One-Step Electrochemical Ethylene-to-Ethylene Glycol Conversion over a Multitasking Molecular Catalyst.

Ethylene glycol is an essential commodity chemical with high demand, which is conventionally produced via thermocatalytic oxidation of ethylene with huge fossil fuel consumption and CO2 emission. The one-step electrochemical approach offers a sustainable route but suffers from reliance on noble metal catalysts, low activity, and mediocre selectivity. Herein, we report a one-step electrochemical oxidation of ethylene to ethylene glycol over an earth-abundant metal-based molecular catalyst, a cobalt phthalocyanine supported on a carbon nanotube (CoPc/CNT). The catalyst delivers ethylene glycol with 100% selectivity and 1.78 min-1 turnover frequency at room temperature and ambient pressure, more competitive than those obtained over palladium catalysts. Experimental data demonstrate that the catalyst orchestrates multiple tasks in sequence, involving electrochemical water activation to generate high-valence Co-oxo species, ethylene epoxidation to afford an ethylene oxide intermediate via oxygen transfer, and eventually ring-opening of ethylene oxide to ethylene glycol facilitated by in situ formed Lewis acid site. This work offers a great opportunity for commodity chemicals synthesis based on a one-step, earth-abundant metal-catalyzed, and renewable electricity-driven route.

Application of Independent Component Analysis and Nelder-Mead Particle Swarm Optimization Algorithm in Non-Contact Blood Pressure Estimation.

In recent years, hypertension has become one of the leading causes of illness and death worldwide. Changes in lifestyle among the population have led to an increasing prevalence of hypertension. This study proposes a non-contact blood pressure estimation method that allows patients to conveniently monitor their blood pressure values. By utilizing a webcam to track facial features and the region of interest (ROI) for obtaining forehead images, independent component analysis (ICA) is employed to eliminate artifact signals. Subsequently, physiological parameters are calculated using the principle of optical wave reflection. The Nelder-Mead (NM) simplex method is combined with the particle swarm optimization (PSO) algorithm to optimize the empirical parameters, thus enhancing computational efficiency and accurately determining the optimal solution for blood pressure estimation. The influences of light intensity and camera distance on the experimental results are also discussed. Furthermore, the measurement time is only 10 s. The superior accuracy and efficiency of the proposed methodology are demonstrated by comparing them with those in other published literature.

[Ameliorative Effects of Cang-ai Volatile Oil on Left Ventricular Remodeling in Rats].

Objective: To evaluate with 7T cardiac magnetic resonance tissue tracking imaging (CMR-TT) the ameliorative effect of Cang-ai volatile oil (CAVO) on left ventricular remodeling (LVR) in rats induced by isoproterenol (ISO), and to make preliminary investigation into CAVO's effects on endothelial dysfunction in LVR. Methods: A total of 35 healthy male Sprague-Dawley (SD) rats were randomly assigned to two groups, the experimental group ( n=27) and the normal control group ( n=8). The rat model of LVR was established by subcutaneous injection of ISO solution at 10 mg·kg -1·d -1 at multiple sites for 10 consecutive days. After modeling was completed, the surviving rats ( n=24) in the experimental group were then randomly assigned to the blank experimental group, CAVO group, and Shexiang Baoxin pill (SXBXP) group ( n=8 in each group). Rats in each group were given via gavage the corresponding intervention medicine or an equivalent amount of normal saline solution for 28 consecutive days. At the end of modeling and intragastric intervention, 7T CMR cine sequence scanning was conducted to collect data. Then, post-processing software CVI42 was used to analyze the images and to compare and contrast the changes in the parameters of left ventricular cardiac function and myocardial strain in each group before and after the administration of the medication. The rats were sacrificed after MRI scanning, and their hearts were harvested for pathological examination. The levels of serum biochemical indicators were measured by enzyme-linked immunosorbent assay (ELISA). Results: CAVO significantly increased LV ejection fraction and overall myocardial strain parameters in LVR rats, while it decreased LV volume, mass, and serum levels of endothelial function indicators in LVR rats. In addition, pathological staining showed marked improvements in the hypertrophy, necrosis and interstitial fibrosis of cardiomyocytes. Conclusion: Through the regulation of myocardial vascular endothelial function, CAVO can significantly improve cardiac functions in LVR rats, delay the process of ventricular remodeling, and have a certain amount of protective effect on cardiac structure and function in rats.

Effects of aldo-keto reductase family 1 member A on osteoblast differentiation associated with lactate production in MC3T3-E1 preosteoblastic cells.

Aldo-keto reductase family 1 member A (AKR1A) is an NADPH-dependent aldehyde reductase widely expressed in mammalian tissues. In this study, induced differentiation of MC3T3-E1 preosteoblasts was found to increase AKR1A gene expression concomitantly increased NOx- (nitrite + nitrate), increased glucose uptake, increased [NAD(P)+]/[NAD(P)H] and lactate production but decreased reactive oxygen species (ROS) without changes in endothelial nitric oxide synthase (eNOS) expression in differentiated osteoblasts (OBs). A study using gain- and loss-of-function MC3T3-E1 cells indicated that AKR1A is essential for modulating OB differentiation and gene expression of collagen 1 A1, receptor activator of nuclear factor kappa-B ligand, and osteoprotegerin in OBs. Immunofluorescence microscopy also revealed that changes in AKR1A expression altered extracellular collagen formation in differentiated OBs. Consistently, analyses of alkaline phosphatase activity and calcium deposits of matrix mineralization by Alizarin Red S staining verified that AKR1A is involved in the regulation of OB differentiation and bone matrix formation. In addition, AKR1A gene alterations affected the levels of NOx-, eNOS expression, glucose uptake, [NAD(P)+]/[NAD(P)H] dinucleotide redox couples, lactate production, and ROS in differentiated OBs. Herein, we report that AKR1A-mediated denitrosylation may play a role in the regulation of lactate metabolism as well as redox homeostasis in cells, providing an efficient way to quickly gain energy and to significantly reduce oxidative stress for OB differentiation.

Environmentally relevant concentrations of microplastics modulated the immune response and swimming activity, and impaired the development of marine medaka Oryzias melastigma larvae.

Microplastics (MPs), due to their impacts on the ecosystem and their integration into the food web either through trophic transfer or ingestion directly from the ambient environment, are an emerging class of environmental contaminants posing a great threat to marine organisms. Most reports on the toxic effects of MPs exclusively focus on bioaccumulation, oxidative stress, pathological damage, and metabolic disturbance in fish. However, the collected information on fish immunity in response to MPs is poorly defined. In particular, little is known regarding mucosal immunity and the role of mucins. In this study, marine medaka (Oryzias melastigma) larvae were exposed to 6.0 µm beads of polystyrene microplastics (PS-MPs) at three environmentally relevant concentrations (102 particles/L, 104 particles/L, and 106 particles/L) for 14 days. The experiment was carried out to explore the developmental and behavioural indices, the transcriptional profiles of mucins, pro-inflammatory, immune, metabolism and antioxidant responses related genes, as well as the accumulation of PS-MPs in larvae. The results revealed that PS-MPs were observed in the gastrointestinal tract, with a concentration- and exposure time-dependent manner. No significant difference in the larval mortality was found between the treatment groups and the control, whereas the body length of larvae demonstrated a significant reduction at 106 particles/L on 14 days post-hatching. The swimming behaviour of the larvae became hyperactive under exposure to 104 and 106 particles/L PS-MPs. In addition, PS-MP exposure significantly up-regulated the mucin gene transcriptional levels of muc7-like and muc13-like, however down-regulated the mucin gene expression levels of heg1, muc2, muc5AC-like and muc13. The immune- and inflammation and metabolism-relevant genes (jak, stat-3, il-6, il-1ß, tnf-а, ccl-11, nf-κb, and sod) were significantly induced by PS-MPs at 104 and 106 particles/L compared to the control. Taken together, this study suggests that PS-MPs induced inflammation response and might obstruct the immune functions and retarded the growth of the marine medaka larvae even at environmentally relevant concentrations.

No differences in 10-year clinical outcomes and quality of life between patients with different mediolateral femoral component positions in fixed-bearing medial unicompartmental knee arthroplasty.

PURPOSE: There has been a paucity of literature evaluating the role of mediolateral femoral component position (FCP) in medial unicompartmental arthroplasty (UKA). Hence, the aim of this study is to evaluate whether the mediolateral FCP in UKA will affect the 10-year clinical outcomes and quality of life of patients who underwent medial UKA. METHODS: Data of 262 patients who underwent medial UKA were analyzed. All patients were assessed at 6 months, 2 years and 10 years using the Knee Society Function Score, Knee Society Knee Score, Oxford Knee Score, Short-Form 36 Physical/Mental Component Scores and postoperative satisfaction. The mediolateral FCP on postoperative radiographs was measured by independent assessors using the Picture Archiving and Communication Systems. 144 patients were distributed into group C (center), 98 into group M (medial) and 20 into group L (lateral) according to FCP, and one-way ANOVA was used to compare the functional outcomes of the three groups. RESULTS: No statistical differences were found between the three groups in terms of 10-year clinical outcomes, quality of life, satisfaction rates and revision rates. CONCLUSION: Differences in mediolateral FCP did not result in significant difference in 10-year postoperative clinical outcomes for patients who underwent fixed-bearing medial UKAs. LEVEL OF EVIDENCE: Retrospective study, Level III.

Microplastics in three typical benthic species from the Arctic: Occurrence, characteristics, sources, and environmental implications.

Microplastics (MPs) in the Arctic have raised increasing concern, but knowledge on MP contamination in benthic organisms from Arctic shelf regions, e.g., the Chukchi Sea is still limited. Therefore, the present study investigated the occurrence, characteristics, sources, and environmental implications of MPs in the three most common benthic species, namely sea anemone (Actiniidae und.), deposit-feeding starfish (Ctenodiscus crispatus), and snow crab (Chionoecetes opilio), from the Chukchi Sea. The abundances of MPs in the three benthic species were significantly greater than those from the Bering Sea, but lower than those from other regions globally. The top three compositions of MPs in the three species were polyester, nylon, and polyethylene terephthalate. The detection limit for MP size in the present study was 0.03 mm and the mean size of MP in the three species was 0.89 ± 0.06 mm. The surfaces of MPs found in the starfish and crabs were covered with many attachments, cracks, and hollows, while the surfaces of MPs found in the sea anemones were smooth, which was likely a consequence of different feeding behaviors. There was a significantly positive correlation between the abundances of MPs and other anthropogenic substances. The mean MP abundances in the sea anemones ranged from 0.2 items/individual to 1.7 items/individual, which was significantly higher than that in the deposit-feeding starfish (0.1-1.4 items/individual) and snow crabs (0.0-0.6 items/individual). Sea anemones inhabiting lower latitudes ingested relatively higher levels of MPs than those inhabiting higher latitudes. The MP abundances in the sea anemones are significantly and positively correlated with the seasonal reduced ratio of sea ice coverage from August to September. Our findings indicate that sea anemones could function as a bioindicator of MP pollution, and that the MPs in the benthos from the Chukchi Sea might originate from the melting sea ice, fishery activities and ocean currents.

Improvements in functional outcome and quality of life are not sustainable for patients ≥ 68 years old 10 years after total knee arthroplasty.

PURPOSE: The aims of this study are to evaluate whether improvements in functional outcome and quality of life are sustainable 10 years after total knee arthroplasty (TKA), and the age cut-off for clinical deterioration in outcomes METHODS: Prospectively collected registry data of 120 consecutive patients who underwent TKA at a tertiary hospital in 2006 was analysed. All patients were assessed at 6 months, 2 years and 10 years using the Knee Society Function Score, Knee Society Knee Score, Oxford Knee Score, Short-Form 36 Physical/Mental Component Scores and postoperative satisfaction. One-way ANOVA was used to compare continuous variables, while Chi-squared test to compare categorical variables. Multivariate logistic regression and receiver operating curve analysis was performed to evaluate the predictive factors associated with deterioration of scores postoperatively. RESULTS: Significant improvements were noted in all functional outcome and quality of life scores at 6 months after TKA. Between 6 months and 2 years, the KSFS and OKS continued to improve but the KSKS, PCS and MCS plateaued. Between 2 and 10 years, there was a deterioration in the KSFS and OKS, whilst KSKS, PCS and MCS were maintained. Increasing age was noted to be a significant risk factor for deterioration of KSFS at 10 years with age ≥ 68 as the cut-off value. 91.7% of patients with KSFS Minimally Clinically Important Difference(MCID) (≥ 7 points) continued to be satisfied after 10 years compared to 100.0% who did not experience KSFS MCID deterioration (p = 0.02). CONCLUSION: Patients ≥ 68 years experience deterioration in functional outcomes and quality of life from 2 to 10 years after TKA. LEVEL OF EVIDENCE: Retrospective study, Level III.

Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

Red Quinoa Bran Extract Prevented Alcoholic Fatty Liver Disease via Increasing Antioxidative System and Repressing Fatty Acid Synthesis Factors in Mice Fed Alcohol Liquid Diet.

Alcohol is metabolized in liver. Chronic alcohol abuse results in alcohol-induced fatty liver and liver injury. Red quinoa (Chenopodium formosanum) was a traditional staple food for Taiwanese aborigines. Red quinoa bran (RQB) included strong anti-oxidative and anti-inflammatory polyphenolic compounds, but it was usually regarded as the agricultural waste. Therefore, this study is to investigate the effect of water and ethanol extraction products of RQB on the prevention of liquid alcoholic diet-induced acute liver injury in mice. The mice were given whole grain powder of red quinoa (RQ-P), RQB ethanol extract (RQB-E), RQB water extract (RQB-W), and rutin orally for 6 weeks, respectively. The results indicated that RQB-E, RQB-W, and rutin decreased alcoholic diet-induced activities of aspartate aminotransferase and alanine aminotransferase, and the levels of serum triglyceride, total cholesterol, and hepatic triglyceride. Hematoxylin and eosin staining of liver tissues showed that RQB-E and RQB-W reduced lipid droplet accumulation and liver injury. However, ethanol extraction process can gain high rutin and antioxidative agents contents from red quinoa, that showed strong effects in preventing alcoholic fatty liver disease and liver injury via increasing superoxide dismutase/catalase antioxidative system and repressing the expressions of fatty acid synthesis enzyme acetyl-CoA carboxylase.

GeSn resonant-cavity-enhanced photodetectors for efficient photodetection at the 2 µm wavelength band.

The 2 µm wavelength band has recently gained increased attention for potential applications in next-generation optical communication. However, it is still challenging to achieve effective photodetection in the 2 µm wavelength band using group-IV-based semiconductors. Here we present an investigation of GeSn resonant-cavity-enhanced photodetectors (RCEPDs) on silicon-on-insulator substrates for efficient photodetection in the 2 µm wavelength band. Narrow-bandgap GeSn alloys are used as the active layer to extend the photodetection range to cover the 2 µm wavelength band, and the optical responsivity is significantly enhanced by the resonant cavity effect as compared to a reference GeSn photodetector. Temperature-dependent experiments demonstrate that the GeSn RCEPDs can have a wider photodetection range and higher responsivity in the 2 µm wavelength band at higher temperatures because of the bandgap shrinkage. These results suggest that our GeSn RCEPDs are promising for complementary metal-oxide-semiconductor-compatible, efficient, uncooled optical receivers in the 2 µm wavelength band for a wide range of applications.

Biomonitoring of aromatic hydrocarbons in clam Meretrix meretrix from an emerging urbanization area, and implications for human health.

Pollution with total petroleum hydrocarbons (TPHs) is a global concern and particularly in coastal environments. Polycyclic aromatic hydrocarbons (PAHs) are regarded as the most toxic components of TPHs and they can also be derived from other sources. Fangcheng Port is considered as a representative emerging coastal city in China, but the status, sources, and hazards to organisms and humans with respect to contamination with PAHs and TPHs are unknown in the coastal regions of this area. Therefore, in this study, we cloned cytochrome P450 family genes (CYP1A1, CYP3A, and CYP4) and heat shock protein 70 gene (HSP70) in the clam Meretrix meretrix as well as optimizing the method for measuring the 7-ethoxyresorufin O-deethylase activity. These molecular indicators and four specific physiological indexes were found to be appropriate biomarkers for indicating the harmful effects of PAHs and TPHs on clams after exposure to the crude oil water-soluble fraction. In field monitoring surveys, we found that the 2- and 3-ring PAHs were dominant in the clams whereas the 4- to 6-ring PAHs were dominant in the sediments at each site. The PAH levels (3.63-12.77 ng/g wet weight) in wild clams were lower, whereas the TPH levels (13.25-70.50 µg/g wet weight) were higher compared with those determined previous in China and elsewhere. The concentrations of PAHs and TPHs in the sediments (19.20-4215.76 ng/g and 3.65-866.40 µg/g dry weight) were moderate compared with those in other global regions. Diagnostic ratio analysis demonstrated that the PAHs were derived mainly from pyrogenic sources. The TPHs may have come primarily from industrial effluents, land and maritime transportation, or fishing activities. The Integrated Biomarker Response version 2 indexes indicated that the clams collected from site S5 exhibited the most harmful effects due to contamination by PAHs and TPHs. Human health risk assessments demonstrated that the risks due to PAHs and TPHs following the consumption of clams can be considered acceptable. Our results suggest that continuous monitoring of contamination by PAHs and TPHs is recommended in this emerging coastal city as well as assessing their human health risks.

[Basic Research on Neuroprotective Effect of Volatile Oil of Cang Ai after Cerebral Ischemia-Reperfusion Injury Based on Diffusion Tensor Imaging].

OBJECTIVE: To study the neuroprotective effect of inhalation of volatile oil of Cang Ai (VOCA) on cerebral ischemia-reperfusion injury model by MRI diffusion tensor imaging. METHODS: Twenty-four healthy adult male SD rats were randomly divided into sham operation group, model (middle cerebral artery occlusion (MCAO) ) group and VOCA group. Evaluated the degree of neurological impairment of rats in each group immediately after successful establishment of model or 7 d later according to Zea Longa scoring. Coronal diffusion tensor imaging (DTI) scan was performed at 3 h, 3 d, and 7 d after the model successfully established by using 7.0 T magnetic resonance imaging. Measured the apparent diffusion coefficient (ADC) and anisotropy score (FA) of the DTI in the striatal region and the motion flat zone of the maximum infarct level and then calculate the relative apparent diffusion coefficient (rADC) and relative anisotropy score (rFA). TTC staining was used to evaluate the cerebral infarction volume of rats in each group at 7 d post model establishment, and the correlation analysis of rFA, rADC and neural score was performed. RESULTS: No neurological defect was detected in mice in the sham operation group. The MCAO group and the VOCA group showed neurological defect to different degrees. The neurological function score of the VOCA group was obviously lower than that of MCAO group at 7 th day (P<0.05). The DTI scan results showed that the rADC value of striatum of rats in VOCA group was higher than that in MCAO group at 3 h and 3 d after modeling (P<0.05), while there was no significant difference between the three groups at 7 th day. The rADC value of the motor cortex in the VOCA group was higher than that in the MCAO group at 3 h after modeling (P<0.01), and there was no significant difference at 3 rdday and 7 thday. The rFA value of striatum in VOCA group was higher than that in MCAO group at 3 rd day and 7 th day after modeling (P<0.05). There were no significant differences in rFA value between the MCAO and the VOCA group at three time points. TTC staining results showed that there was no infarcted area in the sham operation group, and the infarct volume in the VOCA group was smaller than that of the MCAO group (P<0.05). Correlation analysis showed that the striatum rFA value was highly correlated with neurological scores (r=－0.847, P<0.01). CONCLUSION: For the first time, we found that VOCA can effectively protect the neurological function of MCAO rats by reducing the toxic edema of cells in the ischemic area and accelerating the recovery of nerve fiber bundles after cerebral ischemia and reperfusion. rFA and rADC values can be used as effective indicators to evaluate the recovery of nerve function after cerebral ischemia and reperfusion.

Clinical outcomes comparing arthroscopic vs open ankle arthrodesis.

BACKGROUND: Over the last twenty years, minimally invasive ankle arthrodesis has evolved into a well-tolerated and safe procedure. It has grown in favor to open ankle arthrodesis due to shorter length of stay and fewer complications recorded. This paper aims to compare the clinical outcomes of arthroscopic vs open ankle arthrodesis at 24-months followup. METHODS: From 2004 to 2015, we reviewed a prospectively collected database in a tertiary hospital foot and ankle registry. 28 feet that underwent arthroscopic ankle arthrodesis were matched to 56 feet that underwent open ankle arthrodesis for age, sex and body mass index (BMI). Visual analogue scale (VAS) scores, American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-hindfoot Scores and Short Form Health Survey (SF-36) were obtained to assess clinical outcomes. These parameters were collected before surgery, at 6months and 24months after surgery. RESULTS: The arthroscopic group demonstrated significant less pain in the perioperative period (arthroscopic: 1.9±1.2, open: 3.8±1.1, p<0.001) and shorter length of hospitalization stay (arthroscopic: 2.1±0.7 open: 3.5±1.7, p<0.001). Patients who underwent arthroscopic ankle arthrodesis also reported a higher SF-36 score on physical functioning at 6months (arthroscopic: 58.4±27.1, open: 47.1±24.0, p<0.05) and higher AOFAS Ankle-hindfoot Scale score at 24-months (arthroscopic: 78.9±18.9, open: 68.9±24.7, p<0.05). There were no postoperative complications in the arthroscopic group but 11 in the open group, including 9 which required followup operations. There was no significant difference in length of operative procedure between both groups. CONCLUSIONS: We conclude that the arthroscopic group displayed better clinical outcomes compared to the open group at the 24months followup. The advantages of arthroscopic ankle arthrodesis include significantly less perioperative pain, higher AOFAS Ankle-hindfoot scores at 24months, shorter length of stay, fewer postoperative complications and followup operations. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Dedicator of cytokinesis 2 silencing therapy inhibits neointima formation and improves blood flow in rat vein grafts.

OBJECTIVE: The high rate of vein graft failure due to neointimal hyperplasia is a major challenge for cardiovascular surgery. Finding novel approaches to prevent neointimal hyperplasia is important. Thus, the purpose of this study was to investigate whether dedicator of cytokinesis 2 (DOCK2) plays a role in the development of neointima formation in the vein grafts. METHODS AND RESULTS: We found that DOCK2 levels were significantly elevated in the vein grafts following grafting surgery. In addition, overexpression of DOCK2 promoted venous smooth muscle cell (SMC) proliferation and migration. Conversely, knocking-down endogenous DOCK2 expression in venous SMCs inhibited SMC proliferation and migration. Consistent with this, knocking-down DOCK2 expression in the grafted veins significantly reduced neointimal formation compared with the controls 28 days after vein transplantation. Moreover, DOCK2 silencing treatment improved hemodynamics in the vein grafts. Mechanistically, knockdown of DOCK2 significantly alleviated the vein graft-induced down regulation of SMC contractile protein expression and impeded the vein graft-induction of both Cyclin D1 and PCNA expression. In particular, to ensure high efficiency when transferring the DOCK2 short hairpin RNA (shDOCK2) into the grafted veins, a 30% poloxamer F-127 gel incorporated with 0.25% trypsin was smeared around the vein grafts to increase the adenovirus contact time and penetration. CONCLUSIONS: DOCK2 silencing gene therapy effectively attenuates neointimal hyperplasia in vein grafts. Knock-down of DOCK2 would be a potential therapeutic approach for the treatment of vein graft failure.

MicroRNA-146a sponge therapy suppresses neointimal formation in rat vein grafts.

The long-term failure of vein grafts due to neointimal hyperplasia remains a difficult problem in cardiovascular surgery. Exploring novel approaches to prevent neointimal hyperplasia is important. MicroRNA-146a (miR-146a) plays an essential role in promoting vascular smooth muscle cell (VSMC) proliferation. Thus, the aim of the present study is to investigate whether adenovirus-mediated miR-146a sponge (Ad-miR-146a-SP) gene therapy could attenuate neointimal formation in rat vein grafts. (Ad-miR-146a-SP) was constructed to transfect cultured VSMCs and grafted veins. To improve the efficiency of transferring the miR-146a sponge gene into the grafted veins, 20% poloxamer F-127 gel incorporated with 0.25% trypsin was used to increase adenovirus contact time and penetration. miR-146a-SP transduction significantly reduced the expression of miR-146a both in cultured VSMCs and vein grafts. miR-146a sponge markedly attenuated VSMC proliferation and migration. Consistent with this, miR-146a sponge gene therapy significantly attenuated neointimal formation and also improved blood flow in the vein grafts. Mechanistically, we identified the Krüppel-like factor 4(KLF4) as a potential downstream target gene of miR-146a in vein grafts. Our data show that miR-146a sponge gene therapy could effectively reduce miR-146a activity and attenuate neointimal formation in vein grafts, suggesting its potential therapeutic application for prevention of vein graft failure. © 2018 IUBMB Life, 71(1):125-133, 2019.

MicroRNA-365 promotes the contractile phenotype of venous smooth muscle cells and inhibits neointimal formation in rat vein grafts.

The high rate of autologous vein graft failure caused by neointimal hyperplasia remains an unresolved issue in the field of cardiovascular surgery; therefore, it is important to explore new methods for protecting against neointimal hyperplasia. MicroRNA-365 has been reported to inhibit the proliferation of vascular smooth muscle cells (SMCs). This study aimed to test whether adenovirus-mediated miR-365 was able to attenuate neointimal formation in rat vein grafts. We found that miR-365 expression was substantially reduced in vein grafts following engraftment. In vitro, overexpression of miR-365 promoted smooth muscle-specific gene expression and inhibited venous SMC proliferation and migration. Consistent with this, overexpression of miR-365 in a rat vein graft model significantly reduced grafting-induced neointimal formation and effectively improved the hemodynamics of the vein grafts. Mechanistically, we identified that cyclin D1 as a potential downstream target of miR-365 in vein grafts. Specially, to increase the efficiency of miR-365 gene transfection, a 30% poloxamer F-127 gel containing 0.25% trypsin was mixed with adenovirus and spread around the vein grafts to increase the adenovirus contact time and penetration. We showed that adenovirus-mediated miR-365 attenuated venous SMC proliferation and migration in vitro and effectively inhibited neointimal formation in rat vein grafts. Restoring expression of miR-365 is a potential therapeutic approach for the treatment of vein graft failure. © 2019 IUBMB Life, 2019.

The characteristics of clinical changes in primary hyperparathyroidism in Chinese patients.

In Western countries, the presentation of primary hyperparathyroidism (PHPT) changed from a symptomatic to an asymptomatic disease after the 1970s, whereas in China, only one study has evaluated the changing clinical characteristics and biochemical profiles of PHPT patients. The aim of this study was to explore changes in the clinical characteristics of PHPT in Chinese patients. Overall, 140 consecutive patients with PHPT were studied between January 1, 2010 and June 30, 2016. The patients were divided into two groups: 32 consecutive patients from January 1, 2010 to March 31, 2013 were included in group 1, and 108 consecutive patients from April 1, 2013 to June 30, 2016 were included in group 2. The most frequent complaints were ostealgia (46.02%), urolithiasis (41.59%), constipation (25.66%), fatigue (18.58%), polydipsia and polyuria (15.93%) and fracture history (15.04%). The number of cases in group 2 was 3.38-fold greater than that of group 1. The parathyroid hormone (PTH) and fasting blood glucose (FPG) levels were higher in group 1 than those in group 2 (p = 0.039, p < 0.001). In 62.14% of patients with PHPT, the proportion of the first diagnosis due to hypercalcemia found using a multichannel autoanalyzer in group 1 was lower than that found in group 2 (p = 0.039), and the proportion of the first diagnosis due to parathyroid lesions captured using routine neck ultrasonography in group 1 was higher than in group 2 (p = 0.003). The proportion of parathyroid carcinoma cases was higher in group 1 than group 2 (p = 0.036). Cases of PHPT increased with time, but the proportion of parathyroid carcinoma cases was lower in group 1 than that in group 2. Over time, the first diagnosis switched from parathyroid lesions captured by routine neck ultrasound to hypercalcemia found by a multichannel autoanalyser. At our centre, PHPT in Chinese patients still demonstrates classic characteristics.

Antimicrobial activity and mechanisms of multiple antimicrobial peptides isolated from rockfish Sebastiscus marmoratus.

Pathogenic disease is a major factor affecting the aquaculture of the rockfish Sebastiscus marmoratus, an important commercial species inhabiting the nearshore waters of the Western Pacific Ocean. Antimicrobial peptides (AMPs), as critical components of innate immunity, have been considered as promising antibiotic substitutes. The aims of this study were 1) to identify major AMPs in the rockfish, 2) to assess their antimicrobial activity and 3) to evaluate their potential therapeutic application. Six AMPs were identified, Hepcidin 1, liver-expressed antimicrobial peptide 2 (LEAP-2), Piscidin, Moronecidin, NK-lysin and ß-defensin through analysis of the liver transcriptome of S. marmoratus. The transcriptional expression profiles of these AMPs were investigated by real-time quantitative PCR (RT-qPCR). These AMPs showed tissue-specific distribution patterns, and S. marmoratus displays a time-, dose- and tissue-dependent expression of AMPs in response to lipopolysaccharide (LPS) challenge. While the synthetic peptides of LEAP-2 and Moronecidin exerted broad-spectrum antimicrobial activity against important aquatic pathogens in vitro by directly disrupting microbial membrane, and no cytotoxicity against murine hepatic cells was observed at the effective concentrations from 5 µM to 40 µM. The existence of multiple AMPs and their distinct tissue distribution patterns and inducible expression patterns suggests a sophisticated, highly redundant, and multilevel network of antimicrobial defensive mechanisms of S. marmoratus. Therefore, S. marmoratus-derived AMPs appear to be potential therapeutic applications against pathogen infections in aquaculture.

Alteration of oncogenic IGF-II gene methylation status associates with hepatocyte malignant transformation.

BACKGROUND: Oncogenic insulin-like growth factor-II (IGF-II) is overexpressed in hepatocellular carcinoma (HCC). The present study aimed to analyze the dynamic alteration of IGF-II CpG site methylation status and its molecular mechanism in HCC progression. METHODS: IGF-II alterations were observed in rat hepatocarcinogenesis models induced by 2-acetylaminofluorene. Liver IGF-II expression was compared by immunohistochemistry or tissue IGF-II specific concentration (nmol/mg protein). Status of human IGF-II promoter 3 (P3) or rat IGF-II P2 CpG site methylation was amplified by methylation-specific polymerase chain reaction (MSP). Serum IGF-II levels were quantitatively detected by an enzyme-linked immunosorbent assay. RESULTS: The levels of hepatic IGF-II expression were significantly elevated in the HCC group (P < 0.001). The unmethylation rate of IGF-II P3 CpG sites was 100% in the HCC-, 52.5% in the paracancerous-, and none (0%) in the distal noncancerous-tissues. Abnormal IGF-II expression was related to differentiation degree, tumor invasion, and positive HBV-DNA (all P < 0.001), with a negative correlation between P3 methylation degree and IGF-II expression. There was a positive correlation between liver IGF-II specific concentration and circulating IGF-II level (r = 0.97, P < 0.001). Significantly negative correlation was found between IGF-II P2 CpG site methylation and circulating IGF-II (rs = -0.89, P < 0.001) or liver IGF-II level (rs = -0.84, P < 0.001). CONCLUSIONS: The increase of serum IGF-II and the alteration of oncogenic gene IGF-II methylation may be biomarkers for HCC diagnosis and DNA methylation may be the therapeutic target of HCC.