allergic asthma. The short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are pleiotropic microbial fermentation products known to induce regulatory T (Treg) cells and exert an immune-regulatory effect. The cellular mechanism underlying SCFA immune regulation in asthma is not fully understood. Objective: We investigated the role of myeloid-derived suppressor cells (MDSCs) and Treg cells, the immune-regulatory cells of innate and adaptive origin, respectively, in SCFA-elicited protection against allergic airway inflammation. Methods: BALB/c mice were given SCFA-containing drinking water before being rendered asthmatic in response to ovalbumen. When indicated, mice were given a GR1-depleting antibody to investigate the function of MDSCs in allergic inflammation of the airways. MDSCs were sorted to examine their immunosuppressive function and interaction with T cells. Results: The mice receiving SCFAs developed less severe asthma that was accompanied by expansion of PMN-MDSCs and Treg cells. Mice depleted of PMN-MDSCs exhibited aggravated asthma, and the protective effect of SCFAs was abrogated after PMN-MDSC depletion. SCFAs were able to directly induce T-cell differentiation toward Treg cells. Additionally, we found that PMN-MDSCs enhanced Treg cell expansion in a cell contact–dependent manner. Whilst membrane-bound TGF-β has been shown to induce Treg cell differentiation, we found that MDSCs upregulated surface expression of TGF-β after coculture with T-cells and that MDSC-induced Treg cell differentiation was partially inhibited by TGF-β blockage. Conclusions: Although previous studies revealed Treg cells as the effector mechanism of SCFA immune regulation, we found that SCFAs ameliorate allergic airway inflammation by relaying immune regulation, with sequential induction of PMN-MDSCs and Treg cells.

Abstract Background The prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC. Methods Data made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse. Results The median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p

In Taiwan, a considerable amount of coffee residue is produced from commercial activities without valuable utilization. To evaluate high-value valorization in the production of highly porous carbon materials, this study investigated the thermochemical properties of coffee residues and further pyrolysis for producing highly porous biochar products at an elevated temperature (i.e., 850 °C) and a moderate residence time of 30 min. Our findings indicate that this biomass has a relatively high calorific value (about 27 MJ/kg, dry basis) due to its low ash and high lignocellulose content. It can be also concluded that the non-activated biochar products are highly porous carbon materials with excellent pore properties (i.e., a BET surface area of about 800 m2/g and a total pore volume of 0.4 cm3/g), which are slightly lower than those of commercial activated carbon products. Based on the above-mentioned results and the high-value circular bio-economy promoted by regulatory policy in Taiwan, the prospects for the possible valorization of coffee residue from commercial shops are addressed here, focusing both on the reuse of plant-based residue (or agricultural waste) as a high-value bioresource in the production of biomass-based fuels and on carbon materials. The former includes solid recovered fuel (SRF) and biomass-to-biogas power. By contrast, the latter aims at the production of plant-based carbon as natural, edible colorants in accordance with the regulation of food safety and sanitation in Taiwan.

Purpose: The purpose of the study is to test the relationships between the antecedents of noneconomic satisfaction and its influence on economic satisfaction from both a seller’s and a purchaser’s perspective. Design/methodology/approach: Purchase and sales managers working for Taiwanese companies were included in the sample. Snowball sampling was applied and a total of 218 purchase managers and 208 sales managers participated in the study. Structural equation modelling was applied to the study. Findings: Opportunism was determined as an antecedent to conflict, while opportunism did not have a negative relationship with noneconomic satisfaction. Conflict was established as having a negative relationship with noneconomic satisfaction, which related positively to economic satisfaction in B2B relationships. Practical implications: The findings give purchase and sales managers insights that enable them to understand how opportunism relates to conflict, how these two antecedents relate to noneconomic satisfaction and how noneconomic satisfaction relates to economic satisfaction in purchase and sales business relationships. The tested model validates the hypothesised relationships between opportunism and conflict, conflict and noneconomic satisfaction, and noneconomic satisfaction and economic satisfaction from both a purchaser’s and a seller’s perspective. However, the negative relationship between opportunism and noneconomic satisfaction in purchaser–seller relationships could not be confirmed. Originality/value: No existing study has focused on relationship marketing in business-to-business relationships from both a purchaser’s and a seller’s perspective to establish whether noneconomic satisfaction functions as a connector between economic satisfaction and opportunism and conflict.

As the importance of forests has increased, continuously monitoring and managing information on forest ecology has become essential. The composition and distribution of tree species in forests are essential indicators of forest ecosystems. Several studies have been conducted to classify tree species using remote sensing data and machine learning algorithms because of the constraints of the traditional approach for classifying tree species in forests. In the machine learning approach, classification accuracy varies based on the characteristics and quantity of the study area data used. Thus, applying various classification models to achieve the most accurate classification results is necessary. In the literature, patch-based deep learning (DL) algorithms that use feature maps have shown superior classification results than point-based techniques. DL techniques substantially affect the performance of input data but gathering highly explanatory data is difficult in the study area. In this study, we analyzed (1) the accuracy of tree classification by convolutional neural networks (CNNs)-based DL models with various structures of CNN feature extraction areas using a high-resolution LiDAR-derived digital surface model (DSM) acquired from a drone platform and (2) the impact of tree classification by creating input data via various geometric augmentation methods. For performance comparison, the drone optic and LiDAR data were separated into two groups according to the application of data augmentation, and the classification performance was compared using three CNN-based models for each group. The results demonstrated that Groups 1 and CNN-1, CNN-2, and CNN-3 were 0.74, 0.79, and 0.82 and 0.79, 0.80, and 0.84, respectively, and the best mode was CNN-3 in Group 2. The results imply that (1) when classifying tree species in the forest using high-resolution bi-seasonal drone optical images and LiDAR data, a model in which the number of filters of various sizes and filters gradually decreased demonstrated a superior classification performance of 0.95 for a single tree and 0.75 for two or more mixed species; (2) classification performance is enhanced during model learning by augmenting training data, especially for two or more mixed tree species.

Several anthrapyrazolone derivatives derived from 7-chloroanthra[1,9-cd]pyrazol-6(2H)-one and 7-chloro-2-(2-hydroxyethyl)anthra[1,9-cd] pyrazol-6(2H)-one have been prepared by the addition or substitution nucleophilic reactions and further transformed into extended tetracyclic systems and fused to different nitrogenheterocyclic rings into the pharmacophore structure moiety. The compounds synthesized were evaluated for their cytotoxic activity and telomerase activity in prostate cancer cell line by SRB assay and in human non-small cell lung carcinoma cell line by TRAP assay, respectively. Compounds 1–6, 13, 14, 16, 17, 19, 21, 23, 28 and 31 were selected by the NCI and only 1, 4, and 16 represent the GI50, TGI and LC50, respectively. Among them, 1 and 16 exhibited distinctive selectivity of GI50 of 10.498 μM and 4.542 μM over 60 cell lines which is better than the average GI50 (20.3 μM) for SP600125 (NSC75890). Overall, the test compounds exhibited different telomerase and cytotoxic activities and only few compounds displayed antitumor activity in the low range. Keywords: Anthrapyrazolone, SRB assay, TRAP assay, Cytotoxicity, NCI 60-cell panel assay, Antiproliferation

Sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. S1R modulates activity of multiple effector proteins and is a well-established drug target. However, signaling functions of S1R in cells are poorly understood. Here, we test the hypothesis that biological activity of S1R in cells can be explained by its ability to interact with cholesterol and to form cholesterol-enriched microdomains in the ER membrane. By performing experiments in reduced reconstitution systems, we demonstrate direct effects of cholesterol on S1R clustering. We identify a novel cholesterol-binding motif in the transmembrane region of human S1R. Mutations of this motif impair association of recombinant S1R with cholesterol beads, affect S1R clustering in vitro and disrupt S1R subcellular localization. We demonstrate that S1R-induced membrane microdomains have increased local membrane thickness and that increased local cholesterol concentration and/or membrane thickness in these microdomains can modulate signaling of inositol-requiring enzyme 1α in the ER. Further, S1R agonists cause disruption of S1R clusters, suggesting that biological activity of S1R agonists is linked to remodeling of ER membrane microdomains. Our results provide novel insights into S1R-mediated signaling mechanisms in cells.

Pathogens find diverse niches for survival including inside a host cell where replication occurs in a relatively protective environment. Vibrio parahaemolyticus is a facultative intracellular pathogen that uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. Analysis of the T3SS2 pathogenicity island encoding the T3SS2 appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of molecular tools, we found that VPA0226, a constitutively secreted lipase, is required for escape of V. parahaemolyticus from the host cells. This lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems and host cell resources to evolve an ingenious scheme for survival and escape.

Business ecosystem concept takes ideas from ecological ecosystems into analysis of complex networks. Business ecosystems emerge either as managed initiatives or organically, impacted by internal or external stimuluses. Ecosystem formation is unpredictable and challenging to control transferring project front-end into an operational ecosystem. The theme of this research is how to form a healthy business ecosystem. If defines a framework for formation analysis and introduces the concept of the anchoring actor as a role leading the formation. Ecosystem health assessment through actors and relationships provides information to support ecosystem formation. Through a case study in Taiwanese health and wellbeing domain, this research presents how the anchoring actors can be identified and how they contribute to ecosystem formation. Building on the anchoring actors’ contribution, the research defines a model for ecosystem health assessment. Practitioners can use the findings to facilitate the ecosystem formation and to monitor the ecosystem health. This research contributes to the business ecosystem and business network literatures by introducing the anchoring actor as an important role for ecosystem formation and by presenting how ecosystem health can be assessed.