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2.
Viruses ; 16(5)2024 04 26.
Article in English | MEDLINE | ID: mdl-38793564

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen that causes severe abortions in sows and high piglet mortality, resulting in huge economic losses to the pig industry worldwide. The emerging and novel PRRSV isolates are clinically and biologically important, as there are likely recombination and pathogenic differences among PRRSV genomes. Furthermore, the NADC34-like strain has become a major epidemic strain in some parts of China, but the characterization and pathogenicity of the latest strain in Inner Mongolia have not been reported in detail. In this study, an NADC34-like strain (CHNMGKL1-2304) from Tongliao City, Inner Mongolia was successfully isolated and characterized, and confirmed the pathogenicity in pigs. The phylogenetic tree showed that this strain belonged to sublineage 1.5 and had high homology with the strain JS2021NADC34. There is no recombination between CHNMGKL1-2304 and any other domestic strains. Animal experiments show that the CHNMGKL1-2304 strain is moderately virulent to piglets, which show persistent fever, weight loss and high morbidity but no mortality. The presence of PRRSV nucleic acids was detected in both blood, tissues, nasal and fecal swabs. In addition, obvious pathological changes and positive signals were observed in lung, lymph node, liver and spleen tissues when subjected to hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). This report can provide a basis for epidemiological investigations and subsequent studies of PRRSV.


Subject(s)
Genome, Viral , Phylogeny , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Animals , Swine , Porcine respiratory and reproductive syndrome virus/genetics , Porcine respiratory and reproductive syndrome virus/pathogenicity , Porcine respiratory and reproductive syndrome virus/isolation & purification , Porcine respiratory and reproductive syndrome virus/classification , China , Porcine Reproductive and Respiratory Syndrome/virology , Porcine Reproductive and Respiratory Syndrome/pathology , Virulence , Evolution, Molecular
3.
Front Plant Sci ; 15: 1354384, 2024.
Article in English | MEDLINE | ID: mdl-38742214

ABSTRACT

One-time application of blended controlled-release nitrogen fertilizer (CRN) has the potential to solve the difficulty of top-dressing fertilizer in the cultivation of rice and reduce the cost of CRN fertilizer application. However, its effects on rice dry matter and nitrogen (N) accumulation and translocation, yield and N-use efficiency (NUE) remain uncertain. Field experiments were carried out at three sites (Mingguang, Chaohu, and Guichi) in the Yangtze River Delta in China to compare the effects of the conventional split applications of urea and the blended CRN and on post-anthesis dry matter and N accumulation and translocation, yield, and NUE in rice at 0, 60, 120, 180, and 240 kg N ha-1. The results showed that at the equal N application rates, compared under the conventional N fertilizer treatment, the blended CRN application significantly increased the rice yield by an average of 0.9-6.9%, mainly due to increase the number of spikelets per panicle. The highest yield achieved with blended CRN treatment occurred at 200 kg N ha-1, with an NUE of 45.9%. Moreover, in comparison to the conventional N fertilizer, the blended CRN treatment increased pre-anthesis N translocation (Pre-NT) by 1.0-19.8%, and the contribution of pre-NT to grain N by 0.2-8.7%, and NUE by 3.2-28.4%. Meanwhile, the blended CRN treatment reduced labor costs by 1800 Yuan ha-1 and enhanced the economic gains by 21.5-68.8%. Therefore, one-time application of blended CRN ≤ 200 kg N ha-1 application rate improved rice yield, NUE, and economic profit compared to equivalent rates of split applied conventional N fertilizers.

4.
Arch Pharm (Weinheim) ; : e2400131, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38678538

ABSTRACT

Three series of N-{[4-([1,2,4]triazolo[1,5-α]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl]methyl}acetamides (14a-d, 15a-n, and 16a-f) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW-7197 (vactosertib) and 14 times that of the clinical candidate LY-2157299. The selectivity index of 16f against p38α mitogen-activated protein kinase was >109, which was much higher than that of positive controls (EW-7197: >41, and LY-2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α-smooth muscle actin (α-SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP-1)/matrix metalloproteinase 13 (MMP-13) in transforming growth factor-ß-induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.

5.
J Am Chem Soc ; 146(15): 10640-10654, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38568727

ABSTRACT

Foreign ions as additives are of great significance for realizing excellent control over the morphology of noble metal nanostructures in the state-of-the-art seed-mediated growth method; however, they remain largely unexplored in chiral synthesis. Here, we report on a Cu2+-dominated chiral growth strategy that can direct the growth of concave chiral Au nanoparticles with C3-dominant chiral centers. The introduction of trace amounts of Cu2+ ions in the seed-mediated chiral growth process is found to dominate the chirality transfer from chiral molecules to chiral nanoparticles, leading to the formation of chiral nanoparticles with a concave VC geometry. Both experimental and theoretical results further demonstrate the correlation between the nanoparticle structure and optical chirality for the concave chiral nanoparticle. The Cu2+ ion is found to dominate the chiral growth by selectively activating the deposition of Au atoms along the [110] and [111] directions, facilitating the formation of the concave VC. We further demonstrate that the Cu2+-dominated chiral growth strategy can be employed to generate a variety of concave chiral nanoparticles with enriched geometric chirality and desired chiroptical properties. Concave chiral nanoparticles also exhibit appealing catalytic activity and selectivity toward electrocatalytic oxidation of enantiomers in comparison to helicoidal nanoparticles. The ability to tune the geometric chirality in a controlled manner by simply manipulating the Cu2+ ions as additives opens up a promising strategy for creating chiral nanomaterials with increasing architectural diversity for chirality-dependent optical and catalytic applications.

6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 770-778, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38621881

ABSTRACT

This paper aims to study the therapeutic effect of Massa Medicata Fermentata on hyperlipidemia model rats and investigate its mechanism of hypolipidemic effect with the help of non-targeted metabolomics. The mixed hyperlipidemia model rats were constructed by giving high-fat chow. After successful modeling, the rats were divided into the model group, pravastatin sodium group(4.4 mg·kg~(-1)), lipotropic group(0.1 g·kg~(-1)), high-dose group(2.4 g·kg~(-1)), medium-dose group(1.2 g·kg~(-1)), and low-dose group(0.6 g·kg~(-1)) of Massa Medicata Fermentata, and they were administered for four weeks once daily. An equal volume of ultrapure water was given to the blank group and model group. Serum lipid level and liver hematoxylin-eosin(HE) staining were used as indicators to estimate the intervention effect of Massa Medicata Fermentata on mixed hyperlipidemia, and the changes in metabolites in plasma of mixed hyperlipidemia model rats were analyzed by non-targeted metabolomics. The mechanism of the hypolipidemic effect of Massa Medicata Fermentata was analyzed through metabolite pathway enrichment. The results showed that compared with the model group, the Massa Medicata Fermentata administration group, especially the high-dose group, could significantly reduce the content of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.05 or P<0.01), and liver HE staining revealed that the number of adipocytes in the high-dose group was reduced to some extent. The potential biomarkers obtained by non-targeted metabolomics screening included glycerol 3-phosphate, sphingomyelin, sphingosine 1-phosphate, and deoxyuridine, which were mainly involved in the sphingolipid metabolism process, glycerophospholipid metabolism process, glycerol ester metabolism pathway, and pyrimidine metabolism pathway, totaling four possible metabolic pathways related to lipid metabolism. This study provides a reference for an in-depth investigation of the hypolipidemic mechanism of Massa Medicata Fermentata, which is of great significance for further promoting the clinical application of Massa Medicata Fermentata and increasing the indications.


Subject(s)
Drugs, Chinese Herbal , Hyperlipidemias , Rats , Animals , Drugs, Chinese Herbal/pharmacology , Liver , Hyperlipidemias/drug therapy , Metabolomics , Cholesterol , Diet, High-Fat/adverse effects
7.
ACS Nano ; 18(13): 9543-9556, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38518176

ABSTRACT

Chirality transfer from chiral molecules to chiral nanomaterials represents an important topic for exploring the origin of chirality in many natural and artificial systems. Moreover, developing a promising class of chiral nanomaterials holds great significance for various applications, including sensing, photonics, catalysis, and biomedicine. Here we demonstrate the geometric control and tunable optical chirality of chiral pentatwinned Au nanoparticles with 5-fold rotational symmetry using the seed-mediated chiral growth method. A distinctive growth pathway and optical chirality are observed using pentatwinned decahedra as seeds, in comparison with the single-crystal Au seeds. By employing different peptides as chiral inducers, pentatwinned Au nanoparticles with two distinct geometric chirality (pentagonal nanostars and pentagonal prisms) are obtained. The intriguing formation and evolution of geometric chirality with the twinned structure are analyzed from a crystallographic perspective upon maneuvering the interplay of chiral molecules, surfactants, and reducing agents. Moreover, the interesting effects of the molecular structure of peptides on tuning the geometric chirality of pentatwinned Au nanoparticles are also explored. Finally, we theoretically and experimentally investigate the far-field and near-field optical properties of chiral pentatwinned Au nanoparticles through numerical simulations and single-particle chiroptical measurements. The ability to tune the geometric chirality in a controlled manner represents an important step toward the development of chiral nanomaterials with increasing architectural complexity for chiroptical applications.

8.
Inquiry ; 61: 469580241241271, 2024.
Article in English | MEDLINE | ID: mdl-38529892

ABSTRACT

Patient readmission for ischemic stroke significantly strains the healthcare and medical insurance systems. Current understanding of the risk factors associated with these readmissions, as well as their subsequent impact on mortality within China, remains insufficient. This is particularly evident in the context of comprehensive, contemporary population studies. This 4-year retrospective cohort study included 125 397 hospital admissions for ischemic stroke from 838 hospitals located in 22 regions (13 urban and 9 rural) of a major city in western China, between January 1, 2015 and December 31, 2018. The Chi-square tests were used in univariate analysis. Accounting for intra-subject correlations of patients' readmissions, accelerated failure time (AFT) shared frailty models were used to examine readmission events and pure AFT models for mortality. Risk factors for patient readmission after ischemic stroke include frequent admission history, male gender, employee's insurance, advanced age, residence in urban areas, index hospitalization in low-level hospitals, extended length of stay (LOS) during index hospitalization, specific comorbidities and subtypes of ischemic stroke. Furthermore, our findings indicated that an additional admission for ischemic stroke increased patient mortality by 16.4% (P < .001). Stroke readmission contributed to an increased risk of hospital mortality. Policymakers can establish more effective and targeted policies to reduce readmissions for stroke by controlling these risk factors.


Subject(s)
Ischemic Stroke , Stroke , Humans , Male , Patient Readmission , Ischemic Stroke/complications , Retrospective Studies , Stroke/epidemiology , Stroke/therapy , Risk Factors , Length of Stay
9.
Neural Netw ; 174: 106265, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38552351

ABSTRACT

Graph Transformers (GTs) have achieved impressive results on various graph-related tasks. However, the huge computational cost of GTs hinders their deployment and application, especially in resource-constrained environments. Therefore, in this paper, we explore the feasibility of sparsifying GTs, a significant yet under-explored topic. We first discuss the redundancy of GTs based on the characteristics of existing GT models, and then propose a comprehensive Graph Transformer SParsification (GTSP) framework that helps to reduce the computational complexity of GTs from four dimensions: the input graph data, attention heads, model layers, and model weights. Specifically, GTSP designs differentiable masks for each individual compressible component, enabling effective end-to-end pruning. We examine our GTSP through extensive experiments on prominent GTs, including GraphTrans, Graphormer, and GraphGPS. The experimental results demonstrate that GTSP effectively reduces computational costs, with only marginal decreases in accuracy or, in some instances, even improvements. For example, GTSP results in a 30% reduction in Floating Point Operations while contributing to a 1.8% increase in Area Under the Curve accuracy on the OGBG-HIV dataset. Furthermore, we provide several insights on the characteristics of attention heads and the behavior of attention mechanisms, all of which have immense potential to inspire future research endeavors in this domain. Our code is available at https://github.com/LiuChuang0059/GTSP.

10.
Plant Commun ; : 100856, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38431772

ABSTRACT

Actinidia arguta, the most widely distributed Actinidia species and the second cultivated species in the genus, can be distinguished from the currently cultivated Actinidia chinensis on the basis of its small and smooth fruit, rapid softening, and excellent cold tolerance. Adaptive evolution of tetraploid Actinidia species and the genetic basis of their important agronomic traits are still unclear. Here, we generated a chromosome-scale genome assembly of an autotetraploid male A. arguta accession. The genome assembly was 2.77 Gb in length with a contig N50 of 9.97 Mb and was anchored onto 116 pseudo-chromosomes. Resequencing and clustering of 101 geographically representative accessions showed that they could be divided into two geographic groups, Southern and Northern, which first diverged 12.9 million years ago. A. arguta underwent two prominent expansions and one demographic bottleneck from the mid-Pleistocene climate transition to the late Pleistocene. Population genomics studies using paleoclimate data enabled us to discern the evolution of the species' adaptation to different historical environments. Three genes (AaCEL1, AaPME1, and AaDOF1) related to flesh softening were identified by multi-omics analysis, and their ability to accelerate flesh softening was verified through transient expression assays. A set of genes that characteristically regulate sexual dimorphism located on the sex chromosome (Chr3) or autosomal chromosomes showed biased expression during stamen or carpel development. This chromosome-level assembly of the autotetraploid A. arguta genome and the genes related to important agronomic traits will facilitate future functional genomics research and improvement of A. arguta.

11.
Entropy (Basel) ; 26(2)2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38392383

ABSTRACT

Analyzing and characterizing the differences between networks is a fundamental and challenging problem in network science. Most previous network comparison methods that rely on topological properties have been restricted to measuring differences between two undirected networks. However, many networks, such as biological networks, social networks, and transportation networks, exhibit inherent directionality and higher-order attributes that should not be ignored when comparing networks. Therefore, we propose a motif-based directed network comparison method that captures local, global, and higher-order differences between two directed networks. Specifically, we first construct a motif distribution vector for each node, which captures the information of a node's involvement in different directed motifs. Then, the dissimilarity between two directed networks is defined on the basis of a matrix, which is composed of the motif distribution vector of every node and the Jensen-Shannon divergence. The performance of our method is evaluated via the comparison of six real directed networks with their null models, as well as their perturbed networks based on edge perturbation. Our method is superior to the state-of-the-art baselines and is robust with different parameter settings.

12.
J Proteomics ; 296: 105112, 2024 03 30.
Article in English | MEDLINE | ID: mdl-38331166

ABSTRACT

Ocean acidification causes severe shell dissolution and threats the survival of marine molluscs. The periostracum in molluscs consists of macromolecules such as proteins and polysaccharides, and protects the inner shell layers from dissolution and microbial erosion. Moreover, it serves as the primary template for shell deposition. However, the chemical composition and formation mechanism of the periostracum is largely unknown. In this study, we applied transcriptomic, proteomics, physical, and chemical analysis to unravel the mysteries of the periostracum formation in the green mussel Perna viridis Linnaeus. FTIR analysis showed that the periostracum layer was an organic membrane mainly composed of polysaccharides, lipids, and proteins, similar to that of the shell matrix. Interestingly, the proteomic study identified components enriched in tyrosine and some enzymes that evolved in tyrosine oxidation, indicating that tyrosine oxidation might play an essential role in the periostracum formation. Moreover, comparative transcriptomics suggested that tyrosine-rich proteins were intensively synthesized in the periostracum groove. After being secreted, the periostracum proteins were gradually tanned by oxidation in the seawater, and the level of crosslink increased significantly as revealed by the ATR-FTIR. Our present study sheds light on the chemical composition and putative tanning mechanism of the periostracum layer in bivalve molluscs. SIGNIFICANCE: The periostracum layer, plays an essential role in the initiation of shell biomineralization, the protection of minerals from dissolution for molluscs and especially ocean acidification conditions in the changing global climate. However, the molecular mechanism underlying the periostracum formation is not fully understood. In this study, we revealed that the oxidation and cross-link of tyrosine-rich proteins by tyrosinase are involved in periostracum formation in the green mussel Perna viridis. This study provides some insights into the first step of mussel shell formation and the robust adaptation of P. viridis to diverse habitats. These findings also help to reveal the potential acclimation of bivalves to the projected acidifying seawater.


Subject(s)
Perna , Animals , Perna/metabolism , Tyrosine , Seawater , Proteomics , Hydrogen-Ion Concentration , Polysaccharides/metabolism
13.
J Proteomics ; 296: 105126, 2024 03 30.
Article in English | MEDLINE | ID: mdl-38364902

ABSTRACT

The hard shells of mollusks are products of biomineralization, a distinctive feature of the Cambrian explosion. Despite our understanding of shell structure and mechanical properties, their origin remains mysterious. In addition to their shell plates, most chitons have calcium deposits on their girdles. However, the similarity of these two mineralized structures still needs to be determined, limiting our comprehension of their origins. In our study, we analyzed the matrix proteins in the spicules of chiton (Acanthopleura loochooana) and compared them with the matrix proteins in the shells of the same species. Proteomics identified 96 unique matrix proteins in spicules. Comparison of biomineralization-related matrix proteins in shell plates and spicules revealed shared proteins, including carbonic anhydrases, tyrosinase-hemocyanin, von Willebrand factor type A, cadherin, and glycine-rich unknown proteins. Based on similarities in key matrix proteins, we propose that spicules and shell plates originated from a common mineralization system in their ancestral lineage, suggesting the existence of a common core or toolkit of matrix proteins among calcifying organisms. SIGNIFICANCE: In this study, we try to understand the types and diversity of matrix proteins in the biomineralization of chiton shell plates and spicules. Through a comparative analysis, we seek insights into the core biomineralization toolkit of ancestral mollusks. To achieve this, we conducted LC-MS/MS and RT-qPCR analyses to identify the types and relative expression levels of matrix proteins in both shell plates and spicules. The analysis revealed 96 matrix proteins in the spicules. A comparison of biomineralization-related matrix proteins in shell plates and spicules from the same species revealed shared proteins including many unknown proteins unique to chitons. Blast searching reveals a universal conservation of these proteins among other chitons. Hence, we propose that spicules and shell plates originated from a common mineralization system in their ancestral lineage. Our work provides a molecular basis for studying biomineralization in polyplacophoran mollusks and understanding biomineralization evolution. In addition, it identifies potential matrix proteins that could be applied to control crystal growth.


Subject(s)
Biomineralization , Polyplacophora , Animals , Chromatography, Liquid , Tandem Mass Spectrometry , Proteins/analysis
14.
Front Microbiol ; 15: 1328289, 2024.
Article in English | MEDLINE | ID: mdl-38333582

ABSTRACT

Introduction: Citrus chlorotic dwarf-associated virus (CCDaV) is an economically important citrus virus associated with leaf curling, deformation, and chlorosis found in China. Plants have evolved RNA silencing to defend against viral infections; however, the mechanism by which CCDaV suppresses RNA silencing in citrus remains unknown. Methods: Six proteins encoded by CCDaV were ectopically expressed in Nicotiana benthamiana 16c using the pCHF3 vector to identify RNA-silencing suppression activities. Results: V2 protein encoded by CCDaV suppressed local RNA silencing and systemic RNA silencing triggered by GFP RNA, but did not impede short-distance movement of the RNA silencing signal in N. benthamiana 16c. GFP fluorescence observations showed that the ability of V2 protein to suppress RNA silencing was weaker than tomato bushy stunt virus P19. Deletion analysis showed that the putative nuclear localization signal (NLS, 25-54 aa) was involved in the RNA silencing suppression activity of V2 protein. Furthermore, V2 protein cannot block dsRNA-triggered RNA silencing. The subcellular localization assay suggested that V2 protein was localized to nucleus of N. benthamiana. Conclusion: Overall, the results of this study demonstrate that CCDaV-V2 acts as an activity of silencing suppression. This is the first reported RNA-silencing suppressor encoded by Citlodavirus and will be valuable in revealing the molecular mechanism of CCDaV infection.

15.
Neural Netw ; 173: 106175, 2024 May.
Article in English | MEDLINE | ID: mdl-38387201

ABSTRACT

As dynamic graphs have become indispensable in numerous fields due to their capacity to represent evolving relationships over time, there has been a concomitant increase in the development of Temporal Graph Neural Networks (TGNNs). When training TGNNs for dynamic graph link prediction, the commonly used negative sampling method often produces starkly contrasting samples, which can lead the model to overfit these pronounced differences and compromise its ability to generalize effectively to new data. To address this challenge, we introduce an innovative negative sampling approach named Enhanced Negative Sampling (ENS). This strategy takes into account two pervasive traits observed in dynamic graphs: (1) Historical dependence, indicating that nodes frequently reestablish connections they held in the past, and (2) Temporal proximity preference, which posits that nodes are more inclined to connect with those they have recently interacted with. Specifically, our technique employs a designed scheduling function to strategically control the progression of difficulty of the negative samples throughout the training. This ensures that the training progresses in a balanced manner, becoming incrementally challenging, and thereby enhancing TGNNs' proficiency in predicting links within dynamic graphs. In our empirical evaluation across multiple datasets, we discerned that our ENS, when integrated as a modular component, notably augments the performance of four SOTA baselines. Additionally, we further investigated the applicability of ENS in handling dynamic graphs of varied attributes. Our code is available at https://github.com/qqaazxddrr/ENS.


Subject(s)
Neural Networks, Computer
16.
J Environ Manage ; 353: 120176, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38295634

ABSTRACT

Conjugation with the increment of consumption of polypropylene (PP) masks and antidepressants during pandemic, PP microplastics (MPs) and Venlafaxine (VEN) widely co-existed in surface waters. However, their environmental fate and the combined toxicity were unclear. Hence, we investigated the adsorption behaviors, and associated mechanisms of PP MPs for VEN. The impact factors including pH, salinity, and MPs aging were estimated. The results indicated PP MPs could adsorb amount of VEN within 24 h. The pseudo second-order kinetic model (R2 = 0.97) and Dubinin-Radushkevich model (R2 = 0.89) fitted well with the adsorption capacity of PP MPs for VEN, implying that chemical adsorption accompanied by electrostatic interaction might be the predominant mode for the interactions between PP MPs and VEN. Meanwhile, the adsorption capacity of PP MPs declined from pH of 2.5-4.5 and then increased from 4.5 to 9.5. The increased salinity (5-35 ppt) significantly suppressed the adsorption capacity. Aging by sunlight and UV triggered the formation of new functional group (carbonyl) on MPs, and then enhanced the adsorption capacity for VEN. Gaussian Model analysis further evidenced the electrostatic adsorption occurring in PP MPs and VEN. The combined exposure to PP MPs and VEN showed significantly antagonistic toxicity on Daphnia magna. The adsorption of VEN by PP MPs mitigated the lethal effects and behavioral function impairment posed by VEN on animals, implying the potential protective effects on zooplankton by PP MPs. This study for the first time provides perspective for assessing the environmental fate of MPs and antidepressants in aquatic system.


Subject(s)
Plastics , Water Pollutants, Chemical , Animals , Venlafaxine Hydrochloride , Adsorption , Microplastics , Polypropylenes , Antidepressive Agents , Water Pollutants, Chemical/toxicity
17.
Genes Immun ; 25(1): 7-13, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38092885

ABSTRACT

Metformin is a synthetic biguanide proven to have beneficial effects against various human diseases. Research has confirmed that metformin exerts its effects by regulating the composition of intestinal microbiota. The composition of intestinal microbiota influences the efficacy of anti-PD-L1 immunotherapy. We assume that the regulation of metformin on intestinal microbiota could enhance the therapeutic efficiency of anti-PD-L1 antibodies. In Lewis lung cancer-bearing C57BL/6J mice, we find that metformin enhances PD-L1 antibody efficacy mainly depending on the existence of gut microbiota, and metformin increases the anti-tumor immunity through modulation of intestinal microbiota and affects the integrity of the intestinal mucosa. Antibiotic depletion of gut microbiota abolished the combination efficacy of PD-L1 antibody and metformin, implying the significance of intestinal microbiota in metformin's antitumor action. Combining anti-PD-L1 antibody with metformin provoked tumor necrosis by causing increased CD8 T-cell infiltration and IFN-γ expression. In conclusion, metformin could be employed as a microecological controller to prompt antitumor immunity and increase the efficacy of anti-PD-L1 antibodies. Our study provided reliable evidence that metformin could be synergistically used with anti-PD-L1 antibody to enhance the anti-cancer effect.


Subject(s)
Gastrointestinal Microbiome , Metformin , Mice , Animals , Humans , Metformin/pharmacology , Metformin/therapeutic use , B7-H1 Antigen , Mice, Inbred C57BL , CD8-Positive T-Lymphocytes , Cell Line, Tumor
18.
Ecol Appl ; 34(1): e2920, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37750229

ABSTRACT

Transgenerational plasticity (TGP) allows a plant to acclimate to external variable environments and is a potential mechanism that explains the range expansion and invasion success of some exotic plants. Most studies explored the traits of TGP associated with the success of exotic plant invasions by comparison studies among exotic, native, invasive, and noninvasive species. However, studies on the TGP of invasive plants in different resource environments are scarce, and the biological mechanisms involved are not well understood. This study aimed to determine the role of TGP in the invasiveness of Xanthium strumarium in northeast China. We measured the plant morphology of aboveground parts and the growth of three generations of the invader under different environmental conditions. The results showed that the intergenerational plasticity of X. strumarium was stronger under stress conditions. We found that the X. strumarium parent generation (F0) grown under water and/or nutrient deficiency conditions transferred the environmental information to their offspring (F1 and F2). The F1 generation grown under high-resource conditions has greater height with larger crown sizes, thicker basal diameters, and higher biomass. Both water and nutrients can affect the intergenerational transmission of plant plasticity, nutrients play a more important role compared with water. The high morphological intergenerational plasticity of X. strumarium under a pressure environment can help it quickly adapt to the new environment and accelerate the rapid expansion of the population in the short term. The root:shoot ratio and reproductive and nutrient distribution of the X. strumarium F0 and F1 generations showed high stability when the growth environment of the F0 generation differed from that of the F1 generation. The stable resource allocation strategy can ensure that the obtained resources are evenly distributed to each organ to maintain the long-term existence of the community. Therefore, the study of intergenerational transmission plasticity is of great significance for understanding the invasion process, mechanism, and prevention of invasive plants.


Subject(s)
Xanthium , Biomass , Plants , Adaptation, Physiological , Water
19.
Plant Biotechnol J ; 22(4): 1017-1032, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38012865

ABSTRACT

Maize is one of the most important crops for food, cattle feed and energy production. However, maize is frequently attacked by various pathogens and pests, which pose a significant threat to maize yield and quality. Identification of quantitative trait loci and genes for resistance to pests will provide the basis for resistance breeding in maize. Here, a ß-glucosidase ZmBGLU17 was identified as a resistance gene against Pythium aphanidermatum, one of the causal agents of corn stalk rot, by genome-wide association analysis. Genetic analysis showed that both structural variations at the promoter and a single nucleotide polymorphism at the fifth intron distinguish the two ZmBGLU17 alleles. The causative polymorphism near the GT-AG splice site activates cryptic alternative splicing and intron retention of ZmBGLU17 mRNA, leading to the downregulation of functional ZmBGLU17 transcripts. ZmBGLU17 localizes in both the extracellular matrix and vacuole and contribute to the accumulation of two defence metabolites lignin and DIMBOA. Silencing of ZmBGLU17 reduces maize resistance against P. aphanidermatum, while overexpression significantly enhances resistance of maize against both the oomycete pathogen P. aphanidermatum and the Asian corn borer Ostrinia furnacalis. Notably, ZmBGLU17 overexpression lines exhibited normal growth and yield phenotype in the field. Taken together, our findings reveal that the apoplastic and vacuolar localized ZmBGLU17 confers resistance to both pathogens and insect pests in maize without a yield penalty, by fine-tuning the accumulation of lignin and DIMBOA.


Subject(s)
Zea mays , beta-Glucosidase , Animals , Cattle , Zea mays/genetics , Zea mays/chemistry , beta-Glucosidase/genetics , Genome-Wide Association Study , Lignin , Plant Breeding , Insecta
20.
J Proteomics ; 291: 105046, 2024 01 16.
Article in English | MEDLINE | ID: mdl-37981007

ABSTRACT

Crustaceans are the champions of mineral mobilization and deposition in the animal kingdom due to their unique ability to rapidly and periodically mineralize and demineralize their exoskeletons. They are commonly covered with mineralized exoskeletons for protection and regularly molt throughout their lives. Mineralized crustacean exoskeletons are formed under the control of macromolecules especially matrix proteins but the types of matrix proteins are understudied compared to those in molluscan shells. This gap hinders our understanding of their evolutionary paths compared with those of molluscs. Here, we comprehensively analyzed matrix proteins in the exoskeleton of two crabs, one shrimp, and one crayfish and resulted in a major improvement (∼10-fold) in the identification of biomineralization proteins compared to conventional methods for decapod crustaceans. By a comparison with well-studied molluscan biomineralization proteins, we found that decapod crustaceans evolved novel proteins to form mineralized exoskeletons while sharing some proteins with those of molluscs. Our study sheds light on their evolution and adaption to different environment for exoskeleton formation and provides a foundation for further studies of mineralization in crustaceans under normal and climate-changed conditions. SIGNIFICANCE: Most crustaceans have mineralized exoskeletons as protection. How they form these hierarchical structures is still unclear. This is due partially to the understudied matrix proteins in the minerals. This study filled such a gap by using proteomic analysis of matrix proteins from four decapod crustacean exoskeletons. Many novel proteins were discovered which enabled a solid comparison with those of molluscs. By comparison, we proposed that crustaceans evolved novel proteins to form mineralized exoskeletons while sharing some proteins with those of molluscs. This is useful for us to understand the evolution of two major biomineralized phylum.


Subject(s)
Biomineralization , Decapoda , Animals , Proteomics , Minerals , Mollusca
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