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As data-driven science, artificial intelligence (AI) has paved a promising path toward an evolving health system teeming with thrilling opportunities for precision oncology. Notwithstanding the tremendous success of oncological AI in such fields as lung carcinoma, breast tumor and brain malignancy, less attention has been devoted to investigating the influence of AI on gynecologic oncology. Hereby, this review sheds light on the ever-increasing contribution of state-of-the-art AI techniques to the refined risk stratification and whole-course management of patients with gynecologic tumors, in particular, cervical, ovarian and endometrial cancer, centering on information and features extracted from clinical data (electronic health records), cancer imaging including radiological imaging, colposcopic images, cytological and histopathological digital images, and molecular profiling (genomics, transcriptomics, metabolomics and so forth). However, there are still noteworthy challenges beyond performance validation. Thus, this work further describes the limitations and challenges faced in the real-word implementation of AI models, as well as potential solutions to address these issues.
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Neoplasias Encefálicas , Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/terapia , Inteligência Artificial , Medicina de Precisão , Medição de RiscoRESUMO
The transformation of the two-electron oxygen reduction reaction (2e-ORR) to produce hydrogen peroxide (H2 O2 ) is a promising green synthesis approach that can replace the high-energy consumption anthraquinone process. However, designing and fabricating low-cost, non-precious metal electrocatalysts for 2e-ORR remains a challenge. In this study, a method of combining complexation precipitation and thermal treatment to synthesize 2D copper-tin composite nanosheets to serve as the 2e-ORR electrocatalysts is utilized, achieving a high H2 O2 selectivity of 92.8% in 0.1 m KOH, and a bulk H2 O2 electrosynthesis yield of 1436 mmol·gcat -1 ·h-1 using a flow cell device. Remarkably, the H2 O2 selectivity of this catalyst decreases by only 0.5% after 10,000 cyclic voltammetry (CV) cycles. In addition, it demonstrates that the same catalyst can achieve 97% removal of the organic pollutant methyl blue in an aqueous system solution within 1 h using the on-site degradation technology. A reasonable control of defect concentration on the 2D copper-tin composite nanosheets that can effectively improve the electrocatalytic performance is found. Density functional theory calculations confirm that the surface of the 2D copper-tin composite nanosheets is conducive to the adsorption of the key intermediate OOH* , highlighting its excellent electrocatalytic performance for ORR with high H2 O2 selectivity.
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Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 µmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor.
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Aminoácidos , Proliferação de Células , Fluoretos , Músculo Liso Vascular , Ratos Sprague-Dawley , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Músculo Liso Vascular/efeitos dos fármacos , Fluoretos/farmacologia , Linhagem Celular , Aminoácidos/metabolismo , Proliferação de Células/efeitos dos fármacos , Ratos , Movimento Celular/efeitos dos fármacos , Masculino , Aorta/patologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Metabolômica , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Redes Reguladoras de Genes/efeitos dos fármacosRESUMO
BACKGROUND: Ectoine as an amino acid derivative is widely applied in many fields, such as the food industry, cosmetic manufacturing, biologics, and therapeutic agent. Large-scale production of ectoine is mainly restricted by the cost of fermentation substrates (e.g., carbon sources) and sterilization. RESULTS: In this study, Halomonas cupida J9 was shown to be capable of synthesizing ectoine using xylose as the sole carbon source. A pathway was proposed in H. cupida J9 that synergistically utilizes both WBG xylose metabolism and EMP glucose metabolism for the synthesis of ectoine. Transcriptome analysis indicated that expression of ectoine biosynthesis module was enhanced under salt stress. Ectoine production by H. cupida J9 was enhanced by improving the expression of ectoine biosynthesis module, increasing the intracellular supply of the precursor oxaloacetate, and utilizing urea as the nitrogen source. The constructed J9U-P8EC achieved a record ectoine production of 4.12 g/L after 60 h of xylose fermentation. Finally, unsterile production of ectoine by J9U-P8EC from either a glucose-xylose mixture or corn straw hydrolysate was demonstrated, with an output of 8.55 g/L and 1.30 g/L of ectoine, respectively. CONCLUSIONS: This study created a promising H. cupida J9-based cell factory for low-cost production of ectoine. Our results highlight the potential of J9U-P8EC to utilize lignocellulose-rich agriculture waste for open production of ectoine.
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Diamino Aminoácidos , Biomassa , Fermentação , Halomonas , Lignina , Xilose , Diamino Aminoácidos/metabolismo , Diamino Aminoácidos/biossíntese , Lignina/metabolismo , Xilose/metabolismo , Halomonas/metabolismo , Halomonas/genética , Tolerância ao Sal , Glucose/metabolismoRESUMO
PURPOSE: This study aimed to assess the safety and efficacy of endoscopic submucosal dissection (ESD) and pre-cutting endoscopic mucosal resection (pEMR) in treating non-ampullary duodenal subepithelial lesions (NADSELs) and to evaluate the clinical utility of endoscopic ultrasound (EUS) before endoscopic resection (ER). METHODS: In this retrospective single-centre cohort study, we compared the clinical outcomes of patients with NADSELs who underwent ESD or pEMR between January 2014 and June 2023. The accuracies of EUS in determining the pathological type and origin of the lesions were evaluated using postoperative histopathology as the gold standard. RESULTS: Overall, 56 patients with NADSELs underwent ER in this study, including 16 and 40 treated with pEMR and ESD, respectively. There were no significant differences between the two groups in terms of en bloc resection rate, complete (R0) resection rate, perioperative complication rate, and postoperative hospital length of stay (P > 0.05). However, the pEMR group had significantly shorter median operational (13.0 min vs. 30.5 min, P < 0.001) and mean fasting (1.9 days vs. 2.8 days, P = 0.006) time and lower median hospital costs (¥12,388 vs. ¥19,579, P = 0.002). The accuracies of EUS in determining the pathological type and origin of the lesions were 76.8% and 94.6%, respectively, compared with histopathological evaluation. CONCLUSIONS: EUS can accurately predict the origin of NADSELs. Suitable lesions determined to originate from the submucosa or more superficial layers using EUS can be treated using pEMR as it shortens the operational and recovery time, reduces hospitalisation costs, and achieves an R0 resection rate similar to ESD.
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Ressecção Endoscópica de Mucosa , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Ressecção Endoscópica de Mucosa/métodos , Idoso , Neoplasias Duodenais/cirurgia , Neoplasias Duodenais/patologia , Neoplasias Duodenais/diagnóstico por imagem , Resultado do Tratamento , Endossonografia , Adulto , Tempo de InternaçãoRESUMO
Understanding selectivity mechanisms of inhibitors towards highly homologous proteins is of paramount importance in the design of selective candidates. Human aldo-keto reductases (AKRs) pertain to a superfamily of monomeric oxidoreductases, which serve as NADPH-dependent cytosolic enzymes to catalyze the reduction of carbonyl groups to primary and secondary alcohols using electrons from NADPH. Among AKRs, AKR1B1 is emerging as a promising target for cancer treatment and diabetes, despite its high structural similarity with AKR1B10, which leads to severe adverse events. Therefore, it is crucial to understand the selectivity mechanisms of AKR1B1 and AKR1B10 to discover safe anticancer candidates with optimal therapeutic efficacy. In this study, multiple computational strategies, including sequence alignment, structural comparison, Protein Contacts Atlas analysis, molecular docking, molecular dynamics simulation, MM-GBSA calculation, alanine scanning mutagenesis and pharmacophore modeling analysis were employed to comprehensively understand the selectivity mechanisms of AKR1B1/10 inhibition based on selective inhibitor lidorestat and HAHE. This study would provide substantial evidence in the design of potent and highly selective AKR1B1/10 inhibitors in future.
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Inibidores Enzimáticos , Simulação de Dinâmica Molecular , Humanos , Simulação de Acoplamento Molecular , NADP/metabolismo , Aldo-Ceto Redutases/metabolismo , Inibidores Enzimáticos/farmacologia , Aldeído Redutase/metabolismoRESUMO
OBJECTIVE: To evaluate corpus callosum (CC) size in fetuses with malformations of cortical development (MCD) and to explore the diagnostic value of three CC length (CCL) ratios in identifying cortical abnormalities. METHODS: This is a single-center retrospective study in singleton fetuses at 20-37 weeks of gestation between April 2017 and August 2022. The midsagittal plane of the fetal brain was obtained and evaluated for the following variables: length, height, area of the corpus callosum, and relevant markers, including the ratios of corpus callosum length to internal cranial occipitofrontal dimension (CCL/ICOFD), corpus callosum length to femur length (CCL/FL), and corpus callosum length to cerebellar vermian diameter (CCL/VD). Intra-class correlation coefficient (ICC) was used to evaluate measurement consistency. The accuracy of biometric measurements in prediction of MCD was assessed using the area under the receiver-operating-characteristics curves (AUC). RESULTS: Fetuses with MCD had a significantly decreased CCL, height (genu and splenium), and area as compared with those of normal fetuses (P < .05), but there was no significant difference in body height (P = .326). The CCL/ICOFD, CCL/FL, and CCL/VD ratios were significantly decreased in fetuses with MCD when compared with controls (P < .05). The CCL/ICOFD ratio offered the highest predictive accuracy for MCD, yielding an AUC of 0.856 (95% CI: 0.774-0.938, P < .001), followed by CCL/FL ratio (AUC, 0.780 (95% CI: 0.657-0.904), P < .001), CCL/VD ratio (AUC, 0.677 (95% CI: 0.559-0.795), P < .01). CONCLUSION: The corpus callosum biometric parameters in fetuses with MCD are reduced. The CCL/ICOFD ratio derived from sonographic measurements is considered a promising tool for the prenatal detection of cortical malformations. External validation of these findings and prospective studies are warranted.
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Corpo Caloso , Ultrassonografia Pré-Natal , Humanos , Feminino , Gravidez , Ultrassonografia Pré-Natal/métodos , Estudos Retrospectivos , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/embriologia , Adulto , Malformações do Desenvolvimento Cortical/diagnóstico por imagem , Malformações do Desenvolvimento Cortical/embriologia , Reprodutibilidade dos TestesRESUMO
Considerable efforts have been made to develop nanoparticle-based magnetic resonance contrast agents (CAs) with high relaxivity. The prolonged rotational correlation time (τR) induced relaxivity enhancement is commonly recognized, while the effect of the water coordination numbers (q) on the relaxivity of nanoparticle-based CAs gets less attention. Herein, we first investigated the relationship between T1 relaxivity (r1) and q in manganese-based hybrid micellar CAs and proposed a strategy to enhance the relaxivity by increasing q. Hybrid micelles with different ratios of amphiphilic manganese complex (MnL) and DSPE-PEG2000 were prepared, whose q values were evaluated by Oxygen-17-NMR spectroscopy. Micelles with lower manganese doping density exhibit increased q and enhanced relaxivity, corroborating the conception. In vivo sentinel lymph node (SLN) imaging demonstrates that DSPE-PEG/MnL micelles could differentiate metastatic SLN from inflammatory LN. Our strategy makes it feasible for relaxivity enhancement by modulating q, providing new approaches for the structural design of high-performance hybrid micellar CAs.
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Micelas , Água , Manganês/química , Linfografia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Meios de Contraste/químicaRESUMO
To evaluate the association between ATP2B1 gene polymorphisms and skeletal fluorosis, a cross-sectional study was conducted. In China, 962 individuals were recruited, including 342 cases of skeletal fluorosis. Four TP2BA1 polymorphisms (rs2070759, rs12817819, rs17249754, and rs7136259) were analysed. The results suggested that rs17249754 and rs7136259 were associated with skeletal fluorosis. After controlling confounders, the protective effect of GG genotype in rs17249754 was apparent in individuals over 45 years old, female, with urine fluoride concentration below 1.6 mg/L, serum calcium above 2.25 mmol/L or serum phosphorus between 1.1 and 1.3. Heterozygote TC in rs7136259 increased the risk of skeletal fluorosis in subjects who are elderly, female, with urinary fluoride more than 1.6 mg/L, serum calcium more than 2.25 mmol/L and blood phosphorus between 1.1 and 1.3 mmol/L. Four loci were found to be tightly related by linkage disequilibrium analysis, and the frequency of distribution of haplotype GCGT was lower in the skeletal fluorosis group.
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Doenças Ósseas Metabólicas , Fluorose Dentária , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Fluoretos , Haplótipos , Cálcio , Polimorfismo de Nucleotídeo Único , Estudos Transversais , Doenças Ósseas Metabólicas/genética , China/epidemiologia , Fósforo , Fluorose Dentária/epidemiologia , Fluorose Dentária/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genéticaRESUMO
Novel therapeutics have significantly improved the survival and quality of life of patients with malignancies in this century. Versatile precision diagnostic data were used to formulate personalized therapeutic strategies for patients. However, the cost of extensive information depends on the consumption of the specimen, raising the challenges of effective specimen utilization, particularly in small biopsies. In this study, we proposed a tissue-processing cascaded protocol that obtains 3-dimensional (3D) protein expression spatial distribution and mutation analysis from an identical specimen. In order to reuse the thick section tissue evaluated after the 3D pathology technique, we designed a novel high-flatness agarose-embedded method that could improve tissue utilization rate by 1.52 fold, whereas it reduced the tissue-processing time by 80% compared with the traditional paraffin-embedding method. In animal studies, we demonstrated that the protocol would not affect the results of DNA mutation analysis. Furthermore, we explored the utility of this approach in non-small cell lung cancer because it is a compelling application for this innovation. We used 35 cases including 7 cases of biopsy specimens of non-small cell lung cancer to simulate future clinical application. The cascaded protocol consumed 150-µm thickness of formalin-fixed, paraffin-embedded specimens, providing 3D histologic and immunohistochemical information approximately 38 times that of the current paraffin-embedding protocol, and 3 rounds of DNA mutation analysis, offering both essential guidance for routine diagnostic evaluation and advanced information for precision medicine. Our designed integrated workflow provides an alternative way for pathological examination and paves the way for multidimensional tumor tissue assessment.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Qualidade de Vida , Mutação , DNA , Inclusão em Parafina/métodos , FormaldeídoRESUMO
PURPOSE: The aim of the current study was to identify the relationship between body composition changes during neoadjuvant therapy (NAT) and the treatment efficiency of NAT in gastrointestinal cancer (GC) patients. METHODS: From January 2015 to July 2020, 277 GC patients treated with NAT had included for retrospective analysis. The body mass index (BMI) and computed tomography (CT) imaging before and after NAT were recorded. The BMI change optimal cut-off value were calculated by ROC curve. Balancing essential characteristic variables using propensity score matching (PSM) method. Exploring the association between BMI changes and tumor response to NAT using logistic regression analysis. The survival outcome of matched patients between different BMI change groups was compared. RESULTS: A cutoff point of BMI change >2% during NAT was defined as BMI loss. Among the 277 patients, 110 (39.7%) patients showed BMI change with a loss after NAT. In total, 71 pairs of patients were selected for further analysis. The median follow-up time was 22 months (range 3 to 63 months). Univariate and multivariate logistic regression analyses in matched cohort showed that BMI change was a prognostic factor for tumor response after NAT in GC patients (odds ratio (OR), .471; 95% confidence interval (CI), .233-.953; P = .036). In addition, patients who experienced BMI loss after NAT showed worse overall survival than those who had BMI gain or stable. CONCLUSION: BMI loss during NAT probably may has negative effects on NAT efficiency and survival for gastrointestinal cancer patients. It is necessary to monitor and maintain weight for patients during treatment.
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Neoplasias Gastrointestinais , Terapia Neoadjuvante , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Neoplasias Gastrointestinais/tratamento farmacológico , Redução de Peso , PrognósticoRESUMO
OBJECTIVES: To establish an effective dynamic nomogram combining magnetic resonance imaging (MRI) findings of primary tumor and regional lymph nodes with tumor stage for the pretreatment prediction of induction chemotherapy (IC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 498 LANPC patients (372 in the training and 126 in the validation cohort) with MRI information were enrolled. All patients were classified as "favorable responders" and "unfavorable responders" according to tumor response to IC. A nomogram for IC response was built based on the results of the logistic regression model. Also, the Cox regression analysis was used to identify the independent prognostic factors of disease-free survival (DFS). RESULTS: After two cycles of IC, 340 patients were classified as "favorable responders" and 158 patients as "unfavorable responders." Calibration curves revealed satisfactory agreement between the predicted and the observed probabilities. The nomogram achieved an AUC of 0.855 (95% CI, 0.781-0.930) for predicting IC response, which outperformed TNM staging (AUC, 0.661; 95% CI 0.565-0.758) and the MRI feature-based model alone (AUC, 0.744; 95% CI 0.650-0.839) in the validation cohort. The nomogram was used to categorize patients into high- and low-response groups. An online dynamic model was built ( https://nomogram-for-icresponse-prediction.shinyapps.io/DynNomapp/ ) to facilitate the application of the nomogram. In the Cox multivariate analysis, clinical stage, tumor necrosis, EBV DNA levels, and cervical lymph node numbers were independently associated with DFS. CONCLUSIONS: The comprehensive nomogram incorporating MRI features and tumor stage could assist physicians in predicting IC response and formulating personalized treatment strategies for LANPC patients. KEY POINTS: ⢠The nomogram can predict IC response in endemic LANPC. ⢠The nomogram combining tumor stage with MRI-based tumor features showed very good predictive performance. ⢠The nomogram was transformed into a web-based dynamic model to optimize clinical application.
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Neoplasias Nasofaríngeas , Nomogramas , Humanos , Carcinoma Nasofaríngeo/patologia , Prognóstico , Quimioterapia de Indução/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is associated with a high rate of pulmonary infections (bacteria, fungi, and viruses). To overcome the low sensitivity and long turnaround time of traditional laboratory-based diagnostic strategies, we adopted metagenomic next-generation sequencing (mNGS) technology to identify and classify pathogens. RESULTS: This study enrolled 75 patients with AIDS and suspected pulmonary infections who were admitted to Nanning Fourth People's Hospital. Specimens were collected for traditional microbiological testing and mNGS-based diagnosis. The diagnostic yields of the two methods were compared to evaluate the diagnostic value (detection rate and turn around time) of mNGS for infections with unknown causative agent. Accordingly, 22 cases (29.3%) had a positive culture and 70 (93.3%) had positive valve mNGS results (P value < 0.0001, Chi-square test). Meanwhile, 15 patients with AIDS showed concordant results between the culture and mNGS, whereas only one 1 patient showed concordant results between Giemsa-stained smear screening and mNGS. In addition, mNGS identified multiple microbial infections (at least three pathogens) in almost 60.0% of patients with AIDS. More importantly, mNGS was able to detect a large variety of pathogens from patient tissue displaying potential infection and colonization, while culture results remained negative. There were 18 members of pathogens which were consistently detected in patients with and without AIDS. CONCLUSIONS: In conclusion, mNGS analysis provides fast and precise pathogen detection and identification, contributing substantially to the accurate diagnosis, real-time monitoring, and treatment appropriateness of pulmonary infection in patients with AIDS.
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Síndrome da Imunodeficiência Adquirida , Pneumonia , Humanos , Síndrome da Imunodeficiência Adquirida/complicações , Sequenciamento de Nucleotídeos em Larga Escala , Corantes Azur , Hospitalização , HospitaisRESUMO
C1q/tumor necrosis factor (TNF) related proteins (CTRPs) is a newly discovered adipokine family with conservative structure and ubiquitous distribution and is secreted by adipose tissues. Recently, CTRPs have attracted increasing attention due to the its wide-ranging effects upon inflammation and metabolism. To-date, 15 members of CTRPs (CTRP1-15) with the characteristic C1q domain have been characterized. Earlier in-depth phenotypic analyses of mouse models of CTRPs deficiency have also unveiled ample function of CTRPs in inflammation and metabolism. This review focuses on the rise of CTRPs, with a special emphasis on the latest discoveries with regards to the effects of the CTRP family on inflammation and metabolism as well as related diseases. We first introduced the structure of characteristic domain and polymerization of CTRPs to reveal its pleiotropic biological functions. Next, intimate association of CTRP family with inflammation and metabolism, as well as the involvement of CTRPs as nodes in complex molecular networks, were elaborated. With expanding membership of CTRP family, the information presented here provides new perspectives for therapeutic strategies to improve inflammatory and metabolic abnormalities.
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Adipocinas , Inflamação , Animais , Camundongos , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Complemento C1q , Inflamação/metabolismoRESUMO
Inflammatory microenvironment may take a promoting role in lung tumorigenesis. However, the molecular characteristics underlying inflammation-related lung cancer remains unknown. In this work, the inflammation-related lung tumorigenesis mouse model was established by treated with B(a)P (1 mg/mouse, once a week for 4 weeks), followed by LPS (2.5 µg/mouse, once every 3 weeks for five times), the mice were sacrificed 30 weeks after exposure. TMT-labeled quantitative proteomics and untargeted metabolomics were used to interrogate differentially expressed proteins and metabolites in different mouse cancer tissues, followed by integrated crosstalk between proteomics and metabolomics through Spearman's correlation analysis. The result showed that compared with the control group, 103 proteins and 37 metabolites in B(a)P/LPS group were identified as significantly altered. By searching KEGG pathway database, proteomics pathways such as Leishmaniasis, Asthma and Intestinal immune network for IgA production, metabolomics pathways such as Vascular smooth muscle contraction, Linoleic acid metabolism and cGMP-PKG signaling pathway were enriched. A total of 22 pathways were enriched after conjoint analysis of the proteomic and metabolomics, and purine metabolism pathway, the unique metabolism-related pathway, which included significantly altered protein (adenylate cyclase 4, ADCY4) and metabolites (L-Glutamine, guanosine monophosphate (GMP), adenosine and guanosine) was found. Results suggested purine metabolism may contribute to the inflammation-related lung tumorigenesis, which may provide novel clues for the therapeutic strategies of inflammation-related lung cancer.
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Neoplasias Pulmonares , Pneumonia , Camundongos , Animais , Proteômica , Lipopolissacarídeos/toxicidade , Carcinogênese/induzido quimicamente , Transformação Celular Neoplásica , Pulmão/metabolismo , Metabolômica , Inflamação/induzido quimicamente , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Purinas/toxicidade , Microambiente TumoralRESUMO
Tunable metasurfaces provide a compact and efficient strategy for optical active wavefront shaping. Varifocal metalens is one of the most important applications. However, the existing tunable metalens rarely serves broadband wavelengths restricting their applications in broadband imaging and color display due to chromatic aberration. Herein, an electrically tunable polarization-multiplexed achromatic metalens integrated with twisted nematic liquid crystals (TNLCs) in the visible region is demonstrated. The phase profiles at different wavelengths under two orthogonal polarization channels are customized by the particle swarm optimization algorithm and matched with the dielectric metaunits database to achieve polarization-multiplexed achromatic performance. By combining the broadband linear polarization conversion ability of TNLC, the tunability of varifocal achromatic metalens is realized by applying different voltages. Further, the electrically tunable customized dispersion-manipulated metalens and switchable color metaholograms are demonstrated. The proposed devices will accelerate the application of metasurfaces in broadband zoom imaging, AR/VR displays and spectral detection.
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Zika virus (ZIKV), which is mainly transmitted by Aedes albopictus in temperate zones, can causes serious neurological disorders. However, the molecular mechanisms that influence the vector competence of Ae. albopictus for ZIKV are poorly understood. In this study, the vector competence of Ae. albopictus mosquitoes from Jinghong (JH) and Guangzhou (GZ) Cities of China were evaluated, and transcripts in the midgut and salivary gland tissues were sequenced on 10 days post-infection. The results showed that both Ae. albopictus JH and GZ strains were susceptible to ZIKV, but the GZ strain was more competent. The categories and functions of differentially expressed genes (DEGs) in response to ZIKV infection were quite different between tissues and strains. Through a bioinformatics analysis, a total of 59 DEGs that may affect vector competence were screened-among which, cytochrome P450 304a1 (CYP304a1) was the only gene significantly downregulated in both tissues of two strains. However, CYP304a1 did not influence ZIKV infection and replication in Ae. albopictus under the conditions set in this study. Our results demonstrated that the different vector competence of Ae. albopictus for ZIKV may be determined by the transcripts in the midgut and salivary gland, which will contribute to understanding ZIKV-mosquito interactions and develop arbovirus disease prevention strategies.
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Aedes , Infecção por Zika virus , Zika virus , Animais , Zika virus/fisiologia , Mosquitos Vetores , Perfilação da Expressão GênicaRESUMO
Malvids is one of the largest clades of rosids, includes 58 families and exhibits remarkable morphological and ecological diversity. Here, we report a high-quality chromosome-level genome assembly for Euscaphis japonica, an early-diverging species within malvids. Genome-based phylogenetic analysis suggests that the unstable phylogenetic position of E. japonica may result from incomplete lineage sorting and hybridization event during the diversification of the ancestral population of malvids. Euscaphis japonica experienced two polyploidization events: the ancient whole genome triplication event shared with most eudicots (commonly known as the γ event) and a more recent whole genome duplication event, unique to E. japonica. By resequencing 101 samples from 11 populations, we speculate that the temperature has led to the differentiation of the evergreen and deciduous of E. japonica and the completely different population histories of these two groups. In total, 1012 candidate positively selected genes in the evergreen were detected, some of which are involved in flower and fruit development. We found that reddening and dehiscence of the E. japonica pericarp and long fruit-hanging time promoted the reproduction of E. japonica populations, and revealed the expression patterns of genes related to fruit reddening, dehiscence and abscission. The key genes involved in pentacyclic triterpene synthesis in E. japonica were identified, and different expression patterns of these genes may contribute to pentacyclic triterpene diversification. Our work sheds light on the evolution of E. japonica and malvids, particularly on the diversification of E. japonica and the genetic basis for their fruit dehiscence and abscission.
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Evolução Molecular , Genoma de Planta/genética , Magnoliopsida/genética , Frutas/genéticaRESUMO
Ideal leading and nominee compounds with inhibiting effects on KRAS G12C were selected from the ZINC database, laying a cornerstone for the progress of anticancer drugs. A variety of computational virtual screening methods were utilized to screen possible inhibitors of KRAS G12C. LibDock was utilized to estimate 17 930 compounds and the top 20 were nominated for additional study, which was absorption, distribution, metabolism, and excretion and harmfulness prediction. Molecule docking was employed to prove the binding connection between certain ligands and KRAS G12C. Natural novel compounds ZINC000012494057 and ZINC000003789195 were selected to bind stably with KRAS G12C. In addition, they had lower scores in Ames mutagenicity, rodent carcinogenicity, cytochrome P450 2D6(CYP2D6) tolerance, and non-developmental toxicity potential. Molecular dynamic simulations demonstrate that the combination of ZINC000012494057 and ZINC000003789195 with KRAS G12C has more favorable potential energy, which provides conditions for their stable existence in the natural environment. Natural compounds ZINC000012494057 and ZINC000003789195 were identified as KRAS G12C potential inhibitors. These two compounds have been verified to have enormous importance for the progress of anticancer medicines.
Assuntos
Antineoplásicos , Citocromo P-450 CYP2D6 , Antineoplásicos/química , Antineoplásicos/farmacologia , Simulação de Acoplamento Molecular , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , ZincoRESUMO
BACKGROUND: This study aimed to explore the incidence and influencing factors for early pregnancy loss (EPL) in infertility patients with first pregnancy undergoing in vitro fertilization (IVF) embryo transfer cycles in Jilin province, China. METHODS: A retrospective study of 2709 first pregnancy embryo transfer cycles collected from January 2016 to January 2021 was performed. The cycles were divided into the EPL group (n = 411) and the live birth group (n = 2298) according to the cycle outcomes. RESULTS: The EPL rate of the first-time pregnancies for infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 14.1%. Female patients aged 40 and older had increased odds of EPL compared to those under 35 (OR = 3.97, 95%CI: 2.80-7.55). Female patients with a body mass index (BMI) of 25 or greater were more likely to have EPLs than those in the normal BMI range (OR = 1.32, 95%CI: 1.03-1.70). The odds of EPL after frozen-thaw embryo transfer were higher than those after fresh embryo transfer (OR = 1.59, 95%CI: 1.11-2.27). A thin endometrium on the day of embryo transfer increased the odds of EPL (OR = 1.84, 95%CI: 1.01-3.33). Transferring more than two embryos had lower odds of EPL than single-embryo transfer (OR = 0.67, 95%CI: 0.50-0.90). Compared with other infertility diagnoses, tubal factor alone was associated with lower odds of EPL (OR = 0.72, 95%CI: 0.53-0.98). CONCLUSIONS: The risk factors for EPL were age 40 and older, obesity, frozen-thaw cycle, thin endometrium, and non-isolated tubal factor.