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1.
Transl Vis Sci Technol ; 11(8): 2, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913416

RESUMO

Purpose: To investigate structural changes in scleral collagen fibers at various tissue depths before and after photosensitized crosslinking (CXL) both isolated scleral patch versus whole globe using second-harmonic generation (SHG) imaging. Methods: Scleral tissues were harvested from Sprague-Dawley rats and separated into three groups: untreated sclera (control), full-thickness scleral patch for CXL (Free Scleral CXL group), and sclera in intact globe for CXL (Globe CXL group). The CXL groups were soaked in 0.1% riboflavin and irradiated with 365 nm ultraviolet-A light (power, 0.45 mW/cm2) for 30 minutes. SHG images were acquired every 5 µm between 10 and 60 µm from the outer scleral surface. Collagen fiber waviness was calculated as the ratio of the total length of a traced fiber and the length of a straight path between the fiber ends. Results: In the Free Scleral CXL group, collagen waviness was significantly increased compared to the control group at 35 to 50 µm (P < 0.05). In the Globe CXL group, collagen waviness was decreased compared to control at all depths with statistical significance (P < 0.05) achieved from 10 to 45 µm. Conclusions: Depending upon its initial state (i.e., free scleral patch versus mechanically loaded intact globe under pressure), collagen may experience different structural changes after CXL. In addition, the extent of the CXL effects may vary at different depths away from the surface. Translational Relevance: Understanding the CXL effects on collagen structure may be important in optimizing the scleral crosslinking protocol for future clinical applications such as preventing myopic progression.


Assuntos
Colágeno , Fármacos Fotossensibilizantes , Riboflavina , Esclera , Animais , Colágeno/química , Reagentes de Ligações Cruzadas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Ratos , Ratos Sprague-Dawley , Riboflavina/farmacologia
3.
Hum Mol Genet ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35925837

RESUMO

Eukaryotic RNA polymerase I (Pol I) products play fundamental roles in ribosomal assembly, protein synthesis, metabolism and cell growth. Abnormal expression of both Pol I transcription-related factors and Pol I products causes a range of diseases, including ribosomopathies and cancers. However, the factors and mechanisms governing Pol I-dependent transcription remain to be elucidated. Here, we report that transcription factor IIB-related factor 1 (BRF1), a subunit of transcription factor IIIB required for RNA polymerase III (Pol III)-mediated transcription, is a nucleolar protein and modulates Pol I-mediated transcription. We showed that BRF1 can be localized to the nucleolus in several human cell types. BRF1 expression correlates positively with Pol I product levels and tumour cell growth in vitro and in vivo. Pol III transcription inhibition assays confirmed that BRF1 modulates Pol I-directed transcription in an independent manner rather than through a Pol III product-to-45S pre-rRNA feedback mode. Mechanistically, BRF1 binds to the Pol I transcription machinery components and can be recruited to the rDNA promoter along with them. Additionally, alteration of BRF1 expression affects the recruitment of Pol I transcription machinery components to the rDNA promoter and the expression of TBP and TAF1A. These findings indicate that BRF1 modulates Pol I-directed transcription by controlling the expression of selective factor 1 subunits. In summary, we identified a novel role of BRF1 in Pol I-directed transcription, suggesting that BRF1 can independently regulate both Pol I- and Pol III-mediated transcription and act as a key coordinator of Pol I and Pol III.

4.
J Environ Sci (China) ; 119: 11-22, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35934456

RESUMO

Manganese (Mn) ores contain substantial concentrations of mercury (Hg), and mining and smelting of Mn ores can bring Hg into the surrounding aquatic environment through atmospheric deposition, leaching of electrolytic Mn residue and Mn gangue dump. However, limited is known that how these processes influence the environmental behaviors of Hg in waterbody. Therefore, the seasonal distribution and existing form of Hg in water and sediment in one Mn ore area in Xiushan County, Chongqing were investigated. Our results showed that the mean Hg and methylmercury (MeHg) concentrations in water (n=35) were 5.8 ± 4.6 ng/L and 0.22 ± 0.14 ng/L, respectively. The mean Hg concentrations in retained riverbed and fluvial bank sediment (n=35) were 0.74 ± 0.26 mg/kg and 0.63 ± 0.27 mg/kg, respectively (the mean MeHg concentrations were 0.64 ± 0.40 µg/kg and 0.51 ± 0.30 µg/kg, respectively). It indicated that the mining and smelting of Mn ores were the main sources of anthropogenic Hg, and Mn may inhibit Hg methylation in rivers in Mn ore areas. Mercury in the bound to iron/ Mn (Fe/Mn) oxides of low crystallinity fraction (Hg-OX) accounted for 4.01% and 5.25% of the total Hg concentrations in the retained riverbed and fluvial bank sediment, respectively. The amount of Hg bound to Fe/Mn oxides in sediment increased significantly due to the manganese mining activities in the investigated area. Therefore, it could be hypothesized that high Hg concentrations in river sediment in Mn mining areas are closely related to high Mn concentration in sediment.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Monitoramento Ambiental , Sedimentos Geológicos/química , Manganês , Mercúrio/análise , Compostos de Metilmercúrio/metabolismo , Mineração , Óxidos , Rios/química , Água , Poluentes Químicos da Água/análise
5.
J Environ Sci (China) ; 119: 139-151, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35934459

RESUMO

The water-level fluctuation zone (WLFZ) has been considered as a hotspot for mercury (Hg) methylation. Flooding-tolerant herbs are gradually acclimated to this water-land ecotone, tending to form substantial root systems for improving erosion resistance. Accompanying rhizosphere microzone plays crucial but unclear roles in methylmercury (MeHg) formation in the WLFZ. Thus, we conducted this study in the WLFZ of the Three Gorges Reservoir, to explore effects of the rhizosphere of a dominant flooding-tolerant herb (bermudagrass) on MeHg production. The elevated Hg and MeHg in rhizosphere soils suggest that the rhizosphere environment provides favorable conditions for Hg accumulation and methylation. The increased bioavailable Hg and microbial activity in the rhizosphere probably serve as important factors driving MeHg formation in the presence of bermudagrass. Simultaneously, the rhizosphere environments changed the richness, diversity, and distribution of hgcA-containing microorganisms. Here, a typical iron-reducing bacterium (Geobacteraceae) has been screened, however, the majority of hgcA genes detected in rhizosphere, near-, and non-rhizosphere soils of the WLFZ were unclassified. Collectively, these results provide new insights into the elevated MeHg production as related to microbial processes in the rhizosphere of perennial herbs in the WLFZ, with general implications for Hg cycling in other ecosystems with water-level fluctuations.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , China , Ecossistema , Monitoramento Ambiental , Mercúrio/análise , Metilação , Solo , Água/análise , Poluentes Químicos da Água/análise
6.
Microbiol Spectr ; : e0154222, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943267

RESUMO

Phytophthora nicotianae is an oomycete pathogen of global significance threatening many important crops. It is mainly controlled by chemosynthetic fungicides, which endangers ecosystem and human health; thus, there is an urgent need to explore alternatives for these fungicides. In this study, a new anti-oomycete aliphatic compound, 2E,4E-decadienoic acid (DDA), was obtained through coculture of Bacillus subtilis Tpb55 and Trichoderma asperellum HG1. Both in vitro and in vivo tests showed that DDA had a strong inhibitory effect against P. nicotianae. In addition, rhizosphere microbiome analysis showed that DDA reduced the relative abundance of Oomycota in rhizosphere soil. Transcriptome sequencing (RNA-Seq) analysis revealed that treatment of P. nicotianae with DDA resulted in significant downregulation of antioxidant activity and energy metabolism, including antioxidant enzymes and ATP generation, and upregulation of membrane-destabilizing activity, such as phospholipid synthesis and degradation. The metabolomic analysis results implied that the pathways influenced by DDA were mainly related to carbohydrate metabolism, energy metabolism, and the cell membrane. The biophysical tests further indicated that DDA produced oxidative stress on P. nicotianae, inhibited antioxidant enzyme and ATPase activity, and increased cell membrane permeability. Overall, DDA exerts inhibitory activity by acting on multiple targets in P. nicotianae, especially on the cell membrane and mitochondria, and can therefore serve as a novel environment-friendly agent for controlling crop oomycete disease. IMPORTANCE P. nicotianae is an oomycete pathogen that is destructive to crops. Although some oomycete inhibitors have been used during crop production, most are harmful to the ecology and lead to pathogen resistance. Alternatively, medium-chain fatty acids have been reported to exhibit antimicrobial activity in the medical field in previous studies; however, their potential as biocontrol agents has rarely been evaluated. Our in vivo and in vitro analyses revealed that the medium-chain fatty acid 2E,4E-decadienoic acid (DDA) displayed specific inhibitory activity against oomycetes. Further analysis indicated that DDA may acted on multiple targets in P. nicotianae, especially on the cell membrane and mitochondria. Our findings highlight the potential of DDA in controlling oomycete diseases. In conclusion, these results provide insights regarding the future use of green and environment-friendly anti-oomycete natural products for the prevention and control of crop oomycete diseases.

7.
Neuro Oncol ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35943350

RESUMO

BACKGROUND: Errors have seldom been evaluated in computer-aided detection on brain metastases. This study aimed to analyze false negatives (FNs) and false positives (FPs) generated by a brain metastasis detection system (BMDS) and by readers. METHODS: A deep learning-based BMDS was developed and prospectively validated in a multicenter, multireader study. Ad hoc secondary analysis was restricted to the prospective participants (148 with 1,066 brain metastases and 152 normal controls). Three trainees and three experienced radiologists read the MRI images without and with the BMDS. The number of FNs and FPs per patient, jackknife alternative free-response receiver operating characteristic figure of merit (FOM), and lesion features associated with FNs were analyzed for the BMDS and readers using binary logistic regression. RESULTS: The FNs, FPs, and the FOM of the stand-alone BMDS were 0.49, 0.38, and 0.97, respectively. Compared with independent reading, BMDS-assisted reading generated 79% fewer FNs (1.98 vs. 0.42, P <0.001); 41% more FPs (0.17 vs. 0.24, P <0.001) but 125% more FPs for trainees (P <0.001); and higher FOM (0.87 vs. 0.98, P <0.001). Lesions with small size, greater number, irregular shape, lower signal intensity, and located on non-brain surface were associated with FNs for readers. Small, irregular, and necrotic lesions were more frequently found in FNs for BMDS. The FPs mainly resulted from small blood vessels for the BMDS and the readers. CONCLUSIONS: Despite the improvement detection performance, attention should be paid to FPs and small lesions with lower enhancement for radiologists, especially for less-experienced radiologists.

8.
J Med Internet Res ; 24(8): e34126, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921135

RESUMO

BACKGROUND: Questionnaires have been used in the past 2 decades to predict the diagnosis of vertigo and assist clinical decision-making. A questionnaire-based machine learning model is expected to improve the efficiency of diagnosis of vestibular disorders. OBJECTIVE: This study aims to develop and validate a questionnaire-based machine learning model that predicts the diagnosis of vertigo. METHODS: In this multicenter prospective study, patients presenting with vertigo entered a consecutive cohort at their first visit to the ENT and vertigo clinics of 7 tertiary referral centers from August 2019 to March 2021, with a follow-up period of 2 months. All participants completed a diagnostic questionnaire after eligibility screening. Patients who received only 1 final diagnosis by their treating specialists for their primary complaint were included in model development and validation. The data of patients enrolled before February 1, 2021 were used for modeling and cross-validation, while patients enrolled afterward entered external validation. RESULTS: A total of 1693 patients were enrolled, with a response rate of 96.2% (1693/1760). The median age was 51 (IQR 38-61) years, with 991 (58.5%) females; 1041 (61.5%) patients received the final diagnosis during the study period. Among them, 928 (54.8%) patients were included in model development and validation, and 113 (6.7%) patients who enrolled later were used as a test set for external validation. They were classified into 5 diagnostic categories. We compared 9 candidate machine learning methods, and the recalibrated model of light gradient boosting machine achieved the best performance, with an area under the curve of 0.937 (95% CI 0.917-0.962) in cross-validation and 0.954 (95% CI 0.944-0.967) in external validation. CONCLUSIONS: The questionnaire-based light gradient boosting machine was able to predict common vestibular disorders and assist decision-making in ENT and vertigo clinics. Further studies with a larger sample size and the participation of neurologists will help assess the generalization and robustness of this machine learning method.


Assuntos
Aprendizado de Máquina , Inquéritos e Questionários , Vertigem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Vertigem/diagnóstico
9.
Medicine (Baltimore) ; 101(31): e29561, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35945780

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is a malignant tumor of urinary system, and clear cell RCC (ccRCC) is the major pathological subtype. A high-frequency mutation in SETD2 gene is related to the occurrence, development, and poor prognosis of RCC. OBJECTIVE: The research of immune-related genes (IRGs) is important to the success of immunotherapy in RCC. The aim of this study was to develop SETD2-related immune prognostic signature (IPS) potentially useful in the prognosis prediction of ccRCC. METHODS: The expression profile, mutation profile, and clinical data related to ccRCC were obtained from the TCGA (Cancer Genome Atlas) and cBioPortal databases. The data of IRGs were downloaded from the ImmPort database. RESULTS: An IPS with 5 genes (PDIA2, PAEP, AMELX, GREM2, and INHA) was constructed by analyzing the correlation between prognosis data and IRGs associated with ccRCC patients with wild type and mutant SETD2 genes. The clinical utility of the IPS and its relationship with immune microenvironment were also studied. CONCLUSIONS: According to the results of this study, the IPS can be a promising biomarker of ccRCC to guide its prognosis and treatment.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Mutação , Prognóstico , Microambiente Tumoral
10.
Front Microbiol ; 13: 944646, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958159

RESUMO

Thermokarst lakes are widely distributed in cold regions as a result of ice-rich permafrost thaw. Disentangling the biogeography of abundant and rare microbes is essential to understanding the environmental influences, assembly mechanisms, and responses to climate change of bacterial communities in thermokarst lakes. In light of this, we assessed the abundant and rare bacterial subcommunities in sediments from thermokarst lakes across the Qinghai-Tibet Plateau (QTP). The operational taxonomic unit (OTU) richness was more strongly associated with location and climate factors for abundant subcommunities, while more strongly associated with physicochemical variables for rare subcommunities. The relative abundance of abundant and rare taxa showed opposite patterns with abundant taxa having greater relative abundance at higher latitude and pH, but at lower mean annual precipitation and nutrients. Both the abundant and rare subcommunities had a clear distribution pattern along the gradient of latitude and mean annual precipitation. Abundant subcommunities were dominantly shaped by dispersal limitation processes (80.9%), while rare subcommunities were shaped almost equally by deterministic (47.3%) and stochastic (52.7%) processes. The balance between stochastic and deterministic processes was strongly environmentally adjusted for rare subcommunities, while not associated with environmental changes for abundant subcommunities. The results shed light on biogeography patterns and structuring mechanisms of bacterial communities in thermokarst lakes, improving our ability to predict the influences of future climate change on these lakes.

11.
Front Cardiovasc Med ; 9: 941946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958407

RESUMO

Post-ischemic angiogenesis is a vital pathophysiological process in diseases such as peripheral arterial disease (PAD), heart ischemia, and diabetic retinopathy. The molecular mechanisms of post-ischemic angiogenesis are complicated and not fully elucidated. The G protein stimulatory alpha subunit (Gsα) is essential for hormone-stimulated cyclic adenosine monophosphate (cAMP) production and is an important regulator for many physiological processes. In the present study, we investigated the role of endothelial Gsα in post-ischemic angiogenesis by generating adult mice with endothelial-specific Gsα deficiency (GsαECKO). GsαECKO mice had impaired blood flow recovery after hind limb ischemic injury, and reduced neovascularization in allograft transplanted tumors. Mechanically, Gsα could regulate the expression of angiogenic factor with G patch and FHA domains 1 (AGGF1) through cAMP/CREB pathway. AGGF1 plays a key role in angiogenesis and regulates endothelial cell proliferation as well as migration. Knockdown of CREB or mutation of the CRE site on the AGGF1 promoter led to reduced AGGF1 promoter activity. In addition, knockdown of AGGF1 reduced the proangiogenic effect of Gsα in endothelial cells, and overexpression of AGGF1 reversed the impaired angiogenesis in GsαECKO mice in vivo. The finding may prove useful in designing new therapeutic targets for treatments of post-ischemic angiogenesis-related diseases.

12.
Int Urol Nephrol ; 2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-35962905

RESUMO

PURPOSE: To study prognostic values of distal ureter involvement (DUI) and survival outcomes in bladder cancer at T1 and T2 stages. METHODS: The national Surveillance, Epidemiology, and End Results database (2004-2015) was applied to obtain bladder cancer patients. We used the Kaplan-Meier method with the log-rank test, subgroup analyses, the multivariable Cox proportional hazard model and propensity score matching (PSM). RESULTS: A total of 490 patients with DUI and 28,498 patients with non-DUI (non-involvement) were enrolled in our study. After 1:1 PSM, 490 matched pairs were picked out. The multivariable Cox regression before and after PSM revealed that the DUI group had a high risk of overall mortality (HR = 1.374, P < 0.001 before PSM; HR = 1.513, P < 0.001 after PSM) and cancer-specific mortality (HR = 1.632, P < 0.001 before PSM; HR = 1.699, P < 0.001 after PSM). The results of survival analyses showed that patients in the DUI group had lower survival probability in OS (P = 0.0011) and CSS (P < 0.0001) analyses. Nevertheless, in the subgroup analysis, significant differences were only observed in the T1 stage in terms of CSS and T2a stage in terms of OS and CSS (all P < 0.05). CONCLUSION: The prognosis of DUI was poorer than that of non-DUI. DUI was an independent risk factor for OM and CSM in bladder cancer at T1 and T2 stages especially for those at T1 and T2a stages.

13.
Circ Res ; : 101161CIRCRESAHA122320771, 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950704

RESUMO

BACKGROUND: Preeclampsia is one of the leading causes of maternal and perinatal morbidity and is characterized by hypertension, inflammation, and placental dysfunction. Gut microbiota plays key roles in inflammation and hypertension. However, its roles and mechanisms in preeclampsia have not been fully elucidated. METHODS: 16S rRNA gene sequencing and targeted metabolomics were conducted on stool samples from 92 preeclamptic patients and 86 normal late-pregnant women. Then, fecal microbiota transplantation and in vitro and in vivo functional experiments were performed to explore the roles and mechanisms of gut microbiota in preeclampsia development. RESULTS: We revealed the gut microbiota dysbiosis in preeclamptic patients, including significant reductions in short-chain fatty acid-producing bacteria and short-chain fatty acids. The gut microbiota of preeclamptic patients significantly exacerbated pathologies and symptoms of preeclamptic rats, whereas the gut microbiota of healthy pregnant women had significant protective effects. Akkermansia muciniphila, propionate, or butyrate significantly alleviated the symptoms of preeclamptic rats. Mechanistically, they significantly promoted autophagy and M2 polarization of macrophages in placental bed, thereby suppressing inflammation. Propionate also significantly promoted trophoblast invasion, thereby improved spiral arterial remodeling. Additionally, we identified a marker set consisting of Akkermansia, Oscillibacter, and short-chain fatty acids that could accurately diagnose preeclampsia. CONCLUSIONS: Our study revealed that gut microbiota dysbiosis is an important etiology of preeclampsia. Gut microbiota and their active metabolites have great potential for the treatment and diagnosis of preeclampsia. Our findings enrich the gut-placenta axis theory and contribute to the development of microecological products for preeclampsia.

14.
Front Immunol ; 13: 905356, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958604

RESUMO

Inflammatory arthritis is an inflammatory disease that involves the joints and surrounding tissues. Synovial hyperplasia often presents when joints become inflamed due to immune cell infiltration. Synovial membrane is an important as well as a highly specific component of the joint, and its lesions can lead to degeneration of the joint surface, causing pain and joint disability or affecting the patients' quality of life in severe cases. Synovial macrophages (SMs) are one of the cellular components of the synovial membrane, which not only retain the function of macrophages to engulf foreign bodies in the joint cavity, but also interact with synovial fibroblasts (SFs), T cells, B cells, and other inflammatory cells to promote the production of a variety of pro-inflammatory cytokines and chemokines, such as TNF-α, IL-1ß, IL-8, and IL-6, which are involved in the pathogenic process of inflammatory arthritis. SMs from different tissue sources have differently differentiated potentials and functional expressions. This article provides a summary on studies pertaining to SMs in inflammatory arthritis, and explores their role in its treatment, in order to highlight novel treatment modalities for the disease.


Assuntos
Artrite Reumatoide , Humanos , Articulações/patologia , Macrófagos/metabolismo , Qualidade de Vida , Membrana Sinovial/patologia
15.
Biomed Environ Sci ; 35(7): 622-632, 2022 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-35945177

RESUMO

Objective: To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC). Methods: In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A. Results: RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells. Conclusion: Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.


Assuntos
Carcinoma Hepatocelular , Hexoquinase/metabolismo , Neoplasias Hepáticas , Proteína Fosfatase 2/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína Fosfatase 2/genética , RNA Interferente Pequeno/metabolismo
16.
Front Immunol ; 13: 920669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911770

RESUMO

Immune-related processes are important in underpinning the properties of clinical traits such as prognosis and drug response in cancer. The possibility to extract knowledge learned by artificial neural networks (ANNs) from omics data to explain cancer clinical traits is a very attractive subject for novel discovery. Recent studies using a version of ANNs called autoencoders revealed their capability to store biologically meaningful information indicating that autoencoders can be utilized as knowledge discovery platforms aside from their initial assigned use for dimensionality reduction. Here, we devise an innovative weight engineering approach and ANN platform called artificial neural network encoder (ANNE) using an autoencoder and apply it to a breast cancer dataset to extract knowledge learned by the autoencoder model that explains clinical traits. Intriguingly, the extracted biological knowledge in the form of gene-gene associations from ANNE shows immune-related components such as chemokines, carbonic anhydrase, and iron metabolism that modulate immune-related processes and the tumor microenvironment play important roles in underpinning breast cancer clinical traits. Our work shows that biological "knowledge" learned by an ANN model is indeed encoded as weights throughout its neuronal connections, and it is possible to extract learned knowledge via a novel weight engineering approach to uncover important biological insights.


Assuntos
Neoplasias da Mama , Descoberta do Conhecimento , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Aprendizagem , Redes Neurais de Computação , Neurônios/fisiologia , Microambiente Tumoral
17.
Spectrochim Acta A Mol Biomol Spectrosc ; 283: 121736, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35973381

RESUMO

Based on the fluorescence resonance energy transfer (FRET), a ratiometric fluorescent probe (NQ) was successfully designed and synthesized, in which quinolinone moiety was selected as the energy donor and naphthalimide block as the energy acceptor. NQ has a super large Stokes shift (231 nm) and a big quantum yield (0.463). Compared with previously reported probes with similar recognition sites, NQ can high sensitively and selectively recognize ClO- with a much low limit of detection (LOD = 21 nM) and extremely rapid response time (20 s). NQ has a strong anti-interference effect and a color change in the solution which can be seen by the "naked eye". Moreover, NQ can be applied to detect ClO- in real water samples and living cells imaging.

18.
Eur J Immunol ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35976660

RESUMO

There is an urgent need for animal models of COVID-19 to study immunopathogenesis and test therapeutic intervenes. In this study we showed that NSG mice engrafted with human lung (HL) tissue (NSG-L mice) could be infected efficiently by SARS-CoV-2, and that live virus capable of infecting Vero cells was found in the HL grafts and multiple organs from infected NSG-L mice. RNA-Sequencing (RNA-Seq) identified a series of differentially expressed genes, which are enriched in viral defense responses, chemotaxis, interferon stimulation and pulmonary fibrosis, between HL grafts from infected and control NSG-L mice. Furthermore, when infected with SARS-CoV-2, humanized mice with both human immune system (HIS) and autologous HL grafts (HISL mice) had bodyweight loss and hemorrhage and immune cell infiltration in HL grafts, which were not observed in immunodeficient NSG-L mice, indicating the development of anti-viral immune responses in these mice. In support of this possibility, the infected HISL mice showed bodyweight recovery and lack of detectable live virus at the later time. These results demonstrate that NSG-L and HISL mice are susceptible to SARS-CoV-2 infection, offering a useful in vivo model for studying SARS-CoV-2 infection and the associated immune response and immunopathology, and testing anti-SARS-CoV-2 therapies. This article is protected by copyright. All rights reserved.

19.
Sci Total Environ ; 849: 157765, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35926624

RESUMO

Improving forage productivity with lower greenhouse gas (GHG) emissions from limited grassland has been a hotspot of interest in global agricultural production. In this study, we analyzed the effects of grasses (tall fescue, smooth bromegrass), legume (alfalfa), and alfalfa-grass (alfalfa + smooth bromegrass and alfalfa + tall fescue) mixtures on GHG emissions, net global warming potential (Net GWP), yield-based greenhouse gas intensity (GHGI), soil chemical properties and forage productivity in cultivated grassland in northwest China during 2020-2021. Our results demonstrated that alfalfa-grass mixtures significantly improved forage productivity. The highest total dry matter yield (DMY) during 2020 and 2021 was obtained from alfalfa-tall fescue (11,311 and 13,338 kg ha-1) and alfalfa-smooth bromegrass mixtures (10,781 and 12,467 kg ha-1). The annual cumulative GHG emissions from mixtures were lower than alfalfa monoculture. Alfalfa-grass mixtures significantly reduced GHGI compared with the grass or alfalfa monocultures. Furthermore, results indicated that grass, alfalfa and alfalfa-grass mixtures differentially affected soil chemical properties. Lower soil pH and C/N ratio were recorded in alfalfa monoculture. Alfalfa and mixtures increased soil organic carbon (SOC) and soil total nitrogen (STN) contents. Importantly, alfalfa-grass mixtures are necessary for improving forage productivity and mitigating the GHG emissions in this region. In conclusion, the alfalfa-tall fescue mixture lowered net GWP and GHGI in cultivated grassland while maintaining high forage productivity. These advanced agricultural practices could contribute to the development of climate-sustainable grassland production in China.

20.
Front Oncol ; 12: 964614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35965571

RESUMO

Background and aims: Recently, the effectiveness of "textbook outcomes (TO)" in the evaluation of surgical quality has been recognized by more and more scholars. This study tended to examine the association between preoperative albumin-bilirubin (ALBI) grades and the incidence of achieving or not achieving TO (non-TO) in patients with hepatocellular carcinoma (HCC) undergoing laparoscopic hepatectomy. Methods: The patients were stratified into two groups: ALBI grade 1 (ALBI ≤ -2.60) and ALBI grade 2/3 (ALBI > -2.60). The characteristics of patients and the incidence of non-TO were compared. Multivariate analyses were performed to determine whether ALBI grade was independently associated with TO. Results: In total, 378 patients were enrolled, including 194 patients (51.3%) in the ALBI grade 1 group and 184 patients (48.7%) in the ALBI grade 2/3 group. In the whole cohort, 198 patients (52.4%) did not achieve TO, and the incidence of non-TO in the ALBI grade 2/3 group was obviously higher than that in the ALBI grade 1 group (n = 112, 60.9% vs. n = 86, 44.3%, P = 0.001). The multivariate analyses showed that ALBI grade 2/3 was an independent risk factor for non-TO (OR: 1.95, 95%CI: 1.30-2.94, P = 0.023). Conclusions: More than half (52.4%) of the patients with hepatocellular carcinoma did not achieve TO after laparoscopic hepatectomy, and preoperative ALBI grade 2/3 was significantly associated with non-TO. Improving the liver function reserve of patients before operation, thereby reducing the ALBI grade, may increase the probability for patients to reach TO and enable patients to benefit more from surgery.

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