An automatic texture feature analysis framework of renal tumor: surgical, pathological, and molecular evaluation based on multi-phase abdominal CT.

OBJECTIVES: To determine whether the texture feature analysis of multi-phase abdominal CT can provide a robust prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. METHODS: A total of 1051 participants with renal tumor were split into the internal cohort (850 patients from four different hospitals) and the external testing cohort (201 patients from another local hospital). The proposed framework comprised a 3D-kidney and tumor segmentation model by 3D-UNet, a feature extractor for the regions of interest based on radiomics and image dimension reduction, and the six classifiers by XGBoost. A quantitative model interpretation method called SHAP was used to explore the contribution of each feature. RESULTS: The proposed multi-phase abdominal CT model provides robust prediction for benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in the internal validation set, with the AUROC values of 0.88 ± 0.1, 0.90 ± 0.1, 0.91 ± 0.1, 0.89 ± 0.1, 0.84 ± 0.1, and 0.88 ± 0.1, respectively. The external testing set also showed impressive results, with AUROC values of 0.83 ± 0.1, 0.83 ± 0.1, 0.85 ± 0.1, 0.81 ± 0.1, 0.79 ± 0.1, and 0.81 ± 0.1, respectively. The radiomics feature including the first-order statistics, the tumor size-related morphology, and the shape-related tumor features contributed most to the model predictions. CONCLUSIONS: Automatic texture feature analysis of abdominal multi-phase CT provides reliable predictions for multi-tasks, suggesting the potential usage of clinical application. CLINICAL RELEVANCE STATEMENT: The automatic texture feature analysis framework, based on multi-phase abdominal CT, provides robust and reliable predictions for multi-tasks. These valuable insights can serve as a guiding tool for clinical diagnosis and treatment, making medical imaging an essential component in the process. KEY POINTS: • The automatic texture feature analysis framework based on multi-phase abdominal CT can provide more accurate prediction of benign and malignant, histological subtype, pathological stage, nephrectomy risk, pathological grade, and Ki67 index in renal tumor. • The quantitative decomposition of the prediction model was conducted to explore the contribution of the extracted feature. • The study involving 1051 patients from 5 medical centers, along with a heterogeneous external data testing strategy, can be seamlessly transferred to various tasks involving new datasets.

Identification of a novel thermostable transaminase and its application in L-phosphinothricin biosynthesis.

Transaminase (TA) is a crucial biocatalyst for enantioselective production of the herbicide L-phosphinothricin (L-PPT). The use of enzymatic cascades has been shown to effectively overcome the unfavorable thermodynamic equilibrium of TA-catalyzed transamination reaction, also increasing demand for TA stability. In this work, a novel thermostable transaminase (PtTA) from Pseudomonas thermotolerans was mined and characterized. The PtTA showed a high specific activity (28.63 U/mg) towards 2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO), with excellent thermostability and substrate tolerance. Two cascade systems driven by PtTA were developed for L-PPT biosynthesis, including asymmetric synthesis of L-PPT from PPO and deracemization of D, L-PPT. For the asymmetric synthesis of L-PPT from PPO, a three-enzyme cascade was constructed as a recombinant Escherichia coli (E. coli G), by co-expressing PtTA, glutamate dehydrogenase (GluDH) and D-glucose dehydrogenase (GDH). Complete conversion of 400 mM PPO was achieved using only 40 mM amino donor L-glutamate. Furthermore, by coupling D-amino acid aminotransferase (Ym DAAT) from Bacillus sp. YM-1 and PtTA, a two-transaminase cascade was developed for the one-pot deracemization of D, L-PPT. Under the highest reported substrate concentration (800 mM D, L-PPT), a 90.43% L-PPT yield was realized. The superior catalytic performance of the PtTA-driven cascade demonstrated that the thermodynamic limitation was overcome, highlighting its application prospect for L-PPT biosynthesis. KEY POINTS: • A novel thermostable transaminase was mined for L-phosphinothricin biosynthesis. • The asymmetric synthesis of L-phosphinothricin was achieved via a three-enzyme cascade. • Development of a two-transaminase cascade for D, L-phosphinothricin deracemization.

Study on the Anti-Ulcerative Colitis Effect of Pseudo-Ginsenoside RT4 Based on Gut Microbiota, Pharmacokinetics, and Tissue Distribution.

The purpose of this study was to explore the therapeutic effect of the oral administration of pseudo-ginsenoside RT4 (RT4) on ulcerative colitis (UC), and to determine the rate of absorption and distribution of RT4 in mice with UC. Balb/c mice were induced using dextran sulfate sodium salts (DSS) to establish the UC model, and 10, 20, or 40 mg/kg of RT4 was subsequently administered via gavage. The clinical symptoms, inflammatory response, intestinal barrier, content of total short-chain fatty acids (SCFAs), and gut microbiota were investigated. Caco-2 cells were induced to establish the epithelial barrier damage model using LPS, and an intervention was performed using 4, 8, and 16 µg/mL of RT4. The inflammatory factors, transient electrical resistance (TEER), and tight-junction protein expression were determined. Finally, pharmacokinetic and tissue distribution studies following the intragastric administration of RT4 in UC mice were performed. According to the results in mice, RT4 decreased the disease activity index (DAI) score, restored the colon length, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and boosted the levels of immunosuppressive cytokine IL-10, increased the content of SCFAs, improved the colonic histopathology, maintained the ultrastructure of colonic mucosal epithelial cells, and corrected disturbances in the intestinal microbiota. Based on the results in caco-2 cells, RT4 reduced the levels of TNF-α, IL-6, and IL-1ß; protected integrity of monolayers; and increased tight-junction protein expression. Additionally, the main pharmacokinetic parameters (Cmax, Tmax, t1/2, Vd, CL, AUC) were obtained, the absolute bioavailability was calculated as 18.90% ± 2.70%, and the main distribution tissues were the small intestine and colon. In conclusion, RT4, with the features of slow elimination and directional distribution, could alleviate UC by inhibiting inflammatory factors, repairing the intestinal mucosal barrier, boosting the dominant intestinal microflora, and modulating the expression of SCFAs.

Deep learning, geometric characterization and hydrodynamic modeling for assessing sewer defect impacts on urban flooding: A case study in Guangzhou, China.

Deep learning techniques have offered innovative and efficient tools for accurate and automated detection of sewer defects by leveraging large-scale sewer data and advanced feature learning algorithms. However, there has been a lack of thorough characterization of the geometric properties of segmented defects, let alone systematically calculate the severity level of sewer defects and quantitatively evaluate their impacts on flood conditions in hydrodynamic models. This study proposed a comprehensive framework and related metrics to accurately and automatically detect, segment, characterize, and evaluate the impacts of sewer defects on flooded nodes and volumes by integrating a DeepLabv3+-based segmentation technique, an automated geometric characterization and severity quantification module, and a GIS and SWMM-based hydrodynamic modeling. The results clearly showed in details where and how much the urban flooding was affected by the different defect types. The segmentation model achieved satisfactory detection performance, with mean pixel accuracy (MPA), mean intersection over union (MIoU), and frequency weighted intersection over union (FWIoU) of 0.99, 0.74 and 0.95, respectively. In terms of severity level quantification, there were 98%, 90%, 90% and 83% of predictions consistent with real conditions for falling off, obstacle, disjoint and leakage. It was shown that the number of surcharging manholes and total flood volume (TFV) were greatly affected by sewer defects, with over 16% increase in TFVs under all investigated rainfall events. The results addressed the impacts of sewer defects on urban flooding and demonstrated the powerful tools provided by the proposed framework for decision-making on sewer defect detection and management.

Modulating Charges of Dual Sites in Multivariate Metal-Organic Frameworks for Boosting Selective Aerobic Epoxidation of Alkenes.

Selective aerobic epoxidation of alkenes without any additives is of great industrial importance but still challenging because the competitive side reactions including C═C bond cleavage and isomerization are difficult to avoid. Here, we show fabricating Cu(I) single sites in pristine multivariate metal-organic frameworks (known as CuCo-MOF-74) via partial reduction of Cu(II) to Cu(I) ions during solvothermal reaction. Impressively, CuCo-MOF-74 is characteristic with single Cu(I), Cu(II), and Co(II) sites, and they exhibit the substantially enhanced selectivity of styrene oxide up to 87.6% using air as an oxidant at almost complete conversion of styrene, ∼25.8% selectivity increased over Co-MOF-74, as well as good catalytic stability. Contrast experiments and theoretical calculation indicate that Cu(I) sites contribute to the substantially enhanced selectivity of epoxides catalyzed by Co(II) sites. The adsorption of two O2 molecules on dual Co(II) and Cu(I) sites is favorable, and the projected density of state of the Co-3d orbital is closer to the Fermi level by modulating with Cu(I) sites for promoting the activation of O2 compared with dual-site Cu(II) and Co(II) and Co(II) and Co(II), thus contributing to the epoxidation of the C═C bond. When other kinds of alkenes are used as substrates, the excellent selectivity of various epoxides is also achieved over CuCo-MOF-74. We also prove the universality of fabricating Cu(I) sites in other MOF-74 with various divalent metal nodes.

Comparison of Neoatherosclerosis and Neovascularization of Restenosis after Drug-Eluting Stent Implantation: An Optical Coherence Tomography Study.

Background: Neoatherosclerosis (NA) is associated with stent failure. However, systematic studies on the manifestations of NA and neovascularization (NV) at different stages after drug-eluting stent (DES) implantation are lacking. Moreover, the relationship between NA and NV in in-stent restenosis (ISR) has not been reported. This study aimed to characterize NA and NV in patients with ISR at different post-DES stages and compare the association between NA and NV in ISR lesions. Methods: A total of 227 patients with 227 lesions who underwent follow-up optical coherence tomography before percutaneous coronary intervention for DES ISR were enrolled and divided into early (E-ISR: < 1 year), late (L-ISR: 1-5 years), and very-late (VL-ISR: > 5 years) ISR groups. Furthermore, ISR lesions were divided into NV and non-NV groups according to the presence of NV. Results: The prevalence of NA and NV was 52.9% and 41.0%, respectively. The prevalence of lipidic NA (E-ISR, 32.7%; L-ISR, 50.0%; VL-ISR, 58.5%) and intimal NV (E-ISR, 14.5%; L-ISR, 30.8%; VL-ISR, 38.3%) increased with time after stenting. NA was higher in ISR patients with NV lesions than in those without (p < 0.001). Patients with both ISR and NV had a higher incidence of macrophage infiltration, thin-cap fibroatheroma, intimal rupture, and thrombosis (p < 0.01). Conclusions: Progression of lipidic NA was associated with L-ISR and VL-ISR but may not be related to calcified NA. NA was more common in ISR lesions with NV; its formation may substantially promote NA progression and plaque instability.

Development of an aminotransferase-driven biocatalytic cascade for deracemization of d,l-phosphinothricin.

2-oxo-4-[(hydroxy)(methyl)phosphinoyl]butyric acid (PPO) is the essential precursor keto acid for the asymmetric biosynthesis of herbicide l-phosphinothricin (l-PPT). Developing a biocatalytic cascade for PPO production with high efficiency and low cost is highly desired. Herein, a d-amino acid aminotransferase from Bacillus sp. YM-1 (Ym DAAT) with high activity (48.95 U/mg) and affinity (Km = 27.49 mM) toward d-PPT was evaluated. To circumvent the inhibition of by-product d-glutamate (d-Glu), an amino acceptor (α-ketoglutarate) regeneration cascade was constructed as a recombinant Escherichia coli (E. coli D), by coupling Ym d-AAT, d-aspartate oxidase from Thermomyces dupontii (TdDDO) and catalase from Geobacillus sp. CHB1. Moreover, the regulation of the ribosome binding site was employed to overcome the limiting step of expression toxic protein TdDDO in E. coli BL21(DE3). The aminotransferase-driven whole-cell biocatalytic cascade (E. coli D) showed superior catalytic efficiency for the synthesis of PPO from d,l-phosphinothricin (d,l-PPT). It revealed the production of PPO exhibited high space-time yield (2.59 g L-1 h-1 ) with complete conversion of d-PPT to PPO at high substrate concentration (600 mM d,l-PPT) in 1.5 L reaction system. This study first provides the synthesis of PPO from d,l-PPT employing an aminotransferase-driven biocatalytic cascade.

An automated surgical decision-making framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features in renal cell carcinoma.

OBJECTIVES: To determine whether 3D-CT multi-level anatomical features can provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma. METHODS: This is a retrospective study based on multi-center cohorts. A total of 473 participants with pathologically proved renal cell carcinoma were split into the internal training and the external testing set. The training set contains 412 cases from five open-source cohorts and two local hospitals. The external testing set includes 61 participants from another local hospital. The proposed automatic analytic framework contains the following modules: a 3D kidney and tumor segmentation model constructed by 3D-UNet, a multi-level feature extractor based on the region of interest, and a partial or radical nephrectomy prediction classifier by XGBoost. The fivefold cross-validation strategy was used to get a robust model. A quantitative model interpretation method called the Shapley Additive Explanations was conducted to explore the contribution of each feature. RESULTS: In the prediction of partial versus radical nephrectomy, the combination of multi-level features achieved better performance than any single-level feature. For the internal validation, the AUROC was 0.93 ± 0.1, 0.94 ± 0.1, 0.93 ± 0.1, 0.93 ± 0.1, and 0.93 ± 0.1, respectively, as determined by the fivefold cross-validation. The AUROC from the optimal model was 0.82 ± 0.1 in the external testing set. The tumor shape Maximum 3D Diameter plays the most vital role in the model decision. CONCLUSIONS: The automated surgical decision framework for partial or radical nephrectomy based on 3D-CT multi-level anatomical features exhibits robust performance in renal cell carcinoma. The framework points the way towards guiding surgery through medical images and machine learning. CLINICAL RELEVANCE STATEMENT: We proposed an automated analytic framework that can assist surgeons in partial or radical nephrectomy decision-making. The framework points the way towards guiding surgery through medical images and machine learning. KEY POINTS: • The 3D-CT multi-level anatomical features provide a more accurate prediction of surgical decision-making for partial or radical nephrectomy in renal cell carcinoma. • The data from multicenter study and a strict fivefold cross-validation strategy, both internal validation set and external testing set, can be easily transferred to different tasks of new datasets. • The quantitative decomposition of the prediction model was conducted to explore the contribution of each extracted feature.

Optimal timing of surgery for gastric cancer after neoadjuvant chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Following neoadjuvant chemotherapy, surgical resection is one of the most preferred treatment options for locally advanced gastric cancer patients. However, the optimal time interval between chemotherapy and surgery is unclear. This review aimed to identify the optimal time interval between neoadjuvant chemotherapy and surgery for advanced gastric cancer. METHODS: Beginning on November 12, 2022, we searched the PubMed, Cochrane Library, Web of Science databases, and Embase.com databases for relevant English-language research. Two authors independently screened the studies, assessed their quality, extracted the data, and analyzed the results. The primary goal was to investigate the relationship between the time interval to surgery (TTS) and long-term survival outcomes for patients. This study has been registered with PROSPERO (CRD42022365196). RESULTS: After an initial search of 4880 articles, the meta-analysis review ultimately included only five retrospective studies. Ultimately, this meta-analysis included 1171 patients, of which 411 patients had TTS of < 4 weeks, 507 patients had TTS of 4-6 weeks, and 253 patients had TTS of > 6 weeks. In survival analysis, patients with TTS of > 6 weeks had poorer overall survival outcomes than patients with TTS of 4-6 weeks (HR = 1.34, 95% CI: 1.03-1.75, P = 0.03). No significant differences were found in terms of disease-free survival the groups. CONCLUSION: Based on the current clinical evidence, patients with locally advanced gastric cancer may benefit better with a TTS of 4-6 weeks; however, this option still needs additional study.

Glutathione-dependent redox homeostasis is critical for chlorothalonil detoxification in tomato leaves.

Glutathione plays a critical role in plant growth, development and response to stress. It is a major cellular antioxidant and is involved in the detoxification of xenobiotics in many organisms, including plants. However, the role of glutathione-dependent redox homeostasis and associated molecular mechanisms regulating the antioxidant system and pesticide metabolism remains unclear. In this study, endogenous glutathione levels were manipulated by pharmacological treatments with glutathione synthesis inhibitors and oxidized glutathione. The application of oxidized glutathione enriched the cellular oxidation state, reduced the activity and transcript levels of antioxidant enzymes, upregulated the expression level of nitric oxide and Ca2+ related genes and the content, and increased the residue of chlorothalonil in tomato leaves. Further experiments confirmed that glutathione-induced redox homeostasis is critical for the reduction of pesticide residues. RNA sequencing analysis revealed that miRNA156 and miRNA169 that target transcription factor SQUAMOSA-Promoter Binding Proteins (SBP) and NUCLEAR FACTOR Y (NFY) potentially participate in glutathione-mediated pesticide degradation in tomato plants. Our study provides important clues for further dissection of pesticide degradation mechanisms via miRNAs in plants.

Acellular dermal matrix for one-stage treatment of lower extremity full-thickness skin defect: a case series.

BACKGROUND: Self-repair of lower limb wounds has always been one of the research hotspots. Flaps and skin graft are the preferred treatment for lower extremity wound reconstruction. However, these treatments have many disadvantages, such as secondary damage, poor healing quality. In recent years, the use of acellular dermal matrix has emerged as an alternative treatment option for extremity ulcers. METHODS: This study aimed to explore whether acellular dermal matrix can be used as a single treatment to promote wound healing. 7 patients with lower extremities cutaneous deficiency exposing bone or tendon, were covered by Pelnac, which was an acellular dermal matrix product approved by China Food and Drug Administration. All the wound was treated by Pelnac without flaps and skin graft. The external dressing was changed every 10 days. RESULTS: After a maximum of 20 weeks, all the wounds were completely healed. During the 12 months follow-up period none of the patients developed skin wear on the treatment area. All patients maintained their postoperative ambulatory ability. All patients were satisfied with the appearance and feeling after wound healing. CONCLUSION: These findings may mean acellular dermal matrix is a novel method offering opportunity for treatment of lower extremities cutaneous deficiency exposing bone or tendon. It also has the potential to close wounds of all uninfected, non-ischemic, full-thickness cutaneous deficiency.

Driving Force Analysis of Natural Wetland in Northeast Plain Based on SSA-XGBoost Model.

Globally, natural wetlands have suffered severe ecological degradation (vegetation, soil, and biotic community) due to multiple factors. Understanding the spatiotemporal dynamics and driving forces of natural wetlands is the key to natural wetlands' protection and regional restoration. In this study, we first investigated the spatiotemporal evolutionary trends and shifting characteristics of natural wetlands in the Northeast Plain of China from 1990 to 2020. A dataset of driving-force evaluation indicators was constructed with nine indirect (elevation, temperature, road network, etc.) and four direct influencing factors (dryland, paddy field, woodland, grassland). Finally, we built the driving force analysis model of natural wetlands changes to quantitatively refine the contribution of different driving factors for natural wetlands' dynamic change by introducing the sparrow search algorithm (SSA) and extreme gradient boosting algorithm (XGBoost). The results showed that the total area of natural wetlands in the Northeast Plain of China increased by 32% from 1990 to 2020, mainly showing a first decline and then an increasing trend. Combined with the results of transfer intensity, we found that the substantial turn-out phenomenon of natural wetlands occurred in 2000-2005 and was mainly concentrated in the central and eastern parts of the Northeast Plain, while the substantial turn-in phenomenon of 2005-2010 was mainly located in the northeast of the study area. Compared with a traditional regression model, the SSA-XGBoost model not only weakened the multicollinearity of each driver but also significantly improved the generalization ability and interpretability of the model. The coefficient of determination (R2) of the SSA-XGBoost model exceeded 0.6 in both the natural wetland decline and rise cycles, which could effectively quantify the contribution of each driving factor. From the results of the model calculations, agricultural activities consisting of dryland and paddy fields during the entire cycle of natural wetland change were the main driving factors, with relative contributions of 18.59% and 15.40%, respectively. Both meteorological (temperature, precipitation) and topographic factors (elevation, slope) had a driving role in the spatiotemporal variation of natural wetlands. The gross domestic product (GDP) had the lowest contribution to natural wetlands' variation. This study provides a new method of quantitative analysis based on machine learning theory for determining the causes of natural wetland changes; it can be applied to large spatial scale areas, which is essential for a rapid monitoring of natural wetlands' resources and an accurate decision-making on the ecological environment's security.

Endophytic fungi of Lycium barbarum: isolation, determination, bioactivity and separation of compounds.

Lycium barbarum is widely distributed in China and used as a traditional Chinese medicine herb to treat dizziness, abdominal pain, dry cough, headache and fatigue. Several studies have examined the endophytes of L. barbarum from northwest China; however, few have focused on that from eastern China. The objective of this study was to isolate and determine the endophytic fungi of L. barbarum from Shandong province, as well as to obtain and identify active secondary metabolites from the endophytes. In this study, 17 endophytic fungi were isolated from L. barbarum and denoted as GQ-1 to GQ-17, respectively. These fungi were further classified into ten genera based on the morphological and ITS identification. The crude extracts of these fungi were obtained by using liquid fermentation and EtOAc extraction, and their antibacterial, cytotoxic, and antioxidant activities were evaluated. The results showed that GQ-6 and GQ-16 exhibited high inhibitory activity; GQ-6 and GQ-9 showed high cytotoxic activity and GQ-5 exhibited high scavenging capability for DPPH free radicals. Additionally, Cladosporium sp. GQ-6 was used to investigate the secondary metabolites. The crude extracts were purified by using column chromatography, reverse column, and liquid chromatography, and four monomeric compounds were identified, including two known compounds (α-acetylorcinol (1) and cladosporester B (2)) and two new compounds (cladosporacid F (3) and cladosporester D (4)). The anti-fungal and antibacterial activities of these compounds were confirmed, but no cytotoxic activity was observed. In conclusion, endophytic fungi of L. barbarum from eastern China can serve as a potential source of active natural products with antibacterial and antioxidant properties.

A comprehensive texture feature analysis framework of renal cell carcinoma: pathological, prognostic, and genomic evaluation based on CT images.

OBJECTIVES: We tried to realize accurate pathological classification, assessment of prognosis, and genomic molecular typing of renal cell carcinoma by CT texture feature analysis. To determine whether CT texture features can perform accurate pathological classification and evaluation of prognosis and genomic characteristics in renal cell carcinoma. METHODS: Patients with renal cell carcinoma from five open-source cohorts were analyzed retrospectively in this study. These data were randomly split to train and test machine learning algorithms to segment the lesion, predict the histological subtype, tumor stage, and pathological grade. Dice coefficient and performance metrics such as accuracy and AUC were calculated to evaluate the segmentation and classification model. Quantitative decomposition of the predictive model was conducted to explore the contribution of each feature. Besides, survival analysis and the statistical correlation between CT texture features, pathological, and genomic signatures were investigated. RESULTS: A total of 569 enhanced CT images of 443 patients (mean age 59.4, 278 males) were included in the analysis. In the segmentation task, the mean dice coefficient was 0.96 for the kidney and 0.88 for the cancer region. For classification of histologic subtype, tumor stage, and pathological grade, the model was on a par with radiologists and the AUC was 0.83 [Formula: see text] 0.1, 0.80 [Formula: see text] 0.1, and 0.77 [Formula: see text] 0.1 at 95% confidence intervals, respectively. Moreover, specific quantitative CT features related to clinical prognosis were identified. A strong statistical correlation (R2 = 0.83) between the feature crosses and genomic characteristics was shown. The structural equation modeling confirmed significant associations between CT features, pathological (ß = - 0.75), and molecular subtype (ß = - 0.30). CONCLUSIONS: The framework illustrates high performance in the pathological classification of renal cell carcinoma. Prognosis and genomic characteristics can be inferred by quantitative image analysis. KEY POINTS: • The analytical framework exhibits high-performance pathological classification of renal cell carcinoma and is on a par with human radiologists. • Quantitative decomposition of the predictive model shows that specific texture features contribute to histologic subtype and tumor stage classification. • Structural equation modeling shows the associations of genomic characteristics to CT texture features. Overall survival and molecular characteristics can be inferred by quantitative CT texture analysis in renal cell carcinoma.

Circ-DONSON Facilitates the Malignant Progression of Gastric Cancer Depending on the Regulation of miR-149-5p/LDHA Axis.

Earlier studies have shown that circular RNA (circRNA) expression is closely related to the malignant progression of cancer, but the role of circ-DONSON in gastric cancer (GC) has not been fully elucidated. The expression of circ-DONSON, miR-149-5p and lactate dehydrogenase A (LDHA) was measured via qRT-PCR. CCK8 assay was used to assess cell viability, and colony formation assay was performed to detect the number of colonies and the radiosensitivity of cells. Besides, flow cytometry, transwell assay and tube formation assay were employed to determine cell apoptosis, migration, invasion and angiogenesis. Western blot analysis was used to assess the protein expression. The interaction between miR-149-5p and circ-DONSON or LDHA was confirmed by dual-luciferase reporter assay. The influence of circ-DONSON on GC tumor growth in vivo was explored through constructing mice xenograft models. Our results suggested that circ-DONSON was highly expressed in GC tissues and cells. Loss-functional assay results confirmed that silenced circ-DONSON could inhibit the proliferation, metastasis and angiogenesis, while enhance the apoptosis and radiosensitivity of GC cells. In terms of mechanism, circ-DONSON could sponge miR-149-5p, which could target LDHA in GC. MiR-149-5p inhibitor or LDHA overexpression could reverse the suppression effect of circ-DONSON knockdown on GC progression. Additionally, our results also suggested that circ-DONSON silencing could restrain the tumor growth of GC in vivo. These results demonstrated that circ-DONSON could facilitate GC progression by increasing LDHA expression via sponging miR-149-5p, indicating that circ-DONSON might be a novel biomarker for GC treatment.

Jasmonic acid promotes glutathione assisted degradation of chlorothalonil during tomato growth.

Glutathione (GSH) biosynthesis and regeneration play a significant role in the metabolism of chlorothalonil (CHT) in tomatoes. However, the specific regulatory mechanism of GSH in the degradation of CHT remains uncertain. To address this, we investigate the critical regulatory pathways in the degradation of residual CHT in tomatoes. The results revealed that the detoxification of CHT residue in tomatoes was inhibited by buthionine sulfoximine and oxidized glutathione pretreatment, which increased by 26% and 46.12% compared with control, respectively. Gene silencing of γECS, GS, and GR also compromised the CHT detoxification potential of plants, which could be alleviated by GSH application and decreased the CHT accumulation by 33%, 25%, and 21%, respectively. Notably, it was found that the jasmonic acid (JA) pathway participated in the degradation of CHT regulated by GSH. CHT residues reduced by 28% after application of JA. JA played a role downstream of the glutathione pathway by promoting the degradation of CHT residue in tomatoes via nitric oxide signaling and improving the gene expression of antioxidant and detoxification-related enzymes. This study unveiled a crucial regulatory mechanism of GSH via the JA pathway in CHT degradation in tomatoes and offered new insights for understanding residual pesticide degradation.

miR-206 as a prognostic and sensitivity biomarker for platinum chemotherapy in epithelial ovarian cancer.

BACKGROUND: Drug resistance is a major obstacle to successful chemotherapy for epithelial ovarian cancer (EOC). We found a subset of miRNAs associated with the response to first-line platinum-based chemotherapy in EOC by microarray, and miR-206 was one of the most significant miRNAs. The purposes of this study were to evaluate the prognostic and platinum-resistance predictive value of miR-206 in EOC patients and to investigate the functional roles of miR-206 in regulating the platinum resistance of EOC and the underlying mechanism. METHODS: MiRNA expression profiling in EOC specimens was performed using a TaqMan miRNA array. miR-206 expression was confirmed by quantitative real-time PCR (qRT-PCR) analysis. Overexpression of miR-206 in EOC cell lines was achieved by the stable transfection of a recombinant plasmid. In vitro assays of cisplatin cytotoxicity, cell cycle distribution, apoptosis, transwell invasion and cell scratching were employed. Connexin 43 (Cx43) expression was detected by Western blotting. Murine xenograft models were used to determine the effects of miR-206 on platinum resistance in vivo. RESULTS: miR-206 expression was increased in primary platinum-resistant EOC. High miR-206 expression was related to poor prognosis in EOC patients who received platinum-based chemotherapy and predicted chemoresistance to platinum treatment. Overexpression of miR-206 in cisplatin-sensitive EOC cell lines significantly increased cell viability, migration and invasion in the presence of cisplatin and decreased cisplatin-induced apoptosis. Cx43, a target gene of miR-206, was negatively regulated by miR-206 in EOC cell lines and significantly related to better prognosis in patients who received platinum-based chemotherapy (KmPlot). miR-206 had high expression and Cx43 had low expression in platinum-sensitive EOC cell lines compared with resistant ones. In vivo murine xenograft models showed that miR-206 profoundly promoted the chemoresistance of EOC to cisplatin treatment. CONCLUSION: miR-206 was highly expressed in primary platinum-resistant EOCs and functionally promoted platinum resistance in part by downregulating Cx43 expression, thereby providing a useful biomarker for prognostic and platinum-resistance prediction.

A Rapid Terrestrial Laser Scanning Method for Coastal Erosion Studies: A Case Study at Freeport, Texas, USA.

Terrestrial laser scanning (TLS) has become a powerful data acquisition technique for high-resolution high-accuracy topographic and morphological studies. Conventional static TLS surveys require setting up numerous reflectors (tie points) in the field for point clouds registration and georeferencing. To reduce surveying time and simplify field operational tasks, we have developed a rapid TLS surveying method that requires only one reflector in the field. The method allows direct georeferencing of point clouds from individual scans to an East-North-Height (ENH) coordinate system tied to a stable geodetic reference frame. TLS datasets collected at a segment of the beach-dune-wetland area in Freeport, Texas, USA are used to evaluate the performance of the rapid surveying method by comparing with kinematic GPS measurements. The rapid surveying method uses two GPS units mounted on the scanner and a reflector for calculating the northing angle of the scanner's own coordinate system (SOCS). The Online Positioning User Service (OPUS) is recommended for GPS data processing. According to this study, OPUS Rapid-Static (OPUS-RS) solutions retain 1-2 cm root mean square (RMS) accuracy in the horizontal directions and 2-3 cm accuracy in the vertical direction for static observational sessions of approximately 30 min in the coastal region of Texas, USA. The rapid TLS surveys can achieve an elevation accuracy (RMS) of approximately 3-5 cm for georeferenced points and 2-3 cm for digital elevation models (DEMs). The elevation errors superimposed into the TLS surveying points roughly fit a normal distribution. The proposed TLS surveying method is particularly useful for morphological mapping over time in coastal regions, where strong wind and soft sand prohibit reflectors from remaining strictly stable for a long period. The theories and results presented in this paper are beneficial to researchers who frequently utilize TLS datasets in their research, but do not have opportunities to be involved in field data acquisition.

Characterization and application of a common epitope recognized by a broad-spectrum C4 monoclonal antibody against capsid proteins of plant potyviruses.

A broad-spectrum monoclonal antibody (C4 MAb) against the capsid proteins (CPs) of plant potyviruses has been generated in previous studies. To clarify which epitope is recognized by this MAb, epitope mapping was performed via phage display library screening and amino acid substitution analysis. Subsequently, a 12-residue epitope in the core region of potyvirus CPs was identified and termed the C4 epitope (WxMMDGxxQxxY/F). This epitope contains tryptophan and tyrosine residues that are crucial for reacting with C4 MAb. The CP of Odontoglossum ringspot tobamovirus (ORSV) separately fused with the C4 epitope of Konjak mosaic potyvirus (KoMV), Zantedeschia mild mosaic potyvirus (ZaMMV), or Dasheen mosaic potyvirus (DsMV) was expressed in a bacterial system and purified. The results of indirect ELISA and Western blotting demonstrated that the C4 epitope of KoMV (Ko) fused to ORSV CP showed the strongest binding affinity to C4 MAb among the three viral epitope tags examined. The binding affinity between Ko tag (WTMMDGEEQIEY) and C4 MAb was determined. To examine the applicability of the Ko tag in planta, GFP and ORSV CP were transiently expressed in Nicotiana benthamiana, and both Ko-tagged proteins were specifically detected using C4 MAb. The Ko tag did not affect the silencing suppressor function of Tomato bushy stunt tombusvirus P19 in N. benthamiana. Furthermore, Ko-tagged EGFP could be successfully expressed, specifically detected and subsequently immunoprecipitated using C4 MAb in a mammalian cell system. Thus, the present study identified a common C4 epitope of potyviruses recognized by the broad-spectrum C4 and PTY 1 MAbs, and the results indicated that the newly designed Ko tag is suitable for application in bacterial, plant, and mammalian cell systems.