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1.
J Imaging Inform Med ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39313716

ABSTRACT

This study developed and validated a deep learning-based diagnostic model with uncertainty estimation to aid radiologists in the preoperative differentiation of pathological subtypes of renal cell carcinoma (RCC) based on computed tomography (CT) images. Data from 668 consecutive patients with pathologically confirmed RCC were retrospectively collected from Center 1, and the model was trained using fivefold cross-validation to classify RCC subtypes into clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). An external validation with 78 patients from Center 2 was conducted to evaluate the performance of the model. In the fivefold cross-validation, the area under the receiver operating characteristic curve (AUC) for the classification of ccRCC, pRCC, and chRCC was 0.868 (95% CI, 0.826-0.923), 0.846 (95% CI, 0.812-0.886), and 0.839 (95% CI, 0.802-0.88), respectively. In the external validation set, the AUCs were 0.856 (95% CI, 0.838-0.882), 0.787 (95% CI, 0.757-0.818), and 0.793 (95% CI, 0.758-0.831) for ccRCC, pRCC, and chRCC, respectively. The model demonstrated robust performance in predicting the pathological subtypes of RCC, while the incorporated uncertainty emphasized the importance of understanding model confidence. The proposed approach, integrated with uncertainty estimation, offers clinicians a dual advantage: accurate RCC subtype predictions complemented by diagnostic confidence metrics, thereby promoting informed decision-making for patients with RCC.

2.
J Org Chem ; 2024 Sep 13.
Article in English | MEDLINE | ID: mdl-39267456

ABSTRACT

The NHC-catalyzed enantioselective [4 + 2] annulation of 9H-fluorene-1-carbaldenydes with cyclic imines was successfully developed. A series of optically enriched polycyclic dihydroisoquinolinones were synthesized in moderate to excellent yields with good to excellent enantioselectivities. In addition, this efficient method could also be amenable to the synthesis of spirocyclic compounds by using isatin-derived ketimines as the electrophiles.

3.
Ecotoxicol Environ Saf ; 284: 116997, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39260215

ABSTRACT

Due to the complexity of environmental exposure factors and the low levels of exposure in the general population, identifying the key environmental factors associated with diabetes and understanding their potential mechanisms present significant challenges. This study aimed to identify key polycyclic aromatic hydrocarbons (PAHs) contributing to increased fasting blood glucose (FBG) concentrations and to explore their potential metabolic mechanisms. We recruited a highly PAH-exposed diesel engine exhaust testing population and healthy controls. Our findings found a positive association between FBG concentrations and PAH metabolites, identifying 1-OHNa, 2-OHPh, and 9-OHPh as major contributors to the rise in FBG concentrations induced by PAH mixtures. Specifically, each 10 % increase in 1-OHNa, 2-OHPh, and 9-OHPh concentrations led to increases in FBG concentrations of 0.201 %, 0.261 %, and 0.268 %, respectively. Targeted metabolomics analysis revealed significant alterations in metabolic pathways among those exposed to high levels of PAHs, including sirtuin signaling, asparagine metabolism, and proline metabolism pathway. Toxic function analysis highlighted differential metabolites involved in various dysglycemia-related conditions, such as cardiac arrhythmia and renal damage. Mediation analysis revealed that 2-aminooctanoic acid mediated the FBG elevation induced by 2-OHPh, while 2-hydroxyphenylacetic acid and hypoxanthine acted as partial suppressors. Notably, 2-aminooctanoic acid was identified as a crucial intermediary metabolic biomarker, mediating significant portions of the associations between the multiple different structures of OH-PAHs and elevated FBG concentrations, accounting for 16.73 %, 10.84 %, 10.00 %, and 11.90 % of these effects for 1-OHPyr, 2-OHFlu, the sum concentrations of 2- and 9-OHPh, and the sum concentrations of total OH-PAHs, respectively. Overall, our study explored the potential metabolic mechanisms underlying the elevated FBG induced by PAHs and identified 2-aminooctanoic acid as a pivotal metabolic biomarker, presenting a potential target for intervention.

5.
Sci Total Environ ; 952: 175897, 2024 Nov 20.
Article in English | MEDLINE | ID: mdl-39222811

ABSTRACT

Due to the lack of relatively long-term, high-resolution terrestrial records in tropical southern China, there is limited published research on terrestrial vegetation changes and their responses to regional and/or global climate forcings since the last glacial period. In this study, a 170-cm-long peat core (covering the interval from ~44.1 to 9.3 cal kyr BP) recovered from the Xialu peatland in Leizhou Peninsula, South China, was analyzed for organic carbon isotope (δ13Corg), along with total organic carbon, total nitrogen, and bulk dry density, to investigate past vegetation and hydroclimatic changes. Our results showed that C4 plants dominated the study region during Marine Isotope Stage (MIS) 2 (29-14 cal kyr BP), indicating generally cooler and drier conditions during MIS 2 relative to late MIS 3 (~ 44.1-29 cal kyr BP) and early MIS 1 (14-9.3 cal kyr BP). In particular, the driest conditions occurred during the Last Glacial Maximum (~ 25-19 cal kyr BP) when sea level was at its lowest. In addition, several millennial-scale climatic events associated with the expansion of C4 plants were clearly identified. Our record is sensitive to a variety of glacial-interglacial forcings, including regional processes and global forcing, among which the inundation history of Beibu Gulf due to sea-level change during the late Quaternary, which has been neglected in previous studies, may have played an important role in modulating paleo-hydroclimatic changes in tropical southern China.

6.
Environ Pollut ; 360: 124705, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39134171

ABSTRACT

The infant gut microbiome matures greatly in the first year of life. Ambient air pollution (AAP) exposure is associated with the infant gut microbiome. However, whether time-varying AAP influences infant gut microbiome variation is rarely investigated. This study aimed to investigate the effects of PM2.5, PM10, and O3 on infant gut microbiome variation longitudinally. Demographic information, stool samples, and AAP exposure concentrations were collected at 6, 12, 24 months from infants. Gut microbiome was processed and analyzed using 16S rRNA V3-V4 gene regions. AAP exposure concentrations were calculated using the China High Air Pollutants (CHAP) database. Multiple pollutant models were used to assess the mixed effects of PM2.5, PM10, and O3 on infant gut microbiome variation. Infants' gut microbiomes at 6, 12, 24 months old had significant differences in alpha diversity, beta diversity, and community composition. PM2.5 and O3 respectively explained 6.3% and 5.3% of the differences in community composition for 24-month-old infants. Single pollutant exposure and multiple pollutant exposure in different periods were both associated with alpha diversity indices and specific gut microbial phyla and genera. AAP was more associated with infant gut microbial alpha diversity indices, phyla variations, and genera variations at 12-24 months than 6-12 months. Multiple pollutant exposure in 0-2 lag months showed negative correlations with 12-24 months variation in Escherichia-Shigella (ß = -0.854, 95%CI: 1.398 to -0.310) and Enterococcus (ß = -0.979, 95%CI: 1.429 to -0.530). This study highlighted that time-varying PM2.5, PM10, and O3 synergistically influenced the variation of alpha diversity and abundance of gut microbial taxa in infants. Further research is needed to explore the effects and mechanisms of other environmental exposures on infant gut microbiome variation.


Subject(s)
Air Pollutants , Air Pollution , Environmental Exposure , Gastrointestinal Microbiome , Gastrointestinal Microbiome/drug effects , Infant , Humans , Air Pollution/statistics & numerical data , Air Pollutants/analysis , Environmental Exposure/statistics & numerical data , China , Male , RNA, Ribosomal, 16S/genetics , Female , Particulate Matter/analysis , Feces/microbiology , Child, Preschool , Bacteria/classification , Bacteria/genetics
7.
Zhongguo Zhen Jiu ; 44(8): 889-93, 2024 Aug 12.
Article in Chinese | MEDLINE | ID: mdl-39111786

ABSTRACT

OBJECTIVE: To observe the clinical effect of guasha-fangsha (scrapping and bleeding) therapy combined with electroacupuncture (EA) on greater occipital neuralgia. METHODS: Ninety patients with greater occipital neuralgia were randomly divided into an observation group (45 cases) and a control group (45 cases, 2 cases dropped out). In the control group, EA was delivered at Fengfu (GV 16) and bilateral Tianzhu (BL 10), Fengchi (GB 20), Wangu (GB 12), Yuzhen (BL 9) and Houxi (SI 3), with disperse-dense wave, at 2 Hz/100 Hz in frequency and 2 mA to 6 mA in intensity, for 30 min in each intervention, once every other days, 3 times a week. In the observation group, on the basis of the intervention as the control group, guasha-fangsha therapy was used along the distribution of the bladder meridian of foot-taiyang on the occipital region and that of the gallbladder meridian of foot-shaoyang on the lateral side of the head, once weekly. The duration of treatment was 3 weeks in the two groups. In the two groups, before treatment, after 1, 2 and 3 weeks of treatment and in follow-up visit after 3 weeks of treatment completion, the score of visual analogue scale (VAS) was observed; before and after treatment, as well as in follow-up visit after 3 weeks of treatment completion, the scores of self-rating anxiety scale (SAS), self-rating depression scale (SDS) and 36-item short-form health survey (SF-36) were observed; after treatment and in follow-up visit after 3 weeks of treatment completion, the clinical efficacy was evaluated. RESULTS: After one week of treatment, the VAS score in the observation group decreased when compared with that before treatment (P<0.05), while the scores in 2 and 3 weeks of treatment and in follow-up visit after 3 weeks of treatment completion were lower than those before treatment in the two groups (P<0.05) separately. At each time point after treatment, the VAS scores in the observation group were lower than those in the control group (P<0.05). After treatment and during the follow-up visit, the scores of SAS and SDS decreased when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05); the scores of each item in SF-36 were elevated in comparison with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment, the total effective rate of the observation group was 91.1% (41/45), higher than that (76.7%, 33/43) of the control group (P<0.05). In follow-up visit, the total effective rate of the observation group was 91.1% (41/45), which was higher than 72.1% (31/43) of the control group (P<0.05). CONCLUSION: Guasha-fangsha therapy combined with electroacupuncture can effectively relieve greater occipital neuralgia, alleviate pain severity, ameliorate anxiety and depression and improve the quality of life in the patients.


Subject(s)
Electroacupuncture , Neuralgia , Humans , Male , Female , Middle Aged , Neuralgia/therapy , Adult , Aged , Treatment Outcome , Combined Modality Therapy , Acupuncture Points , Acupuncture Therapy , Young Adult
9.
Blood ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39190466

ABSTRACT

Immune thrombocytopenia (ITP) is a complicated bleeding disease characterized by sharp platelet reduction. As a dominating element involved in ITP, megakaryocytes (MKs) are responsible for thrombopoiesis. However, the mechanism underlying the dysregulation of thrombopoiesis that occurs in ITP remains unidentified. In this study, we examined the role of yes-associated protein 1 (YAP1) in thrombopoiesis during ITP. We observed a reduced YAP1 expression with cytoskeletal actin misalignment in MKs from ITP patients. By using an experimental ITP mouse model, we showed that reduced YAP1 expression induced aberrant MK distribution, reduced the percentage of late MKs among total MKs, and caused submaximal platelet recovery. Mechanistically, YAP1 upregulation by binding of GATA binding protein 1 (GATA1) to its promoter promoted MK maturation. Phosphorylated YAP1 promoted cytoskeletal activation by binding of its WW2 domain to myosin heavy chain 9 (MYH9), facilitating thrombopoiesis. Targeting YAP1 by its activator XMU-MP-1 was sufficient to rescue cytoskeletal defects and thrombopoiesis dysregulation in YAP1+/- mice with ITP and patients. Taken together, these results demonstrate a crucial role for YAP1 in thrombopoiesis, providing a potential for the development of diagnostic markers and therapeutic options for ITP.

11.
Foods ; 13(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998537

ABSTRACT

Different grain sources of whiskey have great potential for aroma expression. In this paper, four whiskeys fermented from different raw materials (barley, wheat, highland barley, and sorghum) were compared. Gas chromatography-mass spectrometry (GC-MS) and sensory evaluation were used to determine the composition of the aromatic compounds. A correlation analysis was further conducted between the aromatic compounds and sensory evaluations. Barley whiskey and wheat whiskey had more pronounced fruity, floral, and grain aromas, attributed to esters and terpenes. Barley whiskey had the most compounds (55), followed by highland barley whiskey (54). Highland barley whiskey had the greatest number of unique aroma compounds (seven). It exhibited a unique cocoa aroma related to concentrations of trans-2-nonenal, γ-nonanolactone, 1-nonanol, isoamyl lactate, 2-butanol, and 6-methyl-5-hepten-2-one. Sorghum whiskey had a specific leather and mushroom aroma attributed to 6-methyl-5-hepten-2-one, ethyl lactate, ethyl caprate, phenethyl octanoate, farnesol, α-terpineol, 3-methyl-1-pentanol, and methyleugenol. Alcohols were the main aroma components of grain whiskeys. Isoamyl alcohol (231.59~281.39 mg/L), phenylethyl alcohol (5.755~9.158 mg/L), citronellol (0.224~4.103 mg/L), ß-damascenone (0.021~2.431 mg/L), geraniol (0.286~1.416 mg/L), isoamyl acetate (0.157~0.918 mg/L), phenylacetaldehyde (0.162~0.470 mg/L), linalool (0.024~0.148 mg/L), 1-octen-3-ol (0.016~0.145 mg/L), trans-2-nonenal (0.027~0.105 mg/L), and trans-2-octen-1-ol (0.011~0.054 mg/L) were all important aroma compounds in the whiskeys.

12.
Sci Total Environ ; 947: 174535, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38972403

ABSTRACT

The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3ß1 plays an important role. CD151 binds to α3ß1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3ß1 in thyroid cell adhesion, which may be mediated by the CD151/α3ß1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3ß1/Rac1 pathway, leading to glandular damage.


Subject(s)
Integrin alpha3beta1 , Thyroid Gland , Vehicle Emissions , Animals , Mice , Thyroid Gland/drug effects , Vehicle Emissions/toxicity , Integrin alpha3beta1/metabolism , Cell Adhesion/drug effects , Air Pollutants/toxicity , Particulate Matter/toxicity , Thyroid Epithelial Cells/drug effects , Thyroid Epithelial Cells/metabolism , Signal Transduction
13.
Ecotoxicol Environ Saf ; 281: 116680, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38964057

ABSTRACT

Inhaling polyhexamethylene guanidine (PHMG) aerosol, a broad-spectrum disinfectant, can lead to severe pulmonary fibrosis. Ferroptosis, a form of programmed cell death triggered by iron-dependent lipid peroxidation, is believed to play a role in the chemical-induced pulmonary injury. This study aimed to investigate the mechanism of ferroptosis in the progression of PHMG-induced pulmonary fibrosis. C57BL/6 J mice and the alveolar type II cell line MLE-12 were used to evaluate the toxicity of PHMG in vivo and in vitro, respectively. The findings indicated that iron deposition was observed in PHMG induced pulmonary fibrosis mouse model and ferroptosis related genes have changed after 8 weeks PHMG exposure. Additionally, there were disturbances in the antioxidant system and mitochondrial damage in MLE-12 cells following a 12-hour treatment with PHMG. Furthermore, the study observed an increase in lipid peroxidation and a decrease in GPX4 activity in MLE-12 cells after exposure to PHMG. Moreover, pretreatment with the ferroptosis inhibitors Ferrostatin-1 (Fer-1) and Liproxstatin-1 (Lip-1) not only restored the antioxidant system and GPX4 activity but also mitigated lipid peroxidation. Current data exhibit the role of ferroptosis pathway in PHMG-induced pulmonary fibrosis and provide a potential target for future treatment.


Subject(s)
Ferroptosis , Guanidines , Lipid Peroxidation , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase , Pulmonary Fibrosis , Animals , Ferroptosis/drug effects , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , Mice , Lipid Peroxidation/drug effects , Cell Line , Guanidines/toxicity , Guanidines/pharmacology , Male , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/pathology , Cyclohexylamines/pharmacology , Phenylenediamines , Quinoxalines , Spiro Compounds
14.
Front Mol Biosci ; 11: 1394902, 2024.
Article in English | MEDLINE | ID: mdl-38903179

ABSTRACT

Background: Cervical cancer (CC) is the fourth most common cancer among women worldwide. As part of the brisk cross-talk between the host and the tumor, prognosis can be affected through inflammatory responses or the tumor microenvironment. However, further exploration of the inflammatory response-related genes that have prognostic value, microenvironment infiltration, and chemotherapeutic therapies in CC is needed. Methods: The clinical data and mRNA expression profiles of CC patients were downloaded from a public database for this study. In the TCGA cohort, a multigene prognostic signature was constructed by least absolute shrinkage and selection operator (LASSO) and Cox analyses. CC patients from the GEO cohort were used for validation. K‒M analysis was used to compare overall survival (OS) between the high- and low-risk groups. Univariate and multivariate Cox analyses were applied to determine the independent predictors of OS. The immune cell infiltration and immune-related functional score were calculated by single-sample gene set enrichment analysis (GSEA). Immunohistochemistry was utilized to validate the protein expression of prognostic genes in CC tissues. Results: A genetic signature model associated with the inflammatory response was built by LASSO Cox regression analysis. Patients in the high-risk group had a significantly lower OS rate. The predictive ability of the prognostic genes was evaluated by means of receiver operating characteristic (ROC) curve analysis. The risk score was confirmed to be an independent predictor of OS by univariate and multivariate Cox analyses. The immune status differed between the high-risk and low-risk groups, and the cancer-related pathways were enriched in the high-risk group according to functional analysis. The risk score was significantly related to tumor stage and immune infiltration type. The expression levels of five prognostic genes (LCK, GCH1, TNFRSF9, ITGA5, and SLC7A1) were positively related to sensitivity to antitumor drugs. Additionally, the expression of prognostic genes was significantly different between CC tissues and myoma patient cervix (non-tumorous) tissues in the separate sample cohort. Conclusion: A model consisting of 5 inflammation-related genes can be used to predict prognosis and influence immune status in CC patients. Furthermore, the inhibition or enhancement of these genes may become a novel alternative therapy.

15.
Food Microbiol ; 122: 104557, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38839221

ABSTRACT

To investigate the potential antifungal mechanisms of rhizosphere Actinobacteria against Ceratocystis fimbriata in sweet potato, a comprehensive approach combining biochemical analyses and multi-omics techniques was employed in this study. A total of 163 bacterial strains were isolated from the rhizosphere soil of sweet potato. Among them, strain MEPS155, identified as Streptomyces djakartensis, exhibited robust and consistent inhibition of C. fimbriata mycelial growth in in vitro dual culture assays, attributed to both cell-free supernatant and volatile organic compounds. Moreover, strain MEPS155 demonstrated diverse plant growth-promoting attributes, including the production of indole-3-acetic acid, 1-aminocyclopropane-1-carboxylate deaminase, phosphorus solubilization, nitrogen fixation, and enzymatic activities such as cellulase, chitinase, and protease. Notably, strain MEPS155 exhibited efficacy against various sweet potato pathogenic fungi. Following the inoculation of strain MEPS155, a significant reduction (P < 0.05) in malondialdehyde content was observed in sweet potato slices, indicating a potential protective effect. The whole genome of MEPS155 was characterized by a size of 8,030,375 bp, encompassing 7234 coding DNA sequences and 32 secondary metabolite biosynthetic gene clusters. Transcriptomic analysis revealed 1869 differentially expressed genes in the treated group that cultured with C. fimbriata, notably influencing pathways associated with porphyrin metabolism, fatty acid biosynthesis, and biosynthesis of type II polyketide products. These alterations in gene expression are hypothesized to be linked to the production of secondary metabolites contributing to the inhibition of C. fimbriata. Metabolomic analysis identified 1469 potential differently accumulated metabolites (PDAMs) when comparing MEPS155 and the control group. The up-regulated PDAMs were predominantly associated with the biosynthesis of various secondary metabolites, including vanillin, myristic acid, and protocatechuic acid, suggesting potential inhibitory effects on plant pathogenic fungi. Our study underscores the ability of strain S. djakartensis MEPS155 to inhibit C. fimbriata growth through the production of secretory enzymes or secondary metabolites. The findings contribute to a theoretical foundation for future investigations into the role of MEPS155 in postharvest black rot prevention in sweet potato.


Subject(s)
Ascomycota , Ipomoea batatas , Plant Diseases , Rhizosphere , Streptomyces , Ipomoea batatas/microbiology , Streptomyces/genetics , Streptomyces/metabolism , Streptomyces/isolation & purification , Plant Diseases/microbiology , Plant Diseases/prevention & control , Ascomycota/growth & development , Ascomycota/metabolism , Ascomycota/genetics , Soil Microbiology , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Multiomics
16.
Technol Health Care ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38875055

ABSTRACT

BACKGROUND: The incidence of kidney tumors is progressively increasing each year. The precision of segmentation for kidney tumors is crucial for diagnosis and treatment. OBJECTIVE: To enhance accuracy and reduce manual involvement, propose a deep learning-based method for the automatic segmentation of kidneys and kidney tumors in CT images. METHODS: The proposed method comprises two parts: object detection and segmentation. We first use a model to detect the position of the kidney, then narrow the segmentation range, and finally use an attentional recurrent residual convolutional network for segmentation. RESULTS: Our model achieved a kidney dice score of 0.951 and a tumor dice score of 0.895 on the KiTS19 dataset. Experimental results show that our model significantly improves the accuracy of kidney and kidney tumor segmentation and outperforms other advanced methods. CONCLUSION: The proposed method provides an efficient and automatic solution for accurately segmenting kidneys and renal tumors on CT images. Additionally, this study can assist radiologists in assessing patients' conditions and making informed treatment decisions.

17.
Anal Chem ; 96(28): 11479-11487, 2024 07 16.
Article in English | MEDLINE | ID: mdl-38943570

ABSTRACT

Accurate orientations and stable conformations of membrane receptor immobilization are particularly imperative for accurate drug screening and ligand-protein affinity analysis. However, there remain challenges associated with (1) traditional recombination, purification, and immobilization of membrane receptors, which are time-consuming and labor-intensive; (2) the orientations on the stationary phase are not easily controlled. Herein, a novel one-step synthesis and oriented-immobilization membrane-receptor affinity chromatography (oSOMAC) method was developed to realize high-throughput and accurate drug screening targeting specific domains of membrane receptors. We employed Strep-tag II as a noncovalent immobilization tag fused into platelet-derived growth factor receptor ß (PDGFRß) through CFPS, and meanwhile, the Strep-Tactin-modified monolithic columns are prepared in batches. The advantages of oSOMAC are as follows: (1) targeted membrane receptors can be expressed independent of living cell within 1-2 h; (2) orientation of membrane receptors can be flexibly controlled and active sites can expose accurately; and (3) targeted membrane receptors can be synthesized, purified, and orientation-immobilized on monolithic columns in one step. Accordingly, three potential PDGFRß intracellular domain targeted ligands: tanshinone IIA (Tan IIA), hydroxytanshinone IIA, and dehydrotanshinone IIA were successfully screened out from Salvia miltiorrhiza extract through oSOMAC. Pharmacological experiments and molecular docking further demonstrated that Tan IIA could attenuate hepatic stellate cells activation by targeting the protein kinase domain of PDGFRß with a KD value of 9.7 µM. Ultimately, the novel oSOMAC method provides an original insight for accurate drug screening and interaction analysis which can be applied in other membrane receptors.


Subject(s)
Receptor, Platelet-Derived Growth Factor beta , Receptor, Platelet-Derived Growth Factor beta/metabolism , Ligands , Humans , Chromatography, Affinity , Drug Evaluation, Preclinical , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/genetics , Oligopeptides/chemistry
18.
Chemosphere ; 362: 142564, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38885762

ABSTRACT

Atmospheric pollution has been demonstrated to be associated with ocular surface diseases characterized by corneal epithelial damage, including impaired barrier function and squamous metaplasia. However, the specific mechanisms underlying the impact of atmospheric pollution on corneal damage are still unknow. To address this gap in knowledge, we conducted a study using a whole-body exposure system to investigate the detrimental effects of traffic-related air pollution, specifically diesel exhaust (DE), on corneal epithelium in C57BL/6 mice over a 28-day period. Following DE exposure, the pathological alterations in corneal epithelium, including significant increase in corneal thickness and epithelial stratification, were observed in mice. Additionally, exposure to DE was also shown to disrupt the barrier functions of corneal epithelium, leading to excessive proliferation of basal cells and even causing squamous metaplasia in corneal epithelium. Further studies have found that the activation of yes-associated protein (YAP), characterized by nuclear translocation, may play a significant role in DE-induced corneal squamous metaplasia. In vitro assays confirmed that DE exposure triggered the YAP/ß-catenin pathway, resulting in squamous metaplasia and destruction of barrier functions. These findings provide the preliminary evidence that YAP activation is one of the mechanisms of the damage to corneal epithelium caused by traffic-related air pollution. These findings contribute to the knowledge base for promoting eye health in the context of atmospheric pollution.


Subject(s)
Air Pollutants , Epithelium, Corneal , Metaplasia , Mice, Inbred C57BL , Vehicle Emissions , YAP-Signaling Proteins , Vehicle Emissions/toxicity , Animals , Epithelium, Corneal/drug effects , Epithelium, Corneal/pathology , Mice , Air Pollutants/toxicity , Male , beta Catenin/metabolism , Cell Proliferation/drug effects
19.
J Cataract Refract Surg ; 50(10): 1020-1025, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38783488

ABSTRACT

PURPOSE: To explore the severity of posterior capsule opacification (PCO) using objective detection techniques and its relationship with visual acuity. SETTING: The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. DESIGN: Prospective cohort study. METHODS: All patients underwent slitlamp examination, intraocular pressure (IOP) measurement, and corrected distance visual acuity (CDVA) testing before Nd:YAG laser capsulotomy, and examination, after fully dilated, with: IOLMaster 700, optical coherence tomography (OCT), Sirius Topographer (CSO) anterior segment analysis, and color fundus photography (CFP). CDVA and IOP were taken post treatment. Thickness and density of the posterior capsule, CFP quality (CFPQ) and OCT signal strength (OCTSS) were recorded. Analysis used Spearman correlation, heatmaps, and receiver operating characteristic curves. RESULTS: 83 eyes in 78 patients were included in this study. Spearman correlation analysis revealed correlations between pretreatment CDVA and IOLMaster 700 PCO thickness (MT), IOLMaster 700 cumulative effect (MCE), Sirius PCO thickness (ST), Sirius maximum density (SMD), Sirius cumulative effect (SCE), OCTSS, and CFPQ (correlation coefficients were 0.500, 0.484, 0.465, -0.256, 0.317, -0.442, -0.412, all P < .05). The improvement of vision acuity (ImpVA) showed correlations with MT, MCE, ST, SCE, OCTSS, and CFPQ (correlation coefficients were -0.452, -0.471, -0.346, -0.278, 0.320, 0.381, all P < .05). For ImpVA, the predictive ability of IOLMaster 700 was superior to Sirius, and the joint model was significantly better than single factors. CONCLUSIONS: Posterior capsule thickness and cumulative effect were reliable indicators for evaluating PCO. Compared with Sirius, the IOLMaster 700 demonstrated superior predictive ability and higher correlation.


Subject(s)
Capsule Opacification , Tomography, Optical Coherence , Visual Acuity , Humans , Visual Acuity/physiology , Capsule Opacification/diagnosis , Prospective Studies , Tomography, Optical Coherence/methods , Male , Female , Middle Aged , Posterior Capsule of the Lens/pathology , Posterior Capsule of the Lens/diagnostic imaging , Aged , Intraocular Pressure/physiology , ROC Curve , Phacoemulsification , Lasers, Solid-State/therapeutic use , Adult , Lens Implantation, Intraocular , Severity of Illness Index
20.
Gene ; 926: 148623, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-38821328

ABSTRACT

Topping, an important tree shaping and pruning technique, can promote the outgrowth of citrus axillary buds. However, the underlying molecular mechanism is still unclear. In this study, spring shoots of Citrus reticulata 'Huagan No.2' were topped and transcriptome was compared between axillary buds of topped and untopped shoots at 6 and 11 days after topping (DAT). 1944 and 2394 differentially expressed genes (DEGs) were found at 6 and 11 DAT, respectively. KEGG analysis revealed that many DEGs were related to starch and sucrose metabolism, signal transduction of auxin, cytokinin and abscisic acid. Specially, transcript levels of auxin synthesis, transport, and signaling-related genes (SAURs and ARF5), cytokinin signal transduction related genes (CRE1, AHP and Type-A ARRs), ABA signal responsive genes (PYL and ABF) were up-regulated by topping; while transcript levels of auxin receptor TIR1, auxin responsive genes AUX/IAAs, ABA signal transduction related gene PP2Cs and synthesis related genes NCED3 were down-regulated. On the other hand, the contents of sucrose and fructose in axillary buds of topped shoots were significantly higher than those in untopped shoots; transcript levels of 16 genes related to sucrose synthase, hexokinase, sucrose phosphate synthase, endoglucanase and glucosidase, were up-regulated in axillary buds after topping. In addition, transcript levels of genes related to trehalose 6-phosphate metabolism and glycolysis/tricarboxylic acid (TCA) cycle, as well to some transcription factors including Pkinase, Pkinase_Tyr, Kinesin, AP2/ERF, P450, MYB, NAC and Cyclin_c, significantly responded to topping. Taken together, the present results suggested that topping promoted citrus axillary bud outgrowth through comprehensively regulating plant hormone and carbohydrate metabolism, as well as signal transduction. These results deepened our understanding of citrus axillary bud outgrowth by topping and laid a foundation for further research on the molecular mechanisms of citrus axillary bud outgrowth.


Subject(s)
Citrus , Gene Expression Profiling , Gene Expression Regulation, Plant , Citrus/genetics , Citrus/growth & development , Citrus/metabolism , Gene Expression Profiling/methods , Transcriptome , Signal Transduction , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Shoots/genetics , Plant Shoots/growth & development , Plant Shoots/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/genetics , Indoleacetic Acids/metabolism , Gene Regulatory Networks
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