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Emergency medical retrieval services (EMRS) in remote Indigenous islands is rarely investigated. We analyzed the characteristics of patients who underwent EMRS in Lanyu, an offshore island of Taiwan, from January 1, 2014 to December 31, 2021. The need for EMRS for Lanyu Indigenous residents (N=132, 3.83) was almost 1.5-fold and 100-fold for non-Indigenous residents (N=16, 2.64) and tourists (N=40, 0.04), respectively. The resident group had a longer hospitalization (12.0 ± 12.9 vs. 5.9 ± 11.7 days, p=.007). The tourist group had more near-drowning or decompression sickness (44.0% vs. 3.0%, p<.001) and secondary transfers (20.0% vs. 5.4%, p=.003). All the patients (N=12) that required multiple retrievals were Lanyu Indigenous residents. The Lanyu Indigenous residents, compared with the non-Indigenous residents, had fewer admissions to intensive care units (47.7% vs. 80.0%) and more in-hospital mortalities (10.6% vs. 0.0%). Multifaceted approaches should be initiated to improve the health care system in remote Indigenous islands.
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Serviços Médicos de Emergência , Humanos , Taiwan , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Serviços Médicos de Emergência/estatística & dados numéricos , Adulto Jovem , Adolescente , Serviços de Saúde do Indígena/organização & administração , Povos IndígenasRESUMO
BACKGROUND: Post-stroke depression (PSD) is closely associated with poor stroke prognosis. However, there are some challenges in identifying and assessing PSD. This study aimed to identify scales for PSD diagnosis, assessment, and follow-up that are straightforward, accurate, efficient, and reproducible. METHODS: A systematic literature search was conducted in 7 electronic databases from January 1985 to December 2023. RESULTS: Thirty-two studies were included, the Patient Health Questionnaire-9 (PHQ-9) and Hamilton Depression Scale (HDRS) had higher diagnostic accuracy for PSD. The sensitivity, specificity, and diagnostic odds ratio of PHQ-9 or diagnosing any depression were 0.82, 0.87, and 29 respectively. And for HDRS, used for diagnosing major depression, the scores were 0.92, 0.89, and 94. Furthermore, these two scales also had higher diagnostic accuracy in assessing depressive symptoms during both the acute and chronic phases of stroke. In patients with post-stroke aphasia and cognitive impairment, highly diagnostic scales have not been identified for assessing depressive symptoms yet. CONCLUSIONS: The PHQ-9 and HDRS scales are recommended to assess PSD. HDRS, which demonstrates high diagnostic performance, can replace structured interviews based on diagnostic criteria.
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Depressão , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/psicologia , Depressão/diagnóstico , Depressão/etiologia , Escalas de Graduação Psiquiátrica/normas , Reprodutibilidade dos TestesRESUMO
Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.
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Background: OTUB1, an essential deubiquitinating enzyme, is upregulated in various types of cancer. Previous studies have shown that OTUB1 may be an oncogene in glioblastoma multiforme (GBM), but its specific regulatory mechanism remains unclear. This study aimed to investigate the mechanism by which OTUB1 and the JAK2/STAT1 signaling pathway co-regulate the growth of GBM. Methods: Using bioinformatics, GBM tissues, and cells, we evaluated the expression and clinical significance of OTUB1 in GBM. Subsequently, we explored the regulatory mechanisms of OTUB1 on malignant behaviors in GBM in vitro and in vivo. In addition, we added the JAK2 inhibitor AZD1480 to explore the regulation of OTUB1 for JAK2/STAT1 pathway in GBM. Results: We found that OTUB1 expression was upregulated in GBM. Silencing OTUB1 promotes apoptosis and cell cycle arrest at G1 phase, inhibiting cell proliferation. Moreover, OTUB1 knockdown effectively inhibited the invasion and migration of GBM cells, and the opposite phenomenon occurred with overexpression. In vivo experiments revealed that OTUB1 knockdown inhibited tumor growth, further emphasizing its crucial role in GBM progression. Mechanistically, we found that OTUB1 was negatively correlated with the JAK2/STAT1 pathway in GBM. The addition of the JAK2 inhibitor AZD1480 significantly reversed the effects of silencing OTUB1 on GBM. Conclusion: Our study reveals a novel mechanism by which OTUB1 inhibits the JAK2/STAT1 signaling pathway. This contributes to a better understanding of OTUB1's role in GBM and provides a potential avenue for targeted therapeutic intervention.
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PURPOSE: To explore the mediating role of trait anxious personality in the association between quality of life (QoL) and death anxiety (DA), as well as to test the moderating effect of social support in the mediation model. METHODS: The Death Anxiety Scale, Quality of Life Scale, State-Trait Anxiety Scale, and Social Support Rating Scale were used to measure 588 family caregivers of advanced cancer patients. We then constructed a moderated mediation model. RESULTS: The presence of QoL was negatively associated with DA (ß = - 0.67, p < 0.01). Trait anxious personality partially mediated the relationship between QoL and DA (indirect effect ß = - 0.08, p < 0.01). Social support moderated both the antecedent and subsequent segments of the mediating paths of "QoL â trait anxious personality â DA" and the direct relationship between QoL and DA. Among caregivers with a low level of social support, the mediating effect coefficient of trait anxious personality was higher at 0.25 (95% confidence interval (CI): 0.059-0.182), in contrast to caregivers with a high level of social support, where the mediating effect coefficient of trait anxious personality was 0.11 (95% CI: 0.029-0.072). CONCLUSION: QoL is directly associated with an increased risk of DA and indirectly related to DA by increasing the risk of trait anxious personality among caregivers. Social support can moderate the mediating effect of trait anxious personality and the relationship between QoL and DA. The intervention strategy for preventing DA among caregivers who have encountered QoL reduction should focus on reducing trait anxious personality and social support.
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Ansiedade , Cuidadores , Neoplasias , Personalidade , Qualidade de Vida , Apoio Social , Humanos , Qualidade de Vida/psicologia , Cuidadores/psicologia , Masculino , Feminino , Neoplasias/psicologia , Pessoa de Meia-Idade , Ansiedade/psicologia , Ansiedade/etiologia , Adulto , Idoso , Atitude Frente a Morte , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study aimed to investigate death anxiety (DA) in caregivers of patients with advanced cancer and identify associated factors in the context of Chinese culture. METHODS: Caregivers (N = 588) of advanced cancer patients in a tertiary cancer hospital completed anonymous questionnaire surveys. Measures included the Chinese version of the Templer Death Anxiety Scale (C-T-DAS), the Quality-of-Life Scale, the State-Trait Anxiety Scale, and the Social Support Rating Scale. Data were analyzed in SPSS (IBM Corp, Armonk, NY, USA) using descriptive statistics, Pearson's correlation test, and linear regression. RESULTS: Respondents returned 588 (93.03%) of the 632 questionnaires. The total C-T-DAS score was 7.92 ± 2.68 points. The top-scoring dimension was "Stress and pain" (3.19 ± 1.29 points), followed by "Emotion" (2.28 ± 1.31 points) and "Cognition" (1.40 ± 0.94 points). In contrast, the lowest-scoring dimension was "Time" (1.06 ± 0.77 points). Factors associated with DA (R2 = 0.274, F = 13.348, p < 0.001) included quality of life (QoL), trait anxious personality, social support, caregiver length of care, caregiver gender, and patients' level of activities of daily living (ADL). CONCLUSIONS: Our results demonstrated high levels of DA in caregivers of patients with advanced cancer. Generally, female caregivers and those with low social support had high DA. Caregivers caring for patients with low ADL levels or with a low QoL and trait anxious personality reported high DA. Certain associated factors help to reduce caregivers DA. Social interventions are recommended to improve the end-of-life transition and trait anxious personality as well as quality of life for caregivers.
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Ansiedade , Cuidadores , Neoplasias , Qualidade de Vida , Apoio Social , Humanos , Masculino , Cuidadores/psicologia , Feminino , Neoplasias/psicologia , Pessoa de Meia-Idade , Estudos Transversais , Ansiedade/etiologia , Ansiedade/epidemiologia , Inquéritos e Questionários , Adulto , Idoso , China , Atitude Frente a MorteRESUMO
Actin-related protein 2/3 complex subunit 1A (ARPC1A) is implicated in several cancers due to its critical role in regulating actin polymerization. However, the exact mechanism of ARPC1A in cancer remains unclear. This study aims to investigate the biological role of ARPC1A in various cancers and the regulatory role of ARPC1A in glioblastoma multiforme (GBM). We analyzed the expression differences, prognostic value, mutations, immune infiltration, immune microenvironment, and single-cell level correlations of ARPC1A in various cancers. Furthermore, we employed gene set enrichment analysis (GSEA) and functional experiments to elucidate the regulatory mechanisms of ARPC1A on GBM. Importantly, we assessed the role of ARPC1A in temozolomide (TMZ) resistance of GBM. ARPC1A expression was up-regulated in most cancer tissues and was associated with poorer prognosis. Genomic mutation analysis revealed that the predominant type of ARPC1A mutation in tumors was amplification. ARPC1A expression was negatively correlated with B-cell and immune scores in most tumors. Both GSEA and single-cell sequencing have revealed that ARPC1A promotes tumor proliferation and epithelial-mesenchymal transition. In vitro experiments confirmed that ARPC1A knockdown inhibited the proliferation and metastatic ability of GBM cells. Notably, silencing ARPC1A reduced TMZ resistance in GBM cells. This study highlights the prognostic value of ARPC1A in various tumors and its potential for application in immunotherapy. Meanwhile, the modulation of GBM malignant behavior and TMZ resistance by ARPC1A provides a new approach for personalized and precise treatment of GBM.
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BACKGROUND: Visceral pain occurs commonly following thoracic surgery, but an effective method to relieve visceral pain in thoracic surgery remains controversial. We test the effect of stellate ganglion blocks (SGB) on perioperative visceral pain following video-assisted thoracoscopic surgery (VATS). METHODS: A prospective, randomized, controlled trial enrolled 77 elderly patients undergoing VATS. Patients were randomized to SGB followed by modified intercostal nerve block (Group S, n=37); or modified intercostal nerve block only (Group C, n=40). Remifentanil 0.02-0.2 µg·kg-1·min-1 was titrated to keep pain threshold index values between 40-65 and maintain mean arterial pressure or heart rate values around 20% of baseline values. Patient-controlled intravenous analgesia with sufentanil was used in the postoperative period. The co-primary outcomes were the perioperative cumulative opioid consumption and pain scores on movement at 24 h after surgery. RESULTS: Compared with control group, SGB greatly reduced the intraoperative remifentanil consumption[300.00(235.00-450.00)µg versus 710.00(500.00-915.00)µg; P<0.01], with no difference in cumulative sufentanil consumption to 48h post-surgery. There was a statistically significant difference in pain scores on movement at 24h between groups [4.00(3.00-4.00) versus 4.00(3.25-5.00); P=0.01]. Further exploratory analyses showed significant difference for intra-chest pain on movement at 24h [3.00(2.00-3.00) versus 3.00(2.25-4.00); P=0.01]. No significant difference was observed in nausea/vomiting, time to pass flatus and postoperative length of stay. CONCLUSION: Preoperative stellate ganglion blocks for elderly patients could effectively blunt intraoperative visceral stress and reduce postoperative visceral pain extending 24 h after VATS. This initial finding deserve further investigation.
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The relationship between antibiotic resistance and bacterial virulence has not yet been fully explored. Here, we use Edwardsiella tarda as the research model to investigate the proteomic change upon oxytetracycline resistance (LTB4-ROTC). Compared to oxytetracycline-sensitive E. tarda (LTB4-S), LTB4-ROTC has 234 differentially expressed proteins, of which the abundance of 84 proteins is downregulated and 15 proteins are enriched to the Type III secretion system, Type VI secretion system, and flagellum pathways. Functional analysis confirms virulent phenotypes, including autoaggregation, biofilm formation, hemolysis, swimming, and swarming, are impaired in LTB4-ROTC. Furthermore, the in vivo bacterial challenge in both tilapia and zebrafish infection models suggests that the virulence of LTB4-ROTC is attenuated. Analysis of immune gene expression shows that LTB4-ROTC induces a stronger immune response in the spleen but a weaker response in the head kidney than that induced by LTB4-S, suggesting it's a potential vaccine candidate. Zebrafish and tilapia were challenged with a sublethal dose of LTB4-ROTC as a live vaccine followed by LTB4-S challenge. The relative percentage of survival of zebrafish is 60% and that of tilapia is 75% after vaccination. Thus, our study suggests that bacteria that acquire antibiotic resistance may attenuate virulence, which can be explored as a potential live vaccine to tackle bacterial infection in aquaculture.
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Farmacorresistência Bacteriana , Edwardsiella tarda , Infecções por Enterobacteriaceae , Oxitetraciclina , Tilápia , Peixe-Zebra , Edwardsiella tarda/patogenicidade , Edwardsiella tarda/efeitos dos fármacos , Edwardsiella tarda/genética , Animais , Oxitetraciclina/farmacologia , Virulência/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/tratamento farmacológico , Tilápia/microbiologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/imunologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteômica/métodos , Vacinas Bacterianas/imunologiaRESUMO
Objective: To assess the effectiveness of suture button fixation Latarjet procedure under total arthroscopy for anterior shoulder instability with severe bone defects. Methods: The clinical data of 15 patients with severe bone defects and anterior shoulder instability treated with suture button fixation Latarjet procedure under total arthroscopy between June 2020 and February 2023 was retrospectively analyzed, including 11 males and 4 females, with an average age of 31.1 years (range, 20-54 years). Three-dimensional CT showed that the average glenoid bone defect was 24.4% (range, 16.3%-35.2%). The average number of shoulder dislocation was 4.2 times (range, 3-8 times). The disease duration ranged from 6 to 21 months with an average of 10.6 months. The operation time and intraoperative blood loss were recorded. The pain relief was evaluated by visual analogue scale (VAS) score, and the functional recovery of shoulder joint was evaluated by Rowe score, Walch-Duplay score, and American Association for Shoulder and Elbow Surgery (ASES) score before and after operation. The range of motion (ROM) of the shoulder joint was assessed, including active flexion, lateral external rotation, abduction 90° external rotation, and internal rotation. Three-dimensional CT was performed at 6 months after operation and at last follow-up to observe the absorption of bone graft, the position of bone graft and glenoid, and the healing of bone graft. Results: The operation was successfully completed in all patients. The operation time was 85-195 minutes, with an average of 123.0 minutes. The intraoperative blood loss was 20-75 mL, with an average of 26.5 mL. All patients were followed up 13-32 months, with an average of 18.7 months. During the follow-up, there was no serious complication such as shoulder joint infection, joint stiffness, or vascular and nerve injury. One patient had partial absorption of the transplanted bone and bone nonunion at 3 months after operation, but the pain of the shoulder joint relieved at last follow-up, and no redislocation of the shoulder joint occurred; no obvious bone fracture or dislocation of the shoulder joint was found in the other patients. Bone union was achieved at 6 months during follow-up. At last follow-up, the VAS score, Rowe score, Walch-Duplay score, and ASES score significantly improved when compared with those before operation ( P<0.05), while the ROM of active flexion, lateral external rotation, abduction 90° external rotation, and internal rotation of the shoulder joint was not significantly different from those before operation ( P>0.05). Conclusion: Suture button fixation Latarjet procedure under total arthroscopy can improve shoulder joint function in patients with severe anterior shoulder instability caused by bone defects, and imaging also indicates satisfactory placement of transplanted bone blocks.
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Artroscopia , Instabilidade Articular , Articulação do Ombro , Humanos , Masculino , Feminino , Artroscopia/métodos , Adulto , Instabilidade Articular/cirurgia , Instabilidade Articular/etiologia , Articulação do Ombro/cirurgia , Adulto Jovem , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Luxação do Ombro/cirurgia , Resultado do Tratamento , Tomografia Computadorizada por Raios XRESUMO
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder featured by abnormal movements, arising from the extensive neuronal loss and glial dysfunction in the striatum. Although the causes and pathogenetic mechanisms of HD are well established, the development of disease-modifying pharmacological therapies for HD remains a formidable challenge. Laduviglusib has demonstrated neuroprotective effects through the enhancement of mitochondrial function in the striatum of HD animal models. Ferroptosis is a nonapoptotic form of cell death that occurs as a consequence of lethal iron-dependent lipid peroxidation and mitochondrial dysfunction. However, the ferroptosis-related mechanisms underlying the neuroprotective effects of laduviglusib in the striatum of HD patients remain largely uncharted. In this study, we leveraged single-nucleus RNA sequencing data obtained from the striatum of HD patients in stages 2-4 to identify differentially expressed genes within distinct cell-type. We subsequently integrated these differentially expressed genes of HD, laduviglusib target genes and ferroptosis-related genes to predict the ferroptosis-related mechanisms underpinning the neuroprotective effects of laduviglusib in HD patients. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses unveiled that the effects of laduviglusib on direct pathway striatal projection neurons (dSPNs) is mainly associated with Th17 cell differentiation pathways. Conversely, its impact on indirect pathway striatal projection neurons (iSPNs) extends to the Neurotrophin signaling pathway, FoxO signaling pathway, and reactive oxygen species pathway. In microglia, laduviglusib appears to contribute to HD pathology via mechanisms related to Th17 cell differentiation and the FoxO signaling pathway. Further, molecular docking results indicated favorable binding of laduviglusib with PARP1 (associated with dSPNs and iSPNs), SCD (associated with astrocytes), ALOX5 (associated with microglia), and HIF1A (associated with dSPNs, iSPNs, and microglia). In addition, the KEGG results suggest that laduviglusib may enhance mitochondrial function and protect against neuronal loss by targeting ferroptosis-related signaling pathways, particularly mediated by ALOX5 in microglia. These findings provide valuable insights into the potential mechanisms through which laduviglusib exerts its effects on distinct cell-types within the HD striatum.
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Corpo Estriado , Ferroptose , Doença de Huntington , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Doença de Huntington/metabolismo , Doença de Huntington/genética , Doença de Huntington/patologia , Humanos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
OBJECTIVE: To understand the prevalence rate of obstructive pulmonary dysfunction in workers exposed to silica dust and analyze its risk factors, so as to provide reference for the formulation of diagnostic criteria for chronic obstructive pulmonary disease caused by occupational dust. METHODS: Data collection and structured questionnaire were used to collect the data of 2064 workers exposed to silica dust who underwent health examination in Hunan Occupational Disease Prevention and Control Hospital and Yuanling Second People's Hospital from January 1, 2021 to June 30, 2022. The prevalence rate of obstructive pulmonary ventilation dysfunction was analyzed and the risk factors were analyzed. RESULTS: The prevalence rate of obstructive pulmonary ventilation dysfunction (FEV1/FVC < 70%) was 2.3% in 2064 silica dust exposed workers. The prevalence of restrictive pulmonary ventilation dysfunction (FVC/Pre < 80%) was 8.1%. The prevalence of obstructive pulmonary ventilation dysfunction in the high level exposure group was higher than that in the low level exposure group, 8.2 vs0.9% (P < 0.05). The rate of obstructive pulmonary ventilation dysfunction in female group was higher than that in male group (5.3% vs. 1.7%, p = 0.00). Workers with obstructive pulmonary dysfunction were older and worked longer than workers without obstructive pulmonary dysfunction, but there was no statistical difference. Multivariate regression analysis showed that high exposure level was a risk factor for obstructive pulmonary ventilation dysfunction in silica dust exposed workers (P < 0.05). Females were the risk factors for obstructive pulmonary ventilation dysfunction (P < 0.05). CONCLUSION: Silica dust exposure can cause obstructive pulmonary ventilation dysfunction and lead to chronic obstructive pulmonary disease. High level of exposure is a risk factor for obstructive pulmonary ventilation dysfunction. Women exposed to dust are more prone to obstructive pulmonary ventilation dysfunction than men. Early diagnosis of chronic obstructive pulmonary disease caused by silica dust and timely intervention measures are very important to delay the decline of lung function and protect the health of workers.
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Poeira , Exposição Ocupacional , Dióxido de Silício , Humanos , Feminino , Masculino , Dióxido de Silício/efeitos adversos , Fatores de Risco , Estudos Transversais , Exposição Ocupacional/efeitos adversos , Prevalência , Pessoa de Meia-Idade , Adulto , China/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Inquéritos e Questionários , Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/fisiopatologia , Análise MultivariadaRESUMO
Autoantibodies against apolipoprotein A-I (ApoA-I) are associated with cardiovascular disease risks. We aimed to examine the 4-hydroxy-2-nonenal (HNE) modification of ApoA-I in coronary artery disease (CAD) and evaluate the potential risk of autoantibodies against their unmodified and HNE-modified peptides. We assessed plasma levels of ApoA-I, HNE-protein adducts, and autoantibodies against unmodified and HNE-peptide adducts, and significant correlations and odds ratios (ORs) were examined. Two novel CAD-specific HNE-peptide adducts, ApoA-I251-262 and ApoA-I70-83, were identified. Notably, immunoglobulin G (IgG) anti-ApoA-I251-262 HNE, IgM anti-ApoA-I70-83 HNE, IgG anti-ApoA-I251-262, IgG anti-ApoA-I70-83, and HNE-protein adducts were significantly correlated with triglycerides, creatinine, or high-density lipoprotein in CAD with various degrees of stenosis (<30% or >70%). The HNE-protein adduct (OR = 2.208-fold, p = 0.020) and IgM anti-ApoA-I251-262 HNE (2.046-fold, p = 0.035) showed an increased risk of progression from >30% stenosis in CAD. HNE-protein adducts and IgM anti-ApoA-I251-262 HNE may increase the severity of CAD at high and low levels, respectively.
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Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.
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Câmbio , Ciclopentanos , Citocininas , Regulação da Expressão Gênica de Plantas , Oxilipinas , Proteínas de Plantas , Populus , Transdução de Sinais , Xilema , Populus/genética , Populus/crescimento & desenvolvimento , Populus/metabolismo , Câmbio/genética , Câmbio/crescimento & desenvolvimento , Câmbio/metabolismo , Citocininas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Xilema/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Oxilipinas/farmacologia , Mutação/genética , Ligação Proteica/efeitos dos fármacos , Diferenciação CelularRESUMO
Eastern China is a major producer of fishery products (including inland aquaculture, coastal mariculture, and coastal fishing products). The quality of the products is affected by hydrophobic organic contaminants (HOCs) in the sediments. Based on in-vitro luminescent bacterial assay, the baseline toxicity (BEQBio) of 56 common HOCs were assessed in the present study. Specifically, the BEQBio of sediments declined from land (31-400 mg/kg) to sea (9.1-270 mg/kg). However, the toxicity contribution explained by the HOCs increased gradually from land (0.70 %) to sea (10 %) using Iceberg Modeling. In the inland pond, current use HOCs (pyrethroid pesticide (PEs), organic tin (OTCs), and antibiotic) exhibited considerable concentrations, although their toxicity contribution was very small (0.076 %), thus more regulations on the use of HOCs should be proposed and further screening is needed to confirm the major toxicants. In coastal mariculture area, the toxicity contribution of current use HOCs further declined (0.010 %), whereas environmental background HOCs, such as polycyclic aromatic hydrocarbons (PAHs), became increasingly significant, with the contribution ratio increasing from 0.37 % to 2.4 %. To minimize the negative impacts of PAHs, optimization of energy structure in transportation and coastal industry is required. In the coastal fishing area, the phased-out persistent organic pollutants (POPs) remained a major concern, in terms of both concentration and toxicity contribution. The phased-out POPs explained 7.0 % of the toxic effects of the sediments from the coastal fishing area, due to historical residue, industrial emissions, and their high toxicities. For this reason, it is critical to improve the relevant emission regulations and standards, so as to eventually reduce the unintentional discharges of POPs.
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Monitoramento Ambiental , Pesqueiros , Sedimentos Geológicos , Poluentes Químicos da Água , Sedimentos Geológicos/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , China , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , AquiculturaRESUMO
Ischemia/reperfusion (I/R) injury significantly contributes to the morbidity and mortality associated with cardiac events. Poloxamer 188 (P188), a nonionic triblock copolymer, has been proposed to mitigate I/R injury by stabilizing cell membranes. However, the underlying mechanisms remain incompletely understood, particularly concerning endothelial cell function and nitric oxide (NO) production. We employed human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) and endothelial cells (ECs) to elucidate the effects of P188 on cellular survival, function, and NO secretion under simulated I/R conditions. iPSC-CMs contractility and iPSC-ECs' NO production were assessed following exposure to P188. Further, an isolated heart model using Brown Norway rats subjected to I/R injury was utilized to evaluate the ex-vivo cardioprotective effects of P188, examining cardiac function and NO production, with and without the administration of a NO inhibitor. In iPSC-derived models, P188 significantly preserved CM contractile function and enhanced cell viability after hypoxia/reoxygenation. Remarkably, P188 treatment led to a pronounced increase in NO secretion in iPSC-ECs, a novel finding demonstrating endothelial protective effects beyond membrane stabilization. In the rat isolated heart model, administration of P188 during reperfusion notably improved cardiac function and reduced I/R injury markers. This cardioprotective effect was abrogated by NO inhibition, underscoring the pivotal role of NO. Additionally, a dose-dependent increase in NO production was observed in non-ischemic rat hearts treated with P188, further establishing the critical function of NO in P188 induced cardioprotection. In conclusion, our comprehensive study unveils a novel role of NO in mediating the protective effects of P188 against I/R injury. This mechanism is evident in both cellular models and intact rat hearts, highlighting the potential of P188 as a therapeutic agent against I/R injury. Our findings pave the way for further investigation into P188's therapeutic mechanisms and its potential application in clinical settings to mitigate I/R-related cardiac dysfunction.
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This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.
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Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente TumoralRESUMO
Potentiation of the effects of currently available antibiotics is urgently required to tackle the rising antibiotics resistance. The pyruvate (P) cycle has been shown to play a critical role in mediating aminoglycoside antibiotic killing, but the mechanism remains unexplored. In this study, we investigated the effects of intermediate metabolites of the P cycle regarding the potentiation of gentamicin. We found that α-ketoglutarate (α-KG) has the best synergy with gentamicin compared to the other metabolites. This synergistic killing effect was more effective with aminoglycosides than other types of antibiotics, and it was effective against various types of bacterial pathogens. Using fish and mouse infection models, we confirmed that the synergistic killing effect occurred in vivo. Furthermore, functional proteomics showed that α-KG downregulated thiosulphate metabolism. Upregulation of thiosulphate metabolism by exogenous thiosulphate counteracted the killing effect of gentamicin. The role of thiosulphate metabolism in antibiotic resistance was further confirmed using thiosulphate reductase knockout mutants. These mutants were more sensitive to gentamicin killing, and less tolerant to antibiotics compared to their parental strain. Thus, our study highlights a strategy for potentiating antibiotic killing by using a metabolite that reduces antibiotic resistance.
Assuntos
Antibacterianos , Gentamicinas , Ácidos Cetoglutáricos , Antibacterianos/farmacologia , Animais , Ácidos Cetoglutáricos/metabolismo , Ácidos Cetoglutáricos/farmacologia , Camundongos , Gentamicinas/farmacologia , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Regulação para Baixo/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Modelos Animais de DoençasRESUMO
Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35â µM. Proprotogracillin selectively inhibited A549 (IC50=0.58â µM) and A549/Taxol (IC50=0.74â µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40â µM.