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PURPOSE: This study aims to evaluate the risk factors of treatment-related pneumonitis (TRP) following thoracic radiotherapy/chemoradiotherapy combined with anti-PD1 monoclonal antibodies (mAbs) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively reviewed 97 patients with advanced ESCC who were treated with thoracic radiotherapy/chemoradiotherapy combined with anti-PD1 mAbs. Among them, 56 patients received concurrent radiotherapy with anti-PD1 mAbs and 41 patients received sequential radiotherapy with anti-PD1 mAbs. The median prescribed planning target volume (PTV) dose was 59.4â¯Gy (range from 50.4 to 66â¯Gy, 1.8-2.2â¯Gy/fraction). Clinical characteristics, the percentage of lung volume receiving more than 5-50â¯Gy in increments of 5â¯Gy (V5-V50, respectively) and the mean lung dose (MLD) were analyzed as potential risk factors for TRP. RESULTS: 46.4% (45/97), 20.6% (20/97), 20.6% (20/97), 4.1% (4/97), and 1.0% (1/97) of the patients developed any grade of TRP, grade 1 TRP, grade 2 TRP, grade 3 TRP, and fatal (grade 5) TRP, respectively. Anti-PD1 mAbs administered concurrently with radiotherapy, V5, V10, V15, V25, V30, V35, V40 and MLD were associated with the occurrence of grade 2 or higher TRP. Concurrent therapy (Pâ¯= 0.010, ORâ¯= 3.990) and V5 (Pâ¯= 0.001, ORâ¯= 1.126) were independent risk factors for grade 2 or higher TRP. According to the receiver operating characteristic (ROC) curve analysis, the optimal V5 threshold for predicting grade 2 or higher TRP was 55.7%. CONCLUSION: The combination of thoracic radiotherapy/chemoradiotherapy with anti-PD1 mAbs displayed a tolerable pulmonary safety profile. Although the incidence of TRP was high, grade 1-2 TRP accounted for the majority. Anti-PD1 mAbs administered concurrently with radiotherapy and the lung V5 were significantly associated with the occurrence of grade 2 or higher TRP. Therefore, it seems safer to control V5 below 55% in clinical, especially for the high-risk populations receiving concurrent therapy.
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BACKGROUND: Hypertrophic scar is a disease of abnormal skin fibrosis caused by excessive fibroblast proliferation, and existing drugs cannot achieve satisfactory therapeutic effects. OBJECTIVES: This study aimed to explore the molecular pathogenesis of hypertrophic scars and screen effective drugs for hypertrophic scars. METHODS: Existing human hypertrophic scar RNA sequencing data were utilized to search for hypertrophic scar-related gene modules and key genes through weighted gene co-expression network analysis (WGCNA). Candidate compounds were screened in a compound library. Potential drugs were screened by molecular docking and verified in human hypertrophic scar fibroblasts and a mouse mechanical force hypertrophic scar model. RESULTS: WGCNA showed that hypertrophic scar-associated gene modules influence focal adhesion, transforming growth factor ß (TGF-ß) signaling pathway, and other biological pathways. Integrin ß1 (ITGB1) is the hub protein. Among the candidate compounds obtained by computer virtual screening and molecular docking, crizotinib, sorafenib, and SU11274 can inhibit the proliferation and migration of human hypertrophic scar fibroblasts and pro-fibrotic gene expression. Crizotinib had the best effect on hypertrophic scar attenuation in mouse models. At the same time, mouse ITGB1 small interfering RNA (siRNA) can also inhibit mouse scar hyperplasia. CONCLUSIONS: ITGB1 and TGF-ß signaling pathways are important for hypertrophic scar formation. Crizotinib could serve as a potential drug for hypertrophic scars.
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OBJECTIVES: To locate the most valuable sites for shear wave elastography (SWE) evaluation and to develop a clinically applicable scoring system based on SWE for systemic sclerosis (SSc) and to verify the accuracy for detection and subdivision and the correlation by modified Rodnan total skin score (mRTSS). METHODS: SSc patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) and symptomatic other rheumatic diseases (ORD) patients were included in this cross-sectional study. We assessed the skin stiffness at forehead, chest, abdomen, and bilateral fingers, hands, forearm, arms, thighs, legs, and feet, by palpation and SWE. Logistic regression was used to screen the most valuable sites for detection of SSc and subdivision of lcSSc and dcSSc, on which a scoring system was developed and verified. RESULTS: A total of 49 lcSSc, 51 dcSSc, and 36 ORD patients were included. The SWE-derived scoring system, including finger, hand, foot, arm, chest, and abdomen, reached a sensitivity and specificity of 80.0% and 94.4%, respectively, for diagnosing SSc at the cut-off value >24. The scoring system, including arm, chest, and abdomen, reached a sensitivity of 72.5% and specificity of 98.0% for subdividing dcSSc at the cut-off value >11. The kappa coefficient between the SWE-derived diagnosis and clinical diagnosis was 0.636 (P<0.001). The SWE-derived total scores of six sites had a strong correlation with mRTSS (r=0.757, p<0.001). CONCLUSIONS: The SWE-derived scoring system can be valuable in detection and evaluation of SSc in clinical application.
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Técnicas de Imagem por Elasticidade , Índice de Gravidade de Doença , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Técnicas de Imagem por Elasticidade/métodos , Estudos Transversais , Adulto , Reprodutibilidade dos Testes , Pele/diagnóstico por imagem , Pele/patologia , Esclerodermia Difusa/diagnóstico por imagem , Idoso , Valor Preditivo dos Testes , Esclerodermia Limitada/diagnóstico por imagem , Escleroderma Sistêmico/diagnóstico por imagemRESUMO
BACKGROUND AND OBJECTIVE: We explore molecular and metabolic pathways involved in interstitial cystitis (IC) with integrating multi-omics analysis for identifying potential diagnostic and therapeutic targets. METHODS: Mouse models of IC/bladder pain syndrome (BPS) were established by intraperitoneal injection of cyclophosphamide and bladder tissue samples were collected for metabolomics and transcriptome analysis. RESULTS: We found a total of 82 and 145 differential metabolites in positive ion modes and negative ion modes, respectively. Glycerophospholipid metabolism, choline metabolism in cancer, and nucleotide metabolism pathways were significantly enriched in the IC/BPS group. Transcriptome analysis demonstrated that 1069 upregulated genes and 1087 downregulated genes were detected. Importantly, the stronger enrichment for cell cycle pathway was observed in IC/BPS than that in normal bladder tissue, which may be involved in the process of bladder remodeling. Moreover, the inflammatory response and inflammatory factors related pathways were enriched in the IC/BPS group. CONCLUSIONS: Our findings provide critical directions for further exploration of the molecular pathology underlying IC/BPS.
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Cistite Intersticial , Animais , Camundongos , Cistite Intersticial/diagnóstico , Transcriptoma , Multiômica , Bexiga Urinária/metabolismo , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Phloem protein 2 (PP2) proteins play a vital role in the Phloem-based defense (PBD) and participate in many abiotic and biotic stress. However, research on PP2 proteins in cotton is still lacking. RESULTS: A total of 25, 23, 43, and 47 PP2 genes were comprehensively identified and characterized in G.arboretum, G.raimondii, G.barbadense, and G.hirsutum. The whole genome duplication (WGD) and allopolyploidization events play essential roles in the expansion of PP2 genes. The promoter regions of GhPP2 genes contain many cis-acting elements related to abiotic stress and the weighted gene co-expression network analysis (WGCNA) analysis displayed that GhPP2s could be related to salt stress. The qRT-PCR assays further confirmed that GhPP2-33 could be dramatically upregulated during the salt treatment. And the virus-induced gene silencing (VIGS) experiment proved that the silencing of GhPP2-33 could decrease salt tolerance. CONCLUSIONS: The results in this study not only offer new perspectives for understanding the evolution of PP2 genes in cotton but also further explore their function under salt stress.
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Gossypium , Proteínas de Plantas , Tolerância ao Sal , Gossypium/genética , Lectinas de Plantas , Estresse Salino , Tolerância ao Sal/genética , Proteínas de Plantas/metabolismoRESUMO
Tissue autotomy is a unique adaptive response to environmental stress, followed by regeneration process compensating for the loss of body parts. The crustaceans present remarkable activity of appendage autotomy and regeneration, however, the molecular mechanism is still unclear. In this study, the Eriocheir sinensis Hedgehog (EsHH) and Smoothened (EsSMO) were identified in the regenerative limbs, and the function of Hedgehog signaling pathway on limb regeneration was evaluated. At the blastema growth stage of limb regeneration, the expression of EsHH and EsSMO was up-regulated in response to limb autotomy stress, and down-regulated at blastema differentiation stage. To clarify the effect of Hedgehog pathway during limb regeneration, the regenerative efficiency was evaluated with Smoothened inhibitor cyclopamine or RNAi (ds-HH) injection. We observed that the regenerative efficiency was significantly repressed with blockage of Hedgehog pathway at both the basal growth stage and the proecdysial growth stage, which was indicated by the delay of wound healing and blastema growth, as well as a decrease in the size of newly formed limbs. In addition, gene expression and BrdU incorporation assay showed that the proliferation and myogenic differentiation of blastema cells were suppressed with either cyclopamine or ds-HH injection. Thus, these results suggest that Hedgehog signaling pathway is essential for the establishment of limb regeneration in E. sinensis through promoting the proliferation and myogenic differentiation of blastema cells.
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Braquiúros , Proteínas Hedgehog , Animais , Proteínas Hedgehog/genética , Transdução de Sinais , Alimentos Marinhos , Regeneração , Braquiúros/genéticaRESUMO
BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. METHODS: To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. RESULTS: HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. CONCLUSIONS: JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation.
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Janus Quinase 2 , Fator de Transcrição STAT3 , Animais , Ratos , Fígado , Estresse do Retículo Endoplasmático , PerfusãoRESUMO
BACKGROUND: It is true that Chronic obstructive pulmonary disease (COPD) will increase social burden, especially in developing countries. Urban-rural differences in the lagged effects of PM2.5 and PM10 on COPD mortality remain unclear, in Chongqing, China. METHODS: In this study, a distributed lag non-linear model (DLNMs) was established to describe the urban-rural differences in the lagged effects of PM2.5, PM10 and COPD mortality in Chongqing, using 312,917 deaths between 2015 and 2020. RESULTS: According to the DLNMs results, COPD mortality in Chongqing increases with increasing PM2.5 and PM10 concentrations, and the relative risk (RR) of the overall 7-day cumulative effect is higher in rural areas than in urban areas. High values of RR in urban areas occurred at the beginning of exposure (Lag 0 ~ Lag 1). High values of RR in rural areas occur mainly during Lag 1 to Lag 2 and Lag 6 to Lag 7. CONCLUSION: Exposure to PM2.5 and PM10 is associated with an increased risk of COPD mortality in Chongqing, China. COPD mortality in urban areas has a high risk of increase in the initial phase of PM2.5 and PM10 exposure. There is a stronger lagging effect at high concentrations of PM2.5 and PM10 exposure in rural areas, which may further exacerbate inequalities in levels of health and urbanization.
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Doença Pulmonar Obstrutiva Crônica , Humanos , China/epidemiologia , Quimiocina CCL4 , Urbanização , Material Particulado/efeitos adversosRESUMO
BACKGROUND: Small airway dysfunction (SAD), a hallmark of early lung function abnormality, is a major component of several chronic respiratory disorders. The role of SAD in patients with connective tissue disease-related interstitial lung disease (CTD-ILD) has not been explored. METHODS: We conducted a two-parts (retrospective and prospective) study to collect pulmonary function tests from CTD-ILD patients. SAD was defined as at least two of the three measures (MMEF, FEF 50%, and FEF 75%) must be 65% of predicted values. Spearman correlation coefficient was used to evaluate association between SAD and other pulmonary function parameters. Mixed effects regression modeling analysis was used to assess response to treatment. RESULTS: CTD-ILD patients with SAD and without SAD were compared in this study. In the retrospective study, pulmonary function tests (PFTs) from 491 CTD-ILD patients were evaluated, SAD were identified in 233 (47.5%). CTD-ILD patients with SAD were less smokers (17.6% vs. 27.9%, p = 0.007) and more females (74.3% vs. 64.0%, p = 0.015) than those without SAD. CTD-ILD patients with SAD had lower vital capacity (% predicted FVC, 70.4 ± 18.3 vs. 80.0 ± 20.9, p < 0.001) and lower diffusion capacity (% predicted DLCO, 58.8 ± 19.7 vs. 63.8 ± 22.1, p = 0.011) than those without SAD. Among 87 CTD-ILD patients prospectively enrolled, significant improvement in % predicted FVC was observed at 12-months follow-up (6.37 ± 1.53, p < 0.001 in patients with SAD; 5.13 ± 1.53, p = 0.002 in patients without SAD), but not in diffusion capacity and SAD parameters. CONCLUSION: In our cohort, about half of CTD-ILD patients have SAD, which is less frequent in smokers and more common in female patients. CTD-ILD patients with SAD have worse pulmonary function compared to those without SAD. Improvement of FVC but no improvement of SAD was observed in CTD-ILD patients after treatment.
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Doenças do Tecido Conjuntivo , Doenças Pulmonares Intersticiais , Humanos , Feminino , Estudos Retrospectivos , Estudos Prospectivos , Doenças Pulmonares Intersticiais/etiologia , Doenças do Tecido Conjuntivo/complicações , PulmãoRESUMO
BACKGROUND: The effect of sleep on the occurrence of prostate cancer (PCa) remains unclear. This study explored the influence of sleep traits on the incidence of PCa using a UK Biobank cohort study. METHODS: In this prospective cohort study, 213,999 individuals free of PCa at recruitment from UK Biobank were included. Missing data were imputed using multiple imputation by chained equations. Cox proportional hazards models were used to calculate the adjusted hazard ratios and 95% confidence intervals for PCa (6747 incident cases) across seven sleep traits (sleep duration, chronotype, insomnia, snoring, nap, difficulty to get up in the morning, and daytime sleepiness). In addition, we newly created a healthy sleep quality score according to sleep traits to assess the impact of the overall status of night and daytime sleep on PCa development. E values were used to assess unmeasured confounding. RESULTS: We identified 6747 incident cases, of which 344 died from PCa. Participants who usually suffered from insomnia had a higher risk of PCa (hazard ratio [HR]: 1.11; 95% confidence interval [CI]: 1.04-1.19, E value: 1.46). Finding it fairly easy to get up in the morning was also positively associated with PCa (HR: 1.09; 95% CI: 1.04-1.15, E value: 1.40). Usually having a nap was associated with a lower risk of PCa (HR: 0.91; 95% CI: 0.83-0.99, E value: 1.42). CONCLUSIONS: Fairly easy to get up in the morning and usually experiencing insomnia were associated with an increased incidence of PCa. Moreover, usually having a nap was associated with a lower risk of PCa. Therefore, sleep behaviors are modifiable risk factors that may have a potential impact on PCa risk.
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Neoplasias da Próstata , Distúrbios do Início e da Manutenção do Sono , Bancos de Espécimes Biológicos , Estudos de Coortes , Humanos , Masculino , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Fatores de Risco , Sono , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Reino Unido/epidemiologiaRESUMO
Chinese sturgeon (Acipenser sinensis) is an indigenous species of China and is listed as a critically endangered species. Recently, second filial generations of Chinese sturgeon in the Yangtze River Fisheries Research Institute suffered from a severe disease. In this study, two kinds of pathogenic bacteria were isolated from diseased sturgeon and identified as Plesiomonas shigelloides and Citrobacter freundii, based on 16S rDNA gene sequence alignment analysis. Antimicrobial susceptibility testing showed that P. shigelloides was resistant to ampicillin, penicillin, midecamycin, oxacillin, and clindamycin; and sensitive to tocefatriaxone, piperacillin, cefoperazone, cefazolin, and ciprofloxacin. C. freundii was resistant to ampicillin, penicillin, midecamycin, oxacillin, and clindamycin; and sensitive to chloramphenicol, cefuroxime, norfloxacin, ciprofloxacin, and ceftazidime. The median lethal dose (LD50) values of P. shigelloides and C. freundii were 4.50 × 103 colony forming units (CFU)/g and 3.20 × 103 CFU/g, respectively. Clinical symptoms of challenged sturgeons were the same as those of naturally infected sturgeons. Histopathological examination disclosed severe damage in the viscera of P. shigelloides and C. freundii-infected sturgeons. This is the first report suggesting that P. shigelloides infection is associated with mortality of Chinese sturgeon. The results of this study revealed the pathogenesis and severe pathogenicity of P. shigelloides and C. freundii in cultured Chinese sturgeon, and offer insights into the prevention and treatment of bacterial infection caused by P. shigelloides and C. freundii in cultured sturgeons.
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Plesiomonas , Animais , Plesiomonas/genética , Citrobacter freundii/genética , Virulência , Clindamicina , Peixes/genética , Oxacilina , Ampicilina , CiprofloxacinaRESUMO
Age-related macular degeneration (AMD) is a complex multifactorial disease associated with the dysfunction of retinal pigment epithelium (RPE). Aloperine is a quinolizidine alkaloid that has been proven to possess broad pharmacological activities. However, the effects of aloperine on AMD remain unclear. In the present study, we used hydrogen peroxide (H2O2) to induce oxidative injury in human RPE cells (ARPE-19 cells). ARPE-19 cells were pretreated with different concentrations of aloperine for 2 h, followed by H2O2 exposure. Cell cytotoxicity was determined using lactate dehydrogenase (LDH) release assay. Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) activity were detected to reflect oxidative status. Western blot was performed to detect the expressions of bcl-2, bax, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). The activity of caspase-3 was also assessed to indicate cell apoptosis. In addition, ARPE-19 cells were transfected with siNrf2 to knock down Nrf2. Our results showed that pretreatment with aloperine elevated the reduced cell viability of H2O2-induced ARPE-19 cells in a dose-dependent manner. Aloperine greatly decreased the production of ROS and MDA, and increased the activities of SOD and GSH-PX in H2O2-stimulated ARPE-19 cells. H2O2-caused a decrease in bcl-2 expression and increases in bax expression and caspase-3 activity were mitigated by aloperine. Moreover, aloperine treatment enhanced the expression levels of Nrf2 in nuclear fraction and the HO-1 expression in lysates. Knockdown of Nrf2 reversed the protective effects of aloperine on H2O2-induced ARPE-19 cells. In conclusion, these findings demonstrated that aloperine protected ARPE-19 cells from H2O2-induced oxidative stress and apoptosis in part via activating the Nrf2/HO-1 signaling pathway. The findings suggested a therapeutic potential of aloperine for the treatment of ADM.
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Peróxido de Hidrogênio , Fator 2 Relacionado a NF-E2 , Apoptose , Sobrevivência Celular , Células Epiteliais/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Quinolizidinas , Espécies Reativas de Oxigênio , Pigmentos da RetinaRESUMO
The animal gut is a dynamic ecosystem. Many factors affect the structure and diversity of the gut microbiota, among which the composition of the diet is a direct determinant. To investigate the effect of dietary components on the gut microbiota of mandarin duck, nine fecal samples were collected from two foraging sites at Shiqian Mandarin Duck Lake National Wetland Park, Guizhou, China. We analyzed the chloroplast rbcL gene, mitochondrial COI gene, and 16S rRNA gene from the total DNA of the fecal samples by high-throughput sequencing to identify plant and animal components of the diet and the composition of the gut microbiota of mandarin duck. We found that the gut microbiota composition was significantly correlated with the number of species in the diet. Mandarin ducks with more diverse diets had a more complex gut microbiota with fewer pathogenic bacteria. This study provides further theoretical support for the effect of dietary differences on the structure of the host gut microbiota and clarifies the feeding preferences of mandarin duck in breeding areas.
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Microbioma Gastrointestinal , Animais , Microbioma Gastrointestinal/genética , Patos , RNA Ribossômico 16S/genética , Ecossistema , Dieta/veterinária , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
The aberrant changes of fussion/fission-related proteins can trigger mitochondrial dynamics imbalance, which cause mitochondrial dysfunctions and result insulin resistance (IR). However, the relationship between the inner mitochondrial membrane fusion protein optic atrophy 1 (Opa1) and hepatic IR as well as the specific molecular mechanisms of signal transduction has not been fully elucidated. In this study, we explore whether abnormalities in the Opa1 cause hepatic IR and whether berberine (BBR) can prevent hepatic IR through the SIRT1/Opa1 signalling pathway. High-fat diet (HFD)-fed mice and db/db mice are used as animal models to study hepatic IR in vivo. IR, morphological changes, and mitochondrial injury of the liver are examined to explore the effects of BBR. SIRT1/Opa1 protein expression is determined to confirm whether the signalling pathway is damaged in the model animals and is involved in BBR treatment-mediated mitigation of hepatic IR. A palmitate (PA)-induced hepatocyte IR model is established in HepG2 cells in vitro. Opa1 silencing and SIRT1 overexpression are induced to verify whether Opa1 deficiency causes hepatocyte IR and whether SIRT1 improves this dysfunction. BBR treatment and SIRT1 silencing are employed to confirm that BBR can prevent hepatic IR by activating the SIRT1/Opa1 signalling pathway. Western blot analysis and JC-1 fluorescent staining results show that Opa1 deficiency causes an imbalance in mitochondrial fusion/fission and impairs insulin signalling in HepG2 cells. SIRT1 and BBR overexpression ameliorates PA-induced IR, increases Opa1, and improves mitochondrial function. SIRT1 silencing partly reverses the effects of BBR on HepG2 cells. SIRT1 and Opa1 expressions are downregulated in the animal models. BBR attenuates hepatic IR and enhances SIRT1/Opa1 signalling in db/db mice. In summary, Opa1 silencing-mediated mitochondrial fusion/fission imbalance could lead to hepatocyte IR. BBR may improve hepatic IR by regulating the SIRT1/Opa1 signalling pathway, and thus, it may be used to treat type-2 diabetes.
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Berberina , Resistência à Insulina , Camundongos , Animais , Berberina/farmacologia , Berberina/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Fígado/metabolismo , Transdução de Sinais , Mitocôndrias/metabolismoRESUMO
AIM: To evaluate the health status of nurses in China and explore the impact of work-related stress, work environment and lifestyle factors on their health outcomes. DESIGN: The Chinese Nurses' Health Study is a multicentred, prospective cohort study. METHODS: We plan to recruit approximately 80,000 registered nurses aged between 18 and 65 years. Eligible nurses will be introduced to complete a series of web-based questionnaires after obtaining their informed consent. Follow-up questionnaires will be completed at 2-year interval to continuously track subsequent exposures. Health-related indicators will be obtained through self-reporting by nurses and the provincial and national registry platforms such as National Central Cancer Registry. The funding was approved in July 2020 and Research Ethics Committee approval was granted in February 2021. DISCUSSION: The study is the first multicentred prospective cohort study that aims to assess the impact of work-related stress, work environment and lifestyle factors on the health of Chinese nurses. The results of the Chinese Nurses' Health Cohort Study will potentially draw a picture of the current situation of general health and well-being among nurses in China and their health risks. This will be critical in recommending locally tailored strategic preventive measures and policies to reduce health and well-being threats for nurses and potentially general public, thereby promoting the quality of healthcare in China and globally. IMPACT: This study will help to understand the health status and working environment characteristics of Chinese nurses, and provide valuable epidemiological evidence for improving working environment and promoting well-being. The results of this study are potentially of great significance for formulating targeted nursing strategies to promote the nurses' health, nursing quality and patient safety in China and even around the world. CLINICAL TRIAL REGISTRATION NUMBER AND NAME OF TRIAL REGISTER: ChiCTR.org (ID:ChiCTR2100043202), The Nurses' Health Cohort Study of Shandong.
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Enfermeiras e Enfermeiros , Estresse Ocupacional , Adolescente , Adulto , Idoso , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Local de Trabalho , Adulto JovemRESUMO
Laser-induced graphene (LIG) is a class of three-dimensional (3D) porous carbon nanomaterial. It can be prepared by direct laser writing on some polymer materials in the air. Because of its features of simplicity, fast production, and excellent physicochemical properties, it was widely used in medical sensing devices. This minireview gives an overview of the characteristics of LIG and LIG-driven sensors. Various methods for preparing graphene were compared and discussed. The applications of the LIG in biochemical sensors for ions, small molecules, microRNA, protein, and cell detection were highlighted. LIG-based physical physiological sensors and wearable electronics for medical applications were also included. Finally, our insights into current challenges and prospects for LIG-based medical sensing devices were presented.
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Técnicas Eletroquímicas/métodos , Grafite/química , Lasers , Monitorização Fisiológica/instrumentação , Nanoestruturas/química , Técnicas Biossensoriais , Humanos , Monitorização Fisiológica/métodos , Dispositivos Eletrônicos VestíveisRESUMO
In wireless sensor networks, it is important to use the right number of sensors to optimize the network and consider the key design and cost. Due to the limited power of sensors, important issues include how to control the state of the sensor through an automatic control algorithm and how to power-save and efficiently distribute work. However, sensor nodes are usually deployed in dangerous or inaccessible locations. Therefore, it is difficult and impractical to supply power to sensors through humans. In this study, we propose a high reliability control algorithm with fast convergence and strong self-organization ability called the sensor activity control algorithm (SACA), which can efficiently control the number of sensors in the active state and extend their use time. In the next round, SACA considers the relationship between the total number of active sensors and the target value and determines the state of the sensor. The data transmission technology of random access is used between the sensor and the base station. Therefore, the sensor in the sleep state does not need to receive the feedback packet from the base station. The sensor can achieve true dormancy and power-saving effects. The experimental results show that SACA has fast convergence, strong self-organization capabilities, and power-saving advantages.
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Algoritmos , Redes de Comunicação de Computadores , Humanos , Reprodutibilidade dos TestesRESUMO
Plants are frequently exposed to a variety of abiotic stresses, such as those caused by salt, drought, cold, and heat. All of these stressors can induce changes in the proteoforms, which make up the proteome of an organism. Of the many different proteoforms, protein ubiquitination has attracted a lot of attention because it is widely involved in the process of protein degradation; thus regulates many plants molecular processes, such as hormone signal transduction, to resist external stresses. Ubiquitin ligases are crucial in substrate recognition during this ubiquitin modification process. In this review, the molecular mechanisms of plant responses to abiotic stresses from the perspective of ubiquitin ligases have been described. This information is critical for a better understanding of plant molecular responses to abiotic stresses.
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Plantas/metabolismo , Estresse Fisiológico/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Transdução de Sinais/fisiologia , Ubiquitinação/fisiologiaRESUMO
Abiotic stress, such as drought and salinity stress, seriously inhibit the growth and development of plants. Therefore, it is vital to understand the drought and salinity resistance mechanisms to enable cotton to provide more production under drought and salt conditions. In this study, we identified 8806 and 9108 differentially expressed genes (DEGs) through a comprehensive analysis of transcriptomic data related to the PEG-induced osmotic and salt stress in cotton. By performing weighted gene co-expression network analysis (WGCNA), we identified four co-expression modules in PEG treatment and five co-expression modules in salinity stress, which included 346 and 324 predicted transcription factors (TFs) in these modules, respectively. Correspondingly, whole genome duplication (WGD) events mainly contribute to the expansion of those TFs. Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses revealed those different modules were associated with stress resistance, including regulating macromolecule metabolic process, peptidase activity, transporter activity, lipid metabolic process, and responses to stimulus. Quantitative RT-PCR analysis was used to confirm the expression levels of 15 hub TFs in PEG6000 and salinity treatments. We found that the hub gene GhWRKY46 could alter salt and PEG-induced drought resistance in cotton through the virus-induced gene silencing (VIGS) method. Our results provide a preliminary framework for further investigation of the cotton response to salt and drought stress, which is significant to breeding salt- and drought-tolerant cotton varieties.
Assuntos
Secas , Regulação da Expressão Gênica de Plantas , Melhoramento Vegetal , Estresse Fisiológico/genética , Estresse Salino/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peptídeo Hidrolases/metabolismo , Lipídeos , Gossypium/genética , Gossypium/metabolismoRESUMO
Soil salinization conditions seriously restrict cotton yield and quality. Related studies have shown that the DUF4228 proteins are pivotal in plant resistance to abiotic stress. However, there has been no systematic identification and analysis of the DUF4228 gene family in cotton and their role in abiotic stress. In this study, a total of 308 DUF4228 genes were identified in four Gossypium species, which were divided into five subfamilies. Gene structure and protein motifs analysis showed that the GhDUF4228 proteins were conserved in each subfamily. In addition, whole genome duplication (WGD) events and allopolyploidization might play an essential role in the expansion of the DUF4228 genes. Besides, many stress-responsive (MYB, MYC) and hormone-responsive (ABA, MeJA) related cis-elements were detected in the promoters of the DUF4228 genes. The qRT-PCR results showed that GhDUF4228 genes might be involved in the response to abiotic stress. VIGS assays and the measurement of relative water content (RWC), Proline content, POD activity, and malondialdehyde (MDA) content indicated that GhDUF4228-67 might be a positive regulator of cotton response to salt stress. The results in this study systematically characterized the DUF4228s in Gossypium species and will provide helpful information to further research the role of DUF4228s in salt tolerance.