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ETHNOPHARMACOLOGICAL RELEVANCE: Hyperlipidemia is a lipid metabolism disorder and a risk factor for obesity, diabetes, and coronary heart disease. It occurs mostly in the old adults; however, its incidence rate is increasing annually and there is a trend towards younger adults. Current clinical drugs for treating hyperlipidemia have multiple side effects. Therefore, it is necessary to develop safe and effective drugs from natural products to prevent and treat hyperlipidemia. Simiao Wan (SMW) is a classic Chinese medicine prescription first recorded in the Cheng Fang Bian Du of the Qing Dynasty. Studies have shown that SMW has excellent efficacy in metabolic diseases, which can effectively improve hyperlipidemia combined with other metabolic diseases. However, its underlying mechanism in hyperlipidemia treatment is yet to be clarified. AIM OF THE STUDY: To investigate the hypolipidemic effect of SMW on hyperlipidemic mice and explore whether the gut microbiota-bile acid (BA) axis is the potential mechanism. MATERIALS AND METHODS: A hyperlipidemic mouse model was established using a high-fat diet (HFD), and the hypolipidemic effect of SMW was detected in vivo. We performed 16S ribosomal RNA sequencing and BA metabolism analysis to explore the hypolipidemic mechanisms of SMW. Western blotting was conducted to detect the expression of proteins involved in the gut microbiota-bile acid axis to determine the potential lipid-lowering pathway. RESULTS: Excessive obesity in hyperlipidemic mice was alleviated after 8 weeks of SMW treatment. The total cholesterol and low-density lipoprotein cholesterol levels decreased significantly, whereas high-density lipoprotein cholesterol levels increased. SMW also reduced hepatic lipid and inguinal white adipose tissue accumulation in HFD-induced hyperlipidemic mice. Furthermore, intestinal bile saline hydrolase (BSH) level, associated with BA excretion, decreased. Meanwhile, SMW decreased the abundance of BSH-enriched microbes in hyperlipidemic mice. SMW increased the intestinal conjugated-BAs contents in hyperlipidemic mice, especially tauro-ß-muricholic acid and tauro-ursodeoxycholic acid, which are ileac farnesoid X receptor (FXR) antagonists. Inhibited intestinal FXR signaling with SMW was accompanied by a decreased expression of intestinal fibroblast growth factor 15 and the activation of hepatic FXR, which promoted hepatic cholesterol conversion to BA. CONCLUSION: SMW indirectly attenuated HFD-induced hyperlipidemia in mice by regulating the gut microbiota-BA axis. Our results provide a pharmacological basis for SMW treating hyperlipidemia and suggest a new idea for developing lipid-lowering drugs.
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This study proposes a comprehensive evaluation method based on a two-stage model to assess greenhouse gas (GHG) emissions and reductions in high-food-waste-content (HFWC) municipal solid waste (MSW) landfills. The proposed method considers typical processes such as fugitive landfill gas (LFG), LFG collection, flaring, power generation, and leachate treatment. A case study of an HFWC MSW landfill in eastern China is considered to illustrate the evaluation. The findings revealed that the GHG emissions equivalent of the case landfill amounted to 21.23 million tons from 2007 to 2022, averaging 1.03 tons CO2-eq per ton of MSW. There was a potential underestimation of LFG generation at the landfill site during the initial stages, which led to delayed LFG collection and substantial fugitive LFG emissions. Additionally, the time distribution of GHG emissions from HFWC MSW was significantly different from that of low-food-waste-content (LFWC) MSW landfills, with peak emissions occurring much earlier. Owing to the rapid degradation characteristics of HFWC MSW, the cumulative LFG production of the landfill by 2022 (2 years after the final cover) was projected to reach 77 % of the total LFG potential. In contrast, it would take until 2030 for LFWC MSW landfills to reach this level. Furthermore, various scenarios were analyzed, in which if the rapid LFG generation characteristics of HFWC MSW are known in advance, and relevant facilities are constructed ahead of time, the collection efficiency can be improved from 31 % to over 78 %, resulting in less GHG emissions.
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Gases de Efeito Estufa , Eliminação de Resíduos , Resíduos Sólidos , Instalações de Eliminação de Resíduos , China , Gases de Efeito Estufa/análise , Eliminação de Resíduos/métodos , Resíduos Sólidos/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , AlimentosRESUMO
Varicella is a vaccine-preventable disease caused by the varicella zoster virus (VZV), but the varicella incidence among children has increased in recent years. This was a retrospective birth cohort study based on the Zhejiang Provincial Immune Information System (ZJIIS) and the China Information System for Disease Control and Prevention (CISDCP) in Quzhou. A total of 1,291 clinically diagnosed varicella cases born from 2009 to 2014 were collected during 2009-2023, which were analyzed the impact of changes in vaccination strategy on the incidence of varicella based on the Cox-proportional hazards model. It was observed that the onset age of varicella shifted to the older age group and later to 9-11 years. After the change to the two-dose varicella vaccination strategy, the population affected by varicella was concentrated among students and received more than one dose of live attenuated varicella vaccine (VarV). Based on the Coxproportional hazards model and adjusting for all covariates, the risk of varicella infection in children decreased after the introduction of the two-dose varicella vaccination strategy (HR = 0.04, 95% CI: 0.03-0.05). Meanwhile, the Kaplan-Meier curves also showed that the hazards were lower after the change in vaccination strategy. It is recommended that two doses of VarV should be included in the national immunization schedule and that full vaccination should be completed approximately four years after the first dose.
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Vacina contra Varicela , Varicela , Humanos , Vacina contra Varicela/administração & dosagem , Vacina contra Varicela/imunologia , Estudos Retrospectivos , Varicela/prevenção & controle , Varicela/epidemiologia , Varicela/imunologia , Feminino , Masculino , Criança , China/epidemiologia , Lactente , Pré-Escolar , Incidência , Coorte de Nascimento , Esquemas de Imunização , Modelos de Riscos Proporcionais , Adolescente , Vacinação/métodos , Vacinação/estatística & dados numéricos , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Herpesvirus Humano 3/imunologiaRESUMO
Wild populations of cartilaginous fish (sharks, skates, rays, and chimaeras) are encountering challenges. Here, we are unveiling genomic data and behavioral ecological records of Okamejei kenojei, a species listed in the IUCN Red List of Threatened Species, aiming to offer insights into the conservation and environmental adaptability of cartilaginous fish.
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INTRODUCTION: The head and neck comprise vital organs and are apparent human body parts. Tumours here impair physical and sensory functions as well as appearance and social interactions, leading to body image distress (BID) and threatening mental health and quality of life. Acceptance and commitment therapy has shown effectiveness in improving BID in groups such as breast cancer patients. This study aims to apply this therapy to intervene in head and neck cancer (HNC) patients, aiming to improve BID and promote better psychological well-being. METHODS AND ANALYSIS: This study is a prospective, parallel-group, randomised controlled trial. A total of 64 HNC patients will be allocated to either an intervention group or a control group. The intervention group will engage in a 3 week, six-session group-based acceptance and commitment therapy programme, while the control group will receive standard treatment. The primary outcome is cancer-related BID, and secondary outcomes are HNC-related BID, psychological flexibility, coping style and psychological distress. These indicators will be measured at baseline, postintervention and 1 month following the intervention's completion. ETHICS AND DISSEMINATION: The trial has received approval from the Institutional Review Board of Shanghai Proton and Heavy Ion Hospital (2308-67-02). The study results will be shared through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077863.
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Terapia de Aceitação e Compromisso , Imagem Corporal , Neoplasias de Cabeça e Pescoço , Qualidade de Vida , Humanos , Terapia de Aceitação e Compromisso/métodos , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/psicologia , China , Imagem Corporal/psicologia , Estudos Prospectivos , Feminino , Masculino , Angústia Psicológica , Ensaios Clínicos Controlados Aleatórios como Assunto , Adaptação Psicológica , Adulto , Pessoa de Meia-IdadeRESUMO
The evolution of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving genetic factors behind it remain unknown. Here we study the evolutionary genetics of liver by comparing the amphioxus hepatic caecum and the vertebrate liver, as well as examining the functional transition within vertebrates. Using in vivo and in vitro experiments, single-cell/nucleus RNA-seq data and gene knockout experiments, we confirm that the amphioxus hepatic caecum and vertebrate liver are homologous organs and show that the emergence of ohnologues from two rounds of whole-genome duplications greatly contributed to the functional complexity of the vertebrate liver. Two ohnologues, kdr and flt4, play an important role in the development of liver sinusoidal endothelial cells. In addition, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with gene duplicates playing a crucial role. We reconstructed the genetic footprint of the transfer of haem detoxification from the liver to the spleen during vertebrate evolution. Together, these findings challenge the previous hypothesis that organ evolution is primarily driven by regulatory elements, underscoring the importance of gene duplicates in the emergence and diversification of a complex organ.
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The aim of this study was to assess the advantages of an industry-scale microfluidizer system (ISMS) to prepare whole-grain highland barley pulp (WHBP) compared with colloid milling. Storage stability was evaluated by particle size, gravity separation stability, and rheological properties, as well as the microstructure observation by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLMS). The results showed that colloid milling failed to effectively homogenize the material, while ISMS sample surfaces were compact and smooth at higher pressures according to visual observation and SEM. The Turbiscan stability index of WHBP by ISMS was much lower as a result of colloid milling, demonstrating ISMS can improve WHBP stability. WHBP by colloid milling displayed a three-peak particle size distribution pattern, while a single-peak pattern was evident after ISMS treatment. A higher shear rate decreased the apparent viscosity, suggesting that WHBP was a shear-thinning fluid. According to CLMS, ISMS can successfully improve homogenization by disrupting the structures of oil bodies, proteins, and starches. The WHBP prepared by ISMS exhibited a higher ß-glucan level than that prepared by colloid milling, and showed a significant increase in ß-glucan level with ISMS pressure. These findings indicate that using ISMS to produce WHBP is viable for enhancing its storage stability and nutritional value.
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In pursuit of sustainable aquaculture, this study was performed to evaluate chicken meal as a substitute for fishmeal in bullfrog diets. Three experimental groups were established: a control group (FM) with 20% fishmeal, a CM50 group with 50% replacement (10% fishmeal), and a CM100 group with 100% replacement (0 fishmeal). Bullfrogs were fed for 56 days. The CM50 group exhibited significant increases in total weight gain and survival rate and a notable decrease in feed coefficient (p < 0.05). However, the CM100 group showed contrary effects. Increasing chicken meal substitution correlated with decreased amino acid content in muscle. Notably, the CM50 group demonstrated enhanced activities of antioxidant enzymes (CAT, T-AOC) and elevated gene expression levels (cat, sod, gst, etc.) in muscle and the intestine (p < 0.05), improved intestinal morphology, enhanced digestive enzyme activities (amylase, lipase), and reduced expression of inflammatory factors (il-1ß, il-8, il-17, etc.). Conversely, the CM100 group's indicators regressed to levels similar to or worse than those of the FM group. Therefore, a 50% substitution of fishmeal with chicken meal effectively promoted bullfrog survival, protected the intestines, and enhanced antioxidant capacity, supporting its potential as a fishmeal alternative. However, the adverse outcomes of the CM100 strategy, including growth retardation and reduced amino acid content in muscle, indicate that complete replacement is unsuitable.
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Highly metastatic and heterogeneous breast cancer affects the health of women worldwide. Abnormal expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein ß (YWHAB), also known as 14-3-3ß, is associated with the tumorigenesis and progression of bladder cancer, lung cancer and hepatocellular carcinoma; however, to the best of our knowledge, the role of YWHAB in breast cancer remains unknown. In the present study, a dual luciferase assay demonstrated that the transcription factor iroquois homeobox 5 may regulate YWHAB expression by affecting the promoter sequence upstream of its transcription start site. Subsequently, it was demonstrated that overexpression of YWHAB did not affect proliferation, but did reduce the migration and invasion of MDA-MB-231 cells. Furthermore, knockdown of YWHAB promoted the migration and invasion of MCF7 cells. Transcriptomics analysis demonstrated that when YWHAB was overexpressed, 61 genes were differentially expressed, of which 43 genes were upregulated and 18 genes were downregulated. These differentially expressed genes (DEGs) were enriched in cancer-related pathways, such as 'TNF signaling pathway' [Kyoto Encyclopedia of Genes and Genomes (KEGG): map04688]. The pathway with the largest number of DEGs was 'Rheumatoid arthritis' (KEGG: map05323). Notably, YWHAB downregulated vimentin, which is a mesenchymal marker, thus suggesting that it may weaken the mesenchymal properties of cells. These findings indicate that YWHAB may be a potential therapeutic target in breast cancer and further work should be performed to assess its actions as a potential tumor suppressor.
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OBJECTIVE: The observational association between blood metabolites and asthma has been extensively studied. However, it is still unclear whether this association is causal. In this study, we aimed to investigate the causal relationship between blood metabolites and asthma using a bidirectional Mendelian randomization (MR) analysis. Additionally, we aimed to explore the potential mechanisms underlying this relationship. METHODS: The study design involved the use of genetic instruments as instrumental variables (IVs) to fulfill the assumptions of MR analysis. The data on 1,091 metabolites and 309 metabolite ratios were obtained from the Canadian Longitudinal Study on Aging (CLSA), while the data on asthma were obtained from the Integrative Epidemiology Unit (IEU) Open GWAS Project. Utilizing the inverse variance-weighted (IVW) method as the primary MR analysis approach, sensitivity tests were conducted to assess the reliability of the findings, which involved employing Cochran's Q and the MR-Egger intercept. Furthermore, Bayesian weighted MR was used to further test the robustness of the results. Additionally, pathway analysis was conducted to explore the metabolic explanations underlying asthma. RESULT: In our study, a comprehensive MR Analysis identified 10 metabolites and 6 metabolite ratios significantly associated with the development of asthma (FDR < 0.05). The metabolites included glycerophosphocholines(GPCs), glycerophosphoethanolamines(GPEs), and an unknown metabolite. Of these, 1-arachidonoyl-GPC, 1-myristoyl-2-arachidonoyl-GPC, 1-palmitoyl-2-arachidonoyl-GPC, and 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC were associated with an increased risk of asthma, whereas 1,2-dilinoleoyl-GPC, 1-palmitoyl-2-linoleoyl-GPC, 1,2-dilinoleoyl-GPE, 1 - oleoyl - 2 - linoleoyl - GPE, 1-palmitoyl-2-linoleoyl-GPE, and X-21470 were found to have a protective effect. No heterogeneity and pleiotropy were observed in the significant metabolites (p > 0.05), and each metabolite exhibited a consistent effect direction across all five methods. BWMR analysis results confirmed the significance and direction of effects across exposures, except for Cholesterol to linoleoyl-arachidonoyl-glycerol ratio(p = 0.673). Pathway analysis suggests that glycerophospholipid metabolism may potentially be a mechanism underlying the development of asthma. CONCLUSION: Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical asthma screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection.
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Background: Surgical pain affects postoperative sleep quality, and they jointly form a vicious cycle of mutual influence. The cycle of postoperative pain and sleep disorders could lead to delirium, cardiovascular disease, and hyperalgesia, which significantly affect patients' postoperative recovery. Thus, exploring this phenomenon is of great importance for surgical patients, and warrants further investigation. Objective: By employing bibliometric methods, this study systematically analyzes the publications on postoperative pain-sleep disorders, identifies research trends and field dynamics, and ultimately provides insights for further progress in this research area. Methods: In this study, we searched the Web of Science database for studies on postoperative pain and sleep disorders from 2013 to 2023, and analyzed the number of publications, journals, authors, institutions, country regions, and keywords by utilizing CiteSpace, VOSviewer, and Bibliometrix. Results: The 1894 retrieved publications showed a trend of increasing number of publications and correlations between postoperative pain and sleep disorders from 2013 to 2023. The top countries for publications included the USA, China, etc., establishing a global collaborative network centered around the USA, China, and Europe. The top institutions for publications included University of California System, Harvard University, etc. The top authors include Christine Miaskowski, Steven M. Paul, Qiuling Shi, etc. These publications involved multiple disciplines including surgery, neurology, and anesthesiology, and various research funds including NIH, HHS, NSFC, etc. The top journals for publications included the European Archives of Oto-Rhino-Laryngology, etc. Keywords that appear most frequently in this field include "pain", "surgery", "quality of life", "sleep", "depression", and "outcomes". The thematic map indicated that the hot topics in this area include obstructive sleep apnea, tonsillectomy, children, pain, quality of life, and sleep. The undeveloped topics with research potential included postoperative pain, analgesia and dexmedetomidine, breast cancer, fatigue, and lung cancer. Conclusion: The increased number of publications and correlations between postoperative pain and sleep disorders, and the collaborative network across the USA, China, and Europe indicate a growing global interest in this area. This study also provides valuable insights into the trend of hot topics and frontiers and shows that this is an evolving and dynamic research area.
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The Penicillium genus exhibits a broad global distribution and holds substantial economic value in sectors including agriculture, industry, and medicine. Particularly in agriculture, Penicillium species significantly impact plants, causing diseases and contamination that adversely affect crop yields and quality. Timely detection of Penicillium species is crucial for controlling disease and preventing mycotoxins from entering the food chain. To tackle this issue, we implement a novel species identification approach called Analysis of whole GEnome (AGE). Here, we initially applied bioinformatics analysis to construct specific target sequence libraries from the whole genomes of seven Penicillium species with significant economic impact: P. canescens, P. citrinum, P. oxalicum, P. polonicum, P. paneum, P. rubens, and P. roqueforti. We successfully identified seven Penicillium species using the target we screened combined with Sanger sequencing and CRISPR-Cas12a technologies. Notably, based on CRISPR-Cas12a technology, AGE can achieve rapid and accurate identification of genomic DNA samples at a concentration as low as 0.01 ng/µL within 30 min. This method features high sensitivity and portability, making it suitable for on-site detection. This robust molecular approach provides precise fungal species identification with broad implications for agricultural control, industrial production, clinical diagnostics, and food safety.
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Genoma Fúngico , Penicillium , Penicillium/genética , Penicillium/classificação , Penicillium/isolamento & purificação , Sistemas CRISPR-Cas , Sequenciamento Completo do Genoma/métodos , Biologia Computacional/métodos , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/economia , FilogeniaRESUMO
Mumps is a vaccine-preventable acute viral infectious disease. To understand the incidence of mumps and population immunity in Quzhou City after measles mumps rubella vaccine (MMR) was included in the immunization program, we analyzed the epidemiological characteristics of mumps cases from 2009 to 2023 and a cross-sectional serosurvey of IgG antibodies to mumps conducted in 2024. We found that 15 years after the MMR vaccine was included in the immunization program, the incidence of mumps was significantly reduced in all populations, but the incidence remained highest in vaccinated children aged 0-12 years. Vaccine escape may explain the high incidence of mumps in highly vaccinated populations. Updating vaccines or developing a new vaccine that targets multiple viral genotypes may be necessary to improve the effectiveness of the vaccine against infection and fully control infections and outbreaks. The positive rate and concentration of mumps IgG antibody were inconsistent with the incidence data. mumps IgG antibody is not an ideal substitute for immunity and cannot be used to accurately predict whether a target population is susceptible or protected. Natural infections may provide longer-lasting immunity than vaccination.
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Anticorpos Antivirais , Programas de Imunização , Imunoglobulina G , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba , Humanos , Caxumba/epidemiologia , Caxumba/prevenção & controle , Caxumba/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Pré-Escolar , Lactente , Anticorpos Antivirais/sangue , Criança , Feminino , Incidência , Adolescente , Imunoglobulina G/sangue , Masculino , Estudos Transversais , Adulto Jovem , Adulto , China/epidemiologia , Estudos Soroepidemiológicos , Pessoa de Meia-Idade , Vírus da Caxumba/imunologia , Vírus da Caxumba/genética , Recém-NascidoRESUMO
BACKGROUND: The newly described inflammatory burden index (IBI) reflects a patient's inflammatory burden. This study aimed to estimate the association between IBI, osteoarthritis (OA), and all-cause mortality in patients with OA. METHODS: We extracted the data of adults from the National Health and Nutrition Examination Survey database between 1999 and 2018. After using appropriate survey weights to correct for sample bias, we conducted multivariate logistic regression analyses to explore the association between IBI and OA across three models: in the unadjusted model, partially adjusted model (adjusting age, sex, race, education level, marital status, PIR, BMI, smoking status, drinking status, stroke, CVD, DM, and hypertension) and fully adjusted model (which included additional variables: HBA1C, ALT, AST, BUN, TC, and HDL). And the odds ratios (OR) and 95% confidence intervals (CI) were calculated. Similarly, using comparable survey weights and covariates adjustments, we employed Cox proportional hazards regression analysis to investigate the association between IBI and all-cause mortality in the other 3 models. The Cox proportional hazards regression models were fitted to calculate the hazard ratios (HR) and 95% CI of the association between IBI and all-cause mortality. A restricted cubic spline (RCS) was used to explore the nonlinear relationships between association effects. Subgroup analysis was performed to validate the reliability of their effects. RESULTS: In total, 22,343 eligible participants were included. Multiple logistic regression models revealed that participants with the highest IBI had 2.54 times (95%CI, 2.23, 2.90)) higher risk of OA than those with the lowest IBI in Model 1, whereas the OR was 1.21 (95%CI, 1.03, 1.42) in Model 2 and 1.23 (95%CI,1.05, 1.45) in Model 3. Multiple Cox regression models showed participants with the highest IBI had 186% (95%CI, 1.50, 2.31) times risk of developing all-cause death than those with the lowest IBI in Model 1. This trend remained stable in Models 2 (HR,1.54; 95%CI,1.22, 1.95) and 3 (HR, 1.41; 95%CI, 1.10, 1.80). The RCS revealed a significant positive association between IBI and OA risk. With respect to the association between IBI and all-cause mortality, a slight decrease in mortality was observed from the lowest quartile to the second quartile of IBI, and the mortality risk increased with increasing IBI. Subgroup analyses showed that age, cardiovascular disease, and hypertension were pivotal in the association of IBI with all-cause mortality, whereas the association of IBI with OA remained stable after stratification by other factors such as sex, race, education level, marital, smoking, and drinking status, hypertension, and most serological indices. CONCLUSIONS: This study provides evidence of a positive association between IBI, OA, and all-cause mortality. IBI may be a promising signature for assessing the inflammatory burden in patients with OA, which, in turn, is conducive to precise references for high-risk population recognition, anti-inflammatory guidance, and reducing mortality intervention.
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Inflamação , Inquéritos Nutricionais , Osteoartrite , Humanos , Masculino , Feminino , Osteoartrite/mortalidade , Pessoa de Meia-Idade , Idoso , Inflamação/mortalidade , Adulto , Causas de Morte , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Background: Perioperative neurocognitive disorders (PND) refer to neurocognitive abnormalities during perioperative period, which are a great challenge for elderly patients and associated with increased morbidity and mortality. Our studies showed that long non-coding RNAs (lncRNAs) regulate mitochondrial function and aging-related pathologies in the aged hippocampus after anesthesia, and lncRNAs are associated with multiple neurodegenerations. However, the regulatory role of lncRNAs in PND-related pathological processes remains unclear. Methods: A total of 18-month mice were assigned to control and surgery (PND) groups, mice in PND group received sevoflurane anesthesia and laparotomy. Cognitive function was assessed with fear conditioning test. Hippocampal RNAs were isolated for sequencing, lncRNA and microRNA libraries were constructed, mRNAs were identified, Gene Ontology (GO) analysis were performed, and lncRNA-microRNA-mRNA networks were established. qPCR was performed for gene expression verification. Results: A total of 312 differentially expressed (DE) lncRNAs, 340 DE-Transcripts of Uncertain Coding Potential (TUCPs), and 2,003 DEmRNAs were identified in the hippocampus between groups. The lncRNA-microRNA-mRNA competing endogenous RNA (ceRNA) network was constructed with 29 DElncRNAs, 90 microRNAs, 493 DEmRNAs, 148 lncRNA-microRNA interaction pairs, 794 microRNA-mRNA interaction pairs, and 110 lncRNA-mRNA co-expression pairs. 795 GO terms were obtained. Based on the frequencies of involved pathological processes, BP terms were divided into eight categories: neurological system alternation, neuronal development, metabolism alternation, immunity and neuroinflammation, apoptosis and autophagy, cellular communication, molecular modification, and behavior changes. LncRNA-microRNA-mRNA ceRNA networks in these pathological categories were constructed, and involved pathways and targeted genes were revealed. The top relevant lncRNAs in these ceRNA networks included RP23-65G6.4, RP24-396L14.1, RP23-251I16.2, XLOC_113622, RP24-496E14.1, etc., and the top relevant mRNAs in these ceRNA networks included Dlg4 (synaptic function), Avp (lipophagy), Islr2 (synaptic function), Hcrt (regulation of awake behavior), Tnc (neurotransmitter uptake). Conclusion: In summary, we have constructed the lncRNA-associated ceRNA network during PND development in mice, explored the role of lncRNAs in multiple pathological processes in the mouse hippocampus, and provided insights into the potential mechanisms and therapeutic gene targets for PND.
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Redes Reguladoras de Genes , Hipocampo , MicroRNAs , RNA Longo não Codificante , RNA Mensageiro , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transtornos Neurocognitivos/genética , Transtornos Neurocognitivos/metabolismo , Transtornos Neurocognitivos/patologia , Masculino , Período Perioperatório , Sevoflurano , Camundongos Endogâmicos C57BL , RNA Endógeno CompetitivoRESUMO
Electrochemical formic acid oxidation reaction (FAOR) is a pivotal model for understanding organic fuel oxidation and advancing sustainable energy technologies. Here, we present mechanistic insights into a novel molecular-like iridium catalyst (Ir-N4-C) for FAOR. Our studies reveal that isolated sites facilitate a preferential dehydrogenation pathway, circumventing catalyst poisoning and exhibiting high inherent activity. In-situ spectroscopic analyses elucidate that weakly adsorbed intermediates mediate the FAOR and are dynamically regulated by potential-dependent redox transitions. Theoretical and experimental investigations demonstrate a parallel mechanism involving two key intermediates with distinct pH and potential sensitivities. The rate-determining step is identified as the adsorption of formate via coupled or sequential proton-electron transfer, which aligns well with the observed kinetic properties, pH dependence, and hydrogen/deuterium isotope effects in experiments. These findings provide valuable insights into the reaction mechanism of FAOR, advancing our understanding at the molecular level and potentially guiding the design of efficient catalysts for fuel cells and electrolyzers.
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Guided bone-regeneration membrane (GBRM) is commonly used in bone-repair surgery because it blocks fibroblast proliferation and provides spatial support in bone-defect spaces. However, the need for removal surgery and the lack of antibacterial properties of conventional GBRM limit its therapeutic applicability for alveolar bone defects. Here we developed a GBRM for alveolar bone-repair and -regeneration applications through double-sided electrospinning of polycaprolactone and chitosan layers on a Zn mesh surface (denoted DSZM). The DSZM showed a UTS of â¼25.6 MPa, elongation of â¼16.1%, strength-elongation product of â¼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times higher than that of commercial Bio-Gide membrane. The DSZM exhibited a corrosion rate of â¼17 µm/y and a Zn ion concentration of â¼0.23 µg/ml after 1 month of immersion in Hanks' solution. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model. Overall, the DSZM fits the requirements for alveolar bone-repair and -regeneration applications as a biodegradable GBRM material due to its spatial support, suitable degradability, cytocompatibility, and antibacterial and osteogenic capabilities. STATEMENT OF SIGNIFICANCE: This work reports the mechanical properties, antibacterial ability and osteogenic properties of electrospun PCL-CS nanofiber on Zn mesh as biodegradable guided bone-regeneration membrane for alveolar bone-repair applications. Our findings demonstrate that the DSZM prepared by double-sided electrospinning of PCL-CS layers on Zn mesh showed a UTS of â¼25.6 MPa, elongation of â¼16.1%, strength-elongation product of â¼0.413 GPa%, and ultrahigh spatial maintenance ability, and the UTS was over 6 times greater than that of commercial Bio-Gide® membrane. The DSZM showed direct and indirect cytocompatibility with exceptional osteogenic differentiation and calcium deposition toward MC3T3-E1 cells. Further, the DSZM showed strongly sustained antibacterial activity against S. aureus and osteogenesis in a rat critical-sized maxillary defect model.
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Antibacterianos , Regeneração Óssea , Quitosana , Nanofibras , Osteogênese , Poliésteres , Zinco , Animais , Poliésteres/química , Poliésteres/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Nanofibras/química , Quitosana/química , Quitosana/farmacologia , Zinco/química , Zinco/farmacologia , Camundongos , Osteogênese/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Ratos Sprague-Dawley , Membranas Artificiais , Staphylococcus aureus/efeitos dos fármacos , Ratos , Masculino , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Regeneração Tecidual Guiada/métodos , Linhagem CelularRESUMO
INTRODUCTION: Esophageal-squamous Cell Carcinoma (ESCC) is often diagnosed at the middle or late stage, thus requiring more effective therapeutic strategies. Pharmacologically, the anti-tumor activity of the principal active constituent of Sophora flavescens, matrine (MA), has been explored widely. Notwithstanding, it is significant to nanotechnologically enhance the anti-tumor activity of MA in view of its potential to distribute non-tumor cells. METHODS: Herein, MA-loaded Nano-Liposomes (MNLs) were prepared to enhance the effect of anti-ESCC. The MNL showed a smaller sized particle (25.95 ± 1.02 nm) with a low polydispersed index (PDI = 0.130 ± 0.054), uniform spherical morphology, good solution stability, and encapsulated efficiency (65.55% ± 2.47). Furthermore, we determined the characteristics of KYSE-150 cells by cell viability assay, IC50, Mitochondrial Membrane Potential (MMP), Western blot, and apoptotic analysis, which indicated that MNLs down-regulated the cell viability and IC50 in a concentration-dependent manner and induced a significant change in JC-1 fluorescence from red to green. RESULTS: The above observations resulted in increased Bax and Caspase-3 levels, coupled with a substantial decrease in Bcl-2 and apoptotic promotion at the advanced stage compared with MA. CONCLUSION: Based on these results, MNLs may serve as a more effective and promising therapeutic option for ESCC.
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Alcaloides , Apoptose , Sobrevivência Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Lipossomos , Matrinas , Quinolizinas , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/administração & dosagem , Quinolizinas/farmacologia , Quinolizinas/química , Quinolizinas/administração & dosagem , Humanos , Apoptose/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Lipossomos/química , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/patologia , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Nanopartículas/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Tamanho da Partícula , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Células Tumorais Cultivadas , Relação Estrutura-AtividadeRESUMO
Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.
RESUMO
Objective: To explore the knowledge, attitude, and practice (KAP) toward interstitial lung disease (ILD) among patients and analyze the factors affecting KAP. Methods: This cross-sectional study enrolled patients with ILD treated at the Respiratory Department of Shanghai Pulmonary Hospital between January 2023 and June 2023. A self-administered questionnaire was developed to evaluate their KAP toward ILD through convenient sampling. Multivariate regression analysis and structural equation model (SEM) were used to analyze the factors influencing KAP and their interactions. Results: A total of 397 patients were enrolled, with 61.71% male. The mean KAP scores were 4.60 ± 3.10 (possible range: 0-12), 16.97 ± 2.16 (possible range: 5-25), and 32.60 ± 7.16 (possible range: 9-45), respectively. Multivariate logistic regression analysis showed that junior high school [OR = 2.003, 95%CI: 1.056-3.798, p = 0.033], high school and above [OR = 2.629, 95%CI: 1.315-5.258, p = 0.006], and duration of disease ≥5 years [OR = 1.857, 95%CI: 1.132-3.046, p = 0.014] were independently associated with adequate knowledge. The knowledge [OR = 1.108, 95%CI: 1.032-1.189, p = 0.005] and duration of disease ≥5 years [OR = 0.525, 95%CI: 0.317-0.869, p = 0.012] were independently associated with a positive attitude. The knowledge [OR = 1.116, 95%CI: 1.036-1.202, p = 0.004], attitude [OR = 1.180, 95%CI: 1.061-1.312, p = 0.002], and the age of >70 years [OR = 0.447, 95%CI: 0.245-0.817, p = 0.009] were independently associated with the proactive practice. SEM showed that patients' knowledge of ILD directly affected their attitude (ß = 0.842, p < 0.001) and practice (ß = 0.363, p < 0.001), and their attitude also affected their practice (ß = 0.347, p = 0.014). Conclusion: Patients with ILD in China had poor knowledge, intermediate attitude, and proactive practice toward ILD, which suggests that the health education of patients should be further strengthened.