Efficient Promoter Research Articles

Copolymer with Tunable Cation Content as an Efficient Promoter in Enzymatic Saccharification of Lignocellulose

Copolymer with Tunable Cation Content as an Efficient Promoter in Enzymatic Saccharification of Lignocellulose

Deep flanking sequence engineering for efficient promoter design using DeepSEED

Designing promoters with desirable properties is essential in synthetic biology. Human experts are skilled at identifying strong explicit patterns in small samples, while deep learning models excel at detecting implicit weak patterns in large datasets. Biologists have described the sequence patterns of promoters via transcription factor binding sites (TFBSs). However, the flanking sequences of cis-regulatory elements, have long been overlooked and often arbitrarily decided in promoter design. To address this limitation, we introduce DeepSEED, an AI-aided framework that efficiently designs synthetic promoters by combining expert knowledge with deep learning techniques. DeepSEED has demonstrated success in improving the properties of Escherichia coli constitutive, IPTG-inducible, and mammalian cell doxycycline (Dox)-inducible promoters. Furthermore, our results show that DeepSEED captures the implicit features in flanking sequences, such as k-mer frequencies and DNA shape features, which are crucial for determining promoter properties.

Penggunaan Media Pemasaran Pada Mahasiswa Perguruan Tinggi Terbuka dan Jarak Jauh Di Indonesia

Research aim: This study aimed to determine the preferences of marketing media used by UT students according to demographic characteristics.
 Design/Methode/Approach: This study uses a quantitative approach with survey methods through convenience sampling with non-probability techniques. This study distributed the questionnaire link and obtained respondents from as many as 6.155 UT students in Indonesia and abroad. The results of this study are the marketing media used by UT students based on demographic characteristics, namely age, gender, region of origin, and occupation using cross-tabulation analysis.
 Research Finding: The formulation of the research problem is how the demographic characteristics and cross-tabulation of the use of marketing media used by UT students. 
 Theoretical contribution/Originality: In addition, the various choices of communication media encourage audiences to use communication media to meet their needs. Before determining this strategy, UT needs to know the marketing media used by students when they search for and obtain information about the open and distance higher education system.
 Practitionel/Policy implication: The implication of this research is the first step in making marketing and promotion strategies and knowing the effective and efficient use of marketing media.
 Research limitation:
 Students at Universitas Terbuka have different characteristics from those at other institutions, which can be seen in demography, geography, psychography, and behavior. To increase the Gross Enrollment Rate for Higher Education, UT has a target of one million students in 2024, so a planned, effective, and efficient marketing and promotion strategy is needed, as well as on target.

An outlook to sophisticated technologies and novel developments for metabolic regulation in the Saccharomyces cerevisiae expression system.

Saccharomyces cerevisiae is one of the most extensively used biosynthetic systems for the production of diverse bioproducts, especially biotherapeutics and recombinant proteins. Because the expression and insertion of foreign genes are always impaired by the endogenous factors of Saccharomyces cerevisiae and nonproductive procedures, various technologies have been developed to enhance the strength and efficiency of transcription and facilitate gene editing procedures. Thus, the limitations that block heterologous protein secretion have been overcome. Highly efficient promoters responsible for the initiation of transcription and the accurate regulation of expression have been developed that can be precisely regulated with synthetic promoters and double promoter expression systems. Appropriate codon optimization and harmonization for adaption to the genomic codon abundance of S. cerevisiae are expected to further improve the transcription and translation efficiency. Efficient and accurate translocation can be achieved by fusing a specifically designed signal peptide to an upstream foreign gene to facilitate the secretion of newly synthesized proteins. In addition to the widely applied promoter engineering technology and the clear mechanism of the endoplasmic reticulum secretory pathway, the innovative genome editing technique CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated system) and its derivative tools allow for more precise and efficient gene disruption, site-directed mutation, and foreign gene insertion. This review focuses on sophisticated engineering techniques and emerging genetic technologies developed for the accurate metabolic regulation of the S. cerevisiae expression system.

Cyanobacterial elicitors as efficient plant growth promoters affect the biomass and metabolic profiles of four species of Mentha L.: A comparative study

Medicinal and aromatic plants contain compounds with industrial and therapeutic applications; among which genus Mentha L. has special economic importance. The present investigation aimed to evaluate the ability of cyanobacterial strains as bio-elicitors on biomass production, as well as the quality and quantity of essential oils of four species of Mentha (M. spicata L., M. piperita L., M. aquatica L., and M. pulegium L.). Following the seedling growth test, two cyanobacterial strains, Wollea vaginicola ISB89 and Nostoc spongiaeforme var. tenue ISB91, were selected as potential bio-elicitors. Then, the growth of plants under 1% cyanobacterial suspensions was assessed by measuring growth factors including length and weight of plants, and leaf area after 90 days of planting. Moreover, the amount of essential oils of plants and their constituents were evaluated. According to the results, both cyanobacterial elicitors significantly increased plant biomasses and essential oils yield. There was a direct relationship between cyanobacterial auxins and biomass and essential oil of Mentha spp.; in this way, Wollea with a higher level of auxins and cations provides essential elements for plants. Therefore, plants treated with Wollea exhibited more growth and essential oil promoting features compared to Nostoc treatments. The most important terpenoids in essential oils of investigated species belong to oxygenated monoterpenes with 79–91% contents; including Piperitenone, Menthol, and Menthone. In M. piperita, the amount of Menthone, as one of the principal constituents of essential oil, increased under cyanobacterial elicitors (115–137%). For M. spicata the enhancement of Piperitenone (46–96%), and for M. pulegium, the increase of neo-Menthol (17–115%) was remarkable. Based on the results, two cyanobacteria strains are considered as a rich source of natural compounds and phytohormones which can be used to increase the yield and essential oil production of studied economically important plant species.

A safe path towards carbon neutrality by 2050: Assessing the impact of oil and gas efficiency using advanced quantile-based approaches

In the present era, we are confronted with a dilemma: how can economic prosperity be attained while addressing the ecological challenges associated with energy resource usage. Sectors such as aviation, refining industries, and transportation face increasing pressure to reduce their reliance on fossil fuels. To achieve this, the promotion of energy efficiency and renewable energy solutions, which have often been overlooked in environmental studies, have become crucial. In this context, the current study aims to assess the environmental impacts of gas efficiency and oil efficiency in Japan. The data used for this evaluation spans from 1990/Q1 to 2020/Q4. Moreover, the roles of environmental innovation and renewable energy are considered in the study. To investigate these interrelationships, the study relies on various quantile-based approaches, including quantile-on-quantile regression, cross-correlation analysis, recursive cross-quantilogram correlation, quantile cointegration, and quantile causality. The findings obtained from the quantile regression and quantile-on-quantile regression approaches indicate that both gas and oil efficiency promote the reduction of CO2. Similarly, across all quantiles, environmental technological innovation and renewable energy positively promote ecological quality by mitigating CO2. Furthermore, the quantile causality analysis reveals a significant causality in both mean and variance from gas efficiency, oil efficiency and environmental technological innovation to CO2, although the strength of the causality is relatively weak in the mean. Additionally, the results from the time-varying recursive cross-quantilogram correlation provide evidence of significant correlations between CO2 and its determinants in the 0.1, 0.5, and 0.90 quantiles throughout the study period. These findings serve as the basis for the formulation of effective policies to mitigate CO2 emissions.

Water-assisted hydrogen spillover in Pt nanoparticle-based metal–organic framework composites

Hydrogen spillover is the migration of activated hydrogen atoms from a metal particle onto the surface of catalyst support, which has made significant progress in heterogeneous catalysis. The phenomenon has been well researched on oxide supports, yet its occurrence, detection method and mechanism on non-oxide supports such as metal–organic frameworks (MOFs) remain controversial. Herein, we develop a facile strategy for efficiency enhancement of hydrogen spillover on various MOFs with the aid of water molecules. By encapsulating platinum (Pt) nanoparticles in MOF-801 for activating hydrogen and hydrogenation of C=C in the MOF ligand as activated hydrogen detector, a research platform is built with Pt@MOF-801 to measure the hydrogenation region for quantifying the efficiency and spatial extent of hydrogen spillover. A water-assisted hydrogen spillover path is found with lower migration energy barrier than the traditional spillover path via ligand. The synergy of the two paths explains a significant boost of hydrogen spillover in MOF-801 from imperceptible existence to spanning at least 100-nm-diameter region. Moreover, such strategy shows universality in different MOF and covalent organic framework materials for efficiency promotion of hydrogen spillover and improvement of catalytic activity and antitoxicity, opening up new horizons for catalyst design in porous crystalline materials.

Catalytic efficiency and thermal stability promotion of the cassava linamarase with multiple mutations for better cyanogenic glycoside degradation

In our previous study, we found that cassava cyanogenic glycosides had an acute health risk. Therefore, to solve this problem, the improvement of specific degradation of cyanogenic glycosides of cassava linamarase during processing is the key. In this study, the catalytic activity and thermal stability of enzymes were screened before investigating the degradation efficiency of cyanogenic glycosides with a cassava linamarase mutant K263P-T53F-S366R-V335C-F339C (CASmut) -controlled technique. The CASmut was obtained with the optimum temperature of 45 °C, which was improved by 10 °C. The specific activity of CASmut was 85.1 ± 4.6 U/mg, which was 2.02 times higher than that of the wild type. Molecular dynamics simulation analysis and flexible docking showed there were more hydrogen bonding interactions at the pocket, and the aliphatic glycoside of the linamarin was partially surrounded by hydrophobic residues. The optimum conditions of degradation reactions was screened with CASmut addition of 47 mg/L at 45 °C, pH 6.0. The CASmut combined with ultrasonication improved the degradation from 478.2 ± 10.4 mg/kg to 86.7 ± 7.4 mg/kg. Those results indicating the great potential of CASmut in applying in the cassava food or cyanogenic food. However, challenges in terms of the catalytic mechanism research is worthy of being noticed in further studies.

Interface Modification via Rare Earth Material to Assist Hole Migration for Efficiency and Stability Promotion of Perovskite Solar Cells

Interface defect is a limiting factor of the charge dynamics and stability of perovskite solar cells (PSCs). Herein, a rare earth metal oxide cerium oxide is introduced into the interface between perovskite and spiro‐OMeTAD [2,2,7,7‐tetrakis (N,N ‐di‐p‐methoxyphenyl‐amine) 9,9‐spirobifluorene] to passivate interfacial defects. Due to the nearest‐neighbor interaction of CeO2 with spiro‐OMeTAD, it can accelerate the oxidization process of spiro‐OMeTAD to form a donor–acceptor complex at this interface, which can overcome the interface barrier for the high hole collecting ability. The bonding formation between lead and oxygen makes this heterojunction show metal conduction behavior at this interface. The insertion of CeO2 between perovskite and spiro‐OMeTAD, can improve hole transferring to balance the extraction of electron and hole by their respective electrodes, for the decreased device hysteresis with the higher efficiency and improved stability. The results show that the CeO2‐based PSC device achieve a power conversion efficiency (PCE) of over 24%, retaining more than 87% of the initial PCE after 2570 h of storage at 20 ≈ 30% humidity.

Genome-Wide and 16S rRNA Sequencing-Based Analysis on the Health Effects of Lacticaseibacillus paracasei XLK401 on Chicks.

Lacticaseibacillus paracasei, serves as a growth promoter used in the poultry industry, contributeing to broiler development. However, practical studies are needed to determine the probiotic potential and growth-promoting effects of specific L. paracasei strains. This study aims to determine whether L. paracasei XLK401 influences broiler chicken growth and the mechanisms involved. Notably, we identified several bile salt and acid tolerance-related genes (Asp23, atpD, atpA, atpH, and atpF) in L. paracasei XLK401. This bacterium demonstrates robust probiotic properties under acidic conditions (pH 2.0) and 0.3% bile salt conditions. It also contains a variety of antioxidant-related genes (trxA, trxB, and tpx), carbohydrate-related genes, gene-encoding glycosidases (e.g., GH and GT), and three clusters of genes associated with antimicrobial compounds. Supplementation with L. paracasei XLK401 significantly increased the body weight of the chicks. In addition, it significantly increased hepatic antioxidant enzyme activities (GSH-Px, SOD, and T-AOC) while significantly decreasing the levels of oxidative damage factors and inflammatory factors (MDA and IL-6), resulting in improved chick health. Improvements in body weight and health status were associated with significant increases in α-amylase activity and the remodeling of the host gut microbiota by L. paracasei XLK401. Among them, actinobacteria abundance in chicken intestines after feeding them L. paracasei XLK401 was significantly decreased, Bifidobacterium sp. abundance was also significantly decreased, and Subdoligranulum sp. abundance was significantly increased. This suggests that L. paracasei XLK401 can regulate the abundance of certain bacteria without changing the overall microbial structure. In addition, in the correlation analysis, Subdoligranulums sp. were positively correlated with SOD and negatively correlated with IL-1β and MDA. Overall, our study demonstrates that L. paracasei XLK401 effectively promotes healthy chick growth. This is made possible by the modulation of gut microbe abundance and the underlying probiotic effect of L. paracasei XLK401. Based on these findings, we postulate L. paracasei XLK401 as a potential efficient growth promoter in broiler farming.

Households’ health insurance status and COVID-19 vaccination in Nigeria: A recursive bivariate probit and decomposition estimation

Health insurance remains a viable option for the promotion of healthcare service utilization and efficiency. Very few studies have analyzed the linkages between health insurance uptake and COVID-19 vaccination decisions. This paper contributes to existing literature by recursively analyzing the effect of health insurance uptake on COVID-19 vaccination status in Nigeria. The data were the second wave of the National Longitudinal Phone Survey (NLPS), comprising 2750 respondents. The data were analyzed with the recently developed Recursive Bivariate Probit and Decomposition Estimation approach. The results showed that 31.50% and 7.78% were vaccinated and health insured, respectively. Health insurance was positively and significantly influenced (p<0.05) by being from the North West zone, urban residence, needing non-COVID maternal health, and adults or households’ heads as the major vaccination decision makers. In addition, being vaccinated or having a vaccinated households’ member was negatively and significantly influenced by three zonal variables (North East, North West, and South East) and urban residence, but positively influenced by age, needing COVID-19 related health services, concurring with making the vaccines mandatory and adults being the major vaccination decision makers. Health insurance recursively influenced being vaccinated or having a vaccinated households’ member with significant positive treatment effects (p<0.05). It was concluded that efforts to promote health insurance will facilitate acceptability of COVID-19 vaccines. In addition, uptake of health insurance and COVID-19 vaccination can be enhanced with proper focus on some peculiar zonal and sectoral factors through initiatives that target adult households’ members.

Growth Transformation of B Cells by Epstein-Barr Virus Requires IMPDH2 Induction and Nucleolar Hypertrophy.

The in vitro growth transformation of primary B cells by Epstein-Barr virus (EBV) is the initial step in the development of posttransplant lymphoproliferative disorder (PTLD). We performed electron microscopic analysis and immunostaining of primary B cells infected with wild-type EBV. Interestingly, the nucleolar size was increased by two days after infection. A recent study found that nucleolar hypertrophy, which is caused by the induction of the IMPDH2 gene, is required for the efficient promotion of growth in cancers. In the present study, RNA-seq revealed that the IMPDH2 gene was significantly induced by EBV and that its level peaked at day 2. Even without EBV infection, the activation of primary B cells by the CD40 ligand and interleukin-4 increased IMPDH2 expression and nucleolar hypertrophy. Using EBNA2 or LMP1 knockout viruses, we found that EBNA2 and MYC, but not LMP1, induced the IMPDH2 gene during primary infections. IMPDH2 inhibition by mycophenolic acid (MPA) blocked the growth transformation of primary B cells by EBV, leading to smaller nucleoli, nuclei, and cells. Mycophenolate mofetil (MMF), which is a prodrug of MPA that is approved for use as an immunosuppressant, was tested in a mouse xenograft model. Oral MMF significantly improved the survival of mice and reduced splenomegaly. Taken together, these results indicate that EBV induces IMPDH2 expression through EBNA2-dependent and MYC-dependent mechanisms, leading to the hypertrophy of the nucleoli, nuclei, and cells as well as efficient cell proliferation. Our results provide basic evidence that IMPDH2 induction and nucleolar enlargement are crucial for B cell transformation by EBV. In addition, the use of MMF suppresses PTLD. IMPORTANCE EBV infections cause nucleolar enlargement via the induction of IMPDH2, which are essential for B cell growth transformation by EBV. Although the significance of IMPDH2 induction and nuclear hypertrophy in the tumorigenesis of glioblastoma has been reported, EBV infection brings about the change quickly by using its transcriptional cofactor, EBNA2, and MYC. Moreover, we present here, for the novel, basic evidence that an IMPDH2 inhibitor, namely, MPA or MMF, can be used for EBV-positive posttransplant lymphoproliferative disorder (PTLD).

Design and Optimization of a Triple‐Cation Perovskite Solar Cell for Efficiency Promotion using Numerical Simulations

AbstractFormamidinium lead iodide (FAPbI3) perovskite has recently gained immense interests as a possible absorber of hybrid halide perovskite (HHP) based solar cells and are extensively investigated both on experimental and theoretical fronts. However, it is unstable against the moisture, making this material domain inappropriate for long run. The compositional engineering i. e., doping in the absorber layer (FAPbI3) of HHP solar cells appears to be very significant for enhancing the stability and overall photovoltaic performance of perovskite solar cells (PSCs). We deal with the numerical simulation and optimization of (GA/FA/Cs)PbI3 based PSC. A diverse set of ETLs and HTLs have been explored to find the optimal combination from 35 device structures. Among them, La‐doped BaSnO3 (LBSO) and CBTS are found to be most appropriate electron/hole transport layers (ETL/HTL) combination for (GA/FA/Cs)PbI3 absorber layer, respectively. In addition, the impact of various parameters such as thickness, defect density, working temperature and back contact work function on the overall device performance have been investigated. After comprehensive optimizations, the proposed PSC demonstrated the superior photovoltaic performance with power conversion efficiency of 24.36 % and fill factor (FF) of 80.17 %. The present simulation work can serve as a benchmark for the fabrication of proposed PSCs.

Explaining the Evidence-Based Policy in Educating and Promoting Students’ Health: A Narrative Review

Background. Evidence-based policymaking is a type of policy based on valid, timely, and appropriate evidence. This study aimed to explain the evidence-based policy in education and health promotion to students. Methods. The method of the present research was a narrative review. The statistical population included 114 Persian and English articles published between 2010 and 2022 which were indexed in ERIC, ScienceDirect, Sage, SID, Irandoc, Magiran, and Medline databases. The search was done using evidence-based policy, health education evidence, health promotion, health education policy, educational policy and health key words. The search was conducted using the SPIDER framework due to the speciality of the subject being studied. Using Downs and Black checklist for quality assessment, the final research sample included 20 references selected through screening. Thematic analysis was used to codify the texts using the Sternberg method. Results. We extracted 59 concepts and six themes based on coding of the findings. Evidence-based policymaking in educating and promoting student health can be categorized into six themes: the necessity for evidence-based policymaking, the characteristics of evidence-based policymaking, the prerequisites of evidence-based policymaking, the impetus for evidence-based policymaking, the barriers to evidence-based policymaking, and the consequences of evidence-based policymaking. Conclusion. Application of evidence-based policymaking in educating and promoting students’ health, based on global trends, technologies and strategies can lead to efficient education and health promotion policies. This study provided useful, practical guidelines such as filling the theoretical gap, ensuring clarity and motivation, influencing political decisions, and building trust among researchers, the scientific community, and other policy stakeholders to use evidence-based policymaking effectively in students’ health promotion.

Improved Yolov5 and Image Morphology Processing Based on UAV Platform for Dike Health Inspection

Dike health inspection is crucial in river channel regulating. The conventional manual collapse inspection is inefficient and costly so that the unmanned aerial vehicle (UAV)-based inspection has been widely applied. However, the existing vision-based defect detection methods face challenges, such as lack of defect sample data and closed specified data sets. To address them, a defect detection method based on improved YOLOv5 recognition combined with image morphology processing is proposed for dike health inspection with zero defect samples. Specifically, the coordinate attention mechanism is introduced in YOLOv5 model to improve recognition capability for dikes. Also, a rotating bounding box target detection is designed for arbitrary orientation of dikes under UAV view, due to ineffective horizontal bounding box detection. Furthermore, for suspected defect locating efficiency promotion, the specific recognized area of the dike is isolated in the image morphology process. The results show that the proposed method outperforms the traditional Yolov5 algorithm on recall rate, F1, and mAP.

Energy-efficient storage of methane and carbon dioxide capture in the form of clathrate hydrates using a novel non-foaming surfactant: An experimental and computational investigation

In recent decades, both rising energy demand and increasing population have led to a significant increase in atmospheric carbon dioxide (CO2). Natural gas, the primary source of energy, and carbon capture and storage must therefore be managed efficiently. Gas hydrates have considerable potential for CO2 capture and energy storage since they can selectively absorb gas molecules and provide a large storage capacity. However, the slow kinetics of the hydrate formation constrained their commercial usage. Although surfactants have been investigated as effective additives to accelerate the rate of gas hydrate formation, intense foaming during the gas hydrate dissociation adversely affects the gas recovery factor. In this study, a novel anionic surfactant based on aconitic acid (ASA) was developed to improve the kinetics of methane and CO2 hydrates formation. The methane hydrate experiments indicated that, even at low concentrations, ASA significantly enhanced the kinetics of methane hydrate formation. The maximum water-to-hydrate conversion of 97 % and the highest storage capacity of 174 v/v were achieved using 50 ppm of ASA. Additionally, 99.1 v/v of storage capacity was achieved for CO2 hydrate in the solution containing 1000 ppm of ASA. Moreover, molecular dynamics simulation revealed that self-assembly behavior of ASA molecules increased the solubility of the gas molecules in the solution, provided more gas molecules for growing hydrate interface, and increased gas hydrate growth. Furthermore, no foam formation occurred in the ASA solution, even at high concentrations. These results show that ASA can be applied as an efficient and foamless gas hydrate promoter for methane storage and CO2 capture applications.

Green finance development and resource efficiency: A financial structure perspective

Resource utilisation efficiency promotion is a crucial focus of green economic recovery, and the development of green finance could ease the liquidity constraints of this process. This paper examines the nexus between green finance and resource utilisation efficiency from a financial structure perspective using panel data from 2008 to 2021. Our findings indicate that the size of green finance could improve resource utilisation efficiency through green technology developments. Regarding green financial structure, direct finance plays a greater role than indirect finance. Additionally, the implementation of green finance policies can significantly facilitate the enhancement of resource utilisation efficiency. For policymakers, accelerating the development of green finance through fiscal measures should be prioritized. Meanwhile, optimising green financial structures through building a market-based green financial system is necessary. Finally, ensuring that green funds flow into the development of green technology should also be considered.

Hydrophobic eutectic and hydrophilic melts of gabapentin-lactam & citric acid mixtures; green promoters for selective synthesis of xanthenes/ benzo[b]pyrans and dihydropyrroles

Gabapentin-lactam and citric acid form a glassy hydrophobic deep eutectic mixture. Certain non-eutectic molar ratios of the two components are also low-melting mixtures and slight differences can be discerned in their differential calorimetric curves. Yet, they impose different selective promotions on the reaction of malononitrile, arylaldehyde, and dimedone. Interestingly, the reaction mixture selectively gives tetrahydrobenzo[b]pyran-2H-ones or 1,8-dioxo-octahydroxanthenes depending on being carried out in the melted 2/1 or 1/2 molar mixtures of gabapentin-lactam/citric acid. An excellent promoting activity was also observed for the melt of gabapentin-lactam and citric acid mixture in 1/1 molar ratio. This melt proved to be an efficient promoter for synthesis of 4‑hydroxy-2,5-dihydropyrrol-5-ones from the domino reaction of an arylaldehyde, an aniline derivative, water, and an acetylenic ester. No additional organic solvents are required to perform the reactions and the bio-compatible melts can be reused several times after easy separation from the products. The eutectic and the non-eutectic melts preserve their viscous liquid state even upon a long-term storage at ambient temperature.

Exploring parents' views of the use of narratives to promote childhood vaccination online.

Negative information about vaccines that spreads online may contribute to parents' vaccine hesitancy or refusal. Studies have shown that false claims about vaccines that use emotive personal narratives are more likely to be shared and engaged with on social media than factual evidence-based public health messages. The aim of this study was to explore parents' views regarding the use of positive narratives to promote childhood vaccination. We identified three ∼4-minute video narratives from social media that counter frequent parental concerns about childhood vaccination: parents and informed decision-making (online misinformation about vaccines); a paediatrician's clinical experience with vaccine-preventable diseases (prevention of still existing diseases); and a mother's experience with vaccine-preventable disease (risks of the disease). Focus group discussions were held with parents of children aged 0 to 5 years to assess their views on these three narratives and their general opinion on the use of narratives as a vaccine promotion intervention. Four focus groups discussions were virtually held with 15 parents in December 2021. In general, parents trusted both health care provider's and parent's narratives, but participants identified more with stories having a parent as the main character. Both narratives featuring personal stories with vaccine-preventable diseases were preferred by parents, while the story about informed decision-making was perceived as less influential. Parents expressed the need for reliable and nuanced information about vaccines and diseases and felt that a short video format featuring a story was an efficient vaccine promotion intervention. However, many mentioned that they generally are not watching such videos while navigating the Web. While vaccine-critical stories are widely shared online, evidence on how best public health could counter these messages remains scarce. The use of narratives to promote vaccination was well-perceived by parents. Future studies are needed to assess reach and impact of such an intervention.

Modulation of taxane binding to tubulin curved and straight conformations by systematic 3′N modification provides for improved microtubule binding, persistent cytotoxicity and in vivo potency

The taxane class of microtubule stabilizers are some of the most effective and widely used chemotherapeutics. The anticancer activity of taxanes arises from their ability to induce tubulin assembly by selectively recognizing the curved (c-) conformation in unassembled tubulin as compared to the straight (s-) conformation in assembled tubulin. We first designed and synthesized a series of 3′N-modified taxanes bearing covalent groups. Instead of discovering covalent taxanes, we found a series of non-covalent taxanes 2, in which the 3′N side chain was found to be essential for cytotoxicity due to its role in locking tubulin in the s-conformation. A representative compound bearing an acrylamide moiety (2h) exhibited increased binding affinity to the unassembled tubulin c-conformation and less cytotoxicity than paclitaxel. Further exploration of chemical space around 2h afforded a new series 3, in which derivatives such as 3l bind more tightly to both the s- and c-conformations of tubulin compared to paclitaxel, leading to more efficient promotion of tubulin polymerization and a greater persistence of in vitro efficacy against breast cancer cells after drug washout. Although 3l also had improved in vivo potency as compared to paclitaxel, it was also associated with increased systemic toxicity that required localized, intratumoral injection to observe potent and prolonged antitumor efficacy.