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1.
Insect Sci ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39121464

RESUMEN

The greater wax moth, Galleria mellonella (Lepidoptera, Pyralidae), is a major bee pest that inflicts considerable harm on beehives, leading to economic losses. It also serves as a valuable resource insect and a model organism. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system plays a crucial role in improving economic insect breeding and developing efficient agricultural pest management systems in Lepidoptera. However, the CRISPR/Cas9 protocols have not been developed for G. mellonella. Here, the Gmebony knockout (KO) strain was established using the CRISPR/Cas9 genome editing system. We obtained Gmebony KO strain in the G4 generation, which took approximately 10 months. When compared with wild-type, the head, notum, and the terminal abdominal surface of 1st to 4th instar larvae in the KO strain changed from yellow to brown, and these regions of the KO strain gradually transformed into a black color from the 5th instar larvae, and the body color of the adult moth in the KO strain changed to black. The developmental period of the early larval and the following larval instars extended. The embryonic hatchability of the Gmebony KO strain was significantly decreased. The pupal body weight of the Gmebony KO strain was not affected. The feasibility of the CRISPR/Cas9 methodology was validated by single-target editing of Gmebony. Our findings provide the first evidence that the ebony gene can serve as a pigmentation reference gene for genetic modifications of G. mellonella. Meanwhile, it can be utilized in the development of genome editing control strategies and for gene function analyses in G. mellonella.

2.
J Am Chem Soc ; 146(32): 22476-22484, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-38961805

RESUMEN

Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, the use of well-tailored photoredox catalysts represented the key to enable efficient pyridoxal phosphate (PLP) enzyme-catalyzed radical reactions. Here, we report a PLP-dependent threonine aldolase-catalyzed asymmetric α-C-H alkylation of abundant amino acids using Katritzky pyridinium salts as alkylating agents. The use of engineered threonine aldolases allowed for this redox-neutral radical alkylation to proceed efficiently, giving rise to challenging α-trisubstituted and -tetrasubstituted ncAA products in a protecting-group-free fashion with excellent enantiocontrol. Mechanistically, this enantioselective α-alkylation capitalizes on the unique reactivity of the persistent enzymatic quinonoid intermediate derived from the PLP cofactor and the amino acid substrate to allow for novel radical C-C coupling. Surprisingly, this photobiocatalytic process does not require the use of well-established photoredox catalysts and operates through an unconventional photoinduced radical generation involving a PLP-derived aldimine. The ability to develop photobiocatalytic reactions without relying on classic photocatalysts or photoenzymes opens up new avenues for advancing stereoselective intermolecular radical reactions that are not known in either organic chemistry or enzymology.


Asunto(s)
Aminoácidos , Procesos Fotoquímicos , Alquilación , Estereoisomerismo , Aminoácidos/química , Radicales Libres/química , Glicina Hidroximetiltransferasa/metabolismo , Glicina Hidroximetiltransferasa/química , Biocatálisis , Luz , Estructura Molecular
3.
Huan Jing Ke Xue ; 45(7): 4321-4331, 2024 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-39022977

RESUMEN

Phosphorus-solubilizing microorganisms convert insoluble phosphorus in the soil into phosphorus that can be absorbed by plants. Soluble phosphate combines with heavy metals to form precipitation, reducing the content of available heavy metals, thereby reducing the absorption of heavy metals by crops, which plays an important role in the remediation of heavy metal-contaminated soil. The effects of the immobilization of Cd and Pb and the release of PO43- by the phosphorus-solubilizing bacterium Klebsiella sp. M2 were studied through solution culture experiments. In addition, the effects of strain M2 on wheat uptake of Cd and Pb and its microbiological mechanism were also explored through pot experiments. The results showed that strain M2 reduced the concentrations of Cd and Pb and increased the concentration of PO43- in the solution through cell wall adsorption and induced phosphate precipitation. Pot experiments showed that compared to those in the CK group and inactivated strain M2 group, inoculation with live strain M2 significantly increased (123%-293%) the contents of Ca2-P and Ca8-P in rhizosphere soil, decreased the content of DTPA-Cd (34.48%) and DTPA-Pb (36.72%) in wheat rhizosphere soil, and thus hindered the accumulation of Cd and Pb in wheat grains. Moreover, high-throughput sequencing results showed that strain M2 significantly increased the diversity of wheat rhizosphere bacterial communities; increased the relative abundance of Proteobacteria, Gemmatimonadetes, and Bacteroidota in wheat rhizosphere soil; and increased the proportion of heavy metal-immobilizing and phosphorus-promoting bacteria in wheat rhizosphere soil (mainly Sphingomonas, Nocardioides, Bacillus, Gemmatimonas, and Enterobacter). These bacterial genera played an important role in immobilizing heavy metals and preventing wheat from absorbing heavy metals. These results provide bacterial resources and theoretical basis for the bioremediation of heavy metal-contaminated farmland.


Asunto(s)
Biodegradación Ambiental , Cadmio , Klebsiella , Plomo , Metales Pesados , Fósforo , Microbiología del Suelo , Contaminantes del Suelo , Triticum , Triticum/metabolismo , Triticum/microbiología , Contaminantes del Suelo/metabolismo , Fósforo/metabolismo , Metales Pesados/metabolismo , Cadmio/metabolismo , Plomo/metabolismo , Klebsiella/metabolismo , Rizosfera , Bacterias/metabolismo , Bacterias/clasificación
4.
J Transl Int Med ; 12(3): 253-262, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39081274

RESUMEN

Objective: To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors. Methods: This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored. Results: There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (µg·kg-1·min-1): norepinephrine (µg·kg-1·min-1). Conclusion: Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.

5.
Emerg Microbes Infect ; 13(1): 2382236, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39017656

RESUMEN

The incompletely eliminated Treponema pallidum (T. pallidum) during primary syphilis chancre infection can result in the progression of secondary, tertiary, or latent syphilis in individuals, suggesting that T. pallidum has successfully evaded the immune response and spread to distant sites. The mechanism underlying the dissemination of T. pallidum is unclear. Here, a syphilitic rabbit model dorsal-injected with recombinant Tp0136 protein or Tp0136 antibody subcutaneously was used to demonstrate the role of Tp0136 protein in promoting the dissemination of T. pallidum to the testis and angiogenesis in vivo; vascular endothelial cell line HMEC-1 was employed to display that Tp0136 protein enhances the angiogenesis. Furthermore, the three-dimensional microfluidic angiogenesis system showed that the angiogenesis would heighten vascular permeability. Then transcriptome sequencing analysis, in conjunction with cell-level validation, elucidated the critical role of the PI3K-AKT signaling pathway in the promotion of angiogenesis by Tp0136 protein, resulting in heightened permeability. These findings elucidate the strategy employed by T. pallidum in evading immune clearance.


Asunto(s)
Angiogénesis , Proteínas Bacterianas , Sífilis , Treponema pallidum , Animales , Humanos , Masculino , Conejos , Angiogénesis/microbiología , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Células Endoteliales/microbiología , Neovascularización Patológica/microbiología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal , Sífilis/microbiología , Treponema pallidum/genética
6.
Pathogens ; 13(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39057785

RESUMEN

We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014-2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools.

7.
Macromol Biosci ; : e2400078, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012275

RESUMEN

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

8.
J Med Internet Res ; 26: e47645, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-38869157

RESUMEN

In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.


Asunto(s)
Enfermedades Cardiovasculares , Aprendizaje Automático , Humanos , Reproducibilidad de los Resultados , Algoritmos
9.
Nature ; 629(8010): 98-104, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38693411

RESUMEN

Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases10-12, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.


Asunto(s)
Aminoácidos , Biocatálisis , Acoplamiento Oxidativo , Procesos Fotoquímicos , Aminoácidos/biosíntesis , Aminoácidos/química , Aminoácidos/metabolismo , Biocatálisis/efectos de la radiación , Evolución Molecular Dirigida , Radicales Libres/química , Radicales Libres/metabolismo , Glicina/química , Glicina/metabolismo , Glicina Hidroximetiltransferasa/metabolismo , Glicina Hidroximetiltransferasa/química , Indicadores y Reactivos , Luz , Acoplamiento Oxidativo/efectos de la radiación , Fosfato de Piridoxal/metabolismo , Estereoisomerismo , Aminoácidos de Cadena Ramificada/química , Aminoácidos de Cadena Ramificada/metabolismo
10.
Virulence ; 15(1): 2350892, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38745370

RESUMEN

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum, NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum, platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum, potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.


Asunto(s)
Plaquetas , Antígenos de Histocompatibilidad Clase I , Células Asesinas Naturales , Sífilis , Treponema pallidum , Células Asesinas Naturales/inmunología , Treponema pallidum/inmunología , Treponema pallidum/genética , Humanos , Plaquetas/inmunología , Plaquetas/microbiología , Antígenos de Histocompatibilidad Clase I/inmunología , Sífilis/inmunología , Sífilis/microbiología , Evasión Inmune
11.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1661-1672, 2024 Mar.
Artículo en Chino | MEDLINE | ID: mdl-38621950

RESUMEN

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.


Asunto(s)
Medicina Tradicional China , Osteoartritis de la Rodilla , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Osteoartritis de la Rodilla/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/administración & dosificación , Riñón/fisiopatología , Evaluación de Resultado en la Atención de Salud , Resultado del Tratamiento
12.
Nat Commun ; 15(1): 2365, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491012

RESUMEN

It remains a challenge to obtain biocompatible afterglow materials with long emission wavelengths, durable lifetimes, and good water solubility. Herein we develop a photooxidation strategy to construct near-infrared afterglow carbon nanodots with an extra-long lifetime of up to 5.9 h, comparable to that of the well-known rare-earth or organic long-persistent luminescent materials. Intriguingly, size-dependent afterglow lifetime evolution from 3.4 to 5.9 h has been observed from the carbon nanodots systems in aqueous solution. With structural/ultrafast dynamics analysis and density functional theory simulations, we reveal that the persistent luminescence in carbon nanodots is activated by a photooxidation-induced dioxetane intermediate, which can slowly release and convert energy into luminous emission via the steric hindrance effect of nanoparticles. With the persistent near-infrared luminescence, tissue penetration depth of 20 mm can be achieved. Thanks to the high signal-to-background ratio, biological safety and cancer-specific targeting ability of carbon nanodots, ultralong-afterglow guided surgery has been successfully performed on mice model to remove tumor tissues accurately, demonstrating potential clinical applications. These results may facilitate the development of long-lasting luminescent materials for precision tumor resection.


Asunto(s)
Nanopartículas , Neoplasias , Animales , Ratones , Luminiscencia
13.
BMC Med ; 22(1): 56, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317226

RESUMEN

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.


Asunto(s)
Inteligencia Artificial , Enfermedades Cardiovasculares , Humanos , Enfermedades Cardiovasculares/diagnóstico , Medición de Riesgo/métodos , Tamizaje Masivo/métodos , Reproducibilidad de los Resultados
14.
Plant Cell Environ ; 47(5): 1852-1864, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38334305

RESUMEN

Zinc (Zn) deficiency not only impairs plant growth and development but also has negative effects on human health. Rice (Oryza Sativa L.) is a staple food for over half of the global population, yet the regulation of Zn deficiency response in rice remains largely unknown. In this study, we provide evidence that two F-group bZIP transcription factors, OsbZIP48/50, play a crucial role in Zn deficiency response. Mutations in OsbZIP48/50 result in impaired growth and reduced Zn/Fe/Cu content under Zn deficiency conditions. The N-terminus of OsbZIP48/OsbZIP50 contains two Zn sensor motifs (ZSMs), deletion or mutation of these ZSMs leads to increased nuclear localization. Both OsbZIP48 and OsbZIP50 exhibit transcriptional activation activity, and the upregulation of 1117 genes involved in metal uptake and other processes by Zn deficiency is diminished in the OsbZIP48/50 double mutant. Both OsbZIP48 and OsbZIP50 bind to the promoter of OsZIP10 and activate the ZDRE cis-element. Amino acid substitution mutation of the ZSM domain of OsbZIP48 in OsbZIP50 mutant background increases the content of Zn/Fe/Cu in brown rice seeds and leaves. Therefore, this study demonstrates that OsbZIP48/50 play a crucial role in regulating metal homoeostasis and identifies their downstream genes involved in the Zn deficiency response in rice.


Asunto(s)
Oryza , Zinc , Humanos , Zinc/metabolismo , Oryza/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Metales/metabolismo , Homeostasis , Regulación de la Expresión Génica de las Plantas
15.
Neurochem Int ; 175: 105705, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38412923

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the quality of life of the elderly. Its pathogenesis has not yet been fully elucidated. Ferroptosis, a cell death caused by excessive accumulation of iron-dependent lipid peroxides, has been implicated in the pathogenesis of AD. Uncontrolled lipid peroxidation is the core process of ferroptosis, and inhibiting lipid peroxidation of ferroptosis may be an important therapeutic target for AD. Based on previous studies, we mixed standards of icariin, astragaloside IV, and puerarin, named the standard mixture YHG, and investigated the effect of YHG on ferroptosis -lipid peroxidation in APP/PS1 mice. DFX, a ferroptosis inhibitor, was used as a control drug. In this study, APP/PS1 mice were used as an AD animal model, and behavioral experiments, iron level detection, Transmission electron microscopy (TEM) observation, lipid peroxidation level detection, antioxidant capacity detection, immunofluorescence, Western blot and real-time qPCR were performed. It was found that YHG could reduce body weight, significantly improve abnormal behaviors and the ultrastructure of hippocampal neurons in APP/PS1 mice. The results of biochemical tests showed that YHG reduced the contents of iron, malondialdehyde (MDA) and lipid peroxide (LPO) in brain tissue and serum, and increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Immunofluorescence, WesternBlot and real-time qPCR results showed that YHG could promote the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4(GPX4). Inhibited the expression of long-chain acyllipid coenzyme a synthetase 4(ACSL4) and lysophosphatidyltransferase 3 (LPCAT3). This study suggests that the mechanism by which YHG improves cognitive dysfunction in APP/PS1 mice may be related to the inhibition of ferroptosis-lipid peroxidation.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Ferroptosis , Flavonoides , Isoflavonas , Enfermedades Neurodegenerativas , Saponinas , Triterpenos , Humanos , Anciano , Animales , Ratones , Peroxidación de Lípido , Calidad de Vida , Peróxidos Lipídicos , Enfermedad de Alzheimer/tratamiento farmacológico , Hierro , 1-Acilglicerofosfocolina O-Aciltransferasa
16.
Brain Behav ; 14(2): e3399, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38340139

RESUMEN

OBJECTIVE: To explore the impact of inflammatory factors on the incidence of cerebral small vessel disease (CSVD), we performed a mendelian randomization (MR) study to analyze the causal relationship between multiple inflammatory factors and CSVD imaging markers and utilized summary-data-based mendelian randomization (SMR) analysis to infer whether the impact of instrumental variables (IVs) on disease is mediated by gene expression or DNA methylation. METHODS: Using public databases such as UKB and IEU, and original genome-wide association studies, we obtained IVs related to exposure (inflammatory factors) and outcome (CSVD imaging markers). We performed the inverse variance weighted, weighted median, and MR-Egger methods to assess causal effects between exposure and outcome in univariate MR analysis. To evaluate their heterogeneity, a series of sensitivity analyses were conducted, including the Cochrane Q test, MR-Egger intercept test, MR-Presso, and leave-one-out analysis. We also applied mediation and multivariate MR analysis to explore the interactions between positive exposures on the same outcome. Additionally, we conducted the SMR, which utilizes instruments within or near relevant genes in blood or brain tissues, to elucidate the causal associations with CSVD markers. RESULTS: ABO Univariate MR of multiple cohorts revealed that the risk of small vessel stroke (SVS) increases with elevated levels of TNF-related apoptosis-inducing ligand (TRAIL, OR, 1.23, 95% CI, 1.08-1.39) and interleukin-1 receptor-like 2, (IL-1RL2, OR, 1.29, 95% CI, 1.04-1.61). IL-18 was a potential risk factor for extensive basal ganglia perivascular space burden (BGPVS, OR, 1.02, 95% CI, 1.00-1.05). Moreover, the risk of extensive white matter perivascular space burden (WMPVS) decreased with rising levels of E-selectin (OR, .98, 95% CI, .97-1.00), IL-1RL2 (OR, .97, 95% CI, .95-1.00), IL-3 receptor subunit alpha (IL-3Ra, OR, .98, 95% CI, .97-1.00), and IL-5 receptor subunit alpha (IL-5Ra, OR, .98, 95% CI, .97-1.00). Mediation and multivariate MR analysis indicated that E-selectin and IL-3Ra might interact during the pathogenesis of WMPVS. SMR estimates showed that TRAIL-related IVs rs5030044 and rs2304456 increased the risk of SVS by increasing the expression of gene Kininogen-1 (KNG1) in the cerebral cortex, particularly in the frontal cortex (ßsmr = .10, Psmr = .003, FDR = .04). Instruments (rs507666 and rs2519093) related to E-selectin and IL-3Ra could increase the risk of WMPVS by enhancing DNA methylation of the gene ABO in blood tissue (ßsmr = .01-.02, Psmr = .001, FDR = .01-.03). CONCLUSION: According to MR and SMR analysis, higher levels of TRAIL increased the risk of SVS by upregulating gene expression of KNG1 in brain cortex tissues. In addition, protective effects of E-selectin and IL-3a levels on WMPVS were regulated by increased DNA methylation of gene ABO in blood tissue.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Selectina E , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Factores de Riesgo , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/genética
17.
Int J Biol Macromol ; 260(Pt 2): 129599, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38246455

RESUMEN

Addressing highly flammable and easily breeding bacteria property via environmentally friendly approach was critical for the large-scale application of lyocell fibers. Herein, a bio-based coating constructed by layer-by-layer deposition of adenosine triphosphate (ATP), chitosan (CS), and polyethyleneimine (PEI) was successfully fabricated to obtain excellent fire-resistant and antimicrobial lyocell fabrics (LBL/Lyocell). The resulted fabrics with add-on of 11.5 wt% achieved the limiting oxygen index (LOI) of 32.0 %. Meanwhile, compared with the pure lyocell fabrics, the peak of heat release rate (PHRR), total heat release (THR), and fire growth rate (FIGRA) of LBL/Lyocell fabrics decreased by 75.2 %, 61.0 % and 69.8 % in cone calorimetric test (CCT), respectively. By characterizing the gaseous products and solid residues, the presence of the ATP/CS/PEI coating could not only quickly form the dense expanded carbon layer by itself, but also promote the conversion of cellulose into thermal-stability residues, thus reducing the release of combustible substances during combustion and protecting the lyocell fabrics. In addition, LBL/Lyocell showed excellent antimicrobial properties with 99.99 % antibacterial rates against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). This bio-based coating was a promising candidate for efficiently flame-retardant cellulose fibers with excellent antibacteria.


Asunto(s)
Quitosano , Retardadores de Llama , Escherichia coli , Polietileneimina , Staphylococcus aureus , Adenosina Trifosfato , Antibacterianos/farmacología , Celulosa
18.
Phys Chem Chem Phys ; 26(5): 4589-4596, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38250962

RESUMEN

Multivalent-ion batteries have garnered significant attention due to their high energy density, low cost, and superior safety. Calcium-ion batteries (CIBs) are regarded as the next-generation energy storage systems for their abundant natural resources and bivalent characteristics. However, the absence of high-performance anode materials poses a significant obstacle to the progress of battery technology. Two-dimensional (2D) Dirac materials have excellent conductivity and abundant active sites, rendering them promising candidates as anode materials. A novel 2D Dirac material known as "graphene+" has been theoretically reported, exhibiting prominent properties including good stability, exceptional ductility, and remarkable electronic conductivity. By using first-principles calculations, we systematically investigate the performance of graphene+ as an anode material for CIBs. Graphene+ exhibits an ultra-high theoretical capacity (1487.7 mA h g-1), a small diffusion barrier (0.21 eV), and a low average open-circuit voltage (0.51 V). Furthermore, we investigate the impact of the electrolyte solvation on the performance of Ca-ion adsorption and migration. Upon contact with electrolyte solvents, graphene+ exhibits strong adsorption strength and rapid migration of Ca-ions on its surface. These results demonstrate the promising potential of graphene+ as a high-performance anode material for CIBs.

19.
Pest Manag Sci ; 80(3): 1016-1025, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37831548

RESUMEN

BACKGROUND: Weeds are one of the critical factors that negatively affect crop yield and quality. Microbial herbicides are a research hotspot for novel herbicides owing to their environmental safety and lack of weed resistance. In the current study, the active ingredients of Serratia marcescens Ha1, a new microbial herbicide, were investigated for their effectiveness against agricultural weeds using bioassay-guided fractionation. RESULTS: The results revealed that petroleum ether and ethyl acetate extracts of S. marcescens Ha1 had high herbicidal activity. Forty-nine compounds were identified from the petroleum ether extract, including 2,4-di-tert-butylphenol (DB; C14 H22 O, 38.82%), ethyl 14-methyl-hexadecanoate, 1-nonadecene, and [1,1'-biphenyl]-2,3'-diol, 3,4',5,6'-tetrakis. Of these, DB showed significant inhibitory effects on root and shoot growth in Amaranthus retroflexus, with half-maximal inhibitory concentration (IC50 ) values of 389.17 and 832.44 mg L-1 , respectively. In addition, 7-hydroxy-3-(2-methylpropyl)-2,3,6,7,8,8a-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione (HPD) was identified as the major active ingredient in the ethyl acetate extract of S. marcescens Ha1 using bioassay-guided fractionation, with IC50 values of 439.86 and 476.95 mg L-1 against A. retroflexus shoot and root growth, respectively. Scanning electron microscopy indicated that DB and HPD exert destructive effects on A. retroflexus root, and the damage is gradually aggravated with increasing treatment time and concentration. CONCLUSION: The S. marcescens Ha1 extract and its active compounds DB and HPD exhibit significant herbicidal activity, which could be utilized further for the development of microbial herbicides. © 2023 Society of Chemical Industry.


Asunto(s)
Acetatos , Alcanos , Herbicidas , Fenoles , Herbicidas/farmacología , Serratia marcescens , Malezas
20.
Curr Med Sci ; 44(1): 102-109, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38079054

RESUMEN

OBJECTIVE: This study aimed to investigate the changes of follicular helper T (TFH) and follicular regulatory T (TFR) cell subpopulations in patients with non-small cell lung cancer (NSCLC) and their significance. METHODS: Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls. Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1 (PD-1) and inducible co-stimulator (ICOS), and TFR cell subpopulation based on cluster determinant 45RA (CD45RA) and forkhead box protein P3 (FoxP3). The levels of interleukin-10 (IL-10), interleukin-17a (IL-17a), interleukin-21 (IL-21), and transforming growth factor-ß (TGF-ß) in the plasma were measured, and changes in circulating B cell subsets and plasma IgG levels were also analyzed. The correlation between serum cytokeratin fragment antigen 21-1 (CYFRA 21-1) levels and TFH, TFR, or B cell subpopulations was further explored. RESULTS: The TFR/TFH ratio increased significantly in NSCLC patients. The CD45RA+FoxP3int TFR subsets were increased, with their proportions increasing in stages II to III and decreasing in stage IV. PD-1+ICOS+TFH cells showed a downward trend with increasing stages. Plasma IL-21 and TGF-ß concentrations were increased in NSCLC patients compared with healthy controls. Plasmablasts, plasma IgG levels, and CD45RA+FoxP3int TFR cells showed similar trends. TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages I-III and negatively correlated with CYFRA 21-1 in stage IV. CONCLUSION: Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC, which is associated with serum CYFRA 21-1 levels and reflects disease progression.


Asunto(s)
Antígenos de Neoplasias , Carcinoma de Pulmón de Células no Pequeñas , Queratina-19 , Neoplasias Pulmonares , Humanos , Células T Auxiliares Foliculares , Receptor de Muerte Celular Programada 1 , Progresión de la Enfermedad , Factores de Transcripción Forkhead , Factor de Crecimiento Transformador beta , Inmunoglobulina G
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