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Background: Breast cancer (BC) is a highly common form of cancer that occurs in many parts of the world. However, early -stage BC is curable. Many patients with BC have poor prognostic outcomes owing to ineffective diagnostic and therapeutic tools. The ubiquitination system and associated proteins were found influencing the outcome of individuals with cancer. Therefore, developing a biomarker associated with ubiquitination genes to forecast BC patient outcomes is a feasible strategy. Objective: The primary goal of this work was to develop a novel risk score signature capable of accurately estimate the future outcome of patients with BC by targeting ubiquitinated genes. Methods: Univariate Cox regression analysis was conducted utilizing the E1, E2, and E3 ubiquitination-related genes in the GSE20685 dataset. Genes with p < 0.01 were screened again using the Non-negative Matrix Factorization (NMF) algorithm, and the resulting hub genes were composed of a risk score signature. Patients were categorized into two risk groups, and the predictive effect was tested using Kaplan-Meier (KM) and Receiver Operating Characteristic (ROC) curves. This risk score signature was later validated using multiple external datasets, namely TCGA-BRAC, GSE1456, GSE16446, GSE20711, GSE58812 and GSE96058. Immuno-microenvironmental, single-cell, and microbial analyses were also performed. Results: The selected gene signature comprising six ubiquitination-related genes (ATG5, FBXL20, DTX4, BIRC3, TRIM45, and WDR78) showed good prognostic power in patients with BC. It was validated using multiple externally validated datasets, with KM curves showing significant differences in survival (p < 0.05). The KM curves also demonstrated superior predictive ability compared to traditional clinical indicators. Single-cell analysis revealed that Vd2 gd T cells were less abundantin the low-risk group, whereas patients in the high-risk group lacked myeloid dendritic cells. Tumor microbiological analysis revealed a notable variation in microorganism diversity between the high- and low-risk groups. Conclusion: This study established an risk score signature consisting of six ubiquitination genes, that can accurately forecast the outcome of patients with BC using multiple datasets. It can provide personalized and targeted assistance to provide the evaluation and therapy of individuals having BC.
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Here, we report the development and application of a novel class of spirosilacycle-based diphosphine ligands (SPOSiPs). This type of diphosphine ligand could be readily prepared in two steps with high efficiency starting from enantiopure spirobiphenoxasilin-diol (SPOSiOL). According to the structural analysis of SPOSiP and its PdCl2 complex, SPOSiPs possess a flexible chiral pocket and feature a rigid configuration, a large dihedral angle, a long P-P distance, and a large P-M-P bite angle in their metal complexes. The potentials of SPOSiPs in asymmetric catalysis have also been preliminarily disclosed.
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Hyperuricemia (HUA) is one of the most common chronic diseases today, with a prevalence exceeding 14 % in both the United States and China. Current clinical treatments for HUA focus on promoting uric acid (UA) excretion and inhibiting UA production, but often neglect the strain on the liver and kidneys. The fruit of Alpinia oxyphylla (A. oxyphylla) is known to improve renal function, regulate metabolism, and exhibit anti-inflammatory effects; however, its effectiveness and mechanisms in treating HUA are not well understood. In this study, HUA mice induced by potassium oxonate and adenine were treated with A. oxyphylla polysaccharide (AFP) for 21 days. The levels associated with HUA were quantified using assay kits to evaluate the impact of AFP on HUA. Serum metabolomics and 16S rRNA sequencing were used to investigate the mechanisms by which AFP ameliorates HUA. The results showed that AFP treatment reduced abnormal biochemical levels, including UA, blood urea nitrogen, and creatinine, in HUA mice. AFP inhibited UA synthesis by regulating pyrimidine metabolism and the metabolism of alanine, aspartate and glutamate, reduced kidney inflammation, and promoted UA excretion by regulating intestinal flora. Thus, AFP appears to be an effective agent for alleviating HUA symptoms.
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With the widespread application of anaerobic digestion technology, biogas slurry become the main source of organic amendments in practice. Comprehensive studies into the inhibitory effects of low molecular weight (LMW) organic acids, essential components in biogas slurry, on the sulfide minerals biooxidation and its bioleaching (AMD) have been lacking. In this study, acetic acid (AA) served as a representative of LMW organic acids in biogas slurry to investigate its impact on the inhibition of chalcopyrite biooxidation by Acidithiobacillus ferrooxidans (A. ferrooxidans). It was shown that AA could slow down the chalcopyrite biooxidation and inhibit the jarosite formation on the mineral surface. Compared with the control group (0 ppm AA), the sulfate increment in the leachate of the 50 ppm, 100 ppm, and 200 ppm AA-treated groups decreased by 36.4%, 66.8%, and 69.0%, respectively. AA treatment (≥50 ppm) could reduce the oxidation of ferrous ions in the leachate by one order of magnitude. At the same time, the bacterial concentration of the leachate in the 50 ppm, 100 ppm, and 200 ppm AA-treated groups decreased by 70%, 93%, and 94%, respectively. These findings provide a scientific basis for new strategies to utilize biogas slurry for mine remediation and contribute to an enhanced comprehension of organic amendments to prevent AMD in situ in mining soil remediation.
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OBJECTIVES: The geographical environment and military activities in the plateau area pose potential work-related stressors for military personnel, leading to burnout which is an external manifestation of internal energy exhaustion caused by stress. Without countermeasures, this can result in serious military problems. This study aims to examine the association between burnout and occupational stressors among military personnel stationed in the plateau area of China. MATERIAL AND METHODS: A stratified randomized cluster sampling survey was conducted among 2026 military personnel from 6 different troops stationed in the plateau area of China. The Chinese Maslach Burnout Inventory-General Survey(MBI-GS in Chinese) was administered from March 2022 to December 2023, and data were analyzed using SPSS version 25. RESULTS: A total of 2026 military personnel participated in the survey. The mean overall burnout score was 3.37 ± 0.73, with emotional exhaustion at 2.69 ± 0.89, depersonalization at 3.58 ± 0.92, and professional achievement at 3.81 ± 0.85 levels respectively reported by participants on average scale scores ranging from zero to six. Severe level of burnout was reported by 43.2% of participants while medium level of burnout was reported by 54 .3%. Age, education level, length of military service, and household income were identified as important factors influencing burnout. CONCLUSION: This study highlights a relatively high prevalence of burnout among military personnel stationed in plateau areas necessitating attention towards their occupational health particularly focusing on working hours and economic aspects so as to formulate effective policies and implement intervention measures that strengthen career development for soldiers deployed in such regions.
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Agotamiento Profesional , Personal Militar , Humanos , China/epidemiología , Personal Militar/psicología , Personal Militar/estadística & datos numéricos , Estudios Transversales , Masculino , Adulto , Prevalencia , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Femenino , Adulto Joven , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: Acer truncatum Bunge is an economic, ecological, oil, and medicinal tree, and its kernel oil is rich in nervonic acid. It is crucial to explore the transcriptional expression patterns of genes affecting fatty acid synthesis to improve the quality of Acer truncatum oil. RESULTS: This study used the seeds from high fatty acid strain YQC and those from low fatty acid strain Y38 as the test materials. Specifically, we performed a comparative transcriptome analysis of Y38 seeds and YQC to identify differentially expressed genes (DEGs) at two time points (seeds 30 days after the blooming period and 90 days after the blooming period). Compared with YQC_1 (YQC seeds at 30 days after the blooming period), a total of 3,618 DEGs were identified, including 2,333 up-regulated and 1,285 downregulated DEGs in Y38_1 (Y38 seeds at 30 days after blooming period). In the Y38_2 (Y38 seeds at 90 days after the blooming period) versus YQC_2 (YQC seeds at 90 days after the blooming period) comparison group, 9,340 genes were differentially expressed, including 5,422 up-regulated and 3,918 down-regulated genes. The number of DEGs in Y38 compared to YQC was significantly higher in the late stages of seed development. Gene functional enrichment analyses showed that the DEGs were mainly involved in the fatty acid biosynthesis pathway. And two fatty acid synthesis-related genes and seven nervonic acid synthesis-related genes were validated by qRT-PCR. CONCLUSIONS: This study provides a basis for further research on biosynthesizing fatty acids and nervonic acidnervonic acids in A. truncatum seeds.
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Acer , Ácidos Grasos , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Semillas , Semillas/genética , Semillas/metabolismo , Semillas/crecimiento & desarrollo , Acer/genética , Acer/metabolismo , Acer/crecimiento & desarrollo , Ácidos Grasos/metabolismo , Transcriptoma , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Ácidos Grasos MonoinsaturadosRESUMEN
Sweet basil (Ocimum basilicum L.) is an important aromatic plant with high edibility and economic value, widely distributed in many regions of the tropics including the south of China. In recent years, environmental problems, especially soil salinization, have seriously restricted the planting and spread of sweet basil. However, the molecular mechanism of the salt stress response in sweet basil is still largely unknown. In this study, seed germination, seedling growth, and chlorophyll synthesis in sweet basil were inhibited under salt stress conditions. Through comparative transcriptome analysis, the gene modules involved in the metabolic processes, oxidative response, phytohormone signaling, cytoskeleton, and photosynthesis were screened out. In addition, the landscape of transcription factors during salt treatment in sweet basil was displayed as well. Moreover, the overexpression of the WRKY transcription factor-encoding gene, ObWRKY16, and the phenylalanine ammonia-lyase-encoding gene, ObPAL2, enhanced the seed germination, seedling growth, and survival rate, respectively, of transgenic Arabidopsis, suggesting that they might be important candidates for the creation of salt-tolerant sweet basil cultivars. Our data enrich the study on salt responses in sweet basil and provide essential gene resources for genetic improvements in sweet basil in the future.
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OBJECTIVES: Periodontitis is associated with Fusobacterium nucleatum (F.n) infection. Although the colonization of renal tissue by F.n is well documented, its specific role in kidney disease has yet to be determined. This study aimed to investigate the potential association between F.n-induced periodontitis and renal interstitial fibrosis. METHODS: The rat gingival sulcus was injected with F.n suspension, while the control group (NC) was injected with PBS. The levels of total protein (TP), albumin (ALB), creatinine, and urea nitrogen (BUN) in rat serum and/or urine were quantified using the appropriate kits. Renal interstitial fibrosis and epithelial-mesenchymal transition (EMT) were evaluated in rats using Masson staining, Periodic Schiff-Methenamine (PASM) staining, and immunohistochemical staining. The levels of fibrosis- and EMT-related proteins and the TGF-ß/SMAD2/3 and ß-catenin signaling pathways were determined using Western blot analysis. F.n in the kidney tissues was quantitatively determined using bacterial 16S rRNA technology. RESULTS: Serum levels of TP, ALB, creatinine, and BUN were not significantly decreased in F.n-infected rats with periodontitis. The levels of creatinine and ALB in the urine were not statistically different between two groups. Masson and PASM staining showed that F.n-induced periodontitis could promote renal interstitial fibrosis in rats. The levels of collagen I, fibronectin (FN), vimentin, and α-SMA were upregulated in the kidney tissues of rats with F.n-induced periodontitis and in F.n-treated HK-2 cells. However, E-cadherin levels were reduced. F.n promoted renal interstitial and HK-2 cell fibrosis in rats by modulating the TGF-ß/SMAD2/3 and ß-catenin signaling pathways. F.n colonization increased renal interstitial fibrosis in rats. CONCLUSION: F.n-induced periodontitis promoted EMT by activating the TGF-ß/SMAD2/3 and ß-catenin signaling pathways, thus promoting renal interstitial fibrosis in rats.
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Transición Epitelial-Mesenquimal , Fibrosis , Fusobacterium nucleatum , Riñón , Periodontitis , Transducción de Señal , Proteína Smad2 , Proteína smad3 , Factor de Crecimiento Transformador beta , beta Catenina , Animales , Fusobacterium nucleatum/patogenicidad , beta Catenina/metabolismo , Ratas , Periodontitis/microbiología , Periodontitis/complicaciones , Periodontitis/patología , Periodontitis/metabolismo , Masculino , Factor de Crecimiento Transformador beta/metabolismo , Proteína smad3/metabolismo , Riñón/patología , Riñón/metabolismo , Proteína Smad2/metabolismo , Enfermedades Renales/metabolismo , Enfermedades Renales/microbiología , Enfermedades Renales/patología , Enfermedades Renales/etiología , Infecciones por Fusobacterium/complicaciones , Infecciones por Fusobacterium/metabolismo , Ratas Sprague-DawleyRESUMEN
Bladder cancer is one of the leading causes of cancer-related mortality in the urinary system. Understanding genomic information is important in the treatment and prognosis of bladder cancer, but the current method used to identify mutations is time-consuming and labor-intensive. There are now many novel and convenient ways to predict cancerous genomics from pathological slides. However, the publicly available datasets are limited, especially for Asian populations. In this study, we developed a dataset consisting of 75 Asian cases of bladder cancers and 112 Whole-Slide Images with one to two images obtained for each patient. This dataset provides information on the most frequently and clinically significant mutated genes derived by whole-exome sequencing in these patients. This dataset will facilitate exploration and development of novel diagnostic and therapeutic technologies for bladder cancer.
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Neoplasias de la Vejiga Urinaria , Humanos , Pueblo Asiatico/genética , Secuenciación del Exoma , Genómica , Mutación , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Introduction: The effectiveness of ultra-high pressure (UHP) technology in retaining the flavor of fresh fruit and vegetable juices has been acknowledged in recent years. Along with previously hypothesized conclusions, the improvement in melon juice flavor may be linked to the reduction of its surface tension through UHP. Methods: In this paper, the particle size, free-water percentage, and related thermodynamic parameters of melon juice were evaluated in a physical point for a deeper insight. Results: The results showed that the UHP treatment of P2-2 (200 MPa for 20 min) raised the free water percentage by 7,000 times than the other treatments and both the melting enthalpy, binding constant and Gibbs free energy of P2-2 were minimized. This significantly increased the volatility of characteristic aromatic compounds in melon juice, resulting in a 1.2-5 times increase in the content of aromatic compounds in the gas phase of the P2-2 group compared to fresh melon juice.
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BACKGROUND: The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. METHODS: ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. RESULTS: After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. CONCLUSION: PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.
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Apoptosis , Supervivencia Celular , Estrés Oxidativo , Peroxirredoxinas , Especies Reactivas de Oxígeno , Epitelio Pigmentado de la Retina , Rayos Ultravioleta , Humanos , Epitelio Pigmentado de la Retina/efectos de la radiación , Epitelio Pigmentado de la Retina/metabolismo , Peroxirredoxinas/metabolismo , Rayos Ultravioleta/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Línea Celular , Western Blotting , Células Cultivadas , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Effective treatment after EGFR-TKI resistance is of great clinical concern. We aimed to investigate the efficacy and safety of anlotinib in combination with an anti-PD-1/PD-L1 antibody in later-line therapy for EGFR-mutant NSCLC patients after TKI treatment failure and to explore the independent predictive factors of therapeutic efficacy. METHODS: A total of 71 patients with confirmed advanced EGFR-mutated NSCLC who progressed after previous standard EGFR-TKI therapy but still failed after multiline treatments were included retrospectively in this study. Most of the patients had previously received at least three lines of treatment. All were treated with anlotinib combined with anti-PD-1 or anti-PD-L1 therapy. The safety of this combined treatment was assessed by the incidence of adverse events. The efficacy of the regimens was evaluated by survival analysis (OS, PFS, ORR, DCR). RESULTS: The median follow-up period was 28.6 months (range: 2.3-54.0 months), and the median number of treatment lines was 4. The overall response rate (ORR) and disease control rate (DCR) were 19.7% and 77.5%, respectively. The median PFS was 5.8 months (95% CI 4.2-7.4 months), and the median OS was 17.1 months (95% CI 12.0-22.3 months). Patients who received immune checkpoint inhibitors plus anlotinib had an encouraging intracranial ORR of 38.5% and a DCR of 80.8%. ECOG performance status < 2 at baseline was independent protective factors of PFS. Metastatic organs and ECOG performance status were independent parameters in predicting OS. Treatment-related adverse events occurred in 66 (93.0%) patients; most of the adverse events were Grade 1-2, and no increase in adverse events was observed compared to monotherapy. CONCLUSION: Anlotinib combined with an anti-PD-1/PD-L1-based regimen exhibited promising efficacy and tolerance in NSCLC patients with EGFR mutations after previous TKI failure. The efficacy of this combined regimen in patients with EGFR mutations should be further evaluated.
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Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico , Indoles , Neoplasias Pulmonares , Mutación , Inhibidores de Proteínas Quinasas , Quinolinas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Indoles/uso terapéutico , Indoles/efectos adversos , Indoles/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Quinolinas/administración & dosificación , Estudios RetrospectivosRESUMEN
ABSTRACT: Background: Diabetic nephropathy (DN) is a complication of diabetes that is the leading cause of death in diabetic patients. Circular RNA (circRNA) is a hot topic in the research of human diseases. However, the role of circ_Supt3 in DN remains unclear. Methods: High glucose (HG) treatment of mouse podocyte (MPC5) cells to mimic DN cell injury. Quantitative real-time polymerase chain reaction was performed to detect the expression of circ_Supt3, microRNA-185-5p (miR-185-5p), and GTPase-activating protein-binding protein 2 (G3bp2). 5-Ethynyl-2'-deoxyuridine (EdU) and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium Bromide (MTT) assays were used to examine cell proliferation, and flow cytometry was used to detect cell apoptosis. Western blot was used to assess the levels of relative proteins. Enzyme-linked immunosorbent assay detected the inflammation cytokines. Dual-luciferase reporter and RNA pull-down assays were used to confirm the interaction of miR-185-5p and circ_Supt3 or G3bp2. Results: Circ_Supt3 and G3bp2 were highly expressed and miR-185-5p expression was diminished in DN mice. HG treatment inhibited cell proliferation and accelerated cell apoptosis and inflammation response, and the knockdown of circ_Supt3 reversed these effects. Bioinformatics predicted that circ_Supt3 contained a binding site for miR-185-5p, and G3bp2 was a direct target of miR-185-5p. Circ_Supt3 regulated G3bp2 expression by miR-185-5p. Moreover, the circ_Supt3/miR-185-5p/G3bp2 axis regulated the cell behavior of HG-induced MPC5 cells. Conclusion: Our findings suggest that the knockdown of circ_Supt3 protects mouse MPC5 cells against HG-induced cell injury via the miR-185-5p/G3bp2 axis.
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Glucosa , MicroARNs , Podocitos , ARN Circular , Animales , MicroARNs/genética , MicroARNs/metabolismo , Ratones , ARN Circular/genética , ARN Circular/metabolismo , Podocitos/metabolismo , Glucosa/toxicidad , Glucosa/farmacología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/genética , Apoptosis/genética , Proliferación Celular , Línea Celular , ARN Endógeno CompetitivoAsunto(s)
Proteínas Bacterianas , Regulón , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sistemas de Secreción Tipo VI/genética , Sistemas de Secreción Tipo VI/metabolismo , Regulación Bacteriana de la Expresión Génica , Transcripción GenéticaRESUMEN
BACKGROUND: Some preceding researches have observed that certain neurological disorders, such as Alzheimer's disease and multiple sclerosis, may affect breast cancer risk. However, whether there are causal relationships between these neurological conditions and breast cancer is inconclusive. This study was designed to explore whether neurological disorders affected the risks of breast cancer overall and of the two subtypes (ER+ and ER-). METHODS: In the course of this study, genome-wide association study (GWAS) data for nine neurological diseases (Alzheimer's disease, multiple sclerosis, Parkinson's disease, myasthenia gravis, generalized epilepsy, intracerebral haemorrhage, cerebral atherosclerosis, brain glioblastoma, and benign meningeal tumour) were collected from the Complex Trait Genetics lab and the MRC Integrative Epidemiology Unit, and single-nucleotide polymorphisms (SNPs) extensively associated with these neurological ailments had been recognized as instrumental variables (IVs). GWAS data on breast cancer were collected from the Breast Cancer Association Consortium (BCAC). Two-sample Mendelian randomization (MR) analyses as well as multivariable MR analyses were performed to determine whether these SNPs contributed to breast cancer risk. Additionally, the accuracy of the results was evaluated using the false discovery rate (FDR) multiple correction method. Both heterogeneity and pleiotropy were evaluated by analyzing sensitivities. RESULTS: According to the results of two-sample MR analyses, Alzheimer's disease significantly reduced the risks of overall (OR 0.925, 95% CI [0.871-0.982], P = 0.011) and ER+ (OR 0.912, 95% CI [0.853-0.975], P = 0.007) breast cancer, but there was a negative result in ER- breast cancer. However, after multiple FDR corrections, the effect of Alzheimer's disease on overall breast cancer was not statistically significant. In contrast, multiple sclerosis significantly increased ER+ breast cancer risk (OR 1.007, 95% CI [1.003-1.011], P = 0.001). In addition, the multivariable MR analyses showed that Alzheimer's disease significantly reduced the risk of ER+ breast cancer (IVW: OR 0.929, 95% CI [0.864-0.999], P=0.047; MR-Egger: OR 0.916, 95% CI [0.846-0.992], P=0.031); however, multiple sclerosis significantly increased the risk of ER+ breast cancer (IVW: OR 1.008, 95% CI [1.003-1.012], P=4.35×10-4; MR-Egger: OR 1.008, 95% CI [1.003-1.012], P=5.96×10-4). There were no significant associations between the remainder of the neurological diseases and breast cancer. CONCLUSIONS: This study found the trends towards a decreased risk of ER+ breast cancer in patients with Alzheimer's disease and an increased risk in patients with multiple sclerosis. However, due to the limitations of Mendelian randomization, we cannot determine whether there are definite causal relationships between neurological diseases and breast cancer risk. For conclusive evidences, more prospective randomized controlled trials will be needed in the future.
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Neoplasias de la Mama , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/epidemiología , Femenino , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/epidemiología , Predisposición Genética a la Enfermedad , Factores de Riesgo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiologíaRESUMEN
The catalytic access of silicon-stereogenic organosilanes remains a big challenge, and largely depends on the desymmetrization of the symmetric precursors with two identical substitutes attached to silicon atom. Here we report the construction of silicon-stereogenic organosilanes via catalytic kinetic resolution of racemic monohydrosilanes with good to excellent selectivity factors. Both Si-stereogenic dihydrobenzosiloles and Si-stereogenic monohydrosilanes could be efficiently accessed in one single operation via Rh-catalyzed enantioselective intramolecular hydrosilylation, employing (R,R)-Et-DuPhos as the optimal ligand. This catalytic protocol features mild conditions, a low catalyst loading (0.1â mol % [Rh(cod)Cl]2), high stereoinduction (S factor up to 152), and excellent scalability. Moreover, further derivatizations led to the efficient synthesis of uncommon middle-size (7- and 8-membered) Si-stereogenic silacycles. Preliminary mechanistic study indicates this reaction might undergo a modified Chalk-Harrod mechanism.
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Lung cancer stands as the most prevalent form of cancer globally, posing a significant threat to human well-being. Due to the lack of effective and accurate early diagnostic methods, many patients are diagnosed with advanced lung cancer. Although surgical resection is still a potential means of eradicating lung cancer, patients with advanced lung cancer usually miss the best chance for surgical treatment, and even after surgical resection patients may still experience tumor recurrence. Additionally, chemotherapy, the mainstay of treatment for patients with advanced lung cancer, has the potential to be chemo-resistant, resulting in poor clinical outcomes. The emergence of liquid biopsies has garnered considerable attention owing to their noninvasive nature and the ability for continuous sampling. Technological advancements have propelled circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), tumor metabolites, tumor-educated platelets (TEPs), and tumor-associated antigens (TAA) to the forefront as key liquid biopsy biomarkers, demonstrating intriguing and encouraging results for early diagnosis and prognostic evaluation of lung cancer. This review provides an overview of molecular biomarkers and assays utilized in liquid biopsies for lung cancer, encompassing CTCs, ctDNA, non-coding RNA (ncRNA), EVs, tumor metabolites, TAAs and TEPs. Furthermore, we expound on the practical applications of liquid biopsies, including early diagnosis, treatment response monitoring, prognostic evaluation, and recurrence monitoring in the context of lung cancer.
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Neoplasias Pulmonares , Células Neoplásicas Circulantes , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/análisis , Recurrencia Local de Neoplasia , Biopsia Líquida/métodos , Pronóstico , Células Neoplásicas Circulantes/metabolismoRESUMEN
BACKGROUND: The causal relationship between breast cancer (BC) and the oral microbiome remains unclear. In this case-control study, using two-sample Mendelian randomization (MR), we thoroughly explored the relationship between the oral microbiome and BC in the East Asian population. METHODS: Genetic summary data related to oral microbiota and BC were collected from genome-wide association studies involving participants of East Asian descent. MR estimates were generated by conducting various analyses. Sequencing data from a case-control study were used to verify the validity of these findings. RESULTS: MR analysis revealed that 30 tongue and 37 salivary bacterial species were significantly associated with BC. Interestingly, in both tongue and salivary microbiomes, we observed the causal effect of six genera, namely, Aggregatibacter, Streptococcus, Prevotella, Haemophilus, Lachnospiraceae, Oribacterium, and Solobacterium, on BC. Our case-control study findings suggest differences in specific bacteria between patients with BC and healthy controls. Moreover, sequencing data confirmed the MR analysis results, demonstrating that compared with the healthy control group, the BC group had a higher relative abundance of Pasteurellaceae and Streptococcaceae but a lower relative abundance of Bacteroidaceae. CONCLUSIONS: Our MR analysis suggests that the oral microbiome exerts a causative effect on BC risk, supported by the sequencing data of a case-control study. In the future, studies should be undertaken to comprehensively understand the complex interaction mechanisms between the oral microbiota and BC.
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Neoplasias de la Mama , Análisis de la Aleatorización Mendeliana , Microbiota , Femenino , Humanos , Neoplasias de la Mama/genética , Neoplasias de la Mama/microbiología , Estudios de Casos y Controles , Pueblos del Este de Asia , Estudio de Asociación del Genoma Completo , Boca/microbiologíaRESUMEN
Background: Breast cancer patients with positive axillary lymph nodes usually require axillary lymph node dissection (ALND), with many postoperative complications, such as lymphedema. For these patients, whether sentinel lymph node biopsy (SLNB) can replace ALND has been a research hotspot in the field of breast cancer. This study developed two risk stratification models for predicting the clinical outcomes of breast cancer patients with positive axillary lymph nodes receiving SLNB alone or ALND to determine which patients could potentially avoid ALND. Methods: A total of 21,942 breast cancer patients, including a training set (n=15,362) and a testing set (n=6,580), were enrolled in this study from Surveillance, Epidemiology, and End Results (SEER) between 2000 and 2017. The risk factors associated with breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using multivariate Cox regression analysis and then integrated into nomograms and risk stratification models examined by receiver operating characteristic (ROC) curves and calibration curves. The survival discrepancies were compared between the SLNB and ALND subgroups with different risk scores with Kaplan-Meier plots. Results: In multivariate Cox regression analyses, grade, marital status, T stage, radiotherapy and lymph node metastasis (GMTRL) were independent risk factors in breast cancer patients with both OS and BCSS status in the ALND cohort from the training set. Nomograms have been developed based on these factors to predict 3- and 5-year OS and BCSS in patients with ALND. Calibration curves and ROC curves in both the training and testing sets confirmed the excellent overall predictive performance of the nomograms. Furthermore, we developed two risk stratification models based on OS and BCSS status, revealing that patients with low GMTRL scores might avoid ALND in both OS and BCSS status [OS: hazard ratio (HR) =0.929, 95% confidence interval (CI): 0.841-1.027, P=0.150; BCSS: HR =0.953, 95% CI: 0.831-1.094, P=0.495], but patients with moderate (OS: HR =0.756, 95% CI: 0.666-0.859, P<0.001; BCSS: HR =0.643, 95% CI: 0.537-0.768, P<0.001) and high GMTRL scores could not (OS: HR =0.719, 95% CI: 0.549-0.940, P=0.014; BCSS: HR =0.731, 95% CI: 0.549-0.974, P=0.031). Conclusions: Breast cancer patients with positive nodes could be treated with SLNB alone rather than ALND without affecting prognosis based on GMTRL scores. Patients with high or moderate GMTRL scores benefited greatly from ALND, but not for patients with low GMTRL scores. This study may assist clinicians in tailoring treatments.
RESUMEN
OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.