Improving Lipid Content in the Diatom Phaeodactylum tricornutum by the Knockdown of the Enoyl-CoA Hydratase Using CRISPR Interference.

The diatom Phaeodactylum tricornutum shows potential as a source for biofuel production because of its considerable lipid content. Fatty acid ß-oxidation plays a critical role in lipid breakdown. However, we still have a limited understanding of the role of fatty acid ß-oxidation in lipid content in this microalga. In our study, we utilized a CRISPR interference method to reduce the expression of enoyl-CoA hydratase (PtECH), which is involved in the hydration of trans-2-enoyl-CoA to produce 3-hydroxyacyl-CoA during the ß-oxidation pathway. Using this method, we developed two transgenic lines, PtECH21 and PtECH1487, which resulted from interference at two different sites of the PtECH gene, respectively. RT-qPCR analysis confirmed that the mRNA levels of PtECH in both mutants were significantly lower compared to the wild type. Surprisingly, the lipid content of both mutants increased notably. Additionally, both knockdown mutants exhibited higher chlorophyll content and improved photosynthetic efficiency of the photosystem II compared to the wild type. This study introduces a new approach for enhancing lipid content in P. tricornutum and expands our knowledge of the functions of enoyl-CoA hydratase in microalgae.

A key component Rxt3 in the Rpd3L histone deacetylase complex regulates development, stress tolerance, amylase production and kojic acid synthesis in Aspergillus oryzae.

Rpd3L is a highly conserved histone deacetylase complex in eukaryotic cells and participates in various cellular processes. However, the roles of the Rpd3L component in filamentous fungi remain to be delineated ultimately. In this study, we constructed two knockout mutants of Rpd3L's Rxt3 subunit and characterized their biological functions in A. oryzae. Phenotypic analysis showed that AoRxt3 played a positive role in hyphal growth and conidia formation. Deletion of Aorxt3 resulted in augmented tolerance to multiple stresses, including cell wall stress, cell membrane stress, endoplasmic reticulum stress, osmotic stress and oxidative stress. Noteworthily, we found that Aorxt3-deleting mutants showed a higher kojic acid production than the control strain. However, the loss of Aorxt3 led to a significant decrease in amylase synthesis. Our findings lay the foundation for further exploring the role of other Rpd3L subunits and provide a new strategy to improve kojic acid production in A. oryzae.

Heterogenous liver parenchymal enhancement in CT is a favorable prognosis of HCC after hepatic resection.

This study aimed to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with hepatocellular carcinoma (HCC) after hepatic resection. The medical records of patients with HCCs and who had undergone hepatic resection were retrospectively reviewed. The standard deviation (SD) of three different enhanced CT scan images was used to estimate the heterogeneity of liver parenchymal enhancement: SD of > 5.6, heterogenous enhancement, and SD of ≤ 5.6, homogeneous enhancement. A total of 57 patients had heterogenous enhancement, and 143 patients had homogeneous enhancement. The patients with heterogenous enhancement had longer disease-free and overall survivals than those with other enhancements (log-rank test, P < 0.001 and P = 0.036). The pathologic exam showed that heterogenous enhancement tended to develop septa in the peritumoral liver tissues. The prevalence of CD8+ cells was significantly higher in the peritumor liver tissues with septa than in those without (0.83% vs. 0.26%, P < 0.001). The peritumoral CD8/Foxp3 ratio was higher in the liver tissues with septa than in those without (1.22 vs. 0.47, P = 0.001), and patients with CD8/Foxp3 of > 0.8 had better overall survival than those with CD8/Foxp3 of ≤ 0.8 (log-rank test, P = 0.028). In conclusion, patients who had undergone hepatic resection with a heterogenous liver parenchymal enhancement tended to develop hepatic septa, which was associated with a higher CD8/Foxp3 ratio and longer survival. Therefore, contrast-enhanced CT scans might be a useful tool to predict the outcome of HCC.

Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population­based cohort study.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn's disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions: Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

Modulation in the d Band of Ir by Core-Shell Construction for Robust Water Splitting Electrocatalysts in Acid.

The realization of commercialization of proton electrolyte membrane water splitting technology significantly depends on the anodic electrocatalyst working at a high potential and strong acidic conditions requiring superior oxygen evolution reaction activity and stability. In this work, we devise the construction of ultrasmall Pd@Ir core-shell nanoparticles (5 nm) with atomic layer Ir (3 atomic layers) on carbon nanotubes (Pd@Ir/CNT) as an exceptional bifunctional electrocatalyst in acidic water splitting. Due to the core-shell structure, strain generated at heterointerfaces leads to an upshifted d band center of Ir atoms contributing to a 62-fold better mass activity at 1.63 V vs RHE than commercial IrO2; besides, the electronic hybridization suppresses the electrochemical dissolution of Ir; as a result, robust stability is also achieved. In hydrogen evolution reaction catalysis, Pd@Ir/CNT exhibits a 3.7 times higher mass activity than Pt/C. Furthermore, only 1.7 V is required to reach a water splitting current density of 100 mA cm-2, 251 mV lower than that of Pt/C-IrO2, indicating its superiority in acidic water splitting.

Efficient alkaline water splitting catalyzed by ultrafine rhodium telluride nanoparticles.

In this study, we report an efficient bifunctional electrocatalyst of rhodium telluride (RhTe2) for alkaline water splitting. With the construction of Rh-Te bonds, the catalytic performance as well as stability are boosted.

Fluorine dopants in tungsten sulfide boost the efficiency of H2O2 electro-synthesis via the oxygen reduction reaction.

In this work, we report fluorine-doped tungsten sulfide as an exceptional electrocatalyst for H2O2 generation (95% at 0.6 V vs. RHE). The fluorine dopants boost the catalytic efficiency by reducing the binding strength between the catalytic center and OOH* species.

Epidemiological Survey of Different Treatments for Choledocholithiasis in Taiwan: A Nationwide, Population-Based Cohort Analysis.

(1) Background: Open, laparoscopic, and endoscopic choledocholithotomy (OC, LC, and EC, respectively) are accepted choledocholithiasis treatment modalities. However, an assessment of the nationwide trends in their outcomes is lacking. This nationwide population-based analysis evaluated treatment outcomes of choledocholithiasis in Taiwan; (2) Methods: A total of 13,139,306 individuals were randomly enrolled from the Longitudinal Health Insurance Database (LHID) between 2000 to 2013 for cohort analysis. All patients with newly diagnosed choledocholithiasis aged 18 years or older who were treated during the study period were enrolled and allocated to the OC, LC, EC, or combined endoscopy and open choledocholithotomy (CEOC) groups. Age, readmission, retained stone, comorbidities, hospital stay, medical cost, complications, mortality were analyzed; (3) Results: A total of 58,064 individuals met the inclusion criteria, including 46.54%, 1.10%, 47.52%, and 4.85% who underwent OC, LC, EC, and CEOC, respectively. The endpoint characteristics showed that the LC group had higher readmission, longer hospital stay, and higher medical cost. Cox regression analysis showed that the adjusted hazard ratio (HR) of complications for EC was 1.259 times higher than that for OC. The adjusted HRs of readmission within 90 days for LC, EC, and CEOC were higher than that of OC. The adjusted HR of retreatment with surgery was higher in LC. The adjusted HR of retreatment with endoscopy was higher in CEOC. The adjusted HR of mortality in EC was 1.603 times that of OC; (4) Conclusions: Different choledocholithiasis treatments lead to different outcomes. However, further studies on other large or national data sets are required to support these findings.

Radioactive Iodine Treatment for Thyroid Cancer Patients Increases the Risk of Long-Term Gastrointestinal Disorders: A Nationwide Population-Based Cohort Analysis.

(1) Background: The study aimed to investigate the association between radioactive iodine (RAI) treatment and long-term gastrointestinal disorders including ulcers, atrophic gastritis, and secondary malignant neoplasm of the stomach in patients with thyroid cancer. (2) Methods: The data of the study were extracted from the National Health Insurance Database (NHIRD) of Taiwan between 2000 to 2015. Patients of ages older than 20 with thyroid cancer after thyroidectomy were included and divided into groups with RAI (study cohort) and without RAI (comparison cohort). Multivariate Cox proportional hazards regression analysis and the Kaplan-Meier method were used for statistical analysis. (3) Results: A total of 7250 (with RAI: 5800, without RAI: 1450) patients were included. The Kaplan-Meier analysis revealed a significantly higher cumulative risk for overall gastrointestinal disorders in the group with RAI (log-rank p = 0.034). The risk for gastrointestinal disorders was higher when receiving a cumulative RAI dose higher than 1.11 GBq in the Cox regression analysis. In the subgroup analysis, the risks of gastric and duodenal ulcers are significantly higher in the group with RAI treatment. (4) Conclusions: This study revealed that RAI was associated with an increased risk for long-term gastrointestinal disorders, specifically gastric and duodenal ulcers, in thyroid cancer, especially when the cumulative dose exceeds 1.11 GBq.

The Clinical Dilemma of Esophagogastroduodenoscopy for Gastrointestinal Bleeding in Cardiovascular Disease Patients: A Nationwide-Based Retrospective Study.

Performing esophagogastroduodenoscopy (EGD) in recently occurring peri-coronary artery disease (CAD) accident settings is always a dilemma. This study used the Taiwan National Health Insurance Research Database to identify patients with CAD and gastrointestinal bleeding who had received EGD or not between 2000 and 2013.The final population included in this study was 15,147 individuals, with 3801 individuals having received EGD (study cohort group) and 11,346 individuals not having received EGD (comparison cohort group). We initially performed a sensitivity test for CAD recurrence-related factors using multivariable Cox regression during the tracking period. A relatively earlier EGD intervention within one week demonstrated a lower risk of CAD recurrence (adjusted HR = 0.712). Although there were no significant differences in the overall tracking period, the adjusted HR of CAD recurrence was still lower in patients in the EGD group. Furthermore, our findings revealed that there were no remarkably short intervals to CAD recurrence in the study group. The Kaplan-Meier survival curve demonstrated that individuals who underwent EGD were not associated with a significantly increased CAD recurrence rate compared with the control (Log-rank test, p = 0.255). CAD recurrence is always an issue in recent episodes of peri-CAD accident settings while receiving EGD. However, there is not a higher risk in comparison with the normal population in our study, and waiting periods may not be required.

The template synthesis of ultrathin metallic Ir nanosheets as a robust electrocatalyst for acidic water splitting.

Ultrathin metallic iridium nanosheets (∼4 nm) were synthesized using MIL-88A as the sacrificing template at room temperature. Ir-NS shows superior and stable water splitting performance in an acidic medium.

Impact of endoscopic sedation on gastric polyp detection: A one-center retrospective observational study.

Sedation esophagogastroduodenoscopy (EGD) has become more prevalent in many countries. However, owing to the limitation of health insurance payment for sedation EGD in Taiwan, non-sedation EGD still accounts for the majority of cases. This study was aimed to explore the differences between the sedation and non-sedation groups in terms of endoscopic findings, such as detection rate of gastric polyp of any size, number of detected gastric polyps, and location of the gastric polyps detected.We enrolled 10,940 patients who underwent EGD between January 1, 2016 and December 31, 2016 at the Tri-Service General Hospital; among the patients, 1900 received intravenous sedation (IVS) and 9040 did not. The data reviewed included demographics, parameters of the polyp (number, size, and location), and pathology.Compared with the non-sedation group, the sedation group had a higher overall polyp detection rate (P < .001); a greater number of detected polyps (Odds ratio 1.50, P = .007); and a higher detection rate of smaller polyps, such as fundic gland polyp, and hyperplastic polyp (P < .001). Among the pathological findings, gastric neuroendocrine tumor (NET) was detected using EGD in 2 cases and manifested as small polyps (<0.05 cm), and it showed significantly better detection rates in the sedation EGD group than in the non-sedation EGD group (P = .002).Sedation EGD could enhance a patients willingness and cooperation during EGD. Furthermore, sedation EGD increased the detection rates of small gastric polyps and was more likely to enable identification of unusual findings, such as gastric NET.

Clinical outcomes of bortezomib-based therapy in Taiwanese patients with multiple myeloma: A nationwide population-based study and a single-institute analysis.

PURPOSE: In a retrospective cohort study, we report the current epidemiology of patients with multiple myeloma (MM) and analyze the real-world clinical outcomes of bortezomib-based therapy. MATERIALS AND METHODS: This retrospective study was mainly designed to evaluate the characteristics, treatment outcomes, and prognostic factors of patients with MM who received bortezomib-based therapy. We identified 5,726 patients in Taiwan with MM newly diagnosed between 2007 and 2015. Confidential data from the National Health Insurance Research Database (NHIRD) was used under strict guidelines, as it was made available in an electronic format for research purposes. In addition, we analyzed 96 patients who have been diagnosed with MM and were treated at the Tri-Service General Hospital (TSGH) between January 1, 2002, and December 31, 2018. RESULTS: Patients receiving first-line treatment with bortezomib had longer overall survival (OS) compared to those who received non-first-line treatment (p<0.001). In addition, the statistically lowest risk of mortality was when patients received first-line bortezomib followed by an autologous hematopoietic stem cell transplant (adjusted hazard ratio = 0.39, p<0.001). In the TSGH study, the patients were enrolled between January 1, 2002, and December 31, 2018, with an initial diagnosis of MM; there were 96 individuals treated with bortezomib. There was no statistically significant difference in the OS or progression-free survival (PFS) according to the gender, myeloma type, International Staging System stage, or treatment regimen. There was a significant difference in the PFS in patients receiving first-line bortezomib treatment with transplantation compared to those without transplantation (p = 0.021). CONCLUSIONS: Bortezomib as a first-line treatment extended the OS in four-year mortality tracking and lowered the mortality risk according to the NHIRD analysis. In the TSGH analysis, the results indicated that the initial conditions of patients with MM have a lower influence on the OS and PFS after bortezomib-based therapy was administered.

Impact of hemodialysis on the prognosis of multiple myeloma: A nationwide population-based study and single-institute analysis.

Myeloma-associated kidney disease (MRKD) occurs in ≤40% patients with multiple myeloma (MM). The impact of hemodialysis (HD) on patients with MM was investigated. Between 2000 and 2010, a total of 1,610 patients in Taiwan were enrolled from the National Health Institute Research Database. MM was an independent risk factor for HD following adjustment via multivariate logistic regression analysis (adjusted hazard ratio, 7.347; 95% confidence interval, 6.156-8.768; log-rank test, P<0.001). In addition, a notable decrease in survival rate was determined in patients with MM who underwent HD in the first year since diagnosis of MM. A total of 198 (61.49%) patients received HD in the first year. Patients with MM with a lower frequency of HD in the first year had a relatively good prognosis. The present study confirmed that MM was a risk factor for HD. Significant early mortality in the first year was determined in patients with MM who underwent HD; however, renal recovery following therapeutic management was a prognostic factor. In addition to anti-myeloma therapy, early initiation of HD was beneficial following risk stratification of MRKD; however, an increased probability of recovery of renal function and discontinuation of dialysis, was demonstrated in patients with MM following HD, compared with patients with MM without HD.

Exploring the relationship between nonalcoholic fatty liver disease and pancreatic cancer by computed tomographic survey.

Pancreatic cancer is difficult to diagnose in an early stage, and has the highest mortality of all types of cancer. Obesity, high body mass index, and increased abdominal girth are established risk factors. Some studies have postulated that there is a correlation between organ steatosis and pancreatic cancer. This study aims to explore whether nonalcoholic fatty liver disease (NAFLD) is a risk factor and a prognostic factor for pancreatic cancer. The study enrolled 557 patients (143 with and 414 without pancreatic cancer) who were diagnosed between January 2009 and December 2013. We reviewed the abdominal computed tomographic scans of the patients to confirm the diagnosis of NAFLD. Clinical parameters, laboratory data, and personal information were analyzed. NAFLD is an independent risk factor for pancreatic cancer according to adjusted multivariate logistic regression analysis (OR 2.63, 95% CI 1.24-5.58, p = 0.011). The Kaplan-Meier survival curve reveals that patients without NAFLD have longer survival than patients with NAFLD (p = 0.005, log-rank test). NAFLD is positively correlated with pancreatic cancer, a result suggesting that NAFLD may increase the incidence and risk of pancreatic cancer. Patients with pancreatic cancer and NAFLD have poorer overall survival than patients without NAFLD, perhaps, because dysregulated cytokine status leads to progression of pancreatic cancer. NAFLD may be a prognostic factor for pancreatic cancer.