bluuebunny/crossref_metadata_2025_split huggingface dataset:
The synergetic effect from the combination of different adsorption resins in batch and semi‐continuous cultivations of S. Cerevisiae cell factories to produce acetylated Taxanes precursors of the anticancer drug Taxol
Authors: Santoyo‐Garcia Jorge H. , Walls Laura E. , Valdivia‐Cabrera Marissa , Malcı Koray , Jonguitud‐Borrego Nestor , Halliday Karen J. , Rios‐Solis Leonardo 
Published: July 2023

AbstractIn situ product recovery is an efficient way to intensify bioprocesses as it can perform adsorption of the desired natural products in the cultivation. However, it is common to use only one adsorbent (liquid or solid) to perform the product recovery. For this study, the use of an in situ product recovery method with three combined commercial resins (HP‐20, XAD7HP, and HP‐2MG) with different chemical properties was performed. A new yeast strain of Saccharomyces cerevisiae was engineered using CRISPR Cas9 (strain EJ2) to deliver heterologous expression of oxygenated acetylated taxanes that are precursors of the anticancer drug Taxol ® (paclitaxel). Microscale cultivations using a definitive screening design (DSD) were set to get the best resin combinations and concentrations to retrieve high taxane titers. Once the best resin treatment was selected by the DSD, semi‐continuous cultivation in high throughput microscale was performed to increase the total taxanes yield up to 783 ± 33 mg/L. The best T5α‐yl Acetate yield obtained was up to 95 ± 4 mg/L, the highest titer of this compound ever reported by a heterologous expression. It was also observed that by using a combination of the resins in the cultivation, 8 additional uncharacterized taxanes were found in the gas chromatograms compared to the dodecane overlay method. Lastly, the cell‐waste reactive oxygen species concentrations from the yeast were 1.5‐fold lower in the resin's treatment compared to the control with no adsorbent aid. The possible future implications of this method could be critical for bioprocess intensification, allowing the transition to a semi‐continuous flow bioprocess. Further, this new methodology broadens the use of different organisms for natural product synthesis/discovery benefiting from clear bioprocess intensification advantages.
Regio‐ and stereo‐selective 1β‐hydroxylation of lithocholic acid by cytochrome P450 BM3 mutants
Authors: Li Haiyan , Dai Wei , Qin Shuaishuai , Li Shan , Yu Yundong , Zhang Lei 
Published: July 2023

AbstractRegio‐ and stereo‐selective hydroxylation of bile acids is a valuable reaction but often lacks suitable catalysts. In the research, semi‐rational design in protein engineering techniques had been applied on cytochrome P450 monooxygenase CYP102A1 (P450 BM3) from Bacillus megaterium, and a mutation library had been set up for the 1β‐hydroxylation of lithocholic acid (LCA) to produce 1β‐OH‐LCA. After four rounds of mutagenesis, a key residue at W72 was identified to regulate the regio‐ and stereo‐selectivity at C1 of LCA. A quadruple variant (G87A/W72T/A74L/L181M) was identified to reach 99.4% selectivity of 1β‐hydroxylation and substrate conversion of 68.1% resulting in a 21.5‐fold higher level of 1β‐OH‐LCA production than the template LG‐23. Molecular docking indicated that introducing hydrogen bonds at W72 was responsible for enhancing selectivity and catalytic activity, which gave some insights into the structure‐based understanding of Csp3‐H activation by the developed P450 BM3 mutants.
Dynamic metagenome‐scale metabolic modeling of a yogurt bacterial community
Authors: Qiu Sizhe , Zeng Hong , Yang Zhijie , Hung Wei‐Lian , Wang Bei , Yang Aidong 
Published: July 2023

AbstractGenome‐scale metabolic models and flux balance analysis (FBA) have been extensively used for modeling and designing bacterial fermentation. However, FBA‐based metabolic models that accurately simulate the dynamics of coculture are still rare, especially for lactic acid bacteria used in yogurt fermentation. To investigate metabolic interactions in yogurt starter culture of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, this study built a dynamic metagenome‐scale metabolic model which integrated constrained proteome allocation. The accuracy of the model was evaluated by comparing predicted bacterial growth, consumption of lactose and production of lactic acid with reference experimental data. The model was then used to predict the impact of different initial bacterial inoculation ratios on acidification. The dynamic simulation demonstrated the mutual dependence of S. thermophilus and L. d. bulgaricus during the yogurt fermentation process. As the first dynamic metabolic model of the yogurt bacterial community, it provided a foundation for the computer‐aided process design and control of the production of fermented dairy products.
Pollen grading prediction scale for patients with Artemisia pollen allergy in China: A 3‐day moving predictive model
Authors: Yin Zhaoyin , Ouyang Yuhui , Dang Bing , Zhang Luo 
Published: July 2023

AbstractBackgroundArtemisia pollen is the most prevalent outdoor aeroallergen causing respiratory allergies in Beijing, China. Pollen allergen concentrations have a direct impact on the quality of life of those suffering from allergies. Artemisia pollen deposition grading predictions can provide early warning for the protection and treatment of patients as well as provide a scientific basis for allergen specific clinical immunotherapy.ObjectiveTo develop a model of Artemisia pollen grading to predict development in patients with pollen allergy.MethodsArtemisia pollen data from four pollen monitoring stations in Beijing as well as the number of Artemisia pollen allergen serum specific immunoglobulin E positive cases in Beijing Tongren Hospital from 2014 to 2016 were used to develop a statistical model of pollen deposition and provide optimised threshold values.ResultsA logarithmic correlation existed between the number of patients with Artemisia pollen allergy and Artemisia pollen deposition, and the average pollen deposition for three consecutive days was most correlated with the number of allergic patients. Based on the threshold of the number of patients and the characteristics of Artemisia pollen, a five‐stage pollen deposition grading model was developed to predict the degree of pollen allergy.ConclusionsGraded prediction of pollen deposition may help pollen allergic populations benefit from preventive interventions before onset.
Total Synthesis and Biological Investigation of Mindapyrroles A and B
Authors: Allen Ryan A. , Wuest William M. 
Published: July 2023

AbstractIn the search for antibacterial compounds that can overcome drug resistant species, molecules that enact novel or polypharmacological mechanisms of action (MoA) are needed. As a preliminary foray into molecules of this background, the total synthesis of mindapyrroles A and B was undertaken leveraging a biomimetic approach. Following their synthesis, they and their monomer pyoluteorin were tested against a range of pathogenic bacteria in minimum inhibitory concentration assays to confirm their activity. These molecules were then tested for their ability to disrupt membrane potential in S. aureus. Our findings indicate that pyoluteorin acts as a protonophore but the mindapyrroles do not. This work encapsulates the first total synthesis of mindapyrrole B and the second total synthesis of mindapyrrole A in 11 % and 30 % overall yields, respectively. It also provides insights into the antibacterial properties and different MoAs between the monomer and dimers.
Deep Eutectic Solvents as Suitable Solvents for Lipase‐Catalyzed Transesterification Reactions
Authors: Noro Jennifer , Cabo Joana , Freitas David S. , Roque Catarina S. , de Castro Mariana , Cavaco‐Paulo Artur , Silva Carla 
Published: July 2023

AbstractIn this work, three deep eutectic mixtures (DES 1: choline chloride/urea; DES 2: choline chloride/glycerol; and DES 3: tetrabutylammonium bromide/imidazole) were investigated as mediums for the synthesis of glucose laurate and glucose acetate. Aiming to achieve a greener and more sustainable approach, the synthesis reactions were catalyzed by lipases from Aspergillus oryzae (LAO), Candida rugosa (LCR), and porcine pancreas (LPP). The hydrolytic activity of lipases against p‐nitrophenyl hexanoate revealed no evidence of enzyme inactivation when DES were used as medium. Regarding the transesterification reactions, combining LAO or LCR with DES 3 resulted in the efficient production of glucose laurate (from glucose and vinyl laurate) (conversion >60 %). The best result for LPP was observed in DES 2, with 98 % of product production after 24 hours of reaction. When replacing vinyl laurate by a smaller hydrophilic substrate, vinyl acetate, a distinct behavior was observed. LCR and LPP performed better in DES 1, yielding more than 80 % of glucose acetate after 48 hours of reaction. The catalytic activity of LAO was less pronounced, reaching only nearly 40 % of product in DES 3. The results highlight the potential of combining biocatalysis with greener and environmentally‐safer solvents, for the synthesis of differentiated chain‐length sugar fatty acid esters (SFAE).
The genetic basis of conspicuous coloration in the Guadeloupean anole: Evolution by sexual and ecological selection
Authors: Crawford Nicholas G. , McGreevy Thomas J. , Mullen Sean P. , Schneider Christopher J. 
Published: July 2023

AbstractUnderstanding how natural selection acts on the genome and contributes to the process of speciation is a primary aim of the study of evolution. Here we used natural variation in two subspecies of the Guadeloupean anole (Anolis marmoratus ssp.), from the island of Guadeloupe in the Lesser Antilles, to explore the genomic basis of adaptation and speciation in Anolis lizards. These subspecies inhabit distinct ecological environments and display marked differences in adult male color and pattern. We sequenced the complete genomes of 20 anoles, 10 from each subspecies, at 1.4× coverage. We used genome‐wide scans of population differentiation, allele frequency spectrum, and linkage disequilibrium to characterize the genomic architecture within and between the subspecies. While most of the genome was undifferentiated, we observed five large divergent regions. Within these regions we identified blocks, 5 kb pairs in length, enriched for fixed single nucleotide polymorphisms. These blocks encompass 97 genes, two of which are candidate pigmentation genes. One is melanophilin (mlph), which helps transport melanosomes within melanocytes. The other is a cluster of differentiation 36 (cd36), which regulates carotenoid pigment sequestration. We used high‐pressure liquid chromatography to confirm that carotenoid pigments are significantly more abundant in the conspicuous orange‐pigmented skin of male A. m. marmoratus suggesting that cd36 may be regulating pigment deposition in this tissue. We identified for the first time a carotenoid gene that is a potential target of divergent sexual selection and may be contributing to the early stages of speciation in Anolis lizards.
cGAS‐STING signaling in cell death: Mechanisms of action and implications in pathologies
Authors: Xu Yifan , Chen Chen , Liao Zhiyong , Xu Pinglong 
Published: July 2023

AbstractCyclic GMP‐AMP synthase (cGAS) monitors dsDNA in the cytosol in response to pathogenic invasion or tissue injury, initiating cGAS‐STING signaling cascades that regulate various cellular physiologies, including IFN /cytokine production, autophagy, protein synthesis, metabolism, senescence, and distinct types of cell death. cGAS‐STING signaling is crucial for host defense and tissue homeostasis; however, its dysfunction frequently leads to infectious, autoimmune, inflammatory, degenerative, and cancerous diseases. Our knowledge regarding the relationships between cGAS‐STING signaling and cell death is rapidly evolving, highlighting their essential roles in pathogenesis and disease progression. Nevertheless, the direct control of cell death by cGAS‐STING signaling, rather than IFN/NF‐κB‐mediated transcriptional regulation, remains relatively unexplored. This review examines the mechanistic interplays between cGAS‐STING cascades and apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagic/lysosomal cell death. We will also discuss their pathological implications in human diseases, particularly in autoimmunity, cancer, and organ injury scenarios. We hope that this summary will stimulate discussion for further exploration of the complex life‐or‐death responses to cellular damage mediated by cGAS‐STING signaling.
Economic analysis of enzyme recycling during enzymatic hydrolysis of sugar beets for soluble sugars production
Authors: Chen Yike , Zicari Steve , Zhang Ruihong 
Published: July 2023

AbstractEnzymatic hydrolysis of sugar beets is an efficient alternative to conventional hot water extraction where overall soluble extraction is valued. The economic analysis of a sugar beet soluble sugar production plant was designed and developed using SuperPro Designer software. The commercial scale operation was sized to process 100 million metric ton (MT)/day of sugar beets. The base case process includes transportation, grinding, thermal pretreatment, enzymatic hydrolysis, solid–liquid separation, and evaporation. The final product from the model was assumed to be a sugar syrup stream at 65% total solids content. Since the breakeven selling price was sensitive to the cost of enzymes, alternative scenario A added an ultrafiltration unit operation to separate the enzymes and reuse them in subsequent batches of hydrolysis. Steam was another major contributor to the operating cost. Alternative scenario B included a natural gas boiler to generate steam from biogas produced from a co‐located dairy manure digester. The breakeven selling price of the sugar syrup from the base case, alternative scenario A, and alternative scenario B were $965, $911, and $955 per metric ton, respectively. Sensitivity analysis showed that the breakeven selling price is sensitive to the raw material cost, especially for the pectic enzymes.
Scenario planning: Reflecting on cases of actionable knowledge
Authors: Oliver John J. 
Published: July 2023

AbstractScenario planning has a long history of academic inquiry and practice in numerous fields and industries; however, its future as a tool to manage strategic uncertainty may well have reached an impasse. While the academic community perpetuates the view that the field is characterized by methodological chaos, the practitioner community is concerned only with how scenario planning can help solve an organizational problem. This paper argues that the academic community would benefit from adopting a philosophical orientation that is “pragmatic” where theoretical and methodological sophistication should be traded‐off against the need to produce a practical outcome that addresses a specific organizational problem. This would enable more academics to generate new knowledge that was “useful” rather than “generalizable.” Adopting a Pragmatic Philosophy would also address three primary issues asserted in literature on the process, content, and implementation of scenario‐informed strategizing. This position paper provides a reflective account of how the narrative on scenario planning theory can be moved more effectively into scenario planning practice by illustrating the author's commitment to developing scenario‐based actionable knowledge, high levels of implementable validity, and instrumental impact with organizations. As such, it presents a reflection on interventions that demonstrate how scenario‐informed strategies were developed and implemented with successful organizational outcomes.
Advances in the application of functional nanomaterial and cold plasma for the fresh‐keeping active packaging of meat
Authors: Umair Muhammad , Sultana Tayyaba , Xun Song , Jabbar Saqib , Riaz Rajoka Muhammad Shahid , Albahi Amgad , Abid Muhammad , Ranjha Muhammad Modassar Ali Nawaz , El‐Seedi Hesham R. , Xie Fengwei , Khan Kashif ur Rehman , Liqing Zhao , Zhendan He 
Published: July 2023

AbstractThe most recent advancements in food science and technology include cold sterilization of food and fresh‐keeping packaging. Active packaging technology has received much interest due to the photocatalytic activity (PCA) of functional nanoparticles, including titanium dioxide (TiO2) and ferric oxide (Fe2O3). However, there are still significant concerns about the toxicity and safety of these functional nanoparticles. This review emphasizes the bacteriostatic and fresh‐keeping properties of functional nanoparticles as well as their packaging strategies using the ultraviolet photo‐catalysis effect. High‐voltage electric field cold plasma (HVEF‐CP) is the most innovative method of cold‐sterilizing food. HVEF‐CP sterilizes by producing photoelectrons, ions, and active free radicals on food media, which come into contact with the bacteria's surface and destroy their cells. Next, this review also assesses the photocatalytic activity and bacteriostasis kinetics of nanosized TiO2 and Fe2O3 in poultry, beef, and lamb. In addition, this review also emphasizes the importance of exploiting the complex interaction processes between TiO2 and Fe2O3, along with dietary components and their utilization in the fresh meat industry.
The association of pain with suicidal ideation and suicide attempts with depressive symptoms among adults aged ≥50 years from low‐ and middle‐income countries
Authors: Smith Lee , Shin Jae Il , Pizzol Damiano , López Sánchez Guillermo F. , Soysal Pinar , Veronese Nicola , Kostev Karel , Jacob Louis , Butler Laurie T. , Barnett Yvonne , Koyanagi Ai 
Published: July 2023

AbstractObjectivesWe aimed to examine the relationship of pain with suicidal ideation and suicide attempts with depressive symptoms among adults aged ≥50 years from six low‐ and middle‐income countries (LMICs) (China, Ghana, India, Mexico, Russia, and South Africa).MethodsCross‐sectional, community‐based, nationally representative data from the WHO Study on global AGEing and adult health were analyzed. Self‐reported information on past 12‐month suicidal ideation and suicide attempts among people with depressive symptoms was collected. Pain was assessed with the question “Overall in the last 30 days, how much of bodily aches or pain did you have?” With answer options: “none”, “mild”, “moderate”, “severe/extreme”. Multivariable logistic regression was done to assess associations.ResultsData on 34,129 adults aged ≥50 years (mean [SD] age 62.4 [16.0] years; males 47.9%) were analyzed. Compared to no pain, mild, moderate, and severe/extreme pain were associated with 2.83 (95% CI = 1.51–5.28), 4.01 (95% CI = 2.38–6.76), and 12.26 (95% CI = 6.44–23.36) times higher odds for suicidal ideation. For suicide attempt, only severe/extreme pain was associated with significantly increased odds (OR = 4.68; 95% CI = 1.67–13.08).ConclusionsIn this large sample of older adults from multiple LMICs, pain was strongly associated with suicidal thoughts and suicide attempts with depressive symptoms. Future studies should assess whether addressing pain among older people in LMICs may lead to reduction in suicidal thoughts and behaviors.
Every subcubic multigraph is (1,27) $(1,{2}^{7})$‐packing edge‐colorable
Authors: Liu Xujun , Santana Michael , Short Taylor 
Published: July 2023

AbstractFor a nondecreasing sequence of positive integers, an ‐packing edge‐coloring of a graph is a decomposition of edges of into disjoint sets such that for each the distance between any two distinct edges is at least . The notion of ‐packing edge‐coloring was first generalized by Gastineau and Togni from its vertex counterpart. They showed that there are subcubic graphs that are not ‐packing (abbreviated to ‐packing) edge‐colorable and asked the question whether every subcubic graph is ‐packing edge‐colorable. Very recently, Hocquard, Lajou, and Lužar showed that every subcubic graph is ‐packing edge‐colorable and every 3‐edge‐colorable subcubic graph is ‐packing edge‐colorable. Furthermore, they also conjectured that every subcubic graph is ‐packing edge‐colorable.In this paper, we confirm the conjecture of Hocquard, Lajou, and Lužar, and extend it to multigraphs.
On pathways and blind alleys—The importance of biomarkers in vitamin B6‐dependent epilepsies
Authors: Plecko Barbara 
Published: July 2023

AbstractOver the past two decades, the field of vitamin B6‐dependent epilepsies has evolved by the recognition of a growing number of gene defects (ALDH7A1, PNPO, ALPL, ALDH4A1, PLPBP as well as defects of the glycosylphosphatidylinositol anchor proteins) that all lead to reduced availability of pyridoxal 5′‐phosphate, an important cofactor in neurotransmitter and amino acid metabolism. In addition, positive pyridoxine response has been observed in other monogenic defects such as MOCS2 deficiency or KCNQ2 and there may be more defects to be discovered. Most entities lead to neonatal onset pharmaco‐resistant myoclonic seizures or even status epilepticus and pose an emergency to the treating physician. Research has unraveled specific biomarkers for several of these entities (PNPO deficiency, ALDH7A1 deficiency, ALDH4A1 deficiency, ALPL deficiency causing congenital hypophosphatasia and glycosylphosphatidylinositol anchoring defects with hyperphosphatasia), that can be detected in plasma or urine, while there is no biomarker to test for PLPHP deficiency. Secondary elevation of glycine or lactate was recognized as diagnostic pitfall. An algorithm for a standardized trial with vitamin B6 should be in place in every newborn unit in order not to miss these well‐treatable inborn errors of metabolism. The Komrower lecture of 2022 provided me with the opportunity to tell the story about the conundrums of research into vitamin B6‐dependent epilepsies that kept some surprises and many novel insights into pathomechanisms of vitamin metabolism. Every single step had benefits for the patients and families that we care for and advocates for a close collaboration of clinician scientists with basic research.
The heat stress during anthesis and the grain‐filling period of spring maize in Northeast China is projected to increase toward the mid‐21st century
Authors: Qiao Suliang , Liu Zhijuan , Zhang Zhentao , Su Zheng'e , Yang Xiaoguang 
Published: July 2023

AbstractBACKGROUNDAgainst the background of global warming, heat stress has become more frequent, which adversely affects the growth and development of spring maize plants in Northeast China. To adapt the regional maize production to climate change, it is imperative to understand the spatio‐temporal characteristics of heat stress. In the present study, we analyzed three of the indices for heat stress, including the number of heat stress days, heating degree days (HDD, the total heat degree‐days during critical stages), and the percentage of stations with heat stress.RESULTSFrom 1981 to 2019, the number of heat stress days varied greatly among the study years, ranging from 0 to 14 and 27 days, respectively. The average HDD was 7.8 and 5.0 °C day from 1981 to 2000, respectively, and the main hot‐spots of heat stress occurred in the southwest regions. Moreover, compared with 1981–2000, the region of HDD during anthesis higher than 10 °C day in 2041–2060 under the SSP1‐2.6 and SSP5‐8.5 climate scenarios increased by 9.1–50.1% and 0.1–28.6%. The average HDD during the critical stages from 2041 to 2060 increased under the SSP5‐8.5 climate scenario, being 1.5 times higher than that during 1981‐2000. HDD during maize anthesis and the grain‐filling period showed an overall increasing trend with years. About 19% and 58% of the study locations showed heat stress during the past 39 years, respectively.CONCLUSIONHeat stress during anthesis and the grain‐filling period for spring maize in Northeast China is projected to increase toward the mid‐21st century. © 2023 Society of Chemical Industry.