Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

Transperineal pelvic drainage combined with lateral position to promote perineal wound healing after abdominoperineal resection: A prospective cohort trial

Background:For the rectal cancer <5 cm from anal margin, extralevator abdominoperineal resection (eAPR) has been accepted widely by surgeons. However, the rate of perineal infection following up eAPR is approximately 70%. We did the study with the aim of evaluating the effect and safety of transperineal pelvic drainage combined with lateral position (TPDLP) on perineal wound in patients undergoing eAPR.Methods:Patients were randomly assigned to N-TPDLP group (standard arm) or TPDLP group (intervention arm). In the standard arm, surgery was completed after abdominal drainage tube was placed in pelvic. Comparatively, an additional transperineal wound drainage tube was applied in the experimental arm. Postoperatively, patients of both 2 groups were informed not to sit to reduce perineal compression until the perineal wound healed. But lateral position was demanded in the intervention arm. The primary endpoint was the rate of uncomplicated perineal wound healing defined as a Southampton wound score of <2 at 30 days postoperatively. Patients were followed for 6 months.Results:In total, 60 patients were randomly assigned to standard arm (n = 31) and intervention arm (n = 29). The mean perineal wound healing time was 34.2 (standard deviation [SD] 10.9) days in TPDLP arm, which significantly differ from 56.4 (SD 34.1) in N-TPDLP arm (P = .001). At 30 days postoperatively, 3 (10%) of 29 patients undergoing TPDLP were classified into grade 4 according to Southampton wound score, however, 16 (52%) of 31 patients were classified into grade 4 in control arm, and significantly difference was observed between randomization groups (P = .001). What''s more, perineal wound pain was assessed at 30 days postoperatively, and it is discovered that the pain degree of patients in control arm was significantly more severe than the interventive arm (P = .015).Conclusion:In the present study, we found that TPDLP generated a favorable prognosis for perineal wounds with acceptable side-effects.     

Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes

Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes. TNFalpha promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNFalpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFalpha induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases.     

Experimental-Numerical Study on the Flexural Ultimate Capacity of Prestressed Concrete Box Girders Subjected to Collision

Precise evaluation for flexural ultimate capacity of bridges which are subjected to the collision of over-height trucks is essential for making decisions on corresponding maintenance, strengthening or replacement. When the span of a cross-line continuous bridge with a double-box girder was hit by an overly high vehicle, the concrete floor of one girder was severely damaged, and part of the prestressed strands and reinforcements in the girder were broken. After the double-box girder was removed and separated into two single box girders, the ultimate flexural capacity of both box girders was studied by destructive tests, and a comparison was made between the damaged and undamaged girders. Moreover, finite element analysis was conducted to simulate the failure process. The results show that the flexural bearing capacity of the damaged box girder decreased by 33%, but it was still 1.07 times greater than the design bearing capacity, which basically meets the design requirements. Also, the damaged box girder showed a desirable serviceable limit state for three-axle vehicles and five-axle vehicles, but showed an undesirable serviceable limit state for six-axle vehicles. This study shows that repairing or strengthening the damaged span may be better than demolishing and rebuilding the whole superstructure bridge.     

Veganism does not reduce the risk of the metabolic syndrome in a Taiwanese cohort

The purpose of the present study was to assess the risk of the metabolic syndrome (MS) with vegan, pescovegetarian, lactovegetarian and nonvegetarian diets in Taiwan. The design was a retrospective cohort study using secondary data analysis from a Taiwan longitudinal health check-up database provided by MJ Health Screening Center during 1996-2006. A total of 93209 participants were classified as vegans (n=1116), pescovegetarians (n=2461), lactovegetarians (n=4313) and nonvegetarians (n=85319) by food frequency list of self-administered questionnaire at baseline. The association between MS or MS components and different dietary groups was evaluated using Cox proportional-hazards regression models with adjustment for confounders. During the mean 3.75 years of follow up, a total 8006 MS incident cases occurred and the incidence of MS was 229 (95% CI, 224, 234) per 10000 person year. Compared with vegans, hazard ratios of MS for nonvegetarians, pescovegetarians, lactovegetarians were 0.75 (95% CI, 0.64, 0.88), 0.68 (95% CI, 0.55, 0.83) and 0.81 (95% CI, 0.67, 0.97) after adjusting for sex, age, education status, smoking status, drinking status, physical activity at work and leisure, respectively. As for MS components, nonvegetarians and pescovegetarians had 0.72 (95% CI, 0.62, 0.84), 0.70 (95% CI, 0.57, 0.84) times risk of developing low high density lipoprotein cholesterol (HDL-C), while nonvegetarians had 1.16 (95% CI, 1.02, 1.32) times risk of developing high fasting plasma glucose. Our data suggest that the vegan diets did not decrease the risk of metabolic syndrome compared with pescovegetarian, lactovegetarian and nonvegetarian diets in a Taiwanese cohort.     

Study on the Polycrystalline Mechanism of Polycrystalline Diamond Synthesized from Graphite by Direct Detonation Method

In this paper, a polycrystalline diamond was synthesized by the direct detonation method using graphite as the carbon source. By comparing the numbers of the obtained diamond particles and the original graphite particles, it was found that when the graphite phase transformed into the polycrystalline diamond during the detonation process, a single graphite particle would form multiple diamond nuclei, and the nuclei would grow simultaneously to form polycrystals. Accordingly, a validation experiment was designed, which added different ratios of inert additives while keeping the ratio of graphite to hexogen (RDX) unchanged. It was found that increasing the ratio of inert additives within a certain range could increase the grain size of a polycrystalline diamond, which is consistent with the obtained polycrystalline mechanism.     

Abnormal Micronutrient Intake Is Associated with the Risk of Periodontitis: A Dose–response Association Study Based on NHANES 2009–2014

The association between micronutrient intake and the risk of periodontitis has received much attention in recent years. However, most studies focused on the linear relationship between them. This study aimed to explore the dose–response association between micronutrient intake and periodontitis. A total of 8959 participants who underwent a periodontal examination, and reported their micronutrient intake levels were derived from the US National Health and Nutrition Examination Survey (NHANES, 2009–2014) database. Logistic regression was performed to evaluate associations between micronutrient intake and periodontitis after propensity score matching (PSM), and restricted cubic splines (RCS) analysis was conducted to explore the dose–response associations. Following PSM, 5530 participants were included in the RCS analysis. The risk of periodontitis was reduced with sufficient intake of the following micronutrients: vitamin A, vitamin B1, vitamin B2, and vitamin E. In addition, the risk of periodontitis was increased with excessive intake of the following micronutrients: vitamin B1 (1.8 mg/day, males; 1.3 mg/day, females), vitamin C (90 mg/day, males), and copper (1.1 mg/day, combined). In conclusion, a linear association was found between vitamin A, vitamin B2, vitamin C, and copper and periodontitis—namely, a sufficient intake of vitamin A and vitamin B2 might help reduce the prevalence of periodontitis; by contrast, a high intake of vitamin C and copper increased the risk. In addition, a nonlinear dose–response association was found for the incidence of periodontitis with vitamin B1 and vitamin E. When within reasonable limits, supplemental intake helped reduce the prevalence of periodontitis, while excessive intake did not help significantly and might even increase the risk. However, confounding factors, such as health awareness, should still be considered.