The myokine CCL5 recruits subcutaneous preadipocytes and promotes intramuscular fat deposition in obese mice.

Intramuscular fat (IMF) refers to the lipid stored in skeletal muscle tissue. The number and size of intramuscular adipocytes are the primary factors that regulate IMF content. Intramuscular adipocytes can be derived from either in situ or ectopic migration. In this study, it was discovered that the regulation of IMF levels is achieved through the chemokine (C-C motif) ligand 5 (CCL5)/chemokine (C-C motif) receptor 5 (CCR5) pathway by modulating adipocyte migration. In coculture experiments, C2C12 myotubes were more effective in promoting the migration of 3T3-L1 preadipocytes than C2C12 myoblasts, along with increasing CCL5. Correspondingly, overexpressing the CCR5, one of the receptors of CCL5, in 3T3-L1 preadipocytes facilitated their migration. Conversely, the application of the CCL5/CCR5 inhibitor, MARAVIROC (MVC), reduced this migration. In vivo, transplanted experiments of subcutaneous adipose tissue (SCAT) from transgenic mice expressing green fluorescent protein (GFP) provided evidence that injecting recombinant CCL5 (rCCL5) into skeletal muscle promotes the migration of subcutaneous adipocytes to the skeletal muscle. The level of CCL5 in skeletal muscle increased with obesity. Blocking the CCL5/CCR5 axis by MVC inhibited IMF deposition, whereas elevated skeletal muscle CCL5 promoted IMF deposition in obese mice. These results establish a link between the IMF and the CCL5/CCR5 pathway, which could have a potential application for modulating IMF through adipocyte migration.NEW & NOTEWORTHY C2C12 myotubes attract 3T3-L1 preadipocyte migration regulated by the chemokine (C-C motif) ligand 5 (CCL5)/ chemokine (C-C motif) receptor 5 (CCR5) axis. High levels of skeletal muscle-specific CCL5 promote the migration of subcutaneous adipocytes to skeletal muscle and induce the intramuscular fat (IMF) content.

Electropolymerization of Preferred-Oriented Conjugated Microporous Polymer Films for Enhanced Fluorescent Sensing.

High-quality conjugated microporous polymer (CMP) films with orientation and controlled structure are extremely desired for applications. Here, we report the effective construction of CMP 3D composite films (pZn/PTPCz) with a controlled porosity structure and preferred orientation using the template-assisted electropolymerization (EP) approach for the first time. The structure of pZn/PTPCz composite thin films and nitrophenol sensing performance were thoroughly studied. When compared to the control CMP film made on flat indium tin oxide (ITO) substrates, the as-prepared pZn/PTPCz composite films showed significantly enhanced fluorescent intensity and much better sensing performance for the model explosive. This was attributed to the metal-enhanced fluorescence (MEF) of porous nanostructured zinc (pZn) and the additional macroporosity of the pZn/PTPCz composite films. This work provides a feasible approach for creating oriented 3D CMP-based thin films for advanced applications.

HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression.

Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune checkpoint inhibitor therapy because of immune evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate immune cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes tumor immune evasion in a CD8+ T cell-dependent manner by activating STAT1/PD-L1 in tumor cells. Mechanistically, HKDC1 binds to and presents cytosolic STAT1 to IFNGR1 on the plasma membrane following IFNγ-stimulation by associating with cytoskeleton protein ACTA2, resulting in STAT1 phosphorylation and nuclear translocation. HKDC1 inhibition in combination with anti-PD-1/PD-L1 enhances in vivo T cell antitumor response in liver cancer models in male mice. Clinical sample analysis indicates a correlation among HKDC1 expression, STAT1 phosphorylation, and survival in patients with hepatocellular carcinoma treated with atezolizumab (anti-PD-L1). These findings reveal a role for HKDC1 in regulating immune evasion by coupling cytoskeleton with STAT1 activation, providing a potential combination strategy to enhance antitumor immune responses.

Novel supramolecular deep eutectic solvent pretreatment for obtaining fluorescent lignin and promoting biomass pyrolytic saccharification.

In this study, ß-CD was used as a receptor to prepare three novel SDES, which were used to pretreat corn stalks for obtaining fluorescent lignin and promoting biomass pyrolytic saccharification. It was found that GA-residue had a high cellulose retention ratio (94.63%) and the highest lignin removal ratio (61.78%). Besides, the yield of carbohydrates in bio-oil was increased from 0.63% to 49.37%, and fluorescent lignin was prepared for explosion detection, fluorescent film, and information encryption. It was confirmed that the weak interaction between ß-CD and HBDs or dimer was mainly performed by hydrogen bond and van der Waals force. The minimum frontier orbital energy difference ΔEU (0.1976 a.u.) and high binding energy (-5456.71 kJ/mol) between molecules were calculated by DFT. Moreover, the mechanism of biomass pretreatment was explored. The green and efficient SDES developed in this study were of great significance for biomass pretreatment and efficient utilization of components.

Mitochondria-localized cGAS suppresses ferroptosis to promote cancer progression.

A well-established role of cyclic GMP-AMP synthase (cGAS) is the recognition of cytosolic DNA, which is linked to the activation of host defense programs against pathogens via stimulator of interferon genes (STING)-dependent innate immune response. Recent advance has also revealed that cGAS may be involved in several noninfectious contexts by localizing to subcellular compartments other than the cytosol. However, the subcellular localization and function of cGAS in different biological conditions is unclear; in particular, its role in cancer progression remains poorly understood. Here we show that cGAS is localized to mitochondria and protects hepatocellular carcinoma cells from ferroptosis in vitro and in vivo. cGAS anchors to the outer mitochondrial membrane where it associates with dynamin-related protein 1 (DRP1) to facilitate its oligomerization. In the absence of cGAS or DRP1 oligomerization, mitochondrial ROS accumulation and ferroptosis increase, inhibiting tumor growth. Collectively, this previously unrecognized role for cGAS in orchestrating mitochondrial function and cancer progression suggests that cGAS interactions in mitochondria can serve as potential targets for new cancer interventions.

Safety and efficacy of thoracic endovascular aortic repair for acute Stanford type B aortic dissection with retrograde type A intramural hematoma.

OBJECTIVE: The aim of this study was to evaluate safety and efficacy of thoracic endovascular aortic repair (TEVAR) for acute Stanford type B aortic dissection (TBAD) with retrograde type A intramural hematoma (TAIMH). METHODS: Patients with acute TBAD with retrograde TAIMH treated with TEVAR between January 1, 2014, to March 31, 2022, were retrospectively reviewed. Aortic diameter and distance were measured using the 3D Slicer image computing platform. Patients' characteristics, procedural, in-hospital and follow-up data, and aortic remodeling were analyzed. RESULTS: Fifty-two patients (average age, 52.6 years; 42 males [80.8%]) were included. The median interval from symptom onset to TEVAR was 11 days (interquartile range, 7.0-16.8 days). The maximal diameter of the ascending aorta (AA) was <50 mm, and the hematoma thickness in the AA was ≤10 mm in all patients. Both the in-hospital and 30-day mortality rates were 0%. The 30-day complication rate was 11.5%. The overall cumulative survival rates were 100% at 1 year, 97.1% at 3 years, and 92.6% at 5 years. Four of 52 patients (7.7%) developed retrograde type A aortic dissection at 10 days to 4 months postoperatively, and one of 52 patients (1.9%) developed an isolated AA dissection 4 months postoperatively; these five patients were treated and alive at late follow-up in March 2022. The rates of cumulative freedom from thoracic aortic re-intervention were 93.7% at 1 year and 90.7% at 5 years. Positive AA remodeling was observed in 92.3% (48/52) of patients during follow-up. The maximal diameter of AA (mean ± standard error of mean) at admission was 42.7 ± 0.8 mm, which decreased to 39.5 ± 0.9 mm at last follow-up. The maximal AA hematoma thickness at admission was 7.6 ± 0.3 mm, which reduced to 2.2 ± 0.9 mm at last follow-up. CONCLUSIONS: For selected patients of acute Stanford TBAD with retrograde TAIMH, endovascular repair may be a safe, effective, and durable alternative treatment, if the maximum diameter of the AA is <50 mm and the intramural hematoma thickness in the AA is ≤10 mm.

Integration of Neuroscience and Entrepreneurship: A Systematic Review and Bibliometric Analysis.

In this study, we investigated the integration between neuroscience and entrepreneurship. First, we explored the concept of neuroentrepreneurship and the investigation of neuroentrepreneurship using scientific research methods. Second, we constructed a road map for entrepreneurial researchers interested in conducting neuroentrepreneurship-related research. This is an emerging research area; therefore, to more clearly analyze the dynamics of the research trends, we used a bibliometric method to capture patterns in current publications on subjects related to neuroentrepreneurship, examining papers published between 1999 and 2021 using the keywords "neuroscience" and "entrepreneurship" or "neuroentrepreneurship." To identify the keywords, we used two academic databases-the Social Science Citation Index and Science Citation Index-accessed through the Web of Science website. The three keywords were identified from studies integrating neuroscience with entrepreneurship. After carefully reviewing the research papers, we identified neuroentrepreneurship as a novel research area. The outcomes of this study provide a guide for describing the theoretical connection between neuroscience and entrepreneurship. In the future, this field of study should be empirically investigated.

Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation.

Mdfi, an inhibitor of myogenic regulatory factors, is involved in myoblast myogenic development and muscle fiber type transformation. However, the regulatory network of Mdfi regulating myoblasts has not been revealed. In this study, we performed microRNAs (miRNAs)-seq on Mdfi overexpression (Mdfi-OE) and wild-type (WT) C2C12 cells to establish the regulatory networks. Comparative analyses of Mdfi-OE vs. WT identified 66 differentially expressed miRNAs (DEMs). Enrichment analysis of the target genes suggested that DEMs may be involved in myoblast differentiation and muscle fiber type transformation through MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling pathways. miRNA-mRNA interaction networks were suggested along with ten hub miRNAs and five hub genes. We also identified eight hub miRNAs and eleven hub genes in the networks of muscle fiber type transformation. Hub miRNAs mainly play key regulatory roles in muscle fiber type transformation through the PI3K-Akt, MAPK, cAMP, and calcium signaling pathways. Particularly, the three hub miRNAs (miR-335-3p, miR-494-3p, and miR-709) may be involved in both myogenic differentiation and muscle fiber type transformation. These hub miRNAs and genes might serve as candidate biomarkers for the treatment of muscle- and metabolic-related diseases.

KDELR2 promotes breast cancer proliferation via HDAC3-mediated cell cycle progression.

BACKGROUND: Histone deacetylases (HDACs) engage in the regulation of various cellular processes by controlling global gene expression. The dysregulation of HDACs leads to carcinogenesis, making HDACs ideal targets for cancer therapy. However, the use of HDAC inhibitors (HDACi) as single agents has been shown to have limited success in treating solid tumors in clinical studies. This study aimed to identify a novel downstream effector of HDACs to provide a potential target for combination therapy. METHODS: Transcriptome sequencing and bioinformatics analysis were performed to screen for genes responsive to HDACi in breast cancer cells. The effects of HDACi on cell viability were detected using the MTT assay. The mRNA and protein levels of genes were determined by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. Cell cycle distribution and apoptosis were analyzed by flow cytometry. The binding of CREB1 (cAMP-response element binding protein 1) to the promoter of the KDELR (The KDEL (Lys-Asp-Glu-Leu) receptor) gene was validated by the ChIP (chromatin immunoprecipitation assay). The association between KDELR2 and protein of centriole 5 (POC5) was detected by immunoprecipitation. A breast cancer-bearing mouse model was employed to analyze the effect of the HDAC3-KDELR2 axis on tumor growth. RESULTS: KDELR2 was identified as a novel target of HDAC3, and its aberrant expression indicated the poor prognosis of breast cancer patients. We found a strong correlation between the protein expression patterns of HADC3 and KDELR2 in tumor tissues from breast cancer patients. The results of the ChIP assay and qRT-PCR analysis validated that HDAC3 transactivated KDELR2 via CREB1. The HDAC3-KDELR2 axis accelerated the cell cycle progression of cancer cells by protecting the centrosomal protein POC5 from proteasomal degradation. Moreover, the HDAC3-KDELR2 axis promoted breast cancer cell proliferation and tumorigenesis in vitro and in vivo. CONCLUSION: Our results uncovered a previously unappreciated function of KDELR2 in tumorigenesis, linking a critical Golgi-the endoplasmic reticulum traffic transport protein to HDAC-controlled cell cycle progression on the path of cancer development and thus revealing a potential therapeutical target for breast cancer.

Mdfi Promotes C2C12 Cell Differentiation and Positively Modulates Fast-to-Slow-Twitch Muscle Fiber Transformation.

Muscle development requires myoblast differentiation and muscle fiber formation. Myod family inhibitor (Mdfi) inhibits myogenic regulatory factors in NIH3T3 cells, but how Mdfi regulates myoblast myogenic development is still unclear. In the present study, we constructed an Mdfi-overexpression (Mdfi-OE) C2C12 cell line by the CRISPR/Cas9 system and performed RNA-seq on Mdfi-OE and wild-type (WT) C2C12 cells. The RNA-seq results showed that the calcium signaling pathway was the most significant. We also established the regulatory networks of Mdfi-OE on C2C12 cell differentiation and muscle fiber type transformation and identified hub genes. Further, both RNA-seq and experimental verification demonstrated that Mdfi promoted C2C12 cell differentiation by upregulating the expression of Myod, Myog, and Myosin. We also found that the positive regulation of Mdfi on fast-to-slow-twitch muscle fiber transformation is mediated by Myod, Camk2b, and its downstream genes, such as Pgc1a, Pdk4, Cs, Cox4, Acadm, Acox1, Cycs, and Atp5a1. In conclusion, our results demonstrated that Mdfi promotes C2C12 cell differentiation and positively modulates fast-to-slow-twitch muscle fiber transformation. These findings further our understanding of the regulatory mechanisms of Mdfi in myogenic development and muscle fiber type transformation. Our results suggest potential therapeutic targets for muscle- and metabolic-related diseases.

MiR-92b-3p inhibits proliferation and migration of C2C12 cells.

Skeletal muscle, a critical component of the mammalian body, is essential for normal body movement. miRNAs are well documented in gene post-transcription regulation in many biological processes, including muscle development and maintenance. miR-92b-3p, which is often associated with tumorigenesis, has never been explored in myoblast development. Here, we used murine-derived C2C12 myoblasts to explore the potential functions of miR-92b-3p in skeletal muscle development. Our results demonstrated that miR-92b-3p mimics inhibited C2C12 cell proliferation and migration, whereas miR-92b-3p inhibitor promoted C2C12 cell proliferation and migration. C2C12 cell differentiation was not affected by miR-92b-3p mimics, according to immunofluorescence and qPCR results. Serum- and glucocorticoid-induced kinase 3 (SGK3) was predicted and validated as a target of miR-92b-3p. Overexpression of SGK3 promoted C2C12 cell proliferation. SGK3 and miR-92b-3p formed a regulatory pathway to modulate C2C12 cell proliferation. In conclusion, miR-92b-3p inhibited C2C12 cell proliferation by targeting SGK3 and impeded C2C12 cell migration.

The efficacy of bidirectional barbed sutures for incision closure in total knee replacement: A protocol of randomized controlled trial.

BACKGROUND: Barbed suture is a novel type of suture introduced in different surgical specialties. Nevertheless, its effect in total knee replacement is still unclear in terms of wound complications and cost effectiveness. The purpose of the present work is to evaluate the safety and efficacy of bidirectional barbed suture in reducing postoperative wound complications in the patients undergoing total knee replacement. METHODS: This prospective, randomized, and controlled study was performed from January 2017 to December 2018. It was authorized via institutional review committee of Yuebei People's Hospital (GDYB1002189). Hundred participants were divided randomly into 2 groups, namely, control group (n = 50) and the study group (n = 50), respectively. All operations were performed using the Miller-Galante prosthesis (Zimmer; Warsaw, IN). For study groups, the joint capsule (Stratafix1-0) and subcutaneous (Stratafix2-0) and intracutaneous (Stratafix3-0) tissues were sutured by a bidirectional barbed suture. At the end, extra 4 to 5 stitches were made to avoid detachment and incision rupture. For control group: the joint capsule was sutured by a traditional absorbable suture (Ethicon VICRYL* Plus 1-0), and the subcutaneous tissue was sutured by an absorbable suture (Ethicon VICRYL* Plus 2-0). The skin was sutured by staples. Incision length, suture time, operation time, postoperative length of hospital stay, and incision complications (such as effusion, infection, hematoma, and skin necrosis) were recorded. All data analyses are implemented through utilizing SPSS for Windows Version 20.0. RESULTS: The results will be shown in Table 1. CONCLUSION: This study can reach a reliable evidence for utilizing bidirectional barbed suture in wound closure in total knee replacement. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5823).