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1.
Artículo en Inglés | MEDLINE | ID: mdl-38885107

RESUMEN

Monocular Depth Estimation (MDE) plays a vital role in applications such as autonomous driving. However, various attacks target MDE models, with physical attacks posing significant threats to system security. Traditional adversarial training methods, which require ground-truth labels, are not directly applicable to MDE models that lack ground-truth depth. Some self-supervised model hardening techniques (e.g., contrastive learning) overlook the domain knowledge of MDE, resulting in suboptimal performance. In this work, we introduce a novel self-supervised adversarial training approach for MDE models, leveraging view synthesis without the need for ground-truth depth. We enhance adversarial robustness against real-world attacks by incorporating L0-norm-bounded perturbation during training. We evaluate our method against supervised learning-based and contrastive learning-based approaches specifically designed for MDE. Our experiments with two representative MDE networks demonstrate improved robustness against various adversarial attacks, with minimal impact on benign performance. Our code: https://github.com/Bob-cheng/DepthModelHardening.

2.
Nat Commun ; 15(1): 5039, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38866775

RESUMEN

Urate, the physiological form of uric acid and a potent antioxidant in serum, plays a pivotal role in scavenging reactive oxygen species. Yet excessive accumulation of urate, known as hyperuricemia, is the primary risk factor for the development of gout. The high-capacity urate transporter GLUT9 represents a promising target for gout treatment. Here, we present cryo-electron microscopy structures of human GLUT9 in complex with urate or its inhibitor apigenin at overall resolutions of 3.5 Å and 3.3 Å, respectively. In both structures, GLUT9 exhibits an inward open conformation, wherein the substrate binding pocket faces the intracellular side. These structures unveil the molecular basis for GLUT9's substrate preference of urate over glucose, and show that apigenin acts as a competitive inhibitor by occupying the substrate binding site. Our findings provide critical information for the development of specific inhibitors targeting GLUT9 as potential therapeutics for gout and hyperuricemia.


Asunto(s)
Apigenina , Microscopía por Crioelectrón , Proteínas Facilitadoras del Transporte de la Glucosa , Ácido Úrico , Humanos , Proteínas Facilitadoras del Transporte de la Glucosa/metabolismo , Proteínas Facilitadoras del Transporte de la Glucosa/antagonistas & inhibidores , Proteínas Facilitadoras del Transporte de la Glucosa/química , Ácido Úrico/metabolismo , Ácido Úrico/química , Apigenina/farmacología , Apigenina/química , Sitios de Unión , Unión Proteica , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Modelos Moleculares , Gota/tratamiento farmacológico , Gota/metabolismo , Células HEK293
3.
Adv Sci (Weinh) ; : e2308384, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38634607

RESUMEN

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38597955

RESUMEN

A nanomicrocapsule system was constructed through the polymerization of tannic acid (TA) and emulsifier OP-10 (OP-10), followed by the chelation of iron ions, to develop a safe and effective method for controlling Rhizoctonia solani in agriculture. The encapsulated active component is a rosin-based triazole derivative (RTD) previously synthesized by our research group (RTD@OP10-TA-Fe). The encapsulation efficiency of the nanomicrocapsules is 82.39%, with an effective compound loading capacity of 96.49%. Through the encapsulation of the RTD via nanomicrocapsules, we improved its water solubility, optimized its stability, and increased its adhesion to the leaf surface. Under acidic conditions (pH = 5.0), the release rate of nanomicrocapsules at 96 h is 96.31 ± 0.8%, which is 2.04 times higher than the release rate under normal conditions (pH = 7.0). Additionally, the results of in vitro and in vivo antifungal assays indicate that compared with the original compound, the nanomicrocapsules exhibit superior antifungal activity (EC50 values of RTD and RTD@OP10-TA-Fe are 1.237 and 0.860 mg/L, respectively). The results of field efficacy trials indicate that compared with RTD, RTD@OP10-TA-Fe exhibits a more prolonged period of effectiveness. Even after 3 weeks, the antifungal rate of RTD@OP10-TA-Fe remains at 40%, whereas RTD, owing to degradation, shows an antifungal rate of 11.11% during the same period. Furthermore, safety assessment results indicate that compared with the control, RTD@OP10-TA-Fe has almost no impact on the growth of rice seedlings and exhibits low toxicity to zebrafish. This study provides valuable insights into controlling R. solani and enhancing the compound performance.

5.
Poult Sci ; 103(1): 103231, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37980764

RESUMEN

The meat production of broilers is crucial to economic benefits of broiler industries, while the slaughter performance of broilers is directly determined by skeletal muscle development. Hence, the broiler breeding for growth traits shows a great importance. As a kind of small noncoding RNA, microRNA (miRNA) can regulate the expression of multiple genes and perform a wide range of regulation in organisms. Currently, more and more studies have confirmed that miRNAs are closely associated with skeletal muscle development of chickens. Based on our previous miR-seq analysis (accession number: PRJNA668199), miR-460b-5p was screened as one of the key miRNAs probably involved in the growth regulation of chickens. However, the regulatory effect of miR-460b-5p on the development of chicken skeletal muscles is still unclear. Therefore, miR-460b-5p was further used for functional validation at the cellular level in this study. The expression pattern of miR-460b-5p was investigated in proliferation and differentiation stages of chicken primary myoblasts. It was showed that the expression level of miR-460b-5p gradually decreased from the proliferation stage (GM 50%) to the lowest at 24 h of differentiation. As differentiation proceeded, miR-460b-5p expression increased significantly, reaching the highest and stabilizing at 72 h and 96 h of differentiation. Through mRNA quantitative analysis of proliferation marker genes, CCK-8 and Edu assays, miR-460b-5p was found to significantly facilitate the transition of myoblasts from G1 to S phase and promote chicken myoblast proliferation. mRNA and protein quantitative analysis of differentiation marker genes, as well as the indirect immunofluorescence results of myotubes, revealed that miR-460b-5p significantly stimulated myotube development and promote chicken myoblast differentiation. In addition, the target relationship was validated for miR-460b-5p according to the dual-luciferase reporter assay and mRNA quantitative analysis, which indicates that miR-460b-5p was able to regulate RBM19 expression by specifically binding to the 3' UTR of RBM19. In summary, miR-460b-5p has positive regulatory effects on the proliferation and differentiation of chicken myoblasts, and RBM19 is a target gene of miR-460b-5p.


Asunto(s)
Pollos , MicroARNs , Animales , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Mioblastos , Regiones no Traducidas 3' , Diferenciación Celular , Desarrollo de Músculos/genética
6.
Food Res Int ; 173(Pt 2): 113414, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803746

RESUMEN

The inhibitory effects of liquiritigenin, liquiritin and glycyrrhizic acid against the hazards during the preparation of thermal reaction beef flavoring were investigated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Liquiritigenin(1.5 mM) inhibited Nε-carboxymethyl-L-lysine and Nε-carboxyethyl-L-lysine by up to 38.69 % and 61.27 %, respectively; 1.5 mM liquiritin inhibited 4-methylimidazole by up to 48.28 %; and 1.5 mM liquiritigenin and 1.0 mM liquiritin inhibited hydroxymethylfurfural by up to 61.20 % and 59.31 %, respectively. The results of the model system showed that the inhibitory effect of the 3 inhibitors could be extended to other thermal reaction flavoring systems. The 3 inhibitors can effectively block key intermediates in beef flavoring, and liquiritigenin can inhibit up to 22.97 % of glyoxal and 22.89 % of methylglyoxal. In addition, liquiritigenin and liquiritin can directly eliminate up to 25.87 % and 21.01 % of methylglyoxal by addition and other means. Free radicals in the simultaneous formation model system were measured using electron spin resonance (ESR), and the results showed that liquiritigenin, liquiritin and glycyrrhizic acid could scavenge free radicals in the system in a dose-dependent manner, with scavenging rates of up to 44.88-57.09 %. Therefore, the inhibitory effects of the 3 inhibitors can be attributed to the intermediate blocking and free radical scavenging pathways.


Asunto(s)
Productos Finales de Glicación Avanzada , Ácido Glicirrínico , Animales , Bovinos , Ácido Glicirrínico/farmacología , Espectrometría de Masas en Tándem , Piruvaldehído , Lisina/análisis , Carne/análisis , Radicales Libres
7.
Neural Netw ; 167: 706-714, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37729786

RESUMEN

Adversarial training is considered one of the most effective methods to improve the adversarial robustness of deep neural networks. Despite the success, it still suffers from unsatisfactory performance and overfitting. Considering the intrinsic mechanism of adversarial training, recent studies adopt the idea of curriculum learning to alleviate overfitting. However, this also introduces new issues, that is, lacking the quantitative criterion for attacks' strength and catastrophic forgetting. To mitigate such issues, we propose the self-paced adversarial training (SPAT), which explicitly builds the learning process of adversarial training based on adversarial examples of the whole dataset. Specifically, our model is first trained with "easy" adversarial examples, and then is continuously enhanced by gradually adding "complex" adversarial examples. This way strengthens the ability to fit "complex" adversarial examples while holding in mind "easy" adversarial samples. To balance adversarial examples between classes, we determine the difficulty of the adversarial examples locally in each class. Notably, this learning paradigm can also be incorporated into other advanced methods for further boosting adversarial robustness. Experimental results show the effectiveness of our proposed model against various attacks on widely-used benchmarks. Especially, on CIFAR100, SPAT provides a boost of 1.7% (relatively 5.4%) in robust accuracy on the PGD10 attack and 3.9% (relatively 7.2%) in natural accuracy for AWP.


Asunto(s)
Benchmarking , Aprendizaje , Redes Neurales de la Computación
8.
Genes (Basel) ; 14(9)2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37761904

RESUMEN

Broiler skeletal muscle growth is significantly influenced by miRNAs. Our earlier research demonstrated that miR-24-3p significantly suppressed the proliferation of chicken myoblasts while promoting their differentiation. The purpose of this study is to investigate miR-24-3p potential target genes in chickens. We collected myoblasts of Jinghai yellow chicken and transfected four samples with mimics of miR-24-3p and another four samples with mimic NC (negative control) for RNA-seq. We obtained 54.34 Gb of raw data in total and 50.79 Gb of clean data remained after filtering. Moreover, 11,635 genes were found to be co-expressed in these two groups. The mimic vs. NC comparison group contained 189 DEGs in total, 119 of which were significantly up-regulated and 70 of which were significantly down-regulated. Important biological process (BP) terminology such as nuclear chromosomal segregation, reproduction, and nuclear division were discovered by GO enrichment analysis for DEGs in the mimic vs. NC comparison group. KEGG pathway analysis showed that focal adhesion, cytokine-cytokine receptor interaction, the TGF-ß signaling pathway, and the MAPK signaling pathway were enriched in the top 20. Variation site analysis illustrated the SNP (single nucleotide polymorphisms) and INDEL (insertion-deletion) in the tested samples. By comparing the target genes predicted by miRDB (MicroRNA target prediction database) and TargetScan with the 189 DEGs found by the transcriptome sequencing, we discovered two up-regulated DEGs (NEURL1 and IQSEC3) and two down-regulated DEGs (REEP1 and ST6GAL1). Finally, we carried out qPCR experiments on eight DEGs and discovered that the qPCR results matched the sequencing outcomes. These findings will aid in identifying potential miR-24-3p target genes in chicken skeletal muscle and offer some new directions for upcoming research on broiler breeding.


Asunto(s)
MicroARNs , Transcriptoma , Animales , Transcriptoma/genética , Pollos/genética , Pollos/metabolismo , Perfilación de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Mioblastos/metabolismo
9.
Microsyst Nanoeng ; 9: 93, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37484502

RESUMEN

Flexible electrodes have demonstrated better biocompatibility than rigid electrodes in relieving tissue encapsulation and long-term recording. Nonhuman primates are closer to humans in their brains' structural and functional properties, thus making them more suitable than rodents as animal models for potential clinical usage. However, the application of flexible electrodes on nonhuman primates has rarely been reported. In the present study, a flexible multichannel electrode array for nonhuman primates was developed and implemented for extracellular recording in behaving monkeys. To minimize the window of durotomy for reducing possible risks, a guide-tube-compatible implantation solution was designed to deliver the flexible electrodes through the dura into the cortex. The proposed structure for inserting flexible electrodes was characterized ex vivo and validated in vivo. Furthermore, acute recording of multichannel flexible electrodes for the primates was performed. The results showed that the flexible electrodes and implantation method used in this study meet the needs of extracellular recording in nonhuman primates. Task-related neuronal activities with a high signal-to-noise ratio of spikes demonstrated that our whole device is currently a minimally invasive and clinically viable approach for extracellular recording.

10.
Anal Bioanal Chem ; 415(24): 5985-5996, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37505235

RESUMEN

Glyphosate (Glyp) is an organophosphorus herbicide, and its abuse causes potential harm to the environment and human health. Thus, the development of simple and portable methods for rapid and visual detection of glyphosate is of great importance. Herein, we successfully developed a new fluorescent probe L with dansyl fluorophore as a fluorescent dye and tetrapeptide (Ala-Ser-Arg-His-NH2) as a recognition group. According to the design, L exhibited a specific fluorescence quenching response to Cu2+ and formed an L-Cu2+ ensemble with a molecular ratio of 2:1, demonstrating a limit of detection (LOD) as low as 12.04 nM. Interestingly, the L-Cu2+ ensemble as a relay response probe exhibited a specific fluorescence "off-on" response to glyphosate without interference from other pesticides and anions based on the strong complexation of glyphosate and Cu2+. The LOD of the L-Cu2+ ensemble for glyphosate was calculated as 12.59 nM. Additionally, the results of three recovery experiments with real samples showed that L has good practicability and accuracy in detecting glyphosate. Test strips were also fabricated to achieve facile detection of glyphosate to demonstrate the practical application potential of the L-Cu2+ ensemble. The L-Cu2+ ensemble was integrated with a smartphone for semi-quantification of glyphosate in a field environment under a 365 nm UV lamp.


Asunto(s)
Colorantes Fluorescentes , Teléfono Inteligente , Humanos , Colorantes Fluorescentes/química , Cobre/química , Espectrometría de Fluorescencia/métodos , Péptidos/química , Glifosato
11.
Animals (Basel) ; 13(9)2023 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-37174466

RESUMEN

The kruppel-like factor (KLF) gene family is a group of transcription factors containing highly conserved zinc-finger motifs, which play a crucial role in cell proliferation and differentiation. Chicken has been widely used as a model animal for analyzing gene function, however, little is known about the function of the KLF gene family in chickens. In this study, we performed genome-wide studies of chicken KLF genes and analyzed their biological and expression characteristics. We identified 13 KLF genes from chickens. Our phylogenetic, motif, and conserved domain analyses indicate that the KLF gene family has remained conserved through evolution. Synteny analysis showed the collinear relationship among KLFs, which indicated that they had related biomolecular functions. Interaction network analysis revealed that KLFs worked with 20 genes in biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that KLF2 was involved in Apelin and Forkhead Box O (FOXO) signaling pathways. Moreover, qPCR showed that 13 KLF genes were expressed in the nine selected tissues and displayed various gene expression patterns in chickens. RNA-seq showed that KLF3 and KLF10 genes were differentially expressed in the normal and high-fat diet fed groups, and KLF4, KLF5, KLF6, KLF7, KLF9, KLF12, and KLF13 genes were differentially expressed between undifferentiated and differentiated chicken preadipocytes. Besides, RNA-seq also showed that KLF genes displayed different expression patterns in muscle at 11 and 16 embryonic days old, and in 1-day-old chickens. These results indicated that the KLF genes were involved in the development of muscle and fat in chickens. Our findings provide some valuable reference points for the subsequent study of the function of KLF genes.

12.
BMC Med Genomics ; 16(1): 97, 2023 05 09.
Artículo en Inglés | MEDLINE | ID: mdl-37161408

RESUMEN

BACKGROUND: circular RNAs (circRNAs) play a crucial role in many physiological and pathological processes including juvenile-onset systemic lupus erythematosus (JSLE). The aim of this study is to investigate the role of circRNA hsa_circ_0008945 in JSLE and evaluate its significance as diagnosing biomarker. METHODS: RT-qPCR was applied to detect the level of circ_0008945 in JSLE and controls. The Spearman correlation test assessed the correlation between circ_0008945 and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. Overexpression or knockdown of circ_0008945 in primary peripheral blood mononuclear cells (PBMCs) was performed to further examine its function in apoptosis. RESULTS: RT-qPCR revealed that there were significantly higher levels of hsa_circ_0008945 in PMBCs from JSLE patients (p < 0.001) compared to healthy controls. In addition, there were significant associations between hsa_circ_0008945 level and the level of C3, C4, anti-ds DNA, IgG, CRP and ESR (p < 0.05) but not associated with the level of Ig A and Ig M. ROC curve of the circ_0008945 showed that the AUC was 0.790 and it may potentially be used as a novel biomarker for the diagnosis of JSLE. The results showed that overexpression of circ-0008945 increased the apoptosis of PBMCs while knockdown of circ-0008945 by siRNA decreased the apoptosis of PBMCs, supporting that circ-0008945 promoted the apoptosis in PBMCs and contributed to the pathogenesis of JSLE. CONCLUSION: The role of circ_0008945 was first investigated in JSLE and proposed herein their possible contribution to the pathogenesis of JSLE. This study provides not only novel insight into the pathological mechanisms but also the potential value as a useful biomarker for JSLE.


Asunto(s)
Leucocitos Mononucleares , Lupus Eritematoso Sistémico , Humanos , Apoptosis , Lupus Eritematoso Sistémico/genética , ARN Circular/genética , ARN Interferente Pequeño
13.
Mol Divers ; 2023 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-36933104

RESUMEN

A variety of myricetin derivatives containing thioether quinoline moiety were designed and synthesized. Their structures of title compounds were determined by 1H NMR, 13C NMR, 19F NMR, and HRMS. Single-crystal X-ray diffraction experiments were carried out with B4. Antiviral activity indicated that some of the target compounds exhibited remarkable anti-tobacco mosaic virus (TMV) activity. In particular, compound B6 possessed significant activity. The half maximal effective concentration (EC50) value of the curative activity of compound B6 was 169.0 µg/mL, which was superior to the control agent ningnanmycin (227.2 µg/mL). Meanwhile, the EC50 value of the protective activity of compound B6 was 86.5 µg/mL, which was better than ningnanmycin (179.2 µg/mL). Microscale thermophoresis (MST) indicated that compound B6 had a strong binding capability to the tobacco mosaic virus coat protein (TMV-CP) with a dissociation constant (Kd) value of 0.013 µmol/L, which was superior to that of myricitrin (61.447 µmol/L) and ningnanmycin (3.215 µmol/L). And the molecular docking studies were consistent with the experimental results. Therefore, these novel myricetin derivatives containing thioether quinoline moiety could become potential alternative templates for novel antiviral agents.

14.
Micromachines (Basel) ; 14(3)2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36984991

RESUMEN

Crystallization often occurs in the processing of amorphous alloys, causing the materials lose their excellent properties. The study adopts chemical mechanical polishing of amorphous alloys, presenting the effect of the rotational speed of the polishing turntable, size of abrasive, polishing pressure, and oxidant concentration. The Taguchi method is used to find the best processing parameters, and AFM is used to characterize the machined material surface. At the same time, XPS is used to detect the change of oxide film composition with the addition of oxidant. The results indicate the optimum process parameters: rotational speed of the polishing turntable is 75 r/min, polishing pressure is 28.3 kPa, the size of abrasive is 0.5 µm, and the size of abrasive is a significant factor affecting surface roughness Sa. In addition, as the size of abrasive increases, the material removal rate increases while the surface roughness Sa increases. At pH 10, with an abrasive particle size of 0.5 µm, as the H2O2 concentration increases, the MRR first rapidly decreases at 0.21 wt.% H2O2, and then gradually increases, while the Sa decreases. Furthermore, with the addition of oxidant, the main composition of the surface oxide film changes from oxide to hydroxide, and the contents of Zr4+ and Cu0/Cu1+ elements increase. The findings can provide a feasible chemical mechanical polishing process for zirconium-based amorphous alloys to obtain a satisfactory polishing effect.

15.
Front Public Health ; 11: 1115128, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36926173

RESUMEN

With the acceleration of the pace of urban life and the development of information technology, the takeout industry has emerged as the times require, which obtains intermediate costs by distributing goods to consumers. People pay more and more attention to public health, which requires takeout workers to drive as fast as possible to ensure the quality and safety of goods, but it also makes takeout workers suffer from various occupational injuries, such as car accidents, stomach diseases caused by eating disorders and long-term psychological pressure. This paper optimized the employment protection of takeout workers in combination with their professional characteristics. This paper used the analytic hierarchy process (AHP) to analyze the indicators that can evaluate the optimization effect of employment protection for takeout workers, and compared the occupation of takeout workers before and after employment protection. The experimental results showed that in Meituan takeout, the rationality of the average delivery management system before and after the optimization of employment protection was 47.2 and 64.4%, respectively; in ELEME takeout, the rationality of the average takeout distribution management system before and after the optimization of employment protection was 55.0% and 69.8%, respectively. Therefore, in the context of public health, the implementation of social security, employment relationship and optimization of service evaluation mechanism for outbound sales personnel can effectively improve the rationality of the delivery management system.


Asunto(s)
Traumatismos Ocupacionales , Humanos , Salud Pública , Empleo , Industrias , Ocupaciones
16.
Pest Manag Sci ; 79(1): 274-283, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36148624

RESUMEN

BACKGROUND: With the long-term use of traditional bactericides and antiviral agents, drug resistance has become increasingly prominent, resulting in impaired crop growth and yields. Based on this, the introduction of small molecular active groups into natural products has become the direction of research for green pesticides. RESULTS: In this study, novel 1,3,4-oxadiazole sulfonate/carboxylate flavonoid derivatives were explored. Among them, D4 exhibited good inhibitory effects on plant bacteria. It is worth mentioning that D4 (15 µg ml-1 ) exhibited an excellent median effective concentration (EC50 ) value against Xanthomonas oryzae pv. oryzae (Xoo), which was better than bismerthiazol (73 µg ml-1 ) and thiodiazole copper (100 µg ml-1 ). The EC50 for D4 was much lower than the two positive controls (bismerthiazol, thiodiazole copper), making D4 more potent in this assay of bacterial growth inhibition. In addition, mechanism research using scanning electron microscopy revealed that D4 could cause deformation or rupture of the cell membranes of Xoo and Pseudomonas syringae pv. actinidiae. Moreover, D4 exhibited the best EC50 for in vivo curative (132 µg ml-1 ) and protective (101 µg ml-1 ) activities against tobacco mosaic virus, which were more effective than ningnanmycin. Microscale thermophoresis data suggested that D4 [dissociation constant (Kd ) = 0.038 ± 0.011 µmol L-1 ] exhibited a stronger binding capacity than the control agent ningnanmycin (Kd = 4.707 ± 2.176 µmol L-1 ). CONCLUSION: The biological activity data and mode of action demonstrated that D4 had the best antibacterial and antiviral effects. Compound D4 discovered in the current work may be a very promising agricultural drug. © 2022 Society of Chemical Industry.


Asunto(s)
Cobre , Flavonoides , Flavonoides/farmacología
17.
Cell Oncol (Dordr) ; 46(2): 451-464, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36512307

RESUMEN

PURPOSE: Chronic myeloid leukemia (CML) is a myeloproliferative disease derived from hematopoietic stem cells (HSCs) that harbor Philadelphia chromosome (Ph chromosome). In clinic, leukemia stem cells (LSCs) in CML are insensitive to the treatment with tyrosine kinase inhibitors, and are responsible for disease relapse. However, the molecular mechanisms for maintaining LSCs survival remain elusive. METHODS: CML patient-derived cell lines and BCR-ABL-induced CML mouse model were used to explore the role of YBX1 in regulating the survival of CML LSCs. Bone marrow transduction and transplantation, and colony-forming unit assay were used to investigate LSC function. The underlying mechanism of how YBX1 regulates LSCs survival were assessed using flow cytometry, RNA sequencing, western blot, RNA decay assay, co-immunoprecipitation and RNA immunoprecipitation. RESULTS: Here we show that RNA-binding protein YBX1 plays an important role in regulating survival of CML LSCs. We find that YBX1 expression is significantly increased in CML cells, and confirm that YBX1 is required for maintaining survival of LSCs. Deletion of YBX1 impairs the propagation of CML through blocking cell proliferation and inducing apoptosis of LSCs. Mechanistically, we find that YBX1 regulates expression of apoptotic associated genes. YBX1 cooperates with RNA m6A reader IGF2BPs to stabilize YWHAZ transcript in an m6A-dependent manner, and loss of YBX1 decreases YWHAZ expression by accelerating mRNA decay. Restoration of YWHAZ efficiently rescues the defects of YBX1-deficient CML cells. CONCLUSION: Our findings reveal a critical role of YBX1 in maintaining survival of CML LSCs, which provides a rationale for targeting YBX1 in CML treatment.


Asunto(s)
Proteínas 14-3-3 , Leucemia Mielógena Crónica BCR-ABL Positiva , Células Madre Neoplásicas , Animales , Ratones , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Células Madre Neoplásicas/metabolismo , ARN/metabolismo , Proteínas 14-3-3/metabolismo
18.
Sci Rep ; 12(1): 19807, 2022 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-36396806

RESUMEN

The selection of materials is a complex and elusive process due to the multiple factors related to health. For the effective selection of materials, a comprehensive model for evaluating the health grade of materials was proposed with the mathematical method of the fuzzy comprehensive evaluation (FCE) and grey relational analysis (GRA). A health evaluation procedure scheme of the AgBB as well as standards of the forestry industry of the People's Republic of China and standards of the health industry of the People's Republic of China were referred to during the process. Based on Qt technology, a computer program was developed to calculate the compound comprehensive evaluation models. The data of Choerospondias axillaris with different lacquers were used as practical examples firstly, and then, the emission and odor characteristics of Xylosma racemosum (Sieb. et Zucc.) Miq. with PU, UV, and waterborne coating were explored with the technology of GC-MS/O. Results showed that: a total of 21 odorants were identified from Xylosma racemosum with PU, UV, and waterborne coating. The health grade of three Xylosma racemosum samples was UV > waterborne > PU, with the health grade of UV coating being "A", and the boards with PU and the waterborne coating were "N", with a fuzzy comprehensive index of PPU = 0.5151, Pwaterborne coatings=0.4950. Based on the results, it is proved that the establishment of the comprehensive evaluation model based on FCE and GRA successfully converts qualitative evaluation into quantitative evaluation; in addition, effectively evaluates the health grade of materials. This study provides a better understanding of materials' health grades, which will aid consumers in reducing indoor air pollution and using their products properly.


Asunto(s)
Contaminación del Aire Interior , Humanos , China , Odorantes , Cromatografía de Gases y Espectrometría de Masas
19.
Animals (Basel) ; 12(22)2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36428392

RESUMEN

Skeletal muscle growth has always been the focus of the broiler industry, and circRNAs play a significant role in this process. We collected leg muscles of slow- and fast-growing Bian chicken embryos in the study at 14 (S14 and F14) and 20 (S20 and F20) days for RNA-seq. Finally, 123 and 121 differentially expressed circRNAs (DECs) were identified in S14 vs. F14 and S20 vs. F20, respectively. GO enrichment analysis for DECs obtained important biological process (BP) terms including nicotinate nucleotide biosynthetic process, nicotinate nucleotide salvage, and NAD salvage in S20 vs. F20 and protein mannosylation in S14 vs. F14. KEGG pathway analysis showed Wnt signaling pathway, Tight junction, Ubiquitin mediated proteolysis, and Notch signaling pathway were enriched in the top 20. Based on the GO and KEGG analysis results, we found some significant host genes and circRNAs such as NAPRT and novel_circ_0004547, DVL1 and novel_circ_0003578, JAK2 and novel_circ_0010289, DERA and novel_circ_0003082, etc. Further analysis found 19 co-differentially expressed circRNAs between the two comparison groups. We next constructed a circRNA-miRNA network for them, and some candidate circRNA-miRNA pairs related to skeletal muscle were obtained, such as novel_circ_0002153-miR-12219-5p, novel_circ_0003578-miR-3064-3p, and novel_circ_0010661-miR-12260-3p. These results would help to reveal the mechanism for circRNAs in skeletal muscle and also provide some guidance for the breeding of broilers.

20.
Science ; 376(6598): eabl8280, 2022 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-35679404

RESUMEN

INTRODUCTION The nuclear pore complex (NPC) resides on the nuclear envelope (NE) and mediates nucleocytoplasmic cargo transport. As one of the largest cellular machineries, a vertebrate NPC consists of cytoplasmic filaments, a cytoplasmic ring (CR), an inner ring, a nuclear ring, a nuclear basket, and a luminal ring. Each NPC has eight repeating subunits. Structure determination of NPC is a prerequisite for understanding its functional mechanism. In the past two decades, integrative modeling, which combines x-ray structures of individual nucleoporins and subcomplexes with cryo-electron tomography reconstructions, has played a crucial role in advancing our knowledge about the NPC. The CR has been a major focus of structural investigation. The CR subunit of human NPC was reconstructed by cryo-electron tomography through subtomogram averaging to an overall resolution of ~20 Å, with local resolution up to ~15 Å. Each CR subunit comprises two Y-shaped multicomponent complexes known as the inner and outer Y complexes. Eight inner and eight outer Y complexes assemble in a head-to-tail fashion to form the proximal and distal rings, respectively, constituting the CR scaffold. To achieve higher resolution of the CR, we used single-particle cryo-electron microscopy (cryo-EM) to image the intact NPC from the NE of Xenopus laevis oocytes. Reconstructions of the core region and the Nup358 region of the X. laevis CR subunit had been achieved at average resolutions of 5 to 8 Å, allowing identification of secondary structural elements. RATIONALE Packing interactions among the components of the CR subunit were poorly defined by all previous EM maps. Additional components of the CR subunit are strongly suggested by the EM maps of 5- to 8-Å resolution but remain to be identified. Addressing these issues requires improved resolution of the cryo-EM reconstruction. Therefore, we may need to enhance sample preparation, optimize image acquisition, and develop an effective data-processing strategy. RESULTS To reduce conformational heterogeneity of the sample, we spread the opened NE onto the grids with minimal force and used the chemical cross-linker glutaraldehyde to stabilize the NPC. To alleviate orientation bias of the NPC, we tilted sample grids and imaged the sample with higher electron dose at higher angles. We improved the image-processing protocol. With these efforts, the average resolutions for the core and the Nup358 regions have been improved to 3.7 and 4.7 Å, respectively. The highest local resolution of the core region reaches 3.3 Å. In addition, a cryo-EM structure of the N-terminal α-helical domain of Nup358 has been resolved at 3.0-Å resolution. These EM maps allow the identification of five copies of Nup358, two copies of Nup93, two copies of Nup205, and two copies of Y complexes in each CR subunit. Relying on the EM maps and facilitated by AlphaFold prediction, we have generated a final model for the CR of the X. laevis NPC. Our model of the CR subunit includes 19,037 amino acids in 30 nucleoporins. A previously unknown C-terminal fragment of Nup160 was found to constitute a key part of the vertex, in which the short arm, long arm, and stem of the Y complex meet. The Nup160 C-terminal fragment directly binds the ß-propeller proteins Seh1 and Sec13. Two Nup205 molecules, which do not contact each other, bind the inner and outer Y complexes through distinct interfaces. Conformational elasticity of the two Nup205 molecules may underlie their versatility in binding to different nucleoporins in the proximal and distal CR rings. Two Nup93 molecules, each comprising an N-terminal extended helix and an ACE1 domain, bridge the Y complexes and Nup205. Nup93 and Nup205 together play a critical role in mediating the contacts between neighboring CR subunits. Five Nup358 molecules, each in the shape of a shrimp tail and named "the clamp," hold the stems of both Y complexes. The innate conformational elasticity allows each Nup358 clamp to adapt to a distinct local environment for optimal interactions with neighboring nucleoporins. In each CR subunit, the α-helical nucleoporins appear to provide the conformational elasticity; the 12 ß-propellers may strengthen the scaffold. CONCLUSION Our EM map-based model of the X. laevis CR subunit substantially expands the molecular mass over the reported composite models of vertebrate CR subunit. In addition to the Y complexes, five Nup358, two Nup205, and two Nup93 molecules constitute the key components of the CR. The improved EM maps reveal insights into the interfaces among the nucleoporins of the CR. [Figure: see text].


Asunto(s)
Proteínas de Complejo Poro Nuclear , Poro Nuclear , Proteínas de Xenopus , Xenopus laevis , Animales , Microscopía por Crioelectrón , Citoplasma/metabolismo , Poro Nuclear/química , Proteínas de Complejo Poro Nuclear/química , Conformación Proteica , Proteínas de Xenopus/química , Xenopus laevis/metabolismo
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