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Body-centred cubic refractory multi-principal element alloys (MPEAs), with several refractory metal elements as constituents and featuring a yield strength greater than one gigapascal, are promising materials to meet the demands of aggressive structural applications1-6. Their low-to-no tensile ductility at room temperature, however, limits their processability and scaled-up application7-10. Here we present a HfNbTiVAl10 alloy that shows remarkable tensile ductility (roughly 20%) and ultrahigh yield strength (roughly 1,390 megapascals). Notably, these are among the best synergies compared with other related alloys. Such superb synergies derive from the addition of aluminium to the HfNbTiV alloy, resulting in a negative mixing enthalpy solid solution, which promotes strength and favours the formation of hierarchical chemical fluctuations (HCFs). The HCFs span many length scales, ranging from submicrometre to atomic scale, and create a high density of diffusive boundaries that act as effective barriers for dislocation motion. Consequently, versatile dislocation configurations are sequentially stimulated, enabling the alloy to accommodate plastic deformation while fostering substantial interactions that give rise to two unusual strain-hardening rate upturns. Thus, plastic instability is significantly delayed, which expands the plastic regime as ultralarge tensile ductility. This study provides valuable insights into achieving a synergistic combination of ultrahigh strength and large tensile ductility in MPEAs.
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Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.
Assuntos
Proteínas de Bactérias , Malatos , Proteínas Quimiotáticas Aceptoras de Metil/química , Proteínas de Bactérias/metabolismo , Ligantes , Escherichia coli/metabolismo , Quimiotaxia/fisiologia , Bactérias/metabolismo , CitratosRESUMO
Glioma is the most prevalent malignant brain tumour. Currently, reshaping its tumour microenvironment has emerged as an appealing strategy to enhance therapeutic efficacy. As the largest group of transmembrane transport proteins, solute carrier proteins (SLCs) are responsible for the transmembrane transport of various metabolites and ions. They play a crucial role in regulating the metabolism and functions of malignant cells and immune cells within the tumour microenvironment, making them a promising target in cancer therapy. Through multidimensional data analysis and experimental validation, we investigated the genetic landscape of SLCs in glioma. We established a classification system comprising 7-SLCs to predict the prognosis of glioma patients and their potential responses to immunotherapy and chemotherapy. Our findings unveiled specific SLC expression patterns and their correlation with the immune-suppressive microenvironment and metabolic status. The 7-SLC classification system was validated in distinguishing subgroups within the microenvironment, specifically identifying subsets involving malignant cells and tumour-associated macrophages. Furthermore, the orphan protein SLC43A3, a core member of the 7-SLC classification system, was identified as a key facilitator of tumour cell proliferation and migration, suggesting its potential as a novel target for cancer therapy.
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Neoplasias Encefálicas , Regulação Neoplásica da Expressão Gênica , Glioma , Proteínas Carreadoras de Solutos , Microambiente Tumoral , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Humanos , Glioma/genética , Glioma/imunologia , Glioma/patologia , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Proteínas Carreadoras de Solutos/genética , Proteínas Carreadoras de Solutos/metabolismo , Prognóstico , Proliferação de Células/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , MultiômicaRESUMO
The small molecule epiberberine (EPI) is a natural alkaloid with versatile bioactivities against several diseases including cancer and bacterial infection. EPI can induce the formation of a unique binding pocket at the 5' side of a human telomeric G-quadruplex (HTG) sequence with four telomeric repeats (Q4), resulting in a nanomolar binding affinity (KD approximately 26 nM) with significant fluorescence enhancement upon binding. It is important to understand (1) how EPI binding affects HTG structural stability and (2) how enhanced EPI binding may be achieved through the engineering of the DNA binding pocket. In this work, the EPI-binding-induced HTG structure stabilization effect was probed by a peptide nucleic acid (PNA) invasion assay in combination with a series of biophysical techniques. We show that the PNA invasion-based method may be useful for the characterization of compounds binding to DNA (and RNA) structures under physiological conditions without the need to vary the solution temperature or buffer components, which are typically needed for structural stability characterization. Importantly, the combination of theoretical modeling and experimental quantification allows us to successfully engineer Q4 derivative Q4-ds-A by a simple extension of a duplex structure to Q4 at the 5' end. Q4-ds-A is an excellent EPI binder with a KD of 8 nM, with the binding enhancement achieved through the preformation of a binding pocket and a reduced dissociation rate. The tight binding of Q4 and Q4-ds-A with EPI allows us to develop a novel magnetic bead-based affinity purification system to effectively extract EPI from Rhizoma coptidis (Huang Lian) extracts.
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Berberina , Quadruplex G , Berberina/química , Berberina/análogos & derivados , Berberina/farmacologia , Humanos , DNA/química , Ácidos Nucleicos Peptídicos/químicaRESUMO
OBJECTIVE: This study aimed to explore the specific function of M2 macrophages in intervertebral disc degeneration (IDD). METHODS: Intervertebral disc (IVD) samples from normal (n = 4) and IDD (n = 6) patients were collected, and the expression of M2-polarized macrophage marker, CD206, was investigated using immunohistochemical staining. Nucleus pulposus cells (NPCs) in a TNF-α environment were obtained, and a mouse caudal IVD puncture model was established. Mice with Rheb deletions, specifically in the myeloid lineage, were generated and subjected to surgery-induced IDD. IDD-induced damage and cell apoptosis were measured using histological scoring, X-ray imaging, immunohistochemical staining, and TdT-mediated dUTP nick end labeling (TUNEL) assay. Finally, mice and NPCs were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in IDD. RESULTS: Accumulation of CD206 in human and mouse IDD tissues was detected. Rheb deletion in the myeloid lineage (RheBcKO) increased the number of CD206+ M2-like macrophages (mean difference 18.6% [15.7-21.6%], P < 0.001), decreased cell apoptosis (mean difference -15.6% [-8.9 to 22.2%], P = 0.001) and attenuated the IDD process in the mouse IDD model. NPCs treated with Rspo2 displayed increased extracellular matrix catabolism and apoptosis; co-culture with a conditioned medium derived from RheBcKO mice inhibited these changes. Anti-Rspo2 treatment in the mouse caudal IVD puncture model exerted protective effects against IDD. CONCLUSIONS: Promoting CD206+ M2-like macrophages could reduce Rspo2 secretion, thereby alleviating experimental IDD. Rheb deletion may help M2-polarized macrophages accumulate and attenuate experimental IDD partially by inhibiting Rspo2 production. Hence, M2-polarized macrophages and Rspo2 may serve as therapeutic targets for IDD.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Camundongos , Animais , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Apoptose , Modelos Animais de Doenças , Macrófagos/metabolismoRESUMO
Shoot branching from axillary bud (AB) directly determines plant architecture. However, the mechanism through which AB remains dormant or emerges to form branches as plants grow remains largely unknown. Here, the auxin-strigolactone (IAA-SL) pathway was first shown to regulate shoot branching in poplar, and we found that PagKNAT2/6b could modulate this pathway. PagKNAT2/6b was expressed mainly in the shoot apical meristem and AB and was induced by shoot apex damage. PagKNAT2/6b overexpressing poplar plants (PagKNAT2/6b OE) exhibited multiple branches that mimicked the branching phenotype of nontransgenic plants after decapitation treatment, while compared with nontransgenic controls, PagKNAT2/6b antisense transgenic poplar and Pagknat2/6b mutant lines exhibited a significantly decreased number of branches after shoot apex damage treatment. In addition, we found that PagKNAT2/6b directly inhibits the expression of the key IAA synthesis gene PagYUC6a, which is specifically expressed in the shoot apex. Moreover, overexpression of PagYUC6a in the PagKNAT2/6b OE background reduced the number of branches after shoot apex damage treatment. Overall, we conclude that PagKNAT2/6b responds to shoot apical injury and regulates shoot branching through the IAA-SL pathway. These findings may provide a theoretical basis and candidate genes for genetic engineering to create new forest tree species with different crown types.
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Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.
Assuntos
Acetatos , Curcuma , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas , Tolerância ao Sal , Terpenos , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Tolerância ao Sal/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Terpenos/metabolismo , Acetatos/farmacologia , Acetatos/metabolismo , Curcuma/metabolismo , Curcuma/genética , Plantas Geneticamente Modificadas , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacosRESUMO
In contrast to the current athermal map's lack of intuitiveness, we introduce a novel composite athermal map to visually evaluate the potential of lens system glass materials in achieving athermal and achromatic designs. Furthermore, unlike graphically manual methods for athermalization, we propose an automatic method to athermalize the optical system by glass selection using simulated annealing with memory augmentation (GlaSAM). This method employs a comprehensive objective function that integrates thermal aberration, chromatic aberration, secondary spectrum aberration, and Petzval curvature aberration. Weight factors are introduced to evaluate each aberration in the function, and filters are applied to streamline the search space. Additionally, the augmentation of memory into the optimization algorithm not only enhances its efficiency but also safeguards against overlooking solutions with superior imaging quality. To test the advantage of the GlaSAM method, a complex telephoto design is optimized to function across a temperature range from -40°C to 70°C, and the results demonstrate the efficacy of athermalizing the lens system while preserving exceptional imaging performance through this proposed method.
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BACKGROUND: The binary diagnosis of Metabolic Syndrome(MetS) fails to accurately evaluate its severity, and the association between MetS severity and frailty progression remains inadequately elucidated. This study aims to clarify the relationship between the severity of MetS and the progression of frailty among the middle-aged and elderly population in China. METHOD: Participants from the 2011-2018 China Health and Retirement Longitudinal Study(CHARLS) were included for a longitudinal analysis. The study employs a frailty index(FI) based on 32 health deficits to diagnose frailty and to assess FI trajectories. An age-sex-ethnicity-specific MetS scoring model (MetS score) was used to assess metabolic syndrome severity in Chinese adults. The Cumulative MetS score from 2012 to 2015 was calculated using the formula: (MetS score in wave 1 + MetS score in wave 3) / 2 × time(2015 - 2012). The association between MetS score, Cumulative MetS score, and the risk and trajectory of frailty were evaluated using Cox regression/logistic regression, and linear mixed models. Restricted Cubic Splines(RCS) models were utilized to detect potential non-linear associations. RESULTS: A higher MetS score was significantly associated with an increased risk of frailty(HR per 1 SD increase = 1.205; 95%CI: 1.14 to 1.273) and an accelerated FI trajectory(ß per 1 SD increase = 0.113 per year; 95%CI: 0.075 to 0.15 per year). Evaluating changes in MetS score using a Cumulative MetS score indicated that each 1 SD increase in the Cumulative MetS score increased the risk of frailty by 22.2%(OR = 1.222; 95%CI: 1.133 to 1.319) and accelerated the rate of increase in FI(ß = 0.098 per year; 95%CI: 0.058 to 0.138 per year). RCS model results demonstrated a dose-response curve relationship between MetS score and Cumulative MetS score with frailty risk. Stratified analysis showed consistency across subgroups. The interaction results indicate that in males and individuals under aged 60, MetS score may accelerate the increase in FI, a finding consistent across both models. CONCLUSIONS: Our findings underscore the positive correlation between the severity of MetS and frailty progression in the middle-aged and elderly, highlighting the urgent need for early identification of MetS and targeted interventions to reduce the risk of frailty.
Assuntos
Progressão da Doença , Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Síndrome Metabólica , Índice de Gravidade de Doença , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Masculino , Feminino , Estudos Longitudinais , China/epidemiologia , Idoso , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores Etários , Fatores de Tempo , Idoso de 80 Anos ou mais , Prognóstico , População do Leste AsiáticoRESUMO
KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.
Assuntos
Mapeamento Cromossômico , Cromossomos de Plantas , Haplótipos , Fenótipo , Locos de Características Quantitativas , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Mapeamento Cromossômico/métodos , Marcadores Genéticos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Sementes/genética , Melhoramento Vegetal , Alelos , Genes de PlantasRESUMO
A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15â:â0 and anteiso-C15â:â0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).
Assuntos
Bactérias , Ácido Succínico , Anaerobiose , Filogenia , Succinatos , DNARESUMO
Four lactic acid bacteria, designated F690T, F697, F790T and F769-2, were isolated from the gut of honeybee (Apis mellifera). Results of 16S rRNA gene sequence analysis indicated that strains F690T and F697 were phylogenetically related to the type strains of Lactobacillus kimbladii, Lactobacillus laiwuensis, Lactobacillus kullabergensis and Lactobacillus huangpiensis, having 99.1-99.6â% 16S rRNA gene sequence similarities; and that strains F790T and F769-2 were most closely related to the type strain of Lactobacillus melliventris, having 99.2-99.3â% 16S rRNA gene sequence similarities. The phylogenies based on concatenated pheS, rpoA, gyrB, hsp60, recA, rpoB and tuf sequences and based on whole genome sequences were identical to that based on 16S rRNA gene sequences. Strains F690T and F697 exhibited the highest average nucleotide identity (ANI; 92.1-93.2â%), digital DNA-DNA hybridization (dDDH; 50-50.1â%) and average amino acid identity (AAI; 94.9-95.1â%) values with L. kimbladii Hma2NT. Strains F790T and F769-2 had the highest ANI (93.1-94â%), dDDH (54.4â%) and AAI (94.4-94.7â%) values with L. melliventris Hma8NT. Based upon the data obtained in the present study, two novel species, Lactobacillus juensis sp. nov. and Lactobacillus rizhaonensis sp. nov., are proposed and the type strains are F690T (=JCM 36259T=CCTCC AB 2023131T) and F790T (=JCM 36260T=CCTCC AB 2023132T), respectively.
Assuntos
Alimentos Fermentados , Genes Bacterianos , Abelhas , Animais , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Filogenia , Microbiologia de Alimentos , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Alimentos Fermentados/microbiologia , LactobacillusRESUMO
A novel bifidobacterium (designated F753-1T) was isolated from the gut of honeybee (Apis mellifera). Strain F753-1T was characterized using a polyphasic taxonomic approach. Strain F753-1T was phylogenetically related to the type strains of Bifidobacterium mizhiensis, Bifidobacterium asteroides, Bifidobacterium choladohabitans, Bifidobacterium mellis, Bifidobacterium apousia and Bifidobacterium polysaccharolyticum, having 98.4-99.8â% 16S rRNA gene sequence similarities. The phylogenomic tree indicated that strain F753-1T was most closely related to the type strains of B. mellis and B. choladohabitans. Strain F753-1T had the highest average nucleotide identity (94.1-94.5â%) and digital DNA-DNA hybridization (56.3â%) values with B. mellis Bin7NT. Acid production from amygdalin, d-fructose, gentiobiose, d-mannose, maltose, sucrose and d-xylose, activity of α-galactosidase, pyruvate utilization and hydrolysis of hippurate could differentiate strain F753-1T from B. mellis CCUG 66113T and B. choladohabitans JCM 34586T. Based upon the data obtained in the present study, a novel species, Bifidobacterium apis sp. nov., is proposed, and the type strain is F753-1T (=CCTCC AB 2023227T=JCM 36562T=LMG 33388T).
Assuntos
Técnicas de Tipagem Bacteriana , Bifidobacterium , DNA Bacteriano , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Abelhas/microbiologia , Animais , RNA Ribossômico 16S/genética , Bifidobacterium/isolamento & purificação , Bifidobacterium/classificação , Bifidobacterium/genética , DNA Bacteriano/genética , Ácidos Graxos , Composição de Bases , Microbioma GastrointestinalRESUMO
A Gram-stain-negative, catalase-positive and oxidase-positive, nonmotile, aerobic, light yellow, spherical-shaped bacterial strain with no flagella, designated strain YIM 152171T, was isolated from sediment of the South China Sea. Colonies were smooth and convex, light yellow and circular, and 1.0-1.5×1.0-1.5 µm in cell diameter after 7 days of incubation at 28°C on YIM38 media supplemented with sea salt. Colonies could grow at 20-45°C (optimum 28-35°C) and pH 6.0-11.0 (optimum, pH 7.0-9.0), and they could proliferate in the salinity range of 0-6.0â% (w/v) NaCl. The major cellular fatty acids were summed feature 8 (C18â:â1 ω7c/C18â:â1 ω6c), C18â:â1 ω7c 11-methyl, C16â:â0, C16â:â1 ω11c, C16â:â1 ω5c, C17â:â1 ω6c and C18â:â1 ω5c. The respiratory quinone was ubiquinone 10, and the polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, one unidentified phospholipid and one unidentified aminolipid. Phylogenetic analyses based on the 16S rRNA gene sequences placed strain YIM 152171T within the order Rhodospirillales in a distinct lineage that also included the genus Geminicoccus. The 16S rRNA gene sequence similarities of YIM 152171T to those of Arboricoccus pini, Geminicoccus roseus and Constrictibacter antarcticus were 92.17, 89.25 and 88.91â%, respectively. The assembled draft genome of strain YIM 152171T had 136 contigs with an N50 value of 134704 nt, a total length of 3â001â346 bp and a G+C content of 70.27 mol%. The phylogenetic, phenotypic and chemotaxonomic data showed that strain YIM 152171T (=MCCC 1K08488T=KCTC 92884T) represents a type of novel species and genus for which we propose the name Marinimicrococcus gen. nov., sp. nov.
Assuntos
Ácidos Graxos , Rhodospirillales , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Análise de Sequência de DNA , Sedimentos Geológicos/microbiologia , Fosfolipídeos/química , ChinaRESUMO
Strain S30A2T, isolated from the acid mine drainage sediment of Mengzi Copper Mine, Yunnan, is proposed to represent a novel species of the sulphur-oxidizing genus Acidithiobacillus. Cells were Gram-stain-negative, non-endospore forming, highly motile with one or two monopolar flagella and rod-shaped. The strain was mesophilic, growing at 30-50 °C (optimum, 38 °C), acidophilic, growing at pH 2.0-4.5 (optimum, pH 2.5), and tolerant of 0-4â% (w/v; 684 mol l-1) NaCl. The 16S rRNA gene-based sequence analysis showed that strain S30A2T belongs to the genus Acidithiobacillus and shows the largest similarity of 96.6â% to the type strain Acidithiobacillus caldus KUT. The genomic DNA G+C content of strain S30A2T was 59.25 mol%. The average nucleotide identity ANIb and ANIm values between strain S30A2T and A. caldus KUT were 70.95 and 89.78â%, respectively and the digital DNA-DNA hybridization value was 24.9â%. Strain S30A2T was strictly aerobic and could utilize elementary sulphur and tetrathionate to support chemolithotrophic growth. The major cellular fatty acid of S30A2T was C19â:â1ω7c. The respiratory quinones were ubiquinone-8 and ubiquinone-7. Based upon its phylogenetic, genetic, phenotypic, physiologic and chemotaxonomic characteristics, strain S30A2T is considered to represent a novel species of the genus Acidithiobacillus, for which the name Acidithiobacillus acidisediminis sp. nov. is proposed. The type strain is S30A2T (=CGMCC 1.17059T=KCTC 72580T).
Assuntos
Acidithiobacillus , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Mineração , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Enxofre , RNA Ribossômico 16S/genética , Enxofre/metabolismo , DNA Bacteriano/genética , Ácidos Graxos/análise , Sedimentos Geológicos/microbiologia , Acidithiobacillus/classificação , Acidithiobacillus/genética , Acidithiobacillus/isolamento & purificação , China , Oxirredução , Crescimento Quimioautotrófico , Ubiquinona , Cobre/metabolismoRESUMO
ABSTRACT: Sepsis is characterized as a systemic inflammatory response syndrome resulting from infection, leading to the development of multiple organ dysfunction syndrome. Sepsis-induced cardiomyopathy (SICM) is a frequently encountered condition in clinical settings. Mesenchymal stem cells (MSCs) possess inherent immunomodulatory and anti-inflammatory attributes, rendering them a promising therapeutic approach to reestablish the equilibrium between anti-inflammatory and proinflammatory systems in septic patients. Consequently, MSCs are frequently employed in clinical investigations. In this study, the author established a mouse SICM model through cecal ligation and puncture and administered MSCs through the tail vein. Following successful modeling, the myocardial function and histopathological changes were detected by echocardiography, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining, enzyme-linked immunosorbent assay,, and other experiments. As a result, MSCs demonstrated the ability to enhance myocardial function, promote cardiac tissue repair, suppress inflammatory response, reduce levels of myocardial injury markers, and mitigate oxidative stress. In addition, transcriptome and proteome analyses were conducted. Through differential expression analysis, functional enrichment analysis, and multiomics association analysis, it was revealed that the transcriptional factors nuclear receptor subfamily 1 (NR1D2) and target gene lipocalin 2 (LCN2) played key roles in mediating the effects of MSCs on SICM. JASPAR website and ChIP-qPCR experiment were used to predict and confirm the targeting relationship between them. Subsequent cell coculture experiments and a series of experiments confirmed that MSCs attenuated cardiomyocyte injury by downregulating the expression of NR1D2 and its downstream target gene LCN2. In conclusion, MSCs alleviate mice SICM through inhibiting NR1D2/LCN2 pathway.
Assuntos
Cardiomiopatias , Modelos Animais de Doenças , Lipocalina-2 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Sepse , Transdução de Sinais , Animais , Sepse/complicações , Sepse/metabolismo , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Células-Tronco Mesenquimais/metabolismo , Masculino , Lipocalina-2/metabolismo , Lipocalina-2/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Células Cultivadas , Estresse Oxidativo , Função Ventricular Esquerda , Camundongos , ApoptoseRESUMO
The quest for novel antibacterial agents is imperative in the face of escalating antibiotic resistance. Naturally occurring tetrahydro-ß-carboline (THßC) alkaloids have been highlighted due to their significant biological derivatives. However, these structures have been little explored for antibacterial drugs development. In this study, a series of 1,2,3,4-THßC derivatives were synthesized and assessed for their antibacterial prowess against both gram-positive and gram-negative bacteria. The compounds exhibited moderate to good antibacterial activity, with some compounds showing superior efficacy against gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), to that of Gentamicin. Among these analogs, compound 3k emerged as a hit compound, demonstrating rapid bactericidal action and a significant post-antibacterial effect, with significant cytotoxicity towards human LO2 and HepG2 cells. In addition, compound 3k (10 mg/kg) showed comparable anti-MRSA efficacy to Ciprofloxacin (2 mg/kg) in a mouse model of abdominal infection. Overall, the present findings suggested that THßC derivatives based on the title compounds hold promising applications in the development of antibacterial drugs.
Assuntos
Antibacterianos , Carbolinas , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Carbolinas/farmacologia , Carbolinas/química , Carbolinas/síntese química , Humanos , Relação Estrutura-Atividade , Animais , Camundongos , Bactérias Gram-Positivas/efeitos dos fármacos , Estrutura Molecular , Bactérias Gram-Negativas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacosRESUMO
In this study, a series of new formylpiperazine-derived ferroptosis inhibitors were designed and synthesized based on the structure of a known ferroptosis inhibitor, ferrostatin-1 (Fer-1). The anti-ferroptosis activity of these synthetic compounds in human umbilical vein endothelial cells (HUVECs) induced by Erastin was evaluated. It was found that some of the new compounds, especially compound 26, showed potent anti-ferroptosis activity, as evidenced by its ability to restore cell viability, reduce iron accumulation, scavenge reactive oxygen species, maintain mitochondrial membrane potential, increase GSH levels, decrease LPO and MDA content, and upregulate GPX4 expression. Moreover, compound 26 exhibited superior microsomal stability than Fer-1. The present results suggest that compound 26 is a promising lead compound for the development of new ferroptosis inhibitors for the treatment of vascular diseases.
Assuntos
Sobrevivência Celular , Cicloexilaminas , Desenho de Fármacos , Ferroptose , Células Endoteliais da Veia Umbilical Humana , Piperazinas , Humanos , Ferroptose/efeitos dos fármacos , Piperazinas/farmacologia , Piperazinas/síntese química , Piperazinas/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Relação Estrutura-Atividade , Cicloexilaminas/farmacologia , Cicloexilaminas/química , Cicloexilaminas/síntese química , Sobrevivência Celular/efeitos dos fármacos , Estrutura Molecular , Fenilenodiaminas/farmacologia , Fenilenodiaminas/química , Fenilenodiaminas/síntese química , Relação Dose-Resposta a Droga , Espécies Reativas de Oxigênio/metabolismo , Compostos Ferrosos/farmacologia , Compostos Ferrosos/química , Compostos Ferrosos/síntese química , Potencial da Membrana Mitocondrial/efeitos dos fármacosRESUMO
Rationale: Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal developmental disorder of lung morphogenesis caused by insufficiency of FOXF1 (forkhead box F1) transcription factor function. The cellular and transcriptional mechanisms by which FOXF1 deficiency disrupts human lung formation are unknown. Objectives: To identify cell types, gene networks, and cell-cell interactions underlying the pathogenesis of ACDMPV. Methods: We used single-nucleus RNA and assay for transposase-accessible chromatin sequencing, immunofluorescence confocal microscopy, and RNA in situ hybridization to identify cell types and molecular networks influenced by FOXF1 in ACDMPV lungs. Measurements and Main Results: Pathogenic single-nucleotide variants and copy-number variant deletions involving the FOXF1 gene locus in all subjects with ACDMPV (n = 6) were accompanied by marked changes in lung structure, including deficient alveolar development and a paucity of pulmonary microvasculature. Single-nucleus RNA and assay for transposase-accessible chromatin sequencing identified alterations in cell number and gene expression in endothelial cells (ECs), pericytes, fibroblasts, and epithelial cells in ACDMPV lungs. Distinct cell-autonomous roles for FOXF1 in capillary ECs and pericytes were identified. Pathogenic variants involving the FOXF1 gene locus disrupt gene expression in EC progenitors, inhibiting the differentiation or survival of capillary 2 ECs and cell-cell interactions necessary for both pulmonary vasculogenesis and alveolar type 1 cell differentiation. Loss of the pulmonary microvasculature was associated with increased VEGFA (vascular endothelial growth factor A) signaling and marked expansion of systemic bronchial ECs expressing COL15A1 (collagen type XV α 1 chain). Conclusions: Distinct FOXF1 gene regulatory networks were identified in subsets of pulmonary endothelial and fibroblast progenitors, providing both cellular and molecular targets for the development of therapies for ACDMPV and other diffuse lung diseases of infancy.
Assuntos
Síndrome da Persistência do Padrão de Circulação Fetal , Recém-Nascido , Humanos , Síndrome da Persistência do Padrão de Circulação Fetal/genética , Síndrome da Persistência do Padrão de Circulação Fetal/patologia , Redes Reguladoras de Genes/genética , Fator A de Crescimento do Endotélio Vascular/genética , Células Endoteliais/patologia , Multiômica , Pulmão/patologia , RNA , Fatores de Transcrição Forkhead/genéticaRESUMO
In 2018, Nouioui et al. proposed that Bifidobacterium coryneforme was a later synonym of Bifidobacterium indicum on the basis of the digital DNA-DNA hybridization (dDDH) value (85.0%) between B. coryneforme LMG 18911T and B. indicum LMG 11587T. However, in the study of Scardovi et al. (1970), the type strains of B. indicum and B. coryneforme only exhibited 60% DNA-DNA hybridization value. In the present study, the genomes of B. coryneforme CGMCC 1.2279T, B. coryneforme JCM 5819T, B. indicum JCM 1302T, B. indicum CGMCC 1.2275T, B. indicum DSM 20214T, B. indicum LMG 27437T, B. indicum ATCC 25912T, B. indicum KCTC 3230T, B. indicum CCUG 34985T, were sequenced, and the taxonomic relationship between B. coryneforme and B. indicum was re-evaluated. On the basis of the results presented here, (i) ATCC 25912 and DSM 20214 deposited by Vittorio Scardovi are two different strains; (ii) the type strain of B. indicum is ATCC 25912T (= JCM 1302T = LMG 27437T = CGMCC 1.2275T = KCTC 3230T), and not DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587); (iii) B. coryneforme and B. indicum represent two different species of the genus Bifidobacterium; (iv) strain DSM 20214 (= BCRC 14674 = CCUG 34985 = LMG 11587) belongs to B. coryneforme.