Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control.

Adult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.

SEPDB: a database of secreted proteins.

Detecting changes in the dynamics of secreted proteins in serum has been a challenge for proteomics. Enter secreted protein database (SEPDB), an integrated secretory proteomics database offering human, mouse and rat secretory proteomics datasets collected from serum, exosomes and cell culture media. SEPDB compiles secreted protein information from secreted protein database, UniProt and Human Protein Atlas databases to annotate secreted proteomics data based on protein subcellular localization and disease markers. SEPDB integrates the latest predictive modeling techniques to measure deviations in the distribution of signal peptide structures of secreted proteins, extends signal peptide sequence prediction by excluding transmembrane structural domain proteins and updates the validation analysis pipeline for secreted proteins. To establish tissue-specific profiles, we have also created secreted proteomics datasets associated with different human tissues. In addition, we provide information on heterogeneous receptor network organizational relationships, reflective of the complex functional information inherent in the molecular structures of secreted proteins that serve as ligands. Users can take advantage of the Refreshed Search, Analyze, Browse and Download functions of SEPDB, which is available online at https://sysomics.com/SEPDB/. Database URL:  https://sysomics.com/SEPDB/.

The Degradation of Aqueous Oxytetracycline by an O3/CaO2 System in the Presence of HCO3-: Performance, Mechanism, Degradation Pathways, and Toxicity Evaluation.

This research constructed a novel O3/CaO2/HCO3- system to degrade antibiotic oxytetracycline (OTC) in water. The results indicated that CaO2 and HCO3- addition could promote OTC degradation in an O3 system. There is an optimal dosage of CaO2 (0.05 g/L) and HCO3- (2.25 mmol/L) that promotes OTC degradation. After 30 min of treatment, approximately 91.5% of the OTC molecules were eliminated in the O3/CaO2/HCO3- system. A higher O3 concentration, alkaline condition, and lower OTC concentration were conducive to OTC decomposition. Active substances including ·OH, 1O2, ·O2-, and ·HCO3- play certain roles in OTC degradation. The production of ·OH followed the order: O3/CaO2/HCO3- > O3/CaO2 > O3. Compared to the sole O3 system, TOC and COD were easier to remove in the O3/CaO2/HCO3- system. Based on DFT and LC-MS, active species dominant in the degradation pathways of OTC were proposed. Then, an evaluation of the toxic changes in intermediates during OTC degradation was carried out. The feasibility of O3/CaO2/HCO3- for the treatment of other substances, such as bisphenol A, tetracycline, and actual wastewater, was investigated. Finally, the energy efficiency of the O3/CaO2/HCO3- system was calculated and compared with other mainstream processes of OTC degradation. The O3/CaO2/HCO3- system may be considered as an efficient and economical approach for antibiotic destruction.

Resolving a nearly 90-year-old enigma: The rare Fagus chienii is conspecific with F. hayatae based on molecular and morphological evidence.

Taxonomic uncertainties of rare species often hinder effective prioritization for conservation. One such taxonomic uncertainty is the 90-year-old enigma of Fagus chienii. F. chienii was previously only known from the type specimens collected in 1935 in Pingwu County of Sichuan Province, China, and has long been thought to be on the verge of extinction. However, morphological similarities to closely related Fagus species have led many to question the taxonomic status of F. chienii. To clarify this taxonomic uncertainty, we used the newly collected samples to reconstruct a molecular phylogeny of Chinese Fagus species against the phylogenetic backbone of the whole genus using seven nuclear genes. In addition, we examined nine morphological characters to determine whether F. chienii is morphologically distinct from its putatively closest relatives (F. hayatae, F.longipetiolata, and F.lucida). Both morphological and phylogenetic analyses indicated that F. chienii is conspecific with F. hayatae. We recommended that F. chienii should not be treated as a separate species in conservation management. However, conservation strategies such as in situ protection and ex situ germplasm preservation should be adopted to prevent the peculiar "F. chienii" population from extinction.

Skeletal muscle-secreted DLPC orchestrates systemic energy homeostasis by enhancing adipose browning.

MyoD is a skeletal muscle-specifically expressed transcription factor and plays a critical role in regulating myogenesis during muscle development and regeneration. However, whether myofibers-expressed MyoD exerts its metabolic function in regulating whole body energy homeostasis in vivo remains largely unknown. Here, we report that genetic deletion of Myod in male mice enhances the oxidative metabolism of muscle and, intriguingly, renders the male mice resistant to high fat diet-induced obesity. By performing lipidomic analysis in muscle-conditioned medium and serum, we identify 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) as a muscle-released lipid that is responsible for MyoD-orchestrated body energy homeostasis in male Myod KO mice. Functionally, the administration of DLPC significantly ameliorates HFD-induced obesity in male mice. Mechanistically, DLPC is found to induce white adipose browning via lipid peroxidation-mediated p38 signaling in male mice. Collectively, our findings not only uncover a novel function of MyoD in controlling systemic energy homeostasis through the muscle-derived lipokine DLPC but also suggest that the DLPC might have clinical potential for treating obesity in humans.

Polyurethane Foam Skeleton-Based Phase Change Hydrogel for Efficient Battery Thermal Management with Favorable Antivibration Performance.

Efficient thermal management is critical to ensure the safe and reliable operation of lithium-ion batteries (LIBs) as they are highly sensitive to temperature changes. Meanwhile, LIBs are exposed to various external forces during operation, such as vibration, shock, and oscillation, which may disrupt the physical and chemical processes inside the battery and lead to a decreased performance and shortened life. Here, we designed a phase change hydrogel (PCH) pad based on the polyurethane (PU) foam skeleton and demonstrated its effectiveness in efficient thermal management and improving antivibration performance. The thermal conductivity of the prepared composite is 0.65 W/(m·K), while the thermal contact resistance could decrease to ∼20 K·cm2/W under 60 °C. It exhibits a flexible contact transformation during the phase transition, resulting in enhanced interfacial heat transfer and storage rate, as well as improved resistance against external impacts. The temperature of the battery module wrapped with a composite plate decreases by 11.4 °C during the 6C discharge. Moreover, the additional heat generated by external vibration is only half that of the bare battery, and the temperature difference could reach 5.2 °C, demonstrating the effective buffering effect of PCH@PU in mitigating long-term discharge-induced increases in internal resistance. The developed PCH@PU, known for its exceptional thermal management and favorable antivibration performance, holds promising potential for widespread utilization in the field of power battery heat dissipation.

CTCF coordinates cell fate specification via orchestrating regulatory hubs with pioneer transcription factors.

CCCTC-binding factor (CTCF), a ubiquitously expressed architectural protein, has emerged as a key regulator of cell identity gene transcription. However, the precise molecular mechanism underlying specialized functions of CTCF remains elusive. Here, we investigate the mechanism through integrative analyses of primary hepatocytes, myocytes, and B cells from mouse and human. We demonstrate that CTCF cooperates with lineage-specific pioneer transcription factors (TFs), including MyoD, FOXA, and PU.1, to control cell identity at 1D and 3D levels. At the 1D level, pioneer TFs facilitate lineage-specific CTCF occupancy via opening chromatin. At the 3D level, CTCF and pioneer TFs form regulatory hubs to govern the expression of cell identity genes. This mechanism is validated using MyoD-null mice, CTCF knockout mice, and CRISPR editing during myogenic differentiation. Collectively, these findings uncover a general mechanism whereby CTCF acts as a cell identity cofactor to control cell identity genes via orchestrating regulatory hubs with pioneer TFs.

Global determination of reaction rates and lipid turnover kinetics in Mus musculus.

Metabolism is fundamental to life, but measuring metabolic reaction rates remains challenging. Here, we applied C13 fluxomics to monitor the metabolism of dietary glucose carbon in 12 tissues, 9 brain compartments, and over 1,000 metabolite isotopologues over a 4-day period. The rates of 85 reactions surrounding central carbon metabolism are determined with elementary metabolite unit (EMU) modeling. Lactate oxidation, not glycolysis, occurs at a comparable pace with the tricarboxylic acid cycle (TCA), supporting lactate as the primary fuel. We expand the EMU framework to track and quantify metabolite flows across tissues. Specifically, multi-organ EMU simulation of uridine metabolism shows that tissue-blood exchange, not synthesis, controls nucleotide homeostasis. In contrast, isotopologue fingerprinting and kinetic analyses reveal the brown adipose tissue (BAT) having the highest palmitate synthesis activity but no apparent contribution to circulation, suggesting a tissue-autonomous synthesis-to-burn mechanism. Together, this study demonstrates the utility of dietary fluxomics for kinetic mapping in vivo and provides a rich resource for elucidating inter-organ metabolic cross talk.

miR-378-mediated glycolytic metabolism enriches the Pax7Hi subpopulation of satellite cells.

Adult skeletal muscle stem cells, also known satellite cells (SCs), are a highly heterogeneous population and reside between the basal lamina and the muscle fiber sarcolemma. Myofibers function as an immediate niche to support SC self-renewal and activation during muscle growth and regeneration. Herein, we demonstrate that microRNA 378 (miR-378) regulates glycolytic metabolism in skeletal muscle fibers, as evidenced by analysis of myofiber-specific miR-378 transgenic mice (TG). Subsequently, we evaluate SC function and muscle regeneration using miR-378 TG mice. We demonstrate that miR-378 TG mice significantly attenuate muscle regeneration because of the delayed activation and differentiation of SCs. Furthermore, we show that the miR-378-mediated metabolic switch enriches Pax7Hi SCs, accounting for impaired muscle regeneration in miR-378 TG mice. Mechanistically, our data suggest that miR-378 targets the Akt1/FoxO1 pathway, which contributes the enrichment of Pax7Hi SCs in miR-378 TG mice. Together, our findings indicate that miR-378 is a target that links fiber metabolism to muscle stem cell heterogeneity and provide a genetic model to approve the metabolic niche role of myofibers in regulating muscle stem cell behavior and function.

Linc-RAM promotes muscle cell differentiation via regulating glycogen phosphorylase activity.

Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes, especially skeletal muscle cell differentiation. Most of the lncRNAs identified to date are localized in the nucleus and play regulatory roles in gene expression. The cytoplasmic lncRNAs are less well understood. We previously identified a long intergenic non-coding RNA (linc-RNA) activator of myogenesis (Linc-RAM) that directly binds MyoD in the nucleus to enhance muscle cell differentiation. Here, we report that a substantial fraction of Linc-RAM is localized in the cytoplasm of muscle cells. To explore the molecular functions of cytoplasmic Linc-RAM, we sought to identify Linc-RAM-binding proteins. We report here that Linc-RAM physically interacts with glycogen phosphorylase (PYGM) in the cytoplasm. Knockdown of PYGM significantly attenuates the function of Linc-RAM in promoting muscle cell differentiation. Loss-of-function and gain-of function assays demonstrated that PYGM enhances muscle cell differentiation in an enzymatic activity-dependent manner. Finally, we show that the interaction between Linc-RAM and PYGM positively regulates the enzymatic activity of PYGM in muscle cells. Collectively, our findings unveil a molecular mechanism through which cytoplasmic Linc-RAM contributes to muscle cell differentiation by regulating PYGM activity. Our findings establish that there is crosstalk between lncRNAs and cellular metabolism during myogenic cell differentiation.

MyoD is a 3D genome structure organizer for muscle cell identity.

The genome exists as an organized, three-dimensional (3D) dynamic architecture, and each cell type has a unique 3D genome organization that determines its cell identity. An unresolved question is how cell type-specific 3D genome structures are established during development. Here, we analyzed 3D genome structures in muscle cells from mice lacking the muscle lineage transcription factor (TF), MyoD, versus wild-type mice. We show that MyoD functions as a "genome organizer" that specifies 3D genome architecture unique to muscle cell development, and that H3K27ac is insufficient for the establishment of MyoD-induced chromatin loops in muscle cells. Moreover, we present evidence that other cell lineage-specific TFs might also exert functional roles in orchestrating lineage-specific 3D genome organization during development.

Rapid photo aging of commercial conventional and biodegradable plastic bags.

Biodegradable plastic (BPs) bags are introduced and widely used as alternatives to conventional commercial plastic bags in an effort to mitigate the adverse impacts of nondegradable (conventional) plastics. However, being used as packaging, the stability and safeness of the BPs and even the conventional plastics with photo irradiation in short duration remain unknown. In this study, we systematically explored the photo aging of commercial BPs bags and conventional plastic bags in film forms in both outdoor and laboratory experiments in short duration (~ one month) under the scenario of ordinary daily use. Conventional plastic bags (polyethylene (PE)) and BPs bags (hybrids of polylatic acid (PLA) and poly(butylene adipate-co-terephthalate) (PBAT) with additives (Magadiite or Starch)) were investigated. In contrast with the visually negligible surface change of PE films in both outdoor and laboratory environments, obvious surface alteration as surface deterioration with cracks and holes was obtained for BPs from SEM images in direct irradiation by both natural and simulated sunlight. Consistently, AFM results also indicated that the surface of BPs had the tendency to be rougher after photo aging process. Further FTIR and XPS results demonstrated that though the visual surface alteration of conventional and biodegradable plastics are distinct, the mechanisms dominating the change of C-H/C-C bonds to carbon­oxygen functional groups (i.e., C-O/C=O/O-C=O) for both conventional plastics and BPs during the photo aging process are similar. Moreover, tensile strength tests demonstrated that BPs bags being easily broken compared with the conventional PE bags might attribute to the difference in their mechanical properties. The findings of this study suggest that the potential risk of MPs and NPs released from the BPs bags via photo aging process are great new threats to natural environment and even human health.

Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.

Long noncoding RNAs (lncRNAs) are known to have profound functions in regulating cell fate specification, cell differentiation, organogenesis, and disease, but their physiological roles in controlling cellular metabolism and whole-body metabolic homeostasis are less well understood. We previously identified a skeletal muscle-specific long intergenic noncoding RNA (linc-RNA) activator of myogenesis, Linc-RAM, which enhances muscle cell differentiation during development and regeneration. Here, we report that Linc-RAM exerts a physiological function in regulating skeletal muscle metabolism and the basal metabolic rate to maintain whole-body metabolic homeostasis. We first demonstrate that Linc-RAM is preferentially expressed in type-II enriched glycolytic myofibers, in which its level is more than 60-fold higher compared to that in differentiated myotubes. Consistently, genetic deletion of the Linc-RAM gene in mice increases the expression levels of genes encoding oxidative fiber versions of myosin heavy chains and decreases those of genes encoding rate-limiting enzymes for glycolytic metabolism. Physiologically, Linc-RAM-knockout mice exhibit a higher basal metabolic rate, elevated insulin sensitivity and reduced fat deposition compared to their wild-type littermates. Together, our findings indicate that Linc-RAM is a metabolic regulator of skeletal muscle metabolism and may represent a potential pharmaceutical target for preventing and/or treating metabolic diseases, including obesity.

Reactive Nitrogen Species Generated by Gas-Liquid Dielectric Barrier Discharge for Efficient Degradation of Perfluorooctanoic Acid from Water.

Perfluorooctanoic acid (PFOA) poses a serious threat to the ecological environment and biological health because of its ubiquitous distribution, extreme persistence, and high toxicity. In this study, we designed a novel gas-liquid dielectric barrier discharge (GLDBD) reactor which could efficiently destruct PFOA. PFOA removal efficiencies can be obtained in various water matrices, which were higher than 98.0% within 50 min, with energy yields higher than 114.5 mg·kWh-1. It was confirmed that the reactive species including e-, ONOOH, •NO2, and hydroxyl radicals (•OH) were responsible for PFOA removal. Especially, this study first revealed the crucial role of reactive nitrogen species (RNS) for PFOA degradation in the plasma system. Due to the generation of a large amount of RNS, the designed GLDBD reactor proved to be less sensitive to various water matrices, which meant a broader promising practical application. Moreover, influential factors including high concentration of various ions and humic acid (HA), were investigated. The possible PFOA degradation pathways were proposed based on liquid chromatograph-mass spectrometer (LC-MS) results and density functional theory (DFT) calculation, which further confirmed the feasibility of PFOA removal with RNS. This research, therefore, provides an effective and versatile alternative for PFOA removal from various water matrices.

Acetoacetate promotes muscle cell proliferation via the miR-133b/SRF axis through the Mek-Erk-MEF2 pathway.

Acetoacetate (AA) is an important ketone body that is used as an oxidative fuel to supply energy for the cellular activities of various tissues, including the brain and skeletal muscle. We recently revealed a new signaling role for AA by showing that it promotes muscle cell proliferation in vitro, enhances muscle regeneration in vivo, and ameliorates the dystrophic muscle phenotype of Mdx mice. In this study, we provide new molecular insight into this function of AA. We show that AA promotes C2C12 cell proliferation by transcriptionally upregulating the expression of muscle-specific miR-133b, which in turn stimulates muscle cell proliferation by targeting serum response factor. Furthermore, we show that the AA-induced upregulation of miR-133b is transcriptionally mediated by MEF2 via the Mek-Erk1/2 signaling pathway. Mechanistically, our findings provide further convincing evidence that AA acts as signaling metabolite to actively regulate various cellular activities in mammalian cells.

Efficient degradation of tetracycline by RGO@black titanium dioxide nanofluid via enhanced catalysis and photothermal conversion.

The applications of photocatalytic pollutant degradation have remained limited due to the low efficiency of solar energy utilization. In this study, a photothermal catalyst consisting of reduced graphene oxide @ black TiO2 (RGO@BT) nanofluid with effective full-spectrum (from ultraviolet to infrared light) absorption was synthesized by a typical two-step method of high temperature calcination and hydrothermal method. Moreover, the photothermal catalytic performance of the RGO@BT nanofluid on tetracycline was verified. Compared with individual processes (i.e, photocatalysis and thermocatalysis), the photothermal catalytic process significantly enhanced tetracycline degradation under simulated global standard spectrum sunlight (AM 1.5G, 1000 W m-2). The maximum photothermal conversion efficiency reached 91.8%, which resulted in 94.7% tetracycline degradation (40 mg L-1) after 120 min of treatment with 200 mg L-1 RGO@BT nanofluid. Holes, OH, and O2- were found to be the main active species during the photothermal catalytic process. Moreover, heat was spontaneously converted from light energy without the use of any external energy source. The elevated system temperature facilitated the tetracycline degradation based on the Arrhenius behavior. These findings provide insights into the improvement of photocatalytic efficiency in organic contaminant degradation via solar energy-efficient photothermal conversion materials.

Molecular cloning and potential role of DiSOC1s in flowering regulation in Davidia involucrata Baill.

Davidia involucrata Baill. (dove tree) is unique Tertiary relic plant in China, also known as 'living fossil' and 'giant panda'. The MADS-box family gene SOC1 is involved in the regulatory pathway that integrates flowering signals to promote flowering at the optimal time. In this study, we isolated and identified two dove tree SOC1 homologues, named DiSOC1-a and DiSOC1-b. These two sequences possess highly conserved domains MADS-box and SOC1-motif, as well as the semi-conserved region K-box. DiSOC1-a and DiSOC1-b were expressed at varying levels in all tested tissues of dove tree and shared high levels of expression in the flower buds. The expression tendencies of both genes in bract were initially upward and then downward and were highest in young bracts. Neither DiSOC1-a nor DiSOC1-b was expressed in immature leaves. Proteins encoded by DiSOC1-a and DiSOC1-b were located in the nucleus. In addition, ectopic overexpression of both genes in WT Arabidopsis promoted early flowering and the growth of the main bolt. Taken together, these results suggest that DiSOC1-a and DiSOC1-b are involved in the flowering initiation and the main bolt growth process of dove tree. Our results provide a foundation for horticultural breeding to control flowering time of dove tree.

MicroRNA-378 Suppressed Osteogenesis of MSCs and Impaired Bone Formation via Inactivating Wnt/ß-Catenin Signaling.

MicroRNAs (miRNAs) have been reported to serve as silencers to repress gene expression at post-transcriptional levels. Multiple miRNAs have been demonstrated to play important roles in osteogenesis. MicroRNA (miR)-378, a conserved miRNA, was reported to mediate bone metabolism and influence bone development, but the detailed function and underlying mechanism remain obscure. In this study, the miR-378 transgenic (TG) mouse was developed to study the role of miR-378 in osteogenic differentiation as well as bone formation. The abnormal bone tissues and impaired bone quality were displayed in the miR-378 TG mice, and a delayed healing effect was observed during bone fracture of the miR-378 TG mice. The osteogenic differentiation of mesenchymal stem cells (MSCs) derived from this TG mouse was also inhibited. We also found that miR-378 mimics suppressed, whereas anti-miR-378 promoted osteogenesis of human MSCs. Two Wnt family members, Wnt6 and Wnt10a, were identified as bona fide targets of miR-378, and their expression was decreased by this miRNA, which eventually induced the inactivation of Wnt/ß-catenin signaling. Finally, the short hairpin (sh)-miR-378-modified MSCs were locally injected into the fracture sites in an established mouse fracture model. The results indicated that miR-378 inhibitor therapy could promote bone formation and stimulate the healing process in vivo. In conclusion, miR-378 suppressed osteogenesis and bone formation via inactivating Wnt/ß-catenin signaling, suggesting that miR-378 may be a potential therapeutic target for bone diseases.

miR-378 and its host gene Ppargc1ß exhibit independent expression in mouse skeletal muscle.

MicroRNAs (miRNAs) are implicated in multiple biological processes in physiological and pathological settings. Nearly half of the known miRNAs are classified as 'intronic' miRNAs because they are embedded within the introns of protein-coding or noncoding genes. Such miRNAs were thought to be processed from primary host gene transcripts and share the promoter of their host. Recent analyses predicted that some intronic miRNAs might be transcribed and regulated as independent units, but there is little direct evidence for this in a specific biological context. Here, we focused on miR-378, which is located within the first intron of the peroxisome proliferator-activated receptor γ coactivator 1-beta (Ppargc1ß) gene and critically regulates skeletal muscle cell differentiation and muscle regeneration. We demonstrate that miR-378 and Ppargc1ß exhibit distinct expression patterns during skeletal muscle cell differentiation. In terminally differentiated adult skeletal muscle tissues of mice, miR-378 is predominantly expressed in glycolytic muscle, whereas Ppargc1ß is mainly expressed in oxidative soleus muscle. Mechanistically, miR-378, but not Ppargc1ß, is regulated by the transcription factor, MyoD, in muscle cells. Our findings identify a regulatory model of miR-378 expression, thereby helping us to understand its physiological function in skeletal muscle.