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1.
Sci Bull (Beijing) ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38879416

RESUMO

Given that it was a once-in-a-century emergency event, the confinement measures related to the coronavirus disease 2019 (COVID-19) pandemic caused diverse disruptions and changes in life and work patterns. These changes significantly affected water consumption both during and after the pandemic, with direct and indirect consequences on biodiversity. However, there has been a lack of holistic evaluation of these responses. Here, we propose a novel framework to study the impacts of this unique global emergency event by embedding an environmentally extended supply-constrained global multi-regional input-output model (MRIO) into the drivers-pressure-state-impact-response (DPSIR) framework. This framework allowed us to develop scenarios related to COVID-19 confinement measures to quantify country-sector-specific changes in freshwater consumption and the associated changes in biodiversity for the period of 2020-2025. The results suggest progressively diminishing impacts due to the implementation of COVID-19 vaccines and the socio-economic system's self-adjustment to the new normal. In 2020, the confinement measures were estimated to decrease global water consumption by about 5.7% on average across all scenarios when compared with the baseline level with no confinement measures. Further, such a decrease is estimated to lead to a reduction of around 5% in the related pressure on biodiversity. Given the interdependencies and interactions across global supply chains, even those countries and sectors that were not directly affected by the COVID-19 shocks experienced significant impacts: Our results indicate that the supply chain propagations contributed to 79% of the total estimated decrease in water consumption and 84% of the reduction in biodiversity loss on average. Our study demonstrates that the MRIO-enhanced DSPIR framework can help quantify resource pressures and the resultant environmental impacts across supply chains when facing a global emergency event. Further, we recommend the development of more locally based water conservation measures-to mitigate the effects of trade disruptions-and the explicit inclusion of water resources in post-pandemic recovery schemes. In addition, innovations that help conserve natural resources are essential for maintaining environmental gains in the post-pandemic world.

2.
Curr Issues Mol Biol ; 46(6): 5561-5581, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38921004

RESUMO

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3ß and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

3.
J Agric Food Chem ; 72(22): 12425-12433, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38781442

RESUMO

Phytoene desaturase (PDS) is a critical functional enzyme in blocking ζ-carotene biosynthesis and is one of the bleaching herbicide targets. At present, norflurazon (NRF) is the only commercial pyridazine herbicide targeting PDS. Therefore, developing new and diverse pyridazine herbicides targeting PDS is urgently required. In this study, diflufenican (BF) was used as the lead compound, and a scaffold-hopping strategy was employed to design and synthesize some pyridazine derivatives based on the action mode of BF and PDS. The preemergence herbicidal activity tests revealed that compound 6-chloro-N-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenoxy)pyridazine-4-carboxamide (B1) with 2,4-diF substitution in the benzeneamino ring showed 100% inhibition rates against the roots and stems of Echinochloa crus-galli and Portulaca oleracea at 100 µg/mL, superior to the inhibition rates of BF. Meanwhile, compound B1 demonstrated excellent postemergence herbicidal activity against broadleaf weeds, which was similar to that of BF (inhibition rate of 100%) but superior to that of NRF. This indicated that 6-Cl in the pyridazine ring is the key group for postemergence herbicidal activity. In addition, compound B1 could induce downregulation of PDS gene expression, 15-cis-phytoene accumulation, and Y(II) deficiency and prevent photosynthesis. Therefore, B1 can be considered as a promising candidate for developing high-efficiency PDS inhibitors.


Assuntos
Echinochloa , Herbicidas , Oxirredutases , Proteínas de Plantas , Plantas Daninhas , Piridazinas , Herbicidas/farmacologia , Herbicidas/química , Piridazinas/farmacologia , Piridazinas/química , Echinochloa/efeitos dos fármacos , Echinochloa/enzimologia , Echinochloa/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Proteínas de Plantas/antagonistas & inibidores , Oxirredutases/genética , Oxirredutases/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/química , Plantas Daninhas/efeitos dos fármacos , Plantas Daninhas/enzimologia , Plantas Daninhas/genética , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Raízes de Plantas/química , Raízes de Plantas/efeitos dos fármacos , Estrutura Molecular
4.
Nature ; 627(8005): 797-804, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480894

RESUMO

Evidence shows a continuing increase in the frequency and severity of global heatwaves1,2, raising concerns about the future impacts of climate change and the associated socioeconomic costs3,4. Here we develop a disaster footprint analytical framework by integrating climate, epidemiological and hybrid input-output and computable general equilibrium global trade models to estimate the midcentury socioeconomic impacts of heat stress. We consider health costs related to heat exposure, the value of heat-induced labour productivity loss and indirect losses due to economic disruptions cascading through supply chains. Here we show that the global annual incremental gross domestic product loss increases exponentially from 0.03 ± 0.01 (SSP 245)-0.05 ± 0.03 (SSP 585) percentage points during 2030-2040 to 0.05 ± 0.01-0.15 ± 0.04 percentage points during 2050-2060. By 2060, the expected global economic losses reach a total of 0.6-4.6% with losses attributed to health loss (37-45%), labour productivity loss (18-37%) and indirect loss (12-43%) under different shared socioeconomic pathways. Small- and medium-sized developing countries suffer disproportionately from higher health loss in South-Central Africa (2.1 to 4.0 times above global average) and labour productivity loss in West Africa and Southeast Asia (2.0-3.3 times above global average). The supply-chain disruption effects are much more widespread with strong hit to those manufacturing-heavy countries such as China and the USA, leading to soaring economic losses of 2.7 ± 0.7% and 1.8 ± 0.5%, respectively.

5.
J Pharm Biomed Anal ; 241: 115999, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38306867

RESUMO

Shengjiang Xiexin decoction (SXD), a well-known traditional Chinese medicine (TCM), was used to alleviate delayed-onset diarrhea induced by the chemotherapeutic agent irinotecan (CPT-11). Our previous study showed that SXD regulated multidrug resistance-associated protein 2 (Mrp-2) to alter the pharmacokinetics of CPT-11 and its metabolites. However, the pharmacodynamic constituents and the related quality markers of SXD are unclear. In this study, ultra-high performance liquid chromatography coupled with quadrupole orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was utilized to identify the prototypes and metabolites in rat plasma after oral administration of SXD. The pharmacokinetic markers (PK markers) were screened through quantification and semiquantification of SXD-related xenobiotics in plasma using liquid chromatography-mass spectrometry (LC-MS) combined with statistical analysis. Computational molecular docking was performed to assess the potential binding ability of the PK markers with the target Mrp-2. The results were verified by evaluating the impact on Mrp-2 function using Caco-2 cells. The quality markers were chosen from these PK markers based on the binding affinities with Mrp-2, the specificity and the traceability. As a result, a total of 142 SXD-related exogenous components, including 77 prototypes and 65 metabolites, were detected in rat plasma. Among these, 83 xenobiotics were selected as PK markers due to their satisfactory pharmacokinetic behaviors. Based on the characteristics of quality markers, the prototype-based PK markers were considered the indices of quality control for SXD, including baicalin, baicalein, wogonoside, wogonin, liquiritigenin, isoliquiritigenin, norwogonin, oroxylin A, dihydrobaicalin, chrysin, glycyrrhizic acid, glycyrrhetinic acid, oroxylin A 7-O-glucuronide, liquiritin and isoliquiritin. This study provided an interesting strategy for screening the quality markers involved in the pharmacokinetics of SXD and its action target, which offered important information for the modernization of SXD and other TCM formulae.


Assuntos
Medicamentos de Ervas Chinesas , Humanos , Ratos , Animais , Ratos Sprague-Dawley , Irinotecano , Células CACO-2 , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Cromatografia Líquida de Alta Pressão/métodos
6.
Risk Anal ; 44(1): 155-189, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37105758

RESUMO

This article investigates the economic impacts of a multi-disaster mix comprising extreme weather, such as flooding, pandemic control, and export restrictions, dubbed a "perfect storm." We develop a compound-hazard impact model that improves on the ARIO model by considering the economic interplay between different types of hazardous events. The model considers simultaneously cross-regional substitution and production specialization, which can influence the resilience of the economy to multiple shocks. We build scenarios to investigate economic impacts when a flood and a pandemic lockdown collide and how these are affected by the timing, duration, and intensity/strictness of each shock. In addition, we examine how export restrictions during a pandemic impact the economic losses and recovery, especially when there is the specialization of production of key sectors. The results suggest that an immediate, stricter but shorter pandemic control policy would help to reduce the economic costs inflicted by a perfect storm, and regional or global cooperation is needed to address the spillover effects of such compound events, especially in the context of the risks from deglobalization.


Assuntos
Desastres , Clima Extremo , Pandemias , Inundações , Políticas
7.
Nature ; 622(7983): 514-520, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37731002

RESUMO

The highly energy-intensive iron and steel industry contributed about 25% (ref. 1) of global industrial CO2 emissions in 2019 and is therefore critical for climate-change mitigation. Despite discussions of decarbonization potentials at national and global levels2-6, plant-specific mitigation potentials and technologically driven pathways remain unclear, which cumulatively determines the progress of net-zero transition of the global iron and steel sector. Here we develop a CO2 emissions inventory of 4,883 individual iron and steel plants along with their technical characteristics, including processing routes and operating details (status, age, operation-years etc.). We identify and match appropriate emission-removal or zero-emission technologies to specific possessing routes, or what we define thereafter as a techno-specific decarbonization road map for every plant. We find that 57% of global plants have 8-24 operational years, which is the retrofitting window for low-carbon technologies. Low-carbon retrofitting following the operational characteristics of plants is key for limiting warming to 2 °C, whereas advanced retrofitting may help limit warming to 1.5 °C. If each plant were retrofitted 5 years earlier than the planned retrofitting schedule, this could lead to cumulative global emissions reductions of 69.6 (±52%) gigatonnes (Gt) CO2 from 2020 to 2050, almost double that of global CO2 emissions in 2021. Our results provide a detailed picture of CO2 emission patterns associated with production processing of iron and steel plants, illustrating the decarbonization pathway to the net-zero-emissions target with the efforts from each plant.

9.
Sci Bull (Beijing) ; 68(20): 2456-2466, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37620230

RESUMO

Chinese cities are core in the national carbon mitigation and largely affect global decarbonisation initiatives, yet disparities between cities challenge country-wide progress. Low-carbon transition should preferably lead to a convergence of both equity and mitigation targets among cities. Inter-city supply chains that link the production and consumption of cities are a factor in shaping inequality and mitigation but less considered aggregately. Here, we modelled supply chains of 309 Chinese cities for 2012 to quantify carbon footprint inequality, as well as explored a leverage opportunity to achieve an inclusive low-carbon transition. We revealed significant carbon inequalities: the 10 richest cities in China have per capita carbon footprints comparable to the US level, while half of the Chinese cities sit below the global average. Inter-city supply chains in China, which are associated with 80% of carbon emissions, imply substantial carbon leakage risks and also contribute to socioeconomic disparities. However, the significant carbon inequality implies a leveraging opportunity that substantial mitigation can be achieved by 32 super-emitting cities. If the super-emitting cities adopt their differentiated mitigation pathway based on affluence, industrial structure, and role of supply chains, up to 1.4 Gt carbon quota can be created, raising 30% of the projected carbon quota to carbon peak. The additional carbon quota allows the average living standard of the other 60% of Chinese people to reach an upper-middle-income level, highlighting collaborative mechanism at the city level has a great potential to lead to a convergence of both equity and mitigation targets.

10.
Plant Physiol Biochem ; 202: 107974, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37632996

RESUMO

Drought severely affects the yield of wheat (Triticum aestivum L.), which is mainly grown in arid and semi-arid regions. Melatonin plays an important role in various types of stress resistance in plants, including drought resistance. However, the molecular mechanism through which melatonin affects drought tolerance remains largely unknown. In this study, we revealed that melatonin (100 µM) significantly improved drought resistance during the maturation stage of Chinese Spring, Shi4185, and Hanxuan10 varieties, but not Chang6878. Further physiological, transcriptomic, and proteomic data analysis at the wheat seedling stage revealed that melatonin increased jasmonic acid (JA) content, upregulating the expression of JA genes (LOX1.5 and LOX2.1) and two transcription factors (HY5 and MYB86) under drought conditions. It also upregulated genes related to lignin biosynthesis (4CL2, P5CS1, and CCR2) as well as starch and sucrose metabolism (PME53 and SUS4). Additionally, melatonin alleviated photosynthetic and cell membrane damage caused by drought stress through maintaining low levels of hydrogen peroxide. The current results elucidate melatonin-regulated pathways in wheat and provide evidence for using melatonin as a potential biostimulant to improve wheat drought resistance under field conditions in the future.


Assuntos
Resistência à Seca , Melatonina , Triticum/genética , Lignina , Proteômica
11.
Environ Sci Pollut Res Int ; 30(40): 92594-92610, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37495804

RESUMO

This study investigates the influence of consumer cooperation, eco-design, and green marketing on the adoption of green supply chain management in developing countries. The mediating role of innovation in this relationship is also examined. A survey method was employed, using a questionnaire adapted from previous studies. The sample comprised 250 respondents who were employees of small and medium size and multinational manufacturing industries in Bangladesh. Smart partial least squares (PLS) are currently being used for data analysis, while PLS-structural equation modeling is being employed to assess measurement and structural models. The findings reveal that consumer cooperation, eco-design, and green marketing significantly affect innovation. Furthermore, innovation acts as a mediator between these variables and the adoption of green supply chain management. This study identifies green supply chain management practices that have the potential to enhance organizational performance and motivate companies to implement strategic and operational changes, leading to significant economic, social, and environmental impacts. The research holds significant importance for emerging economies and green supply chain adoption considering the constraints at both organizational and government levels. It provides a framework for a synergistic combination of asset-based elements, innovation, and green supply chain management, benefiting small and medium size organization, multinational corporations, and the supply chain sector in achieving sustainable development goals. The implications of this study extend to supervisors and managers in the corporate world, assisting them in making informed decisions. By expanding the existing literature on the consumer cooperation, eco-design, and green marketing model to include green supply chain management, this study contributes to the field. However, it should be noted that the findings and recommendations may be influenced by contextual factors, and therefore, future research should explore other countries to identify regional and specific sectors, enabling a broader perspective and comparisons as well as green related aspects and performances.


Assuntos
Países em Desenvolvimento , Marketing , Humanos , Desenvolvimento Sustentável , Meio Ambiente , Indústria Manufatureira , Comércio
12.
Front Pharmacol ; 14: 1162134, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37361203

RESUMO

Objective: Astragali Radix (AR, Huangqi in Chinese) has a neuroprotective effect on cerebral infarction (CI). In order to explore the biological basis and therapeutic mechanism of AR in CI, a double-blind randomized controlled trial was established in this study, and proteomics analysis was carried out on serum samples of patients. Methods: The patients were divided into the AR group (n = 35) and the control group (n = 30). The curative effect was evaluated by the traditional Chinese medicine (TCM) syndrome score and clinical indicators, and the serum of the two groups was analyzed by proteomics. Based on bioinformatics analysis methods, the changes in differential proteins between two groups of samples were explored, and the key proteins were validated through enzyme-linked immunosorbent assay (ELISA). Results: The results of this study showed that the scores of deficiency of vital energy (DVE), blood stasis (BS), and NIH Stroke Scale (NIHSS) decreased significantly (p < 0.05), while the scores of the Barthel Index (BI) increased, indicating that AR could significantly improve the symptoms of CI patients. In addition, we found that compared with the control group, AR upregulated 43 proteins and downregulated 20 proteins, especially focusing on anti-atherosclerosis and neuroprotective effects. Moreover, ELISA indicated the levels of IL-6, TNF-α, VCAM-1, MCP-1, and ICAM-1 were significantly decreased in the serum of the AR group (p < 0.05, p < 0.01). Conclusion: This study found that AR can significantly recover the clinical symptoms of CI. Serum proteomics research results show that AR may act on IL-6, TNF-α, VCAM-1, MCP-1, and ICAM-1, and play anti-atherosclerosis and neuroprotective roles. Clinical Trial Registration: [clinicaltrials.gov], identifier [NCT02846207].

13.
Sci Rep ; 13(1): 7393, 2023 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149722

RESUMO

Rice-rape rotation is a widely practiced cropping system in China. However, changes in soil properties and management could change the bioavailability of Cd, In order to explore the occurrence state, transportation and transformation characteristics of heavy metals Cd and Zn in rice-rape rotation system in Guizhou karst area with high background value of Cd. In the karst rice-rape rotation area, the physical and chemical properties of soil, chemical specifications and activities of Cd and Zn at different soil depths and during various crop growth stages, and the bioaccumulation of Cd and Zn in different tissues of rice and rape were studied by field experiment and laboratory analysis. The bioaccumulation of Cd and Zn and the effects of physical and chemical soil properties on the activities and bioavailabilities of Cd and Zn during rice-rape rotation were explored. The findings revealed that soil particle size, composition, pH, redox potential, soil organic matter, and Cd and Zn contents varied dramatically, especially in deep soils. The physical and chemical properties of the deep and surface soils were significantly related to the bioaccumulation of Cd and Zn. Cd and Zn are activated during crop rotation. Cd was easier to be enriched in rice, while Zn was easier to be enriched in rape. The correlation between Cd and Zn contents in Brassica campestris L and their enrichment abilities were not significant, but that in Oryza sativa L were significant. During rice-rape rotation, the chemical speciations and activities of Cd and Zn changed with the changes of soil properties and waterlogging environment. This study had important basic guiding significance for the evaluation, prevention and control of heavy metal pollution, and improving soil quality in different rotation systems in karst areas, and was conducive to promoting the safe production of rape and rice.


Assuntos
Brassica napus , Brassica rapa , Metais Pesados , Oryza , Poluentes do Solo , Solo/química , Cádmio/análise , Agricultura , Metais Pesados/análise , Zinco/farmacologia , China , Poluentes do Solo/análise
14.
Int J Mol Sci ; 24(7)2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37047827

RESUMO

Aberrant expression of the phosphatidylinositol 3-kinase (PI3K) signalling pathway is often associated with tumourigenesis, progression and poor prognosis. Hence, PI3K inhibitors have attracted significant interest for the treatment of cancer. In this study, a series of new 6-(imidazo[1,2-a]pyridin-6-yl)quinazoline derivatives were designed, synthesized and characterized by 1H NMR, 13C NMR and HRMS spectra analyses. In the in vitro anticancer assay, most of the synthetic compounds showed submicromolar inhibitory activity against various tumour cell lines, among which 13k is the most potent compound with IC50 values ranging from 0.09 µΜ to 0.43 µΜ against all the tested cell lines. Moreover, 13k induced cell cycle arrest at G2/M phase and cell apoptosis of HCC827 cells by inhibition of PI3Kα with an IC50 value of 1.94 nM. These results suggested that compound 13k might serve as a lead compound for the development of PI3Kα inhibitor.


Assuntos
Antineoplásicos , Quinazolinas , Quinazolinas/química , Estrutura Molecular , Relação Estrutura-Atividade , Fosfatidilinositol 3-Quinases/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células , Antineoplásicos/química , Linhagem Celular Tumoral , Desenho de Fármacos
15.
Nat Commun ; 14(1): 1569, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944651

RESUMO

Ensuring a more equitable distribution of vaccines worldwide is an effective strategy to control global pandemics and support economic recovery. We analyze the socioeconomic effects - defined as health gains, lockdown-easing effect, and supply-chain rebuilding benefit - of a set of idealized COVID-19 vaccine distribution scenarios. We find that an equitable vaccine distribution across the world would increase global economic benefits by 11.7% ($950 billion per year), compared to a scenario focusing on vaccinating the entire population within vaccine-producing countries first and then distributing vaccines to non-vaccine-producing countries. With limited doses among low-income countries, prioritizing the elderly who are at high risk of dying, together with the key front-line workforce who are at high risk of exposure is projected to be economically beneficial (e.g., 0.9%~3.4% annual GDP in India). Our results reveal how equitable distributions would cascade more protection of vaccines to people and ways to improve vaccine equity and accessibility globally through international collaboration.


Assuntos
COVID-19 , Vacinas , Humanos , Idoso , Vacinas contra COVID-19 , Saúde Global , COVID-19/epidemiologia , COVID-19/prevenção & controle , Controle de Doenças Transmissíveis
16.
Sci Total Environ ; 873: 162074, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36758691

RESUMO

Effectively reducing transportation carbon emissions is greatly significant to achieve the carbon peaking and neutral goals of China. On the basis of considering regional technology heterogeneity, we employ the parametric meta-frontier approach to analyze the carbon emission performance and reduction potential of the transportation sector in China. Then, we further decompose the emission reduction potential's contributors into removing management inefficiencies and filling technology gaps. The estimated potential carbon emission reductions from transportation sector in China are 12.3 million tons, accounting for 8.4 % of the annual transportation carbon emissions. Specifically, the eastern regions, especially Shandong, Shanghai, and Liaoning have the greatest carbon emission reduction potential; while Qinghai, Jiangxi, and Ningxia have the smallest potential. As the major contributors to the potential emission reductions, filling technology gaps and removing management inefficiencies account for 57.5 % and 42.5 % of the total potential, respectively. Moreover, removing management inefficiencies dominate for the eastern region and filling technology gaps for the central and western regions. Finally, we provide provincial-specific emission mitigation strategies based on the identification of the reduction potential and its contributors. Our policy implications help decision-makers to facilitate the low-carbon development of transportation sector.

17.
Bioorg Chem ; 132: 106352, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36682147

RESUMO

Aurora A (Aurora kinase A), a critical regulator of cell mitosis, is frequently overexpressed in many malignant cancers, and has been considered as a promising drug target for cancer therapy. Likewise, Phosphatidylinositol 3-kinase alpha (PI3Kα) is also regarded as one of the most important targets in cancer therapy by mediating the cell growth and angiogenesis of various human cancers. In addition, Bromodomain-containing protein 4 (BRD4) modulates oncogene expressions of Myc, Aurora kinase and various RTKs. Recently, accumulating evidences indicated that hyperactivated or abnormally expressed Aurora A, PI3Kα or BRD4 are closely associated with drug resistance and poor prognosis of non-small cell lung cancer (NSCLC). Hence, simultaneous inhibition of Aurora A, PI3Kα, and BRD4 is expected to be a new strategy for NSCLC therapy. In this study, we performed further structure optimization of 6-(2-amino-1H-benzo[d]imidazole-6-yl)-quinazolin-4(3H) -one based on previous study to obtain a series of derivatives for discovering potential Aurora A, PI3Kα and BRD4 multi-targeted inhibitors. MTT assay showed that most of the newly synthesized compounds exhibited an evident anticancer activity against the NSCLC cells. Among them, the IC50 values of the most potent compound 9a were 0.83, 0.26 and 1.02 µM against A549, HCC827 and H1975 cells, respectively. In addition, 9a markedly inhibited the Aurora A and PI3Kα kinase activities with IC50 values of 10.19 nM and 13.12 nM. Compound 9a induced G2/M phase arrests and apoptosis of HCC827 cells by simultaneous inhibition of Aurora A/PI3K/ BRD4 signaling pathways. Collectively, our studies suggested that 9a might be a potential multi-targeted inhibitor for NSCLC therapy.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Relação Estrutura-Atividade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Nucleares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Proteínas Quinases , Aurora Quinase A/metabolismo , Aurora Quinase A/farmacologia , Fatores de Transcrição , Antineoplásicos/química , Proliferação de Células , Imidazóis/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular
18.
J Soc Psychol ; 163(2): 174-190, 2023 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35098889

RESUMO

Although there have been studies in the past that have highlighted the important role of leadership in motivating employees to speak up, relational leadership has been scarcely investigated in this context. Therefore, the current research investigates the relationship between inclusive leadership, as a form of relational leadership, and employees' voice behavior directly and indirectly via psychological empowerment. Using the data collected from 252 employees and their respective supervisors working in cargo companies across the United Kingdom, this study finds a positive relationship between inclusive leadership and voice behavior. The results further confirm the mediating role of psychological empowerment in the relationship between inclusive leadership and voice behavior. We use causal attribution theory to support the findings and discuss implications for research and practice.


Assuntos
Liderança , Humanos , Reino Unido
19.
Natl Sci Rev ; 9(12): nwac223, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36540615

RESUMO

International efforts to avoid dangerous climate change have historically focused on reducing energy-related CO2 emissions from countries with either the largest economies (e.g. the EU and the USA) and/or the largest populations (e.g. China and India). However, in recent years, emissions have surged among a different and much less-examined group of countries, raising concerns that a next generation of high-emitting economies will obviate current mitigation targets. Here, we analyse the trends and drivers of emissions in each of the 59 countries where emissions in 2010-2018 grew faster than the global average (excluding China and India), project their emissions under a range of longer-term energy scenarios and estimate the costs of decarbonization pathways. Total emissions from these 'emerging emitters' reach as much as 7.5 GtCO2/year in the baseline 2.5° scenario-substantially greater than the emissions from these regions in previously published scenarios that would limit warming to 1.5°C or even 2°C. Such unanticipated emissions would in turn require non-emitting energy deployment from all sectors within these emerging emitters, and faster and deeper reductions in emissions from other countries to meet international climate goals. Moreover, the annual costs of keeping emissions at the low level are in many cases 0.2%-4.1% of countries' gross domestic production, pointing to potential trade-offs with poverty-reduction goals and/or the need for economic support and low-carbon technology transfer from historically high-emitting countries. Our results thus highlight the critical importance of ramping up mitigation efforts in countries that to this point have been largely ignored.

20.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362085

RESUMO

Drought is the major limiting factor that directly or indirectly inhibits the growth and reduces the productivity of sorghum (Sorghum bicolor (L.) Moench). As the main vegetative organ of sorghum, the response mechanism of the leaf to drought stress at the proteomic level has not been clarified. In the present study, nano-scale liquid chromatography mass spectrometry (nano-LC-MS/MS) technology was used to compare the changes in the protein expression profile of the leaves of drought-sensitive (S4 and S4-1) and drought-resistant (T33 and T14) sorghum varieties at the seedling stage under 25% PEG-6000 treatment for 24 h. A total of 3927 proteins were accurately quantitated and 46, 36, 35, and 102 differentially abundant proteins (DAPs) were obtained in the S4, S4-1, T14, and T33 varieties, respectively. Four proteins were randomly selected for parallel reaction monitoring (PRM) assays, and the results verified the reliability of the mass spectrometry (MS) results. The response mechanism of the drought-sensitive sorghum leaves to drought was attributed to the upregulation of proteins involved in the tyrosine metabolism pathway with defense functions. Drought-resistant sorghum leaves respond to drought by promoting the TCA cycle, enhancing sphingolipid biosynthesis, interfering with triterpenoid metabolite synthesis, and influencing aminoacyl-tRNA biosynthesis. The 17 screened important candidate proteins related to drought stress were verified by quantitative real-time PCR (qRT-PCR), the results of which were consistent with the results of the proteomic analysis. This study lays the foundation for revealing the drought-resistance mechanism of sorghum at the protein level. These findings will help us cultivate and improve new drought-resistant sorghum varieties.


Assuntos
Secas , Sorghum , Sorghum/metabolismo , Proteômica , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Grão Comestível , Estresse Fisiológico , Regulação da Expressão Gênica de Plantas
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