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1.
Alzheimers Dement ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747519

RESUMO

INTRODUCTION: This study addresses the urgent need for non-invasive early-onset Alzheimer's disease (EOAD) prediction. Using optical coherence tomography angiography (OCTA), we present a choriocapillaris model sensitive to EOAD, correlating with serum biomarkers. METHODS: Eighty-four EOAD patients and 73 controls were assigned to swept-source OCTA (SS-OCTA) or the spectral domain OCTA (SD-OCTA) cohorts. Our hypothesis on choriocapillaris predictive potential in EOAD was tested and validated in these two cohorts. RESULTS: Both cohorts revealed diminished choriocapillaris signals, demonstrating the highest discriminatory capability (area under the receiver operating characteristic curve: SS-OCTA 0.913, SD-OCTA 0.991; P < 0.001). A sparser SS-OCTA choriocapillaris correlated with increased serum amyloid beta (Aß)42, Aß42/40, and phosphorylated tau (p-tau)181 levels (all P < 0.05). Apolipoprotein E status did not affect choriocapillaris measurement. DISCUSSION: The choriocapillaris, observed in both cohorts, proves sensitive to EOAD diagnosis, and correlates with serum Aß and p-tau181 levels, suggesting its potential as a diagnostic tool for identifying and tracking microvascular changes in EOAD. HIGHLIGHTS: Optical coherence tomography angiography may be applied for non-invasive screening of Alzheimer's disease (AD). Choriocapillaris demonstrates high sensitivity and specificity for early-onset AD diagnosis. Microvascular dynamics abnormalities are associated with AD.

2.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731410

RESUMO

Cirsium japonicum Fisch. ex DC. (CF) and Cirsium setosum (Willd.) MB (CS) are commonly used clinically to stop bleeding and eliminate carbuncles. Still, CF is mainly used for treating inflammation, while CS favors hemostasis. Therefore, the present study used UHPLC-MS to analyze the main chemical constituents in CF-CS extract. We optimized the extraction process using single-factor experiments and response surface methodology. Afterward, the hemostatic and anti-inflammatory effects of CF-CS extract were investigated by determining the clotting time in vitro, the bleeding time of rabbit trauma, and the induction of rabbit inflammation using xylene and lipopolysaccharide. The study of hemostatic and anti-inflammatory effects showed that the CF-CS, CF, and CS extract groups could significantly shorten the coagulation time and bleeding time of rabbits compared with the blank group (p < 0.01); compared with the model group, it could dramatically inhibit xylene-induced ear swelling in rabbits and the content of TNF-α, IL-6, and IL-1ß in the serum of rabbits (p < 0.01). The results showed that combined CF and CS synergistically increased efficacy. CF-CS solved the problem of the single hemostatic and anti-inflammatory efficacy of a single drug, which provided a new idea for the research and development of natural hemostatic and anti-inflammatory medicines.


Assuntos
Anti-Inflamatórios , Cirsium , Hemostáticos , Extratos Vegetais , Animais , Coelhos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Cirsium/química , Hemostáticos/farmacologia , Hemostáticos/química , Hemostáticos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino
3.
J Colloid Interface Sci ; 668: 484-491, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691958

RESUMO

Suppressing carrier recombination in bulk and facilitating carrier transfer to surface via rational structure design is of great significance to improve solar-to-H2 conversion efficiency. We demonstrate a facile hydrothermal method to synthesize porous SrTiO3 single crystals (SrTiO3-P) with exposed (001) facets by introducing carbon spheres as templates. The obviously increased surface photovoltage and photocurrent response indicate that the interconnected pore walls act as enormous charge transfer "highways", accelerating carrier transport from bulk to surface. Furthermore, the absence of grain boundaries and high crystallinity could also lower the carrier recombination rate. Thus, the SrTiO3-P photocatalyst loaded with Rh/Cr2O3 as cocatalyst exhibits 1.5 times higher overall water splitting activity than that of solid SrTiO3, with gas evolution rate of 19.99 µmol h-1 50 mg-1 for H2 and 11.37 µmol h-1 50 mg-1 for O2. Additionally, SrTiO3-P also shows superior stability without any decay during cycling testing. This work provides a new insight into designing efficient multicomponent photocatalysts with a single-crystal porous structure.

4.
Gene ; : 148558, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740353

RESUMO

Recessive genic male sterility (RGMS) provides an effective approach for the commercial exploitation of heterosis, especially in Brassica crops. Although some artificial RGMS mutants have been reported in B. rapa, no causal genes derived from these natural mutants have been identified so far. In this study, a spontaneous RGMS mutant Bcajh97-01A derived from the 'Aijiaohuang' line traced back to the 1980 s was identified. Genetic analysis revealed that the RGMS trait was controlled by a single locus in the Bcajh97-01A/B system. Bulk segregant analysis (BSA) in combination with linkage analysis was employed to delimit the causal gene to an approximate 129 kb interval on chromosome A02. The integrated information of transcriptional levels and the predicted genes in the target region indicated that the Brmmd1 (BraA02g017420) encoding a PHD-containing nuclear protein was the most likely candidate gene. A 374 bp miniature inverted-repeat transposable element (MITE) was inserted into the first exon to prematurely stop the Brmmd1 gene translation, thus blocking the normal expression of this gene at the tetrad stage in the Bcajh97-01A. Additionally, a co-segregating structure variation (SV) marker was developed to rapidly screen the RGMS progenies from Bcajh97-01A/B system. Our findings reveal that BraA02g017420 is the causal gene responsible for the RGMS trait. This study lays a foundation for marker-assisted selection and further molecular mechanism exploration of pollen development in B. rapa.

5.
Zygote ; 32(2): 170-174, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619002

RESUMO

Oocytes with excessively large first polar bodies (PB1) often occur in assisted reproductive procedures. Many times these oocytes are discarded without insemination and, as a result, the application of this portion of oocytes has scarcely been reported to date. Few studies have examined large PB1 oocytes in infertile women and have virtually entirely studied genetic variations for large PB1 oocyte abnormalities. Here, we describe an unusual case of a live birth from a remarkably large PB1 oocyte in a frozen embryo transfer (FET) cycle. This is the first instance of a successful live birth resulting from a PB1 oocyte with an extremely large polar body measuring 80 µM × 40 µM in size. The large PB1 oocyte was performed by an early rescue intracytoplasmic sperm injection (r-ICSI) and was formed into a blastocyst on day 5. Following FET, a healthy boy baby weighing 3100 g was finally delivered by caesarean section at 37 weeks and 5 days after conception. Additionally, there were no complications throughout the antenatal period or the perinatal phase of this following full-term delivery. In this study, it is revealed for the first time that a huge PB1 oocyte can be fertilized, resulting in the growth of a blastocyst, a subsequent pregnancy, and a live birth. This new information prompts us to reconsider the use of large PB1 oocytes. More insightful talks should be given attention to prevent the waste of embryos because not all oocytes with aberrant morphology are unavailable.


Assuntos
Transferência Embrionária , Nascido Vivo , Oócitos , Corpos Polares , Injeções de Esperma Intracitoplásmicas , Humanos , Feminino , Gravidez , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Oócitos/fisiologia , Oócitos/citologia , Masculino , Transferência Embrionária/métodos , Recém-Nascido , Blastocisto/citologia , Blastocisto/fisiologia , Criopreservação
6.
ACS Appl Mater Interfaces ; 16(13): 15701-15717, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38507687

RESUMO

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, ß-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.


Assuntos
Minoxidil , Fator A de Crescimento do Endotélio Vascular , Humanos , Minoxidil/farmacologia , Minoxidil/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Alopecia/metabolismo , Cabelo , Folículo Piloso , Resultado do Tratamento
7.
Opt Express ; 32(5): 7307-7317, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38439414

RESUMO

The Fourier single-pixel imaging technique exhibits great potential for compressive imaging. However, the utilization of low sampling ratio can introduce unwanted ringing artifacts, thereby compromising the fidelity of reconstructed image detail. To address this issue, Vector guided Fourier single-pixel imaging (V-FSI) has been proposed. We analyze the statistical properties in the edge vector field derived from images with low sampling ratio. Based on this information, a tailored sampling map is designed to acquire the significant high-frequency components for image reconstruction. Experimental results demonstrate the remarkable effectiveness of the proposed V-FSI method in enhancing image quality. Notably, V-FSI exhibits exceptional capabilities in perceiving and preserving the details of the objects, particularly for objects characterized by pronounced periodicity and directionality.

8.
J Org Chem ; 89(7): 5170-5180, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38545893

RESUMO

A chiral NHC-catalyzed [3 + 3] cycloaddition reaction of 3-aminobenzofurans with isatin-derived enals has been documented, furnishing 3,4'-piperidinoyl spirooxindoles bearing a quaternary stereocenter with good yields and excellent enantioselectivities. Further gram-scale preparation and synthetic transformation of the cycloadducts to δ-amino acid derivative demonstrated good practicality and applicability of this reaction.

9.
Adv Mater ; 36(19): e2309972, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38324725

RESUMO

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.


Assuntos
Cápsulas , Colite , Microbioma Gastrointestinal , Nanogéis , Óxido Nítrico , Colite/tratamento farmacológico , Animais , Cápsulas/química , Camundongos , Nanogéis/química , Óxido Nítrico/metabolismo , Probióticos , Polietilenoimina/química , Gases/química , Camundongos Endogâmicos C57BL , Polietilenoglicóis
10.
Appl Environ Microbiol ; 90(3): e0224223, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38358247

RESUMO

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.


Assuntos
Hidrolases , Polietilenotereftalatos , Polietilenotereftalatos/metabolismo , Filogenia , Estabilidade Enzimática , Hidrolases/metabolismo , Dissulfetos , Temperatura
11.
Ecol Appl ; 34(3): e2944, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38379442

RESUMO

In China, the Grain for Green Program (GGP) is an ambitious project to convert croplands into natural vegetation, but exactly how changes in vegetation translate into changes in soil organic carbon remains less clear. Here we conducted a meta-analysis using 734 observations to explore the effects of land recovery on soil organic carbon and nutrients in four provinces in Southwest China. Following GGP, the soil organic carbon content (SOCc) and soil organic carbon stock (SOCs) increased by 33.73% and 22.39%, respectively, compared with the surrounding croplands. Similarly, soil nitrogen increased, while phosphorus decreased. Outcomes were heterogeneous, but depended on variations in soil and environmental characteristics. Both the regional land use and cover change indicated by the landscape type transfer matrix and net primary production from 2000 to 2020 further confirmed that the GGP promoted the forest area and regional mean net primary production. Our findings suggest that the GGP could enhance soil and vegetation carbon sequestration in Southwest China and help to develop a carbon-neutral strategy.


Assuntos
Carbono , Solo , Carbono/análise , Florestas , Grão Comestível , China
12.
J Biosci Bioeng ; 137(5): 335-343, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38413318

RESUMO

A high-yielding microbial polysaccharide-producing strain, named RM1603, was isolated from rhizosphere soil and identified by morphological and phylogenetic analysis. The extracellular polysaccharides (EPS) were identified by thin-layer chromatography and infrared spectroscopy. The fermentation conditions were optimized by single factor experiments in shake flasks and a 5-L fermentor. The results of morphological and phylogenetic tree analysis showed that RM1603 was a strain of Aureobasidium pullulans. Its microbial polysaccharide was identified as pullulan, and the EPS production capacity reached 33.07 ± 1.03 g L-1 in shake flasks. The fermentation conditions were optimized in a 5-L fermentor, and were found to encompass an initial pH of 6.5, aeration rate of 2 vvm, rotor speed of 600 rpm, and inoculum size of 2 %. Under these conditions, the pullulan yield of RM1603 reached 62.52 ± 0.24 g L-1. Thus, this study contributes RM1603 as a new isolation with high-yielding pullulan and potential application value in biotechnology.


Assuntos
Ascomicetos , Aureobasidium , Glucanos , Fermentação , Filogenia , Ascomicetos/genética , Polissacarídeos/química
13.
Environ Toxicol ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38366283

RESUMO

RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy. A machine-learning model of 23 m6A genes was constructed. Single-cell analysis revealed a surprising enrichment of IGFBP3 in astrocytes, prompting the exploration of associated signaling pathways. Experimental verification shows that IGFBP3 is significantly enhanced in normal tissues, while immunohistochemical analysis shows that its expression is lower in tumor tissues, indicating its protective effect in HCC and a good prognosis. Importantly, high IGFBP3 expression is associated with better outcomes in patients receiving immunotherapy. Moreover, cytotoxic T lymphocyte (CTL) experiments have confirmed that high expression of IGFBP3 is associated with stronger T cell-killing ability. In summary, the comprehensive evaluation of m6A modification, immune characteristics, and single-cell analysis in this study not only revealed the TME of HCC but also made significant contributions to the progress of personalized HCC immunotherapy targeting IGFBP3. This study provides a solid theoretical foundation for clinical translation and emphasizes its potential impact on developing effective treatment strategies.

14.
Chemistry ; 30(26): e202400278, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38406889

RESUMO

A novel [3+3] annulation reaction of 2-alkenylindoles with hydrazonyl chlorides in the presence of base for the formation of pyridazino[4,5-b]indoles was developed. This approach provided a convenient and efficient way to synthesize a series of functionalized pyridazino[4,5-b]indoles derivatives. The method exhibited a broad substrate scope and provided the corresponding pyridazino[4,5-b]indoles products with excellent yields.

15.
J Agric Food Chem ; 72(8): 4023-4034, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38357881

RESUMO

In this study, an effective method for preparation of bioactive galloylated procyanidin B2-3'-O-gallate (B2-3'-G) was first developed by incomplete depolymerization of grape seed polymeric procyanidins (PPCs) using l-cysteine (Cys) in the presence of citric acid. The structure-activity relationship of B2-3'-G was further evaluated in vitro through establishing lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. The results suggested that the better protective effects of B2-3'-G against inflammation were attributed to its polymerization degree and the introduction of the galloyl group, compared to its four corresponding structural units. In vivo experiments demonstrated that the B2-3'-G prototype was distributed in plasma, small intestine, liver, lung, and brain. Remarkably, B2-3'-G was able to penetrate the blood-brain barrier and appeared to play an important role in improving brain health. Furthermore, a total of 18 metabolites were identified in tissues. Potential metabolic pathways, including reduction, methylation, hydration, desaturation, glucuronide conjugation, and sulfation, were suggested.


Assuntos
Biflavonoides , Catequina , Proantocianidinas , Humanos , Proantocianidinas/farmacologia , Proantocianidinas/química , Cisteína , Distribuição Tecidual , Biflavonoides/farmacologia , Biflavonoides/química , Catequina/química , Inflamação , Anti-Inflamatórios/farmacologia
16.
Neurol Sci ; 45(6): 2615-2623, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38216851

RESUMO

PURPOSE: To compare the peripapillary retinal nerve fiber layer (pRNFL), retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) thickness measurement in early-onset Alzheimer's disease (EOAD) and controls using spectral domain optical coherence tomography (SD-OCT). We also assessed the relationship between SD-OCT measurements and cognitive measures, serum biomarkers for Alzheimer's disease (AD), and cerebral microstructural volume. METHODS: pRNFL, RNFL, and GCC thicknesses were measured in 43 EOAD and 42 controls using SD-OCT. Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were used to assess cognitive status, magnetic resonance imaging (MRI) tool was used to quantify cerebral microstructural volume, and serum biomarkers were quantified from peripheral blood. RESULTS: EOAD patients had thinner pRNFL (P < 0.001), RNFL (P = 0.008), and GCC (P = 0.018) thicknesses compared to controls after adjusting for multiple factors. pRNFL thickness correlated (P = 0.016) with serum t-tau level. Serum Aß42 (P < 0.05) concentration correlated with RNFL thickness. Importantly, occipital lobe volume (P = 0.010) correlated with GCC thicknesses in EOAD patients. CONCLUSION: Our findings suggest that retinal thickness may be useful markers for assessing neurodegenerative process in EOAD.


Assuntos
Doença de Alzheimer , Biomarcadores , Encéfalo , Tomografia de Coerência Óptica , Humanos , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Masculino , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Retina/patologia , Retina/diagnóstico por imagem , Idoso , Neurônios Retinianos/patologia , Fibras Nervosas/patologia , Fragmentos de Peptídeos/sangue
17.
Appl Microbiol Biotechnol ; 108(1): 146, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240862

RESUMO

2,3-Butanediol (2,3-BDO) is an important gateway molecule for many chemical derivatives. Currently, microbial production is gradually being recognized as a green and sustainable alternative to petrochemical synthesis, but the titer, yield, and productivity of microbial 2,3-BDO remain suboptimal. Here, we used systemic metabolic engineering strategies to debottleneck the 2,3-BDO production in Enterobacter aerogenes. Firstly, the pyruvate metabolic network was reconstructed by deleting genes for by-product synthesis to improve the flux toward 2,3-BDO synthesis, which resulted in a 90% increase of the product titer. Secondly, the 2,3-BDO productivity of the IAM1183-LPCT/D was increased by 55% due to the heterologous expression of DR1558 which boosted cell resistance to abiotic stress. Thirdly, carbon sources were optimized to further improve the yield of target products. The IAM1183-LPCT/D showed the highest titer of 2,3-BDO from sucrose, 20% higher than that from glucose, and the yield of 2,3-BDO reached 0.49 g/g. Finally, the titer of 2,3-BDO of IAM1183-LPCT/D in a 5-L fermenter reached 22.93 g/L, 85% higher than the wild-type strain, and the titer of by-products except ethanol was very low. KEY POINTS: Deletion of five key genes in E. aerogenes improved 2,3-BDO production The titer of 2,3-BDO was increased by 90% by regulating metabolic flux Response regulator DR1558 was expressed to increase 2,3-BDO productivity.


Assuntos
Enterobacter aerogenes , Enterobacter aerogenes/genética , Enterobacter aerogenes/metabolismo , Engenharia Metabólica/métodos , Butileno Glicóis/metabolismo , Reatores Biológicos , Fermentação
18.
Nucleic Acids Res ; 52(D1): D963-D971, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37953384

RESUMO

Polygenic score (PGS) is an important tool for the genetic prediction of complex traits. However, there are currently no resources providing comprehensive PGSs computed from published summary statistics, and it is difficult to implement and run different PGS methods due to the complexity of their pipelines and parameter settings. To address these issues, we introduce a new resource called PGS-Depot containing the most comprehensive set of publicly available disease-related GWAS summary statistics. PGS-Depot includes 5585 high quality summary statistics (1933 quantitative and 3652 binary trait statistics) curated from 1564 traits in European and East Asian populations. A standardized best-practice pipeline is used to implement 11 summary statistics-based PGS methods, each with different model assumptions and estimation procedures. The prediction performance of each method can be compared for both in- and cross-ancestry populations, and users can also submit their own summary statistics to obtain custom PGS with the available methods. Other features include searching for PGSs by trait name, publication, cohort information, population, or the MeSH ontology tree and searching for trait descriptions with the experimental factor ontology (EFO). All scores, SNP effect sizes and summary statistics can be downloaded via FTP. PGS-Depot is freely available at http://www.pgsdepot.net.


Assuntos
Bioestatística , Herança Multifatorial , Estudo de Associação Genômica Ampla , Herança Multifatorial/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Bioestatística/métodos
19.
Water Res ; 249: 120971, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101042

RESUMO

The digital transformation of sludge treatment processes requires online sensing of dewaterability. This topic has been attempted for many years based on macroscopic shear rheology. However, the relationship between rheological behavior and dewaterability remains noncommittal, and the reason is unclear. Herein, a binary gel-like structure model was proposed including the interactions network at the supra-flocs level and the gel-like structure at the flocs level. Multiple advanced techniques including optical tweezers were employed to precisely understand the binary gel-like structure and to classify the correlation mechanism between this gel-like structure, rheological behavior, and dewaterability. The analysis of sludge from eight wastewater treatment plants showed the binary gel-like structures at both supra-flocs and flocs levels have significant relationships with sludge dewaterability (p < 0.05). Further deconstruction of the sludge viscoelastic behavior illustrated that the gel-like structure at the supra-flocs level dominates the rheological behavior of sludge. Moreover, the direct description of the binary gel-like structure in four typical sludge treatment processes highlighted the importance of the flocs level's structure in determining the dewaterability. Overall, this study revealed that shear rheology may prefer to stress the interactions network at the supra-flocs level but mask the flocs level's structure, although the latter is important. This observation may provide a general guideline for the design of robust sensors for dewaterability.


Assuntos
Esgotos , Purificação da Água , Esgotos/química , Água/química , Purificação da Água/métodos , Reologia , Eliminação de Resíduos Líquidos/métodos
20.
J Pharm Biomed Anal ; 240: 115929, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38147703

RESUMO

A quantitative structure retention relationship (QSRR) method was developed to identify flavonoid isomers auxiliary using an ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method based on the linear relationships between the Ln(k') values of flavonoids and their hydrogen bonding energy (XAH) and dissolution energy (ES). Chromatographic separation was achieved with a Hypersil GOLD C18 (100 mm × 2.1 mm, 1.9 µm) column and Agilent SB-C18 (2.1 ×50 mm, 1.8 µm) column on a Dionex Ultimate 3000 RSLC chromatograph. Compounds were eluted isocratically using a mobile phase containing 0.1% formic acid/water solution and methanol at a ratio of 55:45 (v/v). Mass spectrometry was performed in the negative and positive ionization modes on a Thermo Fisher Q Exactive Orbitrap mass spectrometer equipped with an electrospray ionization interface. The established QSRR model was Ln(k') = 5.6163 + 0.0469ES - 0.0984XAH, with a determination coefficient (R2) of 0.9981, adjusted determination coefficient (adjR2) of 0.9976, and corrected root mean square error of 0.0682. The determination coefficient of the leave-one-out (LOO) cross-validation (Q2LOO) was 0.9976, and the cross-verification root mean square error was 0.0754. Simulated samples containing 7 flavonoids were used to validate the feasibility of the method. The classical method (UHPLC-MS/MS combined the CD software and the mzCloud, mzVault and Chemspider databases) was used to identify the seven flavonoids in the simulated samples. This classic identification strategy cannot provide accurate identification results, which provided multiple identification results for each compound in the simulated samples. On the basis of the results, the 7 flavonoids were accurately identified by the established QSRR model, and the reference standards were used to validate it. The relative error of retention time(RE(tR)) between the model calculation and experimental results was less than 10%. This method effectively complements and improves the classical methods, that UHPLC-MS/MS combined the CD software and the mass spectra databases were used to identify flavonoids identification.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Flavonoides , Cromatografia Líquida de Alta Pressão/métodos , Padrões de Referência
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