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AST-120 (KREMEZIN®) consists of oral, spherical carbon particles that adsorb uremic toxins and their precursors within the gastrointestinal tract, allowing them to be excreted in the feces. Uremic toxins such as indoxyl sulfate and p-cresyl sulfate are abundant in the blood of chronic kidney disease (CKD) patients and are related to the progression of both CKD and cardiovascular disease. AST-120 was approved in Japan in 1991 followed by Korea (2004), Taiwan (2007) and the Philippines (2010) for treating uremic symptoms and prolonging the time to initiation of dialysis in patients with progressive CKD. In this review, we provide an overview of the past clinical data on AST-120 from 1982 to 2013. The effect of AST-120 for renal events was not supported in the primary analysis of randomized clinical trials. However, post-hoc analyses revealed significant differences between the AST-120 and control groups in the second Japanese phase III trial and in the multinational Evaluating Prevention of Progression in CKD (EPPIC) trials. Furthermore, inhibitory effects on the progression of CKD, as represented by amelioration in the estimated glomerular filtration rate (eGFR) decline and serum creatinine (sCr) elevation were suggested. These results suggest that AST-120 delays the decline in renal function. In addition, AST-120 may prolong the time to the initiation of dialysis, especially in patients with progressive CKD. For further verification of the clinical efficacy of AST-120, future study inclusion criteria should be determined carefully, defining progressive CKD using markers such as declines in eGFR and sCr elevation.

Soil organic carbon sequestration has been promoted to combat climate change while improving soil fertility. However, its quantitative contribution to crop productivity has proven elusive. Using data from 13,662 controlled field trials with 66,593 treatments across a broad range of soils, climates and management practices, we here show that yields increase with increased soil organic carbon, until no further increase (p < 0.05) occurs above mean optimum soil organic carbon of 43.2–43.9 g kg−1 for maize, 12.7–13.4 g kg−1 for wheat and 31.2–32.4 g kg−1 for rice. Sequestering soil organic carbon is one-fifth as effective (that is, 80% less) as nitrogen fertilization for improving crop yield where soil management is optimized. By increasing soil organic carbon beyond current technology to optimum levels, global production of the three most important staple crops increases by 4.3% (sufficient to provide calories for 640 million people). However, currently available management practices would increase crop production by only 0.7% once other production constraints have already been addressed. Therefore, yield improvements under currently available technologies are unlikely to drive adoption of soil organic carbon sequestration globally, except in hot-spot regions where crop production benefits most, or unless novel practices that allow greater soil organic carbon sequestration beyond current limitations can further increase yields cost-effectively.Increasing soil organic carbon can, under optimum management only, enhance global production of maize, wheat and rice by up to 0.7% with important regional differences, according to 13,662 field trials across a broad range of soils, climates and management practices.

Many protein-coding genes in higher eukaryotes can produce circular RNAs (circRNAs) through back-splicing of exons. CircRNAs differ from mRNAs in their production, structure and turnover and thereby have unique cellular functions and potential biomedical applications. In this Review, I discuss recent progress in our understanding of the biogenesis of circRNAs and the regulation of their abundance and of their biological functions, including in transcription and splicing, sequestering or scaffolding of macromolecules to interfere with microRNA activities or signalling pathways, and serving as templates for translation. I further discuss the emerging roles of circRNAs in regulating immune responses and cell proliferation, and the possibilities of applying circRNA technologies in biomedical research.Circular RNAs, which are produced through back-splicing of exons, are emerging as key regulators of immune responses and cell proliferation. Recent studies have shed new light on the biogenesis and functions of circular RNAs, which include the modulation of transcription and splicing, and interference with microRNAs and other cellular signalling pathways.

Climate change mitigation not only requires reductions of greenhouse gas emissions, but also withdrawal of carbon dioxide (CO 2 ) from the atmosphere. Here we review the relationship between emissions reductions and CO 2 removal by biochar systems, which are based on pyrolysing biomass to produce biochar, used for soil application, and renewable bioenergy. Half of the emission reductions and the majority of CO 2 removal result from the one to two orders of magnitude longer persistence of biochar than the biomass it is made from. Globally, biochar systems could deliver emission reductions of 3.4–6.3 PgCO 2 e, half of which constitutes CO 2 removal. Relevant trade-offs exist between making and sequestering biochar in soil or producing more energy. Importantly, these trade-offs depend on what type of energy is replaced: relative to producing bioenergy, emissions of biochar systems increase by 3% when biochar replaces coal, whereas emissions decrease by 95% when biochar replaces renewable energy. The lack of a clear relationship between crop yield increases in response to fertilizer and to biochar additions suggests opportunities for biochar to increase crop yields where fertilizer alone is not effective, but also questions blanket recommendations based on known fertilizer responses. Locally specific decision support must recognize these relationships and trade-offs to establish carbon-trading mechanisms that facilitate a judicious implementation commensurate with climate change mitigation needs. Climate change mitigation strategies based on biochar generation—and its application to agricultural soils—can effectively sequester carbon, although biogeochemical and economic trade-offs must be considered.

Single-atom catalysts have recently attracted considerable attention because of their highly efficient metal utilization and unique properties. Finding a green, facile method to synthesize them is key to their widespread commercialization. Here we show that single-atom catalysts (including iron, cobalt, nickel and copper) can be prepared via a top-down abrasion method, in which the bulk metal is directly atomized onto different supports, such as carbon frameworks, oxides and nitrides. The level of metal loading can be easily tuned by changing the abrasion rate. No synthetic chemicals, solvents or even water were used in the process and no by-products or waste were generated. The underlying reaction mechanism involves the mechanochemical force in situ generating defects on the supports, then trapping and stably sequestering atomized metals. A solvent-free and zero-waste method was reported for the synthesis of single-atom catalysts via abrading bulk metal into single atoms. This strategy works for different metals (iron, cobalt, nickel and copper or their alloys) and supports (carbons, oxides or nitrides).

The methylotrophic yeast Pichia pastoris is widely used in the manufacture of industrial enzymes and pharmaceuticals. Like most biotechnological production hosts, P. pastoris is heterotrophic and grows on organic feedstocks that have competing uses in the production of food and animal feed. In a step toward more sustainable industrial processes, we describe the conversion of P. pastoris into an autotroph that grows on CO 2 . By addition of eight heterologous genes and deletion of three native genes, we engineer the peroxisomal methanol-assimilation pathway of P. pastoris into a CO 2 -fixation pathway resembling the Calvin–Benson–Bassham cycle, the predominant natural CO 2 -fixation pathway. The resulting strain can grow continuously with CO 2 as a sole carbon source at a µ max of 0.008 h −1 . The specific growth rate was further improved to 0.018 h −1 by adaptive laboratory evolution. This engineered P. pastoris strain may promote sustainability by sequestering the greenhouse gas CO 2 , and by avoiding consumption of an organic feedstock with alternative uses in food production. A yeast species used to produce proteins and chemicals is engineered to grow solely on the greenhouse gas CO 2 .

Extensive ecosystem restoration is increasingly seen as being central to conserving biodiversity 1 and stabilizing the climate of the Earth 2 . Although ambitious national and global targets have been set, global priority areas that account for spatial variation in benefits and costs have yet to be identified. Here we develop and apply a multicriteria optimization approach that identifies priority areas for restoration across all terrestrial biomes, and estimates their benefits and costs. We find that restoring 15% of converted lands in priority areas could avoid 60% of expected extinctions while sequestering 299 gigatonnes of CO 2 —30% of the total CO 2 increase in the atmosphere, or 14% of total emissions, since the Industrial Revolution. The inclusion of several biomes is key to achieving multiple benefits. Cost effectiveness can increase up to 13-fold when spatial allocation is optimized using our multicriteria approach, which highlights the importance of spatial planning. Our results confirm the vast potential contributions of restoration to addressing global challenges, while underscoring the necessity of pursuing these goals synergistically. Multicriteria optimization identifies global priority areas for ecosystem restoration and estimates their benefits for biodiversity and climate, providing cost–benefit analyses that highlight the importance of optimizing spatial planning and incorporating several biomes in restoration strategies.

IRON MAN (IMA) peptides, a family of small peptides, control iron (Fe) transport in plants, but their roles in Fe signaling remain unclear. BRUTUS (BTS) is a potential Fe sensor that negatively regulates Fe homeostasis by promoting the ubiquitin-mediated degradation of bHLH105 and bHLH115, two positive regulators of the Fe deficiency response. Here, we show that IMA peptides interact with BTS. The C-terminal parts of IMA peptides contain a conserved BTS interaction domain (BID) that is responsible for their interaction with the C terminus of BTS. Arabidopsis thaliana plants constitutively expressing IMA genes phenocopy the bts-2 mutant. Moreover, IMA peptides are ubiquitinated and degraded by BTS. bHLH105 and bHLH115 also share a BID, which accounts for their interaction with BTS. IMA peptides compete with bHLH105/bHLH115 for interaction with BTS, thereby inhibiting the degradation of these transcription factors by BTS. Genetic analyses suggest that bHLH105/bHLH115 and IMA3 have additive roles and function downstream of BTS. Moreover, the transcription of both BTS and IMA3 is activated directly by bHLH105 and bHLH115 under Fe-deficient conditions. Our findings provide a conceptual framework for understanding the regulation of Fe homeostasis: IMA peptides protect bHLH105/bHLH115 from degradation by sequestering BTS, thereby activating the Fe deficiency response.

Calcium ions (Ca2+) are some of the most versatile signalling molecules, and they have many physiological functions, prominently including muscle contraction, neuronal excitability, cell migration and cell growth. By sequestering and releasing Ca2+, mitochondria serve as important regulators of cellular Ca2+. Mitochondrial Ca2+ also has other important functions, such as regulation of mitochondrial metabolism, ATP production and cell death. In recent years, identification of the molecular machinery regulating mitochondrial Ca2+ accumulation and efflux has expanded the number of (patho)physiological conditions that rely on mitochondrial Ca2+ homeostasis. Thus, expanding the understanding of the mechanisms of mitochondrial Ca2+ regulation and function in different cell types is an important task in biomedical research, which offers the possibility of targeting mitochondrial Ca2+ machinery for the treatment of several disorders.

China’s large-scale tree planting programs are critical for achieving its carbon neutrality by 2060, but determining where and how to plant trees for maximum carbon sequestration has not been rigorously assessed. Here, we developed a comprehensive machine learning framework that integrates diverse environmental variables to quantify tree growth suitability and its relationship with tree numbers. Then, their correlations with biomass carbon stocks were robustly established. Carbon sink potentials were mapped in distinct tree-planting scenarios. Under one of them aligned with China’s ecosystem management policy, 44.7 billion trees could be planted, increasing forest stock by 9.6 ± 0.8 billion m³ and sequestering 5.9 ± 0.5 PgC equivalent to double China’s 2020 industrial CO 2 emissions. We found that tree densification within existing forests is an economically viable and effective strategy and so it should be a priority in future large-scale planting programs. China’s large-scale tree planting could sequester 5.9 ± 0.5 PgC by planting 44.7 billion trees. Tree densification in existing forests may be a more cost-effective strategy than afforestation.