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Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group ( P <0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups ( P <0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P <0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm 3 vs. 75.76 (48.20, 115.64) mm 3 , P >0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P >0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm 3 vs. 72.49 (51.91, 199.59) mm 3 , P <0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P <0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm 3 ) and (12.71% (8.39%, 24.41%)) at 24 months (both P <0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups( P >0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months ( P >0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.

Objective: To explore the effect of remote "Internet+" interactive management strategy on blood pressure control in patients with hypertension during normalized epidemic prevention and control of COVID-19. Methods: This is a randomized controlled study. A total of 394 patients with hypertension who were treated in Chinese People's Liberation Army General Hospital from October 2019 to December 2020 were randomly divided into experimental group (197 cases) and control group (197 cases). The experimental group adopted remote "Internet+" interaction mode to carry out remote blood pressure intervention, and the control group received traditional blood pressure control mode, and the intervention time was 6 months. Evaluation indicators included blood pressure level, blood pressure lowering speed, time to target blood pressure, blood pressure measurement times, communication times with doctors, medication compliance, blood pressure measurement compliance and disease awareness after 6 months of intervention. The evaluation indexes of the two groups were compared, and the bivariate Pearson correlation analysis was used to explore the relationship between the speed of blood pressure reduction and the times of blood pressure measurement and doctor communication in all patients. Results: A total of 394 patients with hypertension were included in this study, including 209 males, aged (67.6±2.8) years old. After 6 months of intervention, the systolic and diastolic blood pressure of the two groups were both lower than the baseline blood pressure before intervention (both P <0.05), the systolic blood pressure ((125.7±11.7) mmHg (1 mmHg=0.133 kPa) vs. (132.6±12.9) mmHg, P <0.001) and diastolic blood pressure ((72.4±10.7) mmHg vs. (79.8±11.6) mmHg, P <0.001) in the experimental group were lower than those in the control group. The blood pressure reduction speed of the experimental group was faster than that of the control group ((18.63±1.59) mmHg/d vs. (13.26±2.85) mmHg/d, P <0.001), and the time to reach the target blood pressure in the experimental group was shorter than that in the control group ((23.69±2.93) d vs. (47.12±5.81) d, P <0.001). Compared with the control group, the blood pressure measurement times ((0.98±0.13) times/d vs. (0.20±0.40) times/d, P <0.05) and the number of communications with doctors ((0.97±0.16) times/week vs. (0.12±0.32) times/week, P <0.05) were significantly higher in the experimental group. Correlation analysis showed that the speed of blood pressure reduction was positively correlated with the number of blood pressure measurements ( r =0.419, P <0.01) and the number of communications with doctors ( r =0.857, P <0.01). The proportion of standardized medication (93.91% (185/197) vs. 51.78% (102/197), P <0.001), timely measurement (97.46% (192/197) vs. 47.21% (93/197), P <0.001) and high-degree disease awareness (94.42% (186/197) vs. 49.24% (97/197), P <0.001) were significantly higher in the experimental group than those in the control group. Conclusions: The remote "Internet+" interactive management strategy can effectively improve patients' blood pressure control. The doctor-patient interaction can improve medication compliance and measurement compliance of patients, and help shorten the time to reach the target blood pressure.

Peroxymonosulfate(PMS)-based advanced oxidation processes were widely used for the degradation of organic pollutants. Electron-rich azo dye Acid Orange 7(AO7) was selected as the target organic matter in this work. The differences, influencing factors, efficiency, and mechanisms of a PMS/Co 2+ homogeneous system in the degradation of organic pollutants with two different buffers of boric acid(Lewis acid) and phosphoric acid(Bronstede acid) were investigated. The k value of AO7 degradation in the PMS/Co 2+ homogeneous system with phosphate buffer was greater than that with borate buffer, but the degradation percentage during the first 10 seconds of the reaction was lower in the former case. These differences were affected by buffer concentration, the PMS and Co 2+ dosages, and pH. In the phosphate buffer, ·OH or SO 4 - · contributed to organic degradation in the PMS/Co 2+ system, while in the borate buffer, the nonradical pathway( 1 O 2 ) made a critical contribution to the removal of organics. This study provides a reference for the application of different types of buffers in the homogeneous catalysis of PMS.

Objective: To investigate the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular outcomes in elderly Chinese patients with comorbid coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM)., Methods: A retrospective cohort study was conducted on 501 elderly inpatients (≥ 60 years) with comorbid CHD/T2DM in Department of Cardiovascular Medicine and Endocrinology, Chinese PLA General Hospital from January 2018 to December 2019. These patients were divided into two groups according to the administration of SGLT2i. All the demographic characteristics and clinical data were collected. Cardiovascular outcomes, including all-cause mortality, major adverse cardiovascular events (MACE), and hospitalization for heart failure (HHF), were followed up., Results: In the cohort, there were 167 patients in the SGLT2i group and 334 patients in the control group. In the efficacy analyses, the incidence of MACE was lower in the SGLT2i group than in the control group: 3.6% vs . 9.3% ( P = 0.022). A lower risk of MACE was observed in the SGLT2i group [hazard ratio (HR) = 0.40, 95% CI: 0.17-0.95]. There was no significant difference in the incidence of all-cause mortality or HHF between the two groups. No significant difference of HR was observed for all-cause mortality (HR = 0.41, 95% CI: 0.12-1.41) or HHF (HR = 0.58, 95% CI: 0.12-2.81)., Conclusions: SGLT2i treatment exhibited benefits for elderly patients with comorbid CHD/T2DM with a lower risk for MACE., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Objective: To observe the biocompatibility of porcine omental derived extracellular matrix (ECM) hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the feasibility of ECM hydrogel as a delivery vector of cell transplantation. Methods: A series of chemical, physical and enzymatic methods were applied to acellularize the porcine omentum. Subsequently, the extracted ECM was prepared into thermosensitive hydrogel. The biochemical composition of the hydrogel was identified by histological staining. The microstructure was observed by scanning electron microscopy. The hydrogel was then injected into the myocardium of mice to observe its in situ gelation ability. Differentiation of human induced pluripotent stem cells into cardiomyocytes was achieved by small molecule induction, and then the obtained hiPSC-CMs were cultured. hiPSC-CMs cultured onto the prepared hydrogel were defined as the hydrogel group, while conventionally cultured hiPSC-CMs were defined as the control group. Cardiomyocyte viability and growth patterns were detected using live/dead staining, CCK-8 and phalloidin staining. Immunofluorescence staining and Western blot of cardiomyocytes were used to determine the survival and phenotypic maintenance markers of cardiomyocytes in materials. Results: The results of HE staining, oil red O staining and DAPI fluorescence staining showed that there was no significant cell debris, nucleus and lipid residue in the prepared ECM hydrogel. The Sirius red staining and Alcian blue staining showed that the hydrogel retained collagen and glycolaminoglycan, which were the main components of ECM. The prepared hydrogel behaves as a viscous liquid at 4 ℃ and as a gel state at 37 ℃. Scanning electron microscope results showed that the microstructure of the hydrogel was composed of irregular fibers and pores of different sizes. Under the guidance of ultrasound, the prepared ECM hydrogel could be successfully injected into the myocardium of mice. Immediately after the injection, the hyperechoic signal could be observed under ultrasound, suggesting that the hydrogel remained in the myocardium. HE staining of myocardial tissue evidenced that there was lump of gel in the injection area. The differentiated hiPSC-CMs were co-cultured with the prepared ECM hydrogel, and the results of live/dead staining showed that most of the hiPSC-CMs in the hydrogel group and the control group were alive, dead cells were scanty. The results of CCK-8 test showed that the absorbance values of the two groups were similar ( P >0.05). The results of phalloidin staining showed that hiPSC-CMs could extend normally when co-cultured with ECM hydrogel. The cell morphology of the hydrogel group was similar with that of the control group, and there was no statistically significant difference in the F-actin coverage area per cell between the two groups ( P >0.05). Immunofluorescence staining of cardiomyocyte markers showed that there was no significant difference in the coverage area of α-actinin and connexin-43 (Cx-43) per field between the hydrogel group and the control group (both P >0.05), the quantitative results of DAPI staining showed that there was no statistically significant difference in the number of cells between the two groups ( P >0.05). Meanwhile, the results of Western blot showed that the expression levels of α-actinin and Cx-43 in cardiomyocytes in the hydrogel group were similar as those in the control group (both P >0.05). Conclusions: These results show that preparation of the ECM hydrogel from porcine omentum is successful. The hydrogel has good biocompatibility and no obvious cytotoxicity. Besides, the hydrogel can support the survival of hiPSC-CMs in vitro and maintain its phenotype. These properties make it a promising injectable cardiac tissue engineering material.

Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians., (© The Author(s) 2020.)

The precise treatment of drug-resistant deep bacterial infections remains a huge challenge in clinic. Herein, a polymer-peptide-porphyrin conjugate (PPPC), which can be real-time monitored in infectious site, is developed for accurate and deep sonodynamic therapy (SDT) based on "in vivo self-assembly" strategy. The PPPC contains four moieties, i.e., a hyperbranched polymer backbone, a self-assembled peptide linked with an enzyme-cleavable peptide-poly (ethylene glycol) terminal, a bacterial targeting peptide, and a porphyrin sonosensitizer (MnTCPP) segment. Once PPPC nanoparticles reach the infectious area, the protecting PEG layers are removed due to the over-expressed gelatinase, leading to the secondary assembly into large nanoaggregates and resultant enhanced accumulation of sonosensitizer. The nanoaggregates exhibit enhanced interaction with bacterial membrane and decrease the minimum inhibitory concentration (MIC) significantly. Meanwhile, compared with free MnTCPP, the concentration of which can not be accurately quantified, the accumulation amount of MnTCPP in PPPCs at infectious site can be in situ monitored by magnetic resonance imaging (MRI) using T 1 combined with T 2 . When the concentration of PPPC-1 reaches MIC, the drug-resistant bacterial infection area is exposed to ultrasound irradiation, causing the precise and efficient elimination of bacteria. Therefore, the MRI-guided SDT system shows extraordinary tissue penetration depth, drug concentration monitoring, morphology-transformation induced accumulation and improved treatment capacity toward drug-resistant bacteria., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Due to the problems of low nitrogen removal efficiency and unclear electron transfer during biological denitrification treatment of an oligotrophic drinking water reservoir, the nitrogen removal characteristics, environmental adaptability, and electron transfer during denitrification were systematically studied using the aerobic denitrifier Acinetobacter junii ZMF5, which has efficient nitrogen removal ability. The results showed that:① Strain ZMF5 exhibited efficient heterotrophic nitrification and aerobic denitrification ability, with an ammonia removal rate of 0.211 mg·(L·h) -1 and a nitrate removal rate of 0.236 mg·(L·h) -1 , and the nitrification intermediates were not accumulated during the treatment process. ② According to analysis of the nitrogen removal efficiency and growth kinetics of strain ZMF5, the strain can effectively utilize different types of carbon source, and show efficient nitrogen removal efficiency under the conditions of low C/N, low pH, and low temperature. ③ Analysis of nitrogen balance showed that carboxylate compound, compared with carbohydrate, could promote the process of aerobic denitrification and change the nitrogen removal pathway of strain ZMF5, i.e., 38.81% of nitrogen was transformed into gas, higher than the 29.81% for assimilation. ④ Analysis of carbon balance indicated that most carbon sources were used as electron donors in the denitrification process, but fewer electrons were used for nitrate reduction, and with respect to different carbon sources, electron transfer to the nitrate respiratory chain was regulated by different reduction potentials, electron donor abundance, and molecular weight. Acinetobacter junii ZMF5 could be used to control nitrogen pollution in drinking water reservoirs.

Objective: To investigate the characteristics and predictors for anastomotic leakage after oesophagectomy for oesophageal carcinoma from the perspective of anastomotic level., Design: Retrospective cohort study., Settings: A single tertiary medical centre in China., Participants: From January 2010 to December 2016, all patients with oesophageal cancer of the distal oesophagus or gastro-oesophageal junction undergoing elective oesophagectomy with a curative intent for oesophageal carcinoma with intrathoracic oesophagogastric anastomosis (IOA) versus cervical oesophagogastric anastomosis (COA) were included. We investigated anastomotic level and perioperative confounding factors as potential risk factors for postoperative leakage by univariate and multivariate logistic regression., Primary Outcome Measures: The primary outcome was the odds of anastomotic leakage by different confounding factors. Secondary outcome was the association of IOA versus COA with other postoperative outcomes., Results: Of 458 patients included, 126 underwent cervical anastomosis and 332 underwent intrathoracic anastomosis. Anastomotic leakage developed in 55 patients (12.0%), with no statistical differences between COA and IOA (16.6% vs 10.2%; p=0.058). Multivariable analysis identified active diabetes mellitus (OR 2.001, p=0.047), surgical procedure (open: reference; minimally invasive: OR 1.770, p=0.049) and anastomotic method (semimechanical: reference; stapled: OR 1.821; handsewn: OR 2.271, p=0.048) rather than anastomotic level (IOA: reference; COA: OR 1.622, p=0.110) were independent predictors of leakage., Conclusions: Surgical and anastomotic techniques rather than the level of anastomotic site were independent predictors of postoperative anastomotic leakage in patients undergoing oesophageal cancer surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The impact of different aeration positions on startup and operation of the continuous flow CANON granular sludge process was considered by inoculating flocculent ANAMMOX activated sludge at room temperature (25±1)℃ in two sets of AUSB reactors. The aeration unit of R1 was installed 0.3 m above the base, while the aeration unit of R2 was set at the bottom. R1 and R2 successfully developed the granule CANON process on the 43rd d and 56th d, respectively. The mean particle diameter of R1 granular sludge increased to 214.79 μm, and the eigenvalue (△NO 3 - -N/△TN) was maintained at 0.128; whereas, the granular sludge size of R2 rose to 205.27 μm with an eigenvalue maintained at 0.129. The nitrogen loading rate (NLR) was gradually increased in the low ammonia-nitrogen (90 mg·L -1 ) wastewater within R1 and R2. This was more beneficial in R1, resulting in the persistent growth of CANON granular sludge and the enhancement of the systematic nitrogen removal rate (NRR). The average particle diameter of R1 rose to 507.46 μm in 88 d, while NRR reached up to 0.277 kg·(m 3 ·d) -1 . R2 granule sludge particle size was 467.72 μm after 108 d of cultivation, and achieved a 0.243 kg·(m 3 ·d) -1 NRR, which was 87.73% of that in R1. During the course of steady operation, the specific anoxic/aerobic mode of R1 effectively suppressed NOB microbial activity, the eigenvalue remained around 0.127±0.003, and the NRR of R1 was maintained at about (0.262±0.019) kg·(m 3 ·d) -1 . However, NOB was propagated observably in the continuously aerobic R2, whose eigenvalue rose to 0.136±0.004, while NRR was merely (0.231±0.015) kg·(m 3 ·d) -1 after 125 d of long-term operation. During the whole experiment period, the intermediate-setting aerated AUSB accelerated the formation of CANON granular sludge evolving from flocculent ANAMMOX sludge, and better nitrogen removal performance and operational stability were achieved.

The effect of organic carbon on the start-up and operation of the CANON granular sludge process was investigated in two SBR reactors with different strategies:gradually increased organic carbon concentration (R1) and without organic carbon (R2). The results showed that adding 50 mg·L -1 organic carbon accelerated the start-up of the CANON granular sludge process. R1 and R2 were started up in 23 d and 32 d, respectively. Moreover, the appropriate organic carbon enhanced the activity of AOB, AnAOB, and denitrification, increasing the ammonia removal rates and total nitrogen (TN) removal rates. The maximum ammonia removal rates and total nitrogen removal rates of R1 were 92% and 88%, respectively. The maximum ammonia removal rates and total nitrogen removal rates of R2 were 89% and 80%, respectively. Further tests showed that excessive organic carbon concentration decreased the activity of AOB and AnAOB and reduced the removal efficiency of ammonia and total nitrogen. Adding organic carbon promoted denitrification activity and increased nitrogen removal efficiency.

A pilot-scale bio-filter coupled nitrification and CANON was started up to remove iron, manganese and ammonia nitrogen from groundwater in a plant, and the main removal route of ammonia nitrogen was analyzed. The experiment showed that the bio-filter could be started up successfully and achieved stable operation after 164 days of culture development. The value of △NH 4 + -N/△NO 3 - -N was 1.49, and the oxidation and removal of Fe(Ⅱ), Mn(Ⅱ), and NH 4 + -N were (9.87±1.17), (2.25±0.06), and (1.51±0.06) mg·L -1 , respectively. The calculation based on the quantitative relationship between nitrogen conservation and dissolved oxygen (DO) measurement indicated that the contribution of CANON to NH 4 + -N removal was 33.48%-38.87%, and the average ratio of ammonia nitrogen removal amount to DO was 1:3.79-1:3.94. The removal ratio of ammonia nitrogen was lower with lower temperature.

Granular adsorbents for arsenic removal (GA) made from the backwashing residuals from iron and manganese removal biofilters for groundwater were characterized and examined as an arsenate sorbent. The GA were characterized by SEM-EDS microscopy, X-ray diffraction (XRD), and BET surface area measurement. The results showed that the GA had rough surfaces, developed pores, and were mainly amorphous, with small fractions of crystalline quartz and hematite. The surface area of the GA, which consists of many mesopores, was 43.8 m 2 ·g -1 . The kinetic studies revealed that arsenate adsorption on the GA was described by a pseudo-second-order kinetic equation, and the Freundlich isotherm equation fit the arsenate adsorption well ( R 2 =0.994). The maximum adsorption capacity calculated by the Langmuir isotherm equation for As(Ⅴ) was 5.05 mg·g -1 . Further studies showed that the GA operated well for As(Ⅴ) removal over a broad range in pH from 1.1 to 9.5. The coexistence of HCO 3 - and SO 4 2- had no great influence on arsenic adsorption, while the H 2 PO 4 - and SiO 3 2- showed negative effects. The GA can be regenerated well, and 82% of the original adsorption capacity was maintained after three regeneration cycles.

A pilot-scale bio-filter was constructed for the removal of high concentrations of iron (TFe 9.0-12.0 mg·L -1 , Fe(Ⅱ) 6.5-8.0 mg·L -1 ), manganese (1.9-2.1 mg·L -1 ), and ammonia nitrogen (1.4-1.7 mg·L -1 ) simultaneously from low temperature (5-6℃) groundwater in a plant. The results showed that iron was removed at the beginning of the bio-filter start-up, and manganese and ammonia nitrogen were removed on day 72 and day 75, respectively. The start-up period was influenced by the culture temperature and the raw water quality. For higher filtration rates, the removal of manganese was lower. When the filtration rate was more than 1.0 m·h -1 , the maximum removal of manganese was about 3.0 mg·L -1 . Manganese was the limiting factor for the increase of filtration rate, and the maximum filtration rate of the single bio-filter was 4.5 m·h -1 . When the filtration rate was less than 6.0 m·h -1 , the removal of ammonia nitrogen was about 1.5 mg·L -1 , which was not affected by the filtration rate. Dissolved oxygen (DO) deficiency led to failure with the removal of more ammonia nitrogen. The required thickness of the bio-filter required for purification increased as the concentration of manganese and ammonia nitrogen increased when DO was sufficient. The removed iron, manganese, and ammonia nitrogen move to the depth of the filter layer, and there will be "manganese dissolution" when the filtration rate is increased. Iron and ammonia nitrogen in the filter layer can be oxidized and removed simultaneously. Manganese is oxidized and removed after the iron and ammonia nitrogen. The effective oxidation and removal section of manganese, iron, and ammonia nitrogen are obviously graded.

Objective: We aimed at identifying the predictive roles of Low-Density Lipoprotein Triglycerides (LDL-TG) for major adverse cardiovascular events (MACEs)., Patients and Methods: A longitudinal study in a routine health check-up population was performed with an average follow-up of 4.8 years. The participants involved in this study were 1680, from 2007 to 2009, and all had followed-up for all-cause mortality, cardiovascular disease mortality, and the development of MACEs. The demographic information and anthropometric parameters at baseline were recorded. The baseline and follow-up conventional lipid parameters were measured. We also examined the level LDL-TG, as well as the relationship between its level and MACEs., Results: MACEs individuals were characterized by statistically higher baseline LDL-TG (17.22 ± 8.05 vs. 16.39 ±7.35 nmol/l, p = 0.017). The univariate regression for MACEs group indicated that the LDL-TG (b = 0.813, HR = 2.254, 95% CI: 1.454-3.494, p < 0.001), older age, sex and other factors were a significant risk for MACEs. Furthermore, in the adjusted Cox model showed that only higher baseline LDL-TG (b =0.512, HR = 1.669, 95% CI: 1.013-2.748, p = 0.044) and older age (b = 0.062, HR = 1.064, 95% CI: 1.034-1.094, p < 0.001, Table IV) were still predictors for MACEs., Conclusions: Higher baseline LDL-TG closely associated with MACEs and it is a moderate and independent predictive factor for MACEs.

A series of novel harmine derivatives bearing a benzylindine substituent in position-1 of β-carboline ring were synthesized and evaluated as antitumor agents. The N2-benzylated β-carboline derivatives 3a-g represented the most interesting anticancer activities and compound 3c was found to be the most active agent to diverse cancer cell lines such as gastric carcinoma, melanoma and colorectal cancer. Notably, compound 3c showed low toxicity to normal cells. The treatment significantly induced cell apoptosis. Mechanistically, PI3K/AKT signaling pathway mediated compound 3c-induced apoptosis. Compound 3c inhibited phosphorylation of AKT and promoted the production of reactive oxygen species (ROS). The ROS scavenger, LNAC and GSH, could disturb the effect of compound 3c induced apoptosis and PI3K activity inhibitor LY294002 synergistically enhanced compound 3c efficacy. Moreover, the results from nude mice xenograft model showed that compound 3c treatment effectively inhibited tumor growth and decreased tumor weight. Collectively, our results demonstrated that compound 3c exerts apoptotic effect in cancer cells via suppression of phosphorylated AKT and evocation of ROS generation, which suggested that compound 3c might be served as a promising therapeutic agent for cancer treatment.

The authors investigated whether plasma total homocysteine (tHcy) is a predictive factor for arterial stiffness (carotid-femoral pulse wave velocity [cf-PWV] and carotid-radial PWV) in 1447 patients from a 4.8-year prospective study in Beijing, People's Republic of China. Baseline tHcy showed a significant relationship with follow-up cf-PWV (β=0.817, P=.015) in a multivariable linear regression analysis. A stepwise logistic regression model showed that baseline levels of tHcy were significantly associated with follow-up cf-PWV in the adjusted models. Furthermore, the baseline tHcy levels showed a significant association with increases in cf-PWV. There was no association between the change in tHcy and increase in PWV. The present study clearly demonstrated an association between tHcy levels and arterial stiffness, indicating that tHcy is an independent predictive factor for arterial stiffness in a community-based population., (© 2015 Wiley Periodicals, Inc.)

Molecular imaging has generated a demand for more sensitive contrast agents for magnetic resonance (MR) imaging. We synthesized, by a novel one-step method, Gd(3+) incorporated mesoporous SiO(2) nanoparticles, Gd(2)O(3)@SiO(2), for use as an efficient contrast agent. The prepared nanoparticles were also coated with poly(lactic-co-glycolic acid) (PLGA). The size, morphology, composition and Brunauer-Emmett-Teller specific surface area of the nanoparticles were evaluated. The Gd(2)O(3)@SiO(2) nanoparticles possess intragranular network morphology with a uniform size distribution and an average size of approximately 20-40 nm. The PLGA-coated nanoparticles were spherical or near-spherical in shape with a diameter of approximately 120 nm, a smooth surface, and neither aggregation nor adhesion tendencies. No free Gd ions were detected to dissociate from Gd(2)O(3)@SiO(2) even up to the limit (<0.03 mg/l) of the ICP equipment (IRIS Advantage). Our theoretical computation based on density functional theory (using DMol3, Materials Studio) revealed that the Gd(2)O(3) molecules are fully absorbed on the interface of mesoporous SiO(2) with a stable state of lower energy. Both Gd(2)O(3)@SiO(2) and PLGA-coated Gd(2)O(3)@SiO(2) samples have a larger T(1) relaxivitiy than commercial gadolinium diethylene triaminepentaacetate (Gd-DTPA). In vitro and in vivo MR images using the Gd(2)O(3)@SiO(2) nanoparticles were observed with a 1.5 T clinical MR scanner and compared with the images using Gd-DTPA. The Gd(2)O(3)@SiO(2) nanoparticles display a better magnetic property than commercial Gd-DTPA. In vivo MR imaging demonstrated that the nanoparticles were mainly distributed in the liver. Strong enhancement was also detected in nasopharyngeal carcinoma CNE-2 xenografted tumors. The Gd(2)O(3)@SiO(2) nanoparticles are not only potential candidates for highly efficient contrast agents for MR imaging, but also might be developed into potent targeted probes for in vivo molecular imaging of cancer., (Copyright © 2010 John Wiley & Sons, Ltd.)

A series of hydroxy- or methoxy-substituted phenylmethylenethiosemicarbazones were designed, synthesized and evaluated as mushroom tyrosinase inhibitors. The results demonstrated that most of target compounds had remarkable inhibitory activities on mushroom tyrosinase. Interestingly, compound 2h was found to be the most potent tyrosinase inhibitor with IC50 value of 0.18 microM. The possible interaction mode between compound 2h and tyrosinase was proposed. In addition, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities of select compounds (IC50<10.0 microM) were also investigated. Compounds 2d, 2e, 2h, 2i and 2l exhibited more potent DPPH radical scavenging activity than well-known antioxidants ascorbic acid (Vc) and tertiary butyl hydroquinone (TBHQ). These results suggested that such compounds might be utilized for the development of new candidate for treatment of dermatological disorders.

Objective: To study the relation of expression change of tumor necrosis factor-alpha (TNF-alpha), angiotensin II (Ang II), and endothelin-1 (ET-1), and the effect of imidapril on myocardial hypertrophy due to overload., Methods: Sixty-three rats were randomly divided into four groups: sham operation (n=15), overload group (n=16), imidapril group (n=16), and Caweidiluo group (n=16). Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. Blood samples and heart were harvested 12 weeks after aorta constriction, and myocardial hypertrophy index, the contents of Ang II, ET-1 in the myocardium and plasma were determined by radioimmunoassay and TNF-alpha in the myocardium and plasma were determined by enzyme linked immunoadsorbent assay., Results: Left ventricle showed obvious hypertrophy 12 weeks after operation. The contents of TNF-alpha, Ang II and ET-1 in the myocardium, and the content of TNF-alpha in serum, Ang II and ET-1 in plasma were increased compared with those of controls (all P<0.01). The treatment of imidapril and Caweidiluo could restrain the development of left ventricle hypertrophy after operation, and imidapril decreased the contents of TNF-alpha, Ang II and ET-1 in myocardium compared with overload group (all P<0.01). Imidapril lowered the contents of TNF-alpha in serum, Ang II and ET-1 in plasma, compared with overload group (all P<0.01), but not ET-1. Caweidiluo lowered the contents of TNF-alpha, Ang II and ET-1 in myocardium, the contents of TNF-alpha in serum, Ang II and ET-1 in plasma (all P<0.01) compared with overload group (both P<0.01)., Conclusion: The activation of rennin-angiotensin system (RAS) by over load results to an elevation of TNF-alpha contents in plasma and myocardium, and it is probably one of the major regulatory pathways of myocardial hypertrophy.

Objective: To evaluate whether RNA interference can protect porcine endothelial cells from complement mediated cytotoxicity., Methods: Immortalized porcine aortic endothelial cells of the line PED were cultured and transfected with alpha1,3-galactosyltransferase (alpha1, 3-GT) specific siRNAs. Cells transfected with mismatch SiRNA was used as negative controls. Forty-eight hours later the cells were collected. The expression of alpha1, 3-GT mRNA was examined by RT-PCR. The expression of alpha-Gal was examined by flow cytometry. PED cells ere labeled with (51)Cr and mixed with normal human serum (NHS). The release of (51)Cr was measured by gamma-ray counter. Heat inactivated NHS (HINHS) was used as control., Results: Two isoforms (isoform 1 and isoform 2) were amplified from the PED cells. The expression of alpha1, 3-GT in the PED cells transfected with SiRNA-1 was lower by 70% in comparison with the mock group (69% for the isoform 1 and 72% for the isoform 2, both P < 0.05). However, the expression of alpha1, 3-GT in the PED cells transfected with SiRNA21 was not different from those in the mock group and mismatch group (both P > 0.05). Flow cytometry showed that the average fluorescence intensity of the PED cells transfected with SiRNA-1 was 52, 9, significantly lower than that of the mismatch group and mock group (493.9 and 5-5.7 respectively, both P < 0.0). Fluorescence microscopy observed the "silence effect" of alphaGal after SiRNA-1 transfection. Added with 20% and 40% NHS, the cell dissolution rate of the SiRNA transfection group was lower than that of the mock group by 70% and 60% respectively., Conclusions: alpha1, 3GT gene silencing actually occurs following transfection of SiRNA-1. Porcine endothelial cells can be the targets of RNAi.

Background: Rejection mediated by antibody recognition of the alpha-Gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) is a major barrier in porcine-to-human xenotransplantation. Because the synthesis of alpha-Gal is dependent on alpha1,3 galactosyltransferase (alpha1,3GT), methods of blocking this enzyme are needed. RNA interference induced by small interfering RNA (siRNA) is a powerful technique for allowing the silencing of mammalian genes with great specificity and potency. In this study, we use siRNA for silencing of alpha1,3GT with the purpose of reducing expression of the alpha-Gal epitope and subsequently decreasing immunogenicity of porcine endothelial cells., Methods: alpha1,3GT-specific and control siRNAs were transfected into the porcine aortic endothelial cell line, PED. alpha-Gal expression was assessed by Western blotting, flow cytometry, and immunofluorescence. Protection from human-complement and natural killer (NK)-cell-mediated cytotoxicity was evaluated by Cr-release assays after incubation of PED with normal human serum (NHS) and NK92 cell, respectively., Results: RNA interference was successfully achieved in PED as witnessed by the specific knock-down of alpha1,3GT mRNA levels. Flow cytometric analysis using the Griffonia simplicifolia isolectin B4 lectin confirmed the suppression of alpha1,3GT activity as evidenced by decreased alpha-Gal. Functional relevance of the knock-down phenotype was illustrated by the finding that silenced PED were protected from cytotoxicity of NHS. Protection from NK-mediated cytotoxicity was not observed., Conclusions: Our data are the first to demonstrate that RNA interference is a potent tool to down modulate alpha-Gal expression and to protect endothelial cells from complement-mediated cytotoxicity. Gene silencing by siRNA may represent a new approach for overcoming hyperacute and acute vascular rejection.

Unlabelled: Human natural killer (NK) cells, which can directly lyse porcine endothelial cells, play an important role in xenotransplantation. HLA-G is a nonclassical major histocompatibility complex (MHC) class I molecules that has been implicated in protecting susceptible target cells from lysis by NK cells. The objective was to study the effect of protecting porcine endothelial cells transfected with HLA-G1 from human NK cell lysis., Methods: The recombinant expression vector pcDNA3-HLA-G1 was transfected into primary cultured porcine aortic endothelial cells (PAECs) by lipofection. Surface expression of HLA-G1 in transected PAECs was confirmed by an immunofluoresence technique. Peripheral blood mononuclear cells (PBMC) and NK cell line (NK92) were used as NK effects cells with pcDNA3-HLA-G1-transfected PAECs as targets in a MTT method using pcDNA3 transfection as a negative control., Results: Expression of HLA-G1 on PAECs conferred significant protection against NK-mediated lysis. The rate of NK92 cytotoxicity was reduced to 41.5% +/- 14.0% from 75.3% +/- 10.5% in the control group (P < .01). Similarly the rate of the PBMC cytotoxicity among different donors (n = 7) was reduced to 45.4% +/- 12.1% in contrast to 74.6% +/- 11.2% in the control group (P < .05)., Conclusions: HLA-G1 molecules can directly protect xenogeneic PAECs against attack by human NK cells. These results indicate that the expression of HLA-G1 on the porcine cell surface may provide a new approach to overcome NK-mediated immunity to xenografts.

Aim: To derive a model that could be used in drug design., Methods: Beta-carbolines are reported to have antitumor activities on cultured cancer cell lines. A comparative molecular field analysis (CoMFA) was undertaken to elucidate the correlation of cytotoxities and structural parameters of 16 beta-carboline analogs (1-16). The compound 12 was finally used as a template for the other compounds in the dataset because of its highest biological activity., Results: The CoMFA applied to the final alignment resulted in a q2(cv) of 0.656 and it showed that the steric fields contributed 43.3% of the model information while the electrostatic fields represented the other 56.7%., Conclusion: Three designed compounds, which were predicted to have high, moderate and low activities respectively, were synthesized. The IC50 values of these compounds indicated the significance of the analysis in this study. The model derived from the current study could be further used in design for more active compounds.