Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21.

Spermidine exerts protective roles in obesity, while the mechanism of spermidine in adipose tissue thermogenesis remains unclear. The present study first investigated the effect of spermidine on cold-stimulation and ß3-adrenoceptor agonist-induced thermogenesis in lean and high-fat diet-induced obese mice. Next, the role of spermidine on glucose and lipid metabolism in different types of adipose tissue was determined. Here, we found that spermidine supplementation did not affect cold-stimulated thermogenesis in lean mice, while significantly promoting the activation of adipose tissue thermogenesis under cold stimulation and ß3-adrenergic receptor agonist treatment in obese mice. Spermidine treatment markedly enhanced glucose and lipid metabolism in adipose tissues, and these results were associated with the activated autophagy pathway. Moreover, spermidine up-regulated fibroblast growth factor 21 (FGF21) signaling and its downstream pathway, including PI3K/AKT and AMPK pathways in vivo and in vitro. Knockdown of Fgf21 or inhibition of PI3K/AKT and AMPK pathways in brown adipocytes abolished the thermogenesis-promoting effect of spermidine, suggesting that the effect of spermidine on adipose tissue thermogenesis might be regulated by FGF21 signaling via the PI3K/AKT and AMPK pathways. The present study provides new insight into the mechanism of spermidine on obesity and its metabolic complications, thereby laying a theoretical basis for the clinical application of spermidine.

A method based on improved ant colony algorithm feature selection combined with GWO-SVR model for predicting chlorophyll-a concentration in Wuliangsu Lake.

Chlorophyll-a (Chl-a) is an important parameter in water bodies. Due to the complexity of optics in water bodies, it is difficult to accurately predict Chl-a concentrations in water bodies by current traditional methods. In this paper, using Sentinel-2 remote sensing images as the data source combined with measured data, taking Wuliangsu Lake as the study area, a new intelligent algorithm is proposed for prediction of Chl-a concentration, which uses the adaptive ant colony exhaustive optimization algorithm (A-ACEO) for feature selection and the gray wolf optimization algorithm (GWO) to optimize support vector regression (SVR) to achieve Chl-a concentration prediction. The ant colony optimization algorithm is improved to select remote sensing feature bands for Chl-a concentration by introducing relevant optimization strategies. The GWO-SVR model is built by optimizing SVR using GWO with the selected feature bands as input and comparing it with the traditional SVR model. The results show that the usage of feature bands selected by the presented A-ACEO algorithm as inputs can effectively reduce complexity and improve the prediction performance of the model, under the condition of the same model, which can provide valuable references for monitoring the Chl-a concentration in Wuliangsu Lake.

Delayed Reconstruction of the Perforator Pedicle Propeller Flap after the Induced Membrane Technique for Gustilo IIIB Open Distal Tibial Fracture.

This study aimed to evaluate the safety and efficacy of delayed reconstruction of the perforator pedicle propeller flap after the induced membrane technique in the treatment of Gustilo IIIB open distal tibial fracture, and to evaluate the clinical outcome and complications of two different perforator pedicle propeller flaps.Thirty-four patients with Gustilo IIIB open distal tibial fractures treated by the induced membrane technique and delayed reconstruction of two different perforator pedicle propeller flaps from May 2017 to March 2022 were retrospectively analyzed. Patients were divided into two groups according to the different kinds of perforator pedicle propeller flaps covered. The operation required two stages. The Radiographic Union Score for Tibial fractures (RUST) was used to evaluate the healing of the tibial bone defect. The American Orthopaedic Foot and Ankle Society (AOFAS) score was used to evaluate ankle function. The complications associated with the technique were recorded.The number of serial debridements, excluding those performed during emergency and final operations, was a mean of 2.28 ± 0.83 in the PAPF group. The PAPF group had a mean bone defect length of 6.76 ± 0.69 cm, the median healing time of 13.11 ± 0.96 months, RUST score 12.68 ± 1.63, and AOFAS score of 84.12 ± 6.38. On the other hand the PTAPF group's mean bone defect length was 6.73 ± 0.95 cm, the median healing time 12.63 ± 1.46 months, RUST score 13.73 ± 1.53 and AOFAS score 82.79 ± 5.49. There were no observed significant differences the two groups in the number of serial debridements, bone defect length, bone union time, RUST score, or AOFAS score (p > 0.05). Flap size ranged from 9 × 6 cm2 to 14 × 7 cm2 in the PAPF group and from 9 × 6 cm2 to 13 × 7 cm2 in the PTAPF group. There were no severe complications such as flap-related complications or amputation. The differences in complications in the two groups were not statistically significant.In cases of severe open tibial fracture, the reconstructive method is important. When delayed reconstruction is inevitable, surgeons should first perform radical debridement, followed by vacuum sealing drainage as a bridging therapy; both PAPF and PTAPF can be considered for definitive soft tissue coverage.

Time-dependent effect of REV-ERBα agonist SR9009 on nonalcoholic steatohepatitis and gut microbiota in mice.

The circadian clock is involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), and the target pathways of many NASH candidate drugs are controlled by the circadian clock. However, the application of chronopharmacology in NASH is little considered currently. Here, the time-dependent effect of REV-ERBα agonist SR9009 on diet-induced NASH and microbiota was investigated. C57BL/6J mice were fed a high-cholesterol and high-fat diet (CL) for 12 weeks to induce NASH and then treated with SR9009 either at Zeitgeber time 0 (ZT0) or ZT12 for another 6 weeks. Pharmacological activation of REV-ERBα by SR9009 alleviated hepatic steatosis, insulin resistance, liver inflammation, and fibrosis in CL diet-induced NASH mice. These effects were accompanied by improved gut barrier function and altered microbial composition and function in NASH mice, and the effect tended to be stronger when SR9009 was injected at ZT0. Moreover, SR9009 treatment at different time points resulted in a marked difference in the composition of the microbiota, with a stronger effect on the enrichment of beneficial bacteria and the diminishment of harmful bacteria when SR9009 was administrated at ZT0. Therefore, the time-dependent effect of REV-ERBα agonist on NASH was partly associated with the microbiota, highlighting the potential role of microbiota in the chronopharmacology of NASH and the possibility of discovering new therapeutic strategies for NASH.

The correlation between blood-lipid ratio in the first trimester and large-for-gestational-age infants.

BACKGROUND: To investigate the correlation between maternal glucose and lipid metabolism indexes and blood-lipid ratio in the first trimester and large-for- gestational-age (LGA) infants. METHODS: Women in the first trimester of pregnancy who underwent regular obstetric examination in the obstetric outpatient department of the Affiliated Hospital of Chengde Medical College from June 2018 to March 2019 were included according to the standard. Basic information were collected based on questionnaires at the first visit of pregnant women, including early fasting blood glucose (FBG), fasting insulin (FINS), glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), apolipoprotein A1 (APO-A1), apolipoprotein B (APO-B), lipoprotein a (LP(a)), LDL/HDL, TG/HDL, TC/HDL, APO-B/APO-A1 ratio, birth weight of newborns, gestational age at delivery etc. RESULTS: A total of 418 cases were included for analysis. The incidence rate of LGA infants was 13.88%, and that of small-for-gestational-age (SGA) infants was 4.78%. Univariate analysis revealed that the age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, APO-B/APO-A1 between LGA group and appropriate-for-gestational-age (AGA) group were significantly different (P < 0.05); multivariate stepwise logistic regression analysis indicated that the correlation between maternal age, pre-pregnancy BMI, weight gain during pregnancy, APO-B/APO-A1 level and LGA were statistically significant (P < 0.05); compared with the reference range of APO-B/APO-A1 of 0.46-0.65, values < 0.46 and > 0.65 were protective factor of LGA (P < 0.05). The receiver operating curve(ROC) indicated that the area under the curve (AUC)s for predicting LGA using maternal age, pre-pregnancy BMI, weight gain during pregnancy, and early pregnancy APO-B/APO-A1 were 0.585, 0.606, 0.637, 0.531, respectively. The AUC for a combined prediction model was 0.742, showing greater predictive value than any other factors individually. CONCLUSION: Maternal age, pre-pregnancy BMI, weight gain during pregnancy, and APO-B/APO-A1 levels in first trimester are significant factors influencing the occurrence of LGA infants, and the combination of the four factors would have certain predictive value for LGA.

Treatment of gorham-stout disease with bisphosphonates and total hip arthroplasty: A case report.

Background: Gorham-Stout disease (GSD) is a rare osteolytic disease with unknown etiology, varied clinical manifestations and unpredictable prognosis. This disease is characterized by progressive massive local osteolysis and resorption caused by intraosseous lymphatic vessel structure and thin-walled vascular proliferation. The diagnosis of GSD has not yet formed a uniform standard, but the combination of clinical manifestations, radiological features and unique histopathological examinations and excluding other diseases contribute to early diagnosis. Although medical therapy, radiotherapy and surgical interventions or combinations have been used for the treatment of GSD, there is currently still no recommended standardized treatment regimen. Case report: This paper presents a case of a previously healthy 70-year-old man presented with a 10-year history of severe right hip pain and progressive walking disorder of the lower limbs. Based on the patient's clear clinical presentation, unique radiological features, and histological findings, a diagnosis of GSD was made with the exclusion of other potential diseases. The patient was treated with bisphosphonates to slow the progression of the disease followed by total hip arthroplasty to help restore walking function. At the 3-year follow-up, the patient returned to normal walking and no recurrence was observed. Conclusion: Bisphosphonates combined with total hip arthroplasty may be an effective method for the treatment of severe GSD in the hip joint.

Prediction of lake chlorophyll concentration using the BP neural network and Sentinel-2 images based on time features.

One of the most important indicators of lake eutrophication is chlorophyll-a (Chl-a) concentration, which is also an essential component of lake water quality monitoring. It is an efficient, economical and convenient method to monitor the Chl-a concentration through remote sensing images. Taking the Wuliangsuhai Lake as an example, the relevant bands of Sentinel-2 images were used as the input and the Chl-a concentration as the output to build neural network models. In the process of building the model, we mainly studied and tested the impact of adding time features to the model input on the model accuracy. Through the experiment, it was found that the month and day difference features of remote sensing images and Chl-a measurement could significantly improve the prediction accuracy of Chl-a concentration in varying degrees. Finally, it was determined that the neural network prediction model with 12 bands of Sentinel-2 images combined month features as inputs and one hidden layer, eight neurons and Chl-a concentration as outputs was the best. Then, the accuracy of the model was validated when the test set accounts for 20 and 30%, and good results were obtained.

Stellate ganglion block relieves acute lung injury induced by severe acute pancreatitis via the miR-155-5p/SOCS5/JAK2/STAT3 axis.

Acute lung injury (ALI), a prevalent complication of severe acute pancreatitis (SAP), is also a leading contributor to respiratory failure and even death of SAP patients. Here, we intended to investigate the function and mechanism of stellate ganglion block (SGB) in ameliorating SAP-induced ALI (SAP-ALI). We engineered an SAP-ALI model in rats and treated them with SGB. HE staining and the dry and wet method were implemented to evaluate pathological alterations in the tissues and pulmonary edema. The rats serum changes of the profiles of TNF-α, IL-6, IL-1ß, and IL-10 were examined. The profiles of miR-155-5p and SOCS5/JAK2/STAT3 were detected. Functional assays were performed for confirming the role of miR-155-5p in modulating the SOCS5/JAK2/STAT3 pathway in pulmonary epithelial cells. Our findings revealed that SGB vigorously alleviated SAP rat lung tissue damage and lung edema and lessened the generation of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß. SGB enhanced SOCS5 expression, hampered miR-155-5p, and suppressed JAK2/STAT3 pathway activation. As evidenced by mechanism studies, miR-155-5p targeted the 3'UTR of SOCS5 and repressed its expression, hence resulting in JAK2/STAT3 pathway activation. During animal trials, we discovered that SGB ameliorated SAP-ALI, boosted SOCS5 expression, and mitigated the levels of pro-inflammatory factors and miR-155-5p in the plasma. In vitro, miR-155-5p overexpression substantially facilitated pulmonary epithelial cell apoptosis, inflammation, and JAK2/STAT3 pathway activation and restrained SOCS5 expression. All in all, our work hinted that SGB could modulate the miR-155-5p/SOCS5/JAK2/STAT3 axis to alleviate SAP-ALI.

Compound dietary fiber and high-grade protein diet improves glycemic control and ameliorates diabetes and its comorbidities through remodeling the gut microbiota in mice.

Dietary intervention with a low glycemic index and full nutritional support is emerging as an effective strategy for diabetes management. Here, we found that the treatment of a novel compound dietary fiber and high-grade protein diet (CFP) improved glycemic control and insulin resistance in streptozotocin-induced diabetic mice, with a similar effect to liraglutide. In addition, CFP treatment ameliorated diabetes-related metabolic syndromes, such as hyperlipidemia, hepatic lipid accumulation and adipogenesis, systemic inflammation, and diabetes-related kidney damage. These results were greatly associated with enhanced gut barrier function and altered gut microbiota composition and function, especially those bacteria, microbial functions, and metabolites related to amino acid metabolism. Importantly, no adverse effect of CFP was found in our study, and CFP exerted a wider arrange of protection against diabetes than liraglutide. Thereby, fortification with balanced dietary fiber and high-grade protein, like CFP, might be an effective strategy for the management and treatment of diabetes.

Corrigendum to "SDF2L1 Inhibits Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma".

[This corrects the article DOI: 10.1155/2020/1970936.].

Construction of a full-length antibody phage display vector.

Antibody phage display technology plays an important role in the development of monoclonal antibodies, humanization, and affinity evolution of antibodies. Thus far, antibody phage display mainly focuses on the display of antibody variable region or antigen-binding fragments. In this study, we constructed a new phage display system that can display full-length IgG antibodies on M13 phage. The phage display vector contains open reading frames (ORFs) encoding full-length the heavy and light chains of the antibody. NcoI/XhoI restriction enzyme sites were used to clone the variable region of the heavy chain into the heavy chain ORF, and SalI/NotI sites were used to clone the light chain variable region. SnaBI and SbfI restriction enzyme sites were designed between the cloning sites of heavy and light chains, respectively, to increase the cloning efficiency. The full-length antibodies of nivolumab against programmed death factor 1, trastuzumab against human epidermal growth factor 2, diL2K against the cluster of differentiation 3 epsilon, and adalimumab against tumor necrosis factor- alpha were displayed on phage with the vector. Phage-displayed antibodies showed their original antigen-binding activity. An amber codon shifted the vector to express IgG in non-suppressed Escherichia coli. The heavy and light chains of the E. coli-expressed antibodies could be detected through western blotting, and the antigen-binding activity was confirmed using an enzyme-linked immunosorbent assay. Biopanning was carried out with a model phage display antibody library, and the results showed that the novel phage system could be used for antibody library construction and highly efficient antibody screening. The reported system is the first full-length antibody phage display system.

SDF2L1 Inhibits Cell Proliferation, Migration, and Invasion in Nasopharyngeal Carcinoma.

The purpose of this study was to explore the relationship between stromal cell-derived factor 2-like 1 (SDF2L1) and nasopharyngeal carcinoma (NPC). 12 NPC tissues and 12 chronic nasopharyngitis tissues were involved in our study. Quantitative real-time PCR (qRT-PCR) and Western Blot were utilized to detect the expression of SDF2L1. Besides, immunofluorescence analysis was utilized to determine the protein expression of 97 paraffin-embedded NPC tissues and 58 nasopharyngitis tissues. Biological functional experiment included Cell Counting Kit-8 (CCK-8) assay, cell clone formation assay, cell scratch migration assay, Transwell migration assay, and Transwell invasion assay. All data were analyzed by SPSS. Results showed that downexpression of SDF2L1 was prominently present in NPC tissues and cells. Furthermore, silencing the expression of SDF2L1 promoted NPC proliferation, migration, and invasion in vitro, while overexpression of SDF2L1 has the opposite effect. In conclusion, SDF2L1 may act as a cancer suppressor gene, play a crucial role in the occurrence and development of NPC, and be a new therapeutic target or prognostic indicator for NPC.

TPPP3 Associated with Prognosis and Immune Infiltrates in Head and Neck Squamous Carcinoma.

Tubulin polymerization promoting protein family member 3 (TPPP3) is a kind of protein that can mediate the dynamics and stability of microtubules. However, the correlations of TPPP3 between prognosis and immune infiltrates in different tumors are still unclear. The analysis of TPPP3 expression was performed via Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) website. We also used GEPIA to assess the impact of TPPPT3 on clinical outcomes. The related pathways involved in TPPP3 were analyzed by gene-set enrichment analysis (GSEA), and the correlation between TPPP3 and immune infiltration was studied by Tumor Immune Estimation Resource2.0 (TIMER 2.0). The TPPP3 expression was significantly reduced in head and neck squamous carcinoma (HNSC) compared to adjacent tissues. In addition, the low expression of TPPP3 in HNSC was significantly associated with prognosis. The pathways closely related to the low expression of TPPP3 are "Antigen Processing and Presentation," "Primary Immunodeficiency," and so on. The TPPP3 expression was negatively correlated with the level of CD8+ T cell, B cell, and myeloid dendritic cell infiltration in HNSC. The TPPP3 expression is closely related to multiple immunomarkers in CD8+ T cell and Myeloid dendritic cells. These data indicate that TPPP3 is associated with multiple cancers and involves multiple immune-related pathways, and TPPP3 is associated with immune infiltration levels. Besides, the TPPP3 expression may help regulate tumor-associated CD8 + T cells, DC cells in HNSC. We conclude TPPP3 can be considered as a biomarker for predicting head and neck squamous cell carcinoma prognosis and immune infiltration.

Development of a fluorescent probe for the detection of hPD-L1.

Interaction of human programmed death factor-1 (hPD-1) of T cells and one of its ligands hPD-L1 which is expressed on cancer cells suppresses effector T cell functions. Studies showed that the hPD-1/hPD-L1 pathway is associated with killing mechanisms of tumor cells evading the immune system. Immunotherapy based on the checkpoint inhibitor on hPD-1 has been an important approach to treat cancer; however, not all cancer cells over-express hPD-L1. Detection of hPD-L1 over-expression in cancer cells may be a key factor for deciding on whether immunotherapy should be conducted. In the present study, we produced recombinant hPD-1 using Escherichia coli, and created a fluorescent probe termed quenched hPD-1 (QPD-1) for the detection of hPD-L1. We found that hPD-1 can quench fluorescence of carboxytetramethylrhodamine labeled on its N-terminal and QPD-1 is a convenient tool to rapidly detect hPD-L1 with a limit of detection of 10 nM and detectable range of 10 nM-1000 nM. QPD-1 may also function as a probe to screen for hPD-L1 over-expressing tumor cells and promote appropriate medical procedure through tumor immunotherapy.

Clinical significance of serum bilirubin in primary Sjögren syndrome patients.

OBJECTIVE: The purpose of our research was to demonstrate the clinical significance of serum bilirubin in primary Sjögren syndrome patients (pSS). PATIENTS AND METHODS: A total of 116 patients with primary Sjögren syndrome and 138 matched individuals were included in our study. The laboratory parameters of patients with pSS and healthy controls were retrospectively analyzed. RESULTS: Serum total bilirubin, direct bilirubin, and indirect bilirubin were significantly reduced (P < .001, P = .001, P < .001) while ESR was significantly increased (P < .001) in patients with pSS when compared with healthy checkup individuals. Statistically, the AUC in patients with pSS is as follows: TBIL = 0.77, P < .001, cutoff value = 7.96; DBIL = 0.617, P = .001 cutoff value = 2.2; and IBIL = 0.786, P < .001 cutoff value = 4.5. Furthermore, our study revealed that TBIL, DBIL, and IBIL were significantly negativity related to ESR (r = -.406, P < .001; r = -.206, P = .026; r = -.429, P < .001). Interestingly, multiple linear regression analysis showed that when adjusted for sex, age, ALT, and AST, the levels of TBIL, DBIL, and IBIL in patients with pSS were independently correlated with ESR. CONCLUSIONS: This study found that the levels of serum bilirubin were reduced and the inflammatory marker was elevated in patients with pSS. Additionally, serum bilirubin was negatively related with ESR and TBIL, DBIL, and IBIL can be used in the clinical diagnosis and follow-up visits of the patients with pSS.

Diagnostic value of hemoglobin and neutrophil-to-lymphocyte ratio in Behcet Disease.

The purpose of our study was to investigate the diagnostic value of NLR, hemoglobin (HB) and combine NLR with HB in the BD patients.Sixty-seven patients with BD were diagnosed in the rheumatology or dermatology between June 2015 and June 2019; 92 matching healthy physical examiners were included in our study. SPSS was used for statistical analysis.Compared with the healthy control, NLR was increased (P < .001), while the HB level was decreased (P < .001) in the patients of BD. In addition, ESR and CRP were increased in BD patients. NLR has no relationship with CRP and ESR, while the HB levels were negatively correlated with CRP and ESR (r = -0.293, P = .046; r = -0.431, P = .002). ROC curve analysis revealed the AUC of NLR and HB were 0.797 and 0.798 (P < .001). When combined NLR with HB, the AUC was 0.897 (P < .001). Besides, logistic regression analysis demonstrated that NLR and HB were independent risk factors in the BD patients.We observed that the diagnostic value of NLR, HB and combined NLR with HB in the BD patients were high, particularly when combine NLR with HB. NLR and HB were independent risk factors in the BD patients. In addition, HB levels related to the disease activity of BD patients.

A novel murine antibody and an open sandwich immunoassay for the detection of clenbuterol.

Clenbuterol (CLEN) is a sympathomimetic amine used as a decongestant and bronchodilator while treating breathing disorders. It is also used in food-producing animals as it improves the rate of red meat production. However, it is prohibited in many countries nowadays due to human health and safety concerns. Unfortunately, the illegal use of CLEN is still rampant. Thus, monitoring it in food and livestock is important. Here, we report a novel murine antibody and an open sandwich enzyme linked immunosorbent assay (OS-ELISA) to detect CLEN based on antigen-antibody reactions. The genes of antibody variable regions in mice immunized with CLEN conjugated with bovine serum albumin were cloned into a phagemid (pDong1/Fab) to construct a phage-display antibody library, from which a novel antibody, A12, was selected. Then, an OS-ELISA was developed to detect CLEN using separated variable regions of the A12 antibody. The limit of detection of the assay was found to be 8 ng/mL, which was useful for monitoring CLEN usage.

Natural silibinin modulates amyloid precursor protein processing and amyloid-ß protein clearance in APP/PS1 mice.

Silibinin has been shown to attenuate cognitive dysfunction and inhibit amyloid-beta (Aß) aggregation in Alzheimer's disease (AD) models. However, the underlying mechanism by which silibinin improves cognition remains poorly understood. In this study, we investigated the effect of silibinin on ß-secretase levels, Aß enzymatic degradation, and oxidative stress in the brains of APP/PS1 mice with cognitive impairments. Oral administration of silibinin for 2 months significantly attenuated the cognitive deficits of APP/PS1 mice in the Y-maze test, novel object recognition test, and Morris water maze test. Biochemical analyses revealed that silibinin decreased Aß deposition and the levels of soluble Aß1-40/1-42 in the hippocampus by downregulating APP and BACE1 and upregulating NEP in APP/PS1 mice. In addition, silibinin decreased the MDA content and increased the activities of the antioxidant enzymes CAT, SOD, and NO. Based on our findings, silibinin is a potentially promising agent for preventing AD-associated Aß pathology.

Low frequency pulsed electromagnetic field promotes differentiation of oligodendrocyte precursor cells through upregulation of miR-219-5p in vitro.

AIM: Spinal cord injury (SCI) is a common demyelinating disorder of the central nervous system. The differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), which induce myelination, plays a critical role in the functional recovery following SCI. In this study, the effect of low frequency pulsed electromagnetic field (PEMF) on the differentiation of OPCs and the potential underlying mechanisms were investigated. MAIN METHODS: OPCs were randomly divided into the PEMF and non-PEMF (NPEMF) groups. Immunofluorescence and western blot assays were performed to assess the expression levels of OLs stage-specific markers after 3, 7, 14, and 21 days of PEMF or NPEMF exposure. qRT-PCR was used to further assess the expression levels of miR-219-5p, miR-338, miR-138, and miR-9, which are associated with OPCs differentiation, and the expression levels of genes associated with miR-219-5p. Finally, following PEMF or NPEMF exposure, qRT-PCR and western blot assays were performed to explore the relationship between miR-219-5p and Lingo1 and between miR-219-5p and PEMF in promoting OPCs differentiation. KEY FINDINGS: PEMF promoted the differentiation of OPCs. PEMF upregulated the expression level of miR-219-5p and downregulated the expression level of Lingo1 during the differentiation of OPCs. Under PEMF exposure, miR-219-5p targeted Lingo1 and reversed the inhibitory effect of miR-219-5p inhibitor on OPCs differentiation. In addition, PEMF synergized with miR-219-5p to promote OPCs differentiation. SIGNIFICANCE: Our results, for the first time, indicated that PEMF promoted OPCs differentiation by regulating miR-219-5p activity in vitro.

Self-assembled ruthenium (II) metallacycles and metallacages with imidazole-based ligands and their in vitro anticancer activity.

Six tetranuclear rectangular metallacycles were synthesized via the [2+2] coordination-driven self-assembly of imidazole-based ditopic donor 1,4-bis(imidazole-1-yl)benzene and 1,3-bis(imidazol-1-yl)benzene, with dinuclear half-sandwich p-cymene ruthenium(II) acceptors [Ru2(µ-η4-oxalato)(η6-p-cymene)2](SO3CF3)2, [Ru2(µ-η4-2,5-dioxido-1,4-benzoquinonato)(η6-p-cymene)2](SO3CF3)2 and [Ru2(µ-η4-5,8-dioxido-1,4-naphtoquinonato)(η6-p-cymene)2](SO3CF3)2, respectively. Likewise, three hexanuclear trigonal prismatic metallacages were prepared via the [2+3] self-assembly of tritopic donor of 1,3,5-tri(1H-imidazol-1-yl)benzene with these ruthenium(II) acceptors respectively. Self-selection of the single symmetrical and stable metallacycle and cage was observed although there is the possibility of forming different conformational isomeric products due to different binding modes of these imidazole-based donors. The self-assembled macrocycles and cage containing the 5,8-dioxido-1,4-naphtoquinonato (donq) spacer exhibited good anticancer activity on all tested cancer cell lines (HCT-116, MDA-MB-231, MCF-7, HeLa, A549, and HepG-2), and showed decreased cytotoxicities in HBE and THLE-2 normal cells. The effect of Ru and imidazole moiety of these assemblies on the anticancer activity was discussed. The study of binding ability of these donq-based Ru assemblies with ctDNA indicated that the complex 9 with 180° linear 1 ligand has the highest bonding constant Kb to ctDNA.