Metabolic engineering of Caldicellulosiruptor bescii for hydrogen production.

Hydrogen is an alternative fuel for transportation vehicles because it is clean, sustainable, and highly flammable. However, the production of hydrogen from lignocellulosic biomass by microorganisms presents challenges. This microbial process involves multiple complex steps, including thermal, chemical, and mechanical treatment of biomass to remove hemicellulose and lignin, as well as enzymatic hydrolysis to solubilize the plant cell walls. These steps not only incur costs but also result in the production of toxic hydrolysates, which inhibit microbial growth. A hyper-thermophilic bacterium of Caldicellulosiruptor bescii can produce hydrogen by decomposing and fermenting plant biomass without the need for conventional pretreatment. It is considered as a consolidated bioprocessing (CBP) microorganism. This review summarizes the basic scientific knowledge and hydrogen-producing capacity of C. bescii. Its genetic system and metabolic engineering strategies to improve hydrogen production are also discussed. KEY POINTS: • Hydrogen is an alternative and eco-friendly fuel. • Caldicellulosiruptor bescii produces hydrogen with a high yield in nature. • Metabolic engineering can make C. bescii to improve hydrogen production.

Examining the role of knowledge and trust on vaccine confidence in North Dakota among university students, faculty, and staff.

BACKGROUND: Vaccination is one of the greatest tools for individuals to stay healthy. Individuals are, however, often exposed to misinformation via digital and social media, and thus, may miss the opportunity to develop scientific knowledge about vaccines and trust in relevant stakeholders. This has a damaging impact on vaccine confidence. Understanding vaccine confidence is particularly important in North Dakota, where vaccination rates are lower than national averages. OBJECTIVES: The objectives of this research are to examine the association between vaccine confidence and three potential sources of it, namely, trust, vaccine knowledge, and vaccine information sources and to investigate the relative strength of three vaccine confidence sources, while accounting for covariates. METHODS: Students (n = 517, 56.6%) and staff and faculty (n = 397, 43.4%) at the University of North Dakota (n = 914) completed an online survey. Logistic regressions estimated odds ratios (OR) and 95% confidence intervals (CI) for associations among trust in doctors, family/friends, government health agencies, charitable organizations, and religious organizations, vaccine knowledge, vaccine information sources as well as vaccine confidence, accounting for gender, race, marital status, age, religion, political ideology, education, and health status. RESULTS: The mean age of participants was 29.43 years (SD = 13.48). Most were females (71.6%) and white (91.5%). Great trust in doctors (OR = 3.29, p < 0.001, 95%CI 1.89, 5.73) government health agencies (OR = 2.95, p < 0.001, 95%CI 2.13, 4.08) and vaccine knowledge (OR = 1.28, p < 0.001, 95%CI 1.18, 1.38) had higher odds of vaccine confidence. Using Internet Government source as the primary source of vaccine information (OR = 1.73, p < 0.05, 95%CI 1.22, 2.44) showed higher odds of vaccine confidence before all independent variables were introduced, but it became non-significant after they were introduced. Trust in government health agencies showed strongest associations with vaccine confidence. CONCLUSION: Multiple stakeholders are necessary to ensure verified, accessible, and accurate information in order to advance vaccine confidence in rural, conservative areas.

Efficient production of natural sunscreens shinorine, porphyra-334, and mycosporine-2-glycine in Saccharomyces cerevisiae.

Mycosporine-like amino acids (MAAs) are promising natural sunscreens mainly produced in marine organisms. Until now, metabolic engineering efforts to produce MAAs in heterologous hosts have mainly focused on shinorine production, and the low production levels are still not suitable for industrial applications. In this study, we successfully developed Saccharomyces cerevisiae strains that can efficiently produce various disubstituted MAAs, including shinorine, porphyra-334, and mycosporine-2-glycine (M2G), which are formed by conjugating serine, threonine, and glycine to mycosporine-glycine (MG), respectively. We first generated an MG-producing strain by multiple integration of the biosynthetic genes from cyanobacteria and applying metabolic engineering strategies to increase sedoheptulose-7-phosphate pool, a substrate for MG production. Next, five mysD genes from cyanobacteria, which encode D-Ala-D-Ala ligase homologues that conjugate an amino acid to MG, were introduced into the MG-producing strain to determine the substrate preference of each MysD enzyme. MysDs from Lyngbya sp., Nostoclinckia, and Euhalothece sp. showed high specificity toward serine, threonine, and glycine, resulting in efficient production of shinorine, porphyra-334, and M2G, respectively. This is the first report on the production of porphyra-334 and M2G in S. cerevisiae. Furthermore, we identified that the substrate specificity of MysD was determined by the omega loop region of 43-45 amino acids predicted based on its structural homology to a D-Ala-D-Ala ligase from Thermus thermophilus involved in peptidoglycan biosynthesis. The substrate specificities of two MysD enzymes were interchangeable by swapping the omega loop region. Using the engineered strain expressing mysD from Lyngbya sp. or N. linckia, up to 1.53 g/L shinorine or 1.21 g/L porphyra-334 was produced by fed-batch fermentation in a 5-L bioreactor, the highest titer reported so far. These results suggest that S. cerevisiae is a promising host for industrial production of different types of MAAs, providing a sustainable and eco-friendly alternative for the development of natural sunscreens.

Purification of phenoloxidase from Haliotis discus hannai and its anti-inflammatory activity in vitro.

Haliotis discus hannai, a food with a high protein content, is widely consumed in Asian countries. It is known to have antioxidant, anticancer, and antibacterial effects. Since the biological significance of H. discus hannai hemolymph has not been widely studied, the objective of the present study was to purify phenoloxidase (PO) and investigate its immunological effects on human colonic epithelial cells. PO was purified through ammonium sulfate precipitation and one step column chromatography. The molecular weight of the protein was about 270 kDa. When PO was mixed with Gram-negative bacteria-derived lipopolysaccharide (LPS) at various ratios (10:1-1:10, w/w), the amount of residual LPS was reduced. PO at concentrations up to 200 µg/mL was not cytotoxic to HT-29 cells. The inflammatory response induced by LPS in HT-29 cells was regulated when the concentration of PO was increased. With increasing concentration of PO, production levels of pro-inflammatory cytokines, cytokines associated with hyperimmune responses such as IL4, IL-5, and INF-γ, and prostaglandin 2 (PGE2) were regulated. It was thought that simultaneous treatment with PO and LPS anti-inflammatory effects in HT-29 cells showed by regulating the ERK1/2-mediated NF-κB pathway. Results of this study suggest that H. discus hannai hemolymph is involved in the regulation of Gram-negative bacteria-related inflammatory immune responses in human colonic epithelial cells.

Investigation of the adsorption affinity of organic micropollutants on seaweed and its QSAR study.

Seaweed, one of the most abundant biomaterials, can be used as a biosorbent to remove organic micropollutants. In order to effectively use seaweed to remove a variety of micropollutants, it is vital to rapidly estimate the adsorption affinity according to the types of micropollutants. Thus, the isothermal adsorption affinities of 31 organic micropollutants in neutral or ionic form on seaweed were measured, and a predictive model using quantitative structure-adsorption relationship (QSAR) modeling was developed. As a result, it was found that the types of micropollutants had a significant effect on the adsorption of seaweed, as expected, and QSAR modeling with a predictability (R2) of 0.854 and a standard error (SE) of 0.27 log units using a training set could be developed. The model's predictability was internally and externally validated using leave-one-out cross validation and a test set. Its predictability for the external validation set was R2 = 0.864, SE = 0.171 log units. Using the developed model, we identified the most important driving forces of the adsorption at the molecular level: Coulomb interaction of the anion, molecular volume, and H-bond acceptor and donor, which significantly affect the basic momentum of molecules on the surface of seaweed. Moreover, in silico calculated descriptors were applied to the prediction, and the results revealed reasonable predictability (R2 of 0.944 and SE of 0.17 log units). Our approach provides an understanding of the adsorption process of seaweed for organic micropollutants and an efficient prediction method to estimate the adsorption affinities of seaweed and micropollutants in neutral and ionic forms.

Roles of Income and Acculturation in the Hispanic Paradox: Breastfeeding Among Hispanic Women.

OBJECTIVES: Despite Hispanics' high prevalence of breastfeeding compared to other racial/ethnic groups, contributing factors remain unclear. This study examines the complex relationship among Hispanic nativity, acculturation, income, and breastfeeding. METHODS: The Fragile Families Child Wellbeing Study baseline (1998-2000) and Year 1 data (1999-2001) were used, including 4,077 women (933 non-Hispanic white, 2,046 non-Hispanic Black, 352 US-born Mexicans [USM], 299 US-born other Hispanics [USH], 302 foreign-born Mexicans [FBM], and 145 foreign-born other Hispanics [FBH]). Logistic regression estimated odds ratios(OR) and 95% confidence intervals(CI) for associations between Hispanic nativity and breastfeeding initiation and 4-month and 6-month breastfeeding, accounting for acculturation (Spanish language use, cultural engagement, religiosity, and traditional gender role attitudes), demographics, income, and health factors. Models were run for the overall sample and stratified by low vs. high income (above median: $21,600). RESULTS: FBM(OR:2.35, 95%CI 1.33,4.15) and FBH(OR:2.28, 95%CI 1.23,4.24) had higher odds, while USM(OR:0.55, 95%CI 0.41,0.73) and USH(OR:0.50, 95%CI 0.37,0.67) had lower odds of breastfeeding initiation, compared to white women. USM had lower odds of 4-month(OR:0.53, 95%CI 0.36,0.80) and 6-month breastfeeding(OR:0.38, 95%CI 0.23,0.63), as did USH for 4-month(OR:0.64, 95%CI 0.42,0.99) and 6-month breastfeeding(OR:0.50, 95%CI 0.30,0.85). In stratified models, low-income (vs. high-income) FBH had higher odds of breastfeeding initiation(OR:3.73 95%CI 1.43,9.75) and 4-month(OR:3.01 95%CI 1.12,8.04) and 6-month breastfeeding(OR:3.08 95%CI 1.07,8.88), yet effects of acculturation across income strata are inconsistent. CONCLUSIONS FOR PRACTICE: The Hispanic paradox operates differentially due to nativity, income, and acculturation. Breastfeeding intervention and promotion may require tailored approaches to Hispanic subgroups.

Anti-inflammatory and anti-pathogenic potential of Lacticaseibacillus rhamnosus IDCC 3201 isolated from feces of breast-fed infants.

OBJECTIVE: We investigated the anti-inflammatory and anti-pathogenic activities of Lacticaseibacillus rhamnosus IDCC 3201 isolated from the feces of breast-fed infants. METHODS: Cell viability, nitric oxide (NO) production, and expression of inflammatory markers by L. rhamnosus IDCC 3201 were quantitatively analyzed in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The antibacterial and antifungal activities of L. rhamnosus IDCC 3201 against various pathogens were also investigated. RESULTS: Treatment of LPS-induced macrophages with cell-free supernatant of L. rhamnosus IDCC 3201 significantly decreased the expression levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) levels also significantly decreased in LPS-induced macrophages. Phenotypically, the treatment of L. rhamnosus IDCC 3201 reduced the production of nitric oxide (NO) in LPS-induced macrophages. Furthermore, L. rhamnosus IDCC 3201 was proven to have potent inhibitory activities against various pathogens responsible for inflammatory responses in the gastrointestinal tract (i.e., Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus, and Salmonella Typhimurium), respiratory system (i.e., Streptococcus pneumoniae), and vagina (i.e., Candida albicans). CONCLUSION: L. rhamnosus IDCC 3201 has anti-inflammatory activity in terms of decreased expression of cytokines, inflammation-inducible enzymes in LPS-induced macrophages, and anti-pathogenic activity.

COVID-19 vaccine hesitancy and short-term and long-term intentions among unvaccinated young adults: a mixed-method approach.

BACKGROUND: Only 63.8% of Americans who are 18-to-24-years-old have been fully vaccinated for COVID-19 as of June 1, 2022. The Grand Forks County, North Dakota is facing a similar challenge. As of June 2022, 47% of individuals in the 19-to-29-year-old age group are vaccinated. Focusing on unvaccinated individuals in their 20s, Study 1 aims to understand the ways in which receiving COVID-19 vaccines is construed using qualitative interviews; and Study 2 compares the predictors of short-term vaccination intention (i.e., next month) with those of long-term vaccination intention (i.e., three to 5 years) using an online survey. METHODS: For Study 1, we conducted five focus groups and four in-depth interviews via Zoom with a total of 26 unvaccinated individuals in their 20s living in the Grand Forks County. Constant comparison process was used to categorize data into themes and to recognize characteristics of the identified themes. The aim was to develop themes and associated characteristics. For Study 2, we conducted an online survey with a convenience sample of 526 unvaccinated individuals. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between attitudes, perceptions, and beliefs in misinformation and short-term and long-term vaccination intentions, accounting for demographics and socioeconomic status. RESULTS: In Study 1, two themes were identified: feelings of uncertainty sparked by profits and monetization and navigating the fear of the unknown. In Study 2, an increase in the confidence of COVID-19 vaccines showed significantly higher odds of short-term intention (OR = 2.658, 95%CI 1.770, 3.990) and long-term intention (OR = 1.568, 95% CI 1.105, 2.226). Believing in misinformation had significantly lower odds of short-term intention (OR = 0.712, 95%CI 0.513, 0.990), while more positive attitudes (OR = 1.439, 95% CI 1.024, 2.024), stronger preference in calculating the benefits of COVID-19 vaccines (OR = 2.108, 95% CI 1.541, 2.882), and greater perceived susceptibility (OR = 1.471, 95% CI 1.045, 2.070) to and severity of contracting COVID-19 (OR = 1.362, 95% CI 1.020, 1.820) were significantly associated with higher odds of long-term intention. CONCLUSIONS: Short-term and long-term intentions were predicted differently. Instilling strong confidence in COVID-19 vaccines should increase both short-term and long-term intentions.

Characterizing the research data management practices of NIH biomedical researchers indicates the need for better support at laboratory level.

BACKGROUND: The study investigated the research data management (RDM) practices of biomedical researchers at the National Institutes of Health (NIH) representing various biomedical disciplines. OBJECTIVES: This study aimed to analyse the state of biomedical researchers' RDM practices based on RDM practice levels (individual, laboratory, institution and external). The findings of the study are expected to provide directions to information professionals for effective RDM services. METHODS: Semi-structured interviews with 11 researchers were conducted. The interviews were analysed by levels of RDM practices. RESULTS: The findings revealed that biomedical researchers focus on storing and sharing data and that RDM is performed mainly at the individual level. There seems to be a lack of laboratory level RDM system that allows consistent RDM practices among researchers. External RDM practice is often challenged by not having one responsible for RDM. DISCUSSION: Findings suggested a need for an agreed RDM system and customized support, particularly at the laboratory level. Also, institutional support can help researchers prepare for long term data preservation. CONCLUSION: Our suggestions emphasize the importance of RDM training and support for long term data preservation, especially at the laboratory level.

In vitro amplification of pathogenic tau conserves disease-specific bioactive characteristics.

The microtubule-associated protein tau (tau) forms hyperphosphorylated aggregates in the brains of tauopathy patients that can be pathologically and biochemically defined as distinct tau strains. Recent studies show that these tau strains exhibit strain-specific biological activities, also referred to as pathogenicities, in the tau spreading models. Currently, the specific pathogenicity of human-derived tau strains cannot be fully recapitulated by synthetic tau preformed fibrils (pffs), which are generated from recombinant tau protein. Reproducing disease-relevant tau pathology in cell and animal models necessitates the use of human brain-derived tau seeds. However, the availability of human-derived tau is extremely limited. Generation of tau variants that can mimic the pathogenicity of human-derived tau seeds would significantly extend the scale of experimental design within the field of tauopathy research. Previous studies have demonstrated that in vitro seeding reactions can amplify the beta-sheet structure of tau protein from a minute quantity of human-derived tau. However, whether the strain-specific pathogenicities of the original, human-derived tau seeds are conserved in the amplified tau strains has yet to be experimentally validated. Here, we used biochemically enriched brain-derived tau seeds from Alzheimer's disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) patient brains with a modified seeding protocol to template the recruitment of recombinant 2N4R (T40) tau in vitro. We quantitatively interrogated efficacy of the amplification reactions and the pathogenic fidelity of the amplified material to the original tau seeds using recently developed sporadic tau spreading models. Our data suggest that different tau strains can be faithfully amplified in vitro from tau isolated from different tauopathy brains and that the amplified tau variants retain their strain-dependent pathogenic characteristics.

Practical considerations for a library's research data management services: the case of the National Institutes of Health Library.

OBJECTIVE: This study investigates research data management (RDM) services using a crosstab framework with the National Institutes of Health (NIH) Library as a case study to provide practical considerations for libraries seeking to improve their RDM services. METHODS: We conducted semistructured interviews with four librarians who provide data services at the NIH Library regarding library user characteristics, RDM services provided, RDM infrastructure, and collaboration experiences. Through the analysis of interview transcripts, we identified and analyzed the NIH Library's RDM services according to Online Computer Library Center (OCLC)'s three categories of RDM services and the six stages of the data lifecycle. RESULTS: The findings show that the two models' crosstab framework can provide an overview of an institution's current RDM services and identify service gaps. The NIH Library tends to take more responsibility in providing education and expertise services while relying more on information technology departments for curation services. The library provides significant support for data creation, analysis, and sharing stages to meet biomedical researchers' needs, suggesting areas for potential expansion of RDM services in the less supported stages of data description, storage, and preservation. Based on these findings, we recommend three key considerations for libraries: identify gaps in current services, identify services that can be supported via partnerships, and get regular feedback from users. CONCLUSION: These findings provide a deeper understanding of RDM support on the basis of RDM service categories and the data lifecycle and promote discussion of issues to be considered for future improvements in RDM services.

Dermatitis Herpetiformis: An Update on Diagnosis, Disease Monitoring, and Management.

Dermatitis herpetiformis (DH), Duhring disease, is caused by gluten sensitivity and affects 11.2 to 75.3 per 100,000 people in the United States and Europe with an incidence of 0.4 to 3.5 per 100,000 people per year. DH is characterized by a symmetrical blistering rash on the extensor surfaces with severe pruritus. The diagnosis continues to be made primarily by pathognomonic findings on histopathology, especially direct immunofluorescence (DIF). Recently, anti-epidermal transglutaminase (TG3) antibodies have shown to be a primary diagnostic serology, while anti-tissue transglutaminase (TG2) and other autoantibodies may be used to support the diagnosis and for disease monitoring. Newly diagnosed patients with DH should be screened and assessed for associated diseases and complications. A gluten-free diet (GFD) and dapsone are still mainstays of treatment, but other medications may be necessary for recalcitrant cases. Well-controlled DH patients, managed by a dermatologist, a gastroenterologist, and a dietician, have an excellent prognosis. Our review comprehensively details the current diagnostic methods, as well as methods used to monitor its disease course. We also describe both the traditional and novel management options reported in the literature.

Characterization of tau binding by gosuranemab.

Deposition of tau aggregates in the brain is a pathological hallmark of several neurodegenerative diseases, termed tauopathies, such as Alzheimer's disease (AD), corticobasal degeneration, and progressive supranuclear palsy (PSP). As transcellular spread of pathological tau aggregates has been implicated in disease progression, immunotherapy is being considered as a treatment for tauopathies. Here we report a detailed biochemical and biophysical characterization of the tau-binding properties of gosuranemab, a humanized monoclonal antibody directed against N-terminal tau that is currently being investigated as a treatment for AD. Binding experiments showed that gosuranemab exhibited high affinity for tau monomer, tau fibrils, and insoluble tau from different tauopathies. Epitope mapping studies conducted using X-ray crystallography and mutagenesis showed that gosuranemab bound to human tau residues 15-22. Immunodepletion of pathological human brain homogenates and transgenic mouse interstitial fluid (ISF) with gosuranemab resulted in reduced tau aggregation in tau biosensor cells. Preincubation of seed-competent AD-tau with gosuranemab significantly inhibited tau aggregation in mouse primary cortical neurons. Gosuranemab also significantly reduced unbound N-terminal tau in cerebrospinal fluid (CSF) from individuals with PSP and AD, and in ISF and CSF of treated transgenic mice. These results are consistent with the >90% target engagement observed in the CSF of some clinical trial dosing cohorts and support the evaluation of gosuranemab as a potential treatment for AD.

Adaptive laboratory evolution of Escherichia coli lacking cellular byproduct formation for enhanced acetate utilization through compensatory ATP consumption.

Acetate has attracted great attention as a carbon source to develop economically feasible bioprocesses for sustainable bioproducts. Acetate is a less-preferred carbon source and a well-known growth inhibitor of Escherichia coli. In this study, we carried out adaptive laboratory evolution of an E. coli strain lacking four genes (adhE, pta, ldhA, and frdA) involved in acetyl-CoA consumption, allowing the efficient utilization of acetate as its sole carbon and energy source. Four genomic mutations were found in the evolved strain through whole-genome sequencing, and two major mutations (in cspC and patZ) mainly contributed to efficient utilization of acetate and tolerance to acetate. Transcriptomic reprogramming was examined by analyzing the genome-wide transcriptome with different carbon sources. The evolved strain showed high levels of intracellular ATP by upregulation of genes involved in NADH and ATP biosynthesis, which facilitated the production of enhanced green fluorescent protein, mevalonate, and n-butanol using acetate alone. This new strain, given its high acetate tolerance and high ATP levels, has potential as a starting host for cell factories targeting the production of acetyl-CoA-derived products from acetate or of products requiring high ATP levels.

Solution-processable multi-color printing using UV nanoimprint lithography.

Recently, coloring based on nanostructure-light interaction has attracted much attention, because it has many advantages over pigment-based conventional coloring in terms of being non-toxic and highly durable in the environment, and providing high resolution. The asymmetric Fabry-Perot (FP) cavity absorber is the most manufacturable structure among coloring structures because it is simply produced and easily tunable. However, it cannot be applied practically because of the lack of a manufacturing technique that enables simultaneous fabrication of multi-color structures with different heights. Here, the fabrication of colored reflective characters based on various asymmetric FP absorbers with micrometer-scale pixel size are reported. Various cavities with different thicknesses are fabricated in a single step using UV imprint lithography and a simple deposition process. UV/visible spectroscopy is used to characterize the fabricated FP resonator. This absorber demonstrates high absorption, close to 90%, resulting in vivid colors with high resolution of 12700 DPI. It can be potentially used in reflective color displays field, functionalized color decorations, and security color patterns area. It is believed that this study would open up new possibilities for high density color printing in practical industry by introducing cost effective nanoimprint lithography technology.

Communicating radon risk via a smartphone app: a pilot intervention study.

BACKGROUND: Residential radon is a major preventable cause of lung cancer. However, prevention requires radon testing and it has proven very challenging to motivate individuals to test their homes for hazards like radon that are invisible and whose health effects occur after a long latency following exposure. Novel approaches to radon communication are urgently needed. METHODS: We created a novel radon-education app for smartphones and examined its effectiveness in increasing radon knowledge and radon testing. We studied radon knowledge and attitudes and behavior relevant to radon testing before and after app use. RESULTS: Ninety-seven undergraduates installed the app on their smartphones and used it for a month. App use resulted in higher scores in the domains of radon knowledge (p < .001); self-efficacy (p < .001), and response efficacy (p < .001). Twenty-three participants (24%) used the app to obtain a free radon test kit. Self-efficacy (p < .05) and response efficacy (p < .01) were positive predictors of ordering a test kit. The test process completion rate (the fraction of participants who ordered test kits, used them to test their houses and sent the kits to the lab) was 9%. CONCLUSIONS: A smartphone app is a promising venue for communicating radon risk and for stimulating radon testing. Future interventions designed to increase actual test kit use are required to maximize the benefit of the app.

Toward More Persuasive Diabetes Messages: Effects of Personal Value Orientation and Freedom Threat on Psychological Reactance and Behavioral Intention.

This study seeks to explore more effective ways of creating tailored health messages in order to help self-management of diabetes symptoms. Personal value orientation and freedom threat as antecedents of psychological reactance are investigated as potential elements reflecting to tailored health messages and leading to more or less persuasive effects on self-management. Using these elements, the current study examines whether invoking an individual's personal value orientation (i.e., two extreme value orientations: self-enhancement and self-transcendence) and threatening an individual's freedom in health news messages about diabetes influence psychological reactance and affect suggested health behaviors. Based on the literature regarding tailored message strategies, value theory, and psychological reactance theory, a 2 (personal value orientation: self-enhancement value vs. self-transcendence value) x 2 (value-invoking message: invoked vs. non-invoked) x 2 (freedom threat: high vs. low) between-subjects factorial design experiment with within-subjects topics on diabetes (2: nutrition and physical activity) was conducted for prediabetes/diabetes adults. The findings are (1) direct effects of personal value orientation on psychological reactance, (2) direct effects of freedom threat on psychological reactance, and (3) the interaction effects of value orientation and freedom threat on psychological reactance and behavioral intention. Implications are discussed.

Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-ß/STAT3 Pathway.

BACKGROUND/AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant tumors with poor prognosis. Conventional chemotherapies including gemcitabine have failed owing to weak response and side effects. Hence novel treatment regimens are urgently needed to improve the therapeutic efficacy. In this study, we aimed to assess the anticancer activity of melatonin and sorafenib as a novel therapy against PDAC. METHODS: We used various apoptosis assay and PDAC xenograft model to assess anticancer effect in vitro and in vivo. We applied phospho-receptor tyrosine kinase (RTK) array and phospho-tyrosine kinase array to explore the mechanism of the combined therapy. Western blotting, proximity ligation assay, and immunoprecipitation assay were also performed for validation. RESULTS: Melatonin synergized with sorafenib to suppress the growth of PDAC both in vitro and in vivo. The effect was due to increased apoptosis rate of PDAC cells that was accompanied by mitochondria dysfunction. The enhanced anticancer efficacy by the co-treatment could be explained by blockade of PDGFR-ß/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. CONCLUSIONS: Melatonin reinforces the anticancer activity of sorafenib by downregulation of PDGFR-ß/STAT3 signaling pathway and melatonin receptor (MT)-mediated STAT3. The combination of the two agents might be a potential therapeutic strategy for treating PDAC.

Multi-omic characterization of laboratory-evolved Saccharomyces cerevisiae HJ7-14 with high ability of algae-based ethanol production.

In this study, an evolved Saccharomyces cerevisiae HJ7-14 with high ability of algae-based ethanol production was characterized by multi-omic approaches. Genome sequencing of the HJ7-14 revealed a point mutation in the GAL83 gene (G703A) involved in the catabolite repression as well as the galactose metabolism. Cultural and transcriptional analyses of a S. cerevisiae mutant with chromosomal GAL83(G703A) indicated that the catabolite repression onto the galactose metabolism was considerably relieved in all cell growth stages. Untargeted metabolomic approach revealed that metabolic phenotypes between the control D452-2 and HJ7-14 strains were clearly discriminated in time-dependent manner. Especially in early growth stage at 6 h, the HJ7-14 showed dramatic and coordinated alteration in central carbon and amino acid metabolisms. Through metabolomic re-organization, fold changes in fatty acid metabolism and metabolites related to stress response system were also found upon glucose depletion and active galactose utilization. Multi-omic characterization using genome sequencing, transcription, and metabolome profiling clearly unveiled that the GAL83 gene mutation partially relieved glucose-dependent catabolite repression and allowed the evolved HJ7-14 to efficiently convert algal sugars to ethanol. Our finding could be applicable for engineering of S. cerevisiae able to covert red algal biomass to other biofuels and biochemicals.

Effect of PelB signal sequences on Pfe1 expression and ω-hydroxyundec-9-enoic acid biotransformation in recombinant Escherichia coli.

ω-Hydroxyundec-9-enoic acid (ω-HUA) was reported as a valuable medium-chain fatty acid with industrial potentials. For bioconversion of ricinoleic acid to ω-HUA, in this study, an alcohol dehydrogenase (Adh) from Micrococcus luteus, a Baeyer-Villiger monooxygenase (BVMO) from Pseudomonas putida KT2440 and an esterase (Pfe1) from Pseudomonas fluorescens SIK WI were overexpressed in Escherichia coli BL21(DE3). In order to enhance accessibility of Pfe1 to the (E)-11-(heptanoyloxy) undec-9-enoic acid (11-HOUA) substrate, a truncated PelB signal sequence without the recognition site of signal peptidase (tPelB) was attached to the N-terminus of Pfe1, resulting in the construction of E. coli AB-tPE strain expressing Adh, BVMO and the tPelB-Pfe1 fusion protein. A batch-type biotransformation of ricinoleic acid by E. coli AB-tPE resulted in 1.8- and 2.2-fold increases in ω-HUA conversion yield and productivity, respectively, relative to those for the control strain without the PelB sequence (AB-E). By fed-batch-type biotransformation with glycerol feeding, the AB-tPE strain produced 23.7 mM (equivalent to 4.7 g/L) of ω-HUA with 60.8%(mol/mol) of conversion yield and 1.2 mM/h of productivity, which were 13.2, 2.9, and 2.6 times higher than those in a batch-type biotransformation using the AB-E strain. In conclusion, combination of the truncated PelB-Pfe1 fusion and fed-batch process with glycerol feeding provided the highest efficiency of ω-HUA biotransformation, of which strategies might be applicable for biotransformation of hydrophobic substances.