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Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19+ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8+ T cell responses. Serum CD19+ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19+ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19+ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19+ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD PrkdcscidIl2rg-/- mice. Thus, decreasing CD19+ EVs holds high potential to improve the chemotherapeutic antitumor effect.
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Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Vesículas Extracelulares/imunologia , Animais , Antígenos CD19/imunologia , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Células HEK293 , Herpesvirus Humano 4/imunologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Células NIH 3T3 , RNA Mensageiro/imunologia , Transcrição Gênica/imunologia , Proteínas rab27 de Ligação ao GTP/imunologiaRESUMO
Schizosaccharomyces pombe Php4 is the regulatory subunit of the CCAAT-binding complexes and plays an important role in the regulation of iron homeostasis and iron-dependent metabolism. Here, we show that Php4 undergoes ubiquitin-dependent degradation in the late logarithmic and stationary phases. The degradation and ubiquitination of Php4 could be attenuated by deletion of hul6, a gene encoding a putative HECT-type E3 ubiquitin ligase. The expression levels of Hul6 and Php4 are oppositely regulated during cell growth. Hul6 interacts with the C-terminal region of Php4. Two lysine residues (K217 and K274) located in the C-terminal region of Php4 are required for its polyubiquitination. Increasing the levels of Php4 by deletion of hul6 or overexpression of php4 decreased expression of Php4 target proteins involved in iron-dependent metabolic pathways such as the tricarboxylic cycle and mitochondrial oxidative phosphorylation, thus causing increased sensitivity to high-iron and reductions in succinate dehydrogenase and mitochondrial complex II activities. Hul6 is located primarily in the mitochondrial outer membrane and most likely targets cytosolic Php4 for ubiquitination and degradation. Taken together, our data suggest that Hul6 regulates iron-dependent metabolism through degradation of Php4 under normal growth conditions. Our results also suggest that Hul6 promotes iron-dependent metabolism to help the cell to adapt to a nutrient-starved growth phase.
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Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Citosol/metabolismo , Ferro/metabolismo , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Proteínas de Schizosaccharomyces pombe/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Ubiquitina/metabolismoRESUMO
Numerous epilepsy-related genes have been identified in recent decades by unbiased genome-wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation. In this study, we reveal the significant role of KCNQ2 and KCNQ3, two M-type potassium channel genes, in the onset of seizures in TLE. Our investigation began with a quantitative analysis of two publicly available TLE patient databases to establish a correlation between seizure onset and the downregulated expression of KCNQ2/3. We then replicated these pathological changes in a pilocarpine seizure mouse model and observed a decrease in spike frequency adaptation due to the affected M-currents in dentate gyrus granule neurons. In addition, we performed a small-scale simulation of the dentate gyrus network and confirmed that the impaired spike frequency adaptation of granule cells facilitated epileptiform activity throughout the network. This, in turn, resulted in prolonged seizure duration and reduced interictal intervals. Our findings shed light on an underlying mechanism contributing to ictogenesis in the TLE hippocampus and suggest a promising target for the development of antiepileptic drugs.
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Epilepsia do Lobo Temporal , Camundongos , Animais , Humanos , Epilepsia do Lobo Temporal/patologia , Giro Denteado/metabolismo , Convulsões/induzido quimicamente , Convulsões/patologia , Hipocampo/metabolismo , Neurônios/fisiologia , Canal de Potássio KCNQ2/genéticaRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). METHODS: In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III-IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin ß1 (ITGB1) expression was analyzed as a biomarker for efficacy. RESULTS: After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. CONCLUSIONS: This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . NCT02923258 (date of registration: October 4, 2016).
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Cisplatino , Docetaxel , Integrina beta1 , Neoplasias Bucais , Humanos , Docetaxel/uso terapêutico , Docetaxel/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/terapia , Idoso , Adulto , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/terapia , Biomarcadores Tumorais , Antineoplásicos/uso terapêutico , Resultado do TratamentoRESUMO
The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).
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Disfunção Cognitiva , Envelhecimento Saudável , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Pequim/epidemiologia , Estudos de Coortes , China/epidemiologia , Disfunção Cognitiva/epidemiologiaRESUMO
Under the influence of periodic temperature variations, biogeochemical cycling in water bodies is markedly affected by the periodic thermal stratification processes in subtropical reservoirs or lakes. In current studies, there is insufficient research on the influence and mechanism of dissolved inorganic carbon (DIC) distribution in karst carbon-rich groundwater-fed reservoirs under the coupled effects of thermal structure stratification and the biological carbon pump (BCP) effect. To address this issue, the Dalongdong (DLD) reservoir in the subtropical region of southern China was chosen as the site for long-term monitoring and research on relevant physicochemical parameters of water, DIC, and its stable carbon isotope (δ13CDIC), CO2 emission flux, as well as the reservoir's thermal stratification index. The results show that: (1) the DLD reservoir is a typical warm monomictic reservoir, which exhibits regular variations of mixing period-stratification period-mixing period on a yearly scale due to thermal structure changes; (2) DIC was consumed by aquatic photosynthetic organisms in the epilimnion during the stratification period, leading to a decrease in DIC concentration, partial pressure of CO2 (pCO2) and CO2 emission flux, and an increase in stable carbon isotope (δ13CDIC). During the mixing period, the trend was reversed; (3) During the thermal stratification, aquatic photosynthesis and water temperature were the primary factors controlling DIC variations in both the epilimnion and thermocline. Regarding the hypolimnion, calcite dissolution, organic matter decomposition, and water temperature were the dominant controlling factors. These results indicate that although carbon-rich karst groundwater provides a plentiful supply of DIC in the DLD reservoir, its availability is still influenced by variations in the reservoir's thermal structure and the metabolic processes of aquatic photosynthetic organisms. Therefore, to better estimate the regional carbon budget in a reservoir or lake, future studies should especially consider the combined effects of BCP and thermal structure variations on carbon variations.
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Água Subterrânea , Fotossíntese , Temperatura , Água Subterrânea/química , China , Carbono/química , Carbono/análise , Monitoramento Ambiental/métodos , Dióxido de Carbono/análise , Dióxido de Carbono/química , Isótopos de Carbono/análiseRESUMO
Revealing the magnitude, dynamics, and influencing factors of CO2 emissions across the water-air interface in karst water with high frequency is crucial for accurately assessing the carbon budget in a karst environment. Due to the limitations of observation methods, the current research is still very insufficient. To solve the above problems and clarify the main influencing factors of CO2 emission in karst water, this study selected Dalongdong (DLD) Reservoir, located in the typical karst peak and valley area in southwest China, to carry out a multi-parameter high-frequency monitoring study from January to December 2021, and used the thin boundary model method to estimate the CO2 flux across the water-air interface (CF). The average annual flux of DLD reservoir is 84.48 mmol·(m2·h)-1, which represents a CO2 source overall. However, during the stratification period in August, there is a transient carbon sink due to negative CO2 emission. The alteration of thermal stratification in water is crucial in regulating the seasonal variation of CF. Meanwhile, the diurnal variation is significantly influenced by changes in hydrochemical parameters during the thermal stratification stage. Compared to low wind speeds (<3 m/s), high wind speeds (≥3 m/s) have a greater impact on the CO2 flux. Furthermore, high-frequency continuous data revealed that the reservoir triggered a CO2 pulse emission during the turnover process, primarily at night, leading to unusually high CO2 flux values. It is of great significance to monitor and reveal the process, flux, and control factors of CO2 flux in land water at a high-frequency strategy. They will help improve the accuracy of regional or watershed carbon budgets and clarify the role of global land water in the global carbon budget.
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Dióxido de Carbono , Monitoramento Ambiental , Água Subterrânea , Dióxido de Carbono/análise , China , Monitoramento Ambiental/métodos , Água Subterrânea/química , Água Subterrânea/análise , Estações do Ano , Poluentes Atmosféricos/análise , VentoRESUMO
OBJECTIVE: To study the changes of retinal function in type 2 diabetes mellitus(DM) patients without apparently diabetic retinopathy via multifocal electroretinogram. METHODS: Thirty-six type 2 DM patients (72 eyes) without visible diabetic retinopathy were selected as the experimental group, and thirty-five healthy subjects (70 eyes) were selected as the control group. All subjects were underwent multifocal electroretinogram (mf- ERG). RESULTS: Compared with the control group, the implicit time delay of the P1 wave in the first ring, third ring, fourth ring, and fifth ring of the experimental group was significant (t = -3.154, p = 0.004, t = -8.21, p = 0.000, t = -3.067, p = 0.004, t = -4.443, p = 0.000, respectively). The implicit time of the N1 wave in the fourth- and fifth-ring were also significantly delayed compared with the control group (t = -3.549, p = 0.001, t = 2.961, p = 0.005, respectively). Compared with the control group, the implicit time of the P1 wave and N1 wave in the temporal region of the experimental group were delayed (t = -2.148, p = 0.037, t = -2.834, p = 0.007, respectively). There were no significant difference between the experimental group and the control group of the temporal area in the amplitude density of P1 wave, N1 wave. There was no difference in the implicit time and amplitude density of the N1 and P1 waves in the nasal region between the experimental group and the control group. The multifocal electroretinogram complex parameters showed better specificity and sensitivity in the diagnosis of diabetic retinopathy. CONCLUSION: The multifocal electroretinogram can detect abnormal changes in the retina of type 2 DM patients without visible diabetic retinopathy. The multifocal electroretinogram complex parameter is a potential indicator for the early diagnosis of diabetic retinopathy.
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Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Retina , Eletrorretinografia , Acuidade VisualRESUMO
Pornography is spreading more and more widely due to websites, applications, and social media. It has attracted the attention of a large number of researchers who are sometimes divided on the impact of pornography. However, the relationship between pornography and sexual violence myths has received little scholarly attention in China. Based on the 3AM model and previous research, the study examined hostile sexism (HS) as a mediator and perceived realism as a moderator in the links between pornography use frequency and sexual violence myths in a sample of Chinese men (N = 376). The results showed that although pornography use and sexual violence myths did not directly correlate with one another, there was an indirect correlation through HS. Further, perceived realism moderated the relationship between pornography use frequency and HS. When participants' perceived realism was high (i.e. +1 SD), the indirect effect of HS was strong; when participants' perceived realism was low (i.e. -1 SD), the indirect effect of HS was not significant. Taken together, the findings reveal the cross-cultural consistency of the 3AM theory in China, and the findings provide new insight into the potential impact of pornography on sexism. At the same time, the results suggest an increase in appropriate education and interventions to reduce the incidence of sexual violence.
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Data from the Operational Land Imager (OLI) and the Thermal Infrared Sensor (TIRS) instruments onboard the Landsat 8 and Landsat 9 satellite platforms are subject to contamination by cloud cover, with cirrus contributions being the most difficult to detect and mask. To help address this issue, a cirrus detection channel (Band 9) centered within the 1.375-µm water vapor absorption region was implemented on OLI, with a spatial resolution of 30 m. However, this band has not yet been fully utilized in the Collection 2 Landsat 8/9 Level 2 surface temperature data products that are publicly released by U.S. Geological Survey (USGS). The temperature products are generated with a single-channel algorithm. During the surface temperature retrievals, the effects of absorption of infrared radiation originating from the warmer earth's surfaces by ice clouds, typically located in the upper portion of the troposphere and re-emitting at much lower temperatures (approximately 220 K), are not taken into consideration. Through an analysis of sample Level 1 TOA and Level 2 surface data products, we have found that thin cirrus cloud features present in the Level 1 1.375-µm band images are directly propagated down to the Level 2 surface data products. The surface temperature errors resulting from thin cirrus contamination can be 10 K or larger. Previously, we reported an empirical and effective technique for removing thin cirrus scattering effects in OLI images, making use of the correlations between the 1.375-µm band image and images of any other OLI bands located in the 0.4-2.5 µm solar spectral region. In this article, we describe a variation of this technique that can be applied to the thermal bands, using the correlations between the Level 1 1.375-µm band image and the 11-µm BT image for the effective removal of thin cirrus absorption effects. Our results from three data sets acquired over spatially uniform water surfaces and over non-uniform land/water boundary areas suggest that if the cirrus-removed TOA 11-µm band BT images are used for the retrieval of the Level 2 surface temperature (ST) data products, the errors resulting from thin cirrus contaminations in the products can be reduced to about 1 K for spatially diffused cirrus scenes.
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BACKGROUND AND OBJECTIVES: It is recommended by Asian Working Group for Sarcopenia to early identify people at risk for sarcopenia using simple screening tools like SARC-F. The modified version SARC-F+EBM showed higher diagnostic performance. However, this cut-off value of body mass index (BMI) remained uncertain to be used in Chinese population. In this study, we used appropriate BMI recommended for Chinese older population and further modified SARC-F+EBM by combining calf circumference. METHODS AND STUDY DESIGN: Diagnostic tests were performed and the receiver operating characteristics analyses were conducted between the SARC-F, SARC-F+EBM (cut-off of BMI: ≤ 21 kg/m2), SARC-F+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2), SARC-CalF and SARC-CalF+EBM (CN) (cut-off of BMI: ≤ 22 kg/m2) in 1660 community-dwelling participants aged ≥ 65 years from China. RESULTS: The participants had an average age of 71.7±5.1 years, of which 56.8% were women. All the modified models could enhance the areas under the receiver operating characteristic curve (AUC) of original SARC-F (all p<0.001). The SARC-F+EBM (CN) also showed a significantly higher sensitivity of 47.4% (p<0.001) and an AUC of 0.809 (p=0.005) than SARC-F+EBM. SARC-CalF+EBM (CN) was validated to be of great diagnostic value of the highest AUC of 0.88 among these sarcopenia screening tools, including SARC-F, SARC-CalF and SARC-F+EBM (CN) (all p<0.001). Using this study population as a reference, the optimal cut-off value of SARC-CalF+EBM (CN) is ≥12 points, with a sensitivity of 79.3% and a specificity of 80.7%. CONCLUSIONS: The SARC-F+EBM (CN) and SARC-CalF+EBM (CN) could enhance the diagnostic performance of SARC-F and SARC-F+EBM and are suitable sarcopenia screening tools for Chinese population.
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Sarcopenia , Humanos , Feminino , Idoso , Masculino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Programas de Rastreamento/métodos , Curva ROC , Vida Independente , China/epidemiologia , Avaliação Geriátrica/métodos , Inquéritos e QuestionáriosRESUMO
The global imperative to mitigate carbon emissions for sustainable development has spurred extensive research into economic, social, and energy-related factors. However, prior studies present a complex landscape, yielding mixed conclusions regarding the influence of geopolitical risk, natural resource rents, corrupt governance, and energy intensity. To untangle this ambiguity, we construct a research model grounded in the Environmental Kuznets Curve, employing panel data from 38 countries spanning 2002 to 2020. Employing panel quantile regression models, we directly assess the impact of identified factors. Our findings affirm the alignment between economic growth and carbon emissions, supporting the Environmental Kuznets Curve hypothesis. Notably, increased geopolitical risk and energy intensity correlate with heightened carbon emissions over time, while corruption governance and natural resource rents exhibit a mitigating effect. Additionally, our study explores the indirect impact of these factors using a panel threshold regression model. Results indicate a diminishing influence of economic growth on carbon emissions. Intriguingly, natural resource rents initially curtail, then amplify the connection between economic growth and carbon emissions. Conversely, rising energy intensity magnifies the relationship between economic expansion and carbon emissions.
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Dióxido de Carbono , Carbono , Modelos Teóricos , Recursos Naturais , Desenvolvimento Sustentável , Desenvolvimento Econômico , Energia RenovávelRESUMO
Increased geopolitical risks are impacting the sustainable development of the ecological environment. To better understand the impact of geopolitical risk on ecological sustainability, this study develops a research framework for the impact of geopolitical risk on ecological efficiency. (i) Measuring ecological efficiency by data envelopment analysis. (ii) Examining the relationship between geopolitical risks and ecological efficiency using the extended STIRPAT. (iii) Heterogeneity analysis and mediation test were used to further explore the impact mechanism of geopolitical risks. The research results show that: (i) There are obvious differences in the ecological efficiency of countries with different income levels. The ecological efficiency of countries with higher income levels is generally higher, while the ecological efficiency of countries with lower income levels is lower. (ii) Geopolitical risks reduce ecological efficiency, which is bad for ecosystem sustainability. (iii) The magnitude of the adverse impact of geopolitical risks on ecological efficiency is different among different income groups. The negative impact of geopolitical risk on eco-efficiency is worse in high-income countries than in low-income countries.
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Conservação dos Recursos Naturais , Ecossistema , Eficiência , Desenvolvimento Sustentável , China , Desenvolvimento EconômicoRESUMO
In order to better understand the impact of different geopolitical factors on energy transition, the impact of geopolitical threats (war threats, peace threats, military buildups, nuclear threats and terror threats), geopolitical acts (beginning of war, escalation of war and terror acts), and geopolitical risks on energy transition were systematically investigated. Green technologies, natural resource rents and trade openness were incorporated into the analytical framework, and a dynamic panel threshold model was utilized to explore the impact of geopolitical risks on energy transition across different income levels. To this end, data on geopolitical threats, geopolitical acts, geopolitical risks, energy transitions and other key social economic factors for 38 countries from 2000 to 2022 were collected. The heterogeneity simulation results show that there is a negative correlation between geopolitical threats, geopolitical acts, geopolitical risks and energy transition. Moreover, geopolitical threats have more significant hindrance to the energy transition than geopolitical acts. The results of the nonlinear panel simulation show that there is a double threshold effect of geopolitical risks on energy transition. When geopolitical risk crosses the threshold (0.5197), the coefficient decreases to -0.29, which means that the rising geopolitical risk increases the inhibition on energy transition, and the inhibitory effect is slightly weakened after a certain level. Finally, policy implications are offered.
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Militares , Humanos , Simulação por Computador , Recursos Naturais , Políticas , Condições Sociais , Desenvolvimento Econômico , Dióxido de Carbono , Energia RenovávelRESUMO
The continuous deepening of aging has posed new challenges for global sustainable development. Measuring the impact of population aging on carbon emissions is crucial for the next stage of climate governance. However, the structural changes in social production and consumption make it difficult to evaluate the impact effects. Therefore, this study constructed a bidirectional fixed Space Durbin Model to explore the mediating pathway of aging's impact on carbon emissions. Furthermore, we have established high-precision prediction models to simulate the evolution trajectory of carbon emissions under multi-factor driving scenarios. The main findings are as follows: (1) The process of carbon emission reduction due to population aging has significant energy hindrance effect and industrial structure effect, while the process of carbon growth is constrained by the consumption enhancement effect, technology progress effect and labor participation effect. (2) The moderating effects of energy consumption and technological innovation on carbon emissions under the aging process are 10.74% and 10.24%, respectively, while the moderating effects of industrial structure and labor force participation are relatively weak. (3) The goodness of fit of the MNGM-ARIMA and MNGM-BPNN models is over 97%. Carbon emissions in the high aging regions show a decreasing trend in all scenarios except the energy consumption-driven scenario, while in the medium and low aging regions decrease slowly only in the R&D- and labor supply-driven scenarios. This study advocates developing heterogeneous emission reduction measures based on the degree of aging, accelerating supply side upgrading, and increasing the proportion of green consumption.
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Carbono , Humanos , Modelos TeóricosRESUMO
Objective To investigate the efficacy of raw corn starch (RCS) in clinical management of insulinoma-induced hypoglycemia. Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively, and analyzed the therapeutic effects of the RCS intervention on blood glucose control, weight change, and its adverse events. Results The study population consisted of 24 cases of insulinoma patients, 7 males and 17 females, aged 46.08±14.15 years. Before RCS-supplemented diet, all patients had frequent hypoglycemic episodes (2.51±3.88 times/week), concurrent with neuroglycopenia (in 83.3% of patients) and autonomic manifestations (in 75.0% of patients), with the median fasting blood glucose (FBG) of 2.70 (interquartile range [IQR]: 2.50-2.90) mmol/L. The patients' weight increased by 0.38 (IQR: 0.05-0.65) kg per month, with 8 (33.3%) cases developing overweight and 7 (29.2%) cases developing obesity. All patients maintained the RCS-supplemented diet until they underwent tumor resection (23 cases) and transarterial chemoembolization for liver metastases (1 case). For 19 patients receiving RCS throughout the day, the median FBG within one week of nutritional management was 4.30 (IQR: 3.30-5.70) mmol/L, which was a significant increase compared to pre-nutritional level [2.25 (IQR: 1.60-2.90) mmol/L; P < 0.001]. Of them, 10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment [3.20 (IQR: 2.60-3.95) mmol/L vs. 2.15 (IQR: 1.83-2.33) mmol/L; P < 0.001). Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management [3.50 (IQR: 2.50-3.65) mmol/L vs. 2.20 (IQR:1.80-2.60) mmol/L; P < 0.001], but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG. No improvement in weight gain was observed upon RCS supplementation. Mild diarrhea (2 cases) and flatulence (1 case) occurred, and were relieved by reduction of RCS dose. Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.
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Hipoglicemia , Insulinoma , Amido , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Insulinoma/complicações , Insulinoma/terapia , Adulto , Amido/uso terapêutico , Estudos Retrospectivos , Glicemia/metabolismo , Neoplasias Pancreáticas/complicações , IdosoRESUMO
The COVID-19 pandemic has resulted in an unprecedented amount of medical waste, presenting significant challenges for the safe disposal of hazardous waste. A systematic review of existing research on COVID-19 and medical waste can help address these challenges by providing insights and recommendations for effective management of the massive medical waste generated during the pandemic. This study utilized bibliometric and text mining methods to survey the scientific outcomes related to COVID-19 and medical waste, drawing on data from the Scopus database. The results show that the spatial distribution of medical waste research is unbalanced. Surprisingly, developing countries rather than developed countries lead research in this area. Especially, China, a major contributor to the field, has the highest number of publications and citations, and is also a centre of international cooperation. The main study authors and research institutions are also mainly from China. And the research on medical waste is a multidisciplinary field. Text mining analysis shows that COVID-19 and medical waste research is mainly organized around four themes: (i) medical waste from personal protective equipment; (ii) research on medical waste in Wuhan, China; (iii) threats of medical waste to the environment and (iv) disposal and management of medical waste. This would serve to better understand the current state of medical waste research and to provide some implications for future research.
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COVID-19 , Resíduos de Serviços de Saúde , Gerenciamento de Resíduos , Humanos , COVID-19/epidemiologia , Pandemias , China/epidemiologiaRESUMO
Although recent studies have revealed an involvement of hippocampal interneurons in learning the association among time-separated events, its underlying cellular mechanisms remained not fully clarified. Here, we combined multichannel recording and optogenetics to elucidate how the hippocampal parvalbumin-expressing interneurons (PV-INs) support associative learning. To address this issue, we trained the mice (both sexes) to learn hippocampus-dependent trace eyeblink conditioning (tEBC) in which they associated a light flash conditioned stimulus (CS) with a corneal air puff unconditioned stimuli (US) separated by a 250 ms time interval. We found that the hippocampal PV-INs exhibited learning-associated sustained activity at the early stage of tEBC acquisition. Moreover, the PV-IN sustained activity was positively correlated with the occurrence of conditioned eyeblink responses at the early learning stage. Suppression of the PV-IN sustained activity impaired the acquisition of tEBC, whereas the PV-IN activity suppression had no effect on the acquisition of delay eyeblink conditioning, a hippocampus-independent learning task. Learning-associated augmentation in the excitatory pyramidal cell-to-PVIN drive may contribute to the formation of PV-IN sustained activity. Suppression of the PV-IN sustained activity disrupted hippocampal gamma but not theta band oscillation during the CS-US interval period. Gamma frequency (40 Hz) activation of the PV-INs during the CS-US interval period facilitated the acquisition of tEBC. Our current findings highlight the involvement of hippocampal PV-INs in tEBC acquisition and reveal insights into the PV-IN activity kinetics which are of key importance for the hippocampal involvement in associative learning.SIGNIFICANCE STATEMENT The cellular mechanisms underlying associative learning have not been fully clarified. Previous studies focused on the involvement of hippocampal pyramidal cells in associative learning, whereas the activity and function of hippocampal interneurons were largely neglected. We herein demonstrated the hippocampal PV-INs exhibited learning-associated sustained activity, which was required for the acquisition of tEBC. Furthermore, we showed evidence that the PV-IN sustained activity might have arisen from the learning-associated augmentation in excitatory pyramidal cell-to-PVIN drive and contributed to learning-associated augmentation in gamma band oscillation during tEBC acquisition. Our findings provide more mechanistic understanding of the cellular mechanisms underlying the hippocampal involvement in associative learning.
Assuntos
Condicionamento Palpebral , Parvalbuminas , Masculino , Feminino , Camundongos , Animais , Condicionamento Palpebral/fisiologia , Interneurônios , Hipocampo/fisiologia , PiscadelaRESUMO
Density functional theory computations reveal mechanistic insights into Cu and chiral phosphoric acid (CPA) catalyzed enantioconvergent amination of racemic benzenesulfonohydrazide. The O-O bond homolysis of tert-butyl 4-phenylbutaneperoxoate was found to be the turnover-limiting step with a total free energy barrier of 19.1â kcal/mol. The enantioconvergent amination is realized to obtain the same intermediate through prochiral carbon atom. The order and mode of hydrogen atom transferred by CPA and tert-butyloxy have a significant influence on the enantioselectivity and energy barriers. The olefinic side product generated by ß-hydride elimination is 9.9â kcal/mol thermodynamically less favourable. A series of phosphoric acids are predicted as promising co-catalysts with lower barriers for O-O bond homolysis.
Assuntos
Cobre , Ácidos Fosfóricos , Aminação , Cobre/química , CatáliseRESUMO
Most metal ions such as iron, calcium, zinc, or copper are essential for all eukaryotes. Organisms must maintain homeostasis of these metal ions because excess or deficiency of metal ions could cause damage to organisms. The steady state of many metal ions such as iron and copper has been well studied in detail. However, how to regulate zinc homeostasis in Schizosaccharomyces pombe is still confusing. In this review, we provide an overview of the molecular mechanisms that how S. pombe is able to maintain the balance of zinc levels in the changes of environment. In response to high levels of zinc, the transcription factor Loz1 represses the expression of several genes involved in the acquisition of zinc. Meanwhile, the CDF family proteins transport excess zinc to the secretory pathway. When zinc levels are limited, Loz1 was inactivated and could not inhibit the expression of zinc acquisition genes, and zinc stored in the secretory pathway is released for use by the cells. Besides, other factors that regulate zinc homeostasis are also discussed.