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1.
Nucleic Acids Res ; 51(D1): D1381-D1387, 2023 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-36243962

RESUMEN

Advances in sequencing technologies have led to the rapid growth of multi-omics data on rheumatoid arthritis (RA). However, a comprehensive database that systematically collects and classifies the scattered data is still lacking. Here, we developed the Rheumatoid Arthritis Bioinformatics Center (RABC, http://www.onethird-lab.com/RABC/), the first multi-omics data resource platform (data hub) for RA. There are four categories of data in RABC: (i) 175 multi-omics sample sets covering transcriptome, epigenome, genome, and proteome; (ii) 175 209 differentially expressed genes (DEGs), 105 differentially expressed microRNAs (DEMs), 18 464 differentially DNA methylated (DNAm) genes, 1 764 KEGG pathways, 30 488 GO terms, 74 334 SNPs, 242 779 eQTLs, 105 m6A-SNPs and 18 491 669 meta-mQTLs; (iii) prior knowledge on seven types of RA molecular markers from nine public and credible databases; (iv) 127 073 literature information from PubMed (from 1972 to March 2022). RABC provides a user-friendly interface for browsing, searching and downloading these data. In addition, a visualization module also supports users to generate graphs of analysis results by inputting personalized parameters. We believe that RABC will become a valuable resource and make a significant contribution to the study of RA.


Asunto(s)
Artritis Reumatoide , Bases de Datos Factuales , Humanos , Artritis Reumatoide/genética , Biomarcadores/metabolismo , Biología Computacional/métodos , Metilación de ADN/genética , Perfilación de la Expresión Génica/métodos , Transcriptoma
2.
Proteomics ; 24(6): e2300235, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38197532

RESUMEN

Changes in the structure of RNA and protein, have an important impact on biological functions and are even important determinants of disease pathogenesis and treatment. Some genetic variations, including copy number variation, single nucleotide variation, and so on, can lead to changes in biological function and increased susceptibility to certain diseases by changing the structure of RNA or protein. With the development of structural biology and sequencing technology, a large amount of RNA and protein structure data and genetic variation data resources has emerged to be used to explain biological processes. Here, we reviewed the effects of genetic variation on the structure of RNAs and proteins, and investigated their impact on several diseases. An online resource (http://www.onethird-lab.com/gems/) to support convenient retrieval of common tools is also built. Finally, the challenges and future development of the effects of genetic variation on RNA and protein were discussed.


Asunto(s)
Variaciones en el Número de Copia de ADN , ARN , ARN/genética , Proteínas/química
3.
Proteomics ; : e2300359, 2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38522029

RESUMEN

Risk prediction and disease prevention are the innovative care challenges of the 21st century. Apart from freeing the individual from the pain of disease, it will lead to low medical costs for society. Until very recently, risk assessments have ushered in a new era with the emergence of omics technologies, including genomics, transcriptomics, epigenomics, proteomics, and so on, which potentially advance the ability of biomarkers to aid prediction models. While risk prediction has achieved great success, there are still some challenges and limitations. We reviewed the general process of omics-based disease risk model construction and the applications in four typical diseases. Meanwhile, we highlighted the problems in current studies and explored the potential opportunities and challenges for future clinical practice.

4.
J Physiol ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747042

RESUMEN

All new drugs must go through preclinical screening tests to determine their proarrhythmic potential. While these assays effectively filter out dangerous drugs, they are too conservative, often misclassifying safe compounds as proarrhythmic. In this study, we attempt to address this shortcoming with a novel, medium-throughput drug-screening approach: we use an automated patch-clamp system to acquire optimized voltage clamp (VC) and action potential (AP) data from human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) at several drug concentrations (baseline, 3×, 10× and 20× the effective free plasma concentrations). With our novel method, we show correlations between INa block and upstroke slowing after treatment with flecainide or quinine. Additionally, after quinine treatment, we identify significant reductions in current during voltage steps designed to isolate If and IKs. However, we do not detect any IKr block by either drug, and upon further investigation, do not see any IKr present in the iPSC-CMs when prepared for automated patch experiments (i.e. in suspension) - this is in contrast to similar experiments we have conducted with these cells using the manual patch setup. In this study, we: (1) present a proof-of-concept demonstration of a single-cell medium-throughput drug study, and (2) characterize the non-canonical electrophysiology of iPSC-CMs when prepared for experiments in a medium-throughput setting. KEY POINTS: Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer potential as an in vitro model to study the proarrhythmic potential of drugs, but insights from these cells are often limited by the low throughput of manual patch-clamp. In this study, we use a medium-throughput automated patch-clamp system to acquire action potential (AP) and complex voltage clamp (VC) data from single iPSC-CMs at multiple drug concentrations. A correlation between AP upstroke and INa transients was identified and drug-induced changes in ionic currents found. We also characterize the substantially altered physiology of iPSC-CMs when patched in an automated system, suggesting the need to investigate differences between manual and automated patch experiments.

5.
Am J Physiol Heart Circ Physiol ; 326(5): H1146-H1154, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38488520

RESUMEN

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) are a promising tool to study arrhythmia-related factors, but the variability of action potential (AP) recordings from these cells limits their use as an in vitro model. In this study, we use recently published brief (10 s), dynamic voltage-clamp (VC) data to provide mechanistic insights into the ionic currents contributing to AP heterogeneity; we call this approach rapid ionic current phenotyping (RICP). Features of this VC data were correlated to AP recordings from the same cells, and we used computational models to generate mechanistic insights into cellular heterogeneity. This analysis uncovered several interesting links between AP morphology and ionic current density: both L-type calcium and sodium currents contribute to upstroke velocity, rapid delayed rectifier K+ current is the main determinant of the maximal diastolic potential, and an outward current in the activation range of slow delayed rectifier K+ is the main determinant of AP duration. Our analysis also identified an outward current in several cells at 6 mV that is not reproduced by iPSC-CM mathematical models but contributes to determining AP duration. RICP can be used to explain how cell-to-cell variability in ionic currents gives rise to AP heterogeneity. Because of its brief duration (10 s) and ease of data interpretation, we recommend the use of RICP for single-cell patch-clamp experiments that include the acquisition of APs.NEW & NOTEWORTHY We present rapid ionic current phenotyping (RICP), a current quantification approach based on an optimized voltage-clamp protocol. The method captures a rich snapshot of the ionic current dynamics, providing quantitative information about multiple currents (e.g., ICa,L, IKr) in the same cell. The protocol helped to identify key ionic determinants of cellular action potential heterogeneity in iPSC-CMs. This included unexpected results, such as the critical role of IKr in establishing the maximum diastolic potential.


Asunto(s)
Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Miocitos Cardíacos/metabolismo , Potenciales de Acción/fisiología , Arritmias Cardíacas/metabolismo , Transporte Iónico
6.
J Nat Prod ; 87(1): 28-37, 2024 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-38204395

RESUMEN

Fengycin has great potential for applications in biological control because of its biosafety and degradability. In this study, the addition of exogenous precursors increased fengycin production by Bacillus subtilis. Corynebacterium glutamicum was engineered to produce high levels of precursors (Thr, Pro, Val, and Ile) to promote the biosynthesis of fengycin. Furthermore, recombinant C. glutamicum and Yarrowia lipolytica providing amino acid and fatty acid precursors were co-cultured to improve fengycin production by B. subtilis in a three-strain artificial consortium, in which fengycin production was 2100 mg·L-1. In addition, fengycin production by the consortium in a 5 L bioreactor reached 3290 mg·L-1. Fengycin had a significant antifungal effect on Rhizoctonia solani, which illustrates its potential as a food preservative. Taken together, this work provides a new strategy for improving fengycin production by a microbial consortium and metabolic engineering.


Asunto(s)
Bacillus subtilis , Consorcios Microbianos , Bacillus subtilis/química , Lipopéptidos/química , Antifúngicos/química
7.
J Exp Bot ; 74(18): 5620-5634, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-37480841

RESUMEN

Rapeseed (Brassica napus) is a major edible oilseed crop consumed worldwide. However, its yield is seriously affected by infection from the broad-spectrum non-obligate pathogen Sclerotinia sclerotiorum due to a lack of highly resistant germplasm. Here, we identified a Sclerotinia-resistant and light-dependent lesion mimic mutant from an ethyl methanesulfonate-mutagenized population of the rapeseed inbred Zhongshuang 11 (ZS11) named lesion mimic mutant 1 (lmm1). The phenotype of lmm1 is controlled by a single recessive gene, named LESION MIMIC MUTANT 1 (LMM1), which mapped onto chromosome C04 by bulked segregant analysis within a 2.71-Mb interval. Histochemical analysis indicated that H2O2 strongly accumulated and cell death occurred around the lesion mimic spots. Among 877 differentially expressed genes (DEGs) between ZS11 and lmm1 leaves, 188 DEGs were enriched in the defense response, including 95 DEGs involved in systemic acquired resistance, which is consistent with the higher salicylic acid levels in lmm1. Combining bulked segregant analysis and transcriptome analysis, we identified a significantly up-regulated gene, BnaC4.PR2, which encodes ß-1,3-glucanase, as the candidate gene for LMM1. Overexpression of BnaC4.PR2 may induce a reactive oxygen species burst to trigger partial cell death and systemic acquired resistance. Our study provides a new genetic resource for S. sclerotiorum resistance as well as new insights into disease resistance breeding in B. napus.


Asunto(s)
Ascomicetos , Brassica napus , Brassica rapa , Brassica napus/genética , Brassica napus/metabolismo , Peróxido de Hidrógeno/metabolismo , Enfermedades de las Plantas/genética , Fitomejoramiento , Brassica rapa/genética , Ascomicetos/fisiología , Resistencia a la Enfermedad/genética
8.
Glob Chang Biol ; 29(8): 2301-2312, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36597706

RESUMEN

The effects in field manipulation experiments are strongly influenced by amplified interannual variation in ambient climate as the experimental duration increases. Soil respiration (SR), as an important part of the carbon cycle in terrestrial ecosystems, is sensitive to climate changes such as temperature and precipitation changes. A growing body of evidence has indicated that ambient climate affects the temperature sensitivity of SR, which benchmarks the strength of terrestrial soil carbon-climate feedbacks. However, whether SR sensitivity to precipitation changes is influenced by ambient climate is still not clear. In addition, the mechanism driving the above phenomenon is still poorly understood. Here, a long-term field manipulation experiment with five precipitation treatments (-60%, -40%, +0%, +40%, and +60% of annual precipitation) was conducted in a marsh in the Yellow River Delta, China, which is sensitive to soil drying-wetting cycle caused by precipitation changes. Results showed that SR increased exponentially along the experimental precipitation gradient each year and the sensitivity of SR (standardized by per 100 mm change in precipitation under precipitation treatments) exhibited significant interannual variation from 2016 to 2021. In addition, temperature, net radiation, and ambient precipitation all exhibited dramatic interannual variability; however, only ambient precipitation had a significant negative correlation with SR sensitivity. Moreover, the sensitivity of SR was significantly positively related to the sensitivity of belowground biomass (BGB) across 6 years. Structural equation modeling and regression analysis also showed that precipitation treatments significantly affected SR and its autotrophic and heterotrophic components by altering BGB. Our study demonstrated that ambient precipitation determines the sensitivity of SR to precipitation treatments in marshes. The findings underscore the importance of ambient climate in regulating ecosystem responses in long-term field manipulation experiments.


Asunto(s)
Ecosistema , Humedales , Suelo/química , Biomasa , Respiración , Cambio Climático
9.
Europace ; 25(9)2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37552789

RESUMEN

AIMS: Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have become an essential tool to study arrhythmia mechanisms. Much of the foundational work on these cells, as well as the computational models built from the resultant data, has overlooked the contribution of seal-leak current on the immature and heterogeneous phenotype that has come to define these cells. The aim of this study is to understand the effect of seal-leak current on recordings of action potential (AP) morphology. METHODS AND RESULTS: Action potentials were recorded in human iPSC-CMs using patch clamp and simulated using previously published mathematical models. Our in silico and in vitro studies demonstrate how seal-leak current depolarizes APs, substantially affecting their morphology, even with seal resistances (Rseal) above 1 GΩ. We show that compensation of this leak current is difficult due to challenges with obtaining accurate measures of Rseal during an experiment. Using simulation, we show that Rseal measures (i) change during an experiment, invalidating the use of pre-rupture values, and (ii) are polluted by the presence of transmembrane currents at every voltage. Finally, we posit that the background sodium current in baseline iPSC-CM models imitates the effects of seal-leak current and is increased to a level that masks the effects of seal-leak current on iPSC-CMs. CONCLUSION: Based on these findings, we make recommendations to improve iPSC-CM AP data acquisition, interpretation, and model-building. Taking these recommendations into account will improve our understanding of iPSC-CM physiology and the descriptive ability of models built from such data.


Asunto(s)
Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Humanos , Potenciales de Acción , Arritmias Cardíacas , Células Madre
10.
Int J Immunogenet ; 50(6): 291-298, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37688529

RESUMEN

The aim of this study was to compare nonrandom associations between physically adjacent single methylation polymorphism loci among rheumatoid arthritis (RA) and normal subjects for investigating RA-risk methylation haplotypes (meplotype). With 354 ACPA-positive RA patients and 335 normal controls selected from a case-control study based on Swedish population, we conducted the first RA epigenome-wide meplotype association study using our software EWAS2.0, mainly including (i) converted the ß value to methylation genotype (menotype) data, (ii) identified methylation disequilibrium (MD) block, (iii) calculated frequent of each meplotypes in MD block and performed case-control association test and (iv) screened for RA-risk meplotypes by odd ratio (OR) and p-values. Ultimately, 545 meplotypes on 334 MD blocks were identified significantly associated with RA (p-value < .05). These meplotypes were mapped to 329 candidate genes related to RA. Subsequently, combined with gene optimization, eight RA-risk meplotypes were identified on three risk genes: HLA-DRB1, HLA-DRB5 and HLA-DQB1. Our results reported the relationship between DNA methylation pattern on HLA-DQB1 and the risk of RA for the first time, demonstrating the co-demethylation of 'cg22984282' and 'cg13423887' on HLA-DQB1 gene (meplotype UU, p-value = 2.90E - 6, OR = 1.68, 95% CI = [1.35, 2.10]) may increase the risk of RA. Our results demonstrates the potential of methylation haplotype analysis to identify RA-related genes from a new perspective and its applicability to the study of other disease.


Asunto(s)
Artritis Reumatoide , Epigenoma , Humanos , Cadenas HLA-DRB1/genética , Haplotipos , Cadenas HLA-DRB5/genética , Metilación , Estudios de Casos y Controles , Cadenas beta de HLA-DQ/genética , Artritis Reumatoide/genética , Factores de Riesgo , Predisposición Genética a la Enfermedad , Alelos
11.
Genomics ; 113(1 Pt 2): 1096-1108, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33171205

RESUMEN

Polygalacturonase (PG) is a hydrolase that participates in pectin degradation, pod shattering and fruit softening. Here, we identified 2786 PG genes across 54 plants, which could be divided into three groups. Evolutionary analysis suggested that PG family originated from the charophyte green algae, and Subgroups A2-A4 evolved from the Subgroup A1 after the tracheophyte-angiosperm split. Whole-genome duplication was the major force leading to PG gene expansion. Interestingly, the PG genes continuously expanded in eudicots, whereas it contracted in monocots after the eudicot-monocot split. PG genes in Group A are expressed at high levels in floral organs, whereas genes in Groups B and C are expressed at high levels in various tissues. Moreover, three BnaPG15 members were found for their potential possibility in pod shattering in Brassica napus. Our results provide new insight into the evolutionary history of PG family, and their potentially functional role in plants.


Asunto(s)
Evolución Molecular , Magnoliopsida/genética , Proteínas de Plantas/genética , Poligalacturonasa/genética , Ecosistema , Magnoliopsida/clasificación , Magnoliopsida/fisiología , Filogenia , Filogeografía
12.
Sep Purif Technol ; 2622021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-34366698

RESUMEN

H2O2 generation by 2-electron oxygen electroreduction reaction (2eORR) has attracted great attention as an alternative to the industry-dominant anthraquinone process. Electro-Fenton (EF) process, which relies on the H2O2 electrogeneration, is regarded as an important environmental application of H2O2 generation by 2eORR. However, its application is hindered by the relatively expensive electrode materials. Proposing cathode materials with low cost and facile synthetic procedures are the priority to advance the EF process. In this work, a composite cathode structure that uses graphitic granular bamboo-based biochar (GB) and stainless steel (SS) mesh (GBSS) is proposed, where SS mesh functions as current distributor and GB supports synergistic H2O2 electrogeneration and activation. The graphitic carbon makes GB conductive and the oxygen-containing groups serve as active sites for H2O2 production. 11.3 mg/L H2O2 was produced from 2.0 g GB at 50 mA after 50 min under neutral pH without external O2/air supply. The O-doped biochar further increased the H2O2 yield to 18.3 mg/L under same conditions. The GBSS electrode is also effective for H2O2 activation to generate ·OH, especially under neutral pH. Ultimately, a neutral Fe-free EF process enabled by GBSS cathode is effective for removal of various model organic pollutants (reactive blue 19, orange II, 4-nitrophenol) within 120 min, and for their partial mineralization (48.4% to 63.5%). Long-term stability of the GBSS electrode for H2O2 electrogeneration, H2O2 activation, and pollutants degradation were also examined and analyzed. This work offers a promising application for biomass waste for removals of organic pollutants in neutral Fe-free EF process.

13.
Biochem J ; 476(7): 1137-1148, 2019 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-30910801

RESUMEN

Intracellular protons and calcium ions are two major chemical factors that regulate connexin43 (Cx43) gap junction communication and the synergism or antagonism between pH and Ca2+ has been questioned for decades. To assess the ability of Ca2+ ions to modulate Cx43 junctional conductance (gj) in the absence of pH-sensitivity, patch clamp experiments were performed on Neuroblastoma-2a (N2a) cells or neonatal mouse ventricular myocytes (NMVMs) expressing either full-length Cx43 or the Cx43-M257 (Cx43K258stop) mutant protein, a carboxyl-terminus (CT) truncated version of Cx43 lacking pH-sensitivity. The addition of 1 µM ionomycin to normal calcium saline reduced Cx43 or Cx43-M257 gj to zero within 15 min of perfusion. This response was prevented by Ca2+-free saline or addition of 100 nM calmodulin (CaM) inhibitory peptide to the internal pipette solution. Internal addition of a connexin50 cytoplasmic loop calmodulin-binding domain (CaMBD) mimetic peptide (200 nM) prevented the Ca2+/ionomycin-induced decrease in Cx43 gj, while 100 µM Gap19 peptide had minimal effect. The investigation of the transjunctional voltage (Vj) gating properties of NMVM Cx43-M257 gap junctions confirmed the loss of the fast inactivation of Cx43-M257 gj, but also noted the abolishment of the previously reported facilitated recovery of gj from inactivating potentials. We conclude that the distal CT domain of Cx43 contributes to the Vj-dependent fast inactivation and facilitated recovery of Cx43 gap junctions, but the Ca2+/CaM-dependent gating mechanism remains intact in its absence. Sequence-specific connexin CaMBD mimetic peptides act by binding Ca2+/CaM non-specifically and the Cx43 mimetic Gap19 peptide has negligible effect on this chemical gating mechanism.


Asunto(s)
Calcio/metabolismo , Calmodulina/metabolismo , Conexina 43/metabolismo , Uniones Comunicantes/metabolismo , Sustitución de Aminoácidos , Animales , Señalización del Calcio , Línea Celular , Conexina 43/química , Conexina 43/genética , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Activación del Canal Iónico , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Imitación Molecular , Mutagénesis Sitio-Dirigida , Miocitos Cardíacos/metabolismo , Dominios Proteicos
14.
Phys Chem Chem Phys ; 20(32): 21136-21143, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-30079418

RESUMEN

Diamondene, a carbon nanomaterial containing both sp2 and sp3 carbon atoms, is obtained by compressing two or more layers of graphene. By curving rectangular diamondene and matching the unsaturated C-C bonds on the two unbent edges, a nanotube is built. We build two diamondene nanotubes (DNTs) with different radii and test their strengths under uniaxial tension. From the stress-strain curves, we discover that DNTs exhibit softening followed by hardening. The mechanism is as follows: the bond lengths and bond angles impart different stiffnesses to the tube at different axial strains. Molecular dynamics simulations demonstrate that the feature of the softening-hardening process is independent of either the tube radii or the system temperature. The critical strain for the tensile strength of a DNT becomes lower at a higher temperature. This is caused by thermal vibration of the atoms in the tubes. At the same temperature, for a DNT with a larger radius, the value of critical strain is higher. These properties will be beneficial for the potential applications of DNTs in nanodevices.

15.
Environ Sci Technol ; 51(21): 12692-12698, 2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-28992404

RESUMEN

Although the literature has reported enhanced indirect sulfation of limestone by adding Na2CO3, the amount of Na2CO3 additive required to achieve high CaO conversion is typically high (∼4.0 mol %), which commonly results in adverse effects in fluidized-bed combustion boiler systems and increased cost of sorbents. In this work, we demonstrate for the first time that trace Na2CO3 (0.1 mol %) can significantly enhance the sulfate conversion of limestone. This enhanced sulfation is attributed to the increased surface area and optimized pore size distribution. The trace Na2CO3 additive splits the pores of the original sorbents peaking at ∼70 nm into pores peaking at ∼4 nm and ∼140 nm due to the slight promotion of sintering. This well-developed pore structure results in a relatively high reactivity for sulfation. Thus, the Na2CO3 additive influences the sorbent reactivity in two ways: (1) at less than 0.5 mol %, tuning its pore structure; (2) at more than 0.5 mol %, promoting the product layer diffusion. We also find that trace amount of other metal salts, such as CaCl2 and NaCl, clearly enhance the sulfation of limestone. The strategy of enhancing limestone sulfation by the addition of trace amount of metal salts offers evident engineering and economic advantage.


Asunto(s)
Carbonato de Calcio , Dióxido de Azufre , Difusión
16.
J Colloid Interface Sci ; 658: 943-951, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38157618

RESUMEN

Exploring the single relationship between the inversion degree of spinel and its catalytic performance is a great challenge, but has important significance for further structural design and application. A series of CoMn inverse spinels were prepared and the general formula [Formula: see text] was deduced through X-ray diffraction refinement to find a decreased inversion degree x as calcination temperature rose. Catalytic oxidation of toluene showed that higher inversion degree (S-300 with x ≈ 0.95) can reach larger conversion rate (90 % at about 250 °C for 400 ppm toluene) with greater reaction stability (140 h). Density Functional Theory (DFT) calculations on density of states indicated its metallic nature, and found that the strength of O-p and Transition metal-d orbitals at Fermi energy is positively correlated to the inversion degree, meaning stronger electron migration ability. Along with the adsorption calculation analysis that lattice oxygen species are proved to work dominantly (S-300 with lowest adsorption energy but highest performance), this work uncovered a theoretical insight into inverse spinel oxide, to provide the possibility of elevated oxidation ability through structural control.

17.
Synth Syst Biotechnol ; 9(1): 176-185, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38348399

RESUMEN

Polymyxin B, produced by Paenibacillus polymyxa, is used as the last line of defense clinically. In this study, exogenous mixture of precursor amino acids increased the level and proportion of polymyxin B1 in the total of polymyxin B analogs of P. polymyxa CJX518-AC (PPAC) from 0.15 g/L and 61.8 % to 0.33 g/L and 79.9 %, respectively. The co-culture of strain PPAC and recombinant Corynebacterium glutamicum-leu01, which produces high levels of threonine, leucine, and isoleucine, increased polymyxin B1 production to 0.64 g/L. When strains PPAC and C. glu-leu01 simultaneously inoculated into an optimized medium with 20 g/L peptone, polymyxin B1 production was increased to 0.97 g/L. Furthermore, the polymyxin B1 production in the co-culture of strains PPAC and C. glu-leu01 increased to 2.21 g/L after optimized inoculation ratios and fermentation medium with 60 g/L peptone. This study provides a new strategy to improve polymyxin B1 production.

18.
Comput Struct Biotechnol J ; 23: 1348-1363, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38596313

RESUMEN

Autoimmune diseases (ADs) are characterized by their complexity and a wide range of clinical differences. Despite patients presenting with similar symptoms and disease patterns, their reactions to treatments may vary. The current approach of personalized medicine, which relies on molecular data, is seen as an effective method to address the variability in these diseases. This review examined the pathologic classification of ADs, such as multiple sclerosis and lupus nephritis, over time. Acknowledging the limitations inherent in pathologic classification, the focus shifted to molecular classification to achieve a deeper insight into disease heterogeneity. The study outlined the established methods and findings from the molecular classification of ADs, categorizing systemic lupus erythematosus (SLE) into four subtypes, inflammatory bowel disease (IBD) into two, rheumatoid arthritis (RA) into three, and multiple sclerosis (MS) into a single subtype. It was observed that the high inflammation subtype of IBD, the RA inflammation subtype, and the MS "inflammation & EGF" subtype share similarities. These subtypes all display a consistent pattern of inflammation that is primarily driven by the activation of the JAK-STAT pathway, with the effective drugs being those that target this signaling pathway. Additionally, by identifying markers that are uniquely associated with the various subtypes within the same disease, the study was able to describe the differences between subtypes in detail. The findings are expected to contribute to the development of personalized treatment plans for patients and establish a strong basis for tailored approaches to treating autoimmune diseases.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38652228

RESUMEN

Although fengycin exhibits broad-spectrum antifungal properties, its application is hindered due to its low biosynthesis level and the co-existence of iturin A and surfactin in Bacillus amyloliquefaciens HM618, a probiotic strain. In this study, transcriptome analysis and gene editing were used to explore the potential mechanisms regulating fengycin production in B. amyloliquefaciens. The fengycin level of B. amyloliquefacien HM-3 (∆itu-ΔsrfAA) was 88.41 mg/L after simultaneously inhibiting the biosyntheses of iturin A and surfactin. The knockout of gene eps associated with biofilm formation significantly increased the fengycin level of the strain HM618, whereas the fengycin level decreased 32.05% after knocking out sinI, a regulator of biofilm formation. Transcriptome analysis revealed that the differentially expressed genes, involved in pathways of amino acid and fatty acid syntheses, were significantly down-regulated in the recombinant strains, which is likely associated with a decrease of fengycin production. The knockout of gene comQXPA and subsequent transcriptome analysis revealed that the ComQXPA quorum sensing system played a positive regulatory role in fengycin production. Through targeted genetic modifications and fermentation optimization, the fengycin production of the engineered strain HM-12 (∆itu-ΔsrfAA-ΔyvbJ) in a 5-L fermenter reached 1.172 g/L, a 12.26-fold increase compared to the fengycin level in the strain HM-3 (∆itu-ΔsrfAA) in the Erlenmeyer flask. Taken together, these results reveal the underlying metabolic mechanisms associated with fengycin synthesis and provide a potential strategy for improving fengycin production in B. amyloliquefaciens.

20.
Int J Surg ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874467

RESUMEN

BACKGROUND: The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer is still unclear but increasingly drawing attention. MATERIALS AND METHODS: In this systematic review and meta-analysis, we searched the PubMed, EMBASE, Web of Science, and Cochrane Library as of January 20, 2024 and referenced list of eligible articles for all published studies comparing RG and LG for patients with gastric cancer, Data on study characteristics, individual characteristics, and outcome parameters were extracted. The quality of studies was assessed using the Revised Cochrane risk-of-bias 2 tool and the risk of bias in non-randomized studies of interventions tool. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 3641 articles, of which 72 studies (30081 patients) were included in the meta-analysis. Compared with LG, RG was associated with higher OS [hazard ratio (HR)=0.89, 95% CI=0.83 to 0.96), lower rate of overall postoperative complications [odds ratio (OR)=0.77, 95% CI=0.71 to 0.84], longer operating time [mean difference (MD)=35.53, 95% CI=29.23 to 41.83], less estimated blood loss (MD=-37.45, 95% CI=-46.24 to -28.67), a higher number of retrieved lymph nodes (MD=1.88, 95% CI=0.77 to 3.00), faster postoperative recovery, and lower rate of conversion (OR=0.44, 95% CI=0.36 to 0.55). Mortality and DFS were not significantly different between the two groups. The subgroup of meta-analysis results also showed the advantages of robotic surgery over laparoscopic surgery in intracorporeal reconstruction, total gastrectomy, Ⅰ/Ⅱ stage, and BMI≥25, especially for patients with stage Ⅰ/Ⅱ, there is better overall survival and disease-free survival. CONCLUSION: Our findings point to robotic surgery having great benefits compared with laparoscopic surgery in gastric cancer. Our study may help inform decision-making in applying robotic surgical systems to clinical treatment.

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