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1.
Theranostics ; 12(1): 396-409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987652

RESUMO

Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs. Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo. Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo. Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.

2.
Biomater Sci ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35006223

RESUMO

Chemotherapy is the main treatment for cancer therapy. However, its anti-tumor efficiency is always impaired by the poor bioavailability and low tumor accumulation of chemotherapeutic drugs. The variation between the tumor microenvironment and normal tissue has been recognized as an effective tool to improve drug anti-tumor efficiency. Herein, we developed an injectable, pH-responsive, in situ self-assembled drug-peptide hydrogel (MTX-KKFKFEFEF(DA)) for highly efficient local tumor chemotherapy with few side effects. The small molecule drug, methotrexate (MTX), and pH-responsive linker, 2,3-dimethylmaleic anhydride (DA), were facilely conjugated onto the chain of the KKFKFEFEF peptide via an amidation reaction. The negatively charged drug-peptide (pH 7.4) can be activated to be positive and achieve a sol-gel phase transition under an acidic microenvironment (pH 6.5) both in vitro and in vivo, resulting in highly efficient cellular uptake and endocytosis capacities. Moreover, the in vivo anti-tumor therapeutic effect revealed that the MTX-KKFKFEFEF(DA) hydrogel exhibits long-term tumor retention time, much better tumor inhibition rate and negligible side effects after intratumoral injection into breast tumor-bearing mice. Therefore, this study reveals a versatile strategy for fabricating a pH-responsive drug-peptide hydrogel to improve the chemotherapeutic efficacy of drugs in cancer treatment.

3.
Infect Genet Evol ; : 105201, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34990849

RESUMO

PURPOSE: Stroke is a multifactorial and complex disease caused by the obstruction or rupture of cerebrovascular. To explore the influence of genetic factors on stroke susceptibility, we investigated the association between four single nucleotide polymorphisms (SNPs) in the paired-like homeodomain transcription factor 2 (PITX2) gene and stroke risk. METHODS: A total of 977 volunteers including 476 stroke patients and 501 control individuals were recruited. The association between PITX2 polymorphisms and stroke risk was evaluated using genetic models and haplotype analyses. The strength of the association between each studied polymorphisms and stroke risk was evaluated by calculating odds ratios (ORs) and 95% confidence intervals (CIs). What's more, multifactor dimensionality reduction (MDR) was used to predict the interaction between SNPs. RESULTS: Our study showed that rs6817105 in PITX2 was related to a significant increase in stroke susceptibility (OR = 1.42, 95% CI = 1.04-1.94, p = 0.028). Stratified analyses based on gender indicated that rs6817105, rs13143308, and rs6843082 polymorphisms were significantly associated with an increased risk of stroke in male (OR = 0.68, 95% CI = 0.47-0.99, p = 0.042; OR = 0.53, 95% CI = 0.30-0.96, p = 0.035; and OR = 0.55, 95% CI = 0.30-0.99, p = 0.047). Besides, SNP rs6817105 was significantly increased the risk of stroke in people at age over 65 years (OR = 1.87, 95% CI =1.12-3.11, p = 0.016). MDR showed that the interaction model of rs6817105 and rs3853445 emerged as the best predictor between the PITX2 gene and stroke susceptibility. CONCLUSIONS: This study indicated that there was a significant association between the PITX2 gene and stroke risk, and provided some data as far as possible to support the prevention of stroke.

4.
Cardiol Young ; : 1-6, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34991769

RESUMO

PURPOSE: This study explored the effects of condition notification based on virtual reality technology on the anxiety levels of parents of children with simple CHD. METHODS: The subjects of the study were the parents of 60 children with simple CHD who were treated in our centre. The state anxiety scale was used to assess the anxiety status of the parents of the children before and after the condition notification in different ways (based on virtual reality explanations and written explanations). RESULTS: In this study, a total of 55 parents of children with CHD successfully completed the survey. At the time of admission, there was no significant difference in the state anxiety scale scores of the parents between the two groups. The anxiety status of the virtual reality group was relieved after the condition notification assisted by virtual reality technology, and there was a significant difference compared with the control group. CONCLUSION: Condition notification based on virtual reality technology can effectively alleviate the anxiety of parents of children with simple CHD, which is worthy of clinical application.

5.
Adv Sci (Weinh) ; : e2104349, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34994113

RESUMO

Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia-responsive macrocycle with small-molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host-guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4A•AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation-mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent-based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.

6.
Rice (N Y) ; 15(1): 1, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982277

RESUMO

BACKGROUND: The rice Waxy (Wx) gene plays a major role in seed amylose synthesis and consequently controls grain amylose content. Wx gene expression is highly regulated at the post-transcriptional level. In particular, the GT/TT polymorphism at the 5'splicing site of its 1st intron greatly affects this intron's splicing efficiency and defines two predominant Wx alleles, Wxa and Wxb. Wxa rice often harbours intermediate to high amylose contents, whereas Wxb rice exhibits low to intermediate amylose contents. By deleting the Wx 1st intron using CRISPR/Cas9 technology, we generate a completely novel Wx allele and further investigate how intron removal affects Wx gene expression and rice grain amylose content. RESULTS: CRISPR/Cas9-mediated targeted deletion of the Wx 1st intron was performed on 4 rice inbred lines: KY131 (Wxb), X32 (Wxb), X35 (Wxa) and X55 (Wxlv). Deletion of the 1st intron occurred in 8.6-11.8% of the primary transformants of these 4 inbred lines. Compared to wild-type plants, amylose content was significantly increased from 13.0% to approximately 24.0% in KY131 and X32 mutant lines, which both carried the Wxb allele. However, no significant difference in amylose content was observed between wild-type plants and X35 and X55 mutant lines, which carried the Wxa and Wxlv alleles, respectively. Wx gene expression analysis of wild-type plants and mutants yielded results that were highly consistent with amylose content results. KY131 and X32 mutants accumulated increased levels of steady mRNA transcripts compared with wild-type plants, whereas steady mRNA levels were not altered in X35 and X55 mutants compared with wild-type plants. Grain quality, including appearance quality and eating and cooking quality, which are tightly associated with amylose content, was also assessed in wild-type and mutant plants, and data were presented and analysed. CONCLUSIONS: This study presents a novel and rapid strategy to increase amylose content in inbred rice carrying a Wxb allele. Our data strongly suggest that the 1st intron of the Wx gene regulates Wx gene expression mainly at the post-transcriptional level in rice. This finding is in contrast to a previous hypothesis suggesting that it influences Wx gene transcription. In addition, removal of the first intron generates a completely novel Wx allele. Further studies on this new Wx allele will provide invaluable insights into the regulation of Wx gene expression, which will help researchers engineer new Wx alleles to facilitate the breeding of rice cultivars with better eating and cooking quality.

7.
Natl Sci Rev ; 8(11): nwab066, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34876993

RESUMO

Synthetic chemotactic micro/nanomotors are envisioned to actively 'seek out' targets by following specific chemicals, but they are mainly powered by bioincompatible fuels and only show pseudochemotaxis (or advanced chemokinesis) due to their weak self-reorientation capabilities. Here we demonstrate that synthetic ZnO-based Janus micromotors can be powered by the alternative biocompatible fuel of CO2, and further provide the first example of self-reorientation-induced biomimetic chemotaxis using them. The ZnO-based micromotors are highly sensitive to dissolved CO2 in water, which enables the corrosion of ZnO to continuously occur by providing H+ through hydration. Thus, they can autonomously move even in water exposed to air based on self-diffusiophoresis. Furthermore, they can sense the local CO2 gradient and perform positive chemotaxis by self-reorientations under the phoretic torque. Our discovery opens a gate to developing intelligent micro/nanomotors powered by, and sensitive to, biocompatible atmospheric or endogenous gaseous chemicals for biomedical and environmental applications.

8.
Elife ; 102021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34866572

RESUMO

G protein-coupled receptors (GPCRs) are among the most promising drug targets. They often form homo- and heterodimers with allosteric cross-talk between receptor entities, which contributes to fine tuning of transmembrane signaling. Specifically controlling the activity of GPCR dimers with ligands is a good approach to clarify their physiological roles and to validate them as drug targets. Here, we examined the mode of action of positive allosteric modulators (PAMs) that bind at the interface of the transmembrane domains of the heterodimeric GABAB receptor. Our site-directed mutagenesis results show that mutations of this interface impact the function of the three PAM tested. The data support the inference that they act at the active interface between both transmembrane domains, the binding site involving residues of the TM6s of the GABAB1 and the GABAB2 subunit. Importantly, the agonist activity of these PAMs involves a key region in the central core of the GABAB2 transmembrane domain, which also controls the constitutive activity of the GABAB receptor. This region corresponds to the sodium ion binding site in class A GPCRs that controls the basal state of the receptors. Overall, these data reveal the possibility of developing allosteric compounds able to specifically modulate the activity of GPCR homo- and heterodimers by acting at their transmembrane interface.

9.
Front Pediatr ; 9: 753032, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869108

RESUMO

Objective: The purpose of this study was to evaluate whether positive and negative religious coping methods were associated with psychological distress and quality of life in parents of infants with congenital heart disease (CHD). Methods: This descriptive, cross-sectional study was conducted at a provincial hospital in Fujian, China. Clinical data from 115 parents of infants with CHD were collected. Chinese Sociodemographic Forms, Brief RCOPE, Beck Depression Interview (BDI), and the Short Form Health Survey (SF-36) were used in this study. Results: The sex of caregivers in infants with CHD was an independent predictor of BDI scores. The positive religious coping score and the negative religious coping score were both independent predictors of the BDI score (ß = -5.365, P = 0.006 and ß = 4.812, p = 0.017). The correlation between the quality-of-life scores and positive or negative religious coping scores indicated that positive religious coping scores were significantly positively correlated with Vitality, Social Functioning, and Mental Health scores. There was a significant negative correlation between negative religious coping scores and mental health scores. Conclusions: Positive or negative religious coping methods may be associated with psychological distress and quality of life among parents of infants with CHD. It is suggested that more attention should be devoted to the influence of religious coping methods on parents of infants with CHD, and the use of religious resources should be encouraged.

10.
Mater Sci Eng C Mater Biol Appl ; 131: 112538, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34857314

RESUMO

Skin injury caused by large doses of ionizing radiation is the common and severe side effect of radiotherapy. However, its therapeutic efficacy is always hindered by early reactive oxygen species generation, repetitive inflammatory microenvironment and bacterial infection risk. Herein, we report an anti-biofouling hydrogel with anti-inflammation and anti-oxidative properties for the treatment of irradiation-induced skin injury. The anti-biofouling hydrogel can be achieved by balancing oppositely charged alginate, hyaluronic acid (HA) and polylysine (PLL) at the optimal ratio, which effectively resist protein and bacterial adhesion, and evades immune response. Moreover, curcumin and epigallocatechin gallate (EGCG) can be facially encapsulated and substantially released from the hydrogel. Results showed that the resulting AHP-Cur/EGCG hydrogel can significantly weaken the development of skin injury and accelerate its healing process by alleviating inflammation, scavenging ROS and promoting angiogenesis. Therefore, the findings presented in this work provide an effective strategy for clinical management and treatment of ionizing radiation-induced skin injury.

11.
Cancer Sci ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859546

RESUMO

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel may be an effective strategy for anti-metastasis of breast cancer. However, the inherent defects of them in short blood circulation half-life and lack of tumor targeting not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by nano-delivery system, and initially explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The anti-metastasis effect was also evaluated in vitro and in vivo. Its mechanism was also explored by western blot assay. The resulted PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake property and stimulated drug release in tumor micro-acidic environment. PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and matrix metalloproteinases. Taken together, PM-nano exhibited superior anti-metastasis effect against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for anti-metastasis.

12.
Brain Behav Immun ; 101: 37-48, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34958862

RESUMO

Opioid addiction remains a severe health problem. While substantial insights underlying opioid addiction have been yielded from neuron-centric studies, the contribution of non-neuronal mechanisms to opioid-related behavioral adaptations has begun to be recognized. Toll-like receptor 4 (TLR4), a pattern recognition receptor, has been widely suggested in opioid-related behaviors. Interleukin-1 receptor-associated kinase 4 (IRAK4) is a kinase essential for TLR4 responses, However, the potential role of IRAK4 in opioid-related responses has not been examined. Here, we explored the role of IRAK4 in cue-induced opioid-seeking behavior in male rats. We found that morphine self-administration increased the phosphorylation level of IRAK4 in the nucleus accumbens (NAc) in rats; the IRAK4 signaling remained activated after morphine extinction and cue-induced reinstatement test. Both systemic and local inhibition of IRAK4 in the NAc core attenuated cue-induced morphine-seeking behavior without affecting the locomotor activity and cue-induced sucrose-seeking. In addition, inhibition of IRAK4 also reduced the cue-induced reinstatement of fentanyl-seeking. Our findings suggest an important role of IRAK4 in opioid relapse-like behaviors and provide novel evidence in the association between innate immunity and drug addiction.

13.
J Nanobiotechnology ; 19(1): 451, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34961540

RESUMO

BACKGROUND: Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). RESULTS: In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4ß1 and αLß2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. CONCLUSION: This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34951851

RESUMO

Nuclei segmentation is an essential step in DNA ploidy analysis by image-based cytometry (DNA-ICM) which is widely used in cytopathology and allows an objective measurement of DNA content (ploidy). The routine fully supervised learning-based method requires often tedious and expensive pixel-wise labels. In this paper, we propose a novel weakly supervised nuclei segmentation framework which exploits only sparsely annotated bounding boxes, without any segmentation labels. The key is to integrate the traditional image segmentation and self-training into fully supervised instance segmentation. We first leverage the traditional segmentation to generate coarse masks for each box-annotated nucleus to supervise the training of a teacher model, which is then responsible for both the refinement of these coarse masks and pseudo labels generation of unlabeled nuclei. These pseudo labels and refined masks along with the original manually annotated bounding boxes jointly supervise the training of student model. Both teacher and student share the same architecture and especially the student is initialized by the teacher. We have extensively evaluated our method with both our DNA-ICM dataset and public cytopathological dataset. Without bells and whistles, our method outperforms all existing weakly supervised entries on both datasets.

15.
Insects ; 12(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34940191

RESUMO

The cigarette beetle Lasioderma serricorne (Fabricius) is a major pest of stored products worldwide, especially tobacco and foods, causing huge economic losses. This study aimed to experimentally investigate the population dynamics of this pest at different temperatures and provide theoretical input for its control. Populations of L. serricorne were established under laboratory conditions at five temperatures (21 °C, 24 °C, 27 °C, 30 °C, and 33 °C). Results showed that an increasing temperature significantly affected the developmental time, longevity, oviposition period, and fecundity of L. serricorne. Both the longevity and fecundity of adult beetles were significantly reduced as the temperature increased. High temperatures significantly reduced the total duration of the preoviposition period but prolonged the oviposition period of L. serricorne. Increasing the temperatures from 21 °C to 33 °C significantly influenced the life table parameters of L. serricorne. The intrinsic increase rate (r), finite increase rate (λ), and gross reproductive rate (GRR) all increased with a greater rearing temperature, but mean generation time (T) was significantly shortened. To our best knowledge, this is the first report to detail the entire life history of the cigarette beetle in response to different temperatures when reared on tobacco dry leaves. This finding may provide basic information on the occurrence of L. serricorne in a warehouse setting and its mass rearing.

16.
Front Plant Sci ; 12: 766548, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956265

RESUMO

Corylus heterophylla (2n = 22) is the most widely distributed, unique, and economically important nut species in China. Chromosome-level genomes of C. avellana, C. heterophylla, and C. mandshurica have been published in 2021, but a satisfactory hazelnut genome database is absent. Northeast China is the main distribution and cultivation area of C. heterophylla, and the mechanism underlying the adaptation of C. heterophylla to extremely low temperature in this area remains unclear. Using single-molecule real-time sequencing and the chromosomal conformational capture (Hi-C) assisted genome assembly strategy, we obtained a high-quality chromosome-scale genome sequence of C. heterophylla, with a total length of 343 Mb and scaffold N50 of 32.88 Mb. A total of 94.72% of the test genes from the assembled genome could be aligned to the Embryophyta_odb9 database. In total, 22,319 protein-coding genes were predicted, and 21,056 (94.34%) were annotated in the assembled genome. A HazelOmics online database (HOD) containing the assembled genome, gene-coding sequences, protein sequences, and various types of annotation information was constructed. This database has a user-friendly and straightforward interface. In total, 439 contracted genes and 3,810 expanded genes were identified through genome evolution analysis, and 17 expanded genes were significantly enriched in the unsaturated fatty acid biosynthesis pathway (ko01040). Transcriptome analysis results showed that FAD (Cor0058010.1), SAD (Cor0141290.1), and KAT (Cor0122500.1) with high expression abundance were upregulated at the ovule maturity stage. We deduced that the expansion of these genes may promote high unsaturated fatty acid content in the kernels and improve the adaptability of C. heterophylla to the cold climate of Northeast China. The reference genome and database will be beneficial for future molecular breeding and gene function studies in this nut species, as well as for evolutionary research on species of the order Fagales.

17.
J Clin Neurosci ; 96: 25-32, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34971993

RESUMO

OBJECTIVE: To investigate hemodynamic stresses associated with the anterior communicating artery (Acom) aneurysm formation using computational fluid dynamics (CFD) analysis. METHODS: Three-dimensional geometries of the anterior cerebral artery (ACA) bifurcations in 20 patients with Acom aneurysms and 20 control subjects were used for CFD analysis to investigate hemodynamic stresses including the total and dynamic pressure, wall shear stress (WSS), vorticity and strain rate. RESULTS: At the direct flow impinging center on the bifurcation apex, the total pressure was the maximal but decreased quickly from the impinging center to both daughter branches. The WSS, dynamic pressure, vorticity and strain rate were the minimal at the direct impinging center but increased rapidly and reached the peaks at both daughter branches. The ACA bifurcation angle was significantly (P < 0.001) greater in patients with than without Acom aneurysms (144.2° ± 4.1° vs. 105.1° ± 3.2°). Most aneurysms (70% and 85%, respectively) were deviated to the smaller daughter branch or to the daughter branch forming a smaller angle with the A1 segment of ACA, where the hemodynamic stresses were significantly (P < 0.05) greater than those on the contralateral daughter branch. After aneurysm formation, the hemodynamic stresses on the aneurysm dome were all significantly decreased compared with at the aneurysm initiation site with aneurysm virtual removal (P < 0.001). CONCLUSION: Formation of the Acom aneurysm is closely associated with and is to decrease the locally abnormally enhanced hemodynamic stresses.

18.
Pest Manag Sci ; 2021 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-34897966

RESUMO

BACKGROUND: Velvet ash (Fraxinus velutina Torr.) is an important wood and ornamental tree species. Emerald ash borer (EAB), Agrilus planipennis Fairmaire, is a major wood borer of velvet ash. The aim of this study was to identify the secondary metabolites of velvet ash involved in regulating the dominant bacterium group of EAB. RESULTS: The amount of lignans in the phloem of infested trees had increased by 290.96% because of A. planipennis infection. The addition of lignans to the artificial diet significantly reduced the weight of the larvae and decreased the dominant bacterial group in the larval midgut, such as Pseudomonadaceae, Xanthomonadaceae, and Enterobacteriaceae. The FvPLR1, a key gene for lignan synthesis, was obtained based on the phloem transcriptome of velvet ash. The expression of FvPLR1 in the phloem of the infested tree was significantly higher than that in the noninfested tree. Meanwhile, FvPLR1 silenced by virus-induced gene silencing showed that its expression level and the lignan content were decreased by 69.91% and 31.65%, respectively. Interestingly, silencing FvPLR1 induced alterations in the dominant bacteria group in the larvae, with the reverse trend in the lignan-fed treatment. CONCLUSION: The evidence showed that FvPLR1 was a positive regulator. The increasing synthesis of lignans leads to resistance improvement in velvet ash, which will provide comprehensive insights into the tree defense system to wood borer infestation.

19.
Curr Alzheimer Res ; 18(13): 1041-1056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34915837

RESUMO

BACKGROUND: Background: Alzheimer's disease (AD) is the most common cause of dementia. As a heterogenous disease, there are several clinically and pathobiological defined subtypes with different molecular signatures. Neuroinflammation contributed to AD pathogenesis, however, the roles it played in the heterogeneity of AD was unclear. OBJECTIVE: We aimed to illustrate the roles neuroinflammation played in the heterogeneity of AD. METHOD: An integrative network analysis based on transcriptomics, miRNOmics, and proteomics was performed to illustrate the heterogeneous characters of AD. Combined-functional-networks and hypothesis- network were constructed and analyzed to explore the roles neuroinflammation played in AD heterogeneity. RESULTS: Astrocytes, microglia, 'M2 macrophage-Neuron', and 'Microglia- Neuron' were shown to be enriched in neuroinflammation related functional terms in a cell- and spatial-specific way. The microglia and neurons could interact with each other in three different ways including indirect interactions via intermediate cells, indirect interactions via soluble factors, and direct interactions established localized and functionally distinct signaling, all of which were used to control different biological processes. The combined network analyses exhibited the key roles neuroinflammation plays in the 'AD hypothesis network'. CONCLUSION: The AD heterogeneity may be caused by the heterogeneous cells involved in neuroinflammation and the crosstalks between spatial-specific molecular signatures.

20.
Am J Transl Res ; 13(10): 11718-11727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786099

RESUMO

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Genetic factors are reported to play an essential role in IgAN progression. This study was designed to investigate the association between LOC105371267 and MRPS30-DT and IgAN risk among the Chinese Han population. METHODS: Six SNPs were genotyped. A logistic regression model was used to calculate the effects of the candidate SNPs on IgAN. The SNP-SNP interaction was analyzed using multifactor dimensionality reduction. RESULTS: We observed that only LOC105371267 had a relationship with IgAN. The results indicated an association between the genotype "CC" and a decreased IgAN risk (OR=0.44, P=0.014). The stratification analysis of the patients over 35 years old showed that rs3931698 contributes to IgAN susceptibility in the "GT" genotype (OR=1.78, P=0.038), while rs8044565 showed a significantly decreased risk-effect with IgAN ("T", OR=0.59, P=0.006; "CC", OR=0.15, P=0.015; "CC-CT", OR=0.59, P=0.023; Log-additive, OR=0.56, P=0.005). rs8044565 was correlated with a decreased susceptibility of IgAN in males ("CC", OR=0.27, P=0.006) and in patients with a Lee's grade ≥III ("CC", OR=0.46, P=0.046). We found rs8044565 is related to systolic blood pressure and urinary casts and rs3852740 has a relationship with the serum C3 and hemoglobin levels (P<0.05). CONCLUSION: The present study demonstrated that the SNPs in long non-coding RNAs might be related to IgAN.

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