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1.
Artigo em Inglês | MEDLINE | ID: mdl-35031995

RESUMO

China has been the world's largest emitter of carbon dioxide since 2006. To achieve the goal of carbon neutrality by 2060, social scientists must become involved in China's deep decarbonization process. However, Chinese social scientists have given little attention to climate change in their bibliometric research. Based on the Chinese Social Sciences Citation Index journal catalog of the four essential social sciences, namely, management, economics, politics, and sociology, we used the China National Knowledge Infrastructure database to quantify the extent to which Chinese social scientists are concerned about climate change. The results showed that from 1978 to 2020, 1179 articles on climate change were published in management, economics, politics, and sociology journals, which represented only 26.8% of the 4397 articles published on pollution in the same journals. Politics journals published the most articles (38.76%), while sociology journals published the fewest (2.37%). Thus, Chinese social scientists rarely considered climate change, mainly because this topic remains controversial in some fields and because of the influence of international politics in addition to the promotion and incentive mechanisms for researchers. We analyzed the keywords and evolution of climate change research in the four social sciences and our results show that social scientists should give greater emphasis to climate change in their research.

2.
FASEB J ; 36(2): e22124, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34972249

RESUMO

Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. We observed that the TGF-ß/Smads signal pathway was significantly suppressed by Nur77, suggesting that Nur77 controlled the activation of key steps in TGF-ß/Smads signaling. We further showed that Nur77 interacted with Smad7, the main repressor of nuclear translocation of Smad2/3, and stabilized Smad7 protein homeostasis. Nur77 deficiency resulted in Smad7 degradation, aggravating Smad2/3 phosphorylation, and promoting transcription of its downstream target genes, ACTA2 and collagen I. Our findings demonstrate that Nur77 is a potential therapeutic target for age-related kidney diseases including CKD. Maintenance of Nur77 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in the elderly.


Assuntos
Envelhecimento/metabolismo , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Envelhecimento/genética , Animais , Fibrose , Camundongos , Camundongos Knockout , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Insuficiência Renal Crônica/genética , Proteínas Smad/genética , Fator de Crescimento Transformador beta/genética
4.
J Cell Mol Med ; 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34866322

RESUMO

In multiple types of cancer, decreased tumour cell apoptosis during chemotherapy is indicative of decreased chemosensitivity. Forkhead box K2 (FOXK2), which is essential for cell fate, regulates cancer cell apoptosis through several post-translational modifications. However, FOXK2 acetylation has not been extensively studied. Here, we evaluated the effects of sirtiun 1 (SIRT1) on FOXK2 deacetylation. Our findings demonstrated that SIRT1 inhibition increased FOXK2-induced chemosensitivity to cisplatin and that K223 in FOXK2 was acetylated. Furthermore, FOXK2 K223 deacetylation reduced chemosensitivity to cisplatin in vitro and in vivo. Mechanistically, FOXK2 was acetylated by the acetyltransferase cAMP response element binding protein and deacetylated by SIRT1. Furthermore, cisplatin attenuated the interaction between FOXK2 and SIRT1. Cisplatin or SIRT1 inhibition enhanced FOXK2 acetylation, thereby reducing the nuclear distribution of FOXK2. Additionally, FOXK2 K223 acetylation significantly affected the expression of cell cycle-related and apoptosis-related genes in cisplatin-stimulated cancer cells, and FOXK2 K223 hyperacetylation promoted mitotic catastrophe, which enhanced chemosensitivity to cisplatin. Overall, our results provided insights into the mechanisms of SIRT1-mediated FOXK2 deacetylation, which was involved in chemosensitivity to cisplatin.

5.
Ying Yong Sheng Tai Xue Bao ; 32(11): 3893-3904, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34898105

RESUMO

As an important ecological compensation project initiated in China, the returning farmland to forest (grassland) project plays a key role in maintaining national ecological security. Systematical analysis for the impacts of the returning farmland to forest (grassland) project on ecosystem services would provide reference for consummating ecological compensation system. Taking the Weihe River Basin as an example, we analyzed the spatiotemporal changes of land use and ecosystem services since the implementation of the project based on land use data, meteorological data and other information. The InVEST model and geographically weighted regression were used to investigate the impacts of the project on the changes of ecosystem services, such as water conservation, soil conservation, carbon storage, and habitat quality. The results showed that since the implementation of the project, the coverage rate of forest and grassland had been fluctuating upwards, with an increase of 2704.49 km2 of forest and grassland area. From 2000 to 2018, in the Weihe River Basin all showed a fluctuating upwards trends. Among those services, water conservation and carbon storage had large increases, while habitat quality and soil conservation had small increases. The project had effectively improved ecosystem services in the Weihe River Basin, but the impacting intensity on ecosystem services varied from one geographical unit to another.


Assuntos
Ecossistema , Rios , China , Conservação dos Recursos Naturais , Fazendas , Florestas , Pradaria
6.
Onco Targets Ther ; 14: 5391-5402, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34908844

RESUMO

Purpose: The increase of both M2-type macrophages and Tregs is closely associated with the development of colorectal cancer. However, the mechanism of their interaction is still unclear. In this study, we investigated the correlation of M2-type macrophages with Tregs and the possible mechanisms between them. Methods: Using immunohistochemistry, we analysed Smad3 (a key protein in the TGF-ß/Smad signalling pathway) expression in colorectal cells, as well as infiltrating numbers of CD163 (a marker for M2-type macrophages), Foxp3 (a marker for Tregs) in 250 surgically resected colorectal cancer tissues, matched normal and paracancerous tissues. The relation of CD163 and Foxp3 was investigated in CRC with clinicopathological characteristics and preoperative tumour markers. Results: CD163, Foxp3 and Smad3 were upregulated in CRC tissues compared to matched normal and paracancerous tissues. Interestingly, CD163 and Foxp3 were significantly positively correlated in CRC, and both were significantly positively correlated with Smad3. Both CD163 and Foxp3 were upregulated with increasing tumour TNM staging, increasing number of lymph node metastases and increasing vascular invasion. Additionally, CD163 was upregulated with increasing depth of infiltration. The number of M2-type macrophages and the expression levels of preoperative CEA, CA19-9 and CA72-4 were significantly positively correlated. The number of Tregs was significantly positively correlated with the expression levels of preoperative CEA and CA19-9. Conclusion: M2-type macrophages may induce Tregs generation through activation of the TGF-ß/Smad signalling pathway, which can promote the development of colorectal cancer.

7.
Acta Pharmacol Sin ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34912007

RESUMO

Excessive exposure to UVB induces skin diseases. Silibinin, a flavonolignan used for treating liver diseases, is found to be effective against UVB-caused skin epidermal and dermal cell damage. In this study we investigated the molecular mechanisms underlying. Human nonmalignant immortalized keratinocyte HaCaT cells and neonatal human foreskin fibroblasts HFFs were exposed to UVB irradiation. We showed that pre-treatment with silibinin dose-dependently decreased UVB-induced apoptosis of HaCaT cells. Furthermore, we showed that silibinin treatment inhibited nuclear translocation of YAP after UVB irradiation. Molecular docking analysis and DARTS assay confirmed the direct interaction of silibinin with YAP. Silencing YAP by siRNA had no influence on the survival of HaCaT cells, whereas inhibiting classical YAP-TEAD signaling pathway by siRNA targeting TEAD1 or its pharmaceutical inhibitor verteporfin further augmented UVB-induced apoptosis, suggesting that YAP-TEAD pathway was prosurvival, which did not participate in the protective effect of silibinin. We then explored the pro-apoptotic YAP-p73 pathway. p73 was upregulated in UVB-irradiated cells, but reduced by silibinin cotreatment. The mRNA and protein levels of p73 target genes (PML, p21 and Bax) were all increased by UVB but decreased by silibinin co-treatment. Inhibiting p73 by using siRNA reduced UVB-induced apoptosis, suggesting that downregulation of p73 was responsible for the cytoprotective effect of silibinin. In HFFs, the upregulated YAP-p73 pathway by UVB irradiation was also suppressed by silibinin. Collectively, YAP-p73 pathway is a major cause of the death of UVB-exposed epidermal HaCaT cells and dermal HFFs. Silibinin directly inhibits YAP-p73 pathway, exerting the protective action on UVB-irradiated skin cells.

8.
Nat Chem Biol ; 17(12): 1314-1323, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34608293

RESUMO

Spindle position control is essential for cell fate determination and organogenesis. Early studies indicate the essential role of the evolutionarily conserved Gαi/LGN/NuMA network in spindle positioning. However, the regulatory mechanisms that couple astral microtubules dynamics to the spindle orientation remain elusive. Here we delineated a new mitosis-specific crotonylation-regulated astral microtubule-EB1-NuMA interaction in mitosis. EB1 is a substrate of TIP60, and TIP60-dependent crotonylation of EB1 tunes accurate spindle positioning in mitosis. Mechanistically, TIP60 crotonylation of EB1 at Lys66 forms a dynamic link between accurate attachment of astral microtubules to the lateral cell cortex defined by NuMA-LGN and fine tune of spindle positioning. Real-time imaging of chromosome movements in HeLa cells expressing genetically encoded crotonylated EB1 revealed the importance of crotonylation dynamics for accurate control of spindle orientation during metaphase-anaphase transition. These findings delineate a general signaling cascade that integrates protein crotonylation with accurate spindle positioning for chromosome stability in mitosis.

9.
Int J Biol Sci ; 17(14): 4047-4059, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671219

RESUMO

The faithful DNA replication is a critical event for cell survival and inheritance. However, exogenous or endogenous sources of damage challenge the accurate synthesis of DNA, which causes DNA lesions. The DNA lesions are obstacles for replication fork progression. However, the prolonged replication fork stalling leads to replication fork collapse, which may cause DNA double-strand breaks (DSB). In order to maintain genomic stability, eukaryotic cells evolve translesion synthesis (TLS) and template switching (TS) to resolve the replication stalling. Proliferating cell nuclear antigen (PCNA) trimer acts as a slide clamp and encircles DNA to orchestrate DNA synthesis and DNA damage tolerance (DDT). The post-translational modifications (PTMs) of PCNA regulate these functions to ensure the appropriate initiation and termination of replication and DDT. The aberrant regulation of PCNA PTMs will result in DSB, which causes mutagenesis and poor response to chemotherapy. Here, we review the roles of the PCNA PTMs in DNA duplication and DDT. We propose that clarifying the regulation of PCNA PTMs may provide insights into understanding the development of cancers.

11.
Ecol Evol ; 11(20): 14042-14055, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34707838

RESUMO

The composition of vegetation on a slope frequently changes substantially owing to the different micro-environments of various slope aspects. To understand how the slope aspect affects the vegetation changes, we examined the variations in leaf mass per area (LMA) and leaf size (LS) within and among populations for 66 species from 14 plots with a variety of slope aspects in a subalpine meadow. LMA is a leaf economic trait that is tightly correlated with plant physiological traits, while the LS shows a tight correlation with leaf temperature, indicating the strategy of plants to self-adjust in different thermal and hydraulic conditions. In this study, we compared the two leaf traits between slope aspects and between functional types and explored their correlation with soil variables and heat load. Our results showed that high-LMA, small-leaved species were favored in south-facing slopes, while the reverse was true in north-facing areas. In detail, small dense-leaved graminoids dominated the south slopes, while large thin-leaved forbs dominated the north slopes. Soil moisture and the availability of soil P were the two most important soil factors that related to both LMA and LS, and heat load also contributed substantially. Moreover, we disentangled the relative importance of intraspecific trait variation and species turnover in the trait variation among plots and found that the intraspecific variation contributed 98% and 56% to LMA and LS variation among communities, respectively, implying a large contribution of intraspecific trait plasticity. These results indicate that LMA and LS are two essential leaf traits that affect the adaptation or acclimation of plants underlying the vegetation composition changes in different slope aspects in the subalpine meadow.

12.
J Mol Cell Biol ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34554241

RESUMO

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent studies show that mitotic motor CENP-E cooperates with SKAP and forms a link between kinetochore core MIS13 complex and spindle microtubule plus-ends to achieve accurate chromosome alignment in mitosis. However, it remains elusive how SKAP regulates kinetochore attachment from lateral association to end-on attachment during metaphase alignment. Here, we identify a novel interaction between Aurora B and SKAP that orchestrates accurate interaction between the kinetochore and dynamic spindle microtubules. Interestingly, SKAP spontaneously phase-separates in vitro via weak, multivalent interactions into droplets with fast internal dynamics. SKAP and Aurora B form heterogeneous coacervates in vitro, which recapitulate the dynamics and behavior of SKAP comets in vivo. Importantly, SKAP interaction with Aurora B via phase separation is essential for accurate chromosome segregation and alignment. Based on those findings, we reason that SKAP-Aurora B interaction via phase separation constitutes a dynamic pool of Aurora B activity during the lateral to end-on conversion of kinetochore-microtubule attachments to achieve faithful cell division.

13.
Nano Lett ; 21(18): 7724-7731, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34477392

RESUMO

The synthesis of metallic transition metal nitrides (TMNs) has traditionally been performed under harsh conditions, which makes it difficult to prepare TMNs with high surface area and porosity due to the grain sintering. Herein, we report a general and rapid (30 s) microwave synthesis method for preparing TMNs with high specific surface area (122.6-141.7 m2 g-1) and porosity (0.29-0.34 cm3 g-1). Novel single-crystal porous WN, Mo2N, and V2N are first prepared by this method, which exhibits strong surface plasmon resonance, photothermal conversion, and surface-enhanced Raman scattering effects. Different from the conventional low-temperature microwave absorbing media such as water and polymers, as new concept absorbing media, hydrated metal oxides and metallic metal oxides are found to have a remarkable high-temperature microwave heating effect and play key roles in the formation of TMNs. The current research results provide a new-concept microwave method for preparing high lattice energy compounds with high specific surface.

14.
NPJ Precis Oncol ; 5(1): 83, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535742

RESUMO

Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients.

15.
Int J Biol Sci ; 17(12): 3080-3090, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421351

RESUMO

Reactive oxygen species (ROS) are generally small, short-lived and highly reactive molecules, initially thought to be a pathological role in the cell. A growing amount of evidence in recent years argues for ROS functioning as a signaling intermediate to facilitate cellular adaptation in response to pathophysiological stress through the regulation of autophagy. Autophagy is an essential cellular process that plays a crucial role in recycling cellular components and damaged organelles to eliminate sources of ROS in response to various stress conditions. A large number of studies have shown that DNA damage response (DDR) transducer ataxia-telangiectasia mutated (ATM) protein can also be activated by ROS, and its downstream signaling pathway is involved in autophagy regulation. This review aims at providing novel insight into the regulatory mechanism of ATM activated by ROS and its molecular basis for inducing autophagy, and revealing a new function that ATM can not only maintain genome homeostasis in the nucleus, but also as a ROS sensor trigger autophagy to maintain cellular homeostasis in the cytoplasm.

16.
Int J Biol Sci ; 17(12): 3173-3187, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421358

RESUMO

Pharmacological stimulation of adipose tissue remodeling and thermogenesis to increase energy expenditure is expected to be a viable therapeutic strategy for obesity. Berberine has been reported to have pharmacological activity in adipose tissue to anti-obesity, while the mechanism remains unclear. Here, we observed that berberine significantly reduced the body weight and insulin resistance of high-fat diet mice by promoting the distribution of brown adipose tissue and thermogenesis. We have further demonstrated that berberine activated energy metabolic sensing pathway AMPK/SIRT1 axis to increase the level of PPARγ deacetylation, which leads to promoting adipose tissue remodeling and increasing the expression of the thermogenic protein UCP-1. These findings suggest that berberine that enhances the AMPK/SIRT1 pathway can act as a selective PPARγ activator to promote adipose tissue remodeling and thermogenesis. This study proposes a new mechanism for the regulation of berberine in adipose tissue and offers a great prospect for berberine in obesity treatment.

17.
Cell ; 184(16): 4348-4371.e40, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34358469

RESUMO

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

18.
Urban Rail Transit ; : 1-16, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34401217

RESUMO

In recent decades, the transit-oriented development (TOD) concept has been widely used all over the world, especially in China, for the massive construction of urban public transportation systems with rail transit as the backbone. However, it is not easy to make significant changes in a city while building a transportation system, and the transit-guided urban development expected by the TOD concept has not been completely realized. The transformation of nearby areas with the guidance of transit is also becoming the choice of many Chinese cities, especially for cities that have only had subways for a few years. Unlike other international metropolitan cities, with metro systems of considerable scale, the modernization process of most of the small and medium-sized cities in China is being carried out simultaneously with metro-based public transportation guidance. For cities which are still in their initial stage of the backbone public transportation system, there is not enough previous experience and evidence to support the suitability of TOD typological analysis based on the node-place model. More research based on the node-place model has also shown practical applications of the TOD in developed cities. However, there are very few studies that analyse cities in which rail transit and urban development are both in a period of rapid growth. The goal of this research is to identify which metro stations in these cities are suitable for TOD improvement and optimization. This article attempts to expand the willingness of residents on the basis of the traditional node-place model as one of the judgment indicators for evaluating whether existing stations and surrounding areas are suitable for TOD improvement. At the same time, traditional statistical analysis is combined with GIS and machine learning technology. Using this method, we propose the TOD improvement-oriented station area classification and identification method based on TOD typology theory. The results show that Ningbo's subway stations can be divided into four categories according to the suitability for TOD improvement, and we selected seven stations suitable for TOD improvement according to the characteristics of the node-place model. The practice in Ningbo has proved that this method is effective for identifying sites suitable for TOD improvement, especially for cities that have recently built subways.

19.
Mitochondrial DNA B Resour ; 6(9): 2628-2629, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34409160

RESUMO

Paeonia rockii subsp. taibaishanica (Paeoniaceae), one of the tree peony species, is endemic to the Qinling Mountains in central China. In this study, we characterized its whole plastid genome sequence using the Illumina sequencing platform. The complete plastid genome size of P. rockii subsp. taibaishanica is 153,368 bp in length, including a large single copy (LSC) region of 85,030 bp, a small single copy (SSC) region of 17,042 bp, and a pair of inverted repeats (IRs) of 25,648 bp. The genome contains 131 genes, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The GC contents in chloroplast genome, LSC region, SSC region, and IR region were 38.3%, 36.6%, 32.6%, and 43.1%, respectively. A total of 16 species are used to construct the phylogenetic tree of Paeoniaceae, the results showed that P. rockii subsp. taibaishanica is more closely related with congeneric Paeonia suffruticosa and Paeonia ostii, these species were clustered into a clade with high bootstrap support.

20.
Blood ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34359073

RESUMO

Acute myeloid leukemia (AML) is a clonal hematopoietic stem and progenitor cell malignancy characterized by poor clinical outcomes. MICA and MICB (MICA/B) are stress-proteins expressed by cancer cells, and antibody-mediated inhibition of MICA/B shedding represents a novel approach to stimulate immunity against cancers. We found that the MICA/B antibody 7C6 potently inhibits the outgrowth of AML in two models in immunocompetent mice. Macrophages were essential for therapeutic efficacy, and 7C6 triggered antibody-dependent phagocytosis of AML cells. Furthermore, we found that romidepsin, a selective histone deacetylase inhibitor, increased MICB mRNA in AML cells and enabled subsequent stabilization of the translated protein by 7C6. This drug combination substantially increased surface MICA/B expression in a human AML line, pluripotent stem cell-derived AML blasts and leukemia stem cells, as well as primary cells from three untreated AML patients. Human macrophages phagocytosed AML cells following treatment with 7C6 and romidepsin, and the combination therapy lowered leukemia burden in a humanized model of AML. Therefore, inhibition of MICA/B shedding promotes macrophage-driven immunity against AML via Fc receptor signaling and synergizes with an epigenetic regulator. These results provide the rationale for the clinical testing of this innovative immunotherapeutic approach for the treatment of AML.

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