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Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries.
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BACKGROUND: Plant-based diets (PBDs) and planetary-health diets (PHDs) are recommended for their potential health and environmental benefits, but population-based evidence in diverse cultures is scarce. METHODS: We included 9364 adults aged 45 years and older (52·3% female, 47·7% male) from the open cohort of the China Health and Nutrition Survey. Dietary intake was assessed using 3-day 24 h dietary recalls combined with weighing methods from 1997 to 2011, and mortality was documented from 1997 to 2015. We calculated the overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI; ranges 18-90), and the PHD score (range 0-140). We also estimated the related greenhouse gas emissions, land appropriation, and total water footprint and examined their associations with mortality. FINDINGS: PBD indices were inversely related to greenhouse gas emissions, land appropriation, and total water footprint, whereas higher PHD score was related to higher environmental burdens (p<0·0001). During follow-up (mean 9·2 years), 792 (8·5%) death cases were documented. PDI (HR 1·08 [95% CI 0·88-1·32]) and hPDI (0·98 [0·80-1·21]) were not significantly associated with mortality, whereas higher uPDI was related to a higher mortality risk (1·55 [1·26-1·91]). In contrast, higher PHD score was associated with lower mortality risk (0·79 [0·63-0·99]). INTERPRETATION: The PBDs showed environmental benefits, but are not necessarily associated with lower mortality risk. The PHD, developed mainly in western populations, was related to lower mortality risk but higher environmental burdens in the Chinese population. FUNDING: Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and National Natural Science Foundation of China.
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Mortalidade , Humanos , China/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Dieta Vegetariana , Gases de Efeito Estufa/análise , Gases de Efeito Estufa/efeitos adversos , Dieta Saudável/estatística & dados numéricosRESUMO
Aim: The present study was designed to investigate the coregulatory effects of multiple histone modifications (HMs) on gene expression in lung adenocarcinoma (LUAD). Materials & methods: Ten histones for LUAD were analyzed using ChIP-seq and RNA-seq data. An innovative computational method is proposed to quantify the coregulatory effects of multiple HMs on gene expression to identify strong coregulatory genes and regions. This method was applied to explore the coregulatory mechanisms of key ferroptosis-related genes in LUAD. Results: Nine strong coregulatory regions were identified for six ferroptosis-related genes with diverse coregulatory patterns (CA9, PGD, CDKN2A, PML, OTUB1 and NFE2L2). Conclusion: This quantitative method could be used to identify important HM coregulatory genes and regions that may be epigenetic regulatory targets in cancers.
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Globally, the incidence of diabetes mellitus (DM) and Alzheimer's disease (AD) is increasing year by year, causing a huge economic and social burden, and their pathogenesis and aetiology have been proven to have a certain correlation. In recent years, more and more studies have shown that vacuolar adenosine triphosphatases (v-ATPases) in eukaryotes, which are biomolecules regulating lysosomal acidification and glycolipid metabolism, play a key role in DM and AD. This article describes the role of v-ATPase in DM and AD, including its role in glycolysis, insulin secretion and insulin resistance (IR), as well as its relationship with lysosomal acidification, autophagy and ß-amyloid (Aß). In DM, v-ATPase is involved in the regulation of glucose metabolism and IR. v-ATPase is closely related to glycolysis. On the one hand, v-ATPase affects the rate of glycolysis by affecting the secretion of insulin and changing the activities of key glycolytic enzymes hexokinase (HK) and phosphofructokinase 1 (PFK-1). On the other hand, glucose is the main regulator of this enzyme, and the assembly and activity of v-ATPase depend on glucose, and glucose depletion will lead to its decomposition and inactivation. In addition, v-ATPase can also regulate free fatty acids, thereby improving IR. In AD, v-ATPase can not only improve the abnormal brain energy metabolism by affecting lysosomal acidification and autophagy but also change the deposition of Aß by affecting the production and degradation of Aß. Therefore, v-ATPase may be the bridge between DM and AD.
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Doença de Alzheimer , Diabetes Mellitus , Glicólise , ATPases Vacuolares Próton-Translocadoras , Doença de Alzheimer/metabolismo , Humanos , ATPases Vacuolares Próton-Translocadoras/metabolismo , Animais , Diabetes Mellitus/metabolismo , Glicólise/fisiologia , Resistência à Insulina , Lisossomos/metabolismo , Autofagia/fisiologiaRESUMO
In mammals, miRNAs recognize target mRNAs via base pairing, which leads to a complex 'multiple-to-multiple' regulatory network. Previous studies have focused on the regulatory mechanisms and functions of individual miRNAs, but alterations of many individual miRNAs do not strongly disturb the miRNA regulatory network. Recent studies revealed the important roles of global miRNA dosage control events in physiological processes and pathogenesis, suggesting that miRNAs can be considered as a 'cellular buffer' that controls cell fate. Here, we review the current state of research on how global miRNA dosage is tightly controlled to regulate development, tumorigenesis, neurophysiology, and immunity. We propose that methods of controlling global miRNA dosage may serve as effective therapeutic tools to cure human diseases.
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MicroRNAs , Animais , Humanos , MicroRNAs/genética , RNA Mensageiro/genética , MamíferosRESUMO
OBJECTIVE@#To investigate the feasibility of mimics software in analyzing a new type of complex anterior cervical fixation -- anterior transpedicular screw fixation+zero notch internal fixation.@*METHODS@#From January 2021 to September 2022, 50 normal pedestrians who underwent cervical spine CT scanning were selected for C1-C7 segment scanning, including 27 males and 23 females, aged from 25 to 65 years old with an average of (46.0 ± 9.0) years old. The dicom format is exported and engraved into the CD, and use the mimics software to perform 3D reconstruction of each segment. A simulated screw is placed on the image according to the critical value of zero notch screw (head and tail angle 44°, internal angle 29°). The position of zero notch screw in each segment is observed to determine the feasibility of anterior transpedicular screw fixation plus zero notch internal fixation.@*RESULTS@#For the upper zero notch screws the three-dimensional images of the cervical spine across all 50 subjects within the C3-C7 segments demonstrated safe position, with no instances of intersection with ATPS. For the lower zero notch screw, in C3-C4 and C4-C5, 4 out of 50 subjects are in the safe position in the three-dimensional images of cervical vertebrae, and 46 cases could achieve secure screw placement when the maximum caudal angle is(32.3±1.9) ° and (36.1±2.2) °, respectively. In C5-C6 and C6-C7 segments, no lower zero notch screws intersected with ATPS, and all screws are in safe positions.@*CONCLUSION@#Lower cervical anterior pedicle screw fixation plus zero notch internal fixation can achieve successful nail placement through the selected entry point and position.
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Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Estudos de Viabilidade , Tomografia Computadorizada por Raios X/métodos , Parafusos Pediculares , Fixação Interna de Fraturas , Vértebras Cervicais/cirurgia , SoftwareRESUMO
Overall cancer hypomethylation had been identified in the past, but it is not clear exactly which hypomethylation site is the more important for the occurrence of cancer. To identify key hypomethylation sites, we studied the effect of hypomethylation in twelve regions on gene expression in colon adenocarcinoma (COAD). The key DNA methylation sites of cg18949415, cg22193385 and important genes of C6orf223, KRT7 were found by constructing a prognostic model, survival analysis and random combination prediction a series of in-depth systematic calculations and analyses, and the results were validated by GEO database, immune microenvironment, drug and functional enrichment analysis. Based on the expression values of C6orf223, KRT7 genes and the DNA methylation values of cg18949415, cg22193385 sites, the least diversity increment algorithm were used to predict COAD and normal sample. The 100 % reliability and 97.12 % correctness of predicting tumor samples were obtained in jackknife test. Moreover, we found that C6orf223 gene, cg18949415 site play a more important role than KRT7 gene, cg22193385 site in COAD. In addition, we investigate the impact of key methylation sites on three-dimensional chromatin structure. Our results will be help for experimental studies and may be an epigenetic biomarker for COAD.
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Adenocarcinoma , Neoplasias do Colo , Humanos , Metilação de DNA , Reprodutibilidade dos Testes , Biomarcadores , Microambiente TumoralRESUMO
Background: While maternal adherence to a healthy lifestyle was shown to be associated with a lower risk of obesity in offspring, the potential role of overall parental lifestyles has not yet been explored. We aimed to address this gap by exploring whether parental adherence to an overall healthy lifestyle was associated with a lower risk of obesity in offspring. Methods: We included 5881 children and adolescents aged 6-15 years at enrolment in the 2010, 2012, and 2014 waves of the China Family Panel Studies (CFPS) who were free of obesity and followed them until 2020. Parental healthy lifestyle score at study baseline was composed of five modifiable lifestyle factors (0-5; 1 for each): never smoking, non-habitual drinking, weekly exercise, modified dietary diversity score ≥5 points, and body mass index (BMI) of 18.5-23.9 kg/m2. We defined obesity according to the age- and gender-specific cutoffs by the BMI percentile curves for Chinese children aged 6-18 years. We used multivariable Cox proportional hazard models to examine the association between parental healthy lifestyle score (both as continuous and categorical variables) and risk of offspring obesity. Results: Overall, 597 (10.2%) offspring developed obesity during a median follow-up of 6 years. Compared to the lowest tertile of parental healthy lifestyle score, participants in the highest tertile had a 42% (hazard ratio (HR) = 0.58; 95% confidence interval (CI) = 0.45-0.74) lower risk of obesity. Both maternal (HR = 0.75; 95% CI = 0.61-0.92) and paternal (HR = 0.73; 95% CI = 0.60-0.89) healthy lifestyle scores were associated with lower risks of obesity in offspring. For specific lifestyle factors, we observed beneficial associations for paternal diverse diet (HR = 0.73; 95% CI = 0.60-0.88) and healthy BMI (HR = 0.65; 95% CI = 0.55-0.78). Conclusions: Adherence to an overall parental healthier lifestyle was associated with a lower risk of obesity in childhood and adolescence. This finding highlights the potential benefits of promoting a healthy lifestyle among parents for the primary prevention of offspring obesity.
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Obesidade Infantil , Masculino , Criança , Adolescente , Humanos , Obesidade Infantil/epidemiologia , Obesidade Infantil/prevenção & controle , Estudos Prospectivos , Estilo de Vida Saudável , Pais , Pai , Fatores de RiscoRESUMO
Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment. Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs. Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new "neural relays" developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion: The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.
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Nanofibras , Células-Tronco Neurais , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Ratos , Animais , Diferenciação Celular , Alicerces Teciduais/químicaRESUMO
Background: Genital inflammation is one of the most frequent clinical complaints among girls, which was easily overlooked by the general public. This study aimed to investigate the patterns and epidemiological characteristics of pediatric and adolescent female genital inflammation in China. Methods: A retrospective observational study (2011 to 2018) was conducted among all female patients under the age of 0-18 years at the Department of Pediatric and Adolescent Gynecology of The Children's Hospital, Zhejiang University School of Medicine. Data were collected from the electronic medical records. The abnormal vaginal discharge of patient was collected for microbiological investigation by bacterial and fungal culture. Descriptive analysis was conducted to evaluate the genital inflammation pattern and epidemiological characteristics, including age, season, and type of infected pathogens. Results: A total of 49,175 patients met the eligibility criteria of genital inflammation and 16,320 patients later came to the hospital for follow-up over the study period. The number of first-visit increased gradually from 3,769 in 2011 to 10,155 in 2018. The peak age of the first visit was 0-6 years old. Non-specific vulvovaginitis, lichen sclerosis, and labial adhesion were the top three genital inflammation. Among the top five potential common pathogens of vaginal infection, the prevalence of Haemophilus influenzae cases was the highest (31.42%, 203/646), followed by Streptococcus pyogenes (27.74%, 176/646), Candida albicans (14.09%, 91/646), Escherichia coli (8.51%, 55/646), and Staphylococcus aureus (6.35%, 41/636). The specific disease categories and pathogens of genital inflammation vary by age groups and season. Conclusion: Our study summarizes the pattern of pediatric and adolescent female genital inflammation over an 8-year period in China, emphasizing the need for more public awareness, healthcare services and research in this field.
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Genitália , Inflamação , Humanos , Criança , Adolescente , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Estudos Retrospectivos , Inflamação/epidemiologia , China/epidemiologia , Escherichia coli , Hospitais Pediátricos , Genitália FemininaRESUMO
Global south countries, including China, have faced a challenging dilemma of reducing carbon emissions while maintaining rapid economic growth. The low-carbon city pilots (LCCPs) policy in China is a demonstration of how state power intervenes and commands national low-carbon development through voluntary policy tools. Our study, based on panel data of 331 cities from 2005 to 2019, evaluates the policy effect of all three batches of LCCPs and presents an analysis of time-varying effects through batch decomposition and synthetic difference-in-difference models. The study found that implementing low-carbon policies can significantly reduce total carbon emissions and carbon emissions per capita. However, the reduction in carbon emissions per unit of GDP is insignificant, and the policy effect varies according to the batches and their characteristics. The reduction effects in the first and second batches, as well as the insignificance or even increasing effects of the third batch, may be due to carbon leakage between different batches of LCCPs. Overall, this research provides novel and quantitative evidence on low-carbon development in China, making theoretical and empirical contributions to the field, and expanding econometric assessment methods to evaluate the effectiveness of environmental and climate change policies.
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Carbono , Pilotos , Humanos , Cidades , Carbono/análise , Dióxido de Carbono/análise , China , Desenvolvimento EconômicoRESUMO
Diseases caused by bacterial infection have resulted in serious harm to human health. It is crucial to develop a multifunctional antibiotic-independent antibacterial platform for combating drug-resistant bacteria. Herein, titanium diboride (TiB2) nanosheets integrated with quaternized chitosan (QCS) and indocyanine green (ICG) were successfully prepared as a synergetic photothermal/photodynamic antibacterial nanoplatform (TiB2-QCS-ICG). The TiB2-QCS-ICG nanocomposites exhibit effective photothermal conversion efficiency (24.92%) and excellent singlet oxygen (1O2) production capacity simultaneously under 808 nm near-infrared irradiation. QCS improved TiB2 stability and dispersion, while also enhancing adhesion to bacteria and further accelerating the destruction of bacteria by heat and 1O2. In vitro experiments indicated that TiB2-QCS-ICG had excellent antibacterial properties with an inhibition rate of 99.99% against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA), respectively. More importantly, in vivo studies revealed that the nanoplatform can effectively inhibit bacterial infection and accelerate wound healing. The effective wound healing rate in the TiB2-QCS-ICG treatment group was 99.6% which was much higher than control groups. Taken together, the as-developed TiB2-QCS-ICG nanocomposite provides more possibilities to develop metal borides for antibacterial infection applications.
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Staphylococcus aureus Resistente à Meticilina , Nanocompostos , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Escherichia coli , Verde de Indocianina/farmacologia , Compostos de Boro/farmacologia , Nanocompostos/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
Several studies have shown the effects of PM2.5 exposure on respiratory and cardiovascular systems. However, there is no cohort study evidence of adverse effects of PM2.5 exposure on survival in patients with hepatocellular carcinoma (HCC) in China. This study is aimed at evaluating this association. This cohort study included 1440 HCC patients treated at the Third Central Clinical College of Tianjin Medical University from September 2013 to December 2018. We collected patient information, including demographic data, medical history, lifestyle characteristics, and disease characteristics. Based on PM2.5 concentrations measured at monitoring stations, the inverse distance weighted (IDW) method was used to assess the individuals' exposure during their survival period. Survival status was analysed by the Kaplan-Meier method. Restricted cubic splines and Cox proportional hazards models were used to estimate the relationship between PM2.5 and mortality, and potential confounders were adjusted for. The mortality rate of HCC patients exposed to PM2.5 ≥ 58.56 µg/m3 was significantly higher than that of HCC patients living in environments with PM2.5 < 58.56 µg/m3 (79.0% vs 50.7%, P < 0.001). The restricted cubic spline model showed a linear relationship between the PM2.5 concentration and mortality risk (P overall-association < 0.0001 and P nonlinear-association = 0.3568). Cox regression analysis showed that after adjusting for confounding factors, for every 10-µg/m3 increase in atmospheric PM2.5, the risk of death for HCC patients increased by 44% [hazard ratio (HR) = 1.44, 95% confidence interval (CI) 1.34, 1.56; P < 0.001]. Compared with patients exposed to PM2.5 <58.56 µg/m3, those exposed to PM2.5 ≥ 58.56 µg/m3 had a 1.55-fold increased risk of death. Stratified analysis results showed that the effects of PM2.5 on HCC mortality were more significant in patients aged ≥60 years or patients living in central urban areas. We found that exposure to elevated PM2.5 after HCC diagnosis may affect survival, with a higher concentration corresponding to a greater effect.
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Poluentes Atmosféricos , Poluição do Ar , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/induzido quimicamente , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , Neoplasias Hepáticas/epidemiologia , Exposição Ambiental/análise , China/epidemiologia , MortalidadeRESUMO
Phototherapy and sonotherapy are recognized by scientific medicine as effective strategies for treating certain cancers. However, these strategies have limitations such as an inability to penetrate deeper tissues and overcome the antioxidant tumor microenvironment. In this study, a novel "BH" interfacial-confined coordination strategy to synthesize hyaluronic acid-functionalized single copper atoms dispersed over boron imidazolate framework-derived nanocubes (HA-NC_Cu) to achieve sonothermal-catalytic synergistic therapy is reported. Notably, HA-NC_Cu demonstrates exceptional sonothermal conversion performance under low-intensity ultrasound irradiation, attained through intermolecular lattice vibrations. In addition, it shows promise as an efficient biocatalyst, able to generate high-toxicity hydroxyl radicals in response to tumor-endogenous hydrogen peroxide and glutathione. Density functional theory calculations reveal that the superior parallel catalytic performance of HA-NC_Cu originates from the CuN4 C/B active sites. Both in vitro and in vivo evaluations consistently demonstrate that the sonothermal-catalytic synergistic strategy significantly improves tumor inhibition rate (86.9%) and long-term survival rate (100%). In combination with low-intensity ultrasound irradiation, HA-NC_Cu triggers a dual death pathway of apoptosis and ferroptosis in MDA-MB-231 breast cancer cells, comprehensively limiting primary triple-negative breast cancer. This study highlights the applications of single-atom-coordinated nanotherapeutics in sonothermal-catalytic synergistic therapy, which may create new opportunities in biomedical research.
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Neoplasias da Mama , Hipertermia Induzida , Humanos , Feminino , Cobre/química , Fototerapia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Peróxido de Hidrogênio/química , Microambiente TumoralRESUMO
Bioinspired by native nervous tracts, a spinal cord-mimicking model system that was composed of multiple nanofibrous yarns (NYs) ensheathed in a nanofibrous tube was constructed by an innovative electrospinning-based fabrication and integration strategy. The infilling NYs exhibited uniaxially aligned nanofibrous architecture that had a great resemblance to spatially-arranged native nervous tracts, while the outer nanofibrous tubes functioned as an artificial dura matter to provide a stable intraluminal microenvironment. The three-dimensional (3D) NYs were demonstrated to induce alignment, facilitate migration, promote neuronal differentiation, and even phenotypic maturation of seeded neural stem and progenitor cells (NSPCs), while inhibiting gliogenesis. Single-cell transcriptome analysis showed that the NSPC-loaded 3D NY model shared many similarities with native spinal cords, with a great increase in excitatory/inhibitory (EI) neuron ratio. Curcumin, as a model drug, was encapsulated into nanofibers of NYs to exert an antioxidant effect and enhanced axon regeneration. Overall, this study provides a new paradigm for the development of a next-generation in vitro neuronal model system via anatomically accurate nervous tract simulation and constructs a blueprint for the research on NSPC diversification in the biomimetic microenvironment.
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Nanofibras , Alicerces Teciduais , Axônios , Regeneração Nervosa , Neurônios , Diferenciação CelularRESUMO
With the COVID-19 pandemic evitably becoming the "New Normality" and will continue to impact human society much longer than anticipated, it is essential to explore effective measures that global ports can take to adapt to unexpected challenges in the post-COVID-19 era. This paper builds a port resilience index system based on the entropy weight method from a multistakeholder's view. We utilize the port resilience index system for 22 major Chinese ports during 2020-2021. We further investigate the direct impact of port resilience on port governance performance. Our results indicate that resiliently-governed ports can guarantee higher port throughput while sustaining lower congestion when facing challenges from the global pandemic.
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BACKGROUND: Maternal adherence to a healthy lifestyle has been associated with a lower risk of obesity in offspring. However, little is known about the potential effect of an overall healthy parental lifestyle on the development of obesity in children. We aimed to investigate the prospective association of parental adherence to a combination of healthy lifestyle factors with the risk of obesity in offspring. METHODS: Participants in the China Family Panel Studies, without obesity at baseline, were enrolled between April and September, 2010; between July, 2012, and March, 2013; and between July, 2014, and June, 2015; and followed up until the end of 2020. Parental healthy lifestyle score (ranged 0-5) was characterised by five modifiable lifestyle factors: smoking, alcohol consumption, exercise, diet, and BMI. The first occurrence of offspring obesity during the study follow-up period was defined by age-specific and sex-specific cutoff values of BMI. We used multivariable-adjusted Cox proportional hazard models to examine the associations between parental healthy lifestyle scores and risk of obesity in children. FINDINGS: We included 5881 participants aged 6-15 years; median follow-up was 6 years (IQR 4-8). A total of 597 (10·2%) participants developed obesity during follow-up. Compared with those in the lowest tertile of parental healthy lifestyle scores, participants in the top tertile had a 42% lower risk of obesity (multivariable-adjusted hazard ratio [HR] 0·58 [95% CI 0·45-0·74]). The association persisted in sensitivity analyses and was similar across major subgroups. Both maternal (HR 0·75 [95% CI 0·61-0·92]) and paternal (0·73 [0·60-0·89]) healthy lifestyle scores were independently associated with lower risks of obesity in offspring, with significant contributions observed for paternal diverse diet and healthy BMI. INTERPRETATION: Adherence to an overall parental healthier lifestyle was associated with a substantially lower risk of obesity in childhood and adolescence. This finding highlights the potential benefits of promoting a healthy lifestyle among parents for the primary prevention of obesity in offspring. FUNDING: Special Foundation for National Science and Technology Basic Research Program of China (grant reference 2019FY101002) and National Natural Science Foundation of China (grant reference 42271433).
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Obesidade Infantil , Adolescente , Criança , Feminino , Masculino , Humanos , Obesidade Infantil/epidemiologia , Estudos Prospectivos , Pais , Estilo de Vida Saudável , China/epidemiologiaRESUMO
The electrocatalytic nitrogen reduction reaction (NRR) for ammonia (NH3) under ambient conditions is emerging as a potentially sustainable alternative to the traditional, energy-intensive Haber-Bosch process for ammonia production. Currently, metal-based electrocatalysts constitute the majority of reported NRR catalysts. However, they often suffer from the shortcomings of competitive reactions of nitrogen adsorption/activation and hydrogen generation. Therefore, there is an urgent need to develop more environmentally friendly, low energy consumption, and non-polluting high-performance metal-free electrocatalysts. In this study, borocarbonitride (BCN) materials derived from boron imidazolate framework (BIF-20) were used to boost efficient electrochemical nitrogen conversion to ammonia under ambient conditions. The BCN catalyst demonstrated excellent performance in 0.1 M KOH, with an ammonia yield of 21.62 µg h-1 mgcat-1 and a Faradaic efficiency of 9.88% at -0.3 V (Reversible Hydrogen Electrode, RHE). This performance is superior to most metal-free catalysts and even some metal catalysts for NRR. The 15N2/14N2 isotope labeling experiments and density functional theory (DFT) calculations showed that N2 can be adsorbed and converted to NH3 on the surface of BCN, and that the energy barrier can be significantly reduced by structural design for BCN. This work highlights the important role played by the presence of Lewis acid-base pairs in metal-free catalysts for enhancing electrochemical NRR performance.
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This study aimed to investigate whether lactating Hu sheep's dietary protein levels could generate dynamic effects on the performance of their offspring. Twelve ewes with similar parity were fed iso-energy diets which contained different protein levels (P1: 9.82%, P2: 10.99%) (n = 6), and the corresponding offspring were divided into SP1 and SP2 (n = 12). At 60 days, half of the lambs were harvested for further study: the carcass weight (p = 0.043) and dressing percentage (p = 0.004) in the SP2 group were significantly higher than SP1. The acetic acid (p = 0.007), propionic acid (p = 0.003), butyric acid (p < 0.001) and volatile fatty acids (p < 0.001) in rumen fluid of SP2 were significantly lower than SP1. The expression of MCT2 (p = 0.024), ACSS1 (p = 0.039) and NHE3 (p = 0.006) in the rumen of SP2 was lower than SP1, while the HMGCS1 (p = 0.026), HMGCR (p = 0.024) and Na+/K+-ATPase (p = 0.020) was higher than SP1. The three dominant phyla in the rumen are Bacteroidetes, Proteobacteria and Firmicutes. The membrane transport, amino acid metabolism and carbohydrate metabolism of SP1 were relatively enhanced, the replication and repair function of SP2 was relatively enhanced. To sum up, the increase of dietary protein level significantly increased the carcass weight and dressing percentage of offspring and had significant effects on rumen volatile fatty acids, acetic acid activation and cholesterol synthesis related genes. HIGHLIGHTSIn the early feeding period, the difference in ADG of lambs was mainly caused by the sucking effect.The increase in dietary protein level of ewes significantly increased the carcass weight and dressing percentage of offspring.The dietary protein level of ewes significantly affected the volatile fatty acids (VFAs) and genes related to acetic acid activation and cholesterol synthesis in the rumen of their offspring.The membrane transport, amino acid metabolism and carbohydrate metabolism of the offspring of ewes fed with a low protein diet were relatively enhanced.The replication and repair function of the offspring of ewes fed with a high protein diet was relatively strengthened.
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Lactação , Rúmen , Gravidez , Animais , Ovinos , Feminino , Rúmen/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis , Acetatos/análise , Acetatos/metabolismo , Proteínas Alimentares/análise , Proteínas Alimentares/metabolismo , Aminoácidos/análise , Aminoácidos/metabolismo , Colesterol/metabolismo , Ração Animal/análise , Leite/química , Suplementos NutricionaisRESUMO
Objective To investigate the impacts of midazolam on the proliferation,migration and invasion of breast cancer MDA-MD-231 cells and its regulation on cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)signaling pathway.Methods MDA-MD-231 cells were cultured in vitro and grouped into control group,midazolam L group,midazolam M group,midazolam H group,and midazolam H+Sp-cAMPS group.Midazolam L group,midazolam M group,midazolam H group were treated with 5μmol/L,10μmol/L,and 20μmol/L of midazolam,respectively,midazolam H+Sp-cAMPS group was added with 20μmol/L of midazolam+10μmol/L of Sp-cAMPS 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)assay was applied to detect cell proliferation;The migration ability was detected by cell scratch test;Transwell test was applied to determine the invasion ability of cells;Cell apoptosis was detected by flow cytometry;The expression level of cAMP was detected by enzyme-linked immunosorbent assay(ELISA);Western blot was applied to verify the expression of phosphorylated(p-)PKA/PKA,p-CREB/CREB protein.Results Compared with control group,the cells in midazolam L group,midazolam M group,midazolam H group showed apoptosis,the apoptosis rate was obviously increased,the cell proliferation,migration and invasion abilities and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins were obviously decreased(P<0.05);Compared with midazolam H group,midazolam H+Sp-cAMPS group had good cell growth,obviously reduced apoptosis rate,and obviously increased cell proliferation,migration and invasion abilities,and the expression levels of cAMP,p-PKA/PKA,p-CREB/CREB proteins(P<0.05).Conclusion Midazolam may inhibit the proliferation,migration and invasion of breast cancer cells by inhibiting the activation of cAMP/PKA/CREB signaling pathway.