Promoting sustainable smallholder farming via multistakeholder collaboration.

Transforming smallholder farms is critical to global food security and environmental sustainability. The science and technology backyard (STB) platform has proved to be a viable approach in China. However, STB has traditionally focused on empowering smallholder farmers by transferring knowledge, and wide-scale adoption of more sustainable practices and technologies remains a challenge. Here, we report on a long-term project focused on technology scale-up for smallholder farmers by expanding and upgrading the original STB platform (STB 2.0). We created a formalized and standardized process by which to engage and collaborate with farmers, including integrating their feedback via equal dialogues in the process of designing and promoting technologies. Based on 288 site-year of field trials in three regions in the North China Plain over 5 y, we find that technologies cocreated through this process were more easily accepted by farmers and increased their crop yields and nitrogen factor productivity by 7.2% and 28.1% in wheat production and by 11.4% and 27.0% in maize production, respectively. In promoting these technologies more broadly, we created a "one-stop" multistakeholder program involving local government agencies, enterprises, universities, and farmers. The program was shown to be much more effective than the traditional extension methods applied at the STB, yielding substantial environmental and economic benefits. Our study contributes an important case study for technology scale-up for smallholder agriculture. The STB 2.0 platform being explored emphasizes equal dialogue with farmers, multistakeholder collaboration, and long-term investment. These lessons may provide value for the global smallholder research and practitioners.

Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation.

BACKGROUND: Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. METHODS: We generated NR4A3-/- mice and 2 different types of medial arterial calcification models to investigate the biological roles of NR4A3 in vascular calcification. RNA-seq was performed to determine the transcriptional profile of NR4A3-/- vascular smooth muscle cells under ß-glycerophosphate treatment. We integrated Cleavage Under Targets and Tagmentation analysis and RNA-seq data to further investigate the gene regulatory mechanisms of NR4A3 in arterial calcification and target genes regulated by histone lactylation. RESULTS: NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH)2VitD3 overload-induced mice, and human calcified aorta. NR4A3 deficiency preserved the vascular smooth muscle cell contractile phenotype, inhibited osteoblast differentiation-related gene expression, and reduced calcium deposition in the vasculature. Further, NR4A3 deficiency lowered the glycolytic rate and lactate production during the calcification process and decreased histone lactylation. Mechanistic studies further showed that NR4A3 enhanced glycolysis activity by directly binding to the promoter regions of the 2 glycolysis genes ALDOA and PFKL and driving their transcriptional initiation. Furthermore, histone lactylation promoted medial calcification both in vivo and in vitro. NR4A3 deficiency inhibited the transcription activation and expression of Phospho1 (phosphatase orphan 1). Consistently, pharmacological inhibition of Phospho1 attenuated calcium deposition in NR4A3-overexpressed vascular smooth muscle cells, whereas overexpression of Phospho1 reversed the anticalcific effect of NR4A3 deficiency in vascular smooth muscle cells. CONCLUSIONS: Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.

Pursuing sustainable productivity with millions of smallholder farmers.

Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.

Strategies for the efficient biosynthesis of ß-carotene through microbial fermentation.

ß-Carotene is an orange fat-soluble compound, which has been widely used in fields such as food, medicine and cosmetics owing to its anticancer, antioxidant and cardiovascular disease prevention properties. Currently, natural ß-carotene is mainly extracted from plants and algae, which cannot meet the growing market demand, while chemical synthesis of ß-carotene cannot satisfy the pursuit for natural products of consumers. The ß-carotene production through microbial fermentation has become a promising alternative owing to its high efficiency and environmental friendliness. With the rapid development of synthetic biology and in-depth study on the synthesis pathway of ß-carotene, microbial fermentation has shown promising applications in the ß-carotene synthesis. Accordingly, this review aims to summarize the research progress and strategies of natural carotenoid producing strain and metabolic engineering strategies in the heterologous synthesis of ß-carotene by engineered microorganisms. Moreover, it also summarizes the adoption of inexpensive carbon sources to synthesize ß-carotene as well as proposes new strategies that can further improve the ß-carotene production.

Vital role of SHMT2 in diverse disease.

One-carbon metabolism is essential for our human cells to carry out nucleotide synthesis, methylation, and reductive metabolism through one-carbon units, and these pathways ensure the high proliferation rate of cancer cells. Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme in one-carbon metabolism. This enzyme can convert serine into a one-carbon unit bound to tetrahydrofolate and glycine, ultimately supporting the synthesis of thymidine and purines and promoting the growth of cancer cells. Due to SHMT2's crucial role in the one-carbon cycle, it is ubiquitous in human cells and even in all organisms and highly conserved. Here, we summarize the impact of SHMT2 on the progression of various cancers to highlight its potential use in the development of cancer treatments.

High-Performance Bifunctional Porous Iron-Rich Phosphide/Nickel Nitride Heterostructures for Alkaline Seawater Splitting.

Seawater is the most abundant natural water resource in the world, which is an inexhaustible and low-cost feedstock for hydrogen production by alkaline water electrolysis. It is appearling to develop robust and stable electrocatalysts for alkaline seawater electrolysis. However, the development of seawater electrolysis is seriously impeded by anodic chloride corrosion and chlorine evolution reaction, and few non-noble electrocatalysts show prominent catalytic performance and excellent durability. Here, a heterogeneous electrocatalyst constructed by in situ growing highly dispersed iron-rich bimetallic phosphide nanoparticles on metallic Ni3 N (Fe2-2 x Co2 x P/Ni3 N), which exhibits outstanding bifunctional catalytic activities for alkaline seawater splitting, is reported. The optimal (Fe0.74 Co0.26 )2 P/Ni3 N and Fe2 P/Ni3 N electrocatalysts demand only 113 and 212 mV to afford 100 mA cm-2 for hydrogen and oxygen evolution reactions (HER and OER) in 1 m KOH, respectively, thus substantially expediting overall water/seawater electrolysis at 100 mA cm-2 with 1.592/1.645 V. Particularly, Fe2 P/Ni3 N displays an unprecedented overpotential of 302 mV at 500 mA cm-2 , which represents the best alkaline seawater oxygen evolution activity among the ever-reported non-noble electrocatalysts; and thus substantially expedites overall water/seawater splitting at 500 mA cm-2 with 1.701/1.768 V, surpassing most of the reported non-noble lectrocatalysts. This work provides a new approach for developing high-performance electrocatalysts for seawater splitting.

Icariin alleviates ferroptosis-related atherosclerosis by promoting autophagy in xo-LDL-induced vascular endothelial cell injury and atherosclerotic mice.

Vascular endothelial cells (VECs) are located between the blood plasma and the vascular tissue, and the ferroptosis (iron-dependent programmed cell death) of VECs can lead to a range of cardiovascular diseases. Icariin is the main active ingredient of Epimedium brevicornum Maxim., which can improve endothelial cell dysfunction. In the present study, the protective effects of icariin on oxidised low-density lipoprotein (ox-LDL)-treated VECs and high-fat diet-fed Apolipoprotein E-deficient mice were investigated. Inflammatory fibrosis in tissues and inflammatory factors in serum and cell supernatants were detected, and mitochondrial membrane potential and the expression levels of ferroptosis-associated proteins were also detected. The results revealed that icariin reduced the endothelial atherosclerotic plaque area and collagen fibres in aortic sinus tissue, and increased the viability and mitochondrial membrane potential, whereas it reduced the reactive oxygen species levels of VECs. The nucleation of transcription factor EB (TFEB) and subsequent autophagy were negatively associated with ferroptosis in endothelial cells, and the more prominent the autophagy, the lower the levels of ferroptosis. Furthermore, by co-treating the cells with icariin and the two autophagy inhibitors, Bafilomycin A1 (blocking autophagosome and lysosome fusion) and 3-methyladenine (blocking autophagosome formation), respectively, the promoting effects of icariin on autophagy were found to be mediated through the process of autophagosome-lysosome fusion. In in vivo experiments, icariin reduced ferroptosis, alleviated atherosclerotic lesions and increased the rate of TFEB nucleation. Additionally, it was found that ARG304, THR308 and GLN311 were the optimal binding sites for the interaction between icariin and TFEB. Taken together, these results suggest that the fusion of autophagosomes and lysosomes promoted by icarrin enhances autophagy and thus reduces ferroptosis. Therefore, icariin may be a potential candidate for the prevention of ferroptosis of VECs and, thus, for the treatment of cardiovascular diseases.

MAPK p38/Ulk1 pathway inhibits autophagy and induces IL-1ß expression in hepatic stellate cells.

In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and to contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells. It is unclear whether autophagy is involved in inflammatory cytokine induction in HSCs. MAPK p38, Ulk1 phosphorylation, and the Ulk1-Atg13 complex were analyzed in HSC-T6 cells after LPS treatment. The relationship between autophagy inhibition and inflammation was investigated in primary rat HSCs. We discovered that LPS inhibited autophagy through MAPK p38. The activation of MAPK p38 induced Ulk1 phosphorylation, which disrupted the Ulk1-Atg13 complex and therefore inhibited autophagy. Furthermore, in primary rat HSCs, we demonstrated that autophagy inhibition regulated IL-1ß induction, which depended on the MAPK p38/Ulk1 pathway. Our results reveal a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1-Atg13 disruption, which inhibits autophagy and induces IL-1ß expression in HSCs.NEW & NOTEWORTHY LPS inhibits autophagy in a concentration- and dose-dependent manner in HSC-T6 cells. MAPK p38 induces phosphorylation of Ulk1, which disrupts the Ulk1-Atg13 complex and is therefore required for the inhibition of autophagy by LPS. LPS induces IL-1ß expression via the MAPK p38/Ulk1 pathway in HSCs.

Atmospheric turbulence resistant heterodyne coherent receiver of few-mode fiber.

We propose and implement a free-space optical (FSO) communication system based on few-mode heterodyne detection that can effectively suppress atmospheric turbulence effects. The experimental results show that the received power gain of the FSO communication system using six-mode fibres is about 6 dB over that using SMF under moderate to strong turbulence conditions.In addition, we have built a coherent detection system for space laser communications with few-mode heterodyne detection and reception, and verified the compensation of atmospheric turbulence effects by the few-mode heterodyne detection and reception technique. Experimental results show that the proposed scheme improves the power budget by 4∼5dB over the single-mode heterodyne coherent reception scheme at BER = 3.8×10-3 under moderate to strong turbulence conditions.

Cooperation between specialized livestock and crop farms can reduce environmental footprints and increase net profits in livestock production.

The rapid specialization of livestock production in China has contributed to spatially decoupled crop and livestock production, leading to various environmental pollution issues. Some regional agro-environmental policies have recently promoted the coupling of specialized crop and livestock farms through cooperation. However, the environmental and economic performances of such cooperation remain unclear. This study investigated multiple environmental footprints of two contrasting production systems: cooperative crop-livestock systems (CCLS) and decoupled specialized livestock systems (DSLS), using survey data of 87 ruminant farms in Northwest China. Results show that farms in CCLS had lower net greenhouse gas (GHG) emissions (12-29%), lower reactive nitrogen (Nr) emissions (21-40%), lower phosphorus footprints (PF) (41-54%), and used less cropland (24-31%) per kg animal product, compared to those in DSLS. The large differences in GHG emissions between the two systems were mainly related to enteric fermentation and resource production (used for feed production). The differences in Nr emissions and PF were mainly related to manure management. Net profits per kg animal product were higher in CCLS (13-35%) than in DSLS, and most profits originated from lower purchasing costs of feed and young livestock. Net profits and environmental footprints were negatively correlated, suggesting an environmental and economic win-win situation for CCLS. The possible obstacles to recoupling specialized crop and livestock farms through cooperation have been discussed, including farm size, contract stability, and local policies. Our study provides science-based evidence to support policymakers and specialized farms to close nutrient loops between crop and livestock production sectors through regional cooperation.

Improving the sustainability of the wheat supply chain through multi-stakeholder engagement.

Feeding the world's growing population, while producing economic benefits with limited environmental effects, is a major challenge faced by global food supply chains. This is especially apparent when the production stage is predominated by smallholders as they each face varying economic and environmental demands, making it difficult to mobilize them on the ground. This study investigated how the environmental and economic sustainability of wheat supply chains could be improved by analyzing the performance of all stakeholders, especially the smallholders. Results showed that 77% of GHG emissions came from wheat cultivation, and less than 8% of the total economic benefits were recouped during this stage. In contrast, smallholders in the Science and Technology Backyards, reduced their GHG emissions by 16.4% and improved their economic benefits by 1.3- fold. Furthermore, a 2.6-fold increase in profit (1808 USD) with GHG emission reduction was achieved simultaneously by integrating all individual stages as a whole. This study found that the sustainability of the wheat supply chain was mainly affected by wheat cultivation. It also demonstrated the potential efficacy of empowering smallholders and integration of all individual stages as a whole to improve the sustainability of food supply chains.

[Effects of ecological factors on shape and ginsenoside of Panax ginseng].

The ecological environment is closely related to the growth and quality of authentic medicinal materials. Ginseng is very strict with its natural environment and grows mostly in the damp valleys of forests, and the appearance and chemical composition of ginseng under different growth environments are very different. This article reviews the effects of different ecological factors(including light, temperature, altitude, moisture, soil factors, etc.)on the appearance and chemical composition(mainly ginsenosides) of ginseng. Through systematic review, it is found that soil physical factors are the most important ecological factors that affect the appea-rance of ginseng, and soil bulk density plays a key role; temperature affects ginsenosides in ginseng medicinal materials The dominant ecological factors for the accumulation of chemical ingredents; strong light, high altitude, high soil moisture, low soil nutrient and strong acid soil can influence the accumulation of secondary metabolites in ginseng. Environmental stress can also stimulate the formation and accumulation of secondary metabolites in medicinal plants. Appropriate low temperature stress, high or low water stress, acid or alkali stress can also promote the accumulation of ginsenosides. This article systematically reviews the ecological factors that affect the appearance and chemical composition of ginseng, and clarifies the dominant ecological factors and limiting factors for the formation of ginseng's appearance and quality, as well as beneficial environmental stress factors, in order to provide a theoretical basis for ginseng ecological planting and ginseng quality improvement.

Lactate accelerates vascular calcification through NR4A1-regulated mitochondrial fission and BNIP3-related mitophagy.

Arterial media calcification is related to mitochondrial dysfunction. Protective mitophagy delays the progression of vascular calcification. We previously reported that lactate accelerates osteoblastic phenotype transition of VSMC through BNIP3-mediated mitophagy suppression. In this study, we investigated the specific links between lactate, mitochondrial homeostasis, and vascular calcification. Ex vivo, alizarin S red and von Kossa staining in addition to measurement of calcium content, RUNX2, and BMP-2 protein levels revealed that lactate accelerated arterial media calcification. We demonstrated that lactate induced mitochondrial fission and apoptosis in aortas, whereas mitophagy was suppressed. In VSMCs, lactate increased NR4A1 expression, leading to activation of DNA-PKcs and p53. Lactate induced Drp1 migration to the mitochondria and enhanced mitochondrial fission through NR4A1. Western blot analysis of LC3-II and p62 and mRFP-GFP-LC3 adenovirus detection showed that NR4A1 knockdown was involved in enhanced autophagy flux. Furthermore, NR4A1 inhibited BNIP3-related mitophagy, which was confirmed by TOMM20 and BNIP3 protein levels, and LC3-II co-localization with TOMM20. The excessive fission and deficient mitophagy damaged mitochondrial structure and impaired respiratory function, determined by mPTP opening rate, mitochondrial membrane potential, mitochondrial morphology under TEM, ATP production, and OCR, which was reversed by NR4A1 silencing. Mechanistically, lactate enhanced fission but halted mitophagy via activation of the NR4A1/DNA-PKcs/p53 pathway, evoking apoptosis, finally accelerating osteoblastic phenotype transition of VSMC and calcium deposition. This study suggests that the NR4A1/DNA-PKcs/p53 pathway is involved in the mechanism by which lactate accelerates vascular calcification, partly through excessive Drp-mediated mitochondrial fission and BNIP3-related mitophagy deficiency.

Benefits and trade-offs of replacing synthetic fertilizers by animal manures in crop production in China: A meta-analysis.

Recycling of livestock manure to agricultural land may reduce the use of synthetic fertilizer and thereby enhance the sustainability of food production. However, the effects of substitution of fertilizer by manure on crop yield, nitrogen use efficiency (NUE), and emissions of ammonia (NH3 ), nitrous oxide (N2 O) and methane (CH4 ) as function of soil and manure properties, experimental duration and application strategies have not been quantified systematically and convincingly yet. Here, we present a meta-analysis of these effects using results of 143 published studies in China. Results indicate that the partial substitution of synthetic fertilizers by manure significantly increased the yield by 6.6% and 3.3% for upland crop and paddy rice, respectively, but full substitution significantly decreased yields (by 9.6% and 4.1%). The response of crop yields to manure substitution varied with soil pH and experimental durations, with relatively large positive responses in acidic soils and long-term experiments. NUE increased significantly at a moderate ratio (<40%) of substitution. NH3 emissions were significantly lower with full substitution (62%-77%), but not with partial substitution. Emissions of CH4 from paddy rice significantly increased with substitution ratio (SR), and varied by application rates and manure types, but N2 O emissions decreased. The SR did not significantly influence N2 O emissions from upland soils, and a relative scarcity of data on certain manure characteristic was found to hamper identification of the mechanisms. We derived overall mean N2 O emission factors (EF) of 0.56% and 0.17%, as well as NH3 EFs of 11.1% and 6.5% for the manure N applied to upland and paddy soils, respectively. Our study shows that partial substitution of fertilizer by manure can increase crop yields, and decrease emissions of NH3 and N2 O, but depending on site-specific conditions. Manure addition to paddy rice soils is recommended only if abatement strategies for CH4 emissions are also implemented.

Producing more grain with lower environmental costs.

Agriculture faces great challenges to ensure global food security by increasing yields while reducing environmental costs. Here we address this challenge by conducting a total of 153 site-year field experiments covering the main agro-ecological areas for rice, wheat and maize production in China. A set of integrated soil-crop system management practices based on a modern understanding of crop ecophysiology and soil biogeochemistry increases average yields for rice, wheat and maize from 7.2 million grams per hectare (Mg ha(-1)), 7.2 Mg ha(-1) and 10.5 Mg ha(-1) to 8.5 Mg ha(-1), 8.9 Mg ha(-1) and 14.2 Mg ha(-1), respectively, without any increase in nitrogen fertilizer. Model simulation and life-cycle assessment show that reactive nitrogen losses and greenhouse gas emissions are reduced substantially by integrated soil-crop system management. If farmers in China could achieve average grain yields equivalent to 80% of this treatment by 2030, over the same planting area as in 2012, total production of rice, wheat and maize in China would be more than enough to meet the demand for direct human consumption and a substantially increased demand for animal feed, while decreasing the environmental costs of intensive agriculture.

[Cultivation strategy on cluster brand of ecological agriculture of Dao-di herbs].

The cluster brand is the embodiment of the core competitiveness of an industry. Developing and cultivating cluster brand of ecological agriculture of Dao-di herbs not only helps to optimize the value chain of the Chinese medicinal materials(CMMs) industry cluster, realize the value-added of the CMMs industry cluster, but also enhance the visibility and influence of the industrial cluster, enhance the core competitiveness of the industrial cluster. This has important practical significance for promoting the "orderly" "safe" and "effective" development of the Dao-di herbs. Based on the industry development status of CMMs, this article introduces several concepts related to cluster brands and their relationships, and focuses on the cultivation models and strategies of cluster brand in the CMMs industry. Based on the current status of the development of the CMMs industry, this article introduces several concepts related to cluster brands and their interrelationships. It discusses the cultivation models and strategies of cluster brands in the CMMs industry, industry associations, Chinese medicine companies and individual growers as the support, insists on the ecological cultivation of authentic medicinal materials and the cultivation of cluster brands. Finally, it points out the direction for the high-quality development of the ecological agriculture of CMMs.

BDNF-mediated mitophagy alleviates high-glucose-induced brain microvascular endothelial cell injury.

Endothelial cell dysfunction and diabetic vascular complications are intrinsically linked. Although BDNF plays a protective role in cerebral microvascular complications caused by diabetes, the mechanisms of this activity are not fully clear. In this study, we investigated the role of BDNF in the hyperglycemic injury of BMECs and its associated intracellular signal transduction pathways. BMECs were treated with 33 mM glucose to imitate the endothelium under hyperglycemic conditions. The high-glucose treatment caused cell dysfunction, as evaluated by oxidative stress and cell apoptosis, which could be alleviated by BDNF. In addition, BDNF preserved mitochondrial function as assessed by mPTP opening, mitochondrial membrane potential, calcium content, and mitochondrial biogenesis markers. Western blot analysis of LC3-II, p62, and TOMM20 and the detection of mRFP-GFP-LC3 adenovirus for autophagy flux revealed that BDNF enhanced autophagy flux. Furthermore, BDNF activated mitophagy, which was confirmed by the observed colocalization of LC3-II with BNIP3 and from transmission electron microscopy observations. The HIF-1α/BNIP3 signaling pathway was associated with BDNF/TrkB-induced mitophagy. In addition, BDNF-induced mitophagy played a protective role against BMEC damage under hyperglycemia. Thus, the results of this study suggest that BDNF/TrkB/HIF-1α/BNIP3-mediated mitophagy protects BMECs from hyperglycemia.

HIF-1α/PDK4/autophagy pathway protects against advanced glycation end-products induced vascular smooth muscle cell calcification.

Osteogenic differentiation of VSMC is one of the main causes of diabetic vascular calcification, and AGEs accumulation accelerates the calcification of VSMCs in diabetic patients. Autophagy has also been found to play an important role in the process of vascular calcification. However, the potential link between AGEs, autophagy and vascular calcification is still unclear and was investigated in this study. Primary VSMCs were isolated from the thoracic aorta of Sprague Dawley rats and cultured with AGEs-BSA to induce osteogenic differentiation. VSMCs calcification was evaluated by measuring the calcium content, RUNX2 protein levels, and by Alizarin red S staining. We demonstrated that treatment of VSMCs with AGE-BSA increased the expression of HIF-1α and PDK4. AGE-BSA treatment increased LC3-II and decreased p62 protein levels. AGE-BSA exposure enhanced autophagic flux determined by mRFP-GFP-LC3 adenovirus, induced co-localization of LC3-II and LAMP-1, and increased the number of autophagasome under TEM. HIF-1α/PDK4 pathway was activated during AGEs-induced autophagy of VSMCs. In addition, autophagy played a protective role during AGE-induced calcification of VSMCs. In conclusion, AGEs enhance autophagy via the HIF-1α/PDK4 signaling pathway, and autophagy helps attenuate AGE-induced calcification of VSMCs.

Exploring Future Food Provision Scenarios for China.

Developing sustainable food systems is essential, especially for emerging economies, where food systems are changing rapidly and affect the environment and natural resources. We explored possible future pathways for a sustainable food system in China, using multiple environmental indicators linked to eight of the Sustainable Development Goals (SDGs). Forecasts for 2030 in a business as usual scenario (BAU) indicate increases in animal food consumption as well as increased shortages of the land available and the water needed to produce the required food in China. Associated greenhouse gas emissions and nitrogen and phosphorus losses could become 10-42% of global emissions in 2010. We developed three main pathways besides BAU [produce more and better food (PMB), consume and waste less food (CWL), and import more food (IMF)] and analyzed their impacts and contributions to achieving one or more of the eight SDGs. Under these scenarios, the demand for land and water and the emissions of GHG and nutrients may decrease by 7-55% compared to BAU, depending on the pathway followed. A combination of PMB and CWL was most effective, while IMF externalizes impacts to countries exporting to China. Modestly increasing feed or food imports in a selective manner could ease the pressure on natural resources. Our modeling framework allows us to analyze the effects of changes in food production-consumption systems in an integrated manner, and the results can be linked to the eight SDGs. Despite formidable technological, social, educational, and structural barriers that need to be overcome, our study indicates that the ambitious targets of China's new agricultural and environmental strategy appear to be achievable.

High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/ß-catenin signalling.

Sperm-associated antigen 5 (SPAG5) has currently emerged as a novel oncogene in various cancers. High expression of SPAG5 has been frequently detected in breast cancer. However, the biological function and regulatory mechanism of SPAG5 in breast cancer remain unclear. In this study, we aimed to investigate the potential biological function of SPAG5 in breast cancer cells. Herein, we found that both the mRNA and protein expression of SPAG5 were significantly up-regulated in breast cancer cell lines. Functional experiments showed that silencing of SPAG5 inhibited the proliferation and invasion of breast cancer cells, while the overexpression of SPAG5 promoted the proliferation and invasion of breast cancer cells. Mechanistic investigation demonstrated that SPAG5 promoted the expression of Wnt3 and ß-catenin, and increased the activation of ß-catenin/TCF4 transcriptional activity. Notably, the inhibition of Wnt3 partially reversed the promotion effect of SPAG5 on breast cancer cell proliferation and invasion and ß-catenin/TCF4 signalling. In addition, the inhibition of ß-catenin also significantly abrogated SPAG5-mediated oncogenic effects in breast cancer. Taken together, these findings demonstrate that SPAG5 promotes the proliferation and invasion of breast cancer cells by activating Wnt/ß-catenin signalling via up-regulating Wnt3 expression.