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1.
Gene ; : 148624, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38824974

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR. METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between 'SNP-SNP' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy. RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele 'A' of rs905670 (OR = 1.36, p = 0.018) and mutant allele 'G' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05). CONCLUSION: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.

2.
Am J Cancer Res ; 14(4): 1712-1729, 2024.
Article in English | MEDLINE | ID: mdl-38726277

ABSTRACT

Melanoma is the most aggressive type of skin cancer and has a high mortality rate once metastasis occurs. Hypoxia is a universal characteristic of the microenvironment of cancer and a driver of melanoma progression. In recent years, long noncoding RNAs (lncRNAs) have attracted widespread attention in oncology research. In this study, screening was performed and revealed seven hypoxia-related lncRNAs AC008687.3, AC009495.1, AC245128.3, AL512363.1, LINC00518, LINC02416 and MCCC1-AS1 as predictive biomarkers. A predictive risk model was constructed via univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Patients were grouped according to the model risk score, and Kaplan-Meier analysis was performed to compare survival between groups. Functional and pathway enrichment analyses were performed to compare gene set enrichment between groups. Moreover, a nomogram was constructed with the risk score as a variable. In both the training and validation sets, patients in the low-risk group had better overall survival than did those in the high-risk group (P<0.001). The 3-, 5- and 10-year area under the curve (AUC) values for the nomogram model were 0.821, 0.795 and 0.820, respectively. Analyses of immune checkpoints, immunotherapy response, drug sensitivity, and mutation landscape were also performed. The results suggested that the low-risk group had a better response to immunotherapeutic. In addition, the nomogram can effectively predict the prognosis and immunotherapy response of melanoma patients. The signature of seven hypoxia-related lncRNAs showed great potential value as an immunotherapy response biomarker, and these lncRNAs might be treatment targets for melanoma patients.

3.
Aesthetic Plast Surg ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811386

ABSTRACT

BACKGROUND: Chest deformity is a potential complication associated with auricular reconstruction using autologous costal cartilage. The impact of the incision size employed for costal cartilage harvesting on chest deformities remains unclear. This study aimed to investigate the correlation between the incision size used for harvesting costal cartilage and the occurrence of chest deformities. METHODS: We retrospectively analyzed patients who underwent ear reconstruction using autologous costal cartilage between June 2021 and September 2022. The patients were categorized into two groups based on the size of the costal cartilage incision: large and small. Chest computed tomography (CT) was performed 18-24 months postoperatively, followed by three-dimensional color map quantification to assess the degree of asymmetry of the chest surface. Subsequently, quantitative data analysis was performed to compare the extent of chest asymmetry between the large- and small-incision groups. The Visual Analog Scale (VAS) was used to assess patient satisfaction with chest morphology. RESULTS: This study included 62 patients, with an equal distribution of 31 in each group. The mean asymmetry value of the small and large incision groups was -3.15 ± 1.88 and -5.27 ± 3.63, respectively. Moreover, the mean VAS score for the small and large incision groups was 7.48 ± 0.72 and 5.09 ± 0.94, respectively. Statistically significant differences were observed between the two groups. CONCLUSIONS: Small incision costal cartilage harvesting can effectively alleviate the severity of chest deformities and significantly enhance patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

4.
Plants (Basel) ; 13(8)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38674536

ABSTRACT

Cotton is the most widely planted fiber crop in the world, and improving cotton fiber quality has long been a research hotspot. The development of cotton fibers is a complex process that includes four consecutive and overlapping stages, and although many studies on cotton fiber development have been reported, most of the studies have been based on cultivars that are promoted in production or based on lines that are used in breeding. Here, we report a phenotypic evaluation of Gossypium hirsutum based on immature fiber mutant (xin w 139) and wild-type (Xin W 139) lines and a comparative transcriptomic study at seven time points during fiber development. The results of the two-year study showed that the fiber length, fiber strength, single-boll weight and lint percentage of xin w 139 were significantly lower than those of Xin W 139, and there were no significant differences in the other traits. Principal component analysis (PCA) and cluster analysis of the RNA-sequencing (RNA-seq) data revealed that these seven time points could be clearly divided into three different groups corresponding to the initiation, elongation and secondary cell wall (SCW) synthesis stages of fiber development, and the differences in fiber development between the two lines were mainly due to developmental differences after twenty days post anthesis (DPA). Differential expression analysis revealed a total of 5131 unique differentially expressed genes (DEGs), including 290 transcription factors (TFs), between the 2 lines. These DEGs were divided into five clusters. Each cluster functional category was annotated based on the KEGG database, and different clusters could describe different stages of fiber development. In addition, we constructed a gene regulatory network by weighted correlation network analysis (WGCNA) and identified 15 key genes that determined the differences in fiber development between the 2 lines. We also screened seven candidate genes related to cotton fiber development through comparative sequence analysis and qRT-PCR; these genes included three TFs (GH_A08G1821 (bHLH), GH_D05G3074 (Dof), and GH_D13G0161 (C3H)). These results provide a theoretical basis for obtaining an in-depth understanding of the molecular mechanism of cotton fiber development and provide new genetic resources for cotton fiber research.

5.
J Plast Reconstr Aesthet Surg ; 92: 145-150, 2024 May.
Article in English | MEDLINE | ID: mdl-38518626

ABSTRACT

BACKGROUND: Lobule transposition, a common procedure in auricle reconstruction, has been successfully performed over the past few decades. However, the transposition methods for unilateral microtia with evident asymmetry of bilateral earlobe positions still remain a challenge. The objective of this study was to investigate the application of prograde transposition for anteriorly low-set earlobes. METHOD: A total of 25 patients with lobule-type microtia with anteriorly low-set residual earlobe underwent prograde transposition during auricle reconstruction between 2020 and 2022. The post-operative earlobe aesthetic assessment and patient satisfaction were evaluated, and the data on any complications that occurred when followed-up were collected. This study provides a comprehensive analysis and summary of the techniques used in earlobe transposition for auricular reconstruction. RESULTS: The patients with evident asymmetry between the residual and healthy earlobes were usually concomitant with hemifacial microsomia and the residual ear was located in the anterior and lower region. No instances of flap necrosis, hematoma, or wound dehiscence were observed following auricular reconstruction. The mean aesthetic score of the auricle was 3.52, with 23 patients attaining good or excellent aesthetic outcomes. The mean Visual Analog Scale satisfaction score was 3.68, with 24 patients reporting relative satisfaction or satisfaction. CONCLUSION: The prograde transposition of anteriorly low-set earlobe in lobule-type microtia reconstruction can effectively ensure adequate blood supply, enhance aesthetic appearance, and significantly improve patient satisfaction.


Subject(s)
Congenital Microtia , Ear Auricle , Esthetics , Patient Satisfaction , Plastic Surgery Procedures , Humans , Congenital Microtia/surgery , Plastic Surgery Procedures/methods , Male , Female , Adolescent , Child , Ear Auricle/surgery , Ear Auricle/abnormalities , Surgical Flaps , Young Adult , Adult , Ear, External/surgery , Ear, External/abnormalities
6.
Sci Rep ; 14(1): 5105, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38429304

ABSTRACT

The water-rich burnt rock may threaten the safe production of coal mines. Identifying the boundaries of burnt rock and the water-rich area is of great practical significance for the ensuring the safety of mining operations. Transient electromagnetic and high-density resistivity methods are commonly employed in geophysical exploration, such as for investigating the presence of groundwater or delineating boundaries of altered rocks. These methods are non-invasive and provide detailed information about subsurface conditions without the need for drilling or excavation. The Jiangjun Gobi No. 1 open-pit coal mine is situated in the Kalamaili fault zone and is characterized by a high groundwater content. In certain mining sites within the study area, the inflow of water reaches tens of thousands of cubic meters per day, which significantly impacts production and presents major risks. To accurately determine the boundaries of burnt rock and water accumulation areas in the Jiangjun Gobi No. 1 open-pit coal mine, this paper uses different geophysical prospecting methods based on the depth of the strata. The middle and deep parts are investigated using the high-resolution transient electromagnetic method, while the shallow parts are examined using the high-accuracy high-density electric method. Through analyzing the electrical characteristics of the study area, it is inferred that the low-resistivity area in the northwest represents a shallow surface water-rich region. This area extends continuously towards the northwest, is not trapped, and is supplied by surface water. The deep low-resistivity zone primarily consists of sandstone and coarse sandstone. It is inferred that the low-resistance area in the southern part of the study area is also a shallow surface water-rich region, extending towards the east and west sides, not trapped, and supplied by surface water. The deep low-resistivity zone mainly comprises a combination of sandstone, coarse sandstone, and burnt rock, with intermittent layers of mudstone and argillaceous sandstone. The boundary line of burnt rock (coal-bearing strata) is located in the south of the study area. The resistivity of burnt rock (coal-bearing strata) is higher than that of the surrounding rocks, and the resistivity of coal seams is slightly higher than that of sandstone with larger porosity. Estimating the boundaries of groundwater and altered rocks serves to prevent geological disasters and provides valuable information for mineral development and ecological protection.

7.
Clin Lung Cancer ; 25(1): e1-e4, 2024 01.
Article in English | MEDLINE | ID: mdl-37880076

ABSTRACT

BACKGROUND: The utility of circulating tumor DNA to monitor molecular residual disease (MRD) has been clinically confirmed to predict disease recurrence in non-small cell lung cancer (NSCLC) patients after radical resection. Patients with longitudinal undetectable MRD show a favorable prognosis and might not benefit from adjuvant therapy. PATIENTS AND METHODS: The CTONG 2201 trial is a prospective, multicenter, single-arm study (ClinicalTrials.gov identifier, NCT05457049), designed to evaluate the hypothesis that no adjuvant therapy is needed for patients with longitudinal undetectable MRD. Pathologically confirmed stage IB-IIIA NSCLC patients who have undergone radical resection will be screened. Only patients with 2 consecutive rounds of undetectable MRD will be enrolled (first at days 3-10, second at days 30 ± 7 after surgery), and admitted for imaging and MRD monitoring every 3 months without adjuvant therapy. The primary endpoint is the 2-year disease-free survival rate for those with longitudinal undetectable MRD. The recruitment phase began in August 2022 and 180 patients will be enrolled. CONCLUSIONS: This prospective trial will contribute data to confirm the negative predictive value of MRD on adjuvant therapy for NSCLC patients. CLINICAL TRIAL REGISTRATION: NCT05457049 (CTONG 2201).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/drug therapy , Chemotherapy, Adjuvant , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Neoplasm Recurrence, Local/drug therapy , Neoplasm, Residual/drug therapy , Prospective Studies
8.
Cell Biol Int ; 48(2): 154-161, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37920124

ABSTRACT

Alopecia areata (AA) is a complex genetic disease that results in hair loss due to an autoimmune-mediated attack on the hair follicle. Mesenchymal stem cells (MSCs) have great potential to induce hair regeneration due to their strong secretion ability and multidirectional differentiation. Recent studies have revealed that the therapeutic potential of MSCs comes from their secretion ability, which can produce large amounts of bioactive substances and regulate the key physiological functions of subjects. The secretion products of MSCs, such as vesicles, exosomes, and conditioned media, have significant advantages in preparing of biological products derived from stem cells. Human umbilical cord mesenchymal stem cells (uMSCs) are the best choice for exosome production. uMSCs are obtained from the human umbilical cord. The umbilical cord is easy to obtain, and the efficiency of uMSCs isolation and culture higher than that of obtaining MSCs from bone marrow or adipose tissue. In this study, we investigated the effects of exosomes released from uMSCs in AA mice. In summary, due to easy isolation and cultivation, simple preparation, and convenient storage, it is possible to obtain uMSCs, or uMSCs exosomes for research and clinical treatment.


Subject(s)
Alopecia Areata , Exosomes , Mesenchymal Stem Cells , Humans , Mice , Animals , Alopecia Areata/therapy , Hair , Umbilical Cord , Cell Proliferation , Keratinocytes
9.
Endocr Pract ; 30(2): 177-186, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38007181

ABSTRACT

OBJECTIVE: We aimed to evaluate the effects of thyroid-stimulating hormone (TSH) suppression therapy on cardiac structure and function in patients with differentiated thyroid cancer (DTC) following thyroidectomy. METHODS: Two investigators independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant studies published from inception to January 6, 2023, without any restrictions on language. Standard mean differences and 95% confidence intervals were calculated using fixed or random effects models. Thirteen clinical outcomes were analyzed, mainly evaluating cardiac morphology, systolic function, and diastolic function. RESULTS: Thirteen studies were included in the quantitative analysis. Compared to healthy controls, left ventricular mass index, left ventricular posterior wall thickness, interventricular septal thickness, and isovolumic relaxation time values increased; the ratio of E-wave velocity to A-wave velocity and E-wave velocity values decreased. The left ventricular ejection fraction and cardiac output did not change in patients with DTC who underwent long-term TSH suppression therapy. Interventricular septal thickness values were significantly correlated with the duration of TSH suppression therapy. CONCLUSION: Long-term TSH suppression therapy leads to cardiac hypertrophy and impaired cardiac diastolic function in patients with DTC. These changes may be related to the duration of TSH suppression therapy. Large prospective studies with long follow-up periods are needed to validate these findings.


Subject(s)
Thyroid Neoplasms , Thyroxine , Humans , Thyroxine/therapeutic use , Stroke Volume , Thyroidectomy , Prospective Studies , Thyrotropin , Ventricular Function, Left , Thyroid Neoplasms/surgery
10.
Small ; 20(22): e2308514, 2024 May.
Article in English | MEDLINE | ID: mdl-38098438

ABSTRACT

Highly robust flexible multifunctional film with excellent electromagnetic interference shielding and electrothermal/photothermal characteristics are highly desirable for aerospace, military, and wearable devices. Herein, an asymmetric gradient multilayer structured bacterial cellulose@Fe3O4/carbon nanotube/Ti3C2Tx (BC@Fe3O4/CNT/Ti3C2Tx) multifunctional composite film is fabricated with simultaneously demonstrating fast Joule response, excellent EMI shielding effectiveness (EMI SE) and photothermal conversion properties. The asymmetric gradient 6-layer composite film with 40% of Ti3C2Tx possesses excellent mechanical performance with exceptional tensile strength (76.1 MPa), large strain (14.7%), and good flexibility. This is attributed to the asymmetric gradient multilayer structure designed based on the hydrogen bonding self-assembly strategy between Ti3C2Tx and BC. It achieved an EMI SE of up to 71.3 dB, which is attributed to the gradient "absorption-reflection-reabsorption" mechanism. Furthermore, this composite film also exhibits excellent low-voltage-driven Joule heating (up to 80.3 °C at 2.5 V within 15 s) and fast-response photothermal performance (up to 101.5 °C at 1.0 W cm-2 within 10 s), which is attributed to the synergistic effect of heterostructure. This work demonstrates the fabrication of multifunctional bacterial cellulose@Fe3O4/carbon nanotube/Ti3C2Tx composite film has promising potentials for next-generation wearable electronic devices in energy conversion, aerospace, and artificial intelligence.


Subject(s)
Cellulose , Nanotubes, Carbon , Wearable Electronic Devices , Cellulose/chemistry , Nanotubes, Carbon/chemistry , Titanium/chemistry , Bacteria , Nanocomposites/chemistry
11.
Math Biosci Eng ; 20(9): 17116-17137, 2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37920049

ABSTRACT

In the two-population game model, we assume the players have certain imitative learning abilities. To simulate the learning process of the game players, we propose a new swarm intelligence algorithm by combining the particle swarm optimization algorithm, where each player can be considered a particle. We conduct simulations for three typical games: the prisoner's dilemma game (with only one pure-strategy Nash equilibrium), the coin-flip game (with only one fully-mixed Nash equilibrium), and the coordination game (with two pure-strategy Nash equilibria and one fully-mixed Nash equilibrium). The results show that when the game has a pure strategy Nash equilibrium, the algorithm converges to that equilibrium. However, if the game does not have a pure strategy Nash equilibrium, it exhibits periodic convergence to the only mixed-strategy Nash equilibrium. Furthermore, the magnitude of the periodical convergence is inversely proportional to the introspection rate. After conducting experiments, our algorithm outperforms the Meta Equilibrium Q-learning algorithm in realizing mixed-strategy Nash equilibrium.

12.
Genes (Basel) ; 14(11)2023 Nov 14.
Article in English | MEDLINE | ID: mdl-38003020

ABSTRACT

The ß-amylase (BAM) gene family encodes important enzymes that catalyze the conversion of starch to maltose in various biological processes of plants and play essential roles in regulating the growth and development of multiple plants. So far, BAMs have been extensively studied in Arabidopsis thaliana (A. thaliana). However, the characteristics of the BAM gene family in the crucial economic crop, cotton, have not been reported. In this study, 27 GhBAM genes in the genome of Gossypium hirsutum L (G. hirsutum) were identified by genome-wide identification, and they were divided into three groups according to sequence similarity and phylogenetic relationship. The gene structure, chromosome distribution, and collinearity of all GhBAM genes identified in the genome of G. hirsutum were analyzed. Further sequence alignment of the core domain of glucosyl hydrolase showed that all GhBAM family genes had the glycosyl hydrolase family 14 domain. We identified the BAM gene GhBAM7 and preliminarily investigated its function by transcriptional sequencing analysis, qRT-PCR, and subcellular localization. These results suggested that the GhBAM7 gene may influence fiber strength during fiber development. This systematic analysis provides new insight into the transcriptional characteristics of BAM genes in G. hirsutum. It may lay the foundation for further study of the function of these genes.


Subject(s)
Gossypium , beta-Amylase , beta-Amylase/genetics , Phylogeny , Multigene Family , Gene Expression Profiling , Plant Proteins/genetics , Plant Proteins/chemistry
13.
Folia Phoniatr Logop ; 2023 Oct 03.
Article in English | MEDLINE | ID: mdl-37788662

ABSTRACT

OBJECTIVE: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial Direct Current Stimulation (tDCS) treatment in patients at different stages post-infarction: the acute phase and the recovery period. METHODS: Twenty-eight patients were selected, consisting of 16 in the acute phase (AP) and 12 in the recovery period (RP), along with 18 healthy controls. Both patient groups underwent two weeks of tDCS treatment. Post-treatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. RESULTS: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased functional connectivity in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Post-treatment assessments revealed significant increases in functional connectivity within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased functional connectivity in the left temporal lobe post-treatment, which had shown increased functional connectivity pre-treatment. CONCLUSIONS: This study suggests that tDCS can effectively enhance graph naming functions in patients with post-infarction aphasia. The therapeutic effects appear to be mediated by enhancing functional connectivity within bilateral frontotemporal lobes.

14.
Angew Chem Int Ed Engl ; 62(49): e202313817, 2023 12 04.
Article in English | MEDLINE | ID: mdl-37852936

ABSTRACT

An epoxycyclohexenone (ECH) moiety occurs in natural products of both bacteria and ascomycete and basidiomycete fungi. While the enzymes for ECH formation in bacteria and ascomycetes have been identified and characterized, it remained obscure how this structure is biosynthesized in basidiomycetes. In this study, we i) identified a genetic locus responsible for panepoxydone biosynthesis in the basidiomycete mushroom Panus rudis and ii) biochemically characterized PanH, the cytochrome P450 enzyme catalyzing epoxide formation in this pathway. Using a PanH-producing yeast as a biocatalyst, we synthesized a small library of bioactive ECH compounds as a proof of concept. Furthermore, homology modeling, molecular dynamics simulation, and site directed mutation revealed the substrate specificity of PanH. Remarkably, PanH is unrelated to ECH-forming enzymes in bacteria and ascomycetes, suggesting that mushrooms evolved this biosynthetic capacity convergently and independently of other organisms.


Subject(s)
Agaricales , Ascomycota , Basidiomycota , Agaricales/metabolism , Cytochrome P-450 Enzyme System/metabolism , Biocatalysis , Basidiomycota/genetics , Ascomycota/metabolism , Bacteria/metabolism , Substrate Specificity
16.
BMC Genomics ; 24(1): 531, 2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37679709

ABSTRACT

BACKGROUND: Due to the influence of extreme weather, the environment in China's main cotton-producing areas is prone to drought stress conditions, which affect the growth and development of cotton and lead to a decrease in cotton yield. RESULTS: In this study, 188 upland cotton germplasm resources were phenotyped for data of 8 traits (including 3 major yield traits) under drought conditions in three environments for two consecutive years. Correlation analysis revealed significant positive correlations between the three yield traits. Genetic analysis showed that the estimated heritability of the seed cotton index (SC) under drought conditions was the highest (80.81%), followed by that of boll weight (BW) (80.64%) and the lint cotton index (LC) (70.49%) With genome-wide association study (GWAS) analysis, a total of 75 quantitative trait loci (QTLs) were identified, including two highly credible new QTL hotspots. Three candidate genes (Gh_D09G064400, Gh_D10G261000 and Gh_D10G254000) located in the two new QTL hotspots, QTL51 and QTL55, were highly expressed in the early stage of fiber development and showed significant correlations with SC, LC and BW. The expression of three candidate genes in two extreme materials after drought stress was analyzed by qRT-PCR, and the expression of these two materials in fibers at 15, 20 and 25 DPA. The expression of these three candidate genes was significantly upregulated after drought stress and was significantly higher in drought-tolerant materials than in drought-sensitive materials. In addition, the expression levels of the three candidate genes were higher in the early stage of fiber development (15 DPA), and the expression levels in drought-tolerant germplasm were higher than those in drought-sensitive germplasm. These three candidate genes may play an important role in determining cotton yield under drought conditions. CONCLUSIONS: This study is helpful for understanding the regulatory genes affecting cotton yield under drought conditions and provides germplasm and candidate gene resources for breeding high-yield cotton varieties under these conditions.


Subject(s)
Droughts , Genome-Wide Association Study , Quantitative Trait Loci , Plant Breeding , Gossypium/genetics
17.
Org Lett ; 25(28): 5345-5349, 2023 07 21.
Article in English | MEDLINE | ID: mdl-37439572

ABSTRACT

Guanacastane diterpenoids with an unusual 5/7/6 tricyclic skeleton mainly produced by basidiomycete fungi represent a structurally intriguing class of natural products. While the chemical synthesis of several members has been achieved, the biochemical and genetic basis of their biosynthesis remain unknown. Herein, we present the identification and characterization of two crucial enzymes in the biosynthesis of guanacastane diterpenoids in Psathyrella candolleana. Heterologous expression reveals that PsaD, a typical class I diterpene synthase, catalyzes the cyclization of geranylgeranyl diphosphate to form a new guanacastane-type diterpene, guanacasta-1,3-diene (7). Moreover, we demonstrate that PsaA, a cytochrome P450 monooxygenase, can catalyze multiple oxidations of 7 to yield guanacastepene U (8). These results provide new opportunities for genome mining and metabolic engineering of guanacastane diterpenoids.


Subject(s)
Basidiomycota , Diterpenes , Basidiomycota/genetics , Diterpenes/chemistry
18.
Nat Commun ; 14(1): 3436, 2023 06 10.
Article in English | MEDLINE | ID: mdl-37301868

ABSTRACT

Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-Seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Cyclization of 3 forms vibralactone (1) whose ß-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.


Subject(s)
Mixed Function Oxygenases , Proteomics , Lactones/metabolism , Flavins , Flavin-Adenine Dinucleotide
19.
Front Plant Sci ; 14: 1135302, 2023.
Article in English | MEDLINE | ID: mdl-37123844

ABSTRACT

Drought is one of the major abiotic stresses seriously affecting cotton yield. At present, the main cotton-producing areas in China are primarily arid and semiarid regions. Therefore, the identification of molecular markers and genes associated with cotton yield traits under drought conditions is of great importance for stabilize cotton yield under such conditions. In this study, resequencing data were used to conduct a genome-wide association study (GWAS) on 8 traits of 150 cotton germplasms. Under drought stress, 18 SNPs were significantly correlated with yield traits (single-boll weight (SBW) and seed (SC)), and 8 SNPs were identified as significantly correlated with effective fruit shoot number (EFBN) traits (a trait that is positively correlated with yield). Finally, a total of 15 candidate genes were screened. The combined results of the GWAS and transcriptome data analysis showed that four genes were highly expressed after drought stress, and these genes had significantly increased expression at 10, 15 and 25 DPA of fiber development. qRT-PCR was performed on two samples with drought tolerance extremes (drought-resistant Xinluzao 45 and drought-sensitive Xinluzao 26), revealing that three of the genes had the same differential expression pattern. This study provides a theoretical basis for the genetic analysis of cotton yield traits under drought stress, and provides gene resources for improved breeding of cotton yield traits under drought stress.

20.
Transl Oncol ; 34: 101691, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37207381

ABSTRACT

Lung adenocarcinoma (LUAD) is the most prevalent form of lung cancer globally, and its treatment remains a significant challenge. Therefore, it is crucial to comprehend the microenvironment to improve therapy and prognosis urgently. In this study, we utilized bioinformatic methods to analyze the transcription expression profile of patient samples with complete clinical information from the TCGA-LUAD datasets. To validate our findings, we also analyzed the Gene Expression Omnibus (GEO) datasets. The super-enhancer (SE) was visualized using the peaks of the H3K27ac and H3K4me1 ChIP-seq signal, which were identified by the Integrative Genomics Viewer (IGV). To further investigate the role of Centromere protein O (CENPO) in LUAD, we conducted various assays including Western blot, qRT-PCR, flow cytometry, wound healing and transwell assays to assess the cell functions of CENPO in vitro. The overexpression of CENPO is linked to a poor prognosis in patients with LUAD. Strong signal peaks of H3K27ac and H3K4me1 were also observed near the predicted SE regions of CENPO. CENPO was found to be positively associated with the expression levels of immune checkpoints and drug IC50 value (Roscovitine and TGX221), but negatively associated with the fraction levels of several immature cells and drug IC50 value (CCT018159, GSK1904529A, Lenaildomide, and PD-173074). Additionally, CENPO-associated prognostic signature (CPS) was identified as an independent risk factor. The high-risk group for LUAD is identified based on CPS enrichment, which involved not only endocytosis that transfers mitochondria to promote cell survival in response to chemotherapy but also cell cycle promotion that leads to drug resistance. The removal of CENPO significantly suppressed metastasis and induced arrest and apoptosis of LUAD cells. The involvement of CENPO in the immunosuppression of LUAD provides a prognostic signature for LUAD patients.

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