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Carassius auratus complex formula (CACF) is a traditional Chinese medicine known for its antidiabetic effects. Hepatocellular carcinoma (HCC) is a major cause of cancer‐related deaths worldwide, and there are currently no effective therapies for advanced HCC. This study explores the comprehensive effects and possible mechanisms of CACF on HCC. The results show that CACF reduces the viability of hepatoma cells in vitro, while benefiting normal hepatocytes. In addition, CACF inhibits hepatoma cell growth in a zebrafish xenotransplantation model and decreases lipid accumulation, represses inflammation and cell proliferation markers in fatty acid translocase (CD36) transgenic zebrafish, and inhibits the expression of cell proliferation and β‐catenin downstream targets in telomerase (tert) transgenic zebrafish models. Ingenuity Pathway Analysis reveals that CACF exerts multiple functions, including reduction of inflammation and inhibition of lipid transporter and PPAR signaling pathway. Surprisingly, CACF also regulates the expression of genes and reduces coronavirus infection and pathogenesis in a zebrafish model. CACF treatment is validated to regulate the expression of genes for anti‐coronavirus activity. Mechanistically, CACF stabilizes G‐quadruplex and reduces cell senescence associated β‐galactosidase activity. In summary, CACF may be a promising therapeutic agent with multiple functions including anticancer, anti‐inflammation, and anti‐microorganisms in a zebrafish model. [ABSTRACT FROM AUTHOR]

Aim: Abnormal fertilization (1PN/3PN) and its accompanying polar body (PB) conditions have been less discussed in poor ovarian responders. By observing the PBs, we analyzed the mechanisms of abnormal fertilization and aimed to explore the role of intracytoplasmic sperm injection/in vitro fertilization (ICSI/IVF) in POSEIDON group 4 patients. Methods: An observational study. All fresh IVF/ICSI cycles from January 2018 to December 2019 were evaluated. The inclusion criteria were POSEIDON group 4. Fertilization and PB conditions were assessed 16–18 h post‐insemination. Primary observation endpoints including normal fertilization, abnormal fertilization, and total fertilization failure rate. Results: A total of 351 cycles involving 180 patients met the inclusion criteria. Of these, 15 cycles reported no retrieved oocytes. Finally, 336 cycles (IVF, n = 267; ICSI, n = 69) were included. A total of 1005 oocytes and 939 embryos were assessed. The mean female age was 40.8 years, and the mean AMH level was 0.6 ng/mL. The normal fertilization rate was 69.7%. The zygote distribution was 18.7% 0PN, 3.9% 1PN, 66.9% 2PN, 9.5% 3PN, and 1.0% ≥4PN. For 1PN zygotes, 59% were denoted as 1PN2PB. The mean 3PN rate was 8.9%. Conclusions: In POSEIDON group 4, most of the monopronucleated zygotes were 1PN2PB. Digyny (3PN1PB), due to failure to extrude the second PB, was the major cause of triploidy in which ICSI could not circumvent. The distribution of abnormally fertilized zygotes was similar in IVF and ICSI. To investigate the mechanisms of abnormal fertilization and assess whether ICSI is necessary, analysis of PB will provide important clues. [ABSTRACT FROM AUTHOR]

Information on genetic variants associated with elevated serum alanine aminotransferase (ALT) levels remains limited. A genome‐wide association study was performed to identify single‐nucleotide polymorphisms (SNPs) associated with ALT levels. The ALT‐associated SNP was further evaluated for hepatocellular carcinoma (HCC) risk. A cohort of 892 anti‐HCV seropositive patients was used for genome‐wide SNP array to examine the associations with baseline ALT levels. SNPs <10−5 were further tested for associations with serial ALT levels then validated in 486 anti‐HCV seropositives. Multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals of SNPs associated with ALT. The SNP was evaluated for HCC risk by using Cox's proportional hazards models. After quality control, 803 participants with 564,464 SNPs were included in the analysis. Of these, 12 SNPs were associated with ALT (p < 10−5). Among the participants, 158 (19.7%) had ALT persistently ≤15 U/L, 327 (40.7%) ever >15 U/L but never >45 U/L, and 318 (39.6%) ever >45 U/L during follow‐up. The rs568800 was associated with serial ALT levels, and this was replicated in the external population significantly (p <.05). The A allele (vs C) of rs568800 was associated with ALT >15 U/L but ≤45 U/L and ALT >45 U/L, with the adjusted ORs of 1.41 (1.11–1.78) and 1.86 (1.34–2.60), respectively. The adjusted HRs for HCC were 2.09 (0.90–4.89) for AC and 2.64 (1.13–6.17) for AA (CC as a reference). In conclusion, the rs568800 was associated with serum ALT levels and HCC risk. Clinical utility should be evaluated among patients who have received antivirals. [ABSTRACT FROM AUTHOR]

Teachers in K‐12 settings often teach out of textbooks in order to provide differentiated instruction. Open educational resources (OER) might be an effective alternative to traditional textbooks for K‐12 teachers because of a free access to a rich collection of open‐licensed educational materials. Understanding how to encourage teachers to accept OER is thus critical. However, existing evidence mainly concerns the advantage of OER in cost reduction but overlooks the merit of openness. To fill this gap, this mixed methods inquiry, implementing the technology acceptance model, integrated qualitative and quantitative findings to obtain a comprehensive understanding of teachers' intentions of adopting OER in K‐12 settings. This study found that perceived ease of use and perceived usefulness predicted K‐12 teachers' intention to adopt OER with attitudes toward OER as a mediating variable. Perceived ease of use also determined perceived usefulness. Teachers' perceptions of OER adoption were also examined for additional insight into the quantitative findings. Practical implications of adopting OER in K‐12 curriculum were discussed. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. Aims: To explore genetic variants associated with chronic HBV infection. Methods: The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole‐genome genotyping by Axiom‐Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method. Results: Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10−35) was significantly associated with HBV chronicity (Pcorrected < 8.6 × 10−8). Imputation analyses showed that HLA‐DPA1*02:02 and HLA‐DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09‐1.89) and 1.61 (1.29‐2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA‐DRB1*13:02, HLA‐DQA1* 01:02 and HLA‐DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17‐0.58), 0.70 (0.56‐0.87) and 0.33 (0.18‐0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. Conclusions: HLA class II variants are relevant for chronicity after HBV acquisition. [ABSTRACT FROM AUTHOR]

G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs. What's new? G protein‐coupled estrogen receptor‐1 (GPER) mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, the role of GPER in breast cancer stem cells (BCSC) biology remains unclear. Here, using patient‐derived xenografts of ER–/PR+ breast cancer, the authors found higher expression of GPER in BCSCs than non‐BCSCs. Moreover, the results indicated that stemness features were sustained via GPER‐mediated PKA/BAD phosphorylation. Stimulation by the GPER ligand tamoxifen enhanced BCSC cell viability and population and BAD phosphorylation. The findings revealed a vital role of GPER‐mediated signaling pathways in BCSC survival, suggesting GPER as a potential therapeutic target for eradicating BCSCs. [ABSTRACT FROM AUTHOR]

Abstract: Cellulose is a renewable feedstock for green industry. It is therefore important to develop a technique to construct a host with a high cellulolytic efficiency to digest cellulose. In this study, we developed a convenient host‐engineering technique to adjust the expression levels of heterologous genes in the host by promoter rearrangement and gene copy number adjustment. Using genes from different glycoside hydrolase (GH) families including GH2, GH3, GH5, GH6, GH7, and GH12 from Aspergillus niger, Trichoderma reesei, and Neocallimastix patriciarum, we constructed a cellulolytic Kluyveromyces marxianus with eight cellulase gene‐cassettes that produced a cellulase cocktail with a high cellulolytic efficiency, leading to a significant reduction in enzyme cost in a rice straw saccharification process. Our technique can be used to design a host that can efficiently convert biomass feedstock to biofuel. [ABSTRACT FROM AUTHOR]

Oestrogens have been reported to attenuate acute inflammation in sepsis. In this study, the effects of long-term oestrogen replacement with 17β-oestradiol (E2) on endotoxaemia-induced circulatory dysfunction and multiple organ dysfunction syndrome were evaluated in ovariectomized (Ovx) rats. E2 (50 μg/kg, s.c., 3 times/week) was administered for 8 weeks, followed by the induction of endotoxaemia by intravenous infusion of lipopolysaccharides (LPS; 30 mg/kg/4 hrs). Oestrogen deficiency induced by ovariectomy for 9 weeks augmented the LPS-induced damage, including endotoxic shock, myocardial contractile dysfunction, renal dysfunction and rhabdomyolysis. Cardiac levels of NF-κB p65, iNOS and oxidized glutathione, free radical production in skeletal muscles, myoglobin deposition in renal tubules, and plasma levels of plasminogen activator inhibitor-1, TNF-α, and IL-6 were more pronounced in the Ovx + LPS group than in the Sham + LPS group. Long-term treatment of E2 prevented this amplified damage in Ovx rats. Six hours after LPS initiation, activation of the autophagic process, demonstrated by increases in Atg12 and LC3B-II/LC3B-I ratios, and induction of haem oxygenase (HO)-1 and heat-shock protein (HSP) 70 protein expression in myocardium were increased significantly in the Ovx + E2 + LPS group. These results suggest that activation of autophagy and induction of HO-1 and HSP70 contribute to the protective effect of long-term E2 replacement on multiple organ dysfunction syndrome in endotoxaemia. [ABSTRACT FROM AUTHOR]

Background The association between hepatitis C virus ( HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality. Methods A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991-1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios ( HRs) with 95% confidence intervals ( CIs). Antibodies against HCV (anti- HCV) were tested for all participants, and serum HCV RNA levels were measured for anti- HCV seropositives. Results During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti- HCV seronegatives and 16.7% for anti- HCV seropositives respectively. The HR for diabetes of anti- HCV seropositivity was 1.53 (95% CI: 1.29-1.81) compared with anti- HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31-2.02) for anti- HCV seropositives with positive HCV RNA compared to anti- HCV seronegatives ( P<.001). Conclusion Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors. [ABSTRACT FROM AUTHOR]

A series of indeno[2,1- b]thiophene-containing organic dyes ( IDT1- IDT5) have been synthesized, and their UV/Vis spectra extend beyond 700 nm. These dyes were employed as sensitizers for dye-sensitized solar cells (DSSCs). Among them, dyes IDT3- IDT5 with a thiophene unit conjugated with an anchor have better light harvesting ability and higher JSC values. Dye aggregation contributes substantially to the photocurrent in the near infrared region. The dye IDT5, with chenodeoxycholic acid (CDCA) as the co-adsorbent, has the highest power conversion efficiency (5.06 %) under AM 1.5G simulated sunlight irradiation, which is 68 % of the standard device based on N719 dye. [ABSTRACT FROM AUTHOR]

ABSTRACT The pyrrolidine side chain makes proline play a unique role in protein structure and function. The Cγ ring pucker preference and the cis - trans peptidyl bond ratio can be mediated via stereoelectronic effects. Here we used a compact triple-stranded antiparallel β-sheet protein, the human Pin1 WW domain, to study the consequences of implanting a preorganized Cγ ring pucker on protein structure and function. The conserved Pro37 is a key residue involved in one hydrophobic core, plays an important role in the WW domain, and adopts a Cγ- endo ring pucker in the native structure. Pro37 was replaced with Cγ- exo biased pucker derivatives: (2 S,4 R)-4-hydroxyproline (4 R-Hyp), (2 S,4 R)-4-fluoroproline (4 R-Flp), (2 S,4 R)-4-methoxyproline (4 R-Mop), and Cγ- endo biased pucker derivatives: (2 S,4 S)-4-hydroxyproline (4 S-hyp), (2 S,4 S)-4-fluoroproline (4 S-flp), (2 S,4 S)-4-methoxyproline (4 S-mop) to examine how a preorganized pucker affects the folding stability and ligand-binding affinity. Circular dichroism measurements indicate that among the variants, only the one with 4 S-flp substitution (P37flp) is more stable than the wild type, suggesting that the stabilization effects originated from preorganization of the backbone conformation and the hydrophobicity of CF group. Analysis of ligand-binding affinity using isothermal titration calorimetry revealed that only P37flp has a stronger ligand affinity than the wild type, showing that 4 S-flp can stabilize the WW domain and increase its ligand affinity. Together we have used 4-substituted proline derivatives and the WW domain to demonstrate that proline ring puckering can be a key factor in determining the folding stability of a protein but the choice of the derivative groups is also critical. Proteins 2014; 82:67-76. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT Purpose This study aimed to examine trends in the first-year pharmacological treatment of newly treated schizophrenia patients in Taiwan between 1999 and 2006. Method We collected data from the National Health Insurance Research Database of all newly treated patients with a diagnosis of schizophrenia-spectrum disorder (ICD-9 295.x). We analyzed all prescription records after diagnosis of schizophrenia and described the patterns of antipsychotics use, other concomitant psychotropic agents use, and mental health system utilization. We tested for trend using multivariate logistic regression and Spearman's partial correlation rank test. Results A total of 2895 newly treated patients with schizophrenia were enrolled. The percentage of prescriptions of second-generation antipsychotics (SGAs) was found to have increased significantly, from 27.5% in 1999 to 76.9% in 2006. The ratio of good antipsychotics adherence (medication possession ratio >0.8) also increased, from 23.2% in 1998 to 38.9% in 2006. Corresponding to this, the percentage of usage of first-generation antipsychotic drugs, anticholinergic agents, and long-term combination therapy declined. However, the prescription of antidepressants and mood stabilizers and the hospitalization rate increased. No change was noted in the number of psychiatric visits. Conclusion In the first-year treatment of newly treated schizophrenic patients between 1999 and 2006, we found pharmacological treatment had changed in terms of types of antipsychotics, adherence, and the use of other concomitant psychotropic agents, with the introduction of SGAs. The benefits and costs of the changes with a trend toward an increasing prescription of SGAs warrant further investigation. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Purpose: This study assesses the sensitivity and specificity of Mandarin versions of two psychosocial screening tools for adjustment, anxiety and depressive disorders: the Hospital Anxiety and Depression Scale (HADS), and the Distress Thermometer (DT). Methods: The two scales were used to screen 103 consecutive cancer patients seen for psychiatric evaluation at KF-SYSCC between May and November 2004 prior to their psychiatric interviews. Each scale was tested against clinical psychiatric diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for their sensitivity and specificity. Results: For the Mandarin version of the DT, receiver operating characteristic (ROC) analyses identified a DT score of 4 as the optimal cut-off, with sensitivity and specificity of 98 and 73%, respectively. For the Mandarin version of the HADS, ROC identified a score of 9 and 8 as the optimal cutoffs for the respective anxiety and depression subscales (HADS-a and HADS-d), with sensitivities and specificities of 84 and 73, 72 and 86%, respectively. For the full scale of the HADS (HADS-t), 15 was identified as the optimal cutoff, which yielded sensitivity and specificity of 84 and 68%, respectively. Using the frequency table, the concordance rate of the two scales was found to be 72-80% based on the above optimal cut-offs. Conclusion: The Mandarin versions of the HADS and the DT are efficacious for screening anxiety and depression for our population. Compared with the HADS-t, the DT appears to have not only higher sensitivity, but also higher specificity. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Southern corn leaf blight (SCLB) is an important foliar disease of maize. In this study, an induced systemic resistance (ISR)-eliciting rhizobacterium Bacillus cereus C1L was used to protect maize against SCLB. Application of B. cereus C1L in maize rhizosphere effectively protected maize from SCLB under greenhouse and field conditions. The protection effect of B. cereus C1L was similar to that of Maneb (2 kg active ingredient per hectare), a recommended fungicide. Furthermore, possible factors of B. cereus C1L to elicit ISR and to promote plant growth were investigated. The results indicate that secreted factors and rhizosphere colonisation ability of B. cereus C1L are involved in ISR elicitation. In addition to biocontrol activity, B. cereus C1L was able to promote growth of maize in field. Compared with a non-treated control, leaf length, leaf width, plant height and fresh and dry weights of B. cereus C1L-treated corn plants significantly increased. Therefore, B. cereus C1L acts as a plant growth-promoting rhizobacterium of maize. [ABSTRACT FROM AUTHOR]

There has been growing interest in polyproline type II (PPII) helices since PPII helices have been found in folded and unfolded proteins and involved in a variety of biological activities. Polyproline can also form type I helices (PPI) which are very different from PPII conformation and only exist in certain organic solvents. Recent studies have shown that stereoelectronic effects play a critical role in stabilizing a PPI or PPII helix. Here, we have synthesized a series of host-guest peptides with an electron-withdrawing substituent at the 4 R or 4 S position of proline and used a kinetic approach to further explore stereoelectronic effects on the transition barrier of the interconversion between PPI and PPII conformations. Time-dependent circular dichroism measurements revealed that the rates of PPII → PPI conversion were reduced upon incorporating the hydroxyl-, fluoro-, and methoxy-groups at the 4 R position while the rates would be increased if these substituents were at the 4 S position. We quantified the changes in transition free energy by comparing their rate constants. (4 R,2 S)-4-Fluoroproline and (4 S,2 S)-4-fluoroproline have the largest effect on the transition energy barrier for PPII → PPI conversion. Our results provide important insights into the role of stereoelectronic effects on the PPII → PPI transition state barrier, which has not been reported in past thermodynamic studies. [ABSTRACT FROM AUTHOR]

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with β-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277-1290, 2007 [ABSTRACT FROM AUTHOR]