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1.
Chem Commun (Camb) ; 60(84): 12241-12244, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39363686

RESUMO

The efficient preparation of long-chain amines via a one-step transfer-hydrogenation/reductive-amination reaction (THRA) of polyenals has been achieved. This strategy, which combines transfer hydrogenation and reductive amination, significantly enhances the synthetic efficiency of amino compounds. Additionally, this protocol offers a practical method for carbon-chain elongation/amination to construct long-chain amino compounds. The reaction system exhibits remarkable versatility in substrate scope using a non-noble ruthenium catalyst with formate and isopropanol as hydrogen sources, making it an appealing method for drug synthesis and molecular modification.

2.
Sci Total Environ ; 954: 176377, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299320

RESUMO

In dryland farming, plastic film mulching can significantly increase crop yields, but the resulting residues impair soil health. Heretofore, only few studies had examined how heat treatment facilitates the rapid degradation of polyethylene (PE) residual films. Herein, we characterized the variations in micro-morphology, functional groups, and crystallinity of PE residual films after moderate heat exposure using a self-made flame-spraying equipment. The results revealed that solid residues (SR) obtained from flame-spraying showed a gravimetric weight loss of 9.39 %-15.35 % compared with untreated PE residual films (UPF). Scanning electron microscope equipped with energy dispersive X-ray spectroscopy revealed considerable pits, cracks, and visible roughness in appearance and an increase in the oxygen-to-carbon (O/C) atomic ratio. Fourier-transform infrared spectroscopy identified characteristic oxygen-containing functional groups and double bonds. X-ray diffraction showed that flame-spraying treatments did not alter the crystal form of polymer, but increased the crystallinity. Higher flame-spraying temperatures resulted in larger oxygen-containing bond indices and lower crystallinity, suggesting a more severe decomposition of PE residual film. The possible volatile gaseous products at different reaction temperatures were predicted using thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TG-FTIR). Degradation of the PE residual film started at 220 °C, and concentrated release of major products such as long-chain aliphatic hydrocarbons, ketones, and CO2, occurred in the temperature range of 340 °C-440 °C. These results highlighted the effectiveness of the moderate flame-spraying method in accelerating rapid decomposition of residual films, and a flame-spraying temperature range of 220 °C-340 °C should be recommended to avoid potential environmental risks induced by the release of large quantities of degradation products. This study will contribute to enhance our understanding of the thermal oxidative degradation behavior of PE waste and provide a scientific basis for the rapid and clean establishment of PE residual films mitigation in agricultural fields.

3.
Plants (Basel) ; 13(18)2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39339586

RESUMO

Tillage practices significantly influence crop yield and soil quality. This study investigated the impact of rotary tillage (RT) and deep tillage (DT) on soil properties, microbial diversity, and melon (Cucumis melo L.) root growth and yield. RT involved breaking up the topsoil to a depth of 15 cm using a rotary tiller, while DT employed a rotary tiller followed by a moldboard plow to turn the soil layer over to a depth of 35 cm. The melon variety "Nasimi" was used as the material. Our findings revealed a remarkable response of soil phosphorus to tillage practices. High-throughput sequencing results revealed a significant impact of tillage practices on the soil fungal composition, richness, and diversity but little impact on the bacterial communities. Compared to RT, DT markedly enhanced melon root length, root surface area, root volume, and mean root diameter by 47.42%, 56.70%, 58.83%, and 27.28%, respectively. Additionally, DT treatments significantly increased melon yield (53.46%) compared to RT. The results indicate that DT improves soil nutrient availability, affects soil fungal community characteristics, and optimizes root distribution in soil, thereby improving melon yield. The findings offer valuable theoretical insights for the implementation of effective tillage practices in open-field melon cultivation.

4.
J Proteome Res ; 23(10): 4658-4673, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39298182

RESUMO

The dormancy of cancer stem cells is a major factor leading to drug resistance and a high rate of late recurrence and mortality in estrogen receptor-positive (ER+) breast cancer. Previously, we demonstrated that a stiffer matrix induces tumor cell dormancy and drug resistance, whereas a softened matrix promotes tumor cells to exhibit a stem cell state with high proliferation and migration. In this study, we present a comprehensive analysis of the proteome and phosphoproteome in response to gradient changes in matrix stiffness, elucidating the mechanisms behind cell dormancy-induced drug resistance. Overall, we found that antiapoptotic and membrane transport processes may be involved in the mechanical force-induced dormancy resistance of ER+ breast cancer cells. Our research provides new insights from a holistic proteomic and phosphoproteomic perspective, underscoring the significant role of mechanical forces stemming from the stiffness of the surrounding extracellular matrix as a critical regulatory factor in the tumor microenvironment.


Assuntos
Neoplasias da Mama , Matriz Extracelular , Células-Tronco Neoplásicas , Fosfoproteínas , Proteômica , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Matriz Extracelular/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Feminino , Proteômica/métodos , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Proteoma/análise , Proteoma/metabolismo , Microambiente Tumoral , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Células MCF-7
6.
iScience ; 27(9): 110602, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39211577

RESUMO

Clinical research indicates that SARS-CoV-2 infection is linked to several neurological consequences, and the virus is still spreading despite the availability of vaccinations and antiviral medications. To determine how hosts respond to SARS-CoV-2 infection, we employed LC-MS/MS to perform ubiquitinome and proteome analyses of the brain cortexes from K18-hACE2 mice in the presence and absence of SARS-CoV-2 infection. A total of 8,024 quantifiable proteins and 5,220 quantifiable lysine ubiquitination (Kub) sites in 2023 proteins were found. Glutamatergic synapse, calcium signaling pathway, and long-term potentiation may all play roles in the neurological consequences of SARS-CoV-2 infection. Then, we observed possible interactions between 26 SARS-CoV-2 proteins/E3 ubiquitin-protein ligases/deubiquitinases and several differentially expressed mouse proteins or Kub sites. We present the first description of the brain cortex ubiquitinome in K18-hACE2 mice, laying the groundwork for further investigation into the pathogenic processes and treatment options for neurological dysfunction following SARS-CoV-2 infection.

7.
Biochem Biophys Res Commun ; 739: 150568, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39178797

RESUMO

Doxorubicin (DOX), as a first-line anticancer drug, is widely used in the treatment of various cancers. However, its clinical application is restricted due to its severe cardiac toxicity. Previous studies have indicated exercise training can alleviate the DOX-induced cardiotoxicity (DIC), but the underlying mechanism remains unclear. Our research has discovered, post-exercise, an elevated expression level of mir-17-3p, but in DIC its level decreases. Therefore, we further studied the effect of exercise mir-17-3p axis on DIC. In vivo, we simulated DIC mouse model, followed by an intervention using swimming and adenovirus to inhibit mir-17-3p. We found that inhibition of mir-17-3p can weaken the protection of exercise against DIC, presenting as weakened heart function. Besides, the levels of Malondialdehyde and Fe2+ in the cardiac tissue increased, along with diminished glutathione peroxidase 4 and Solute Carrier Family 7 Member 11 levels, and a decline in the concentration of glutathione, causing an increase in ferroptosis. Moreover, in vitro, we used dual-luciferase assay to confirm that Kelch Like ECH Associated Protein 1 (KEAP1) can be a target gene of mir-17-3p. We used Keap1/NFE2 Like BZIP Transcription Factor 2 (NRF2) inhibitor brusatol and Stimulator of Interferon Response CGAMP Interactor 1 (STING) agonist SR-717 to verify the mir-17-3p/KEAP1 axis can affect the Cyclic GMP-AMP Synthase (CGAS)/STING pathway, leading to further ferroptosis in DIC. This manifested as a reduction in ferroptosis. In summary, our research suggests swimming training enhances the levels of mir-17-3p, thereby activating the KEAP1/NRF2 pathway, and weakening the CGAS/STING pathway, improving ferroptosis in DIC.

8.
PLOS Glob Public Health ; 4(7): e0003387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38990924

RESUMO

Understanding public preferences concerning vaccination is critical to inform pandemic response strategies. To investigate Chinese adults' preferences regarding COVID-19 vaccine attributes, we conducted a cross-sectional online survey in 12,000 Chinese adults in June-July, 2021. Participants were requested to answer a series of discrete choice questions related to hypothetical COVID-19 vaccines. Using mixed logit models, our analysis revealed that participants had a higher preference for COVID-19 vaccines with longer duration of protection (coefficient: 1.272, 95% confidence interval [1.016 to 1.529]) and higher efficacy (coefficient: 1.063, [0.840, 1.287]). Conversely, participants demonstrated a lower preference associated with higher risk of rare but serious side-effects (coefficient: -1.158, [-1.359, -0.958]), oral administration (coefficient: -0.211, [-0.377, -0.046]), more doses (coefficient: -0.148, [-0.296, 0.000]) and imported origin (coefficient: -0.653, [-0.864, -0.443]). Moreover, preferences were heterogeneous by individual factors: highly educated participants were more sensitive to the negative vaccine attributes including price (coefficient -0.312, [-0.370, -0.253]) and imported vaccine (coefficient -0.941, [-1.186, -0.697]); there was also substantial heterogeneity in vaccine preferences with respect to age group, marital status, work status, income, chronic diagnosis history, COVID-19 vaccination history and geographic regions. As the first study of examining the public preferences for COVID-19 vaccine in China with a large nationwide sample of 12,000 adults, our results indicate that future vaccine should pose lower risk, possess longer protection period, have higher efficacy, be domestically produced, and have lower costs to increase the COVID-19 vaccination coverage. Our current study findings from this study provide insights and recommendations for not only COVID-19 vaccine design but also vaccine attribute preferences to increase vaccine uptake in potential future pandemics.

9.
Nat Commun ; 15(1): 6123, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033143

RESUMO

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major cause of salmonellosis, and the emergence of multidrug-resistant pathovariants has become a growing concern. Here, we investigate a distinct rough colony variant exhibiting a strong biofilm-forming ability isolated in China. Whole-genome sequencing on 2,212 Chinese isolates and 1,739 publicly available genomes reveals the population structure and evolutionary history of the rough colony variants. Characterized by macro, red, dry, and rough (mrdar) colonies, these variants demonstrate enhanced biofilm formation at 28 °C and 37 °C compared to typical rdar colonies. The mrdar variants exhibit extensive multidrug resistance, with significantly higher resistance to at least five classes of antimicrobial agents compared to non-mrdar variants. This resistance is primarily conferred by an IncHI2 plasmid harboring 19 antimicrobial resistance genes. Phylogenomic analysis divides the global collections into six lineages. The majority of mrdar variants belong to sublineage L6.5, which originated from Chinese smooth colony strains and possibly emerged circa 1977. Among the mrdar variants, upregulation of the csgDEFG operons is observed, probably due to a distinct point mutation (-44G > T) in the csgD gene promoter. Pangenome and genome-wide association analyses identify 87 specific accessory genes and 72 distinct single nucleotide polymorphisms associated with the mrdar morphotype.


Assuntos
Antibacterianos , Biofilmes , Farmacorresistência Bacteriana Múltipla , Genoma Bacteriano , Filogenia , Salmonella typhimurium , Sequenciamento Completo do Genoma , Salmonella typhimurium/genética , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Biofilmes/efeitos dos fármacos , China , Genoma Bacteriano/genética , Plasmídeos/genética , Testes de Sensibilidade Microbiana , Humanos , Infecções por Salmonella/microbiologia
10.
Syst Rev ; 13(1): 189, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030630

RESUMO

BACKGROUND: The COVID-19 pandemic has caused a large mortality and morbidity burden globally. For individuals, a strong immune response is the most effective means to block SARS-CoV-2 infection. To inform clinical case management of COVID-19, development of improved vaccines, and public health policy, a better understanding of antibody response dynamics and duration following SARS-CoV-2 infection and after vaccination is imperatively needed. METHODS: We systematically analyzed antibody response rates in naturally infected COVID-19 patients and vaccinated individuals. Specifically, we searched all published and pre-published literature between 1 December 2019 and 31 July 2023 using MeSH terms and "all field" terms comprising "COVID-19" or "SARS-CoV-2," and "antibody response" or "immunity response" or "humoral immune." We included experimental and observational studies that provided antibody positivity rates following natural COVID-19 infection or vaccination. A total of 44 studies reporting antibody positivity rate changes over time were included. RESULTS: The meta-analysis showed that within the first week after COVID-19 symptom onset/diagnosis or vaccination, antibody response rates in vaccinated individuals were lower than those in infected patients (p < 0.01), but no significant difference was observed from the second week to the sixth month. IgG, IgA, and IgM positivity rates increased during the first 3 weeks; thereafter, IgG positivity rates were maintained at a relatively high level, while the IgM seroconversion rate dropped. CONCLUSIONS: Antibody production following vaccination might not occur as quickly or strongly as after natural infection, and the IgM antibody response was less persistent than the IgG response.


Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Vacinação , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , SARS-CoV-2/imunologia , Imunidade Inata/imunologia , Formação de Anticorpos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia
11.
BMC Musculoskelet Disord ; 25(1): 509, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38956545

RESUMO

BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values < 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.


Assuntos
Tecido Adiposo , Dor Lombar , Vértebras Lombares , Músculos Paraespinais , Humanos , Feminino , Masculino , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Dor Lombar/diagnóstico por imagem , Estudos Prospectivos , Estudos Transversais , Pessoa de Meia-Idade , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/patologia , Adulto , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Idoso , Imageamento por Ressonância Magnética , Dor Crônica/diagnóstico por imagem
12.
Med Image Anal ; 97: 103248, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38941859

RESUMO

The conventional pretraining-and-finetuning paradigm, while effective for common diseases with ample data, faces challenges in diagnosing data-scarce occupational diseases like pneumoconiosis. Recently, large language models (LLMs) have exhibits unprecedented ability when conducting multiple tasks in dialogue, bringing opportunities to diagnosis. A common strategy might involve using adapter layers for vision-language alignment and diagnosis in a dialogic manner. Yet, this approach often requires optimization of extensive learnable parameters in the text branch and the dialogue head, potentially diminishing the LLMs' efficacy, especially with limited training data. In our work, we innovate by eliminating the text branch and substituting the dialogue head with a classification head. This approach presents a more effective method for harnessing LLMs in diagnosis with fewer learnable parameters. Furthermore, to balance the retention of detailed image information with progression towards accurate diagnosis, we introduce the contextual multi-token engine. This engine is specialized in adaptively generating diagnostic tokens. Additionally, we propose the information emitter module, which unidirectionally emits information from image tokens to diagnosis tokens. Comprehensive experiments validate the superiority of our methods.


Assuntos
Pneumoconiose , Humanos , Pneumoconiose/diagnóstico por imagem , Pneumoconiose/diagnóstico , Algoritmos
13.
Mol Cancer ; 23(1): 127, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38880903

RESUMO

The clinical heterogeneity of early-stage endometrial cancer (EC) is worthy of further study to identify high-quality prognostic markers and their potential role in aggressive tumor behavior. Mutation of TP53 was considered as an important primary triage in modified molecular typing for EC, it still cannot precisely predict the prognosis of EC. After proteomic analysis of cancer and para-cancerous tissues from 24 early-stage endometrioid EC patients with different survival outcomes, 13 differentially expressed proteins were screen out while 2 proteins enriched in p53 signaling pathway were further identified by single-cell transcriptome (scRNA-seq). Interestingly, tumor necrosis factor type-1 receptor-associated protein (TRAP1) and calmodulin-regulated spectrin-associated protein family member 3 (CAMSAP3) were found to be significantly downregulated in the specific cell cluster. Expectedly, the signature genes of TRAP1low/CAMSAP3low cluster included classical oncogenes. Moreover, close cellular interactions were observed between myeloid cells and the TRAP1low/CAMSAP3low cluster after systematically elucidating their relationship with tumor microenvironment (TME). The expression of TRAP1 and CAMSAP3 was verified by immunohistochemistry. Thus, a novel prediction model combining TRAP1, CAMSAP3 and TP53 was construct by multi-omics. Compared with the area under the curve, it demonstrated a significantly improvemrnt in the diagnostic efficacy in EC patients from TCGA bank. In conclusion, this work improved the current knowledge regarding the prognosis of early-stage EC through proteomics and scRNA-seq. These findings may lead to improvements in precise risk stratification of early-stage EC patients.


Assuntos
Biomarcadores Tumorais , Neoplasias do Endométrio , Regulação Neoplásica da Expressão Gênica , Estadiamento de Neoplasias , Proteômica , Humanos , Feminino , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Proteômica/métodos , Microambiente Tumoral/genética , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Transcriptoma , Multiômica , Proteínas de Choque Térmico HSP90
14.
Sci Rep ; 14(1): 11993, 2024 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796576

RESUMO

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63-0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.


Assuntos
Doença das Coronárias , Estudo de Associação Genômica Ampla , Lipídeos , Análise da Randomização Mendeliana , Globulina de Ligação a Hormônio Sexual , Feminino , Humanos , Masculino , Doença das Coronárias/genética , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Lipídeos/sangue , Análise de Mediação , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/metabolismo , Globulina de Ligação a Hormônio Sexual/genética , Globulina de Ligação a Hormônio Sexual/análise
15.
BMC Cardiovasc Disord ; 24(1): 281, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811879

RESUMO

BACKGROUND: Acute coronary syndrome due to coronary artery embolism in the setting of ascending aortic thrombus is an uncommon condition, even rarer when there is no aortic pathology such as aneurysm, severe atherosclerosis, aortic dissection, or thrombophilia (whether inherited or acquired). CASE PRESENTATION: We report a case of a 58-year-old male presented with acute chest pain, electrocardiogram showing non-ST-elevation acute coronary syndrome. The computed tomography angiography of coronary artery revealed a mural thrombus in the proximal part of ascending aorta, located above the left coronary artery ostium, without any aortic pathologies. With the exception of hypertension and cigarette smoking, no other risk factors were identified in this patient that may increase the risk of thrombosis. Given the life-threatening risk of interventional therapy and surgery, the patient determinedly opted for anticoagulant and dual antiplatelet therapy. Then he experienced the reoccurrence of chest pain after 6-day treatment, progressed to anterior and inferior ST-segment elevation myocardial infarction. Coronary artery embolism originating from the ascending aortic thrombus was suspected. Considering the hemodynamic instability of the patient, the medical treatment was continued and bridged to warfarin and aspirin after discharge. Follow-up computed tomography angiography at 6 months showed no obstruction in coronary artery and complete resolution of the thrombus. No thromboembolic events occurred henceforward. CONCLUSIONS: Acute coronary syndrome could be a manifestation of secondary coronary embolism due to ascending aortic thrombus. Currently, there is no standardized guideline for the treatment of aortic mural thrombus, individualized treatment is recommended. When surgical therapy is not applicable for the patient, anticoagulation and dual antiplatelet treatment are alternative treatments that may successfully lead to the resolution of the aortic thrombus.


Assuntos
Síndrome Coronariana Aguda , Doenças da Aorta , Recidiva , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/etiologia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico por imagem , Resultado do Tratamento , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etiologia , Doenças da Aorta/complicações , Trombose/diagnóstico por imagem , Trombose/etiologia , Trombose/tratamento farmacológico , Anticoagulantes/uso terapêutico , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Infarto do Miocárdio sem Supradesnível do Segmento ST/etiologia , Aortografia
16.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(2): 147-153, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38686709

RESUMO

Objective To screen out the biomarkers linked to prognosis of breast invasive carcinoma based on the analysis of transcriptome data by random forest (RF),extreme gradient boosting (XGBoost),light gradient boosting machine (LightGBM),and categorical boosting (CatBoost). Methods We obtained the expression data of breast invasive carcinoma from The Cancer Genome Atlas and employed DESeq2,t-test,and Cox univariate analysis to identify the differentially expressed protein-coding genes associated with survival prognosis in human breast invasive carcinoma samples.Furthermore,RF,XGBoost,LightGBM,and CatBoost models were established to mine the protein-coding gene markers related to the prognosis of breast invasive cancer and the model performance was compared.The expression data of breast cancer from the Gene Expression Omnibus was used for validation. Results A total of 151 differentially expressed protein-coding genes related to survival prognosis were screened out.The machine learning model established with C3orf80,UGP2,and SPC25 demonstrated the best performance. Conclusions Three protein-coding genes (UGP2,C3orf80,and SPC25) were screened out to identify breast invasive carcinoma.This study provides a new direction for the treatment and diagnosis of breast invasive carcinoma.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Aprendizado de Máquina , Humanos , Neoplasias da Mama/genética , Feminino , Biomarcadores Tumorais/genética , Prognóstico , Perfilação da Expressão Gênica
17.
Mol Cell Proteomics ; 23(6): 100770, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641226

RESUMO

Inhalation of crystalline silica dust induces incurable lung damage, silicosis, and pulmonary fibrosis. However, the mechanisms of the lung injury remain poorly understood, with limited therapeutic options aside from lung transplantation. Posttranslational modifications can regulate the function of proteins and play an important role in studying disease mechanisms. To investigate changes in posttranslational modifications of proteins in silicosis, combined quantitative proteome, acetylome, and succinylome analyses were performed with lung tissues from silica-injured and healthy mice using liquid chromatography-mass spectrometry. Combined analysis was applied to the three omics datasets to construct a protein landscape. The acetylation and succinylation of the key transcription factor STAT1 were found to play important roles in the silica-induced pathophysiological changes. Modulating the acetylation level of STAT1 with geranylgeranylacetone effectively inhibited the progression of silicosis. This report revealed a comprehensive landscape of posttranslational modifications in silica-injured mouse and presented a novel therapeutic strategy targeting the posttranslational level for silica-induced lung diseases.


Assuntos
Lisina , Processamento de Proteína Pós-Traducional , Proteoma , Fator de Transcrição STAT1 , Silicose , Animais , Silicose/metabolismo , Silicose/tratamento farmacológico , Silicose/patologia , Fator de Transcrição STAT1/metabolismo , Proteoma/metabolismo , Lisina/metabolismo , Acetilação/efeitos dos fármacos , Camundongos , Dióxido de Silício , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Proteômica/métodos , Masculino , Ácido Succínico/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-38687336

RESUMO

Aims: Diabetic heart damage can lead to cardiomyocyte death, which endangers human health. Baicalin (BAI) is a bioactive compound that plays an important role in cardiovascular diseases. Sentrin/SUMO-specific protease 1 (SENP1) regulates the de-small ubiquitin-like modifier (deSUMOylation) process of Sirtuin 3 (SIRT3) and plays a crucial role in regulating mitochondrial mass and preventing cell injury. Our hypothesis is that BAI regulates the deSUMOylation level of SIRT3 through SENP1 to enhance mitochondrial quality control and prevent cell death, ultimately improving diabetic cardiomyopathy (DCM). Results: The protein expression of SENP1 decreased in cardiomyocytes induced by high glucose and in db/db mice. The cardioprotective effects of BAI were eliminated by silencing endogenous SENP1, whereas overexpression of SENP1 showed similar cardioprotective effects to those of BAI. Furthermore, co-immunoprecipitation experiments showed that BAI's cardioprotective effect was due to the inhibition of the SUMOylation modification level of SIRT3 by SENP1. Inhibition of SENP1 expression resulted in an increase in SUMOylation of SIRT3. This led to increased acetylation of mitochondrial protein, accumulation of reactive oxygen species, impaired autophagy, impaired mitochondrial oxidative phosphorylation, and increased cell death. None of these changes could be reversed by BAI. Conclusion: BAI improves DCM by promoting SIRT3 deSUMOylation through SENP1, restoring mitochondrial stability, and preventing the cell death of cardiomyocytes. Innovation: This study proposes for the first time that SIRT3 SUMOylation modification is involved in the development of DCM and provides in vivo and in vitro data support that BAI inhibits cardiomyocyte ferroptosis and apoptosis in DCM through SENP1. [Figure: see text].

20.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385873

RESUMO

Lysine lactylation (Kla) is a newly discovered posttranslational modification that is involved in important life activities, such as glycolysis-related cell function, macrophage polarization and nervous system regulation, and has received widespread attention due to the Warburg effect in tumor cells. In this work, we first design a natural language processing method to automatically extract the 3D structural features of Kla sites, avoiding potential biases caused by manually designed structural features. Then, we establish two Kla prediction frameworks, Attention-based feature fusion Kla model (ABFF-Kla) and EBFF-Kla, to integrate the sequence features and the structure features based on the attention layer and embedding layer, respectively. The results indicate that ABFF-Kla and Embedding-based feature fusion Kla model (EBFF-Kla), which fuse features from protein sequences and spatial structures, have better predictive performance than that of models that use only sequence features. Our work provides an approach for the automatic extraction of protein structural features, as well as a flexible framework for Kla prediction. The source code and the training data of the ABFF-Kla and the EBFF-Kla are publicly deposited at: https://github.com/ispotato/Lactylation_model.


Assuntos
Lisina , Processamento de Linguagem Natural , Sequência de Aminoácidos , Domínios Proteicos , Processamento de Proteína Pós-Traducional
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