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1.
New Phytol ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38978318

RESUMO

Rare variants contribute significantly to the 'missing heritability' of quantitative traits. The genome-wide characteristics of rare variants and their roles in environmental adaptation of woody plants remain unexplored. Utilizing genome-wide rare variant association study (RVAS), expression quantitative trait loci (eQTL) mapping, genetic transformation, and molecular experiments, we explored the impact of rare variants on stomatal morphology and drought adaptation in Populus. Through comparative analysis of five world-wide Populus species, we observed the influence of mutational bias and adaptive selection on the distribution of rare variants. RVAS identified 75 candidate genes correlated with stomatal size (SS)/stomatal density (SD), and a rare haplotype in the promoter of serine/arginine-rich splicing factor PtoRSZ21 emerged as the foremost association signal governing SS. As a positive regulator of drought tolerance, PtoRSZ21 can recruit the core splicing factor PtoU1-70K to regulate alternative splicing (AS) of PtoATG2b (autophagy-related 2). The rare haplotype PtoRSZ21hap2 weakens binding affinity to PtoMYB61, consequently affecting PtoRSZ21 expression and SS, ultimately resulting in differential distribution of Populus accessions in arid and humid climates. This study enhances the understanding of regulatory mechanisms that underlie AS induced by rare variants and might provide targets for drought-tolerant varieties breeding in Populus.

2.
Biomol Biomed ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38843496

RESUMO

Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.

3.
J Colloid Interface Sci ; 662: 367-376, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38354563

RESUMO

The development and preparation of multifunctional photothermal conversion materials has far-reaching significance for the utilization of solar energy resources in response to the energy crisis. Herein, we propose a Janus membrane for interfacial solar evaporation and phase change energy storage. The membranes were fabricated via combining the PVA film with multi-shelled hollow spheres (MHS). The membranes have asymmetric wettability, that is, one side is hydrophilic and the other side is hydrophobic. The as-resulted membranes obtain outstanding light absorption without further processing. According to these two advantages, the membranes were applied to solar evaporation. The evaporation rate of the membrane is 1.41 kg*m-2h-1 and the evaporation efficiency is 92.4 % under 1sun irradiation. Moreover, the membrane prepared by impregnating 1-Hexadecanamine (HDA) into MHS possesses excellent tensile strength (2.21 MPa) and photothermal conversion ability. The light-to-thermal conversion efficiency can reach 81.9 % under 1sun irradiation. Therefore, the membranes have broad application prospects in the field of photothermal conversion.

4.
New Phytol ; 242(3): 1113-1130, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38418427

RESUMO

Leaf development is a multifaceted and dynamic process orchestrated by a myriad of genes to shape the proper size and morphology. The dynamic genetic network underlying leaf development remains largely unknown. Utilizing a synergistic genetic approach encompassing dynamic genome-wide association study (GWAS), time-ordered gene co-expression network (TO-GCN) analyses and gene manipulation, we explored the temporal genetic architecture and regulatory network governing leaf development in Populus. We identified 42 time-specific and 18 consecutive genes that displayed different patterns of expression at various time points. We then constructed eight TO-GCNs that covered the cell proliferation, transition, and cell expansion stages of leaf development. Integrating GWAS and TO-GCN, we postulated the functions of 27 causative genes for GWAS and identified PtoGRF9 as a key player in leaf development. Genetic manipulation via overexpression and suppression of PtoGRF9 revealed its primary influence on leaf development by modulating cell proliferation. Furthermore, we elucidated that PtoGRF9 governs leaf development by activating PtoHB21 during the cell proliferation stage and attenuating PtoLD during the transition stage. Our study provides insights into the dynamic genetic underpinnings of leaf development and understanding the regulatory mechanism of PtoGRF9 in this dynamic process.


Assuntos
Estudo de Associação Genômica Ampla , Populus , Folhas de Planta/anatomia & histologia , Redes Reguladoras de Genes , Regulação da Expressão Gênica de Plantas
5.
Cancer Imaging ; 24(1): 14, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38246984

RESUMO

BACKGROUND: Classifying and characterizing pulmonary lesions are critical for clinical decision-making process to identify optimal therapeutic strategies. The purpose of this study was to develop and validate a radiomics nomogram for distinguishing between benign and malignant pulmonary lesions based on robust features derived from diffusion images. MATERIAL AND METHODS: The study was conducted in two phases. In the first phase, we prospectively collected 30 patients with pulmonary nodule/mass who underwent twice EPI-DWI scans. The robustness of features between the two scans was evaluated using the concordance correlation coefficient (CCC) and dynamic range (DR). In the second phase, 139 patients who underwent pulmonary DWI were randomly divided into training and test sets in a 7:3 ratio. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator, and logistic regression were used for feature selection and construction of radiomics signatures. Nomograms were established incorporating clinical features, radiomics signatures, and ADC(0, 800). The diagnostic efficiency of different models was evaluated using the area under the curve (AUC) and decision curve analysis. RESULTS: Among the features extracted from DWI and ADC images, 42.7% and 37.4% were stable (both CCC and DR ≥ 0.85). The AUCs for distinguishing pulmonary lesions in the test set for clinical model, ADC, ADC radiomics signatures, and DWI radiomics signatures were 0.694, 0.802, 0.885, and 0.767, respectively. The nomogram exhibited the best differentiation performance (AUC = 0.923). The decision curve showed that the nomogram consistently outperformed ADC value and clinical model in lesion differentiation. CONCLUSION: Our study demonstrates the robustness of radiomics features derived from lung DWI. The ADC radiomics nomogram shows superior clinical net benefits compared to conventional clinical models or ADC values alone in distinguishing solitary pulmonary lesions, offering a promising tool for noninvasive, precision diagnosis in lung cancer.


Assuntos
Neoplasias Pulmonares , Radiômica , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Área Sob a Curva , Nomogramas , Pulmão
6.
Plant Biotechnol J ; 22(4): 970-986, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37988335

RESUMO

Wood formation, intricately linked to the carbohydrate metabolism pathway, underpins the capacity of trees to produce renewable resources and offer vital ecosystem services. Despite their importance, the genetic regulatory mechanisms governing wood fibre properties in woody plants remain enigmatic. In this study, we identified a pivotal module comprising 158 high-priority core genes implicated in wood formation, drawing upon tissue-specific gene expression profiles from 22 Populus samples. Initially, we conducted a module-based association study in a natural population of 435 Populus tomentosa, pinpointing PtoDPb1 as the key gene contributing to wood formation through the carbohydrate metabolic pathway. Overexpressing PtoDPb1 led to a 52.91% surge in cellulose content, a reduction of 14.34% in fibre length, and an increment of 38.21% in fibre width in transgenic poplar. Moreover, by integrating co-expression patterns, RNA-sequencing analysis, and expression quantitative trait nucleotide (eQTN) mapping, we identified a PtoDPb1-mediated genetic module of PtoWAK106-PtoDPb1-PtoE2Fa-PtoUGT74E2 responsible for fibre properties in Populus. Additionally, we discovered the two PtoDPb1 haplotypes that influenced protein interaction efficiency between PtoE2Fa-PtoDPb1 and PtoDPb1-PtoWAK106, respectively. The transcriptional activation activity of the PtoE2Fa-PtoDPb1 haplotype-1 complex on the promoter of PtoUGT74E2 surpassed that of the PtoE2Fa-PtoDPb1 haplotype-2 complex. Taken together, our findings provide novel insights into the regulatory mechanisms of fibre properties in Populus, orchestrated by PtoDPb1, and offer a practical module for expediting genetic breeding in woody plants via molecular design.


Assuntos
Populus , Populus/genética , Populus/metabolismo , Desequilíbrio de Ligação , Ecossistema , Melhoramento Vegetal , Celulose/metabolismo , Madeira/genética , Regulação da Expressão Gênica de Plantas/genética
7.
World J Clin Cases ; 11(30): 7502-7507, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37969449

RESUMO

BACKGROUND: For the treatment of distal clavicle fractures, each treatment method has its own advantages and disadvantages, and there is no optimal surgical solution. CASE SUMMARY: Based on this, we report 2 cases of distal clavicle fractures treated utilizing an anterior inferior plate with a single screw placed in the distal, in anticipation of providing a better surgical approach to distal clavicle fracture treatment. Two patients were admitted to the hospital after trauma with a diagnosis of distal clavicle fracture, and were admitted to the hospital for internal fixation of clavicle fracture by incision and reduction, with good postoperative functional recovery. CONCLUSION: With solid postoperative fixation and satisfactory prognostic functional recovery, this technique has been shown to be simple, easy to perform and effective.

8.
Plant Cell ; 35(11): 4046-4065, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37522322

RESUMO

Perennial trees must maintain stem growth throughout their entire lifespan to progressively increase in size as they age. The overarching question of the molecular mechanisms that govern stem perennial growth in trees remains largely unanswered. Here we deciphered the genetic architecture that underlies perennial growth trajectories using genome-wide association studies (GWAS) for measures of growth traits across years in a natural population of Populus tomentosa. By analyzing the stem growth trajectory, we identified PtoP4H9, encoding prolyl 4-hydroxylase 9, which is responsible for the natural variation in the growth rate of diameter at breast height (DBH) across years. Quantifying the dynamic genetic contribution of PtoP4H9 loci to stem growth showed that PtoP4H9 played a pivotal role in stem growth regulation. Spatiotemporal expression analysis showed that PtoP4H9 was highly expressed in cambium tissues of poplars of various ages. Overexpression and knockdown of PtoP4H9 revealed that it altered cell expansion to regulate cell wall modification and mechanical characteristics, thereby promoting stem growth in Populus. We showed that natural variation in PtoP4H9 occurred in a BASIC PENTACYSTEINE transcription factor PtoBPC1-binding promoter element controlling PtoP4H9 expression. The geographic distribution of PtoP4H9 allelic variation was consistent with the modes of selection among populations. Altogether, our study provides important genetic insights into dynamic stem growth in Populus, and we confirmed PtoP4H9 as a potential useful marker for breeding or genetic engineering of poplars.


Assuntos
Populus , Estudo de Associação Genômica Ampla , Prolil Hidroxilases/genética , Prolil Hidroxilases/metabolismo , Genes de Plantas , Fenótipo
9.
Plant Biotechnol J ; 21(10): 2002-2018, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37392407

RESUMO

Heterozygous alleles are widespread in outcrossing and clonally propagated woody plants. The variation in heterozygosity that underlies population adaptive evolution and phenotypic variation, however, remains largely unknown. Here, we describe a de novo chromosome-level genome assembly of Populus tomentosa, an economic and ecologically important native tree in northern China. By resequencing 302 natural accessions, we determined that the South subpopulation (Pop_S) encompasses the ancestral strains of P. tomentosa, while the Northwest subpopulation (Pop_NW) and Northeast subpopulation (Pop_NE) experienced different selection pressures during population evolution, resulting in significant population differentiation and a decrease in the extent of heterozygosity. Analysis of heterozygous selective sweep regions (HSSR) suggested that selection for lower heterozygosity contributed to the local adaptation of P. tomentosa by dwindling gene expression and genetic load in the Pop_NW and Pop_NE subpopulations. Genome-wide association studies (GWAS) revealed that 88 single nucleotide polymorphisms (SNPs) within 63 genes are associated with nine wood composition traits. Among them, the selection for the homozygous AA allele in PtoARF8 is associated with reductions in cellulose and hemicellulose contents by attenuating PtoARF8 expression, and the increase in lignin content is attributable to the selection for decreases in exon heterozygosity in PtoLOX3 during adaptive evolution of natural populations. This study provides novel insights into allelic variations in heterozygosity associated with adaptive evolution of P. tomentosa in response to the local environment and identifies a series of key genes for wood component traits, thereby facilitating genomic-based breeding of important traits in perennial woody plants.


Assuntos
Populus , Alelos , Populus/genética , Populus/metabolismo , Madeira/genética , Madeira/metabolismo , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único/genética , Genômica
11.
Plant Physiol ; 193(1): 736-755, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37247391

RESUMO

Drought stress limits woody species productivity and influences tree distribution. However, dissecting the molecular mechanisms that underpin drought responses in forest trees can be challenging due to trait complexity. Here, using a panel of 300 Chinese white poplar (Populus tomentosa) accessions collected from different geographical climatic regions in China, we performed a genome-wide association study (GWAS) on seven drought-related traits and identified PtoWRKY68 as a candidate gene involved in the response to drought stress. A 12-bp insertion and/or deletion and three nonsynonymous variants in the PtoWRKY68 coding sequence categorized natural populations of P. tomentosa into two haplotype groups, PtoWRKY68hap1 and PtoWRKY68hap2. The allelic variation in these two PtoWRKY68 haplotypes conferred differential transcriptional regulatory activities and binding to the promoters of downstream abscisic acid (ABA) efflux and signaling genes. Overexpression of PtoWRKY68hap1 and PtoWRKY68hap2 in Arabidopsis (Arabidopsis thaliana) ameliorated the drought tolerance of two transgenic lines and increased ABA content by 42.7% and 14.3% compared to wild-type plants, respectively. Notably, PtoWRKY68hap1 (associated with drought tolerance) is ubiquitous in accessions in water-deficient environments, whereas the drought-sensitive allele PtoWRKY68hap2 is widely distributed in well-watered regions, consistent with the trends in local precipitation, suggesting that these alleles correspond to geographical adaptation in Populus. Moreover, quantitative trait loci analysis and an electrophoretic mobility shift assay showed that SHORT VEGETATIVE PHASE (PtoSVP.3) positively regulates the expression of PtoWRKY68 under drought stress. We propose a drought tolerance regulatory module in which PtoWRKY68 modulates ABA signaling and accumulation, providing insight into the genetic basis of drought tolerance in trees. Our findings will facilitate molecular breeding to improve the drought tolerance of forest trees.


Assuntos
Arabidopsis , Populus , Resistência à Seca , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Populus/metabolismo , Alelos , Estudo de Associação Genômica Ampla , Regulação da Expressão Gênica de Plantas , Arabidopsis/metabolismo , Secas , Ácido Abscísico/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética
12.
Plant Cell Environ ; 46(2): 479-497, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36385613

RESUMO

Little information is known about DNA methylation variation in shaping environment-specific drought resistance and resilience for tree adaptation. In this study, we leveraged RNA sequencing and whole-genome bisulfite sequencing data to dissect the distinction of epigenetic regulation under drought stress and rewater condition of Populus tomentosa accessions from three geographical regions. We demonstrated low resistance and high resilience for accessions from South. Non-CG methylation levels in promoter regions of Southern accessions were lower than accessions from higher latitudes and negatively regulated gene expression. CHH context methylation was more sensitive to drought stress, and the geographical-specific differentially methylated regions were scarcely changed by environmental fluctuation. We identified 60 conserved hub genes within the co-expression networks that correlate with photosynthetic and stomatal morphological traits. Epigenome-wide association studies and genome-wide association studies of these 60 hub genes revealed the interdependency between genetic and epigenetic variation in GATA9 and LECRK-VIII.2, which was associated with stomatal morphology and chlorophyll content. The natural epigenetic variation in GATA9 was also faithfully transmitted to progenies in two family-based F1 populations. This study indicates a functional relationship of DNA methylation diversity with drought resistance and resilience which offers new insights into plants' local adaptation to a stressful environment.


Assuntos
Metilação de DNA , Populus , Metilação de DNA/genética , Epigênese Genética , Populus/genética , Resistência à Seca , Estudo de Associação Genômica Ampla
13.
Plant Cell Environ ; 46(1): 150-170, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36285358

RESUMO

Stomata are essential for photosynthesis and abiotic stress tolerance. Here, we used multiomics approaches to dissect the genetic architecture and adaptive mechanisms that underlie stomatal morphology in Populus tomentosa juvenile natural population (303 accessions). We detected 46 candidate genes and 15 epistatic gene-pairs, associated with 5 stomatal morphologies and 18 leaf development and photosynthesis traits, through genome-wide association studies. Expression quantitative trait locus mapping revealed that stomata-associated gene loci were significantly associated with the expression of leaf-related genes; selective sweep analysis uncovered significant differentiation in the allele frequencies of genes that underlie stomatal variations. An allelic regulatory network operating under drought stress and adequate precipitation conditions, with three key regulators (DUF538, TRA2 and AbFH2) and eight interacting genes, was identified that might regulate leaf physiology via modulation of stomatal shape and density. Validation of candidate gene variations in drought-tolerant and F1 hybrid populations of P. tomentosa showed that the DUF538, TRA2 and AbFH2 loci cause functional stabilisation of spatiotemporal regulatory, whose favourable alleles can be faithfully transmitted to offspring. This study provides insights concerning leaf physiology and stress tolerance via the regulation of stomatal determination in perennial plants.


Assuntos
Populus , Populus/genética , Estudo de Associação Genômica Ampla , Folhas de Planta/genética
14.
Microbiol Spectr ; 10(6): e0342422, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36453911

RESUMO

Due to the changes in pathogenic species and the absence of research on topical skin antibiotics, the therapy of skin and soft tissue infections (SSTIs) is facing more and more severe challenges. It is particularly urgent to look for alternative therapies without induction of drug resistance. UV C (UVC) light within the range of 200 to 280 nm is one of the most common techniques used to kill and/or inactivate pathogenic microorganisms. However, the traditional most commonly used wavelength of 254 nm irradiated from a low-pressure mercury lamp is hazardous to human health, being both carcinogenic and damaging to eye tissues, which limits its applications in vivo. This research aimed to investigate the antimicrobial properties and influence of 275-nm UVC light from a light-emitting diode (UVC-LED light) on wound healing time. Five bacteria, three fungi, and scalded-mouse models combined with SSTIs were used to evaluate the antimicrobial effect in vitro and in vivo. 275-nm UVC-LED light inactivated both bacteria and fungi with a very short irradiation time in vitro and induced neither DNA damage nor epidermal lesions in the mice's skin. Furthermore, in mouse models of SSTIs induced by either methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans, the 275-nm UVC-LED light showed significant antimicrobial effects and shortened the wound healing time compared with that in the no-irradiation group. UVC-LED light at 275 nm has the potential to be a new form of physical therapy for SSTIs. IMPORTANCE As a common clinical problem, the therapy of SSTIs is facing growing challenges due to an increase in the number of drug-resistant bacteria and fungi. UV C (UVC) light sterilization has been widely used in all aspects of daily life, but there are very few reports about in vivo therapy using UVC light. It is well known that prolonged exposure to UVC light increases the possibility of skin cancer. In addition, it is also very harmful for eyes. UV irradiation with 254-nm UVC light can cause corneal damage, like thinning of the corneal epithelial layer, superficial punctate keratitis, corneal erosion, etc. In this study, we focused on looking for a more accessible light source and safer UVC wavelength, and 275-nm UVC LED light was chosen. We investigated its applicability for SSTIs therapy with relative skin safety and expected that it could be used as a new physical therapy method for SSTIs.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Humanos , Animais , Camundongos , Cicatrização , Fungos , Bactérias/efeitos da radiação
15.
Pharmaceutics ; 14(9)2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36145681

RESUMO

The increasing resistance of human pathogens promotes the development of novel antimicrobial agents. Due to the physical bactericidal mechanism of membrane disruption, antimicrobial peptides are considered as potential therapeutic candidates without inducing microbial resistance. Scorpion venom-derived peptide, Androctonus amoreuxi Antimicrobial Peptide 1 (AamAP1), has been proved to have broad-spectrum antimicrobial properties. However, AamAP1 can induce hemolysis and shows strong toxicity against mammalian cells. Herein, the antimicrobial activity and mechanism of a novel synthetic antimicrobial peptide, GK-19, derived from AamAP1 and its derivatives, was evaluated. Five bacteria and three fungi were used to evaluate the antimicrobial effects of GK-19 in vitro. Scalded mice models combined with skin and soft tissue infections (SSTIs) were used to evaluate its applicability. The results indicated that GK-19 could not only inhibit Gram-positive and Gram-negative bacterial growth, but also kill fungi by disrupting the microbial cell membrane. Meanwhile, GK-19 showed negligible toxicity to mammalian cells, low hemolytic activity and high stability in plasma. Furthermore, in scalded mice models combined with SSTIs induced by either Methicillin-Resistant Staphylococcus aureus (MRSA) or Candida albicans, GK-19 showed significant antimicrobial and healing effects. Overall, it was demonstrated that GK-19 might be a promising drug candidate in the battle against drug-resistant bacterial and fungal infections.

16.
Front Plant Sci ; 13: 829888, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968119

RESUMO

Drought frequency and severity are exacerbated by global climate change, which could compromise forest ecosystems. However, there have been minimal efforts to systematically investigate the genetic basis of the response to drought stress in perennial trees. Here, we implemented a systems genetics approach that combines co-expression analysis, association genetics, and expression quantitative trait nucleotide (eQTN) mapping to construct an allelic genetic regulatory network comprising four key regulators (PtoeIF-2B, PtoABF3, PtoPSB33, and PtoLHCA4) under drought stress conditions. Furthermore, Hap_01PtoeIF-2B, a superior haplotype associated with the net photosynthesis, was revealed through allelic frequency and haplotype analysis. In total, 75 candidate genes related to drought stress were identified through transcriptome analyses of five Populus cultivars (P. tremula × P. alba, P. nigra, P. simonii, P. trichocarpa, and P. tomentosa). Through association mapping, we detected 92 unique SNPs from 38 genes and 104 epistatic gene pairs that were associated with six drought-related traits by association mapping. eQTN mapping unravels drought stress-related gene loci that were significantly associated with the expression levels of candidate genes for drought stress. In summary, we have developed an integrated strategy for dissecting a complex genetic network, which facilitates an integrated population genomics approach that can assess the effects of environmental threats.

17.
Mater Today Bio ; 16: 100350, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35856043

RESUMO

Effective systemic treatment for hepatocellular carcinoma (HCC) remains urgently needed. Sorafenib is the first FDA-approved systemic treatment for HCC. However, individual HCC patents' response to sorafenib varies greatly. How to enhance the anti-HCC effect of sorafenib is still a significant challenge. T cell immunoglobulin mucin-3 (Tim-3) is a newly identified immune checkpoint molecule and a promising target for HCC treatment. Herein, we developed a novel pH-triggered drug-eluting nanoparticle (CC@SR&SF@PP) for simultaneously delivery of Tim-3 siRNA and sorafenib to HCC in situ. By a single emulsification method, a representative HCC targeted-therapeutic drug sorafenib (SF) was encapsulated into the pH-triggered positive-charged mPEG5K-PAE10K (PP) nanoparticles, followed by condensing of negative-charged Tim-3 siRNA. Then, carboxymethyl chitosan (CMCS), an amphoteric polysaccharide with negative charge in the physiological pH and positive charge in the acidic environment of the tumor, was eventually adsorbed onto the surface of nanoparticles. This co-delivery nanoparticle rapidly and specifically accumulated in the tumor site of the liver and enhanced the targeted, specific and multiple release of siRNA and sorafenib. Enhanced Tim-3 siRNA transfected into tumor cells can not only directly inhibit the growth of tumor cells by knock down the expression Tim-3, but also induce the immune response and enhance the recruitment of cytotoxic T cells to kill tumor cells. The following pH-triggered sorafenib release from SF@PP NPs greatly inhibited the tumor proliferation and angiogenesis, resulting in remarkable tumor growth inhibition in a mouse hepatoma 22 (H22) orthotopic tumor model. Thus, co-delivery of Tim-3 siRNA and sorafenib via this novel pH triggered drug-eluting nanoparticle enhances their anti-tumor efficacy. We expect that such combination treatment strategy will have great potential in future clinical applications.

18.
Braz J Med Biol Res ; 55: e12096, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584453

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.


Assuntos
Berberina , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Animais , Berberina/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Quinazolinas , Ratos
19.
Opt Express ; 30(1): 195-209, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35201199

RESUMO

The major challenges in traditional color phase hologram generation are the time-consuming iterative procedure and aberration caused by different wavelengths in color holographic display. Based on the original non-iterative phase hologram generation method-optimized random phase (ORAP), combined with the physical limitations of color holographic display, this paper proposes a full-support optimized random phase (FS-ORAP) method for non-iterative color phase hologram generation. FS-ORAP breaks through the limitation of the original ORAP method in the fixed support constraint of the target amplitude in the spatial domain, the full support constraint can be used to generate phase holograms of target amplitudes with arbitrary support size, which fits well with the generation mode of the three-color channel of the color phase hologram. In addition, the color aberration of the reconstructed image is eliminated by scaling the size of the three-color component. At the same time, FS-ORAP is used for the non-iterative fast generation of three-color channel holograms, which can greatly improve the generation speed of color phase holograms and can be adapted to various color holographic display techniques. Experimental results verify the feasibility of our proposed method.

20.
Braz. j. med. biol. res ; 55: e12096, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1374702

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is considered to be a manifestation of hepatic metabolic syndrome. Some studies on the pathogenesis of NAFLD by targeting gut microbiota have attracted wide attention. Previous studies have demonstrated the positive effects of berberine and evodiamine on metabolic diseases and gut microbiota dysbiosis. However, it is not known whether the combination of berberine and evodiamine (BE) can prevent the development of high-fat diet (HFD)-induced NAFLD. Therefore, we aimed to explore the protective effects of BE on the development of HFD-induced NAFLD from the perspective of the gut microbiota. Gut microbiota profiles were established by high throughput sequencing of the bacterial 16S ribosomal RNA gene. The effects of BE on liver and intestinal tissue, intestinal barrier integrity, and hepatic inflammation were also investigated. The results showed that the abundance and diversity of gut microbiota were enriched by BE treatment, with an increase in beneficial bacteria, such as Lactobacillus, Ruminococcus, and Prevotella, and a decrease in pathogenic bacteria such as Fusobacterium and Lachnospira. In addition, BE effectively improved liver fat accumulation and tissue damage, inhibited the apoptosis of intestinal epithelial cells, increased the contents of intestinal tight junction proteins, and decreased the expression of pro-inflammatory factors. Consequently, BE treatment could be an effective and alternative strategy for alleviating NAFLD by modulating gut microbiota and safeguarding the intestinal barrier.

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