General reversal of N-decomposition relationship during long-term decomposition in boreal and temperate forests.

Decomposition of dead organic matter is fundamental to carbon (C) and nutrient cycling in terrestrial ecosystems, influencing C fluxes from the biosphere to the atmosphere. Theory predicts and evidence strongly supports that the availability of nitrogen (N) limits litter decomposition. Positive relationships between substrate N concentrations and decomposition have been embedded into ecosystem models. This decomposition paradigm, however, relies on data mostly from short-term studies analyzing controls on early-stage decomposition. We present evidence from three independent long-term decomposition investigations demonstrating that the positive N-decomposition relationship is reversed and becomes negative during later stages of decomposition. First, in a 10-y decomposition experiment across 62 woody species in a temperate forest, leaf litter with higher N concentrations exhibited faster initial decomposition rates but ended up a larger recalcitrant fraction decomposing at a near-zero rate. Second, in a 5-y N-enrichment experiment of two tree species, leaves with experimentally enriched N concentrations had faster decomposition initial rates but ultimately accumulated large slowly decomposing fractions. Measures of amino sugars on harvested litter in two experiments indicated that greater accumulation of microbial residues in N-rich substrates likely contributed to larger slowly decomposing fractions. Finally, a database of 437 measurements from 120 species in 45 boreal and temperate forest sites confirmed that higher N concentrations were associated with a larger slowly decomposing fraction. These results challenge the current treatment of interactions between N and decomposition in many ecosystems and Earth system models and suggest that even the best-supported short-term controls of biogeochemical processes might not predict long-term controls.

Exchangeable manganese regulates carbon storage in the humus layer of the boreal forest.

The huge carbon stock in humus layers of the boreal forest plays a critical role in the global carbon cycle. However, there remains uncertainty about the factors that regulate below-ground carbon sequestration in this region. Notably, based on evidence from two independent but complementary methods, we identified that exchangeable manganese is a critical factor regulating carbon accumulation in boreal forests across both regional scales and the entire boreal latitudinal range. Moreover, in a novel fertilization experiment, manganese addition reduced soil carbon stocks, but only after 4 y of additions. Our results highlight an underappreciated mechanism influencing the humus carbon pool of boreal forests.

Rapid Analysis of Compounds from Piperis Herba and Piperis Kadsurae Caulis and Their Differences Using High-Resolution Liquid-Mass Spectrometry and Molecular Network Binding Antioxidant Activity.

There is a serious mixing of Piperis Herba and Piperis Kadsurae Caulis in various parts of China due to the similar traits of lianas, and there is a lack of systematic research on the compound and activity evaluation of the two. Likewise, the differences in compounds brought about by the distribution of origin also need to be investigated. In this study, high-resolution liquid-mass spectrometry (UPLC-Q-Zeno-TOF-MS/MS) was used to analyze samples of Piperis Herba from five origins and Piperis Kadsurae Caulis from five origins, with three batches collected from each origin. The compounds were identified based on precise molecular weights, secondary fragments, and an online database combined with node-to-node associations of the molecular network. The t-test was used to screen and analyze the differential compounds between the two. Finally, the preliminary evaluation of antioxidant activity of the two herbs was carried out using DPPH and ABTS free radical scavenging assays. The results showed that a total of 72 compounds were identified and deduced in the two Chinese medicines. These compounds included 54 amide alkaloids and 18 other compounds, such as flavonoid glycosides. The amide alkaloids among them were then classified, and the cleavage pathways in positive ion mode were summarized. Based on the p-value of the t-test, 32 differential compounds were screened out, and it was found that the compounds of Piperis Herba were richer and possessed a broader spectrum of antioxidant activity, thus realizing a multilevel distinction between Piperis Herba and Piperis Kadsurae Caulis. This study provides a preliminary reference for promoting standardization and comprehensive quality research of the resources of Piperis Herba using Piperis Kadsurae Caulis as a reference.

[Driving Factors Analyze of Phytoplankton Community by Comparison of Population and Functional Groups and Water Quality Evaluation in Dongting Lake].

Phytoplankton is the most important component of water ecosystems, which could indicate the state of the water environment owing to its sensitivity to water environment variation. However, its response to the environment is influenced by classification methods. To understand the phytoplankton population(phyla and genera) and functional groups(FG) for driving response characteristics and applicability to the environment in Dongting Lake, a total of four samples were collected from the lake from March to December 2019, and the distribution characteristics of the phytoplankton population and functional groups and their responses to environmental factors were compared and analyzed. Meanwhile, the applicability of the TLI index, Shannon-Wiener index, and Q index was compared in Dongting Lake. The results showed that a total of 61 genera belonging to six phyla of phytoplankton were detected in Dongting Lake, which could be divided into 23 functional groups and nine dominant functional groups. The succession trend of functional groups was P/MP/D(March)→MP/P/J(June)→MP/H1(September)→Y/P/MP(December). The results of hierarchical segmentation showed that the population distribution and change in phytoplankton were driven by environmental factors more than the area in Dongting Lake. The main environmental factors affecting phytoplankton population and functional groups were water temperature(WT), permanganate index, dissolved oxygen(DO), conductivity(Cond), water level(WL), and total phosphorus(TP). RDA analysis showed that phytoplankton functional groups identified phytoplankton response to environmental factors better than phytoplankton population. It was shown that using the Q index to evaluate water quality had better applicability in Dongting Lake.

Effects of Summer and Autumn Drought on Eutrophication and the Phytoplankton Community in Dongting Lake in 2022.

Since July 2022, the Yangtze River basin has experienced the most severe hydro-meteorological drought since record collection started in 1961, which has greatly affected the ecological environment of the Dongting Lake (DTL) basin. To investigate the effects of drought events on the eutrophication and phytoplankton community structure of DTL, the lake was sampled twice in August and September 2022 based on the water level fluctuations resulting in 47 samples. Furthermore, we combined the comprehensive trophic level index (TLI) and phytoplankton Shannon-Wiener diversity index (H) to characterize and evaluate the eutrophication status. The key influencing factors of the phytoplankton community were identified using redundancy analysis (RDA), hierarchical partitioning, and the Jaccard similarity index (J). Our results showed that the TLI of DTL changed from light-moderate eutrophication status (August) to mesotrophic status (September), whereas the H changed from light or no pollution to medium pollution. The phytoplankton abundance in August (122.06 × 104 cells/L) was less than that in September (351.18 × 104 cells/L) in DTL. A trend in phytoplankton community succession from Bacillariophyta to Chlorophyta and Cyanophyta was shown. The combination of physiochemical and ecological assessment more accurately characterized the true eutrophic status of the aquatic ecosystem. The RDA showed that the key influencing factors in the phytoplankton community were water temperature (WT), pH, nitrogen and phosphorus nutrients, and the permanganate index (CODMn) in August, while dissolved oxygen (DO) and redox potential (ORP) were the key factors in September. Hierarchical partitioning further indicated that temporal and spatial variations had a greater impact on the phytoplankton community. And the J of each region was slightly similar and very dissimilar, from August to September, which indicated a decreased hydrological connectivity of DTL during drought. These analyses indicated that the risk to the water ecology of DTL intensified during the summer-autumn drought in 2022. Safeguarding hydrological connectivity in the DTL region is a prerequisite for promoting energy flow, material cycle, and water ecosystem health.

Enhancing textural properties in plant-based meat alternatives: The impact of hydrocolloids and salts on soy protein-based products.

Consumer studies suggest that the meat-like texture of plant-based meat alternatives is crucial for the market success of these products. Many meat analogues contain wheat gluten, because it is cost-effective and give rise to nice fibrous structures. However, individuals with celiac disease cannot consume products containing wheat gluten producing a fibrous structure. To provide meat-like textures, different hydrocolloids with appropriate salt concentrations could be used. Therefore, this study investigated the influence of different hydrocolloids, including high acyl gellan gum, low acyl gellan gum, high methoxyl pectin, low methoxyl pectin, and xanthan at 2%, as well as two types of salts (CaCl2 and NaCl) at three concentrations (0%, 0.5%, and 1%) on the macrostructure, microstructure, and mechanical properties of plant-based meat alternatives containing only soy protein isolate and without wheat gluten. The addition of hydrocolloids and salts increased the cross-link bonds and structural compactness at the microscopic level and enhanced the fibrous structure at the microscopic level at different extent. These findings provide insight into how the addition of salts and hydrocolloids can effect plant-based meat alternatives without wheat gluten, which have practical implications for the food industry and are important for their success in the market.

Two-dimensional metal-organic framework catalyzed chemiluminescent reaction for alpha-glucosidase inhibitor screening.

α-Glucosidase inhibitors (AGIs) are oral antidiabetic drugs used in the treatment of type Ⅱ diabetes. It is integral to establish methods for AGIs screening. For the detection of α-glucosidase (α-Glu) activity and screening of AGIs, a chemiluminescence (CL) platform was established based on cascade enzymatic reactions. Firstly, the catalytic activity of a two-dimensional (2D) metal-organic framework (MOF) with iron as central metal atoms and 1,3,5-benzene tricarboxylic acid as a ligand (denoted as 2D Fe-BTC) in the luminol-hydrogen peroxide (H2O2) CL reaction were studied. Mechanism studies showed that the Fe-BTC may react with H2O2 to produce ·OH and act as catalase to facilitate the decomposition of H2O2 to produce O2, thus showing good catalytic activity in the luminol-H2O2 CL reaction. The proposed luminol-H2O2-Fe-BTC CL system exhibited an outstanding response to glucose with the aid of glucose oxidase (GOx). The luminol-GOx-Fe-BTC system showed a detection linear range from 50 nM to 10 µM with a detection limit (LOD) of 3.62 nM for glucose detection. Then, the luminol-H2O2-Fe-BTC CL system was applied to the detection of α-glucosidase (α-Glu) activity and screening of AGIs based on cascade enzymatic reactions using acarbose and voglibose as model drugs. The IC50 of acarbose and voglibose was 7.39 µM and 1.89 mM, respectively.

Genome-wide identification of the WRKY gene family in Camellia oleifera and expression analysis under phosphorus deficiency.

Camellia oleifera Abel. is an economically important woody edible-oil species that is mainly cultivated in hilly areas of South China. The phosphorus (P) deficiency in the acidic soils poses severe challenges for the growth and productivity of C. oleifera. WRKY transcription factors (TFs) have been proven to play important roles in biological processes and plant responses to various biotic/abiotic stresses, including P deficiency tolerance. In this study, 89 WRKY proteins with conserved domain were identified from the C. oleifera diploid genome and divided into three groups, with group II further classified into five subgroups based on the phylogenetic relationships. WRKY variants and mutations were detected in the gene structure and conserved motifs of CoWRKYs. Segmental duplication events were considered as the primary driver in the expanding process of WRKY gene family in C. oleifera. Based on transcriptomic analysis of two C. oleifera varieties characterized with different P deficiency tolerances, 32 CoWRKY genes exhibited divergent expression patterns in response to P deficiency stress. qRT-PCR analysis demonstrated that CoWRKY11, -14, -20, -29 and -56 had higher positive impact on P-efficient CL40 variety compared with P-inefficient CL3 variety. Similar expression trends of these CoWRKY genes were further observed under P deficiency with longer treatment period of 120d. The result indicated the expression sensitivity of CoWRKYs on the P-efficient variety and the C. oleifera cultivar specificity on the P deficiency tolerance. Tissue expression difference showed CoWRKYs may play a crucial role in the transportation and recycling P in leaves by affecting diverse metabolic pathways. The available evidences in the study conclusively shed light on the evolution of the CoWRKY genes in C. oleifera genome and provided a valuable resource for further investigation of functional characterization of WRKY genes involved to enhance the P deficiency tolerance in C. oleifera.

A turn-on chemiluminescent assay for alkaline phosphatase using two-dimensional Fe-centered metal-organic frameworks as the signaling probe.

Alkaline phosphatase (ALP) is an essential enzyme involved in cell phosphorus metabolism. Developing sensitive and accurate ALP quantitative assays is significant. In this study, a turn-on chemiluminescence (CL) analysis platform for the detection of ALP activity in human serum was established based on two-dimensional (2D) Fe-centered metal-organic frameworks with 1,3,5-benzene tricarboxylic acid as ligands (denoted as 2D Fe-BTC). The 2D Fe-BTC as the signaling probe reacts with ascorbic acid forming reduced Fe-BTC which catalyzes the luminol CL reaction producing a strong CL signal. The 2D Fe-BTC-based luminol CL reaction exhibited good CL responses when the concentration of ascorbic acid was in the range of 5-500 nM. By employing magnesium ascorbyl phosphate (MAP) as the substrate which can be hydrolyzed by ALP to generate ascorbic acid, a turn-on CL assay for the detection of ALP was established. Under optimal conditions, as low as 0.00046 U L-1 of ALP could be sensitively detected with a linear range of 0.001-0.1 U L-1. ALP in human serum can be detected after a simple dilution process without any other pretreatment.

Evaluating IL-6 and IL-10 as rapid diagnostic tools for Gram-negative bacteria and as disease severity predictors in pediatric sepsis patients in the intensive care unit.

Background: To explore the diagnostic performance of interleukin (IL)-6 and IL-10 in discriminating Gram bacteria types and predicting disease severity in intensive care unit (ICU)-hospitalized pediatric sepsis patients. Method: We retrospectively collected Th1/Th2 cytokine profiles of 146 microbiologically documented sepsis patients. Patients were categorized into Gram-positive (G+) or Gram-negative (G-) sepsis groups, and cytokine levels were compared. Subgroup analysis was designed to eliminate the influence of other inflammatory responses on cytokine levels. Results: After propensity score matching, 78 patients were matched and categorized according to Gram bacteria types. Compared with G+ sepsis, IL-6 and IL-10 were significantly elevated in G- sepsis (p < 0.05). Spearman test proved the linear correlation between IL-6 and IL-10 (r = 0.654, p < 0.001), and their combination indicators (ratio and differences) were effective in identifying G- sepsis. In the subgroup analysis, such cytokine elevation was significant regardless of primary infection site. However, for patients with progressively deteriorating organ function [new or progressive multiple organ dysfunction syndrome (NPMODS)], differences in IL-6 and IL-10 levels were less significant between G+ and G- sepsis. In the receiver operating characteristic (ROC) curves of the G- sepsis group, the area under the curve (AUC) value for IL-6 and IL-10 was 0.679 (95% CI 0.561-0.798) and 0.637 (95% CI 0.512-0.762), respectively. The optimal cutoff value for diagnosing G- sepsis was 76.77 pg/ml and 18.90 pg/ml, respectively. While for the NPMODS group, the AUC for IL-6 and IL-10 was 0.834 (95% CI 0.766-0.902) and 0.781 (95% CI 0.701-0.860), respectively. Conclusion: IL-6 and IL-10 are comparably effective in discriminating G+/G- sepsis in pediatric intensive care unit (PICU) patients. The deteriorated organ function observed in ICU patients reveals that complex inflammatory responses might have contributed to the cytokine pattern observed in severe sepsis patients, therefore confounding the discriminating efficacy of Th1/Th2 cytokines in predicting Gram bacteria types.

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial.

Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo. LNA043 exerts at least part of these effects through binding to the fibronectin receptor, integrin α5ß1 on mesenchymal stem cells and chondrocytes. In a first-in-human (phase 1), randomized, double-blinded, placebo-controlled, single ascending dose, single-center trial ( NCT02491281 ; sponsored by Novartis Pharmaceuticals), 28 patients with knee OA were injected intra-articularly with LNA043 or placebo (3:1 ratio) either 2 h, 7 d or 21 d before total knee replacement. LNA043 met its primary safety endpoint and showed short serum pharmacokinetics, cartilage penetration and a lack of immunogenicity (secondary endpoints). Post-hoc transcriptomics profiling of cartilage revealed that a single LNA043 injection reverses the OA transcriptome signature over at least 21 d, inducing the expression of hyaline cartilage matrix components and anabolic signaling pathways, while suppressing mediators of OA progression. LNA043 is a novel disease-modifying OA drug candidate that is currently in a phase 2b trial ( NCT04864392 ) in patients with knee OA.

Enhancement effect of 2, 3-dimethyl maleic acid on luminol chemiluminescence reactions and its application in detection of sequence-specific DNA related to hepatitis B virus.

2, 3-dimethyl maleic acid (DMMA) was found to enhance luminol-H2O2 chemiluminescent (CL) reactions, among which the strongest enhancement effect was observed by using polyethyleneimine-templated gold nanoclusters (PEI-Au NCs) as the catalyst. With the addition of DMMA, the CL signal of the PEI-Au NCs-catalyzed luminol-H2O2 reaction enhanced about 630-fold, and a flash-type CL profile was obtained. Mechanism studies showed that the luminophore was still 3-aminophthalate anions in the excited state (3-APA*), and superoxide radical (O2·-) played an important role during the CL process. Under the optimized experimental conditions, the lowest concentration of PEI-Au NCs can be detected was 0.168 nM which was 82-fold lower than that without an enhancer. Furthermore, the catalytic activity of biotinylated PEI-Au NCs in the DMMA-enhanced luminol system was similar to PEI-Au NCs, providing a good opportunity for the development of CL bioanalysis platforms using PEI-Au NCs as the label. Thus, the DMMA-enhanced luminol-H2O2 system was applied to the CL detection of sequence-specific DNA related to the hepatitis B virus (HBV) using PEI-Au NCs as the label. The CL platform exhibited linearly enhanced CL response with the increasing amount of target DNA ranging from 0.0025 to 0.5 pmol. As low as 0.002 pmol of HBV DNA could be sensitively detected, which was superior to the previously reported methods.

Progress and prospects of reversible solid oxide fuel cell materials.

Reversible solid oxide fuel cell (RSOFC) is an energy device that flexibly interchanges between electrical and chemical energy according to people's life and production needs. The development of cell materials affects the stability and cost of the cell, but also restricts its market-oriented development. After decades of research by scientists, a lot of achievements and progress have been made on RSOFC materials. According to the composition and requirements of each component of RSOFC, this article summarizes the research progress based on materials and discusses the merits and demerits of current cell materials in electrochemical performance. According to the efficiency of different materials in solid oxide fuel cell (SOFC mode) and solid oxide electrolyzer (SOEC mode), the challenges encountered by RSOFC in the operation are evaluated, and the future development of RSOFC materials is boldly prospected.

Signaling pathways and intervention therapies in sepsis.

Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection. Over decades, advanced understanding of host-microorganism interaction has gradually unmasked the genuine nature of sepsis, guiding toward new definition and novel therapeutic approaches. Diverse clinical manifestations and outcomes among infectious patients have suggested the heterogeneity of immunopathology, while systemic inflammatory responses and deteriorating organ function observed in critically ill patients imply the extensively hyperactivated cascades by the host defense system. From focusing on microorganism pathogenicity, research interests have turned toward the molecular basis of host responses. Though progress has been made regarding recognition and management of clinical sepsis, incidence and mortality rate remain high. Furthermore, clinical trials of therapeutics have failed to obtain promising results. As far as we know, there was no systematic review addressing sepsis-related molecular signaling pathways and intervention therapy in literature. Increasing studies have succeeded to confirm novel functions of involved signaling pathways and comment on efficacy of intervention therapies amid sepsis. However, few of these studies attempt to elucidate the underlining mechanism in progression of sepsis, while other failed to integrate preliminary findings and describe in a broader view. This review focuses on the important signaling pathways, potential molecular mechanism, and pathway-associated therapy in sepsis. Host-derived molecules interacting with activated cells possess pivotal role for sepsis pathogenesis by dynamic regulation of signaling pathways. Cross-talk and functions of these molecules are also discussed in detail. Lastly, potential novel therapeutic strategies precisely targeting on signaling pathways and molecules are mentioned.

[Fine root biomass, production, and turnover rate in a temperate deciduous broadleaved forest in the Maoer Mountain, China]. / å¸½å„¿å±±æ¸©å¸¦è½å¶é˜”å¶æž—ç»†æ ¹ç”Ÿç‰©é‡ã€ç”Ÿäº§åŠ›å’Œå‘¨è½¬çŽ‡.

Fine roots play an important role in energy flow and substance cycling in forests. How-ever, the estimates of biomass, production and turnover of fine roots remain large uncertainties, and the mechanism underlying local-scale spatial variation in fine roots is still unclear. In a temperate secondary forest in the Maoer Mountain in Northeast China, we investigated the vertical distribution of fine root biomass and necromass at the 0-100 cm profile and the dynamics, production and turnover rate of fine root in 0-20 cm soil layer. The sequential coring (including the Decision Matrix and the Maximum-Minimum formula) and the ingrowth core (3 cm diameter and 5 cm diameter) were compared in estimating production and turnover rate of fine roots. Forest stand variables that might affect fine roots were also explored. The results showed that 76.8% of fine root biomass and 62.9% of necromass concentrated in the 0-20 cm soil layer, and that both decreased exponentially with increa-sing soil depth. The seasonal variation in both fine root biomass and necromass was not significant in 0-20 cm soil layer, which might be related to the negligible snowfall in winter and the extremely high precipitation in summer. There was no significant difference in the results of the estimated fine root production between two diameter ingrowth cores. After log-transformed, fine root production and turnover rate estimated by the Decision Matrix, the Maximum-Minimum formula and ingrowth cores were significantly different among methods. With the increases of soil nutrient concentrations, fine root biomass/fine root necromass ratio significantly increased, fine root necromass significantly decreased, whereas fine root biomass, productivity, and turnover rate were not related to soil nutrient. There was a significant positive correlation between fine root production and aboveground woody biomass increment in the previous-year but not current-year.

MOFs based on the application and challenges of perovskite solar cells.

In recent years, perovskite solar cells (PSCs) have attracted much attention because of their high energy conversion efficiency, low cost, and simple preparation process. Up to now, the photoelectric conversion efficiency of solar cells has been increased from 3.8% to 25.5%. Metal-organic skeleton-derived metal oxides and their composites (MOFs) are widely considered for application in PSCs due to their low and flat charge/discharge potential plateau, high capacity, and stable cycling performance. By combining MOFs and PSCs, based on the composition materials of perovskite film, electron transport layer, hole transport layer, and interfacial interlayer of PSCs, this article discusses the photovoltaic performance or structure optimization effect of MOFs in each function layer, which is of great significance to improve the photovoltaic performance of the cell. The problems faced by MOFs on perovskite solar cells are summarized, the next research directions are discussed, and the development of this crossover area of MOFs-PSC is foreseen to accelerate the comprehensive research and popularization of MOFs on PSCs.

Photothermal Effect: The Amygdaloidal Nano-Structure Based on Bi2S3 for the Enhanced Degradation of Rhodamine B Under Irradiation by NIR.

In recent years the photothermal effect, an auxiliary strategy for increasing the degradation rate of pollutants under irradiation by near-infrared (NIR), has become a research focus. In this study a novel amygdaloidal nanophotocatalyst, Bi2S3, was synthesized by a traditional approach using a hydrothermal process, in which Bi2S3 nanostructures were spread out like a peacock's tail. The produced Bi2S3 photocatalyst exhibited excellent performance in the rapid degradation of Rhodamine B (RB). This proved that the photothermal effect is mainly responsible for the rapid degradation of RB under NIR laser irradiation. Moreover, it was found that the photothermal effect could not degrade the products with NIR radiation in darkness. However, with the support of visible radiation, the photothermal effect of the Bi2S3 photocatalyst enhanced degradation of RB (degradation rate 90% under 1 h). This novel structure exhibited a potential ability for degrading pollution in industry or agriculture.

New insights into molecular changes in skeletal muscle aging and disease: Differential alternative splicing and senescence.

Progressive loss of muscle mass and function due to muscle fiber atrophy and loss in the elderly and chronically ill is now defined as sarcopenia. It is a major contributor to loss of independence, disability, need of long-term care as well as overall mortality. Sarcopenia is a heterogenous disease and underlying mechanisms are not completely understood. Here, we newly identified and used Tmem158, alongside Cdkn1a, as relevant senescence and denervation markers (SDMs), associated with muscle fiber atrophy. Subsequent application of laser capture microdissection (LCM) and RNA analyses revealed age- and disease-associated differences in gene expression and alternative splicing patterns in a rodent sarcopenia model. Of note, genes exhibiting such differential alternative splicing (DAS) are mainly involved in the contractile function of the muscle. Many of these splicing events are also found in a mouse model for myotonic dystrophy type 1 (DM1), underscoring the premature aging phenotype of this disease. We propose to add differential alternative splicing to the hallmarks of aging.