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Despite genome-wide association studies (GWAS) have identified more than 200 risk loci associated with colorectal cancer (CRC), the causal genes or risk variants within these loci and their biological functions remain not fully revealed. Recently, the genomic locus 19q13.2, with the lead SNP rs1800469 was identified as a crucial CRC risk locus in Asian populations. However, the functional mechanism of this region has not been fully elucidated. Here we employed an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk locus 19q13.2. Notably, we found that RPS19 exhibited the most significant effect among the identified genes and acted as a critical oncogene facilitating CRC cell proliferation. Subsequently, combining integrative fine-mapping analysis and a large-scale population study consisting of 6027 cases and 6099 controls, we prioritized rs1025497 as a potential causal candidate for CRC risk, demonstrating that rs1025497[A] allele significantly reduced the risk of CRC (OR 0.70, 95% confidence interval = 0.56-0.83, P = 1.12 × 10-6), which was further validated in UK Biobank cohort comprising 5,313 cases and 21,252 controls. Mechanistically, we experimentally elucidated that variant rs1025497 might acted as an allele-specific silencer, inhibiting the expression level of oncogene RPS19 mediated by the transcription suppressive factor HBP1. Taken together, our sturdy unveils the significant role of RPS19 during CRC pathogenesis and delineates its distal regulatory mechanism mediated by rs1025497, advancing our understanding of the etiology of CRC and provided new insights into the personalized medicine of human cancer.
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Aortic aneurysm/dissection (AAD) is a serious cardiovascular condition characterized by rapid onset and high mortality rates. Currently, no effective drug treatment options are known for AAD. AAD pathogenesis is associated with the phenotypic transformation and abnormal proliferation of vascular smooth muscle cells (VSMCs). However, endogenous factors that contribute to AAD progression remain unclear. We aimed to investigate the role of histone deacetylase 9 (HDAC9) in AAD pathogenesis. HDAC9 expression was considerably increased in human thoracic aortic dissection specimens. Using RNA-sequencing (RNA-seq) and chromatin immunoprecipitation, we demonstrated that HDAC9 transcriptionally inhibited the expression of superoxide dismutase 2 and insulin-like growth factor-binding protein-3, which are critically involved in various signaling pathways. Furthermore, HDAC9 triggered the transformation of VSMCs from a systolic to synthetic phenotype, increasing their proliferation and migration abilities and suppressing their apoptosis. Consistent with these results, in vivo experiments revealed that TMP195, a pharmacological inhibitor of HDAC9, suppressed the formation of the ß-aminopropionitrile-induced AAD phenotype in mice. Our findings indicate that HDAC9 may be a novel endogenous risk factor that promotes the onset of AAD by mediating the phenotypic transformation of VSMCs. Therefore, HDAC9 may serve as a potential therapeutic target for drug-based AAD treatment. Furthermore, TMP195 holds potential as a therapeutic agent for AAD treatment.
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Aneurisma de la Aorta , Disección Aórtica , Benzamidas , Oxadiazoles , Humanos , Ratones , Animales , Músculo Liso Vascular/patología , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/genética , Histona Desacetilasas/genética , Aneurisma de la Aorta/tratamiento farmacológico , Aneurisma de la Aorta/genética , Aneurisma de la Aorta/patología , Fenotipo , Miocitos del Músculo Liso/patología , Células CultivadasRESUMEN
This work aimed to investigate the microbial mechanisms for the improvement of composting efficiency driven by the compound microbial inoculum (MI) (Bacillus subtilis SL-44, Enterobacter hormaechei Rs-189 and Trichoderma reesei) during co-composting of spent mushroom substrate (SMS) and chicken manure (CM). The treatments used in the study were as follows: 1) MI (inoculation with microbial inoculum), 2) CI (inoculation with commercial microbial inoculum), and 3) CK (without inoculation). The results demonstrated that MI increased the seed germination index (GI) by 25.11%, and contents of humus, humic acid (HA) and available phosphorus (AP) were correspondingly promoted by 12.47%, 25.93% and 37.16%, respectively. The inoculation of MI increased the temperature of the thermophilic stage by 3-7 °C and achieved a cellulose degradation rate of 52.87%. 16S rRNA gene analysis indicated that Actinobacteria (11.73-61.61%), Firmicutes (9.46-65.07%), Proteobacteria (2.86-32.17%) and Chloroflexi (0.51-10.92%) were the four major phyla during the inoculation composting. Bacterial metabolic functional analysis revealed that pathways involved in amino acid and glycan biosynthesis and metabolism were boosted in the thermophilic phase. There was a positive correlation between bacterial communities and temperature, humification and phosphorus fractions. The average dry weight, fresh weight and seedling root length in the seedling substrates adding MI compost were 1.13, 1.23 and 1.06 times higher than those of the CK, respectively. This study revealed that biological inoculation could improve the composting quality and efficiency, potentially benefiting the resource utilization of agricultural waste resources.
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Agaricales , Compostaje , Animales , Estiércol , Pollos , ARN Ribosómico 16S , Suelo , FósforoRESUMEN
OBJECTIVES: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. METHODS: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. RESULTS: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). CONCLUSIONS: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. CLINICAL RELEVANCE STATEMENT: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. KEY POINTS: ⢠Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. ⢠The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. ⢠Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Metástasis Linfática/patología , Axila/patología , Radiómica , Estudios Retrospectivos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Tomografía Computarizada de Haz CónicoRESUMEN
Ferroptosis, which is caused by iron-dependent accumulation of lipid peroxides, is an emerging form of regulated cell death and is considered a potential target for cancer therapy. However, the regulatory mechanisms underlying ferroptosis remain unclear. This study defines a distinctive role of ferroptosis. Inhibition of CARM1 can increase the sensitivity of tumor cells to ferroptosis inducers in vitro and in vivo. Mechanistically, it is found that ACSL4 is methylated by CARM1 at arginine 339 (R339). Furthermore, ACSL4 R339 methylation promotes RNF25 binding to ACSL4, which contributes to the ubiquitylation of ACSL4. The blockade of CARM1 facilitates ferroptosis and effectively enhances ferroptosis-associated cancer immunotherapy. Overall, this study demonstrates that CARM1 is a critical contributor to ferroptosis resistance and highlights CARM1 as a candidate therapeutic target for improving the effects of ferroptosis-based antitumor therapy.
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Neoplasias Colorrectales , Ferroptosis , Humanos , Metilación , Proteína-Arginina N-Metiltransferasas/genética , Neoplasias Colorrectales/genéticaRESUMEN
PURPOSE: Cone-beam breast CT (CBBCT) has an inherent limitation that the axilla cannot be imaged in its entirety. We aimed to develop and validate a nomogram based on clinical factors and contrast-enhanced (CE) CBBCT radiomics features to predict axillary lymph node (ALN) metastasis and complement limited axilla coverage. MATERIAL AND METHODS: This retrospective study included 312 patients with breast cancer from two hospitals who underwent CE-CBBCT examination in a clinical trial (NCT01792999) during 2012-2020. Patients from TCIH comprised training set (n = 176) and validation set (n = 43), and patients from SYSUCC comprised external test set (n = 93). 3D ROIs were delineated manually and radiomics features were extracted by 3D Slicer software. RadScore was calculated and radiomics model was constructed after feature selection. Clinical model was built on independent predictors. Nomogram was developed with independent clinical predictors and RadScore. Diagnostic performance was compared among three models by ROC curve, and decision curve analysis (DCA) was used to evaluate the clinical utility of nomogram. RESULTS: A total of 139 patients were ALN positive and 173 patients were negative. Twelve radiomics features remained after feature selection. Location and focality were selected as independent predictors for ALN status. The AUC of nomogram in external test set was higher than that of clinical model (0.80 vs. 0.66, p = 0.012). DCA demonstrated that the nomogram had higher overall net benefit than that of clinical model. CONCLUSION: The nomogram combined CE-CBBCT-based radiomics features and clinical factors could have potential in distinguishing ALN positive from negative and addressing the limitation of axilla coverage in CBBCT.
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Ganglios Linfáticos , Nomogramas , Humanos , Estudios Retrospectivos , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Axila/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
Alternative polyadenylation (APA) is emerging as a major mechanism of posttranscriptional regulation. APA can impact the development and progression of cancer, suggesting that the genetic determinants of APA might play an important role in regulating cancer risk. Here, we depicted a pan-cancer atlas of human APA quantitative trait loci (apaQTL), containing approximately 0.7 million apaQTLs across 32 cancer types. Systematic multiomics analyses indicated that cancer apaQTLs could contribute to APA regulation by altering poly(A) motifs, RNA-binding proteins (RBP), and chromatin regulatory elements and were preferentially enriched in genome-wide association studies (GWAS)-identified cancer susceptibility loci. Moreover, apaQTL-related genes (aGene) were broadly related to cancer signaling pathways, high mutational burden, immune infiltration, and drug response, implicating their potential as therapeutic targets. Furthermore, apaQTLs were mapped in Chinese colorectal cancer tumor tissues and then screened for functional apaQTLs associated with colorectal cancer risk in 17,789 cases and 19,951 controls using GWAS-ChIP data, with independent validation in a large-scale population consisting of 6,024 cases and 10,022 controls. A multi-ancestry-associated apaQTL variant rs1020670 with a C>G change in DNM1L was identified, and the G allele contributed to an increased risk of colorectal cancer. Mechanistically, the risk variant promoted aberrant APA and facilitated higher usage of DNM1L proximal poly(A) sites mediated by the RBP CSTF2T, which led to higher expression of DNM1L with a short 3'UTR. This stabilized DNM1L to upregulate its expression, provoking colorectal cancer cell proliferation. Collectively, these findings generate a resource for understanding APA regulation and the genetic basis of human cancers, providing insights into cancer etiology. SIGNIFICANCE: Cancer risk is mediated by alternative polyadenylation quantitative trait loci, including the rs1020670-G variant that promotes alternative polyadenylation of DNM1L and increases colorectal cancer risk.
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Neoplasias Colorrectales , Estudio de Asociación del Genoma Completo , Humanos , Poliadenilación/genética , Regulación de la Expresión Génica , Sitios de Carácter Cuantitativo , Neoplasias Colorrectales/genética , Regiones no Traducidas 3'/genéticaRESUMEN
Tens of thousands of long non-coding RNAs (lncRNAs) have been identified through RNA-seq analysis, but the biological and pathological significance remains unclear. By integrating the genome-wide lncRNA data with a cross-ancestry meta-analysis of PDAC GWASs, we depicted a comprehensive atlas of pancreatic ductal adenocarcinoma (PDAC)-associated lncRNAs, containing 1,204 lncRNA (445 novel lncRNAs and 759 GENCODE annotated lncRNAs) and 4,368 variants. Furthermore, we found that PDAC-associated lncRNAs could function by altering chromatin activity, transcription factors, and RNA-binding proteins binding affinity. Importantly, genetic variants linked to PDAC are preferentially found at PDAC-associated lncRNA regions, supporting the biological and clinical relevance of PDAC-associated lncRNAs. Finally, we prioritized a novel transcript (MICT00000110172.1) of RP11-638I2.4 as a potential tumor promoter. MICT00000110172.1 is able to reinforce the interaction with YY1, which could reverse the effect of YY1 on pancreatic cancer cell cycle arrest to promote the pancreatic cancer growth. G > A change at rs2757535 in the second exon of MICT00000110172.1 induces a spatial structural change and creates a target region for YY1 binding, which enforces the effect of MICT00000110172.1 in an allele-specific manner, and thus confers susceptibility to tumorigenesis. In summary, our results extend the repertoire of PDAC-associated lncRNAs that could act as a starting point for future functional explorations, and the identification of lncRNA-based target therapy.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/genética , Alelos , Factor de Transcripción YY1/genéticaRESUMEN
Synchronous gastrointestinal multiple primary tumors including gastric, colonic, and rectal cancers are rare. Moreover, it was a challenge to find an appropriate procedure without negatively impacting the overall outcome. We described the case of a 63-year-old woman who presented with a 4 month history of upper abdominal pain, acid regurgitation, and anemia. Gastroscopy with biopsy suggested early cancer of gastric antrum. Abdominal contrast-enhanced computerized tomography and colonoscopy revealed ascending colon and rectum tumors. She had no family history of malignancy. Endoscopic submucosal dissection was performed for gastric cancer, and the pathological result presented that it was poorly differentiated and invaded into deep submucosa. The laparoscopy-assisted radical surgery combined with distal gastrectomy, right hemicolectomy, and anterior resection of rectum was performed for these three tumors via eight ports and a 7 cm midline upper-abdominal incision. No other perioperative complications were encountered except postoperative ileus. The patient was discharged on the 12th postoperative day. The pathological results revealed gastric cancer (T1N0M0), right colonic cancer (T3N1M0), and rectal cancer (T2N0M0), indicating complete surgical resection. We reported that our laparoscopic approach for synchronous triple primary gastrointestinal malignant tumors was feasible and minimally invasive.
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BACKGROUND: Complete mesocolic excision (CME) or D3 lymphadenectomy led to survival benefits for locally advanced right colon cancer, but with vague definitions in anatomy and debated surgical hazard in clinic. Aiming to achieve a precise definition of it in anatomy, we proposed laparoscopic right hemicolectomy (D3 + CME) as a novel procedure for colon cancer. However, the surgical and oncological results of this procedure in clinic were uncertain. METHODS: We performed a cohort study involving prospective data collected from a single-center in China. Data from all patients who underwent right hemicolectomy between January 2014 and December 2018 were included. We compared the surgical and oncological outcomes between D3 + CME and conventional CME. RESULTS: After implementation of exclusion criteria, a total of 442 patients were included. D3 + CME group performed better in lymph nodes harvested (25.0 [17.0, 33.8] vs. 18.0 [14.0, 25.0], P < 0.001) and the proportion of intraoperative blood loss ≥ 50 mL (31.7% vs. 51.8%, P < 0.001); no significant difference was observed in the complication rates between two groups. Kaplan-Meier analysis demonstrated that a better cumulative 5-year disease-free survival (91.3% vs. 82.2%, P = 0.026) and a better cumulative 5-year overall survival (95.2% vs. 86.1%, P = 0.012) were obtained in the D3 + CME group. Multivariate COX regression revealed that D3 + CME was an independent protective factor for disease-free survival (P = 0.026). CONCLUSION: D3 + CME could improve surgical and oncological outcomes simultaneously for right colon cancer compared to conventional CME. Large-scale randomized controlled trials were further required to confirm this conclusion, if possible.
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Neoplasias del Colon , Laparoscopía , Mesocolon , Humanos , Estudios de Cohortes , Estudios Prospectivos , Resultado del Tratamiento , Laparoscopía/métodos , Neoplasias del Colon/patología , Escisión del Ganglio Linfático/métodos , Colectomía/métodos , Mesocolon/cirugíaRESUMEN
Introduction: Triclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association. Methods: This case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells. Results: Significant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGF2α, RTL, and BC risk, with the odds ratios (95% confidence intervals) being 1.58 (1.32-1.91), 3.08 (1.55-6.23), 3.39 (2.45-4.77), 3.99 (2.48-6.54), and 1.67 (1.35-2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2α (all p<0.05) but not with 8-OHdG (p = 0.060) after adjusting for covariates. The mediated proportions of 8-isoPGF22α and RTL in the relationship between TCS and BC risk were 12.84% and 8.95%, respectively (all p<0.001). Discussion: In conclusion, our study provides epidemiological evidence to confirmed the deleterious effects of TCS on BC and indicated the mediating effect of oxidative stress and RTL on the correlation between TCS and BC risk. Moreover, exploring the contribution of TCS to BC can clarify the biological mechanisms of TCS exposure, provide new clues for the pathogenesis of BC, which is of great significance to improving public health systems.
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Neoplasias de la Mama , Triclosán , Humanos , Femenino , Triclosán/efectos adversos , Leucocitos Mononucleares , Estudios de Casos y Controles , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina , TelómeroRESUMEN
The objective of this study was to investigate the microbial mechanisms for the improvement of composting efficiency after Bacillus subtilis inoculation with soluble phosphorus function in the spent mushroom substrate (SMS) aerobic composting. The methods in this study, including redundant analysis (RDA), co-occurrence network analyze and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt 2) were carried out studying the dynamic changes of phosphorus (P) components, microbial interactions and metabolic characteristics in the SMS aerobic composting inoculated with phosphorus-solubilizing B. subtilis (PSB). An increase in germination index (GI) (up to 88.4%), total nitrogen (TN) (16.6 g kg-1), available P content (0.34 g kg-1) and total P (TP) content (3.20 g kg-1) and a decrease in total organic carbon (TOC), C/N and electrical conductivity (EC) in final composting stage indicated B. subtilis inoculation could further improve maturity quality of the composting product compared with CK. Other results also demonstrated that PSB inoculation increased the stability of compost, humification degree and bacterial diversity, contributing to P fractions transformation in the composting process. Co-occurrence analysis suggested that PSB strengthened microbial interactions. Metabolic function of bacterial community analysis showed pathways such as carbohydrate metabolism, and amino acid metabolism in the composting were increased by effects of PSB inoculation. In summary, this study reveals a useful basis for better regulating the P nutrient level of the SMS composting and reducing environmental risks by inoculating B. subtilis with P solubilizing function.
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Agaricales , Compostaje , Fosfatos/química , Bacillus subtilis , Filogenia , Suelo/química , Fósforo , Nitrógeno , EstiércolRESUMEN
Expecting to gain an excellent operating temperature window and superior catalytic activity of the catalyst in SCR reaction, the Fe-Ce bimetallic oxide catalyst was firstly prepared and sulfated with two different sulfation strategies by H2SO4. It is interestingly found that both the two sulfation strategies can significantly broaden the operating temperature window of the catalyst. In particular, the SFC and FCS both exhibit superior resistance to H2O + SO2, and the NOx conversion of the SFC even displays no changes in the coexistence of H2O and SO2. The characterization results show that different sulfation strategies can generate amorphous sulfate species rather than bulk sulfate species. Furthermore, more surface-adsorbed oxygen as well as higher contents of Ce3+ and Fe3+ can be obtained on the sulfated catalysts, especially for the SFC catalyst. Meanwhile, different sulfation strategies will progressively enhance the redox ability and amounts of strong acid sites, which will contribute to broadening the operating temperature window for the NH3-SCR reaction. Additionally, different sulfation methods do not change the reaction pathway of catalysts. However, the adsorption of ad-NH3 species and reactivity of ad-NOx species are significantly changed. These lead to the reaction pathway shifts to E-R direct over the SFC and the promotion of E-R and L-H mechanisms over the FCS catalyst.
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Amoníaco , Óxidos , Temperatura , Oxidación-Reducción , Catálisis , Óxidos de Azufre , SulfatosRESUMEN
BACKGROUND: Calcifications are important abnormal findings in breast imaging and help in the diagnosis of breast cancer. PURPOSE: To compare breast cone-beam computed tomography (CBCT) with digital mammography (DM) in terms of the ability to identify malignant calcifications. MATERIAL AND METHODS: In total, 115 paired examinations were performed utilizing breast CBCT and DM; 86 pathology-proven malignant lesions with calcifications detected on DM and 29 randomly selected breasts without calcifications were reviewed by three radiologists. The ability to detect calcifications was assessed on CBCT images. The characterization agreement of two imaging modalities was evaluated by the kappa coefficient. For breast CBCT images, the parameters for the display of calcifications were recorded. The Kruskal-Wallis test was used to compare the preferred slice thickness chosen by each of the three radiologists. The degree of calcification clarity was compared between two modalities using the Mann-Whitney U-test. RESULTS: The combined sensitivity and specificity of three radiologists in 85 DM-detected calcifications detection on breast CBCT images were 98.43% (251/255) and 98.85% (86/87), respectively. CBCT images showed substantial agreement with mammograms in terms of the characterization of calcifications morphology (k = 0.703; P < 0.05) and distribution (k = 0.629; P < 0.05). CBCT images with a slice thickness of 0.273â mm and three-dimensional maximum-intensity projection (3D-MIP) were more beneficial for calcifications identification. No statistically significant difference was found between standard DM views and CBCT images for three radiologists on calcification display clarity. CONCLUSION: CBCT images were comparable to mammograms in calcification identification and may be sufficient for malignant calcifications detection and characterization.
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Neoplasias de la Mama , Calcinosis , Humanos , Femenino , Mamografía/métodos , Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Tomografía Computarizada de Haz Cónico/métodosRESUMEN
Guar gum has been used in the management of hypercholesterolemia, constipation, weight loss, type 2 diabetes mellitus and hypertension. Our aim was to verify the hypothesis that Guar gum can be used as an alternative to pharmacological agents in the treatment of mild hypertension. Thus, we conducted a systematic review and meta-analysis to evaluate the effectiveness of Guar gum in reducing blood pressure. We searched the Cochrane Library, PubMed/Medline, Scopus and Google Scholar databases for studies published in the English language up to June 2020 which evaluated the effects of gum consumption on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Nine randomized clinical trials with suitable comparison groups (placebo/control) reported SBP and DBP as outcome measures. These trials involved in total 640 participants. The overall results indicated that the consumption of gum resulted in a significant change in SBP (WMD: -1.190 mmHg, 95% CI: -2.011, -0.370) and DBP (WMD: -1.101 mmHg, 95% CI: -1.597, -0.605). Moreover, the greatest reduction in blood pressure was seen in patients with type 2 diabetes mellitus and metabolic syndrome who consumed Guar gum (WMD: -3.375 mmHg). In addition, there was a significant decrease in SBP if the gum dosage was > 15 g (WMD: -6.637 mmHg) and if the intervention duration was > 12 weeks (WMD: -1.668 mmHg). The results of the present dose-response meta-analysis support the employment of gum consumption in the reduction of SBP and DBP. Based on the sub-group analyses, we highlight that the greatest decrease in SBP was experienced if the gum dosage was > 15 g and when the intervention lasted > 12 weeks.
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Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Presión Sanguínea , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Factores de RiesgoRESUMEN
N-isopropylbenzylamine, an isomer of methamphetamine, has been used to adulterate methamphetamine, and distributed as fake "Ice" methamphetamine by illicit manufacturers, leading to a world problem of N-isopropylbenzylamine exposure. Though it is unclear whether N-isopropylbenzylamine has addictive potential like methamphetamine, N-isopropylbenzylamine users reported side effects such as headaches and confusion. However, the pharmacological targets and cytotoxicity of this chemical remained unknown. In this study, in vitro toxicity of N-isopropylbenzylamine and its toxicity-related targets were investigated in SN4741, SH-SY5Y or PC12 cell lines that model neurons. The cell viability was analyzed by using MTT assay after incubation with N-isopropylbenzylamine for 24 h in cells. N-isopropylbenzylamine caused cell death with IC50 values at around 1-3 mM in these cell lines. N-isopropylbenzylamine time- and concentration-dependently facilitated the expression of neuronal nitric oxide synthase (nNOS), and increased intracellular nitric oxide (NO) in SN4741 cells. Furthermore, 7-nitroindazole, a specific inhibitor of nNOS, significantly prevented N-isopropylbenzylamine-induced toxicity in vitro. These results suggested that N-isopropylbenzylamine-induced toxicity is at least partially related to the increased intracellular NO levels and the activated nNOS. Considering the circumstances that N-isopropylbenzylamine was used to adulterate and mimic methamphetamine, and the side effects associated with N-isopropylbenzylamine in abusers, our findings sounded an alarm for abuser and warn the dangerousness of N-isopropylbenzylamine for public health.
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Metanfetamina , Neuroblastoma , Aminas , Humanos , Metanfetamina/toxicidad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismoRESUMEN
Two composting experiments were conducted to investigate the effects of commercial microbial agents on microbial succession and nutrient flow such as humification, maturation, and stability during the aerobic composting of the spent mushroom substrate (SMS). The cellulose degradation rate of T (added microbial agents at the initial stage) reached 41.8%, which was much significantly (p < 0.05) higher than that of CK (14.9%). The seed germination index (GI) in T (82.38%) was significantly (p < 0.05) higher than that in CK (74.74%) in the maturation phase. Moreover, the total organic carbon/total nitrogen ratio (C/N) and electrical conductivity (EC) value of T decreased to 10.5 and 2.37 mS/cm, respectively. Chemical detection and fluorescence excitation-emission region integration method (EEM-FRI) analysis showed that the microbial agents significantly accelerated the organic matter (OM) decomposition and promoted the quality of mature compost using SMS as a single raw material. The bacterial abundance of T was significantly richer than the CK due to the addition of microbial agents. The results could provide a comprehensive understanding of adding microbial agents into composting SMS and a scientific feasibility strategy to rational utilization of resources in the edible fungi industry, which was conducive to the waste management and sustainable development of the edible fungi industry.
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Agaricales , Compostaje , Estiércol , Suelo , NitrógenoRESUMEN
Pesticide research and development has entered an era of safety, efficiency, and environmental friendliness. Discovery of effective active products directly or indirectly from plant secondary metabolites as pesticide candidates has been one of the current research focuses. Herein, two series of new ester and amide derivatives were prepared by structural modifications of a natural coumarin-type product osthole at its C-4' position. Their structures were characterized by IR, mp, 1H NMR, and HRMS. Confirmation of steric configuration of seven compounds was based on single-crystal analysis. Against Tetranychus cinnabarinus Boisduval (Acari: Tetranychidae), (2'E)-3'-ethoxycarbonylosthole (4b) and (2'E)-3'-(n)hexyloxycarbonylosthole (4e) exhibited 3.2 and 3.1 times acaricidal activity of osthole, and particularly, they also showed 2.4 and 2.2 times control efficiency on the 5th day of osthole. Against Aphis citricola Van der Goot (Homoptera: Aphididae), (2'E)-3'-(p-CF3)benzyloxycarbonylosthole (4w), (2'E)-3'-benzylaminocarbonylosthole (5f), and (2'E)-3'-phenylethylaminocarbonylosthole (5g) showed 1.9-2.1-fold aphicidal activity of osthole. Furthermore, the changes in two detoxification enzyme [carboxylesterase (CarE) and glutathione S-transferase (GST)] activities over time in treated T. cinnabarinus were investigated. These results can pave the foundation for future design and preparation of osthole derivatives as botanical agrochemicals.