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BACKGROUND: Patients with non-alcoholic fatty liver disease (NAFLD) often exhibit hepatic steatosis and dyslipidemia. Studies have shown that intestinal microorganisms are closely related to the occurrence of NAFLD and atherosclerosis. Our previous study has underscored the protective role of microRNA-30a-5p (miR-30a-5p) against atherosclerosis. METHODS AND RESULTS: In the present study, we aimed to elucidate the effect and underlying mechanism of the intestinal microorganisms of miR-30a-5p knockout (KO) mice on NAFLD. Our findings demonstrated that KO exacerbated high-fat diet (HFD)-induced hepatic steatosis and disrupted liver function, as evidenced by elevated levels of total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, and total bile acids in serum. Fecal microbiota from HFD-fed KO mice induced hepatic steatosis, dyslipidemia, and higher levels of enzymes indicative of liver damage in wild-type mice. Remarkably, KO mice significantly intensified the above effects. 16s rDNA sequencing and metabolomics of the intestinal microbiota in the HFD-treated KO and WT mice showed that the loss of miR-30a-5p resulted in intestinal microbiota imbalance and was highly related to the arachidonic acid metabolic pathway. Targeted metabolomic in the liver tissues unveiled upregulation of COX-related (PGF2a, 8-iso-PGF2a and PGF2) and LOX-related (LTB4, LTD4, 12S-HETE and 15S-HETE) factors in HFD-treated KO mice. Immunohistochemistry and transcriptional analyses showed that miR-30a-5p affected arachidonic acid metabolism through the LOX/COX pathways. Besides, COX/LOX pathways and hepatic steatosis were reversed after reintroducing miR-30a-5p in HFD-treated KO mice. CONCLUSIONS: This study reveals the pivotal mechanism by which miR-30a-5p and intestinal microbes regulate hepatic steatosis and abnormal lipid metabolism, offering promising avenues for NAFLD and atherosclerosis therapeutics. HIGHLIGHTS: MiR-30a-5p deletion aggravated hepatic steatosis and lipid disorder induced by an HFD in mice. Gut microbiota participated in the regulation of hepatic steatosis in the context of miR-30a-5p. Gut microbiota metabolism-related arachidonic acid metabolic pathway contributed to miR-30a-5p-regulated hepatic steatosis and lipid disorder. Reintroducing miR-30a-5p reversed hepatic steatosis and arachidonic acid metabolism disorder caused by HFD and miR-30a-5p deletion.

Assuntos

Ácido Araquidônico , Dieta Hiperlipídica , Microbioma Gastrointestinal , Camundongos Knockout , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ácido Araquidônico/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL

RESUMO

Background/purpose: 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) primary Sjögren's syndrome (SS) diagnostic criteria did not incorporate radiographic examination while staging SS according to salivary gland imaging and serological autoantibody tests was not discussed. The aim is to study the value of parotid sialography for diagnosing SS, and to initially explore the method of staging SS based on the results of imaging and serological autoantibody tests. Materials and methods: 287 patients' clinical records were included. The sensitivity and specificity of parotid sialography in the diagnosis of SS were investigated. SS patients were categorized into early stage (autoantibody positive, imaging does not support SS), active stage (autoantibody positive, imaging supports SS), and quiescent stage (autoantibody negative, imaging supports SS), clinical characteristics of different stages were compared. Results: The sensitivity of parotid sialography for the diagnosis of SS was 82.6%, the specificity was 71.5%. 10-minute USFR of the patients in the active stage (0.18 ± 0.38 ml/10min) was significantly lower than that of early stage (0.34 ± 0.47 ml/10min) and quiescent stage (0.54 ± 0.52 ml/10min), P = 0.010, and the rate of confirmed SS was significantly higher in the active stage (82.9%) than that in the early stage (44.4%) and the quiescent stages (14.8%), P < 0.001. Conclusion: Parotid sialography remains valuable in the diagnosis of SS. Performing imaging and serological autoantibody tests before lip gland biopsy may reduce invasive examinations for patients without significantly increasing the rate of missed diagnosis. According to imaging and serological autoantibody tests, SS can be categorized into early, active, and quiescent stages.

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Rapid advances in single-cell RNA sequencing (scRNA-seq) have made it possible to characterize cell states at a high resolution view for large scale library. scRNA-seq data contains a great deal of biological information, which can be mainly used to discover cell subtypes and track cell development. However, traditional methods face many challenges in addressing scRNA-seq data with high dimensions and high sparsity. For better analysis of scRNA-seq data, we propose a new framework called MSVGAE based on variational graph auto-encoder and graph attention networks. Specifically, we introduce multiple encoders to learn features at different scales and control for uninformative features. Moreover, different noises are added to encoders to promote the propagation of graph structural information and distribution uncertainty. Therefore, some complex posterior distributions can be captured by our model. MSVGAE maps scRNA-seq data with high dimensions and high noise into the low-dimensional latent space, which is beneficial for downstream tasks. In particular, MSVGAE can handle extremely sparse data. Before the experiment, we create 24 simulated datasets to simulate various biological scenarios and collect 8 real-world datasets. The experimental results of clustering, visualization and marker genes analysis indicate that MSVGAE model has excellent accuracy and robustness in analyzing scRNA-seq data.

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In bacterial cellulose (BC)-based living materials, the effective and permanent incorporation of bactericidal agents into BC remains a persistent challenge. In this study, midazole quaternary ammonium salt was grafted onto a dispersion of bacterial cellulose, which was subsequently directly added to the fermentation medium of BC-producing bacteria to obtain BC-based hydrogel materials (BC/BC-[PQVI]Br) with inherent antibacterial properties. The BC/BC-[PQVI]Br hydrogel prepared in this study exhibits favorable tensile properties, with a maximum tensile stress of 970 KPa and water retention for up to 6 h. Moreover, it demonstrates acceptable antibacterial activity against S. aureus (93 %) and E. coli (71 %), respectively. Additionally, the hydrogel displays a high cell survival rate of 98 % after contact with NIH 3T3 cells, indicating its non-cytotoxic nature. Furthermore, the mouse wound experiment confirms the excellent wound healing effect of the hydrogel. This research presents an innovative approach towards developing environmentally friendly active wound dressings with microbial-derived antibacterial functionality.

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OBJECTIVE: To evaluate multisite effects on fetal brain MRI. Specifically, to identify crucial acquisition factors affecting fetal brain structural measurements and developmental patterns, while assessing the effectiveness of existing harmonization methods in mitigating site effects. MATERIALS AND METHODS: Between May 2017 and March 2022, T2-weighted fast spin-echo sequences in-utero MRI were performed on healthy fetuses from retrospectively recruited pregnant volunteers on four different scanners at four sites. A generalized additive model (GAM) was used to quantitatively assess site effects, including field strength (FS), manufacturer (M), in-plane resolution (R), and slice thickness (ST), on subcortical volume and cortical morphological measurements, including cortical thickness, curvature, and sulcal depth. Growth models were selected to elucidate the developmental trajectories of these morphological measurements. Welch's test was performed to evaluate the influence of site effects on developmental trajectories. The comBat-GAM harmonization method was applied to mitigate site-related biases. RESULTS: The final analytic sample consisted of 340 MRI scans from 218 fetuses (mean GA, 30.1 weeks ± 4.4 [range, 21.7-40 weeks]). GAM results showed that lower FS and lower spatial resolution led to overestimations in selected brain regions of subcortical volumes and cortical morphological measurements. Only the peak cortical thickness in developmental trajectories was significantly influenced by the effects of FS and R. Notably, ComBat-GAM harmonization effectively removed site effects while preserving developmental patterns. CONCLUSION: Our findings pinpointed the key acquisition factors in in-utero fetal brain MRI and underscored the necessity of data harmonization when pooling multisite data for fetal brain morphology investigations. KEY POINTS: Question How do specific site MRI acquisition factors affect fetal brain imaging? Finding Lower FS and spatial resolution overestimated subcortical volumes and cortical measurements. Cortical thickness in developmental trajectories was influenced by FS and in-plane resolution. Clinical relevance This study provides important guidelines for the fetal MRI community when scanning fetal brains and underscores the necessity of data harmonization of cross-center fetal studies.

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Staphylococcus aureus (S. aureus)-induced bone loss is a significant challenge in the treatment of osteomyelitis. Our previous study was the first to confirm that granulocyte colony-stimulating factor (G-CSF) mediates S. aureus-induced bone loss. However, the underlying mechanism remains unknown. The objective of this study was to elucidate this. We found G-CSF mediated BMSC senescence and increased IL-1ß concentration of serum and bone marrow in mice after S. aureus infection. Furthermore, we demonstrated that G-CSF promoted the expression of IL1b in murine bone marrow-derived neutrophils. Notably, we identified that IL-1ß mediated BMSC (bone marrow mesenchymal stromal cell) senescence in mice after S. aureus infection. Importantly, IL-1ß neutralizing antibody effectively alleviated BMSC senescence and bone loss caused by S. aureus infection in mice. In terms of molecular mechanism, we found IL-1ß induced BMSC senescence by JNK/P53 and JNK/BCL2 pathways. Collectively, G-CSF promotes IL-1ß production which induces BMSC senescence via JNK/P53 and JNK/BCL2 pathways, leading to S. aureus-induced bone loss. This study identified novel targets for preventing and treating S. aureus-induced bone loss in osteomyelitis.

Assuntos

Fator Estimulador de Colônias de Granulócitos , Interleucina-1beta , Osteomielite , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Interleucina-1beta/metabolismo , Osteomielite/microbiologia , Osteomielite/imunologia , Osteomielite/metabolismo , Infecções Estafilocócicas/imunologia , Fator Estimulador de Colônias de Granulócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Mesenquimais/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neutrófilos/imunologia , Senescência Celular/efeitos dos fármacos , Reabsorção Óssea/imunologia , Células Cultivadas , Masculino , Transdução de Sinais

RESUMO

In this paper, a physics-based ANN assisting method for extracting transient properties of extrinsically triggering photoconductive semiconductor switches (ET-PCSSs) is proposed. It exploits the nonlinear mapping of ANN between transient current (input) and doping concentration (output). According to the basic laws of photoelectric device operating, two types of ANN models are constructed by gaussian and polynomial fitting. The mean absolute error (MAE) of forecasting transient photocurrent can be less than 10 A under low triggering optical powers, which verifies the feasibility of ANN assisting TCAD applied to PCSSs. The results are comparable to computation by Mixed-Mode simulation, yet even thousands of seconds of CPU runtime cost are saved in every period. To improve the robustness of the Poly-ANN predictor, Bayesian optimization (BO) is implemented for minimizing the curl deviation of photocurrent-time curves.

RESUMO

Microplastics, such as polylactic acid (PLA), are ubiquitous environmental pollutants with unclear implications for health impact. This study aims to elucidate the mechanisms of PLA-induced inflammatory liver injury, focusing on disturbance of bile acid metabolism. The in vitro PLA exposure experiment was conducted using HepG2 cells to assess cell viability, cytokine secretion, and effects on bile acid metabolism. In vivo, male C57BL/6 J mice were exposed to PLA for ten days continuously, liver function and histopathological assessment were evaluated after the mice sacrificed. Molecular analyses including quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, were applied to evaluate the expression of bile acid metabolizing enzymes and transporters. PLA exposure resulted in decreased cell viability in HepG2 cells, increased inflammation and altered bile acid metabolism. In mice, PLA exposure resulted in decreased body weight and food intake, impaired liver function, increased hepatic inflammation, altered bile acid profiles, and dysregulated expression of bile acid metabolic pathways. PLA exposure disrupts bile acid metabolism through inhibition of the CYP7A1 enzyme and activation of the FGF-JNK/ERK signaling pathway, contributing to liver injury. These findings highlight the potential hepatotoxic effects of environmentally friendly plastics PLA and underscore the need for further research on their biological impact.

Assuntos

Ácidos e Sais Biliares , Camundongos Endogâmicos C57BL , Poliésteres , Animais , Masculino , Ácidos e Sais Biliares/metabolismo , Humanos , Células Hep G2 , Camundongos , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Microplásticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Sobrevivência Celular/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia

RESUMO

OBJECTIVE: This study aimed to investigate the differences in clinical features, diagnostic examination, treatment, and pathological results between adult-onset and pediatric-onset tethered cord syndrome (TCS). METHODS: The authors searched the PubMed, Embase, and Cochrane Library databases through January 2023 for reports on TCS, extracting information on clinical features, imaging data, treatment modalities, prognosis, and pathological research results. A total of 6135 cases from 246 articles were included in the analysis. This review was conducted in accordance with the 2020 PRISMA guidelines and registered on PROSPERO. RESULTS: The most common adult clinical manifestations were pain, urinary symptoms, and numbness; in children, they were urinary symptoms, skin lesions, bowel symptoms, and unspecific motor deficits. Surgical treatment was the primary approach for both adults and children, with a higher clinical improvement rate observed in adults. However, adults also had a higher rate of surgical complications than children. TCS pathological studies have not yet identified the differences between adults and children, and the pathogenesis of adult-onset TCS requires further investigation. CONCLUSIONS: Adult-onset and pediatric-onset TCS exhibit certain differences in clinical characteristics, diagnostic examinations, and treatments. However, significant differences have not been found in current pathological studies between adults and children. Systematic review registration no.: CRD42023479450 (www.crd.york.ac.uk/prospero).

Assuntos

Defeitos do Tubo Neural , Humanos , Defeitos do Tubo Neural/cirurgia , Defeitos do Tubo Neural/diagnóstico , Criança , Adulto , Idade de Início

RESUMO

Background: Recurrent aphthous ulcer (RAU) had high prevalence and lacked widely recognized treatment. Total glucosides of paeony (TGP) was used in the treatment of RAU in recent years. This study was to summarize the efficacy and safety of TGP in the treatment of RAU. Methods: We searched eight commonly used databases for relevant studies that published before 1 November 2023. Primary outcome was visual analogue scale (VAS). Secondary outcomes included overall response rate, significant response rate, ulcer healing time, interval, number of ulcers, and serum inflammatory factors. We conducted the meta-analysis, assessed risk of bias and the confidence of the evidence, by using Stata 15.0, Review Manager 5.4, and Gradepro. Results: Nine randomized controlled trials (RCTs) encompassing 883 patients with RAU were included in the final analysis. The VAS in the TGP group was lower than that in the control group (MD = -1.18, 95% CI = -1.58 to -0.78, p < 0.001, moderate-certainty evidence), subgroup analysis suggested longer (>8 weeks) medication and observation led to a more significant reduction in pain (p = 0.02). Moreover, TGP had higher overall response rate (RR = 1.18, 95% CI = 1.04 to 1.33, p = 0.008, very low-certainty evidence) and significant response rate (RR = 1.72, 95% CI = 1.38 to 2.14, p < 0.001, very low-certainty evidence), accelerated ulcer healing (MD = -1.79, 95% CI = -2.67 to -0.91, p < 0.001, low-certainty evidence), and extended intervals (MD = 23.60, 95% CI = 14.17 to 33.03, p < 0.001, very low-certainty evidence). The efficacy of TGP in reducing the number of ulcers showed no significant difference compared to the control group (MD = -1.66, 95% CI = -3.60 to 0.28, p = 0.09, low-certainty evidence). Moreover, TGP treatment was associated with a higher incidence of abdominal symptoms (RR = 3.27, 95% CI = 1.62 to 6.60, p < 0.001). Conclusion: TGP appears to hold promise as a widely-used clinical therapeutic option for treating RAU. Nevertheless, further rigorous studies of high quality are required to validate its effectiveness. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=471154, Identifier CRD42023471154.

RESUMO

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Assuntos

Hiperglicemia , Vida Independente , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Vida Independente/estatística & dados numéricos , Hiperglicemia/mortalidade , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Adulto , Idoso , Causas de Morte , Fatores de Risco , Mortalidade/tendências , Estresse Fisiológico , Estados Unidos/epidemiologia , Prognóstico , Estimativa de Kaplan-Meier

RESUMO

Although smoking is a significant risk factor for osteomyelitis, there is limited experimental evidence that nicotine, a key tobacco constituent, is associated with this condition, leaving its mechanistic implications uncharacterized. This study revealed that nicotine promotes Staphylococcus aureus-induced osteomyelitis by increasing Nrf2 and Slc7a11 expression in vivo and in vitro. Inhibition of Slc7a11 using Erastin augmented bacterial phagocytosis/killing capabilities and fortified antimicrobial responses in an osteomyelitis model. Moreover, untargeted metabolomic analysis demonstrated that Erastin mitigated the effects of nicotine on S. aureus-induced osteomyelitis by altering glutamate/glutathione metabolism. These findings suggest that nicotine aggravates S. aureus-induced osteomyelitis by activating the Nrf2/Slc7a11 signaling pathway and that Slc7a11 inhibition can counteract the detrimental health effects of nicotine.

Assuntos

Sistema y+ de Transporte de Aminoácidos , Fator 2 Relacionado a NF-E2 , Nicotina , Osteomielite , Transdução de Sinais , Infecções Estafilocócicas , Staphylococcus aureus , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Nicotina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Osteomielite/microbiologia , Osteomielite/tratamento farmacológico , Osteomielite/metabolismo , Camundongos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Camundongos Endogâmicos C57BL , Humanos , Masculino , Fagocitose/efeitos dos fármacos , Modelos Animais de Doenças

RESUMO

OBJECTIVE: The objective of this study is to investigate the variances in transcriptome gene expression of normal oral mucosa-derived mesenchymal stem cell (OM-MSC), oral leukoplakia-derived MSC (OLK-MSC) and oral squamous cell carcinoma-derived MSC(OSCC-MSC). as Additionally, the study aims to compare the in vitro proliferation, migration, invasion ability, and response to photodynamic therapy (PDT) of these three MSC, HOK, DOK, leuk1, and Cal27 cell lines. METHODS: HOK, DOK, leuk1, Cal27 cells were cultured in vitro. 3 MSC cells were obtained from OM, OLK, OSCC tissue (n = 3) and identified through flow cytometry. They were also cultured in vitro for osteogenic and lipogenic-induced differentiation. Based on the Illumina HiSeq high-throughput sequencing platform, OM-MSC, OLK-MSC, OSCC-MSC (n = 3) were subjected to transcriptome sequencing, functional annotation, and enrichment analysis of differentially expressed genes and related genes. CCK8 assay, wound healing assay, and transwell assay were performed to compare the proliferation, migration, and invasion of the seven types of cells. The 7 cells were incubated with 0, 0.125 mM, 0.25 mM, 0.5 mM, 1 mM, and 2 mM of the photosensitizer (5-aminolevulinic acid, 5-ALA) in vitro. Subsequently, they were irradiated with a 150 mM, 635 nm laser for 1 min, and the cell activity was detected using the CCK8 assay after 24 h. The mitochondrial changes in the 7 cells before and after the treatment of PDT were detected using the JC-10 probe, and the changes in ATP content were measured before and after the PDT treatment. RESULTS: OM-MSC, OLK-MSC, and OSCC-MSC expressed positive MSC surface markers. After osteogenic and lipogenic-induced differentiation culture, stained calcium nodules and lipid droplets were visible, meeting the identification criteria of MSC. Pathway enrichment analysis revealed that the differentially expressed genes (DEGs) of OSCC-MSC compared to OLK-MSC were primarily associated with the PI3K-Akt signaling pathway and tumor-related pathways. OSCC-MSC exhibited stronger migratory and invasive abilities compared to Cal27. The IC50 values required for OM, OLK, and OSCC-derived MSC were lower than those required for epithelial cells treated with PDT, which were 1.396 mM, 0.9063 mM, and 2.924 mM, respectively. Cell membrane and mitochondrial disruption were observed in seven types of cells after 24 h of PDT treatment. However, HOK, DOK, leuk1, and Cal27 cells had an ATP content increased. CONCLUSIONS: OLK, OSCC epithelial cells require higher concentrations of 5-ALA for PDT treatment than MSC of the same tissue origin. The concentration of 5-ALA required increases with increasing cell malignancy. Differences in the response of epithelial cells and MSC to PDT treatment may have varying impacts on OLK recurrence and malignancy.

Assuntos

Carcinoma de Células Escamosas , Movimento Celular , Proliferação de Células , Células Epiteliais , Leucoplasia Oral , Células-Tronco Mesenquimais , Mucosa Bucal , Neoplasias Bucais , Fotoquimioterapia , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Mucosa Bucal/patologia , Mucosa Bucal/citologia , Leucoplasia Oral/patologia , Leucoplasia Oral/terapia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Movimento Celular/efeitos dos fármacos , Movimento Celular/efeitos da radiação , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/terapia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Linhagem Celular Tumoral , Ácido Aminolevulínico/farmacologia , Diferenciação Celular/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos

RESUMO

Background: Previous studies have established blood pressure (BP) as a pivotal factor influencing no-reflow following primary percutaneous coronary intervention (PCI) in patients with ST-elevation acute coronary infarction (STEMI). However, no relevant study has been conducted to investigate the optimal range of BP associated with the lowest risk of no-reflow among STEMI patients so far. Therefore, our objective was to evaluate the association between pre-PCI BP and the occurrence of no-reflow in patients with STEMI. Method: We included 1025 STEMI patients undergoing primary PCI. The BP pre-PCI was categorized into 20-mmHg increments. Logistic models were employed to assess the association of no-reflow with systolic blood pressure (SBP) or diastolic blood pressure (DBP). Three sensitivity analyses were conducted to further confirm the robustness of the association between blood pressure and no-reflow. Results: SBP or DBP exhibited a U-shaped curve association with no-reflow. No-reflow was higher in patients with lower SBP (<100 mmHg) (adjusted hazard ratio (OR) 3.64, 95% confidence interval (CI) 1.84,7.21; p < 0.001) and lower DBP (<60 mmHg) (OR 3.28, 95% CI 1.63,6.49; p < 0.001) [reference: 120 ≤SBP <140; 80 ≤DBP <100 mmHg], respectively. Furthermore, no-reflow was higher in patients with higher SBP (≥160 mmHg) (OR 2.07, 95% CI 1.27,3.36; p = 0.003) and DBP (≥100 mmHg) (OR 3.36, 95% CI 2.07,5.46; p < 0.001), respectively. The results of sensitivity analyses were consistent with the above findings. Conclusion: Maintaining a pre-PCI SBP within the range of 120 to 140 mmHg and a DBP within the range of 80 to 100 mmHg may be confer benefits to patients with STEMI in no-reflow.

Assuntos

Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Pressão Sanguínea

RESUMO

MicroRNAs (miRNA) are endogenous non-coding RNAs, typically around 23 nucleotides in length. Many miRNAs have been founded to play crucial roles in gene regulation though post-transcriptional repression in animals. Existing studies suggest that the dysregulation of miRNA is closely associated with many human diseases. Discovering novel associations between miRNAs and diseases is essential for advancing our understanding of disease pathogenesis at molecular level. However, experimental validation is time-consuming and expensive. To address this challenge, numerous computational methods have been proposed for predicting miRNA-disease associations. Unfortunately, most existing methods face difficulties when applied to large-scale miRNA-disease complex networks. In this paper, we present a novel subgraph learning method named SGLMDA for predicting miRNA-disease associations. For miRNA-disease pairs, SGLMDA samples K-hop subgraphs from the global heterogeneous miRNA-disease graph. It then introduces a novel subgraph representation algorithm based on Graph Neural Network (GNN) for feature extraction and prediction. Extensive experiments conducted on benchmark datasets demonstrate that SGLMDA can effectively and robustly predict potential miRNA-disease associations. Compared to other state-of-the-art methods, SGLMDA achieves superior prediction performance in terms of Area Under the Curve (AUC) and Average Precision (AP) values during 5-fold Cross-Validation (5CV) on benchmark datasets such as HMDD v2.0 and HMDD v3.2. Additionally, case studies on Colon Neoplasms and Triple-Negative Breast Cancer (TNBC) further underscore the predictive power of SGLMDA. The dataset and source code of SGLMDA are available at https://github.com/cunmeiji/SGLMDA.

RESUMO

Objective: To evaluate the prognostic value of the systemic immune-inflammatory index (SII) for predicting in-hospital major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) and establish a relevant nomogram. Methods: This study included 954 AMI patients. We examined three inflammatory factors (SII, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR)) to see which one predicts in-hospital MACEs better. The predictors were subsequently screened using bidirectional stepwise regression method, and a MACE nomogram was constructed via logistic regression analysis. The predictive value of the model was evaluated using the area under the curve (AUC), sensitivity and specificity. In addition, the clinical utility of the nomogram was evaluated using decision curve analysis. We also compared the nomogram with the Global Registry of Acute Coronary Events (GRACE) scoring system. Results: 334 (35.0%) patients had MACEs. The SII (AUC =0.684) had a greater predictive value for in-hospital MACEs in AMI patients than the PLR (AUC =0.597, P<0.001) or NLR (AUC=0.654, P=0.01). The area under the curve (AUC) of the SII-based multivariable model for predicting MACEs, which was based on the SII, Killip classification, left ventricular ejection fraction, age, urea nitrogen (BUN) concentration and electrocardiogram-based diagnosis, was 0.862 (95% CI: 0.833-0.891). Decision curve and calibration curve analysis revealed that SII-based multivariable model demonstrated a good fit and calibration and provided positive net benefits than the model without SII. The predictive value of the SII-based multivariable model was greater than that of the GRACE scoring system (P<0.001). Conclusion: SII is a promising, reliable biomarker for identifying AMI patients at high risk of in-hospital MACEs, and SII-based multivariable model may serve as a quick and easy tool to identify these patients.

RESUMO

Diabetes causes a loss of sensation in the skin, so diabetics are prone to burns when using heating devices. Diabetic scalded skin is often difficult to heal due to the microenvironment of high glucose, high oxidation, and low blood perfusion. The treatment of diabetic scald mainly focuses on three aspects: 1) promote the formation of the epithelium; 2) promote angiogenesis; and 3) maintain intracellular homeostasis. In response to these three major repair factors, we developed a cadherin-responsive hydrogel combined with FGF21 and dental pulp stem cells (DPSCs) to accelerate epithelial formation by recruiting cadherin to the epidermis and promoting the transformation of N cadherin to E cadherin; promoting angiogenesis to increase wound blood perfusion; regulating the stability of lysosomal and activating autophagy to maintain intracellular homeostasis in order to comprehensively advance the recovery of diabetic scald.

RESUMO

This paper studies the class-agnostic counting problem, which aims to count objects regardless of their class, and relies only on a limited number of exemplar objects. Existing methods usually extract visual features from query and exemplar images, compute similarity between them using convolution operations, and finally use this information to estimate object counts. However, these approaches often overlook the scale information of the exemplar objects, leading to lower counting accuracy for objects with multi-scale characteristics. Additionally, convolution operations are local linear matching processes that may result in a loss of semantic information, which can limit the performance of the counting algorithm. To address these issues, we devise a new scale-aware transformer-based feature fusion module that integrates visual and scale information of exemplar objects and models similarity between samples and queries using cross-attention. Finally, we propose an object counting algorithm based on a feature extraction backbone, a feature fusion module and a density map regression head, called SATCount. Our experiments on the FSC-147 and the CARPK demonstrate that our model outperforms the state-of-the-art methods.

Assuntos

Algoritmos , Semântica

RESUMO

Background: Lung cancer is the most common malignant tumor in the world, and its prognosis is still not optimistic. The aim of this study was to establish an immune-related gene (IRG) prognostic index (IRGPI) for lung adenocarcinoma (LUAD) based on IRGs, and to explore the prognosis, molecular and immune features, and response to immune checkpoint inhibitor (ICI) therapy in IRGPI-classified different subgroups of LUAD. Methods: Based on the LUAD transcriptome RNA-sequencing data in TCGA database, the differentially expressed genes (DEGs) were selected. Subsequently, DEGs were intersected with IRGs to obtain differentially expressed immune-related genes (DEIRGs). Weighted gene co-expression network analysis (WGCNA) identified hub genes in DEIRGs. Finally, univariate and multivariate Cox regression analyses were used to build an IRGPI model. Subsequently, TCGA patients were divided into high- and low-risk groups, and the survival of patients in different groups was further analyzed. Besides, we validated the molecular and immune characteristics, relationship with immune checkpoints, angiogenesis-related genes, and immune subtypes distribution in different subgroups. Meanwhile, we further validated the response to ICI therapy in different subgroups. Results: The IRGPI was constructed based on 13 DEIRGs. Compared with the low-risk group, overall survival (OS) was lower in the high-risk group, and the high-risk score was independently associated with poorer OS. Besides, the high-risk score was associated with cell cycle pathway, high mutation rate of TP53 and KRAS, high infiltration of M0 macrophages, and immunosuppressive state, and these patients had poorer prognosis but the TIDE score of the high-risk group was lower than that of the other group, which means that the high-risk group could benefit more from ICI treatment. In contrast, the low-risk score was related to low mutation rate of TP53 and KRAS, high infiltration of plasma cells, and immunoactive state, and these patients had better prognosis but the low-risk group less benefit from ICI treatment based on the results of TIDE score. Conclusions: IRGPI is a prospective biomarker based on IRGs that can distinguish high- and low-risk groups to predict patient prognosis, help characterize the tumor immune microenvironment, and evaluate the benefit of ICI therapy in LUAD.