Structural Characters and Pharmacological Activity of Protopanaxadiol-Type Saponins and Protopanaxatriol-Type Saponins from Ginseng.

Ginseng has a long history of drug application in China, which can treat various diseases and achieve significant efficacy. Ginsenosides have always been deemed important ingredients for pharmacological activities. Based on the structural characteristics of steroidal saponins, ginsenosides are mainly divided into protopanaxadiol-type saponins (PDS, mainly including Rb1, Rb2, Rd, Rc, Rh2, CK, and PPD) and protopanaxatriol-type saponins (PTS, mainly including Re, R1, Rg1, Rh1, Rf, and PPT). The structure differences between PDS and PTS result in the differences of pharmacological activities. This paper provides an overview of PDS and PTS, mainly focusing on their chemical profile, pharmacokinetics, hydrolytic metabolism, and pharmacological activities including antioxidant, antifatigue, antiaging, immunodulation, antitumor, cardiovascular protection, neuroprotection, and antidiabetes. It is intended to contribute to an in-depth study of the relationship between PDS and PTS.

Quantification of Charge Transport and Mass Deprivation in Solid Electrolyte Interphase for Kinetically-Stable Low-Temperature Lithium-Ion Batteries.

Graphite (Gr)-based lithium-ion batteries with admirable electrochemical performance below -20 °C are desired but are hindered by sluggish interfacial charge transport and desolvation process. Li salt dissociation via Li+-solvent interaction enables mobile Li+ liberation and contributes to bulk ion transport, while is contradictory to fast interfacial desolvation. Designing kinetically-stable solid electrolyte interphase (SEI) without compromising strong Li+-solvent interaction is expected to compatibly improve interfacial charge transport and desolvation kinetics. However, the relationship between physicochemical features and temperature-dependent kinetics properties of SEI remains vague. Herein, we propose four key thermodynamics parameters of SEI potentially influencing low-temperature electrochemistry, including electron work function, Li+ transfer barrier, surface energy, and desolvation energy. Based on the above parameters, we further define a novel descriptor, separation factor of SEI (SSEI), to quantitatively depict charge (Li+/e-) transport and solvent deprivation processes at Gr/electrolyte interface. A Li3PO4-based, inorganics-enriched SEI derived by Li difluorophosphate (LiDFP) additive exhibits the highest SSEI (4.89×103) to enable efficient Li+ conduction, e- blocking and rapid desolvation, and as a result, much suppressed Li-metal precipitation, electrolyte decomposition and Gr sheets exfoliation, thus improving low-temperature battery performances. Overall, our work originally provides visualized guides to improve low-temperature reaction kinetics/thermodynamics by constructing desirable SEI chemistry.

Nomogram to predict radicular grooves in maxillary lateral incisors in preoperative orthodontic population.

OBJECTIVES: This study aimed to develop and validate a predictive nomogram for diagnosing radicular grooves (RG) in maxillary lateral incisors (MLIs), integrating demographic information, anatomical measurements, and Cone Beam Computed Tomography (CBCT) data to diagnose the RG in MLIs based on the clinical observation before resorting to the CBCT scan. MATERIALS AND METHODS: A retrospective cohort of orthodontic patients from the School and Hospital of Stomatology, Wuhan University, was analyzed, including demographic characteristics, photographic anatomical assessments, and CBCT diagnoses. The cohort was divided into development and validation groups. Univariate and multivariate logistic regression analyses identified significant predictors of RG, which informed the development of a nomogram. This nomogram's performance was validated using receiver operating characteristic analysis. RESULTS: The study included 381 patients (64.3% female) and evaluated 760 MLIs, with RG present in 26.25% of MLIs. The nomogram incorporated four significant anatomical predictors of RG presence, demonstrating substantial predictive efficacy with an area under the curve of 0.75 in the development cohort and 0.71 in the validation cohort. CONCLUSIONS: A nomogram for the diagnosis of RG in MLIs was successfully developed. This tool offers a practical checklist of anatomical predictors to improve the diagnostic process in clinical practice. CLINICAL RELEVANCE: The developed nomogram provides a novel, evidence-based tool to enhance the detection and treatment planning of MLIs with RG in diagnostic and therapeutic strategies.

All-Fluorinated Electrolyte Engineering Enables Practical Wide-Temperature-Range Lithium Metal Batteries.

The development of lithium metal batteries (LMBs) is severely hindered owing to the limited temperature window of the electrolyte, which renders uncontrolled side reactions, unstable electrolyte/electrode interface (EEI) formation, and sluggish desolvation kinetics for wide temperature operation condition. Herein, we developed an all-fluorinated electrolyte composed of lithium bis(trifluoromethane sulfonyl)imide, hexafluorobenzene (HFB), and fluoroethylene carbonate, which effectively regulates solvation structure toward a wide temperature of 160 °C (-50 to 110 °C). The introduction of thermostable HFB induces the generation of EEI with a high LiF ratio of 93%, which results in an inhibited side reaction and gas generation on EEI and enhanced interfacial ion transfer at extreme temperatures. Therefore, an unparalleled capacity retention of 88.3% after 400 cycles at 90 °C and an improved cycling performance at -50 °C can be achieved. Meanwhile, the practical 1.3 Ah-level pouch cell delivers high energy density of 307.13 Wh kg-1 at 60 °C and 277.99 Wh kg-1 at -30 °C after 50 cycles under lean E/C ratio of 2.7 g/Ah and low N/P ratio of 1.2. This work not only offers a viable strategy for wide-temperature-range electrolyte design but also promotes the practicalization of LMBs.

The long-term efficacy of eltrombopag in children with immune thrombocytopenia.

Immune thrombocytopenia (ITP) is the most common autoimmune disorder characterized by decreased platelet counts and impaired platelet production. Eltrombopag has been demonstrated to be safe and effective for children with ITP. It is reported eltrombopag can achieve a sustained response off treatment. However, data on its overall efficacy and safety profile are scarce in children. This study aimed to investigate the long-term efficacy of eltrombopag in children with ITP. Treatment overall response (OR), complete response (CR), response (R), durable response (DR), no response (NR), treatment free remission (TFR), and relapse rate, were assessed in 103 children with ITP during eltrombopag therapy. The OR rate, CR rate, R rate, DR rate, NR rate, TFR rate, and relapse rate were 67.0%, 55.3%, 11.7%, 56.3%, 33.0%, 60%, 36.2%, respectively. Importantly, we discovered that newly diagnosed ITP patients showed a higher DR rate, TFR rate and lower relapse rate compared to persistent and chronic ITP patients. Furthermore, the CR rate, DR rate, and TFR rate of 5 patients under six months were 100%. None of them suffered relapse. The most common adverse event (AEs) was hepatotoxicity (7.77%). Our study highlighted the critical role of eltrombopag as the second-line treatment in children with ITP who were intolerant to first-line therapy.

Establishment of a Cleavage-Based Single-Plasmid Dual-Luciferase Surrogate Reporter for the Cleavage Efficiency Evaluation of CRISPR-Cas12a Systems and Its Primary Application.

CRISPR-Cas technology is a widely utilized gene-editing tool that involves gRNA-guided sequence recognition and Cas nuclease-mediated cleavage. The design and evaluation of gRNA are essential for enhancing CRISPR/Cas editing efficiency. Various assays such as single-strand annealing, in vitro cleavage, and T7 endonuclease I (T7EI) are commonly used to assess gRNA-mediated Cas protein cleavage activity. In this study, a firefly luciferase and Renilla luciferase co-expressed and a cleavage-based single-plasmid dual-luciferase surrogate reporter was built to evaluate the gRNA-mediated Cas12a cleavage efficiency. The cleavage activities of CRISPR-Cas12a can be quantitatively determined by the recovery degree of firefly luciferase activity. The cleavage efficiency of CRISPR-Cas12a can be quantitatively measured by the recovery of firefly luciferase activity. By using this system, the cleavage efficiency of CRISPR-Cas12a on hepatitis B virus (HBV)/D expression plasmid was evaluated, revealing a negative correlation between gRNA cleavage efficiency and HBV gene expression measured using an enzyme-linked immunosorbent assay. This simple, efficient, and quantifiable system only requires the dual-luciferase vector and CRISPR-Cas12a vector, making it a valuable tool for selecting effective gRNAs for gene editing.

Enhanced near-infrared optical transmission in zinc germanium phosphide crystals via precise magnesium doping.

A zinc germanium phosphorus (ZnGeP2) crystal with a chalcopyrite structure is an efficient frequency converter in the mid-infrared region. However, point defect-induced optical absorption at the pumping wavelength (near infrared region) blocked the further application of ZnGeP2. To alleviate the absorption losses caused by point defects, in situ magnesium doping compensation was presented during the ZnGeP2 bulk crystal growth process via the vertical Bridgman method. Combined with theoretical calculations, the structural distortion of the magnesium-doped ZnGeP2 crystals in different orientations was illustrated. The thermodynamic and kinetic stability of the magnesium-doped ZnGeP2 structure were demonstrated. The transmission results indicated the improvement of transmittance within a wavelength range of 1.8-2.4 µm when doped with magnesium, which revealed the powerful ability of the appropriate dopant in optimizing near-infrared optical properties. Thus, the introduction of magnesium is a practical approach to improve the transmittance performance and extend the pumping source wavelengths of ZnGeP2 crystals.

Autophagy-related protein 5 (ATG5) interacts with bone marrow stromal cell antigen 2 (BST2) to stimulate HBV replication through antagonizing the antiviral activity of BST2.

Hepatitis B virus (HBV) infection is a major global health burden with 820 000 deaths per year. In our previous study, we found that the knockdown of autophagy-related protein 5 (ATG5) significantly upregulated the interferon-stimulated genes (ISGs) expression to exert the anti-HCV effect. However, the regulation of ATG5 on HBV replication and its underlying mechanism remains unclear. In this study, we screened the altered expression of type I interferon (IFN-I) pathway genes using RT² Profiler™ PCR array following ATG5 knock-down and we found the bone marrow stromal cell antigen 2 (BST2) expression was significantly increased. We then verified the upregulation of BST2 by ATG5 knockdown using RT-qPCR and found that the knockdown of ATG5 activated the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. ATG5 knockdown or BST2 overexpression decreased Hepatitis B core Antigen (HBcAg) protein, HBV DNA levels in cells and supernatants of HepAD38 and HBV-infected NTCP-HepG2. Knockdown of BST2 abrogated the anti-HBV effect of ATG5 knockdown. Furthermore, we found that ATG5 interacted with BST2, and further formed a ternary complex together with HBV-X (HBx). In conclusion, our finding indicates that ATG5 promotes HBV replication through decreasing BST2 expression and interacting with it directly to antagonize its antiviral function.

The Numerical Simulations and Experimental Study of an 8-Inch SiC Single Crystal with Reduced BPD Density.

The basal plane dislocation (BPD) density is one of the most important defects affecting the application of SiC wafers. In this study, numerical simulations and corresponding experiments were conducted to investigate the influence of cooling processes, seed-bonding methods, and graphite crucible materials on the BPD density in an 8-inch N-type 4H-SiC single crystal grown by the physical vapor transport (PVT) method. The results showed that the BPD density could be effectively reduced by increasing the cooling rate, optimizing the seed-bonding method, and adopting a graphite crucible with a similar coefficient of thermal expansion as the SiC single crystal. The BPD density in the experiments showed that a high cooling rate reduced the BPD density from 4689 cm-2 to 2925 cm-2; optimization of the seed-bonding method decreased the BPD density to 1560 cm-2. The BPD density was further reduced to 704 cm-2 through the adoption of a graphite crucible with a smaller thermal expansion coefficient.

Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.

BACKGROUND: A series of studies have demonstrated the emerging involvement of transfer RNA (tRNA) processing during the progression of tumours. Nevertheless, the roles and regulating mechanisms of tRNA processing genes in neuroblastoma (NB), the prevalent malignant tumour outside the brain in children, are yet unknown. METHODS: Analysis of multi-omics results was conducted to identify crucial regulators of downstream tRNA processing genes. Co-immunoprecipitation and mass spectrometry methods were utilised to measure interaction between proteins. The impact of transcriptional regulators on expression of downstream genes was measured by dual-luciferase reporter, chromatin immunoprecipitation, western blotting and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) methods. Studies have been conducted to reveal impact and mechanisms of transcriptional regulators on biological processes of NB. Survival differences were analysed using the log-rank test. RESULTS: c-Myc was identified as a transcription factor driving tRNA processing gene expression and subsequent malate-aspartate shuttle (MAS) in NB cells. Mechanistically, c-Myc directly promoted the expression of glutamyl-prolyl-tRNA synthetase (EPRS) and leucyl-tRNA synthetase (LARS), resulting in translational up-regulation of glutamic-oxaloacetic transaminase 1 (GOT1) as well as malate dehydrogenase 1 (MDH1) via inhibiting general control nonrepressed 2 or activating mechanistic target of rapamycin signalling. Meanwhile, lamin A (LMNA) inhibited c-Myc transactivation via physical interaction, leading to suppression of MAS, aerobic glycolysis, tumourigenesis and aggressiveness. Pre-clinically, lobeline was discovered as a LMNA-binding compound to facilitate its interaction with c-Myc, which inhibited aminoacyl-tRNA synthetase expression, MAS and tumour progression of NB, as well as growth of organoid derived from c-Myc knock-in mice. Low levels of LMNA or elevated expression of c-Myc, EPRS, LARS, GOT1 or MDH1 were linked to a worse outcome and a shorter survival time of clinical NB patients. CONCLUSIONS: These results suggest that targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for MAS and tumour progression.

Precise Capture and Dynamic Release of Circulating Liver Cancer Cells with Dual-Histidine-Based Cell Imprinted Hydrogels.

Circulating tumor cells (CTCs) detection presents significant advantages in diagnosing liver cancer due to its noninvasiveness, real-time monitoring, and dynamic tracking. However, the clinical application of CTCs-based diagnosis is largely limited by the challenges of capturing low-abundance CTCs within a complex blood environment while ensuring them alive. Here, an ultrastrong ligand, l-histidine-l-histidine (HH), specifically targeting sialylated glycans on the surface of CTCs, is designed. Furthermore, HH is integrated into a cell-imprinted polymer, constructing a hydrogel with precise CTCs imprinting, high elasticity, satisfactory blood compatibility, and robust anti-interference capacities. These features endow the hydrogel with excellent capture efficiency (>95%) for CTCs in peripheral blood, as well as the ability to release CTCs controllably and alive. Clinical tests substantiate the accurate differentiation between liver cancer, cirrhosis, and healthy groups using this method. The remarkable diagnostic accuracy (94%), lossless release of CTCs, material reversibility, and cost-effectiveness ($6.68 per sample) make the HH-based hydrogel a potentially revolutionary technology for liver cancer diagnosis and single-cell analysis.

Cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of Shigella flexneri.

Pathogen infections including Shigella flexneri have posed a significant threat to human health for numerous years. Although culturing and qPCR were the gold standards for pathogen detection, time-consuming and instrument-dependent restrict their application in rapid diagnosis and economically less-developed regions. Thus, it is urgently needed to develop rapid, simple, sensitive, accurate, and low-cost detection methods for pathogen detection. In this study, an immunomagnetic beads-recombinase polymerase amplification-CRISPR/Cas12a (IMB-RPA-CRISPR/Cas12a) method was built based on a cascaded signal amplification strategy for ultra-specific, ultra-sensitive, and visual detection of S. flexneri in the laboratory. Firstly, S. flexneri was specifically captured and enriched by IMB (Shigella antibody-coated magnetic beads), and the genomic DNA was released and used as the template in the RPA reaction. Then, the RPA products were mixed with the pre-loaded CRISPR/Cas12a for fluorescence visualization. The results were observed by naked eyes under LED blue light, with a sensitivity of 5 CFU/mL in a time of 70 min. With no specialized equipment or complicated technical requirements, the IMB-RPA-CRISPR/Cas12a diagnostic method can be used for visual, rapid, and simple detection of S. flexneri and can be easily adapted to monitoring other pathogens.

Total Infectome Characterization of Respiratory Infections during the 2022-23 COVID-19 Outbreak in China Revealed Extensive Coinfections with Links to SARS-CoV-2 Status, Age, and Disease Severity.

Between 7 December 2022 and 28 February 2023, China experienced a new wave of COVID-19 that swept across the entire country and resulted in an increasing amount of respiratory infections and hospitalizations. The purpose of this study is to reveal the intensity and composition of coinfecting microbial agents. In total, 196 inpatients were recruited from The Third People's Hospital of Shenzhen, and 169 respiratory and 73 blood samples were collected for metagenomic next-generation sequencing. The total "Infectome" was characterized and compared across different groups defined by the SARS-CoV-2 detection status, age groups, and severity of disease. Our results revealed a total of 22 species of pathogenic microbes (4 viruses, 13 bacteria, and 5 fungi), and more were discovered in the respiratory tract than in blood. The diversity of the total infectome was highly distinguished between respiratory and blood samples, and it was generally higher in patients that were SARS-CoV-2-positive, older in age, and with more severe disease. At the individual pathogen level, HSV-1 seemed to be the major contributor to these differences observed in the overall comparisons. Collectively, this study reveals the highly complex respiratory infectome and high-intensity coinfection in patients admitted to the hospital during the period of the 2023 COVID-19 pandemic in China.

A Fast-Charge Graphite Anode with a Li-Ion-Conductive, Electron/Solvent-Repelling Interface.

Graphite has been serving as the key anode material of rechargeable Li-ion batteries, yet is difficultly charged within a quarter hour while maintaining stable electrochemistry. In addition to a defective edge structure that prevents fast Li-ion entry, the high-rate performance of graphite could be hampered by co-intercalation and parasitic reduction of solvent molecules at anode/electrolyte interface. Conventional surface modification by pitch-derived carbon barely isolates the solvent and electrons, and usually lead to inadequate rate capability to meet practical fast-charge requirements. Here we show that, by applying a MoOx-MoNx layer onto graphite surface, the interface allows fast Li-ion diffusion yet blocks solvent access and electron leakage. By regulating interfacial mass and charge transfer, the modified graphite anode delivers a reversible capacity of 340.3 mAh g-1 after 4000 cycles at 6 C, showing promises in building 10-min-rechargeable batteries with a long operation life.

Metagenomic analysis of individual mosquito viromes reveals the geographical patterns and drivers of viral diversity.

Mosquito transmitted viruses are responsible for an increasing burden of human disease. Despite this, little is known about the diversity and ecology of viruses within individual mosquito hosts. Here, using a meta-transcriptomic approach, we determined the viromes of 2,438 individual mosquitoes (81 species), spanning ~4,000 km along latitudes and longitudes in China. From these data we identified 393 viral species associated with mosquitoes, including 7 (putative) species of arthropod-borne viruses (that is, arboviruses). We identified potential mosquito species and geographic hotspots of viral diversity and arbovirus occurrence, and demonstrated that the composition of individual mosquito viromes was strongly associated with host phylogeny. Our data revealed a large number of viruses shared among mosquito species or genera, enhancing our understanding of the host specificity of insect-associated viruses. We also detected multiple virus species that were widespread throughout the country, perhaps reflecting long-distance mosquito dispersal. Together, these results greatly expand the known mosquito virome, linked viral diversity at the scale of individual insects to that at a country-wide scale, and offered unique insights into the biogeography and diversity of viruses in insect vectors.

Combining dredging with modified zeolite thin-layer capping to control nitrogen release from eutrophic lake sediment.

Dredging is widely used to control internal sediment nitrogen (N) pollution during eutrophic lake restoration. However, the effectiveness of dredging cannot be maintained for long periods during seasonal temperature variations. This study used modified zeolite (MZ) as a thin-layer capping material to enhance dredging efficiency during a year-long field sediment core incubation period. Our results showed that dredging alone more effectively reduced pore water N, N flux, and sediment N content than MZ capping but showed more dramatic changes during the warm seasons. The N flux in dredged sediment in summer was 1.8 and 2.5 times that in spring and autumn, respectively, indicating a drastic N regeneration process in the short term. In contrast, the combination method reduced the extra 10% pore water N, 22% N flux, and 8% sediment organic N content compared with dredging alone and maintained high stability during seasonal changes. The results indicated that the addition of MZ to the surface of dredged sediment not only enhanced the control effect of dredging by its adsorption capacity but may also smooth the N regeneration process via successive accumulation (in the channel of the material) and activation of bacteria for months, which was evidenced by the variation in microbial diversity in the MZ treatment. As a result, the combination of dredging with modified zeolite simultaneously enhanced the efficiency and stability of the single dredging method in controlling sediment N content and its release, exhibiting great prospects for long-term application in eutrophic lakes with severe pollution from internal N loading.

Automating the Human Connectome Project's Temporal ICA Pipeline.

Functional magnetic resonance imaging (fMRI) data are dominated by noise and artifacts, with only a small fraction of the variance relating to neural activity. Temporal independent component analysis (tICA) is a recently developed method that enables selective denoising of fMRI artifacts related to physiology such as respiration. However, an automated and easy to use pipeline for tICA has not previously been available; instead, two manual steps have been necessary: 1) setting the group spatial ICA dimensionality after MELODIC's Incremental Group-PCA (MIGP) and 2) labeling tICA components as artifacts versus signals. Moreover, guidance has been lacking as to how many subjects and timepoints are needed to adequately re-estimate the temporal ICA decomposition and what alternatives are available for smaller groups or even individual subjects. Here, we introduce a nine-step fully automated tICA pipeline which removes global artifacts from fMRI dense timeseries after sICA+FIX cleaning and MSMAll alignment driven by functionally relevant areal features. Additionally, we have developed an automated "reclean" Pipeline for improved spatial ICA (sICA) artifact removal. Two major automated components of the pipeline are 1) an automatic group spatial ICA (sICA) dimensionality selection for MIGP data enabled by fitting multiple Wishart distributions; 2) a hierarchical classifier to distinguish group tICA signal components from artifactual components, equipped with a combination of handcrafted features from domain expert knowledge and latent features obtained via self-supervised learning on spatial maps. We demonstrate that the dimensionality estimated for the MIGP data from HCP Young Adult 3T and 7T datasets is comparable to previous manual tICA estimates, and that the group sICA decomposition is highly reproducible. We also show that the tICA classifier achieved over 0.98 Precision-Recall Area Under Curve (PR-AUC) and that the correctly classified components account for over 95% of the tICA-represented variance on multiple held-out evaluation datasets including the HCP-Young Adult, HCP-Aging and HCP-Development datasets under various settings. Our automated tICA pipeline is now available as part of the HCP pipelines, providing a powerful and user-friendly tool for the neuroimaging community.

Hsa_circ_0007321 regulates Zika virus replication through miR-492/NFKBID/NF-κB signaling pathway.

IMPORTANCE: Over the past decade, increasing evidence has shown that circular RNAs (circRNAs) play important regulatory roles in viral infection and host antiviral responses. However, reports on the role of circRNAs in Zika virus (ZIKV) infection are limited. In this study, we identified 45 differentially expressed circRNAs in ZIKV-infected A549 cells by RNA sequencing. We clarified that a downregulated circRNA, hsa_circ_0007321, regulates ZIKV replication through targeting of miR-492 and the downstream gene NFKBID. NFKBID is a negative regulator of nuclear factor-κB (NF-κB), and we found that inhibition of the NF-κB pathway promotes ZIKV replication. Therefore, this finding that hsa_circ_0007321 exerts its regulatory role on ZIKV replication through the miR-492/NFKBID/NF-κB signaling pathway has implications for the development of strategies to suppress ZIKV and possibly other viral infections.

Sodium salicylate ameliorates exercise-induced muscle damage in mice by inhibiting NF-kB signaling.

BACKGROUND: Eccentric muscle contraction can cause muscle damage, which reduces the efficiency of exercise. Previous evidence suggested that Sodium salicylate (SS) could improve the repair of aged muscle. This study intends to investigate whether SS can impact skeletal muscle damage caused by eccentric exercise. METHODS: Eccentric treadmill exercise was performed to induce muscle damage in mice. Plasma levels of muscle damage markers were estimated. RT-qPCR was employed for detecting mRNA levels of proinflammatory mediators in murine gastrocnemius muscle. Immunofluorescence staining of laminin/DAPI was utilized for quantifying centrally nucleated myofibers in the gastrocnemius muscle. Western blotting was implemented to examine protein levels of mitsugumin 53 (MG53), matrix metalloproteinase (MMP)-2/9, and NF-κB signaling-related markers. RESULTS: SS administration reduced muscle damage marker production in the plasma and decreased the levels of proinflammatory mediators, MG53 and MMP-2/9 in mice after exercise. SS alleviated the severity of muscle damage in the gastrocnemius of mice after eccentric exercise. SS blocked NF-κB signaling pathway in the gastrocnemius muscle. CONCLUSION: SS administration ameliorates skeletal muscle damage caused by eccentric exercise in the mouse model.

circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.

BACKGROUND: Recent evidence reveals the emerging functions of circular RNA (circRNA) and protein glycosylation in cancer progression. However, the roles of circRNA in regulating glycosyltransferase expression in gastric cancer remain to be determined. METHODS: Circular RNAs (circRNAs) were validated by Sanger sequencing. Co-immunoprecipitation, mass spectrometry, and RNA sequencing assays were applied to explore protein interaction and target genes. Gene expression regulation was observed by chromatin immunoprecipitation, RNA immunoprecipitation, dual-luciferase reporter, real-time quantitative RT-PCR, and western blot assays. Gain- and loss-of-function studies were performed to observe the impacts of circRNA and its partners on the glycosylation, growth, invasion, and metastasis of gastric cancer cells. RESULTS: Circ-hnRNPU, an exonic circRNA derived from heterogenous nuclear ribonuclear protein U (hnRNPU), was identified to exert tumor suppressive roles in protein glycosylation and progression of gastric cancer. Mechanistically, circ-hnRNPU physically interacted with non-POU domain containing octamer binding (NONO) protein to induce its cytoplasmic retention, resulting in down-regulation of glycosyltransferases (GALNT2, GALNT6, MGAT1) and parental gene hnRNPU via repression of nuclear NONO-mediated c-Myc transactivation or cytoplasmic NONO-facilitated mRNA stability. Rescue studies indicated that circ-hnRNPU inhibited the N- and O-glycosylation, growth, invasion, and metastasis of gastric cancer cells via interacting with NONO protein. Pre-clinically, administration of lentivirus carrying circ-hnRNPU suppressed the protein glycosylation, tumorigenesis, and aggressiveness of gastric cancer xenografts. In clinical cases, low circ-hnRNPU levels and high NONO or c-Myc expression were associated with poor survival outcome of gastric cancer patients. CONCLUSIONS: These findings indicate that circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.