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Cropland is a main source of global nitrogen pollution1,2. Mitigating nitrogen pollution from global croplands is a grand challenge because of the nature of non-point-source pollution from millions of farms and the constraints to implementing pollution-reduction measures, such as lack of financial resources and limited nitrogen-management knowledge of farmers3. Here we synthesize 1,521 field observations worldwide and identify 11 key measures that can reduce nitrogen losses from croplands to air and water by 30-70%, while increasing crop yield and nitrogen use efficiency (NUE) by 10-30% and 10-80%, respectively. Overall, adoption of this package of measures on global croplands would allow the production of 17 ± 3 Tg (1012 g) more crop nitrogen (20% increase) with 22 ± 4 Tg less nitrogen fertilizer used (21% reduction) and 26 ± 5 Tg less nitrogen pollution (32% reduction) to the environment for the considered base year of 2015. These changes could gain a global societal benefit of 476 ± 123 billion US dollars (USD) for food supply, human health, ecosystems and climate, with net mitigation costs of only 19 ± 5 billion USD, of which 15 ± 4 billion USD fertilizer saving offsets 44% of the gross mitigation cost. To mitigate nitrogen pollution from croplands in the future, innovative policies such as a nitrogen credit system (NCS) could be implemented to select, incentivize and, where necessary, subsidize the adoption of these measures.
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Produção Agrícola , Produtos Agrícolas , Poluição Ambiental , Nitrogênio , Solo , Humanos , Análise Custo-Benefício , Ecossistema , Fertilizantes/análise , Nitrogênio/análise , Solo/química , Poluição Ambiental/economia , Poluição Ambiental/prevenção & controle , Produção Agrícola/economia , Produção Agrícola/métodos , Produção Agrícola/tendênciasRESUMO
OBJECTIVE: To analyze recurrent factors in patients with clinical early-stage cervical cancer (ESCC) following hysterectomy and adjuvant radiotherapy. METHODS: We collected data from patients with ESCC, staged according to the 2009 Federation International of Gynecology and Obstetrics (FIGO) staging criteria, who underwent hysterectomy followed by adjuvant radiotherapy between 2012 and 2019. These patients were subsequently restaged using the 2018 FIGO criteria. Univariable and multivariable analyses, along with nomogram analyses, were conducted to explore factors associated with recurrence-free survival (RFS). RESULTS: A total of 310 patients met the inclusion criteria, with a median follow-up time of 46 months. Among them, 126 patients with ESCC were restaged to stage III C1 or III C2 after surgery due to lymph node metastasis (LNM) based on the 2018 FIGO staging criteria. Of these, 60 (19.3%) experienced relapse. The 1-, 3-, and 5-year RFS rates were 93.9%, 82.7%, and 79.3%, respectively. Multivariate analysis revealed that the number of positive lymph nodes (LNs), tumor diameter (TD) > 4 cm, and parametrial invasion (PI) were associated with recurrence. The nomogram indicated their predictive value for 3-year and 5-year RFS. Notably, the 5-year recurrence rate (RR) increased by 30.2% in patients with LNM, particularly those with ≥ 3 positive LNs (45.5%). Patients with stage III C2 exhibited a significantly higher RR than those with IIIC1 (56.5% vs. 24.3%, p < 0.001). The 5-year RFS for patients with TD > 4 cm was 65.8%, significantly lower than for those with TD ≤ 4 cm (88.2%). Subgroup analysis revealed higher 5-year RRs in patients with stage III C2 than that in patients with III-C1 (56.5% vs. 24.3%, p < 0.001), demonstrating a significant difference in the RFS survival curve. CONCLUSION: RR in patients with clinical ESCC after hysterectomy followed by adjuvant radiotherapy is correlated with the number of positive LNs, TD > 4 cm, and PI. Emphasis should be placed on the common high-risk factor of LNM association with recurrence after radical hysterectomy in ESCC.
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Neoplasias do Colo do Útero , Feminino , Humanos , Radioterapia Adjuvante , Resultado do Tratamento , Intervalo Livre de Doença , Neoplasias do Colo do Útero/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Histerectomia , Excisão de LinfonodoRESUMO
BACKGROUND: One of the challenges of physical training in extreme condition is frostbite, especially in Northeast China. In this study, we aimed to construct a risk prediction model for frostbite among soldiers in Northeast China, and verify its effect. METHODS: 698 participants were selected via convenience sampling from Northeast China from December 2021 to January 2022 (winter). They were randomly divided into a training set (N = 479) and a testing set (N = 202) in a ratio of 7:3. All participants completed a researcher-made questionnaire on frostbite. The prediction model was constructed through the use of Logistic regression analysis, which was used to predict the independent risk factors for frostbite formation and screen significant indicators. The model's performance was assessed using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) to evaluate the prediction efficiency and goodness of fit. RESULTS: The incidence of frostbite in the training set was 19.83% (95 people), all of which were first-degree frostbite. Among them, frostbite in multiple parts was the most common (58.95%), followed by singular body parts like hands (24.21%), ears (11.58%) and feet (5.26%). Single factor logistic regression analyses showed that ambient temperature, ambient wind speed, outdoor stationary time, stationary status, and history of frostbite are independent risk factors that affect the occurrence of frostbite. Furthermore, we constructed the frostbite risk prediction model for soldiers in the northeastern region of China. The area under the receiver operating characteristic curve (AUC) for the risk of frostbite in the training set and testing set was 0.816 (95% CI, 0.770 ~ 0.862) and 0.787 (95% CI, 0.713 ~ 0.860), respectively. The Hosmer-Lemeshow test of the model showed χ2 = 11.328 and P = 0.184 (> 0.05). The DCA curve indicated that most of the clinical net benefits of the model are greater than 0, demonstrating good clinical usefulness. CONCLUSION: The constructed frostbite prediction model can effectively identify soldiers with a higher risk of frostbite. It provided theoretical support for commanders to take preventive measures to reduce the incidence of frostbite among soldiers and was of great clinical guiding significance.
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Congelamento das Extremidades , Militares , Humanos , China/epidemiologia , Congelamento das Extremidades/epidemiologia , Militares/estatística & dados numéricos , Masculino , Estudos Transversais , Medição de Risco , Adulto , Adulto Jovem , Fatores de Risco , Feminino , Curva ROC , Modelos Logísticos , Inquéritos e QuestionáriosRESUMO
In tumor metastasis, the margination and adhesion of tumor cells are two critical and closely related steps, which may determine the destination where the tumor cells extravasate to. We performed a direct three-dimensional simulation on the behaviors of the tumor cells in a real microvascular network, by a hybrid method of the smoothed dissipative particle dynamics and immersed boundary method (SDPD-IBM). The tumor cells are found to adhere at the microvascular bifurcations more frequently, and there is a positive correlation between the adhesion of the tumor cells and the wall-directed force from the surrounding red blood cells (RBCs). The larger the wall-directed force is, the closer the tumor cells are marginated towards the wall, and the higher the probability of adhesion behavior happen is. A relatively low or high hematocrit can help to prevent the adhesion of tumor cells, and similarly, increasing the shear rate of blood flow can serve the same purpose. These results suggest that the tumor cells may be more likely to extravasate at the microvascular bifurcations if the blood flow is slow and the hematocrit is moderate.
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Biologia Computacional/métodos , Microcirculação , Modelos Cardiovasculares , Neoplasias/genética , Neoplasias/metabolismo , Animais , Adesão Celular , Simulação por Computador , Elasticidade , Eritrócitos/citologia , Hematócrito , Hemodinâmica , Humanos , Metástase Neoplásica , Ratos , Estresse MecânicoRESUMO
BACKGROUND: It is well known that decision aids can promote patients' participation in decision-making, increase patients' decision preparation and reduce decision conflict. The goal of this study is to explore the effects of a "Shared Decision Making Assistant" smartphone application on the decision-making of informed patients with Primary Liver Cancer (PLC) in China. METHODS: In this quasi-experimental study , 180 PLC patients who knew their real diagnoses in the Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China, from April to December 2020 were randomly assigned to a control group and an intervention group. Patients in the intervention group had an access to the "Shared Decision Making Assistant" application in decision-making, which included primary liver cancer treatment knowledge, decision aids path, continuing nursing care video clips, latest information browsing and interactive platforms. The study used decision conflict scores to evaluate the primary outcome, and the data of decision preparation, decision self-efficacy, decision satisfaction and regret, and knowledge of PLC treatment for secondary outcomes. Then, the data were entered into the SPSS 22.0 software and were analyzed by descriptive statistics, Chi-square, independent t-test, paired t-test, and Mann-Whitney tests. RESULTS: Informed PLC patients in the intervention group ("SDM Assistant" group) had significantly lower decision conflict scores than those in the control group. ("SDM Assistant" group: 16.89 ± 8.80 vs. control group: 26.75 ± 9.79, P < 0.05). Meanwhile, the decision preparation score (80.73 ± 8.16), decision self-efficacy score (87.75 ± 6.87), decision satisfaction score (25.68 ± 2.10) and knowledge of PLC treatment score (14.52 ± 1.91) of the intervention group were significantly higher than those of the control group patients (P < 0.05) at the end of the study. However, the scores of "regret of decision making" between the two groups had no statistical significance after 3 months (P > 0.05). CONCLUSIONS: Access to the "Shared Decision Making Assistant" enhanced the PLC patients' performance and improved their quality of decision making in the areas of decision conflict, decision preparation, decision self-efficacy, knowledge of PLC treatment and satisfaction. Therefore, we recommend promoting and updating the "Shared Decision Making Assistant" in clinical employment and future studies.
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Tomada de Decisão Compartilhada , Neoplasias Hepáticas , China , Humanos , Neoplasias Hepáticas/terapia , Participação do Paciente , SmartphoneRESUMO
BACKGROUND: This study aimed to determine the level of benefit finding among COVID-19 patients in a hospital in mainland China, and to identify its associated impact and public health factors. METHODS: Using a cross-sectional design, a total of 288 COVID-19 patients were recruited in Huoshenshan Hospital in Wuhan, China to complete a survey on benefit finding. The level of benefit finding evaluated by the Benefit Finding Scale (BFS), mental resilience evaluated by the Connor-Davidson Resilience Scale (CD-RISC), social support evaluated by the Multidimensional Scale of Perceived Social Support (MSPSS), medical coping modes evaluated by the Medical Coping Modes Questionnaire (MCMQ), and general information was collected by self-designed questionnaires. T-test and chi-square test were used for single-factor analyses. For multiple factor analyses, multivariate regression analyses were performed. RESULT: The mean BFS score of 288 participants was 61.26±10.25. Multivariate regression analysis showed that the factors associated with the level of benefit finding among COVID-19 patients in China included education level, having experienced major event, social support, optimism, confrontive coping and resigned coping mode. CONCLUSIONS: In general, the patients with COVID-19 in this study had a middle level of benefit finding. Health professionals should take measures to identify the influencing factors on the quality of the life and take targeted intervention measures.
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COVID-19 , Adaptação Psicológica , Ansiedade , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Depressão , Humanos , Saúde Pública , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
PYCR2 has previously been shown to be related to a range of malignancies including hepatocellular carcinoma and melanoma, but its mechanistic functions and prognostic relevance in colon cancer patients remain to be defined. Herein, we used the Oncomine, Human Protein Atlas, The Cancer Genome Atlas (TCGA), and UALCAN databases to explore the expression of this gene in different human cancer, after which the relationship between PYCR2 expression and patient clinicopathologic characteristics was evaluated. We utilized an in vitro approach to evaluate the association between PYCR2 expression and colon cancer cell proliferation, migration, invasion, and tumor microsphere formation. The cell apoptosis was analyzed by flow cytometry. Gene set enrichment analysis (GSEA) approaches were additionally used to probe signaling pathways related to PYCR2. These analyses confirmed that PYCR2 was upregulated in several cancer types including colon cancer, with such upregulation correlating with a poor patient prognosis and with malignant clinicopathological characteristics. PYCR2 expression was identified as an independent predictor of colon cancer patients' survival, and in vitro analyses suggested that knocking down this gene was sufficient to disrupt the proliferative, migratory, invasive, and microsphere formation activities of colon cancer cells. Moreover, shPYCR2 transfection induced colon cancer cell apoptosis. GSEA suggested that high PYCR2 expression correlates with the differential enrichment of the Wnt ß-catenin signaling, MYC targets, RNA polymerase, and Notch signaling pathways. Overall, these data indicate that PYCR2 is an important mediator of tumor progression and metastasis, and suggest that it may be a valuable prognostic indicator for colon cancer patient evaluation.
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Neoplasias do Colo/metabolismo , Pirrolina Carboxilato Redutases/metabolismo , Regulação para Cima , Neoplasias do Colo/diagnóstico , Humanos , Células Tumorais CultivadasRESUMO
We have proposed an interference and frequency-to-time mapping based high anti-jamming and anti-interception frequency hopping receiving scheme. By changing the delay difference between the interference arms through high-speed switchable delay lines and using electrooptical sampling, fast and large-range frequency hopping signals can be received. Benefited from the high shaping resolution for using the interference as the spectral shaping method, more receiving passbands in high frequency bands can be available to enhance the anti-jamming and anti-interception performance. By fast pulse shaping through switchable delay lines, the bandwidth of the electric end, the sampling rate, and the number of frequencies in the frequency hopping pattern are decoupled, and the bandwidth of the electric end can be reduced to improve the receiving selectivity. In experiments, the signal hopping from 15.2 GHz to 35.4 GHz with the switching time up to that of the used optical switch is received. Utilizing a switchable delay line in the interference arm with the tuning step of 2.5 ps, eight available receiving passbands within 25 GHz to 42 GHz are generated. The receiving selectivity is also improved from 18.3 to 43.7 in terms of Q factor by decreasing the electric end's bandwidth in experiments.
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We propose a frequency hopping receiving method that can receive signals with a large frequency hopping range and rapid hopping speed simultaneously. It is based on simultaneous photonic filtering and digitizing, and the reception frequency is tuned by changing the temporal shape of the sampling optical pulse. The proposed receiving method is verified by an experimental verification scheme. In the verification scheme, the optical pulse from a mode-locked laser is shaped to obtain several sub-pulses with different temporal shapes by spectral shaping and frequency-to-time mapping. The reception of the frequency hopping signal is performed by introducing certain delay through a switchable delay line to select different sub-pulses as the optical sampling pulse. The frequency hopping speed and range of the verification scheme are limited mainly by the speed of the optical switches and the bandwidth of electro-optic modulators, respectively. In experiments, with available devices, frequency hopping signals with a switching time of 250 ns and signals whose carrier frequency hops from 13.35 GHz to 39.30 GHz are successfully received.
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BACKGROUND: Colon cancer is a serious malignant tumor. It has been reported that paired-like homeodomain transcription factor 2 (PITX2) can promote the progression of several types of cancer via regulating the Wnt/ß-catenin pathway. It has also been demonstrated that high levels of long non-coding RNA (lncRNA) gastric carcinoma high expressed transcript 1 (GHET1) can also promote the development of cervical cancer via activating the Wnt/ß-catenin pathway. However, whether PITX2 can affect the development of colon cancer via regulating the expression of lncRNA GHET1 remains unclear. RESULTS: The results demonstrated that PITX2 knockdown attenuated the proliferation, migration and invasion abilities of colon cancer cells. Additionally, PITX2 promoted the expression of lncRNA GHET1 via binding to its promoter. Overexpression of lncRNA GHET1 induced the expression of Wnt/ß-catenin signaling-related proteins, cyclin D1, c-Myc and MMP-7. Furthermore, lncRNA GHET1 overexpression abrogated the PITX2 silencing-mediated decreased proliferation, migration and invasion abilities of colon cancer cells. CONCLUSION: The findings of the present study suggested that PITX2 could enhance the proliferation, migration and invasion abilities of colon cancer cells via upregulating lncRNA GHET1 and activating the Wnt/ß-catenin pathway.
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Neoplasias do Colo , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias do Colo/genética , Humanos , RNA Longo não Codificante/genética , Via de Sinalização WntRESUMO
The development of medical technology provides medical specialists with a variety of choices for their primary liver cancer patients, including partial liver resection, transcatheter arterial chemoembolization, liver transplantation, and so on. However, in this context, because patients with primary liver cancer frequently do not receive adequate information to help make complicated medical decisions, those patients, who are usually otherwise ignorant about their disease, are facing multiple difficult choices. The problem might be alleviated with a process called "shared decision making." Accordingly, researchers developed a smartphone application named "Shared Decision Making Assistant" for primary liver cancer patients in China, and in this article, we report the process of its development. First, individual interviews were conducted to identify the specific needs and status of primary liver cancer patients participating in shared decision making. Next, expert group discussions were held among primary liver cancer medical experts, nurses, and software engineers, using a decision-making process called the Delphi method, which was used to arrive at a group opinion or decision by surveying a panel of experts, to draft the framework and decide on the contents of the mobile health-based decision aids program. Feedbacks and suggestions were collected to optimize the workflow of "Shared Decision Making Assistant." The resulting application consisted of seven modules: personal information, primary liver cancer treatment knowledge center, decision aids path, continuing care, interactive platform, health education, and backstage management.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Tomada de Decisões , Tomada de Decisão Compartilhada , Humanos , Neoplasias Hepáticas/terapia , Participação do Paciente , SmartphoneRESUMO
Oncolytic Newcastle disease virus (NDV) induces immunogenic cell death (ICD), liberating danger-associated molecular patterns (DAMPs) that provokes defiance in neoplastic malignancy. The present study aims to investigate whether and how oncolytic NDV triggers ICD in prostate cancer cells. We show that NDV/FMW, an oncolytic NDV strain FMW, elicited the expression and release of several ICD markers, that is calreticulin (CRT), heat shock proteins (HSP70/90) and high-mobility group box 1 (HMGB1), in prostate cancer cells. Furthermore, pharmacological repression of apoptosis, necroptosis, autophagy or endoplasmic reticulum (ER) stress exerted diverse effects on the HMGB1 and HSP70/90 evacuation in NDV/FMW-infected prostate cancer cells. Moreover, ICD markers induced in prostate cancer cells upon NDV/FMW infection, were enhanced by either treatment with a STAT3 (signal transducer and activator of transcription 3) inhibitor or shRNA-mediated knockdown of STAT3. In nude mice bearing prostate cancer cell-derived tumours, the tumours injected with the supernatants of NDV/FMW-infected cells grew smaller than mock-treated tumours. These results indicate that oncolytic NDV provokes the expression of ICD makers in prostate cancer cells. Our data also suggest that a combination of inhibition of STAT3 with oncolytic NDV could boost NDV-based anti-tumour effects against prostate cancer.
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Morte Celular Imunogênica/genética , Terapia Viral Oncolítica , Neoplasias da Próstata/genética , Fator de Transcrição STAT3/genética , Animais , Apoptose/genética , Autofagia/genética , Calreticulina/genética , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteína HMGB1/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP90/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Necroptose/genética , Vírus da Doença de Newcastle/genética , Vírus Oncolíticos/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/virologia , Fator de Transcrição STAT3/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this Letter, we propose a high-speed, broadband photonic digital receiver that can realize the matched filtering of the digital signal through shaping the optical sampling pulse according to the specific waveform of the transmitted digital signal. The receiver's filtering response is matched with the spectrum of the digital signal's specific waveform, and the instantaneous signal-to-average-noise ratio of the filtered signal is maximized at the sampling points. The principle of proposed receiver is theoretically analyzed and experimentally verified. The weak digital signals with different signal-to-noise ratio are detected and correctly distinguished in the experiments.
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Particulate matter (PM) concentrations are affected by anthropogenic emissions and sand transport jointly; however, the relative contributions from those two aspects are usually unknown. In our work, statistical analysis and back trajectories model were used to identify the dominant source in such area, by taking Yumen City as an example. We come to the conclusion that local emissions dominate the concentration of airborne pollutants, while sand transport plays a significant role on PM concentration. The conclusions were supported by the following results. (1) PM monthly mean concentrations at the two air quality stations, which are 70 km far away from each other, have the similar levels and variation trend; furthermore, a regression analysis of PM2.5 and PM10 daily concentrations between both stations indicated a significant correlation, suggesting that PM at both locations was influenced by the same emission sources; (2) statistical analysis results revealed that PM concentration has a positive correlation with wind speed, indicating the wind-blown dust and sand contribute mainly on PM concentration; (3) back-trajectory clustering analysis indicates that long-distance transport particulates from dust sources and their pathways had a significant impact on local PM concentrations.
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Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluentes Ambientais , China , Cidades , Monitoramento Ambiental , Material Particulado/análiseRESUMO
We present a photonic compressive receiver, where the frequency information of the captured signal is directly mapped to the time intervals between compressed pulses for multiple microwave frequency measurement. The theoretical measurement error, multiple-frequency resolution and effective measurement range are derived. The effects of dispersion deviation and the electrical bandwidth are also discussed. The theoretical results are verified by the measured pulse waveforms and frequency-time mapping relationship. A photonic compressive receiver with an effective measurement range of 42 GHz, a multiple-frequency resolution of 1.2 GHz, a measurement accuracy of 88 MHz and a signal interception period of 27 ns is experimentally obtained.
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We propose a generic integrated filtering and digitizing approach that can complete signal filtering and digitizing simultaneously based on periodic signal multiplying. The filtering response can be reconfigured flexibly by adjusting the temporal shape of the local periodic signal and/or the impulse response of photodetection. The principle and features of proposed structure are analyzed and experimentally verified in the electrical domain and the photonic domain. The system responses in line with the theoretical and simulation results are experimentally measured.
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Cross-frequency phase-amplitude coupling (PAC) in neuronal oscillations network plays an important functional role in large scale neuronal communication and neuronal encoding. In the present study, a novel approach named permutation mutual information (PMI) was applied in measuring PAC. It is derived from the permutation entropy based on the mutual information theory, by which the mutual information of permutations of two time series can be evaluated. In order to verify the ability of PMI, a numerical test was performed by using both simulation data and experimental data. The performances of PMI were compared with that of two well-known methods, which were the mean vector length (MVL) and the modulation index (MI). It was found that the performance of PMI was similar to that of MI when measuring PAC intensity, but the coupling sensitivity of PMI was the highest among all these three approaches. Moreover, there was the lowest sensitivity in the MVL measurement, suggesting that MVL was a more conservative approach in detecting the existence of PAC. In addition, an ROC analysis showed that PMI performed better in measuring PAC compared to that of others. Furthermore, the experimental data, obtained from rats' hippocampal CA3 regions, were analyzed by using the three approaches. The result was essentially in line with that of the simulation performances. In a word, the results suggest that PMI is a better choice for assessing PAC under the certain conditions.
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Encéfalo/fisiologia , Potenciais da Membrana/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Animais , Simulação por Computador , Masculino , Ratos , Ratos WistarRESUMO
The mitigation of methane (CH4) emissions from livestock production is crucial to China's carbon neutrality. Here we established a high-spatiotemporal-resolution dataset of the country's livestock CH4 emissions from 1990 to 2020 using four large-scale national livestock greenhouse gas inventory surveys. We estimate CH4 emissions to be 14.1 ± 2.0 Mt in 2020 and to increase by 13% until 2030 despite CH4 intensity per kg animal protein having decreased by 55% in the past 30 years. Approximately half of the emissions come from 13% of all Chinese counties. The technical CH4 mitigation potential is projected to be 36 ± 8% (4.4-6.9 Mt CH4) in 2030, and reducing food loss and waste could mitigate an additional 1.6 Mt of CH4. Overall, most CH4 mitigation could be achieved by increasing animal productivity and coverage of lagoon storage at carbon prices below US$100 tCO2e-1, being more cost-effective than livestock nitrous oxide mitigation in China.
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Gado , Metano , Metano/análise , China , Animais , Gases de Efeito Estufa/análise , Poluentes Atmosféricos/análise , Criação de Animais Domésticos/economia , Criação de Animais Domésticos/métodosRESUMO
Immunotherapy has emerged as a revolutionizing therapeutic modality for cancer. However, its efficacy has been largely limited by a weak immune response and an immunosuppressive tumor microenvironment. Herein, we report a metal-organic framework (MOF)-derived titanium oxide nanoparticle (MCTx NP) as an immune booster that can greatly improve the immunotherapy efficacy by inducing "immunogenic cell death" (ICD) and remodeling the tumor microenvironment. The NPs, inheriting the characteristic structure of MIL-125 and enriched with oxygen vacancies (OVs), demonstrate both high photothermal conversion efficiency and a reactive oxygen species (ROS) generation yield upon near-infrared (NIR) activation. Moreover, the NPs can release O2 and reduce glutathione (GSH) in the tumor environment, showcasing their potential to reverse the immunosuppressive microenvironment. In vitro/vivo results demonstrate that MCTx NPs directly kill tumor cells and effectively eliminate primary tumors by exerting dual photodynamic/photothermal therapy under a single NIR irritation. At the same time, MCTx NPs augment the PD-L1 blockade efficacy by potently inducing ICDs and reversing the immunosuppressive tumor microenvironment, including promoting dendritic cell (DC) maturation, decreasing regulatory T cells (Tregs)' infiltration, and increasing cytotoxic T lymphocytes (CTLs) and helper T cells (Ths), resulting in effective distant tumor suppression. This work highlights MCTx NP-mediated photodynamic- and photothermal-enhanced immunotherapy as an effective strategy for tumor treatment.