Gas explosion characteristics and spray control mechanism in underground square.

The spray system mechanism during a gas explosion in an underground square pipeline is complex. In this paper, the underground square of Fuxin City is selected as the research object. FLACS numerical simulation software is used to analyze the spatial and temporal distribution characteristics of a gas explosion in an underground square pipeline with an unopened spray system using combustion and combustion rate models. Different spray pressures were compared and analyzed to determine the optimal spray control pressure, and the spray system mechanism was clarified. The results revealed that the gas explosion overpressure is divided into the overpressure gentle, overpressure rising, and overpressure decay stages, corresponding to a trend of rapid growth and slow decline. The influence of spray pressure on the gas explosion exhibits a promotion-inhibition-promotion trend, corresponding to 0-0.2 MPa, 0.2-0.6 MPa, and 0.6-1.6 Mpa, respectively. The peak overpressure and overpressure propagation rates are the lowest at 0.6 MPa, and the explosion suppression effect is the most pronounced. The spray system mechanism varies with the explosion overpressure stages. Generally, the time to peak value, that is, the peak time, the overall duration of the explosion, and the duration of the explosion stage decrease, whereas the peak explosion overpressure decreases.

Comparison of rehabilitation outcomes between robot-assisted and freehand screw placement in treatment of femoral neck fractures: a systematic review and meta-analysis.

PURPOSE: To compare the postoperative rehabilitation of femoral neck fractures treated with robot-assisted nailing and freehand nailing. METHODS: We systematically searched the PubMed, EMBASE, Cochrane, China National Knowledge Infrastructure(CNKI), WanFang database, China Science and Technology Journal Database (VIP) and Web of Science databases to identify potentially eligible articles. Indispensable data such as the year of publication, country, study type, robot type, age, number of patients, sex distribution, study design, and outcome indicators were extracted. The outcome indicators of interest included healing rate, length of healing time, Harris score, operation time, frequency of X-ray fluoroscopy, frequency of guide pin insertion, and intraoperative blood loss. RevMan 5.4.1 was used for the meta-analysis. RESULTS: Fourteen studies with 908 participants were included in this meta-analysis. The results showed that in terms of healing rate (SMD = 2.75, 95% CI, 1.03 to 7.32, P = 0.04) and Harris score (SMD = 2.27, 95% CI, 0.79 to 3.75, P = 0.003), robot-assisted screw placement technique scores were higher than the traditional freehand technique. Additionally, operative time (SMD = -12.72, 95% CI, -19.74 to -5.70, P = 0.0004), healing time (SMD = -13.63, 95% CI, -20.18 to -7.08, P < 0.0001), frequency of X-ray fluoroscopy (SMD = - 13.64, 95% CI, - 18.32 to - 8.95, P < 0.00001), frequency of guide pin insertion (SMD = - 7.95, 95% CI, - 10.13 to - 5.76, P < 0.00001), and intraoperative blood loss (SMD = - 17.33, 95% CI, - 23.66 to - 11.00, P < 0.00001) were lower for patients who underwent robotic-assisted screw placement than those for patients who underwent the conventional freehand technique. CONCLUSION: Compared to the freehand nailing technique, robot-assisted nailing helps improve postoperative healing rates in patients with femoral neck fractures; shortens healing times; better restores hip function; reduces the number of intraoperative fluoroscopies, guides pin placements; reduces intraoperative bleeding; and increases perioperative safety.

Multi-objective pedestrian tracking method based on YOLOv8 and improved DeepSORT.

A multi-objective pedestrian tracking method based on you only look once-v8 (YOLOv8) and the improved simple online and real time tracking with a deep association metric (DeepSORT) was proposed with the purpose of coping with the issues of local occlusion and ID dynamic transformation that frequently arise when tracking target pedestrians in real complex traffic scenarios. To begin with, in order to enhance the feature extraction network's capacity to learn target feature information in busy traffic situations, the detector implemented the YOLOv8 method with a high level of small-scale feature expression. In addition, the omni-scale network (OSNet) feature extraction network was then put on top of DeepSORT in order to accomplish real-time synchronized target tracking. This increases the effectiveness of picture edge recognition by dynamically fusing the collected feature information at various scales. Furthermore, a new adaptive forgetting smoothing Kalman filtering algorithm (FSA) was created to adapt to the nonlinear condition of the pedestrian trajectory in the traffic scene in order to address the issue of poor prediction attributed to the linear state equation of Kalman filtering once more. Afterward, the original intersection over union (IOU) association matching algorithm of DeepSORT was replaced by the complete-intersection over union (CIOU) association matching algorithm to fundamentally reduce the target pedestrians' omission and misdetection situation and to improve the accuracy of data matching. Eventually, the generalized trajectory feature extractor model (GFModel) was developed to tightly merge the local and global information through the average pooling operation in order to get precise tracking results and further decrease the impact of numerous disturbances on target tracking. The fusion algorithm of YOLOv8 and improved DeepSORT method based on OSNet, FSA and GFModel was named YOFGD. According to the experimental findings, YOFGD's ultimate accuracy can reach 77.9% and its speed can reach 55.8 frames per second (FPS), which is more than enough to fulfill the demands of real-world scenarios.

M2 macrophages secrete glutamate-containing extracellular vesicles to alleviate osteoporosis by reshaping osteoclast precursor fate.

Osteoclast precursors (OCPs) are thought to commit to osteoclast differentiation, which is accelerated by aging-related chronic inflammation, thereby leading to osteoporosis. However, whether the fate of OCPs can be reshaped to transition into other cell lineages is unknown. Here, we showed that M2 macrophage-derived extracellular vesicles (M2-EVs) could reprogram OCPs to downregulate osteoclast-specific gene expression and convert OCPs to M2 macrophage-like lineage cells, which reshaped the fate of OCPs by delivering the molecular metabolite glutamate. Upon delivery of glutamate, glutamine metabolism in OCPs was markedly enhanced, resulting in the increased production of α-ketoglutarate (αKG), which participates in Jmjd3-dependent epigenetic reprogramming, causing M2-like macrophage differentiation. Thus, we revealed a novel transformation of OCPs into M2-like macrophages via M2-EVs-initiated metabolic reprogramming and epigenetic modification. Our findings suggest that M2-EVs can reestablish the balance between osteoclasts and M2 macrophages, alleviate the symptoms of bone loss, and constitute a new approach for bone-targeted therapy to treat osteoporosis.

Mechanism Analysis for the Enhancement of Low-Temperature Impact Toughness of Nodular Cast Iron by Heat Treatment.

The low-temperature impact toughness of nodular cast iron can be significantly enhanced by heat treatment, and thus meet the severe service requirements in the fields of high-speed rail and power generation, etc. In order to explore the enhancement mechanism, microstructure, hardness, composition and other characteristics of as-cast and heat-treated nodular cast iron is systematically tested and compared by optical microscopy, microhardness tester, EBSD, SEM, electron probe, and impact toughness testing machine in this study. The results show that heat treatment has little effect on the morphology and size of graphite in nodular cast iron, ignores the effect on the grain size, morphology, and distribution of ferritic matrix, and has little effect on the hardness and exchange of elements, while it is meaningful to find that heat treatment brings about significant decrease in high-angle grain boundaries (HAGB) between 59° and 60°, decreasing from 10% to 3%. Therefore, the significant enhancement of low-temperature impact toughness of nodular cast iron by heat treatment may result from the obvious decrease in HAGB between 59° and 60°, instead of other reasons. From this perspective, the study can provide novel ideas for optimizing the heat treatment process of nodular cast iron.

[Research progress in influence of microstructure on performance of triply-periodic minimal surface bone scaffolds].

Objective: To summarize the influence of microstructure on performance of triply-periodic minimal surface (TPMS) bone scaffolds. Methods: The relevant literature on the microstructure of TPMS bone scaffolds both domestically and internationally in recent years was widely reviewed, and the research progress in the imfluence of microstructure on the performance of bone scaffolds was summarized. Results: The microstructure characteristics of TPMS bone scaffolds, such as pore shape, porosity, pore size, curvature, specific surface area, and tortuosity, exert a profound influence on bone scaffold performance. By finely adjusting the above parameters, it becomes feasible to substantially optimize the structural mechanical characteristics of the scaffold, thereby effectively preempting the occurrence of stress shielding phenomena. Concurrently, the manipulation of these parameters can also optimize the scaffold's biological performance, facilitating cell adhesion, proliferation, and growth, while facilitating the ingrowth and permeation of bone tissue. Ultimately, the ideal bone fusion results will obtain. Conclusion: The microstructure significantly and substantially influences the performance of TPMS bone scaffolds. By deeply exploring the characteristics of these microstructure effects on the performance of bone scaffolds, the design of bone scaffolds can be further optimized to better match specific implantation regions.

[Research progress on the design of bone scaffolds with different single cell structures].

Objective: To review the research progress of design of bone scaffolds with different single cell structures. Methods: The related literature on the study of bone scaffolds with different single cell structures at home and abroad in recent years was extensively reviewed, and the research progress was summarized. Results: The single cell structure of bone scaffold can be divided into regular cell structure, irregular cell structure, cell structure designed based on topology optimization theory, and cell structure designed based on triply periodic minimal surface. Different single cell structures have different structural morphology and geometric characteristics, and the selection of single cell structure directly determines the mechanical properties and biological properties of bone scaffold. It is very important to choose a reasonable cell structure for bone scaffold to replace the original bone tissue. Conclusion: Bone scaffolds have been widely studied, but there are many kinds of bone scaffolds at present, and the optimization of single cell structure should be considered comprehensively, which is helpful to develop bone scaffolds with excellent performance and provide effective support for bone tissue.

The integration of machine learning and multi-omics analysis provides a powerful approach to screen aging-related genes and predict prognosis and immunotherapy efficacy in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly malignant tumor with high incidence and mortality rates. Aging-related genes are closely related to the occurrence and development of cancer. Therefore, it is of great significance to evaluate the prognosis of HCC patients by constructing a model based on aging-related genes. METHOD: Non-negative matrix factorization (NMF) clustering analysis was used to cluster the samples. The correlation between the risk score and immune cells, immune checkpoints, and Mismatch Repair (MMR) was evaluated through Spearman correlation test. Real Time Quantitative PCR (RT-qPCR) and immunohistochemistry were used to validate the expression levels of key genes in tissue and cells for the constructed model. RESULT: By performing NMF clustering, we were able to effectively group the liver cancer samples into two distinct clusters. Considering the potential correlation between aging-related genes and the prognosis of liver cancer patients, we used aging-related genes to construct a prognostic model. Spearman correlation analysis showed that the model risk score was closely related to MMR and immune checkpoint expression. Drug sensitivity analysis also provided guidance for the clinical use of chemotherapy drugs. RT-qPCR showed that TFDP1, NDRG1, and FXR1 were expressed at higher levels in different liver cancer cell lines compared to normal liver cells. CONCLUSION: In summary, we have developed an aging-related model to predict the prognosis of hepatocellular carcinoma and guide clinical drug treatment for different patients.

Comparison of short-term clinical outcomes between robot-assisted and freehand pedicle screw placement in spine surgery: a meta-analysis and systematic review.

STUDY DESIGN: Meta-analysis and systematic review. BACKGROUND: Robot-assisted pedicle screw placement technique offers greater accuracy than the traditional freehand screw placement technique. However, it is controversial whether there is a difference between the two procedures in terms of improved clinical outcomes. MATERIALS AND METHODS: We systematically searched PubMed, EMBASE, Cochrane, and Web of Science to identify potentially eligible articles. Indispensable data such as the year of publication, study type, age, number of patients, sex distribution, and outcomes were extracted. The outcome indicators of interest included Oswestry disability index (ODI), visual analog scale (VAS) score, operative time, intraoperative blood loss, and post-operative length of stay. RevMan 5.4.1 was used for the meta-analysis. RESULTS: A total of eight studies with 508 participants were included. Eight were related to ΔVAS, six were related to ΔODI, seven were related to operative time, five were related to intraoperative blood loss, and seven were related to the length of hospitalization. The results showed that, in terms of ΔVAS (95% CI, -1.20 to -0.36, P = 0.0003) and ΔODI (95% CI, -2.50 to -0.48, P = 0.004), robot-assisted pedicle screw placement technique scored higher than traditional freehand technique. Additionally, the intraoperative blood loss (95% CI, -140.34 to -10.94, P = 0.02) and the length of hospitalization (95% CI, -2.59 to -0.31, P = 0.01) for patients who underwent robotic-assisted pedicle screw placement were less than that of those who underwent the conventional freehand screw placement. No significant difference was found between robot-assisted techniques and conventional freehand techniques in pedicle screw placement in surgical time (95% CI, -2.24 to 26.32, P = 0.10). CONCLUSIONS: Robot-assisted technique helps improve short-term clinical outcomes, reduce intraoperative blood loss and patient suffering, and shorten recovery time compared to the freehand technique.

Case report: Idiopathic pulmonary fibrosis induced by nab-paclitaxel: A rare complication.

Background: Ovarian cancer is one of the deadliest gynecological cancers, with the most advanced disease and poor survival. Although BRCA genes play a key role in maintaining genomic stability and providing the possibility of clinically individualized treatments, with the emergence of new and more appropriate treatment options, new treatment-related adverse events are challenging and difficult for clinicians. Case presentation: An 80-year-old Chinese woman was diagnosed with stage IIIC ovarian high-grade serous adenocarcinoma (CT3cN1MX) with BRCA2 as the causative gene. She underwent three courses of neoadjuvant chemotherapy with nab-paclitaxel 400 mg and carboplatin 450 mg before surgery. Chest HRCT prior to chemotherapy demonstrated bilateral interstitial pneumonia. During chemotherapy, there were four episodes of dry cough, shortness of breath, dyspnea, and three episodes of bone marrow suppression. The symptoms became intermittent and progressively worse, and after three sessions of empirical cough and phlegm relief, oxygen inhalation, corticosteroids, anti-infectives, and leukopenia therapy, the symptoms became intermittent and progressively worse. The diagnosis of idiopathic pulmonary fibrosis came a week after the third round of chemotherapy. After a strong dose of corticosteroids and nintedanib anti-fibrosis therapy, the pulmonary symptoms abated, and intermediate tumor starvation was performed. The combination therapy was subsequently discontinued, and the patient experienced significant relief from pulmonary symptoms. Treatment response was positive following single-agent nab-paclitaxel 400 mg chemotherapy in combination with nintedanib 150 mg anti-fibrosis therapy. Conclusion: In this report, we describe a rare case of idiopathic pulmonary fibrosis associated with the use of nab-paclitaxel and carboplatin in ovarian cancer. During treatment, it is necessary to maintain a high level of vigilance for patients with interstitial pneumonia and engage the attention of clinicians to improve medication safety. Early diagnosis and anti-fibrosis therapy can reverse lung damage.

Clinical and Pathological Features of Hydroa Vacciniforme-Like Lymphoproliferative Disorder Along with Risk Factors Indicating Poor Prognosis.

Purpose: To examine the clinical and pathological features, laboratory markers, therapeutic options and risk factors indicating poor prognosis of hydroa vacciniforme-like lymphoproliferative disorder (HVLPD). Patients and Methods: Seven patients with HVLPD had their clinical and pathological data collected. Immunohistochemical staining, Epstein-Barr virus-encoded RNA (EBER) in situ hybridization experiments, T-cell receptor (TCR) gene rearrangement, RT-PCR tests and the Elisa assay were carried out. Results: The main clinical manifestations were papulovesicular lesions and ulcers on the face, neck, or trunk. Five cases had systemic symptoms. Three of the deceased patients had significant facial edema, deep body necrosis, and ulceration. The pathological results demonstrated that lymphocytes infiltrated blood vessels and sweat glands in addition to the dermis and subcutaneous tissues. All patients tested positive for CD3 and EBER. Six cases tested positive for TCRßF1, but none tested positive for TCRδ. TCRγ monoclonal rearrangement, strongly positive expression of TIA-1 and a Ki67 proliferation index of 40% occurred in 3 fatal cases. When compared to the survival group, the plasma EBV DNA in the deceased group was considerably higher (P<0.05). IFN-γ and TNF-α cytokine levels in patients were higher than in the control group, particularly in the deceased group (P<0.05). The skin lesions on all patients recovered quickly underwent conservative care. Nonetheless, 3 patients passed away as the disease progressed in its latter stages. Conclusion: In our cases, the main infiltrating cells were T cells and the dominant lymphocyte subclass was αßT cells. A significant increase in lgE level, plasma EBV DNA, IFN-γ, and TNF-α cytokine levels, decreased hemoglobin level, strongly positive expression of TIA-1, high Ki67 proliferation index, and positive TCR gene rearrangement are all indicators of a poor prognosis.

Mo2TiC2 MXene-Supported Ru Clusters for Efficient Photothermal Reverse Water-Gas Shift.

Driving metal-cluster-catalyzed high-temperature chemical reactions by sunlight holds promise for the development of negative-carbon-footprint industrial catalysis, which has yet often been hindered by the poor ability of metal clusters to harvest and utilize the full spectrum of solar energy. Here, we report the preparation of Mo2TiC2 MXene-supported Ru clusters (Ru/Mo2TiC2) with pronounced broadband sunlight absorption ability and high sintering resistance. Under illumination of focused sunlight, Ru/Mo2TiC2 can catalyze the reverse water-gas shift (RWGS) reaction to produce carbon monoxide from the greenhouse gas carbon dioxide and renewable hydrogen with enhanced activity, selectivity, and stability compared to their nanoparticle counterparts. Notably, the CO production rate of MXene-supported Ru clusters reached 4.0 mol·gRu-1·h-1, which is among the best reported so far for photothermal RWGS catalysts. Detailed studies suggest that the production of methane is kinetically inhibited by the rapid desorption of CO from the surface of the Ru clusters.

Extracellular Vesicles in Bone Homeostasis: Emerging Mediators of Osteoimmune Interactions and Promising Therapeutic Targets.

An imbalance in bone homeostasis results in bone loss and poor healing in bone diseases and trauma. Osteoimmune interactions, as a key contributor to bone homeostasis, depend on the crosstalk between mesenchymal stem cell-osteoblast (MSC-OB) and monocyte-macrophage (MC-Mφ) lineages. Currently, extracellular vesicles (EVs) are considered to be involved in cell-to-cell communication and represent a novel avenue to enhance our understanding of bone homeostasis and to develop novel diagnostic and therapeutic options. In this comprehensive review, we aim to present recent advances in the study of the effect of MC-Mφ-derived EVs on osteogenesis and the regulatory effects of MSC-OB-derived EVs on the differentiation, recruitment and efferocytosis of Mφ. Furthermore, we discuss the role of EVs as crucial mediators of the communication between these cell lineages involved in the development of common bone diseases, with a focus on osteoporosis, osteoarthritis, bone fracture, and periodontal disease. Together, this review focuses on the apparent discrepancies in current research findings and future directions for translating fundamental insights into clinically relevant EV-based therapies for improving bone health.

Corrigendum: DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

[This corrects the article DOI: 10.3389/fonc.2021.629974.].

The increase of α-synuclein and alterations of dynein in A53T transgenic and aging mouse.

The dynein protein plays a key role in the degradation pathway by attaching to targeted molecules and transporting the autophagosome to the centrosome. Aging plays an important role in the pathogenesis of Parkinson's disease (PD), but its effect on dynein is not clear. In this study we analyzed behavioral characteristics using the rod endurance test and climbing rod time test in different aged mice (3 months, 12 months, 20 months), and measured protein expression of dynein, α-synuclein, Tctex-1, and LC3 in the substantianigra of the mice by Western blot. The mRNA levels of dynein, α-synuclein, LC3 and Tctex-1 were measured by quantitative real time reverse transcription PCR, and detecting expression of dynein and α-synuclein by immunofluorescence. We found the motor functions of A53T mutant mice, in 12 months and 20 months, decreased more significantly compared with normal mice (p < 0.05). In addition, the expression of dynein, LC3-Ⅱ and Tctex-1 proteins in the substantia nigra of the two groups decreased with age. However, α-synuclein protein increased gradually with age, with significantly higher levels in the PD groups compared with age matched controls (p < 0.05). These results were confirmed by immunofluorescence. Our data demonstrates that dynein and other autophagy proteins change with age, and this is associated with increased α-synuclein. Therefore, therapeutics that prevent dynein dysfunction may offer novel treatments for PD and other autophagy related diseases.

Mechanical and Acoustic Properties of Jute Fiber-Reinforced Polypropylene Composites.

Chemical fibers such as glass fiber and aramid cover a large proportion of sound-absorbing composite materials on the current commercial market. These materials possess superior mechanical properties but have the disadvantages of high production costs and energy consumption and difficult recovery and degradation. In this paper, jute fiber and polypropylene were selected as raw materials, and a series of jute fiber-reinforced polypropylene composite materials were prepared by a mixing-hot-pressing process. The acoustic and mechanical performances of the composites with different fiber contents and fiber residue ratios were discussed. The results showed that the sound absorption coefficient values increased with the increasing fiber content and decreasing residual gum ratio. The mechanical properties varied inversely with the residual gum rate. With the increase of fiber content, the tensile and bending strengths first increased and then decreased. Therefore, the jute fiber-reinforced polypropylene composites can possess favorable sound absorption performance with no mechanical property penalty by adjusting the parameters properly, demonstrating that the composite materials have promising applications in the acoustic field.

Correlation Analysis Between MTHFR C677T Polymorphism and Uterine Fibroids: A Retrospective Cohort Study.

BACKGROUND: Uterine fibroids(UF) are the most common benign tumors in women, with high incidence and unknown causes. We aimed to explore the correlation between Methylenetetra-hydrofolate reductase (MTHFR) C677T polymorphism and UF. METHODS: This is a retrospective cohort study. Data were collected from 2411 women detected for MTHFR C677T polymorphism in the Fifth Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. B-ultrasound (BU) and the first page of medical records were used to analyze whether they had ever been diagnosed with UF. The collected data were analyzed. Using the chi-square test and regression analysis to explore the correlation, and the risk factors was screened by multifactor logistic regression analysis. RESULTS: A total of 2411 pregnant women were in the MTHFR C677T polymorphism detection. Among them, 226(9.37%) were diagnosed as UF by BU or clinical diagnosis. The allele and genotype of MTHFR C677T were significantly different between the case and control group (p<0.05), and the distribution of the allele was following Hardy-Weinberg (H-W) equilibrium. Comparing with the wild-type (C/C), the mutant group (C/T+T/T) was more likely to form UF(OR,1.43;OR95%CI,1.07-1.89). After adjusting for confoundings, the heterozygous mutant (C/T) was more susceptible to UF than the wild-type (aOR,1.41;aOR95%CI,1.41-1.91). In the case group, BMI, gravidity and parity were not associated with the size and number of UF and the MTHFR C677T polymorphism (p>0.05). However, older maternal age was associated with the incidence of UF, especially the multiple UF (p<0.05). CONCLUSION: Our results found that MTHFR C677T polymorphism was associated with UF occurrence for the first time. This could imply that it may increase the risk of forming UF in women of gestational age.

DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production.

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.

Cardamonin induces G2/M arrest and apoptosis via activation of the JNK-FOXO3a pathway in breast cancer cells.

Cardamonin (CD), a naturally occurring chalcone isolated from large black cardamom, was previously reported to suppress the proliferation of breast cancer cells. However, its precise molecular anti-tumor mechanisms have not been well elucidated. In this study, we found that CD markedly inhibited the proliferation of MDA-MB 231 and MCF-7 breast cancer cells through the induction of G2/M arrest and apoptosis. Reactive oxygen species (ROS) plays a pivotal role in the inhibition of CD-induced cell proliferation. Treatment with N-acetyl-cysteine (NAC), an ROS scavenger, blocked CD-induced G2/M arrest and apoptosis in this study. Quenching of ROS by overexpression of catalase also blocked CD-induced cell cycle arrest and apoptosis. We showed that CD enhanced the expression and nuclear translocation of Forkhead box O3 (FOXO3a) via upstream c-Jun N-terminal kinase, inducing the expression of FOXO3a and its target genes, including p21, p27, and Bim. This process led to the reduction of cyclin D1 and enhancement of activated caspase-3 expression. The addition of NAC markedly reversed these effects, knockdown of FOXO3a using small interfering RNA also decreased CD-induced G2/M arrest and apoptosis. In vivo, CD efficiently suppressed the growth of MDA-MB 231 breast cancer xenograft tumors. Taken together, our data provide a molecular mechanistic rationale for CD-induced cell cycle arrest and apoptosis in breast cancer cells.

Transplantation of neuregulin 4-overexpressing adipose-derived mesenchymal stem cells ameliorates insulin resistance by attenuating hepatic steatosis.

IMPACT STATEMENT: Due to high-fat and high-sugar diets accompanied by sedentary lifestyles, diabetes has become a global epidemic. Literature findings suggest a potential therapeutic effect of Nrg4 on treating obesity-related metabolic disorders including type 2 diabetes (T2D). Adipose tissue-derived MSCs (ADSCs) were used in our study as they are abundant and can be harvested with minimally invasive procedures. In the end, our study reveals that ADSC transplantation improves glucose tolerance and metabolic balance in HFD-fed mice by multiple mechanisms, including upregulating GLUT4 expression and suppressing inflammation. More importantly, our study shows that Nrg4 overexpression could improve the efficacy of ADSCs in ameliorating insulin resistance (IR) and other obesity-related metabolic disorders, given the function of Nrg4 in attenuating hepatic lipogenesis. It would provide a new therapeutic strategy for the treatment of obesity, IR, and T2D.