Seasonal variations and sources of atmospheric EPFRs in a megacity in severe cold region: Implications for the influence of strong coal and biomass combustion.

Environmentally persistent free radicals (EPFRs) can pose exposure risks by inducing the generation of reactive oxygen species. As a new class of pollutants, EPFRs have been frequently detected in atmospheric particulate matters. In this study, the seasonal variations and sources of EPFRs in a severe cold region in Northeastern China were comprehensively investigated, especially for the high pollution events. The geomean concentration of EPFRs in the total suspended particle was 6.58 × 1013 spins/m3 and the mean level in winter was one order of magnitude higher than summer and autumn. The correlation network analysis showed that EPFRs had significantly positive correlation with carbon component, K+ and PAHs, indicating that EPFRs were primarily emitted from combustion and pyrolysis process. The source appointment by the Positive Matrix Factorization (PMF) model indicated that the dominant sources in the heating season were coal combustion (48.4%), vehicle emission (23.1%) and biomass burning (19.4%), while the top three sources in the non-heating season were others (41.4%), coal combustion (23.7%) and vehicle emissions (21.2%). It was found that the high EPFRs in cold season can be ascribed to the extensive use of fossil fuel for heating demand; while the high EPFRs occurred in early spring were caused by the large-scale opening combustion of biomass. In summary, this study provided important basic information for better understanding the pollution characteristics of EPFRs, which suggested that the implementation of energy transformation and straw utilization was benefit for the control of EPFRs in severe cold region.

The Effects of Health Education and the Sunrise Model of Nursing Care on Blood Pressure Control and Psychological Status in Elderly Patients with Hypertension.

Objective: Our aim was to investigate the effect of health education and a positive attitude nursing model on blood pressure (BP) control and psychological status in elderly patients with hypertension (HTN). Methods: A total of 80 elderly patients with HTN in the Affiliated Hangzhou First People's Hospital in China were selected as the study participants. They were randomly divided into a control group and an observation group, with 40 patients in each group. The control group received the routine nursing intervention, while the observation group received health education and the positive attitude nursing intervention based on the nursing care in the control group. The BP control effect, changes in systolic and diastolic BP, psychological status and nursing satisfaction were compared in the 2 groups. Results: The BP control rate in the control group was 77.5% and was 95.0% in the observation group, which was significantly better (P < .05). Before the intervention, there was no significant difference in average systolic and diastolic BP between the 2 groups (P > .05); after the intervention, average systolic and diastolic BP in the observation group were significantly lower than in the control group (P < .05). Before the intervention, there was no significant difference in Self-rating Anxiety Scale (SAS) and Self-rating Anxiety Scale (SDS) scores between the 2 groups (P > .05). After the intervention, the SAS and SDS scores in the observation group were significantly better than those in the control group (P < .05). The nursing satisfaction in the control group was 75.0% and was 95.0% in the observation group, which was significantly higher (P < .05). Conclusion: Compared with routine nursing intervention, the health education and positive attitude nursing intervention can further improve BP control, psychological status and satisfaction and recognition level of elderly patients with HTN; it can be an important clinical nursing intervention.

Salidroside protects pulmonary artery endothelial cells against hypoxia-induced apoptosis via the AhR/NF-κB and Nrf2/HO-1 pathways.

BACKGROUND: The apoptosis of pulmonary artery endothelial cells (PAECs) is an important factor contributing to the development of pulmonary hypertension (PH), a serious cardio-pulmonary vascular disorder. Salidroside (SAL) is a bioactive compound derived from an herb Rhodiola, but the potential protective effects of SAL on PAECs and the underlying mechanisms remain elusive. PURPOSE: The objective of this study was to determine the role of SAL in the hypoxia-induced apoptosis of PAECs and to dissect the underlying mechanisms. STUDY DESIGN: Male Sprague-Dawley (SD) rats were subjected to hypoxia (10% O2) for 4 weeks to establish a model of PH. Rats were intraperitoneally injected daily with SAL (2, 8, and 32 mg/kg/d) or vehicle. To define the molecular mechanisms of SAL in PAECs, an in vitro model of hypoxic cell injury was also generated by exposed PAECs to 1% O2 for 48 h. METHODS: Various techniques including hematoxylin and eosin (HE) staining, immunofluorescence, flow cytometry, CCK-8, Western blot, qPCR, molecular docking, and surface plasmon resonance (SPR) were used to determine the role of SAL in rats and in PAECs in vitro. RESULTS: Hypoxia stimulation increases AhR nuclear translocation and activates the NF-κB signaling pathway, as evidenced by upregulated expression of CYP1A1, CYP1B1, IL-1ß, and IL-6, resulting in oxidative stress and inflammatory response and ultimately apoptosis of PAECs. SAL inhibited the activation of AhR and NF-κB, while promoted the nuclear translocation of Nrf2 and increased the expression of its downstream antioxidant proteins HO-1 and NQO1 in PAECs, ameliorating the hypoxia-induced oxidative stress in PAECs. Furthermore, SAL lowered right ventricular systolic pressure, and decreased pulmonary vascular remodeling and right ventricular hypertrophy in hypoxia-exposed rats. CONCLUSIONS: SAL may attenuate the apoptosis of PAECs by suppressing NF-κB and activating Nrf2/HO-1 pathways, thereby delaying the progressive pathology of PH.

Cysteine protease inhibitor 1 promotes metastasis by mediating an oxidative phosphorylation/MEK/ERK axis in esophageal squamous carcinoma cancer.

Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Insights into the relationship between serum uric acid and pulmonary hypertension (Review).

Pulmonary hypertension (PH) is a progressive lethal disease, which is characterized by abnormal vascular remodeling and persistently elevated pulmonary artery pressure, eventually leading to right heart failure and even death. Although great progress has been made in treating PH, the mortality rate remains high. Metabolic disorders are one of the important hallmarks of PH. Obesity, lipids, glucose tolerance and insulin resistance are risk factors for numerous cardiovascular diseases and are often accompanied by a considerable increase in serum uric acid (SUA) concentrations. Uric acid (UA) is the end product of purine nucleotide metabolism and is closely related to cardiovascular diseases including PH. Hyperuricemia promotes the development and progression of PH through endothelial dysfunction, oxidative stress, inflammatory responses and activation of the renin­angiotensin system. In the present review, the advancements in knowledge about UA metabolism and PH, and the current understanding of the potential interactions and mechanisms of SUA in PH were systematically summarized, which may provide new insights into the pathogenesis of PH.

A novel risk score model of esophageal stricture for patients undergoing endoscopic submucosal dissection.

BACKGROUND AND PURPOSE: Endoscopic submucosal dissection (ESD) is a promising technique for superficial esophageal lesions. However, stricture is a frequent adverse complication. This study was performed to develop a precise and convenient score prediction model for esophageal strictures after ESD, and compare its efficacy with a previously published predictive model. METHODS: This study enrolled clinical data of patients who underwent esophageal ESD for superficial esophageal lesions. Possible risk factors for esophageal stricture were identified by univariate and multivariate logistic regression analysis. Then we developed a prediction model according to the Framingham system for the first time and presented a convenient table containing the risk probability for each patient. In addition, we validated our score model and the previously published model in our center. RESULTS: A total of 838 patients were enrolled in this study and 6 variables, including age, surgery time, location of the lesion, circumference of the lesion, longitudinal resection length, and depth of infiltration were comprised in the score model. The total score ranged from 0 to 16 points and the risk probability was presented in one concise table for each patient. Areas under receiver-operator characteristic curves for the prediction model were 0.715 in derivation group and 0.804 in validation group. CONCLUSION: We designed and validated a prediction score model for esophageal stricture after ESD, which can be applied conveniently to stratify the stricture risk after esophageal ESD and may facilitate appropriate clinical decision-making for these patients.

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.

Health Risk Assessment of Organophosphate Flame Retardants in Soil Across China Based on Monte Carlo Simulation.

Health risks from exposure to contaminants are generally estimated by evaluating concentrations of the contaminants in environmental matrixes. However, accurate health risk assessment is difficult because of uncertainties regarding exposures. This study aims to utilize data on the concentrations of organophosphate flame retardants (OPFRs) in surface soil across China coupled with Monte Carlo simulations to compensate for uncertainties in exposure to evaluate the health risks associated with contamination of soil with this class of flame retardants. Results revealed that concentrations of ∑OPFRs were 0.793-406 ng/g dry weight (dw) with an average of 23.2 ng/g dw. In terms of spatial distribution, higher OPFRs concentrations were found in economically developed regions. Although the values of health risk of OPFRs in soil across China were below the threshold, the high concentrations of OPFRs in soil in some regions should attract more attentions in future. Sensitivity analysis revealed that concentrations of OPFRs in soil, skin adherence factor, and exposure duration were the most sensitive parameters in health risk assessment. In summary, the study indicated that the national scale soil measurement could provide unique information on OPFRs exposure and health risk assessment, which was useful for the management of soil in China and for better understanding of the environmental fate of OPFRs in the global perspective.

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma: A real-world retrospective cohort study.

BACKGROUND: Signet-ring cell carcinoma (SRCC) was previously thought to have a worse prognosis than other differentiated gastric cancer (GC), however, recent studies have shown that the prognosis of SRCC is related to pathological type. We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis (LNM). AIM: To establish models to predict LNM in early GC (EGC), including early gastric SRCC. METHODS: Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed. The patients were divided into three groups based on type: Pure SRCC, mixed SRCC, and non-signet ring cell carcinoma (NSRC). The risk factors were identified through statistical tests using SPSS 23.0, R, and Em-powerStats software. RESULTS: A total of 1922 subjects with EGC were enrolled in this study, and included 249 SRCC patients and 1673 NSRC patients, while 278 of the patients (14.46%) presented with LNM. Multivariable analysis showed that gender, tumor size, depth of invasion, lymphovascular invasion, ulceration, and histological subtype were independent risk factors for LNM in EGC. Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy (98.0% vs 58.1%, P = 0.034; 88.4% vs 86.8%, P < 0.001, respectively). Among the 249 SRCC patients, LNM was more common in mixed (35.06%) rather than in pure SRCC (8.42%, P < 0.001). The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760 (95%CI: 0.682-0.843), while the area under the operating characteristic curve of the internal validation set was 0.734 (95%CI: 0.643-0.826). The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size > 2 cm (OR = 5.422, P = 0.038). CONCLUSION: A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC, which can aid in pre-surgical decision making of the best method of treatment for patients.

A day-to-day management model improves patient compliance to treatment for Helicobacter pylori infection: a prospective, randomized controlled study.

BACKGROUND: The day-to-day (DTD) management model encourages patients to actively participate in their healthcare by setting goals. We determined the effectiveness of the DTD model in the treatment of Helicobacter pylori (H. pylori) infection, as compared with conventional outpatient education (OE). METHODS: We randomized 254 H. pylori-positive patients into a DTD group (127 patients) and an OE group (127 patients) prior to primary treatment with 14-day bismuth-containing quadruple therapy, including esomeprazole, amoxicillin, and clarithromycin. Both groups received consistent medication instructions. Patients in the DTD group recorded daily attendance after completing their daily medication plan from day 1 to day 14. The medication compliance, follow-up compliance, H. pylori eradication rates, and adverse events (AEs) were evaluated. RESULTS: In the modified intention-to-treat (MITT) and per-protocol (PP) analyses, the DTD group showed significantly higher medication compliance than the OE group (P = 0.001 and P = 0.031, respectively). Both the MITT and PP analyses showed significant differences in follow-up compliance (P < 0.001 and P = 0.003, respectively) and timing of the review urea breath test (P < 0.001 and P = 0.001, respectively) between the two groups. However, no significant differences were observed in the H. pylori eradication rates (95.8% vs. 93.8%, P = 0.529) in the PP analysis, or AEs incidence (25.4% vs. 28.3%, P = 0.603) between the two groups. CONCLUSION: This study demonstrated the novel application of the DTD model in the treatment of H. pylori infection, which enabled patients to develop habitual medication-taking behaviors without physician intervention.

Eugenilones A-N: sesquiterpenoids from the fruits of Eugenia uniflora.

(+) and (-)-Eugenilones A-K, 11 pairs of undescribed enantiomeric sesquiterpenoids, together with three undescribed biogenetically related members eugenilones L-N, were discovered from the fruits of Eugenia uniflora Linn. (Myrtaceae). Structurally, eugenilones A-D were four caged sesquiterpenoids featuring 9,10-dioxatricyclo [6.2.2.02,7]dodecane, 11-oxatricyclo [5.3.1.03,8]undecane, and tricyclo [4.4.0.02,8]decane cores, respectively. Eugenilones E-K were eudesmane-type sesquiterpenoids, while eugenilones L-N were epoxy germacrane-type sesquiterpenoids. Notably, eugenilones A-K were efficiently resolved by chiral HPLC to give 11 pairs of optically pure enantiomers. The structures and absolute configurations of eugenilones A-N were determined through spectroscopic analyses, X-ray crystallography, and ECD calculations. The putative biosynthetic pathways for these undescribed isolates were proposed. Moreover, eugenilones A and E exhibited significant anti-inflammatory effects by inhibiting LPS-stimulated NO overproduction in RAW264.7 cells (IC50 values of 4.89 ± 0.37 µM and 20.89 ± 1.49 µM, respectively) and TNF-α-induced NF-κB activation in HEK293 cells (IC50 values of 10.97 ± 1.03 µM and 28.63 ± 1.59 µM, respectively).

Xanchryones I-N, Six Unusual Phloroglucinol-Amino Acid Hybrids from the Leaves of Xanthostemon chrysanthus.

Six new phloroglucinol derivatives, xanchryones I-N (1-6), were isolated from the leaves of Xanthostemon chrysanthus. Compounds 1-6 are unusual phloroglucinol-amino acid hybrids constructed through C2 -N and O-C1 ' bonds forming a peculiar oxazole ring. The structures and absolute configurations of compounds 1-6 were determined by MS, NMR, and single-crystal X-ray diffraction. Moreover, the anti-inflammatory and antibacterial activities of these compounds were evaluated.

Ni-Doped BiVO4 photoanode for efficient photoelectrochemical water splitting.

BiVO4 (BVO) based photoanode is one of the most mega-potential materials for solar water splitting while suffers from poor charge transfer and separation efficiency limit its practical application. Herein, FeOOH/Ni-BiVO4 photoanode synthesized by the facile wet chemical method were investigated for improved charge transport and separation efficiency. The photoelectrochemical (PEC) measurements demonstrate that the water oxidation photocurrent density can reach as high as 3.02 mA cm-2 at 1.23 V vs RHE, and the surface separation efficiency can be boosted to 73.3 %, which increases around 4 times comparing with that of pure sample. Further depth studies showed that the Ni doping can effectively promote hole transport/trapping and introduce more active sites for the oxidation of water, while FeOOH co-catalyst could passivate the Ni-BiVO4 photoanode surface. This work provides a model for the design of BiVO4-based photoanodes with combined thermodynamic and kinetic advantages.

Comparison of statins with steroids and botulinum toxin A in the prevention of benign strictures after esophageal endoscopic submucosal dissection: a retrospective cohort study.

BACKGROUND: Preventing benign strictures following esophageal endoscopic submucosal dissection (ESD) remains difficult, and finding a safe, effective, and simple management method is vital. We previously reported that rosuvastatin significantly reduced the incidence and severity of strictures in a rabbit model of esophageal stricture. Accordingly, in this study, we compared the effects of statins, steroids, and botulinum toxin A (BTX-A) on stricture prevention after ESD involving more than three-fourths of the luminal circumference. METHODS: Of the 1019 ESD cases treated between January 2015 and December 2020, 246 met the inclusion criteria, with 21 cases excluded due to loss to follow-up, tumor recurrence, death, or need for additional surgery, radiotherapy, and/or chemotherapy. Of the 225 included cases, 145 received no intervention, while the remaining 80 were treated: 16 with oral steroids, 20 with topical triamcinolone acetonide (TA) injection, 21 with topical BTX-A injection, and 23 with statins. RESULTS: The occurrence stricture rate in the statins group (17.4%, 4/23) was significantly lower than in the non-intervention (75.2%, 109/145, P = 0.000), oral steroids (56.3%, 9/16, P = 0.011) and TA injection (50%, 10/20, P = 0.023) groups, but comparable to in the BTX-A injection (38.1%, 8/21, P = 0.124) group. The dysphagia score was lower in the statin than non-intervention group (P = 0.000). Although there was no significant difference in the number of required dilations between groups, the maximum number of dilations in the statins group was only six. CONCLUSIONS: Statins may be a potential treatment to prevent esophageal strictures after extensive ESD; however, clinical trials should be conducted to validate this.

Boosting photoelectrochemical water splitting of bismuth vanadate photoanode via novel co-catalysts of amorphous manganese oxide with variable valence states.

Bismuth vanadate (BVO) is a promising photoanode while suffers from sluggish oxygen evolution kinetics. Herein, an ultra-thin manganese oxide (MnOx) is selected as co-catalyst to modify the surface of BVO photoanode by a facile spray pyrolysis method. The photoelectrochemical measurements demonstrate that surface charge transport efficiency (ηsurface) of MnOx modified BVO photoanode (BVO/MnOx) is strikingly increased from 6.7 % to 22.3 % at 1.23 VRHE (reversible hydrogen electrode (VRHE)). Moreover, the ηsurface can be further boosted to 51.3 % at 1.23 VRHE after applying Ar plasma on the BVO/MnOx sample, which is around 7 times higher comparing with that of pristine BVO samples. Additional characterizations reveal that the remarkable PEC performance of the Ar-plasma treated BVO/MnOx photoanode (BVO/MnOx/Ar plasma) could be attributed to the increased charge carrier density, extended carrier lifetime and additional exposed Mn3+ active sites on the BVO surface. This investigation could provide a new understanding for the design of BVO photoanode with superior PEC performance based on the modification of MnOx and plasma surface treatment.

3CLpro inhibitors: DEL-based molecular generation.

Molecular generation (MG) via machine learning (ML) has speeded drug structural optimization, especially for targets with a large amount of reported bioactivity data. However, molecular generation for structural optimization is often powerless for new targets. DNA-encoded library (DEL) can generate systematic, target-specific activity data, including novel targets with few or unknown activity data. Therefore, this study aims to overcome the limitation of molecular generation in the structural optimization for the new target. Firstly, we generated molecules using the structure-affinity data (2.96 million samples) for 3C-like protease (3CLpro) from our own-built DEL platform to get rid of using public databases (e.g., CHEMBL and ZINC). Subsequently, to analyze the effect of transfer learning on the positive rate of the molecule generation model, molecular docking and affinity model based on DEL data were applied to explore the enhanced impact of transfer learning on molecule generation. In addition, the generated molecules are subjected to multiple filtering, including physicochemical properties, drug-like properties, and pharmacophore evaluation, molecular docking to determine the molecules for further study and verified by molecular dynamics simulation.

Ventricular septal defect complicating myocardial infarction: A case of delayed percutaneous transcatheter closure.

A 57-year-old man suffered chest pain during the COVID-19 pandemic, but he delayed medical treatment due to fear of infection. After 4 months, symptoms of chest tightness and shortness of breath appeared. Electrocardiogram (ECG) revealed old myocardial infarction; color sonography and myocardial computed tomography revealed apical myocardial defect. He refused surgery and percutaneous transcatheter closure, and follow-up observation. After 22 months, the symptoms of chest tightness and shortness of breath aggravated. He recovered after percutaneous transcatheter closure, and was discharged. This case shows delayed closure is one of the possible options for patients without severe organ dysfunction or hemodynamic disturbance.

Major League Baseball Marketing Strategies and Industry Promotion Approaches.

The sport of baseball is one of the chief pillars of the American sports industry. Major League Baseball (MLB) is the oldest professional sports league in the United States. It has long since formulated comprehensive marketing strategies and global industry promotion approaches that have proved exceptionally successful. Accordingly, the study of MLB's marketing strategies and industry promotion approaches will be crucial for the development of baseball in China and the establishment of an industrial chain. This study employed the literature consultation method, the comparative analysis method, and the inductive method to analyze MLB's localized marketing strategies and development trends in China and obtained the following insights concerning MLB's promotion and industry development efforts in China: (1) MLB has used a "family sport" concept to promote baseball culture and employed a project culture approach to promoting the universal spread of the sport of baseball; (2) MLB has sought to join baseball with school sports as a means of developing baseball talent; (3) MLB has promoted its brand, established a baseball industry chain, and engaged in comprehensive market cultivation; and (4) MLB has strengthened baseball infrastructure and encouraged baseball's rapid development.

Single nucleotide mutation changes the capability of CCN3 in osteosarcoma cell invasion and differentiation.

This study aimed to identify significant mutations in CCN3 gene in osteosarcoma, and to explore the influence of this gene on cell invasion and differentiation and the underlying mechanism. Sanger sequencing was used to identify CCN3 gene sequence in human osteosarcoma cell lines, peripheral blood mononuclear cells (PBMC), and osteosarcoma tissues. Wild-type and mutant CCN3 (mCCN3) were ectopically expressed by lentivirus in human osteosarcoma cell lines. Tumor cell invasion was measured by trans-well assay. Osteogenic differentiation was induced by osteogenic differentiating medium and evaluated based on alkaline phosphatase activity and collagen type I alpha 1 chain and osteocalcin expression. Western blotting was used to detect protein levels of CCN3 and mCCN3 in cytoplasmic, nuclear and secreted fractions of cells. A G-to-A single nucleotide mutation in the coding region of CCN3 was found in both osteosarcoma cells and tissues. The frequency of this mutation in osteosarcoma tissue was much higher than that in para-carcinoma tissue and PBMC of healthy people. This nucleotide mutation decreased nuclear glycosylated full length protein level of CCN3 and affected osteosarcoma cell invasion and differentiation. A lower nuclear ratio of glycosylated/non-glycosylated isoforms accounted for the different behavior of mCCN3 compared with CCN3. The G-to-A mutation identified in CCN3 resulted in differential glycosylated full-length protein levels and altered the functional role of CCN3 in osteosarcoma cell invasion and 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.