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The unique structural properties of porous ceramics, such as low thermal conductivity, high surface area, controlled permeability, and low density, make this material valuable for a wide range of applications. Its uses include insulation, catalyst carriers, filters, bio-scaffolds for tissue engineering, and composite manufacturing. However, existing processing methods for porous ceramics, namely replica techniques and sacrificial templates, are complex, release harmful gases, have limited microstructure control, and are expensive. In contrast, the direct foaming method offers a simple and cost-effective approach. By modifying the surface chemistry of ceramic particles in a colloidal suspension, the hydrophilic particles are transformed into hydrophobic ones using surfactants. This method produces porous ceramics with interconnected pores, creating a hierarchical structure that is suitable for applications like nano-filters. This review emphasizes the importance of interconnected porosity in developing advanced ceramic materials with tailored properties for various applications. Interconnected pores play a vital role in facilitating mass transport, improving mechanical properties, and enabling fluid or gas infiltration. This level of porosity control allows for the customization of ceramic materials for specific purposes, including filtration, catalysis, energy storage, and biomaterials.

The purpose of this study was to enhance the stability of montelukast and levocetirizine for the development of a fixed-dose combination (FDC) monolayer tablet. To evaluate the compatibility of montelukast and levocetirizine, a mixture of the two drugs was prepared, and changes in the appearance characteristics and impurity content were observed in a dry oven at 60 °C. Excipients that contributed minimally to impurity increases were selected to minimize drug interactions. Mannitol, microcrystalline cellulose, croscarmellose sodium, hypromellose, and sodium citrate were chosen as excipients, and montelukast–levocetirizine FDC monolayer tablets were prepared by wet granulating the two drugs separately. A separate granulation of montelukast and levocetirizine, along with the addition of sodium citrate as a pH stabilizer, minimized the changes in tablet appearance and impurity levels. The prepared tablets demonstrated release profiles equivalent to those of commercial products in comparative dissolution tests. Subsequent stability testing at 40 ± 2 °C and 75 ± 5% RH for 6 months confirmed that the drug content, dissolution rate, and impurity content met the specified acceptance criteria. In conclusion, the montelukast–levocetirizine FDC monolayer tablet developed in this study offers a potential alternative to commercial products.

Purpose: Previous studies showed inconsistent results concerning the relationship between chronic smoking and blood pressure. Most of the studies involved self-reported smoking status. This study was performed to evaluate the association of urinary cotinine or self-reported smoking status with hypertension and blood pressure in Korean adults. Materials and methods: Among individuals enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study, 167,868 participants (men, 55.7%; age, 37.5 ± 6.9 years) between 2011 and 2013 who had urinary cotinine measurements were included. Individuals with urinary cotinine levels ≥50 ng/mL were defined as cotinine-verified current smokers. Results: The prevalence of hypertension and cotinine-verified current smokers in the overall population was 6.8% and 22.7%, respectively (10.0% in men and 2.8% in women for hypertension: 37.7% in men and 3.9% in women for cotinine-verified current smokers). In a multivariate regression analysis adjusted for age, sex, body mass index, waist circumference, alcohol drinking, vigorous exercise, and diabetes, cotinine-verified current smoking was associated with lower prevalence of hypertension compared with cotinine-verified never smoking (OR[95% CI], 0.79 [0.75, 0.84]). Log-transformed cotinine levels and unobserved smoking were negatively associated with hypertension, respectively (0.96 [0.96, 0.97] and 0.55 [0.39, 0.79]). In a multivariate linear regression analysis, the cotinine-verified current smoking was inversely associated with systolic and diastolic blood pressure (BP) (regression coefficient[95% CI], −1.23[−1.39, −1.07] for systolic BP and −0.71 [−0.84, −0.58] for diastolic BP). In subgroup analyses according to sex, the inverse associations between cotinine-verified current smoking and hypertension were observed only in men. Conclusions: This large observational study showed that cotinine-verified current smoking and unobserved smoking were inversely associated with hypertension in Korean adults, especially only in men.

Abstract The porous ceramics based on Al2O3–TiO2/ZrO2–SiO2 from particle-stabilized wet foam by direct foaming were discussed. The initial Al2O3–TiO2 suspension was prepared by adding TiO2 suspension to partially hydrophobized colloidal Al2O3 suspension with equimolar amount, to form Al2TiO5 on sintering. The secondary ZrO2–SiO2 suspension was prepared using the equimolar composition, and to obtain ZrSiO4, ZrTiO4, and mullite phases in the sintered samples, the secondary suspension was blended into the initial suspension at 0, 10, 20, 30, and 50 vol%. The wet foam exhibited an air content up to 87%, Laplace pressure from 1.38 to 2.23 mPa, and higher adsorption free energy at the interface of approximately 5.8×108 to 7.5×108 J resulting an outstanding foam stability of 87%. The final suspension was foamed, and the wet foam was sintered from 1400 to 1600 °C for 1 h. The porous ceramics with pore size from 150 to 400 μm on average were obtained. The phase identification was accomplished using X-ray diffraction (XRD), differential thermal analysis (DTA), and thermogravimetric analysis (TGA), and microstructural analysis was performed using field emission scanning electron microscopy (FESEM).

Background/Aims: Endoscopic submucosal dissection (ESD) for tumors occurring in the remnant stomach is technically difficult to perform because of limited working space and severe fibrosis and staples present around the suture line. We aimed to elucidate the feasibility and clinical outcomes of performing ESD for tumors in the remnant stomach. Methods: Between December 2007 and January 2013, 18 patients underwent ESD for tumors (six adenomas and 12 differentiated-type early gastric cancers [EGCs]) occurring in the remnant stomach after distal gastrectomy. Clinicopathologic features and clinical outcomes after ESD were retrospectively analyzed. Results: Two-thirds of the lesions were located on the body, and half were located on the suture line. En bloc resection, R0 resection, and en bloc with R0 resection rates were 88.9%, 100%, and 88.9%, respectively. Curative resection rate for EGC was 91.7%. Perforation occurred in one patient (5.6%) and was successfully managed by endoscopic closure with metallic clips and conservative management. There was no significant bleeding after ESD. During a median follow-up of 47.5 months, no local, metachronous, or extragastric recurrence was seen for either EGC or adenoma lesions. Conclusions: ESD is a feasible and effective treatment modality and can be considered a primary intervention for early gastric neoplasia occurring in the remnant stomach.

The identification and three step synthesis of 3-O-protocatechuoylceanothic acid, a novel and natural GPR120 agonist, is described. This ceanothane-type triterpenoid was identified from the components of Ziziphus jujuba roots and was found to be a new GPR120 agonist with a novel structure. We synthetically converted ceanothic acid, which does not have GPR120 agonist activity, into 3-O-protocatechuoylceanothic acid in three steps. In addition, we present the corrected NMR spectrum of 3-O-protocatechuoylceanothic acid based on our synthesis.

Abstract Background Studies of the efficacy of vitamin C treatment for fatigue have yielded inconsistent results. One of the reasons for this inconsistency could be the difference in delivery routes. Therefore, we planned a clinical trial with intravenous vitamin C administration. Methods We evaluated the effect of intravenous vitamin C on fatigue in office workers. A group of 141 healthy volunteers, aged 20 to 49 years participated in this randomized, double-blind, controlled clinical trial. The trial group received 10 grams of vitamin C with normal saline intravenously, while the placebo group received normal saline only. Since vitamin C is a well-known antioxidant, oxidative stress was measured. Fatigue score, oxidative stress, and plasma vitamin C levels were measured before intervention, and again two hours and one day after intervention. Adverse events were monitored. Results The fatigue scores measured at two hours after intervention and one day after intervention were significantly different between the two groups (p = 0.004); fatigue scores decreased in the vitamin C group after two hours and remained lower for one day. Trial also led to higher plasma vitamin C levels and lower oxidative stress compared to the placebo group (p < 0.001, p < 0.001, respectively). When data analysis was refined by dividing each group into high-baseline and low-baseline subgroups, it was observed that fatigue was reduced in the lower baseline vitamin C level group after two hours and after one day (p = 0.004). The same did not hold for the higher baseline group (p = 0.206). Conclusion Thus, intravenous vitamin C reduced fatigue at two hours, and the effect persisted for one day. There were no significant differences in adverse events between two groups. High dose intravenous vitamin C proved to be safe and effective against fatigue in this study. Trial Registration The clinical trial registration of this trial is http://ClinicalTrials.govNCT00633581.

Abstract Background Varicella-zoster virus (VZV) causes chickenpox in children and shingles in older people. Currently, live attenuated vaccines based on the Oka strain are available worldwide. In Korea, an attenuated VZV vaccine has been developed from a Korean isolate and has been commercially available since 1994. Despite this long history of use, the mechanism for the attenuation of the vaccine strain is still elusive. We attempted to understand the molecular basis of attenuation mechanism by full genome sequencing and comparative genomic analyses of the Korean vaccine strain SuduVax. Results SuduVax was found to contain a genome that was 124,759 bp and possessed 74 open reading frames (ORFs). SuduVax was genetically most close to Oka strains and these Korean-Japanese strains formed a strong clade in phylogenetic trees. SuduVax, similar to the Oka vaccine strains, underwent T- > C substitution at the stop codon of ORF0, resulting in a read-through mutation to code for an extended form of ORF0 protein. SuduVax also shared certain deletion and insertion mutations in ORFs 17, 29, 56 and 60 with Oka vaccine strains and some clinical strains. Conclusions The Korean VZV vaccine strain SuduVax is genetically similar to the Oka vaccine strains. Further comparative genomic and bioinformatics analyses will help to elucidate the molecular basis of the attenuation of the VZV vaccine strains.

Abstract Background Valproic acid (VPA), a commonly used mood stabilizer that promotes neuronal differentiation, regulates multiple signaling pathways involving extracellular signal-regulated kinase (ERK) and glycogen synthase kinase3β (GSK3β). However, the mechanism by which VPA promotes differentiation is not understood. Results We report here that 1 mM VPA simultaneously induces differentiation and reduces proliferation of basic fibroblast growth factor (bFGF)-treated embryonic day 14 (E14) rat cerebral cortex neural progenitor cells (NPCs). The effects of VPA on the regulation of differentiation and inhibition of proliferation occur via the ERK-p21Cip/WAF1 pathway. These effects, however, are not mediated by the pathway involving the epidermal growth factor receptor (EGFR) but via the pathway which stabilizes Ras through β-catenin signaling. Stimulation of differentiation and inhibition of proliferation in NPCs by VPA occur independently and the β-catenin-Ras-ERK-p21Cip/WAF1 pathway is involved in both processes. The independent regulation of differentiation and proliferation in NPCs by VPA was also demonstrated in vivo in the cerebral cortex of developing rat embryos. Conclusion We propose that this mechanism of VPA action may contribute to an explanation of its anti-tumor and neuroprotective effects, as well as elucidate its role in the independent regulation of differentiation and inhibition of proliferation in the cerebral cortex of developing rat embryos.

Microbial cell factories provide sustainable alternatives to petroleum-based chemical production using cost-effective substrates. A deep understanding of their metabolism is essential to harness their potential along with continuous efforts to improve productivity and yield. However, the construction and evaluation of numerous genetic variants are time-consuming and labor-intensive. Cell-free systems (CFSs) serve as powerful platforms for rapid prototyping of genetic circuits, metabolic pathways, and enzyme functionality. They offer numerous advantages, including minimizing unwanted metabolic interference, precise control of reaction conditions, reduced labor, and shorter Design-Build-Test-Learn cycles. Additionally, the introduction of in vitro compartmentalization strategies in CFSs enables ultra-high-throughput screening in physically separated spaces, which significantly enhances prototyping efficiency. This review highlights the latest examples of using CFS to overcome prototyping limitations in living cells with a focus on rapid prototyping, particularly regarding gene regulation, enzymes, and multienzymatic reactions in bacteria. Finally, this review evaluates CFSs as a versatile prototyping platform and discusses its future applications, emphasizing its potential for producing high-value chemicals through microbial biosynthesis., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Acetate is a cost-effective and sustainable carbon source that, despite its potential, remains underutilized. This study employed biosensor-assisted adaptive laboratory evolution (ALE) to enhance itaconic acid production and acetate metabolism in Escherichia coli. The evolved E. coli W strains exhibited 65% increase in itaconic acid production and 71% increase in growth rate, and 45% increase in itaconic acid yield. A common 31-kb genomic deletion was identified in the evolved strains, with two genes, ecw&#95;m2276 and ecw&#95;m2277, driving the observed phenotypic changes. The evolved strains exhibited an intensified stringent response, which enhanced the acetate-utilizing pathway and resulted in over a 5,000% increase in the expression of the glyoxylate shunt, thereby boosting microbial growth. Overexpression of relA further replicated these enhanced phenotypes. Our findings highlight not only significant physiological improvements but also present a novel strategy for enhancing microbial growth and bioproduction from acetate, offering valuable insights for industrial biotechnology applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Donghyuk Kim reports financial support was provided by National Research Foundation of Korea. Gyoo Yeol Jung reports financial support was provided by National Research Foundation of Korea. Gyoo Yeol Jung reports financial support was provided by Korea Institute of Marine Science and Technology Promotion. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

True random numbers are essential for ensuring information security and supporting simulations across various industries. With the exponential growth of data driven by advancements in artificial intelligence, robust encryption for communications has become increasingly important. While software-based deterministic random number algorithms are cost-effective and easy to use, they are vulnerable to attacks by powerful supercomputers, highlighting the need for more secure alternatives. As portable electronic devices and information-gathering sensors proliferate, portable true random number generators (TRNGs) are critical for maintaining security. In this work, hybrid material-based photodetectors composed of anionic polymers and perovskites that maximize stochastic photogeneration for TRNG applications are presented. By integrating perovskite photodetectors with simple electronic circuits, compact, low-power TRNG devices have been developed that are versatile and resilient to environmental factors. These devices generate 10 000 bits s -1 without resets or delays, achieving significant miniaturization. The generated 10 Mbit random number is validated through US National Institute of Standards and Technology (NIST) testing. Using a 480 000-bit random sequence, perfect image encryption, ensuring protection against hacking are demonstrated. Additionally, the perovskite TRNG can operate under external light even when embedded in pork skin, realizing its potential as an implantable device for personal security and authentication., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Methylated and inorganic arsenic species are frequently detected in natural water systems due to anthropogenic activities and geological origins. However, the impact of arsenic species on microbial activity, particularly on methanogens responsible for methane production, remains underexplored. This study investigates the effects of arsenic on methanogenesis by adding iAs(V) and DMA(V) to wetland sediment batches and monitoring arsenic speciation in the supernatant and methane production over time. Changes in arsenic behavior in the sediment were analyzed using X-ray Absorption Fine Structure (XAFS). Microbial diversity analysis revealed that while iAs(V) acted as an electron acceptor and its reduction to iAs(III) inhibited methanogen activity due to its toxicity, DMA showed minimal effects on methane production. These findings demonstrate that arsenic dynamics in wetlands influence methane-producing microorganisms, with inorganic form of arsenic species posing significant inhibitory effects, whereas less toxic DMA(V) appears to have limited impact. This might shed light on the potential for regulating methane emissions in arsenic-contaminated wetlands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

A seven-year-old spayed female dog presented with multiple, small oval-shaped masses on the abdominal skin. The excised tissue was submitted for histopathological evaluation. Routine histology revealed basaloid nodules with stippled chromatin and pleomorphic nuclei. Morphologically, the tumor resembled a solid papillary carcinoma of the breast or an endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC is a rare neuroendocrine-differentiated neoplasm. This study aimed to compare different immunohistochemical markers for distinguishing between canine sweat gland carcinoma (SGC) and mammary gland carcinoma (MGC). CK19 and Sox9 were useful in identifying SGC. Additionally, the tumor was positive for CK5, AE1/AE3+CK8/18, p63, vimentin, E-cadherin, and synaptophysin, while estrogen receptor staining was negative. The final diagnosis of canine EMPSGC was based on the tumor's morphological and neuroendocrine immunohistopathological features. Our report provides the first detailed description of a canine EMPSGC, an exceedingly rare tumor in dogs.

Raffinose, a trisaccharide abundantly found in soybeans, is a potential alternative carbon source for biorefineries. Nevertheless, residual intermediate di- or monosaccharides and low catabolic efficiency limit raffinose use through conventional microbial hosts. This study presents a Vibrio-based platform to convert raffinose efficiently. Vibrio sp. dhg was selected as the starting strain for the Adaptive Laboratory Evolution (ALE) strategy to leverage its significantly higher metabolic efficiency. We conducted ALE on a solid minimal medium supplemented with raffinose to prevent the enrichment of undesired phenotypes due to the shared effect of extracellular raffinose hydrolysis among multiple strains. As a result, we generated the VRA10 strain that efficiently utilizes raffinose without leaving behind degraded di- or monosaccharides, achieving a notable growth rate (0.40 h -1 ) and raffinose consumption rate (1.2 g/g dcw /h). Whole genome sequencing and reverse engineering identified that a missense mutation in the melB gene (encoding a melibiose/raffinose:sodium symporter) and the deletion of the two galR genes (encoding transcriptional repressors for galactose catabolism) facilitated rapid raffinose utilization. The further engineered strain produced 6.2 g/L of citramalate from 20 g/L of raffinose. This study will pave the way for the efficient utilization of diverse raffinose-rich byproducts and the expansion of alternative carbon streams in biorefinery applications., Competing Interests: Declaration of interest The authors declare no competing interests., (Copyright © 2024 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Recent advancements in biosensor technology have revolutionized the field of microbial engineering, enabling efficient and precise optimization of strains for the production of valuable chemicals. This review comprehensively explores the innovative integration of biosensors to enhance microbial cell factories, with a particular emphasis on the crucial role of high-throughput biosensor-assisted screening. Biosensor-assisted approaches have enabled the identification of novel transporters, the elucidation of underlying transport mechanisms, and the fine-tuning of metabolic pathways for enhanced production. Furthermore, this review illustrates the utilization of biosensors for manipulating cellular behaviors, including interactions with environmental factors, and the reduction of nongenetic cell-to-cell variations. This review highlights the indispensable role of biosensors in advancing the field of microbial engineering through the modulation and exploitation of diverse cellular physiological processes.

Itaconate is a promising platform chemical with broad applicability, including the synthesis of poly(methyl methacrylate). Most studies on microbial itaconate production entail the use of crop-based feedstock, which imposes constraints due to its limited supply. Brown macroalgae have recently gained attention as next-generation biomass owing to their high biomass productivity and carbohydrate content and amenability to mass production. Therefore, the use of macroalgae for itaconate production warrants exploration. In this study, the direct production of itaconate from brown macroalgae was demonstrated using engineered Vibrio sp. dhg, which has emerged as an efficient platform host for brown macroalgal biorefineries. Specifically, to enhance production, cis -aconitate decarboxylase (Cad) from Aspergillus terreus was heterologously expressed and isocitrate dehydrogenase ( icd ) was deleted. Notably, the resulting strain, VIC, achieved itaconate titers of 2.5 and 1.5 g/L from a mixture of alginate and mannitol (10 g/L of each) and 40 g/L of raw Saccharina japonica ( S. japonica ), respectively. Overall, this study highlights the utility of brown macroalgae as feedstock, as well as that of Vibrio sp. dhg as a platform strain for improving itaconate bioproduction.

Selective spectral discrimination of visible and near-infrared light, which accurately distinguishes different light wavelengths, holds considerable promise in various fields, such as automobiles, defense, and environmental monitoring. However, conventional imaging technologies suffer from various issues, including insufficient spatial optimization, low definition, and optical loss. Herein, a groundbreaking advancement is demonstrated in the form of a dual-band photodiode with distinct near-infrared- and visible-light discrimination obtained via simple voltage control. The approach involves the monolithic stacking integration of methylammonium lead iodide (MAPbI 3 ) and Si semiconductors, resulting in a p-Si/n-phenyl-C 61 -butyric acid methyl ester/i-MAPbI 3 /p-spiro-MeOTAD (PNIP) device. Remarkably, the PNIP configuration can independently detect the visible and near-infrared regions without traditional optical filters under a voltage range of 3 to -3 V. In addition, an imaging system for a prototype autonomous vehicle confirms the capability of the device to separate visible and near-infrared light via an electrical bias and practicality of this mechanism. Therefore, this study pushes the boundaries of image sensor development and sets the stage for fabricating compact and power-efficient photonic devices with superior performance and diverse functionality., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

It is shown that structural disorder-in the form of anisotropic, picoscale atomic displacements-modulates the refractive index tensor and results in the giant optical anisotropy observed in BaTiS 3 , a quasi-1D hexagonal chalcogenide. Single-crystal X-ray diffraction studies reveal the presence of antipolar displacements of Ti atoms within adjacent TiS 6 chains along the c-axis, and threefold degenerate Ti displacements in the a-b plane. 47/49 Ti solid-state NMR provides additional evidence for those Ti displacements in the form of a three-horned NMR lineshape resulting from a low symmetry local environment around Ti atoms. Scanning transmission electron microscopy is used to directly observe the globally disordered Ti a-b plane displacements and find them to be ordered locally over a few unit cells. First-principles calculations show that the Ti a-b plane displacements selectively reduce the refractive index along the ab-plane, while having minimal impact on the refractive index along the chain direction, thus resulting in a giant enhancement in the optical anisotropy. By showing a strong connection between structural disorder with picoscale displacements and the optical response in BaTiS 3 , this study opens a pathway for designing optical materials with high refractive index and functionalities such as large optical anisotropy and nonlinearity., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Strategic allocation of metabolic flux is essential for achieving a higher production performance in genetically engineered organisms. Flux optimization between cell growth and chemical production has led to the establishment of cost-effective chemical production methods in microbial cell factories. This effect is amplified when utilizing a low-cost carbon source. γ-Aminobutyric acid (GABA), crucial in pharmaceuticals and biodegradable polymers, can be efficiently produced from acetate, a cost-effective substrate. However, a balanced distribution of acetate-derived flux is essential for optimizing the production without hindering growth. In this study, we demonstrated GABA production from acetate using Escherichia coli by focusing on optimizing the metabolic flux at isocitrate and α-ketoglutarate nodes. Through a series of flux optimizations, the final strain produced 2.54 g/L GABA from 5.91 g/L acetate in 24 h (0.43 g/g yield). These findings suggest that delicate flux balancing with the application of a cheap substrate can contribute to cost-effective production of GABA.

Genome engineering has revolutionized several scientific fields, ranging from biochemistry and fundamental research to therapeutic uses and crop development. Diverse engineering toolkits have been developed and used to effectively modify the genome sequences of organisms. However, there is a lack of extensive reviews on genome engineering technologies based on mobile genetic elements (MGEs), which induce genetic diversity within host cells by changing their locations in the genome. This review provides a comprehensive update on the versatility of MGEs as powerful genome engineering tools that offers efficient solutions to challenges associated with genome engineering. MGEs, including DNA transposons, retrotransposons, retrons, and CRISPR-associated transposons, offer various advantages, such as a broad host range, genome-wide mutagenesis, efficient large-size DNA integration, multiplexing capabilities, and in situ single-stranded DNA generation. We focused on the components, mechanisms, and features of each MGE-based tool to highlight their cellular applications. Finally, we discussed the current challenges of MGE-based genome engineering and provided insights into the evolving landscape of this transformative technology. In conclusion, the combination of genome engineering with MGE demonstrates remarkable potential for addressing various challenges and advancing the field of genetic manipulation, and promises to revolutionize our ability to engineer and understand the genomes of diverse organisms., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Electrostatic capacitors are foundational components of advanced electronics and high-power electrical systems owing to their ultrafast charging-discharging capability. Ferroelectric materials offer high maximum polarization, but high remnant polarization has hindered their effective deployment in energy storage applications. Previous methodologies have encountered problems because of the deteriorated crystallinity of the ferroelectric materials. We introduce an approach to control the relaxation time using two-dimensional (2D) materials while minimizing energy loss by using 2D/3D/2D heterostructures and preserving the crystallinity of ferroelectric 3D materials. Using this approach, we were able to achieve an energy density of 191.7 joules per cubic centimeter with an efficiency greater than 90%. This precise control over relaxation time holds promise for a wide array of applications and has the potential to accelerate the development of highly efficient energy storage systems.

Biological production of citramalate has garnered attention due to its wide application for food additives and pharmaceuticals, although improvement of yield is known to be challenging. When glucose is used as the sole carbon source, carbon loss through decarboxylation steps for providing acetyl-CoA from pyruvate is inevitable. To avoid this, we engineered a strain to co-utilize glucose and cost-effective acetate while preventing carbon loss for enhancing citramalate production. The production pathway diverged to independently supply the precursors required for the synthesis of citramalate from glucose and acetate, respectively. Moreover, the phosphotransferase system was inactivated and the acetate assimilation pathway and the substrate ratio were optimized to enable the simultaneous and efficient utilization of both carbon sources. This yielded results (5.0 g/L, 0.87 mol/mol) surpassing the yield and titer of the control strain utilizing glucose as the sole carbon source in flask cultures, demonstrating an economically efficient strain redesign strategy for synthesizing various products.

Microbial production of genistein, an isoflavonoid primarily found in soybeans, is gaining prominence in the food industry due to its significant nutritional and health benefits. However, challenges arise in redesigning strains due to intricate regulatory nodes between cell growth and genistein production and in systematically exploring core enzymes involving genistein biosynthesis. To address this, this study devised a strategy that simultaneously and precisely rewires flux at both acetyl-CoA and malonyl-CoA nodes toward genistein synthesis. In particular, naringenin, the primary precursor of genistein, was accumulated 2.6 times more than the unoptimized strain through transcriptional repressor-based genetic regulators. Building upon this, a combination of isoflavone synthase and cytochrome P450 reductase with the remarkable conversion of naringenin to genistein was screened from enzyme homologue libraries. The integrated metabolic engineering strategy yields the highest reported production (98 mg/L of genistein) to date, providing a framework for the biosynthesis of diverse flavonoids, including genistein.

Brown macroalgae is a promising feedstock for biorefinery owing to its high biomass productivity and contents of carbohydrates such as alginate and mannitol. However, the limited availability of microbial platforms efficiently catabolizing the brown macroalgae sugars has restricted its utilization. In this study, the direct production of citramalate, an important industrial compound, was demonstrated from brown macroalgae by utilizing Vibrio sp. dhg, which has a remarkably efficient catabolism of alginate and mannitol. Specifically, citramalate synthase from Methanocaldococcus jannaschii was synthetically expressed, and competing pathways were removed to maximally redirect the carbon flux toward citramalate production. Notably, a resulting strain, VXHC, produced citramalate up to 9.8 g/L from a 20 g/L mixture of alginate and mannitol regardless of their ratios. Citramalate was robustly produced even when diverse brown macroalgae were provided directly. Collectively, this study showcased the high potential of brown macroalgae biorefinery using Vibrio sp. dhg., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gyoo Yeol Jung and Hyun Gyu Lim report financial support was provided by Korea Institute of Marine Science & Technology Promotion. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a key molecular scaffold for various flavonoids, naringenin is a value-added chemical with broad pharmaceutical applicability. For efficient production of naringenin from acetate, it is crucial to precisely regulate the carbon flux of the oxaloacetate-phosphoenolpyruvate (OAA-PEP) regulatory node through appropriate pckA expression control, as excessive overexpression of pckA can cause extensive loss of OAA and metabolic imbalance. However, considering the critical impact of pckA on naringenin biosynthesis, the conventional strategy of transcriptional regulation of gene expression is limited in its ability to cover the large and balanced solution space. To overcome this hurdle, in this study, pckA expression was fine-tuned at both the transcriptional and translational levels in a combinatorial expression library for the precise exploration of optimal naringenin production from acetate. Additionally, we identified the effects of regulating pckA expression by validating the correlation between phosphoenolpyruvate kinase (PCK) activity and naringenin production. As a result, the flux-optimized strain exhibited a 49.8-fold increase compared with the unoptimized strain, producing 122.12 mg/L of naringenin. Collectively, this study demonstrated the significance of transcriptional and translational flux rebalancing at the key regulatory node, proposing a pivotal metabolic engineering strategy for the biosynthesis of various flavonoids derived from naringenin using acetate., One-Sentence Summary: In this study, transcriptional and translational regulation of pckA expression at the crucial regulatory node was conducted to optimize naringenin biosynthesis using acetate in E. coli., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society of Industrial Microbiology and Biotechnology.)

A variety of chemicals have been produced through metabolic engineering approaches, and enhancing biosynthesis performance can be achieved by using enzymes with high catalytic efficiency. Accordingly, a number of efforts have been made to discover enzymes in nature for various applications. In addition, enzyme engineering approaches have been attempted to suit specific industrial purposes. However, a significant challenge in enzyme discovery and engineering is the efficient screening of enzymes with the desired phenotype from extensive enzyme libraries. To overcome this bottleneck, genetically encoded biosensors have been developed to specifically detect target molecules produced by enzyme activity at the intracellular level. Especially, the biosensors facilitate high-throughput screening (HTS) of targeted enzymes, expanding enzyme discovery and engineering strategies with advances in systems and synthetic biology. This review examines biosensor-guided HTS systems and highlights studies that have utilized these tools to discover enzymes in diverse areas and engineer enzymes to enhance their properties, such as catalytic efficiency, specificity, and stability., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

As one of the most fundamental physical phenomena, charge density wave (CDW) order predominantly occurs in metallic systems such as quasi-1D metals, doped cuprates, and transition metal dichalcogenides, where it is well understood in terms of Fermi surface nesting and electron-phonon coupling mechanisms. On the other hand, CDW phenomena in semiconducting systems, particularly at the low carrier concentration limit, are less common and feature intricate characteristics, which often necessitate the exploration of novel mechanisms, such as electron-hole coupling or Mott physics, to explain. In this study, an approach combining electrical transport, synchrotron X-ray diffraction, and density-functional theory calculations is used to investigate CDW order and a series of hysteretic phase transitions in a dilute d-band semiconductor, BaTiS 3 . These experimental and theoretical findings suggest that the observed CDW order and phase transitions in BaTiS 3 may be attributed to both electron-phonon coupling and non-negligible electron-electron interactions in the system. This work highlights BaTiS 3 as a unique platform to explore CDW physics and novel electronic phases in the dilute filling limit and opens new opportunities for developing novel electronic devices., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Materials with large birefringence (Δn, where n is the refractive index) are sought after for polarization control (e.g., in wave plates, polarizing beam splitters, etc.), nonlinear optics, micromanipulation, and as a platform for unconventional light-matter coupling, such as hyperbolic phonon polaritons. Layered 2D materials can feature some of the largest optical anisotropy; however, their use in most optical systems is limited because their optical axis is out of the plane of the layers and the layers are weakly attached. This work demonstrates that a bulk crystal with subtle periodic modulations in its structure-Sr 9/8 TiS 3 -is transparent and positive-uniaxial, with extraordinary index n e = 4.5 and ordinary index n o = 2.4 in the mid- to far-infrared. The excess Sr, compared to stoichiometric SrTiS 3 , results in the formation of TiS 6 trigonal-prismatic units that break the chains of face-sharing TiS 6 octahedra in SrTiS 3 into periodic blocks of five TiS 6 octahedral units. The additional electrons introduced by the excess Sr form highly oriented electron clouds, which selectively boost the extraordinary index n e and result in record birefringence (Δn > 2.1 with low loss). The connection between subtle structural modulations and large changes in refractive index suggests new categories of anisotropic materials and also tunable optical materials with large refractive-index modulation., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Brachybacterium species have been identified in various ecological niches and belong to the family Dermabacteriaceae within the phylum Actinobacteria . In this study, we isolated a novel Brachybacterium equifaecis JHP9 strain from horse feces and compared its kinetic, biochemical, and genomic features with those of other Brachybacterium strains. Moreover, comparative genomic analysis using publicly available Brachybacterium genomes was performed to determine the properties involved in their ecological adaptation and metabolic potential. Novel species delineation was determined phylogenetically through 16S rRNA gene similarity (up to 97.9%), average nucleotide identity (79.5-82.5%), average amino acid identity (66.7-75.8%), and in silico DNA-DNA hybridization (23.7-27.9) using closely related strains. This study also presents the first report of the kinetic properties of Brachybacterium species. Most of the Brachybacterium strains displayed high oxygen ( K m(app) =1.6-24.2 µM) and glucose ( K m(app) =0.73-1.22 µM) affinities, which may manifest niche adaptations. Various carbohydrate metabolisms under aerobic and anaerobic conditions, antibiotic resistance, mobile genetic elements, carbohydrate-active enzymes, lactic acid production, and the clustered regularly interspaced short palindromic repeats-Cas and bacteriophage exclusion systems were observed in the genotypic and/or phenotypic properties of Brachybacterium species, suggesting their genome flexibility, defense mechanisms, and adaptability. Our study contributes to the knowledge of the kinetic, physiological, and genomic properties of Brachybacterium species, including the novel JHP9 strain, which advocates for their tolerant and thriving nature in various environments, leading to their ecological adaptation. IMPORTANCE Basic physiological and genomic properties of most of the Brachybacterium isolates have been studied; however, the ability of this bacterium to adapt to diverse environments, which may demonstrate its role in niche differentiation, is to be identified yet. Therefore, here, we explored cellular kinetics, metabolic diversity, and ecological adaptation/defensive properties of the novel Brachybacterium strain through physiological and comparative genomic analysis. In addition, we presented the first report examining Brachybacterium kinetics, indicating that all strains of Brachybacterium , including the novel one, have high oxygen and glucose affinity. Furthermore, the comparative genomic analysis also revealed that the novel bacterium contains versatile genomic properties, which provide the novel bacterium with significant competitive advantages. Thus, in-depth genotypic and phenotypic analysis with kinetic properties at the species level of this genus is beneficial in clarifying its differential characteristics, conferring the ability to inhabit diverse ecological niches.

The anterior interosseous artery (AIA) perforator flap is not commonly used in hand dorsum reconstruction compared with alternatives. However, it is a versatile flap with several advantages. Literature on the AIA perforator flap is based on the dorsal septocutaneous branch (DSB), which branches from the AIA and passes through fascia between the extensor pollicis longus (EPL) and extensor pollicis brevis muscles. In the described case, the authors reconstructed a hand dorsum defect in a 78-year-old man using an AIA perforator flap with double perforators supplied by the DSB and a new perforator branching from the distal than DSB. No complication was encountered, and the flap survived completely. A retrospective computed tomography review revealed the presence of the new perforator in 14 of 21 patients. Two types of new perforator were observed. One passed through the ulnar side of the extensor indicis proprius (EIP) muscle and penetrated fascia between the extensor digitorum minimi and extensor digitorum communis tendons, whereas the other passed between the EPL and EIP muscles. This report describes the anatomical location and clinical application of the new AIA perforators. The double perforators-based AIA flap provides a straightforward, reliable means of reconstructing hand dorsum defects., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Camellia sinensis L. (Theaceae) leaves have been used as a beverage in both Eastern and Western cultures for a long time, while its root has not been intensively studied. In this study, seven undescribed triterpenoid saponins (1-7) and twelve known saponins (8-19) with different combinations of substituents, such as oxygenated isoprenyl substituents and sugar moieties, and lengths of sugar chains, were isolated from the C. sinensis roots. Their structures were unequivocally determined using one- and two-dimensional nuclear magnetic resonance data and acid hydrolysis analysis. Investigation of the biological activities of isolated compounds revealed that only those without functional acetyl groups exhibited cytotoxic activities against mouse and human cancer cells (B16F10) and human cervical cancer cell line (HeLa) at 50 μM. Compounds with an aldehyde group at C-23 of aglycone showed immunomodulatory activity against Th1 and Th17 cells at 10 μM. Ten compounds with biological activities from C. sinensis roots extracts, including three previously undescribed ones (3, 6, and 7), were identified., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

As an alternative to petrochemical synthesis, well-established industrial microbes, such as Escherichia coli , are employed to produce a wide range of chemicals, including dicarboxylic acids (DCAs), which have significant potential in diverse areas including biodegradable polymers. The demand for biodegradable polymers has been steadily rising, prompting the development of efficient production pathways on four- (C4) and five-carbon (C5) DCAs derived from central carbon metabolism to meet the increased demand via the biosynthesis. In this context, E. coli is utilized to produce these DCAs through various metabolic engineering strategies, including the design or selection of metabolic pathways, pathway optimization, and enhancement of catalytic activity. This review aims to highlight the recent advancements in metabolic engineering techniques for the production of C4 and C5 DCAs in E. coli .

Platinum single-atom catalysts hold promise as a new frontier in heterogeneous electrocatalysis. However, the exact chemical nature of active Pt sites is highly elusive, arousing many hypotheses to compensate for the significant discrepancies between experiments and theories. Here, we identify the stabilization of low-coordinated Pt II species on carbon-based Pt single-atom catalysts, which have rarely been found as reaction intermediates of homogeneous Pt II catalysts but have often been proposed as catalytic sites for Pt single-atom catalysts from theory. Advanced online spectroscopic studies reveal multiple identities of Pt II moieties on the single-atom catalysts beyond ideally four-coordinated Pt II -N 4 . Notably, decreasing Pt content to 0.15 wt.% enables the differentiation of low-coordinated Pt II species from the four-coordinated ones, demonstrating their critical role in the chlorine evolution reaction. This study may afford general guidelines for achieving a high electrocatalytic performance of carbon-based single-atom catalysts based on other d 8 metal ions., (© 2023. The Author(s).)

As biomolecules essential for sustaining life, proteins are generated from long chains of 20 different α-amino acids that are folded into unique 3D structures. In particular, many proteins have molecular recognition functions owing to their binding pockets, which have complementary shapes, charges, and polarities for specific targets, making these biopolymers unique and highly valuable for biomedical and biocatalytic applications. Based on the understanding of protein structures and microenvironments, molecular complementarity can be exhibited by synthesizable and modifiable materials. This has prompted researchers to explore the proteomimetic potentials of a diverse range of materials, including biologically available peptides and oligonucleotides, synthetic supramolecules, inorganic molecules, and related coordination networks. To fully resemble a protein, proteomimetic materials perform the molecular recognition to mediate complex molecular functions, such as allosteric regulation, signal transduction, enzymatic reactions, and stimuli-responsive motions; this can also expand the landscape of their potential bio-applications. This review focuses on the recognitive aspects of proteomimetic designs derived for individual materials and their conformations. Recent progress provides insights to help guide the development of advanced protein mimicry with material heterogeneity, design modularity, and tailored functionality. The perspectives and challenges of current proteomimetic designs and tools are also discussed in relation to future applications., (© 2023 Wiley-VCH GmbH.)

Hidradenitis suppurativa (HS) is a chronic inflammatory condition that is difficult to diagnose, with a period of 10.0± 9.6 years from symptom onset to diagnosis. A 32-year-old Asian man presented with bilateral postauricular abscesses that first appeared 5 years previously. Despite several incisions and drainage, the symptoms only temporarily improved and continued to recur. On physical examination, chronic scars and sinus tracts were observed around the lesion. Postauricular HS was diagnosed, and surgical treatment was performed. We performed a wide excision and reconstructed the defect using a posterior auricular artery perforator-based keystone flap. Histological examination confirmed the diagnosis of HS. The reconstruction was successful, and there was no recurrence for 2 years after surgery. HS is difficult to diagnose without specific attention. Although the postauricular region is not a typical site of HS, it can occur in this area. Therefore, if a patient presents with recurrent abscesses in the postauricular region, HS should be considered. Additionally, if HS is diagnosed in the postauricular region, wide excision with reconstruction using a posterior auricular artery perforator-based keystone flap can lead to a favorable outcome.

Natural guanidines, molecules that contain the guanidine moiety, are structurally unique and often exhibit potent biological activities. A phytochemical investigation of the leaves of Alchornea rugosa (Lour.) Müll.Arg. by MS/MS-based molecular networking revealed eight undescribed guanidine-flavanol conjugates named rugonines A-H. The chemical structures of the isolated compounds were comprehensively elucidated by NMR spectroscopy, HRESIMS, and circular dichroism (CD) analysis. All isolated compounds were tested for autophagosome formation in HEK293 cells stably expressing GFP-LC3. The results revealed that compounds rugonines D-G showed potential autophagy inhibitory activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Flavonoids are a group of secondary metabolites from plants that have received attention as high value-added pharmacological substances. Recently, a robust and efficient bioprocess using recombinant microbes has emerged as a promising approach to supply flavonoids. In the flavonoid biosynthetic pathway, the rate of chalcone synthesis, the first committed step, is a major bottleneck. However, chalcone synthase (CHS) engineering was difficult because of high-level conservation and the absence of effective screening tools, which are limited to overexpression or homolog-based combinatorial strategies. Furthermore, it is necessary to precisely regulate the metabolic flux for the optimum availability of malonyl-CoA, a substrate of chalcone synthesis. In this study, we engineered CHS and optimized malonyl-CoA availability to establish a platform strain for naringenin production, a key molecular scaffold for various flavonoids. First, we engineered CHS through synthetic riboswitch-based high-throughput screening of rationally designed mutant libraries. Consequently, the catalytic efficiency (k cat /K m ) of the optimized CHS enzyme was 62% higher than that of the wild-type enzyme. In addition to CHS engineering, we designed genetic circuits using transcriptional repressors to fine-tune the malonyl-CoA availability. The best mutant with synergistic effects of the engineered CHS and the optimized genetic circuit produced 98.71 mg/L naringenin (12.57 mg naringenin/g glycerol), which is the highest naringenin concentration and yield from glycerol in similar culture conditions reported to date, a 2.5-fold increase compared to the parental strain. Overall, this study provides an effective strategy for efficient production of flavonoids., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Rationale: Extramammary Paget's disease (EMPD) is a rare skin cancer that commonly occurs in sites rich in apocrine glands, such as perineum, vulva, axilla, scrotum, and penis. On the other hand, condyloma acuminatum (CA; also referred to as anogenital warts) is a common benign neoplasm caused by human papillomavirus. Few cases of coexistent EMPD and CA have been reported because of the rarity of the condition., Patient Concerns and Diagnosis: A 72-year-old man with a genital mass, which appeared to be composed of multiple papillomatous masses, was referred for surgical resection. The lesion was first noticed 6 months previously and grew rapidly. CO2 ablative laser therapy was performed twice at a primary clinic, but the mass recurred., Intervention and Outcomes: Excisional biopsy revealed the presence of coexistent EMPD and CA. Additional wide excision was performed, and postoperative biopsy confirmed no residual tumor. Two years after surgery, no recurrence had occurred., Lessons: CA can co-occur with several types of skin malignancies, and a skin malignancy coexisting with CA is difficult to diagnose visually. Therefore, even if a skin lesion in the genital region is considered to be CA, we recommend punch biopsy before treatment because it can benefit prognosiss., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Microbial consortia have been considered potential platforms for bioprocessing applications. However, the complexity in process control owing to the use of multiple strains necessitates the use of an efficient population control strategy. Herein, we report circuit-guided synthetic acclimation as a strategy to improve biochemical production by a microbial consortium. We designed a consortium comprising alginate-utilizing Vibrio sp. dhg and 3-hydroxypropionic acid (3-HP)-producing Escherichia coli strains for the direct conversion of alginate to 3-HP. We introduced a genetic circuit, named "Population guider", in the E. coli strain, which degrades ampicillin only when 3-HP is produced. In the presence of ampicillin as a selection pressure, the consortium was successfully acclimated for increased 3-HP production by 4.3-fold compared to that by a simple co-culturing consortium during a 48-h fermentation. We believe this concept is a useful strategy for the development of robust consortium-based bioprocesses., (© 2022. The Author(s).)

The utility of engineering enzyme activity is expanding with the development of biotechnology. Conventional methods have limited applicability as they require high-throughput screening or three-dimensional structures to direct target residues of activity control. An alternative method uses sequence evolution of natural selection. A repertoire of mutations was selected for fine-tuning enzyme activities to adapt to varying environments during the evolution. Here, we devised a strategy called sequence co-evolutionary analysis to control the efficiency of enzyme reactions (SCANEER), which scans the evolution of protein sequences and direct mutation strategy to improve enzyme activity. We hypothesized that amino acid pairs for various enzyme activity were encoded in the evolutionary history of protein sequences, whereas loss-of-function mutations were avoided since those are depleted during the evolution. SCANEER successfully predicted the enzyme activities of beta-lactamase and aminoglycoside 3'-phosphotransferase. SCANEER was further experimentally validated to control the activities of three different enzymes of great interest in chemical production: cis-aconitate decarboxylase, α-ketoglutaric semialdehyde dehydrogenase, and inositol oxygenase. Activity-enhancing mutations that improve substrate-binding affinity or turnover rate were found at sites distal from known active sites or ligand-binding pockets. We provide SCANEER to control desired enzyme activity through a user-friendly webserver., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2022 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

A multifunctional electrolyte additive for lithium oxygen batteries (LOBs) was designed to have (1) a redox-active moiety to mediate decomposition of lithium peroxide (Li 2 O 2 as the final discharge product) during charging and (2) a solvent moiety to solvate and stabilize lithium superoxide (LiO 2 as the intermediate discharge product) in electrolyte during discharging. 4-Acetamido-TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidin-1-yl)oxyl) or AAT was employed as the additive working for both charge and discharge processes ( amphi -active). The redox-active moiety was rooted in TEMPO, while the acetamido (AA) functional group inherited the high donor number (DN) of N , N -dimethylacetamide (DMAc). Integrating two functional moieties (TEMPO and AA) into a single molecule resulted in the bifunctionality of AAT (1) facilitating Li 2 O 2 decomposition by the TEMPO moiety and (2) encouraging the solvent mechanism of Li 2 O 2 formation by the high-DN AA moiety. Significantly improved LOB performances were achieved by the superoxide-solvating charge redox mediator, which were not obtained by a simple cocktail of TEMPO and DMAc.

Physical compartmentalization of metabolism using membranous organelles in eukaryotes is helpful for chemical biosynthesis to ensure the availability of substrates from competitive metabolic reactions. Bacterial hosts lack such a membranous system, which is one of the major limitations for efficient metabolic engineering. Here, we employ kinetic compartmentalization with the introduction of an unnatural enzymatic reaction by an engineered enzyme as an alternative strategy to enable substrate availability from competitive reactions through kinetic isolation of metabolic pathways. As a proof of concept, we kinetically isolate the itaconate synthetic pathway from the tricarboxylic acid cycle in Escherichia coli, which is natively separated by mitochondrial membranes in Aspergillus terreus. Specifically, 2-methylcitrate dehydratase is engineered to alternatively catalyze citrate and kinetically secure cis-aconitate for efficient production using a high-throughput screening system. Itaconate production can be significantly improved with kinetic compartmentalization and its strategy has the potential to be widely applicable., (© 2022. The Author(s).)

Background: Microbial production of naringenin has received much attention owing to its pharmaceutical applicability and potential as a key molecular scaffold for various flavonoids. In the microbial fermentation, a cheap and abundant feedstock is required to achieve an economically feasible bioprocess. From this perspective, utilizing acetate for naringenin production could be an effective strategy, with the advantages of both low-cost and abundant feedstock. For the efficient production of naringenin using acetate, identification of the appropriate regulatory node of carbon flux in the biosynthesis of naringenin from acetate would be important. While acetyl-CoA is a key precursor for naringenin production, carbon flux between the TCA cycle and anaplerosis is effectively regulated at the isocitrate node through glyoxylate shunt in acetate metabolism. Accordingly, appropriate rerouting of TCA cycle intermediates from anaplerosis into naringenin biosynthesis via acetyl-CoA replenishment would be required., Results: This study identified the isocitrate and oxaloacetate (OAA) nodes as key regulatory nodes for the naringenin production using acetate. Precise rerouting at the OAA node for enhanced acetyl-CoA was conducted, avoiding extensive loss of OAA by fine-tuning the expression of pckA (encoding phosphoenolpyruvate carboxykinase) with flux redistribution between naringenin biosynthesis and cell growth at the isocitrate node. Consequently, the flux-optimized strain exhibited a significant increase in naringenin production, a 27.2-fold increase (with a 38.3-fold increase of naringenin yield on acetate) over that by the unoptimized strain, producing 97.02 mg/L naringenin with 21.02 mg naringenin/g acetate, which is a competitive result against those in previous studies on conventional substrates, such as glucose., Conclusions: Collectively, we demonstrated efficient flux rerouting for maximum naringenin production from acetate in E. coli. This study was the first attempt of naringenin production from acetate and suggested the potential of biosynthesis of various flavonoids derived from naringenin using acetate., (© 2022. The Author(s).)

A parallel screening of 27 different flavonoids and chalcones was conducted using 6 artificial naringenin-activated riboswitches (M1, M2, M3, O, L and H). A quantitative structure-property relationship approach was applied to understand the physicochemical properties of the flavonoid structures resulting in specificity differences relied on the fluorescence intensity of a green fluorescent protein reporter. Robust models of riboswitches M1, M2 and O that had good predictive power were constructed with descriptors selected for their high correlation. Increased electronegativity and hydrophilicity of the flavonoids structures were identified as two properties that increased binding affinity to RNA riboswitches. Hydroxyl groups at the C-3' and C-4' positions of the flavonoid molecule were strictly required for ligand-activation with riboswitches M1 and M2. Riboswitches O and L preferred multi-hydroxylated flavones as ligands. Substitutions on the A ring of the flavonoid molecule were not important in the molecular recognition process. O -glycosylated derivatives were not recognized by any of the riboswitches, presumably due to steric hindrances. Despite the challenges of detecting RNA conformational change after ligand binding, the resulting models elucidate important physicochemical features in the ligands for conformational structural studies of artificial aptamer complexes and for design of ligands having higher binding specificity., Competing Interests: We declare that we have no conflicts of interest., (© 2022 The Authors.)

The biogeochemical reactions of dimethylarsinic acid (DMAs(V)) were investigated using simulated wetland systems in a laboratory. DMAs(V) was injected into the wetland water, and the As concentrations in the water, plants, and sediments were monitored. Aqueous and solid-phase As speciation was evaluated, and the results revealed that the DMAs(V) was completely transported to the sediments and plants. X-ray absorption spectroscopic measurement of the As in the sediment revealed that approximately 85-95% of As existed as inorganic As species, demonstrating the important role of microorganisms in the biogeochemical reaction of DMAs(V). The influences of microbes were further investigated in smaller batches under aerobic and anaerobic conditions. The microbial batch results showed that DMAs(V) demethylation reduced the total aqueous As concentration, demonstrating that As(V) has higher affinity to wetland sediment than DMAs(V). The redox conditions were also revealed as an important controlling factor of the As reaction and, under anaerobic conditions, we observed the presence of the most toxic form of inorganic As(III) in the aqueous phase. Although this study reports one example from a specific wetland, the important roles of the redox conditions and microbial influences were identified from the comprehensive analysis of As speciation and mass balance., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

An 88-year-old man presented with a left temporal pulsatile mass that developed after blunt trauma. Based on suspicion of hematoma, needle aspiration was performed with the removal of approximately 15 mL of blood. No evident improvement was noted, and active arterial bleeding was observed at the needle puncture site. Doppler ultrasonography revealed a "yin-yang" sign, and the mass was diagnosed as a pseudoaneurysm of the left superficial temporal artery. Under general anesthesia, the superficial temporal artery was ligated and the pseudoaneurysm was removed. Superficial temporal artery pseudoaneurysm is a rare facial tumor that generally occurs after blunt trauma. Due to its rarity, pseudoaneurysms are often misdiagnosed as hematoma. The treatment of choice is excision, although endovascular intervention is a potential treatment option. However, when a pseudoaneurysm is small, conservative treatment can be used.

Background: Owing to increasing concerns about climate change and the depletion of fossil fuels, the development of efficient microbial processes for biochemical production from lignocellulosic biomass has been a key issue. Because process efficiency is greatly affected by the inherent metabolic activities of host microorganisms, it is essential to utilize a microorganism that can rapidly convert biomass-derived sugars. Here, we report a novel Vibrio-based microbial platform that can rapidly and simultaneously consume three major lignocellulosic sugars (i.e., glucose, xylose, and arabinose) faster than any previously reported microorganisms., Results: The xylose isomerase pathway was constructed in Vibrio sp. dhg, which naturally displays high metabolic activities on glucose and arabinose but lacks xylose catabolism. Subsequent adaptive laboratory evolution significantly improved xylose catabolism of initial strain and led to unprecedently high growth and sugar uptake rate (0.67 h -1 and 2.15 g g dry cell weight -1  h -1 , respectively). Furthermore, we achieved co-consumption of the three sugars by deletion of PtsG and introduction of GalP. We validated its superior performance and applicability by demonstrating efficient lactate production with high productivity (1.15 g/L/h) and titer (83 g/L)., Conclusions: In this study, we developed a Vibrio-based microbial platform with rapid and simultaneous utilization of the three major sugars from lignocellulosic biomass by applying an integrated approach of rational and evolutionary engineering. We believe that the developed strain can be broadly utilized to accelerate the production of diverse biochemicals from lignocellulosic biomass., (© 2022. The Author(s).)