SpliceInfo: an information repository for mRNA alternative splicing in human genome

We have developed an information repository named SpliceInfo to collect the occurrences of the four major alternative-splicing (AS) modes in human genome; these include exon skipping, 5′-alternative splicing, 3′-alternative splicing and intron retention. The dataset is derived by comparing the nucleotide and protein sequences available for a given gene for evidence of AS. Additional features such as the tissue specificity of the mRNA, the protein domain contained by exons, the GC-ratio of exons, the repeats contained within the exons, and the Gene Ontology are annotated computationally for each exonic region that is alternatively spliced. Motivated by a previous investigation of AS-related motifs such as exonic splicing enhancer and exonic splicing silencer, this resource also provides a means of identifying motifs candidates and this should help to identify potential regulatory mechanisms within a particular exonic sequence set and its two flanking intronic sequence sets. This is carried out using motif discovery tools to identify motif candidates related to alternative splicing regulation and together with a secondary structure prediction tool, will help in the identification of the structural properties of such regulatory motifs. The integrated resource is now available on http://SpliceInfo.mbc.NCTU.edu.tw/

Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis

INTRODUCTION: We conducted the present study to evaluate the changes in serum total antioxidant capacity (TAC) in patients with severe sepsis and to investigate the association between serum TAC and clinical severity. METHOD: This was a prospective observational study involving a sample of patients who met established criteria for severe sepsis and were admitted to the emergency department of a university teaching hospital. Serum TAC was determined using the total radical-trapping antioxidant parameter method. The levels of TAC, uric acid, albumin, and bilirubin in sera were obtained in the emergency department and evaluated to determine whether there were any correlations between the major antioxidant biomarkers and clinical severity of sepsis. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was used for clinical evaluation of the severity of sepsis. RESULTS: A total of 73 patients with sepsis, with a mean (± standard deviation) APACHE II score of 23.2 ± 8.2 and a mortality rate of 26.0%, were included. Seventy-six healthy individuals served as control individuals. Among the patients, serum TAC levels correlated significantly with APACHE II scores. Patients who died also had higher TAC than did those who survived. Serum uric acid levels correlated significantly with serum TAC and APACHE II scores in patients with severe sepsis. CONCLUSION: Elevated serum TAC level may reflect clinical severity of sepsis. In addition, serum uric acid levels appear to contribute importantly to the higher TAC levels observed in patients with severe sepsis

Pilot Scheme of Health Policy in Stroke Adjuvant Acupuncture Therapy for Acute and Subacute Ischemic Stroke in Taiwan

To reduce the health care burden of strokes, the Taiwan Department of Health launched the Pilot Scheme of the Health Policy in Stroke Adjuvant Acupuncture Therapy (HPSAAT) in 2006. This cross-sectional, hospital-based, match-controlled study at Chang Gung Memorial Hospital-Kaohsiung Medical Center during 2006∼2008 retrospectively evaluated the clinical characteristics of acute and subacute ischemic stroke patients who electively joined the HPSAAT. The study also evaluated the safety and clinical benefits of adjuvant acupuncture in treating acute and subacute ischemic stroke patients. Twenty-six HPSAAT participants and 52 age-sex matched random controls were enrolled. The stroke baseline of the HPSAAT participants was more severe than the non-HPSAAT controls. Although the stroke severity closely correlates to mortality and comorbidity, this study noted no significant complications in the HPSAAT participants during the acupuncture treatment course. Adjuvant acupuncture was considered safe at the acute and subacute stages of ischemic stroke. Due to uneven baseline severity, the clinical benefits in reducing neurological deficits and functional recovery were not concluded in this study

Postchemoradiotherapy Pathologic Stage Classified by the American Joint Committee on the Cancer Staging System Predicts Prognosis of Patients with Locally Advanced Esophageal Squamous Cell Carcinoma

IntroductionTo determine whether the postchemoradiotherapy (post-CRT) pathologic stage predicts the outcomes of patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing preoperative CRT followed by surgery.MethodsFrom three phase II trials of preoperative CRT for locally advanced ESCC, 140 patients were included. Preoperative CRT comprised twice weekly paclitaxel and cisplatin-based regimens and 40-Gy radiotherapy in 20 fractions. The post-CRT pathologic stage was classified according to the American Joint Committee on Cancer, 7th edition staging system. The prognostic effects of clinicopathologic factors were analyzed using Cox regression.ResultsWith a median follow-up of 61.9 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort were 24.5 and 30.9 months, respectively. The post-CRT pathologic stage was 0 in 34.5%, I in 12.9%, II in 29.3%, III in 13.6%, and ypT0N1-2 in 6.4% of the patients. The median PFS was 47.2, 25.9, 16.0, 9.4, and 15.1 months, and the median OS was 57.4, 34.1, 26.2, 14.1, and 17.6 months for patients with post-CRT pathologic stage 0, I, II, III, and ypT0N1-2, respectively. In multivariate analysis, performance status (p < 0.001), tumor location (p = 0.016), and extranodal extension (p = 0.024) were independent prognostic factors for PFS, whereas performance status (p < 0.001) and post-CRT pathologic stage (p = 0.027) were independent prognostic factors for OS.ConclusionsThe post-CRT pathologic stage classified by American Joint Committee on Cancer, 7th edition staging system predicted the survival of locally advanced ESCC patients who underwent preoperative paclitaxel and cisplatin-based CRT followed by esophagectomy

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients:Dabigatran versus rivaroxaban

Abstract Objective This study assesses the mortality outcomes of non‐vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). Methods Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer‐related death. Secondary outcomes were all‐cause mortality, major bleeding, and gastrointestinal (GI) bleeding. Results Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer‐related death at one year (HR = 0.71, 95% CI = 0.54–0.93) and at the end of follow‐ups (HR = 0.79, 95% CI = 0.64–0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all‐cause mortality (HR = 0.81, 95% CI = 0.67–0.97), major bleeding (HR = 0.64, 95% CI = 0.47–0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39–0.84) at the end of follow‐ups compared with rivaroxaban. Conclusion Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer‐related death and all‐cause mortality

Void Structures in Regularly Patterned ZnO Nanorods Grown with the Hydrothermal Method

The void structures and related optical properties after thermal annealing with ambient oxygen in regularly patterned ZnO nanrorod (NR) arrays grown with the hydrothermal method are studied. In increasing the thermal annealing temperature, void distribution starts from the bottom and extends to the top of an NR in the vertical (c-axis) growth region. When the annealing temperature is higher than 400°C, void distribution spreads into the lateral (m-axis) growth region. Photoluminescence measurement shows that the ZnO band-edge emission, in contrast to defect emission in the yellow-red range, is the strongest under the n-ZnO NR process conditions of 0.003 M in Ga-doping concentration and 300°C in thermal annealing temperature with ambient oxygen. Energy dispersive X-ray spectroscopy data indicate that the concentration of hydroxyl groups in the vertical growth region is significantly higher than that in the lateral growth region. During thermal annealing, hydroxyl groups are desorbed from the NR leaving anion vacancies for reacting with cation vacancies to form voids

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

Lobocrassins A–E: New Cembrane-Type Diterpenoids from the Soft Coral Lobophytum crassum

Five new cembrane-type diterpenoids, lobocrassins A–E (1–5), were isolated from the soft coral Lobophytum crassum. The structures of cembranes 1–5 were established by spectroscopic and chemical methods and by comparison of the spectral data with those of known cembrane analogues. Lobocrassin A (1) is the first cembranoid possessing an α-chloromethyl-α-hydroxy-γ-lactone functionality and is the first chlorinated cembranoid from soft corals belonging to the genus Lobophytum. Lobocrassins B (2) and C (3) were found to be the stereoisomers of the known cembranes, 14-deoxycrassin (6) and pseudoplexaurol (7), respectively. Lobocrassin B (2) exhibited modest cytotoxicity toward K562, CCRF-CEM, Molt4, and HepG2 tumor cells and displayed significant inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils

Natural Product Chemistry of Gorgonian Corals of Genus Junceella—Part II

The structures, names, bioactivities, and references of 81 new secondary metabolites obtained from gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from sea whip gorgonian corals Junceella fragilis and Junceella juncea, collected from the tropical and subtropical Indo-Pacific Ocean