Evolutionary unraveling: new insights into the Persicaria amphibia complex.

The Persicaria amphibia complex exhibits significant morphological variation depending on its habitat, existing in either aquatic or terrestrial forms. Traditionally, four distinct elements have been recognized based on morphological features along with their distinct geographical distributions. Recent studies suggest that the Asian element may be genetically distinct from the European and American elements. However, a comprehensive study on the genetic differentiation among all four elements remains lacking. This study aimed to leverage whole plastid genome sequences and ITS2 haplotypes to comprehensively assess the genomic diversity within the P. amphibia complex. Notably, we included multiple individuals from New York State to resolve the ongoing debate regarding the taxonomic status of two American elements - whether they represent a single species or distinct entities. Our analysis revealed a well-supported monophyletic clade encompassing all four elements, endorsing their own section, Amphibia. Notably, the terrestrial form of the American element is sister to all other elements, suggesting it deserves its own species status. This reinstates its historical name, P. coccinea, separating it from the broader P. amphibia. Furthermore, distinct compositions of the ITS2 haplotypes differentiated the four elements, although the European element should be further investigated with more sampling. The most intriguing discovery is the identification of putative hybrids between the two American elements. In one population out of four putative hybrid populations, all three entities - the two parent species and their hybrid offspring - thrive together, showcasing a fascinating microcosm of ongoing evolutionary processes. Unraveling the intricate genetic tapestry within each American species and their hybrid populations remains a compelling next step. By delving deeper into their genetic makeup, we can gain a richer understanding of their evolutionary trajectories and the intricacies of their interactions. Finally, it is estimated that the two species of sect. Amphibia diverged approximately 4.02 million years ago during the Pliocene epoch, when there was a significant global cooling and drying trend.

Cranial-first approach for laparoscopic extended right hemicolectomy.

Complete mesocolic excision and central vascular ligation with D3 lymphadenectomy are important surgical principles for improving oncological outcomes in colon cancer. The cranial-first approach is a colonic mobilization-first approach to radical right hemicolectomy, which has several advantages, including early feasibility assessment, safe dissection from surrounding organs, preestablished inferior margin of lymph node dissection, and revelation of the tangible anatomy of the tributaries of the gastrocolic trunk. This video demonstrates the cranial-first approach to radical right hemicolectomy in a 66-year-old man with locally advanced cecal cancer.

Efficacy of personalized rTMS to enhance upper limb function in subacute stroke patients: a protocol for a multi-center, randomized controlled study.

Background: Repetitive transcranial magnetic stimulation (rTMS) is widely used therapy to enhance motor deficit in stroke patients. To date, rTMS protocols used in stroke patients are relatively unified. However, as the pathophysiology of stroke is diverse and individual functional deficits are distinctive, more precise application of rTMS is warranted. Therefore, the objective of this study was to determine the effects of personalized protocols of rTMS therapy based on the functional reserve of each stroke patient in subacute phase. Methods: This study will recruit 120 patients with stroke in subacute phase suffering from the upper extremity motor impairment, from five different hospitals in Korea. The participants will be allocated into three different study conditions based on the functional reserve of each participant, measured by the results of TMS-induced motor evoked potentials (MEPs), and brain MRI with diffusion tensor imaging (DTI) evaluations. The participants of the intervention-group in the three study conditions will receive different protocols of rTMS intervention, a total of 10 sessions for 2 weeks: high-frequency rTMS on ipsilesional primary motor cortex (M1), high-frequency rTMS on ipsilesional ventral premotor cortex, and high-frequency rTMS on contralesional M1. The participants of the control-group in all three study conditions will receive the same rTMS protocol: low-frequency rTMS on contralesional M1. For outcome measures, the following assessments will be performed at baseline (T0), during-intervention (T1), post-intervention (T2), and follow-up (T3) periods: Fugl-Meyer Assessment (FMA), Box-and-block test, Action Research Arm Test, Jebsen-Taylor hand function test, hand grip strength, Functional Ambulatory Category, fractional anisotropy measured by the DTI, and brain network connectivity obtained from MRI. The primary outcome will be the difference of upper limb function, as measured by FMA from T0 to T2. The secondary outcomes will be the differences of other assessments. Discussion: This study will determine the effects of applying different protocols of rTMS therapy based on the functional reserve of each patient. In addition, this methodology may prove to be more efficient than conventional rTMS protocols. Therefore, effective personalized application of rTMS to stroke patients can be achieved based on their severity, predicted mechanism of motor recovery, or functional reserves. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT06270238.

PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals.

Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγnull) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.

PAR2-mediated cellular senescence promotes inflammation and fibrosis in aging and chronic kidney disease.

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2-mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2-deficient kidneys are protected from adenine- and cisplatin-induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury.

An Exercise Prescription for Patients with Stroke and Sarcopenia Based on the Modified Delphi Study.

BACKGROUND: We aimed to develop a consensus on the need for and priorities of exercise to treat preexisting sarcopenia with hemiplegic stroke. METHODS: A modified three-round Delphi study was conducted. The panelists responded to the questionnaire on a 7-point Likert scale. Responses were returned with descriptive statistics in the next round. Consensus was defined as >75% agreement (score of 5-7) with a median > 5. The percentage of strong agreement (score of 6-7) and Kendall's coefficient of concordance were calculated to demonstrate a more refined interpretation of the consensus. RESULTS: Fifteen panelists contributed to all rounds. The need for exercise was demonstrated. The consensus was reached on 53 of 58 items in the first round and all items in the second and final rounds. The percentage of strong agreement was high for all but eight items. CONCLUSIONS: This study is the first Delphi study to investigate the need for and priorities of exercise for treating preexisting sarcopenia in stroke hemiplegia. We present a standard recommendation including 57 priorities and a strong recommendation including 49 priorities. The eight items that were excluded reflected factors that are less important to hemiplegic patients with poor balance, cognitive decline, or mental vulnerability.

Physiological and Molecular Modulations to Drought Stress in the Brassica Species.

Climate change, particularly drought stress, significantly impacts plant growth and development, necessitating the development of resilient crops. This study investigated physiological and molecular modulations to drought stress between diploid parent species and their polyploid progeny in the Brassica species. While no significant phenotypic differences were observed among the six species, drought stress reduced growth parameters by 2.4% and increased oxidative stress markers by 1.4-fold. Drought also triggered the expression of genes related to stress responses and led to the accumulation of specific metabolites. We also conducted the first study of perfluorooctane sulfonic acid (PFOS) levels in leaves as a drought indicator. Lower levels of PFOS accumulation were linked to plants taking in less water under drought conditions. Both diploid and polyploid species responded to drought stress similarly, but there was a wide range of variation in their responses. In particular, responses were less variable in polyploid species than in diploid species. This suggests that their additional genomic components acquired through polyploidy may improve their flexibility to modulate stress responses. Despite the hybrid vigor common in polyploid species, Brassica polyploids demonstrated intermediate responses to drought stress. Overall, this study lays the framework for future omics-level research, including transcriptome and proteomic studies, to deepen our understanding of drought tolerance mechanisms in Brassica species.

Chaenomelin, a New Phenolic Glycoside, and Anti-Helicobacter pylori Phenolic Compounds from the Leaves of Salix chaenomeloides.

Salix chaenomeloides Kimura, commonly known as pussy willow, is a deciduous shrub and tree belonging to the Salicaceae family. The genus Salix spp. has been known as a healing herb for the treatment of fever, inflammation, and pain relief. The current study aimed to investigate the potential bioactive natural products from S. chaenomeloides leaves and evaluate their antibacterial activity against Helicobacter pylori. A phytochemical investigation of the ethanol (EtOH) extract of S. chaenomeloides leaves led to the isolation of 13 phenolic compounds (1-13) from the ethyl acetate (EtOAc) fraction, which showed antibacterial activity against H. pylori strain 51. The chemical structure of a new phenolic glycoside, chaenomelin (1), was established by a detailed analysis of 1D and 2D (1H-1H correlation spectroscopy (COSY), heteronuclear single-quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC)) nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), and chemical reactions. The other known compounds were identified as 5-O-trans-p-coumaroyl quinic acid methyl ester (2), tremulacin (3), citrusin C (4), benzyl 3-O-ß-d-glucopyranosyl-7-hydroxybenzoate (5), tremuloidin (6), 1-[O-ß-d-glucopyranosyl(1→2)-ß-d-glucopyranosyl]oxy-2-phenol (7), arbutin cinnamate (8), tremulacinol (9), catechol (10), 4-hydroxybenzaldehyde (11), kaempferol 3-rutinoside (12), and narcissin (13), based on the comparison of their NMR spectra with the reported data and liquid chromatography/mass spectrometry (LC/MS) analysis. The isolated compounds were evaluated for antibacterial activity against H. pylori strain 51. Among the isolates, 1-[O-ß-d-glucopyranosyl(1→2)-ß-d-glucopyranosyl]oxy-2-phenol (7) and arbutin cinnamate (8) exhibited antibacterial activity against H. pylori strain 51, with inhibitions of 31.4% and 33.9%, respectively, at a final concentration of 100 µM. These results were comparable to that of quercetin (38.4% inhibition), which served as a positive control. Generally, these findings highlight the potential of the active compounds 7 and 8 as antibacterial agents against H. pylori.

Systemic reserve dysfunction and contrast-associated acute kidney injury following percutaneous coronary intervention.

BACKGROUND: Developing contrast-associated acute kidney injury (CA-AKI) following percutaneous coronary intervention (PCI) is closely related to patient-related risk factors as well as contrast administration. The diagnostic and prognostic roles of neutrophil gelatinase-associated lipocalin (NGAL) in CA-AKI following PCI are not well established. METHODS: Consecutive patients undergoing PCI were enrolled prospectively. CA-AKI was defined as an increase in the serum creatinine level ≥0.3 mg/dL within 48 hours or ≥1.5 times the baseline within 7 days after PCI. Serum NGAL concentrations were determined immediately before and 6 hours after PCI. The participants were classified into four NGAL groups according to the pre- and post-PCI NGAL values at 75th percentile. RESULTS: CA-AKI occurred in 38 (6.4%) of 590 patients. With chronic kidney disease status (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.06-2.52), NGAL groups defined by the combination of pre- and 6 h post-PCI values were independently associated with the occurrence of CA-AKI (HR 1.69, 95% CI: 1.16-2.45). All-cause mortality for 29-month follow-ups was different among NGAL groups (log-rank p<0.001). Pre-PCI NGAL levels significantly correlated with baseline cardiac, inflammatory, and renal markers. Although post-PCI NGAL levels increased in patients with larger contrast administration, contrast media made a relatively limited contribution to the development of CA-AKI. CONCLUSION: In patients undergoing PCI, the combination of pre- and post-PCI NGAL values may be a useful adjunct to current risk-stratification of CA-AKI and long-term mortality. CA-AKI is likely caused by systemic reserve deficiency rather than contrast administration itself.

The pathophysiology of visceral adipose tissues in cardiometabolic diseases.

Central pattern of fat distribution, especially fat accumulation within the intraabdominal cavity increases risks for cardiometabolic diseases. Portal hypothesis combined with a pathological remodeling in visceral fat is considered the major etiological factor explaining the independent contribution of visceral obesity to cardiometabolic diseases. Excessive remodeling in visceral fat during development of obesity leads to dysfunctions in the depot, characterized by hypertrophy and death of adipocytes, hypoxia, inflammation, and fibrosis. Dysfunctional visceral fat secretes elevated levels of fatty acids, glycerol, and proinflammatory and profibrotic cytokines into the portal vein directly impacting the liver, the central regulator of systemic metabolism. These metabolic and endocrine products induce ectopic fat accumulation, insulin resistance, inflammation, and fibrosis in the liver, which in turn causes or exacerbates systemic metabolic derangements. Elucidation of underlying mechanisms that lead to the pathological remodeling and higher degree of dysfunctions in visceral adipose tissue is therefore, critical for the development of therapeutics to prevent deleterious sequelae in obesity. We review depot differences in metabolic and endocrine properties and expendabilities as well as underlying mechanisms that contribute to the pathophysiological aspects of visceral adiposity in cardiometabolic diseases. We also discuss impacts of different weight loss interventions on visceral adiposity and cardiometabolic diseases.

Cloning and Expression Analysis of Bioluminescence Genes in Omphalotus guepiniiformis Reveal Stress-Dependent Regulation of Bioluminescence.

Bioluminescence is a type of chemiluminescence that arises from a luciferase-catalyzed oxidation reaction of luciferin. Molecular biology and comparative genomics have recently elucidated the genes involved in fungal bioluminescence and the evolutionary history of their clusters. However, most studies on fungal bioluminescence have been limited to observing the changes in light intensity under various conditions. To understand the molecular basis of bioluminescent responses in Omphalotus guepiniiformis under different environmental conditions, we cloned and sequenced the genes of hispidin synthase, hispidin-3-hydroxylase, and luciferase enzymes, which are pivotal in the fungal bioluminescence pathway. Each gene showed high sequence similarity to that of other luminous fungal species. Furthermore, we investigated their transcriptional changes in response to abiotic stresses. Wound stress enhanced the bioluminescence intensity by increasing the expression of bioluminescence pathway genes, while temperature stress suppressed the bioluminescence intensity via the non-transcriptional pathway. Our data suggested that O. guepiniiformis regulates bioluminescence to respond differentially to specific environmental stresses. To our knowledge, this is the first study on fungal bioluminescence at the gene expression level. Further studies are required to address the biological and ecological meaning of different bioluminescence responses in changing environments, and O. quepiniiformis could be a potential model species.

Comparison of the stress distribution in base materials and thicknesses in composite resin restorations.

Resin-based composite materials are commonly used for restorations, but their dimensional changes during the polymerization could cause various clinical problems. This study evaluated the influence of a base of different materials and thicknesses on the stress magnitude and distribution in a second maxillary premolar with an MOD resin composite restoration using three-dimensional finite element analysis. A sound tooth without cavity was considered as the control group (ST), and another group was restored with composite resin without applying a base material in a MOD cavity (CR). The other three groups were restored with composite resin along with the following base materials: glass ionomer cement, low-viscosity resin, and tricalcium silicate, respectively (CR-GIC, CR-LR, and CR-TS). These three groups were further divided into two subgroups according to the thickness of the base layer: thin (0.5 mm) and thick (1.0 mm). The stress distribution was compared using the maximum principal stress after polymerization shrinkage and vertical loading with 600 N on the occlusal surface. Group ST showed the lowest stress value, and its stress propagation was confined to outer enamel surfaces only. Group CR demonstrated the highest stress distribution in the tooth-restoration interface with increased failure risk on marginal areas. The thin and thick subgroups of the three groups with a base layer had lower stress levels than Group CR. The base materials reduced the marginal stress caused by polymerization shrinkage of composite resin in MOD cavities. Different base materials and thicknesses did not affect the stress distribution.

Electric field simulation and appropriate electrode positioning for optimized transcranial direct current stimulation of stroke patients: an in Silico model.

Transcranial Direct Current Stimulation (tDCS) has benefits for motor rehabilitation in stroke patients, but its clinical application is limited due to inter-individual heterogeneous effects. Recently, optimized tDCS that considers individual brain structure has been proposed, but the utility thereof has not been studied in detail. We explored whether optimized tDCS provides unique electrode positions for each patient and creates a higher target electric field than the conventional approach. A comparative within-subject simulation study was conducted using data collected for a randomized controlled study evaluating the effect of optimized tDCS on upper extremity function in stroke patients. Using Neurophet tES LAB 3.0 software, individual brain models were created based on magnetic resonance images and tDCS simulations were performed for each of the conventional and optimized configurations. A comparison of electrode positions between conventional tDCS and optimized tDCS was quantified by calculation of Euclidean distances. A total of 21 stroke patients were studied. Optimized tDCS produced a higher electric field in the hand motor region than conventional tDCS, with an average improvement of 20% and a maximum of 52%. The electrode montage for optimized tDCS was unique to each patient and exhibited various configurations that differed from electrode placement of conventional tDCS. Optimized tDCS afforded a higher electric field in the target of a stroke patient compared to conventional tDCS, which was made possible by appropriately positioning the electrodes. Our findings may encourage further trials on optimized tDCS for motor rehabilitation after stroke.

Flavivirga spongiicola sp. nov. and Flavivirga abyssicola sp. nov., Isolated from Marine Environments.

Two novel Gram-stain-negative, strictly-aerobic, rod-shaped (1.2 ± 3.4 µm × 0.3 ± 0.7 µm), and non-motile marine bacterial species, designated MEBiC05379T and MEBiC07777T, were isolated from a marine sponge Pseudaxinella sp. in Gangneung City and deep-sea sediments of the Ulleung basin in the East Sea of Korea, respectively. The 16S rRNA gene sequence analysis revealed high levels of similarities between these strains and members of the genus Flavivirga (97.0-98.4% sequence identities). Both novel strains revealed as mesophilic, neutrophilic in pH and slightly halophilic. Similar to those of other Flavivirga members, the primary cellular fatty acids of both strains were iso-C15:0, iso-C15:1 G, iso-C15:03-OH, and iso-C17:0 3-OH, with MEBiC05379T and MEBiC07777T containing relatively higher proportions of C12:0 and summed feature 3 (C16:1ω7c and/or C16:1ω6c). In both taxa, the major isoprenoid quinone was MK-6. The DNA G + C contents of MEBiC05379T and MEBiC07777T genomes were 32.62 and 32.46 mol%, respectively. Compared to other members of Flavivirga, both strains exhibited similar DNA G + C ratio and fatty acids pattern, yet enzyme expression and carbon sources utilization pattern were different. Genomes of the genus Flavivirga showed enzyme preferences to fucoidan and sulfated galactans. Considering the monophyly rule, AAI values delineate the genus Flavivirga from adjacent genera calculated to be 76.0-78.7%. Based on the phenotypic, genomic and biochemical data, strains for MEBiC05379T and MEBiC07777T thus represent two novel species in the genus Flavivirga, for which the names Flavivirga spongiicola sp. nov. (MEBiC05379T [= KCTC 92527 T = JCM 16662 T]), and Flavivirga abyssicola sp. nov. (MEBiC07777T [= KCTC 92563 T = JCM 36477 T]) are proposed.

Metabolic and structural remodeling during browning of primary human adipocytes derived from omental and subcutaneous depots.

OBJECTIVE: This study investigated remodeling of cellular metabolism and structures during browning of primary human adipocytes derived from both visceral and subcutaneous adipose tissues. Effects of glucocorticoids on the browning were also assessed. METHODS: Differentiated omental and subcutaneous human adipocytes were treated with rosiglitazone, with or without dexamethasone, and expression levels of brite adipocyte markers, lipolysis, and lipid droplet and mitochondrial structures were examined. RESULTS: Both omental and subcutaneous adipocytes acquired brite phenotypes upon peroxisome proliferator-activated receptor-γ agonist treatment, and dexamethasone tended to enhance the remodeling. Although rosiglitazone increased lipolysis during treatment, brite adipocytes exhibited lower basal lipolytic rates and enhanced responses to ß-adrenergic agonists or atrial natriuretic peptide. Transcriptome analysis identified induction of both breakdown and biosynthesis of lipids in brite adipocytes. After 60+ days in culture, lipid droplet size increased to ~50 microns, becoming almost unilocular in control adipocytes, and after browning, they acquired paucilocular morphology, clusters of small lipid droplets (1-2 micron) surrounded by mitochondria appearing on the periphery of the central large one. CONCLUSIONS: Metabolic and structural remodeling during browning of primary human adipocytes is similar to previous findings in human adipocytes in vivo, supporting their uses for mechanical studies investigating browning with translational relevance.

Investigation of regulatory divergence between homoeologs in the recently formed allopolyploids, Tragopogon mirus and T. miscellus (Asteraceae).

Polyploidy is an important evolutionary process throughout eukaryotes, particularly in flowering plants. Duplicated gene pairs (homoeologs) in allopolyploids provide additional genetic resources for changes in molecular, biochemical, and physiological mechanisms that result in evolutionary novelty. Therefore, understanding how divergent genomes and their regulatory networks reconcile is vital for unraveling the role of polyploidy in plant evolution. Here, we compared the leaf transcriptomes of recently formed natural allotetraploids (Tragopogon mirus and T. miscellus) and their diploid parents (T. porrifolius X T. dubius and T. pratensis X T. dubius, respectively). Analysis of 35 400 expressed loci showed a significantly higher level of transcriptomic additivity compared to old polyploids; only 22% were non-additively expressed in the polyploids, with 5.9% exhibiting transgressive expression (lower or higher expression in the polyploids than in the diploid parents). Among approximately 7400 common orthologous regions (COREs), most loci in both allopolyploids exhibited expression patterns that were vertically inherited from their diploid parents. However, 18% and 20.3% of the loci showed novel expression bias patterns in T. mirus and T. miscellus, respectively. The expression changes of 1500 COREs were explained by cis-regulatory divergence (the condition in which the two parental subgenomes do not interact) between the diploid parents, whereas only about 423 and 461 of the gene expression changes represent trans-effects (the two parental subgenomes interact) in T. mirus and T. miscellus, respectively. The low degree of both non-additivity and trans-effects on gene expression may present the ongoing evolutionary processes of the newly formed Tragopogon polyploids (~80-90 years).

Genomic potential and physiological characteristics of C1 metabolism in novel acetogenic bacteria.

Acetogenic bacteria can utilize C1 compounds, such as carbon monoxide (CO), formate, and methanol, via the Wood-Ljungdahl pathway (WLP) to produce biofuels and biochemicals. Two novel acetogenic bacteria of the family Eubacteriaceae ES2 and ES3 were isolated from Eulsukdo, a delta island in South Korea. We conducted whole genome sequencing of the ES strains and comparative genome analysis on the core clusters of WLP with Acetobacterium woodii DSM1030T and Eubacterium limosum ATCC8486T. The methyl-branch cluster included a formate transporter and duplicates or triplicates copies of the fhs gene, which encodes formyl-tetrahydrofolate synthetase. The formate dehydrogenase cluster did not include the hydrogenase gene, which might be replaced by a functional complex with a separate electron bifurcating hydrogenase (HytABCDE). Additionally, duplicated copies of the acsB gene, encoding acetyl-CoA synthase, are located within or close to the carbonyl-branch cluster. The serum bottle culture showed that ES strains can utilize a diverse range of C1 compounds, including CO, formate, and methanol, as well as CO2. Notably, ES2 exhibited remarkable resistance to high concentrations of C1 substrates, such as 100% CO (200 kPa), 700 mM formate, and 500 mM methanol. Moreover, ES2 demonstrated remarkable growth rates under 50% CO (0.45 h-1) and 200 mM formate (0.34 h-1). These growth rates are comparable to or surpassing those previously reported in other acetogenic bacteria. Our study introduces novel acetogenic ES strains and describes their genetic and physiological characteristics, which can be utilized in C1-based biomanufacturing.

Thiobarbiturate-Derived Compound MHY1025 Alleviates Renal Fibrosis by Modulating Oxidative Stress, Epithelial Inflammation, and Fibroblast Activation.

Chronic kidney disease (CKD) is a kidney structure and function abnormality. CKD development and progression are strongly influenced by oxidative stress and inflammatory responses, which can lead to tubulointerstitial fibrosis. Unfortunately, there are no effective or specific treatments for CKD. We investigated the potential of the thiobarbiturate-derived compound MHY1025 to alleviate CKD by reducing oxidative stress and inflammatory responses. In vitro experiments using NRK52E renal tubular epithelial cells revealed that MHY1025 significantly reduced LPS-induced oxidative stress and inhibited the activation of the NF-κB pathway, which is involved in inflammatory responses. Furthermore, treatment with MHY1025 significantly suppressed the expression of fibrosis-related genes and proteins induced by TGFß in NRK49F fibroblasts. Furthermore, we analyzed the MHY1025 effects in vivo. To induce kidney fibrosis, mice were administered 250 mg/kg folic acid (FA) and orally treated with MHY1025 (0.5 mg/kg/day) for one week. MHY1025 effectively decreased the FA-induced inflammatory response in the kidneys. The group treated with MHY1025 exhibited a significant reduction in cytokine and chemokine expression and decreased immune cell marker expression. Decreased inflammatory response was associated with decreased tubulointerstitial fibrosis. Overall, MHY1025 alleviated renal fibrosis by directly modulating renal epithelial inflammation and fibroblast activation, suggesting that MHY1025 has the potential to be a therapeutic agent for CKD.