Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammat...Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions.Here,we investigated for the first time the therapeutic effect of DMF on periodontitis.In vivo studies showed that DMF significantly inhibited periodontal destruction,enhanced mitophagy,and decreased the M1/M2 macrophage ratio.In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages,with improved mitochondrial function,inhibited oxidative stress,and increased mitophagy in RAW 264.7 cells.Furthermore,DMF increased intracellular mitochondrial Tu translation elongation factor(TUFM)levels to maintain mitochondrial homeostasis,promoted mitophagy,and modulated macrophage polarization,whereas TUFM knockdown decreased the protective effect of DMF.Finally,mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway.Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages,resulting in a shift in the balance of macrophage polarization,thereby attenuating periodontitis.Importantly,this study provides new insights into the prevention of periodontitis.展开更多
BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological brea...BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological breakthroughs in patients during TAF treatment are rare,patients with incomplete responses to TAF are occasionally observed.AIM To investigate responsible mutations in the reverse transcriptase region of hepatitis B virus(HBV)for TAF-incomplete responses.METHODS Thirteen chronic hepatitis B patients who received TAF monotherapy were included.A TAF-incomplete responder was defined as one who was continuously positive for HBV DNA over 2 years after TAF treatment initiation.The emergences of mutations in TAF-incomplete responders were evaluated before,one year after,and two years after treatment by deep sequencing of HBV DNA and RNA.RESULTS Two patients were continuously positive for HBV DNA over two years.The rtL269I mutation,one of the CYEI mutations linked to tenofovir resistance,was detected in both patients by direct sequencing.The deep sequencing analysis revealed that a combination of rtT118A and rtL220I mutations and the rtL269I mutation were predominantly detected in HBV DNA even when these mutations were barely detected in HBV RNA.This suggests a superior replication capability of the HBV variants with these mutations under TAF treatment.CONCLUSION The deep sequencing analysis of HBV DNA and RNA and comparing the detection rates of mutations were useful for estimating responsible mutations for TAF-incomplete responses.Such analysis is needed to evaluate the association between mutations that emerge during TAF treatment and incomplete responses to TAF.展开更多
BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alan...BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.展开更多
The aim of this work was to study effects of ketotifen fumarate(KF)on prevention of tissue damage in testes of rats with experimental autoimmune orchitis(EAO)and on the contralateral testis in a model of prolonged tes...The aim of this work was to study effects of ketotifen fumarate(KF)on prevention of tissue damage in testes of rats with experimental autoimmune orchitis(EAO)and on the contralateral testis in a model of prolonged testicular cord torsion(TCT).Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution(vehicle group).Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score.Mast cells(MC)were identified by histochemistry and quantified.In EAO model,KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group.KF also reduced the number of testicular MC compared to vehicle group.Similarly,in TCT model,multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium,seminiferous tubule atrophy,and interstitial edema.Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed.In contrast,sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features.A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals.In conclusion,we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models.The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.展开更多
To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, t...To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.展开更多
A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electroc...A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.展开更多
Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats wer...Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.展开更多
Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflam...Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.展开更多
[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcita...[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.展开更多
Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with a...[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of （89.2 ±0.2） g were fed with the basal fodder supplemented with different levels of ferrous fumarate （0, 20, 40, 80,160 and 480 mg/kg iron） for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously （ P 〉 0.05）. With the increase of dietary iron level, hemoglobin （Hb） content and number of red blood cells（RBC） rose firstly and then leveled off. No significance was found in hematocrit （Hct） among the six groups （P 〉0.05）. Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level（ P 〈0.05）, and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups （ P〉0.05）, while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups （ P〈0.05）, and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups （ P 〈0.05）. Copper content in the whole body increased significantly with the increase of dietary iron level （P 〈 0.05 ）, while no significant difference was observed in the vertebrae （ P 〉0.05）, and copper concentration in the muscle in control group was significantly lower than that of other groups （ P 〈0.05）. Serum lysozyme （LZM） activity of group DO was significantly lower than that of other groups （ P 〈 0.05） except for group D480 （ P 〉 0.05）. Catalase （CAT） activity of serum enhanced significantly （ P 〈 0.05） from DO to EH0 and then decreased obviously （P 〈0.05）. [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.展开更多
Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into ...Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.展开更多
Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and me...Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.展开更多
Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective ...Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm<sup>-1</sup> (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.展开更多
Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarat...Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.展开更多
Methane in rice paddies is mainly produced by methanogenic communities feeding on carbon from root exudates and debris.However,the dominant root secretion governing methane emissions is not yet identified after decade...Methane in rice paddies is mainly produced by methanogenic communities feeding on carbon from root exudates and debris.However,the dominant root secretion governing methane emissions is not yet identified after decades of studies,even though secreted carbohydrates and organic acids have been shown to contribute to methane emissions.In this study,we discovered that fumarate and ethanol are two major rice-orchestrated secretions and play a key role in regulating methane emissions.Fumarate released in the rhizosphere is metabolized by microorganisms,supporting the growth of methanogenic archaea that produce methane as an end carbon product,while ethanol mitigates methane emissions through inhibition of methanogenic activity and growth as well as reducing fumarate synthesis in the rice root.Furthermore,we elucidated the route of fumarate metabolism in the anoxic rhizospheric zone.We found that fumarate in the rice root is produced from acetate via propionate and succinate,and when released into soil directly is oxidized to propionate before conversion via acetate into methane as the end product.The knowledge on fumarate and ethanol metabolism in rice was then used for hybrid breeding of new rice varieties with the property of low methane emission.Cultivation of these novel rice lines or employing our findings for rice cultivation managements showed up to 70%reductions in methane production from seven paddy field sites during 3 years of cultivation trials.Taken together,these findings offer great possibilities for effective mitigation of the global climatic impact of rice cultivation.展开更多
Poly(diethyl fumarate-co-methoxyethyl acrylate-co-vinyl chloroacetate)(PDEFMV),a novel bio-based elastomer with a saturated structure,was synthesized via redox emulsion polymerization.The glass-transition temperatures...Poly(diethyl fumarate-co-methoxyethyl acrylate-co-vinyl chloroacetate)(PDEFMV),a novel bio-based elastomer with a saturated structure,was synthesized via redox emulsion polymerization.The glass-transition temperatures of PDEFMV,adjusted through the variation of the diethyl fumarate-to-methoxyethyl acrylate feeding ratio,ranged from-36.1 to-14.8 ℃.The number-average molecular weights of PDEFMV ranged from 384,000 to 46,000 g/mol.In designing the molecular structure,vinyl chloroacetate was used to provide active sites for subsequent vulcanization and crosslinking.The active chlorine groups within the PDEFMV chain reacted with the crosslinking agent trithiocyanuric acid under high temperature and pressure to form a nonsulfur crosslinked three-dimensional network structure.To achieve the desired properties,carbon black(CB,N330) was incorporated to reinforce PDEFMV,leading to the formation of PDEFMV/CB composites.A comprehensive study was conducted on the high-temperature oil resistance of PDEFMV/CB composites.Following immersion in IRM903 oil at temperatures of 150 and 200 ℃ for 72 h,the mass and volume changes in PDEFMV/CB were lower than those observed in commercially available acrylate rubber(AR)/CB,indicating that PDEFMV exhibited superior oil resistance.Furthermore,the aging characteristics and mechanisms of oil resistance in the PDEFMV/CB and AR/CB composites were investigated at different temperatures(150,200,and 250 ℃).The results provide insights into the operational temperature ranges suitable for PDEFMV/CB and offer valuable guidance for potential industrial applications.展开更多
Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumara...Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.展开更多
基金Natural Science Foundation of China(grant nos.82270991)Zhejiang Provincial Natural Science Foundation of China/Outstanding Youth Science Foundation(grant no.LR21H140002)+4 种基金Medical Health Science and Technology Major Project of Zhejiang Provincial Health Commission(grant no.WKJ-ZJ-2311)Wenzhou Science and Technology Bureau Public Welfare Social Development(Medical and Health)Science and Technology Project(grant no.ZY2021015)Opening Research Fund from Shanghai Key Laboratory of Stomatology,Shanghai Ninth People’s Hospital,College of Stomatology,Shanghai Jiao Tong University School of Medicine(grant no.2022SKLS-KFKT011)Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research(grant no.GXKLRROM2106)State Key Laboratory of Oral Diseases Open Fund(grant no.SKLOD2024OF08).
文摘Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions.Here,we investigated for the first time the therapeutic effect of DMF on periodontitis.In vivo studies showed that DMF significantly inhibited periodontal destruction,enhanced mitophagy,and decreased the M1/M2 macrophage ratio.In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages,with improved mitochondrial function,inhibited oxidative stress,and increased mitophagy in RAW 264.7 cells.Furthermore,DMF increased intracellular mitochondrial Tu translation elongation factor(TUFM)levels to maintain mitochondrial homeostasis,promoted mitophagy,and modulated macrophage polarization,whereas TUFM knockdown decreased the protective effect of DMF.Finally,mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway.Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages,resulting in a shift in the balance of macrophage polarization,thereby attenuating periodontitis.Importantly,this study provides new insights into the prevention of periodontitis.
基金Supported by the Japan Agency for Medical Research and Development(AMED),No.JP22fk0310503.
文摘BACKGROUND Tenofovir alafenamide fumarate(TAF)is one of the first-line treatments used to treat chronic hepatitis B patients;TAF has strong antiviral activity and a high barrier to resistance.Although virological breakthroughs in patients during TAF treatment are rare,patients with incomplete responses to TAF are occasionally observed.AIM To investigate responsible mutations in the reverse transcriptase region of hepatitis B virus(HBV)for TAF-incomplete responses.METHODS Thirteen chronic hepatitis B patients who received TAF monotherapy were included.A TAF-incomplete responder was defined as one who was continuously positive for HBV DNA over 2 years after TAF treatment initiation.The emergences of mutations in TAF-incomplete responders were evaluated before,one year after,and two years after treatment by deep sequencing of HBV DNA and RNA.RESULTS Two patients were continuously positive for HBV DNA over two years.The rtL269I mutation,one of the CYEI mutations linked to tenofovir resistance,was detected in both patients by direct sequencing.The deep sequencing analysis revealed that a combination of rtT118A and rtL220I mutations and the rtL269I mutation were predominantly detected in HBV DNA even when these mutations were barely detected in HBV RNA.This suggests a superior replication capability of the HBV variants with these mutations under TAF treatment.CONCLUSION The deep sequencing analysis of HBV DNA and RNA and comparing the detection rates of mutations were useful for estimating responsible mutations for TAF-incomplete responses.Such analysis is needed to evaluate the association between mutations that emerge during TAF treatment and incomplete responses to TAF.
文摘BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.
基金This work was supported by grants from Found ation“Florencio Fiorini”the University of Buenos Aires(UBACYT 2014-201722320160100058BA).
文摘The aim of this work was to study effects of ketotifen fumarate(KF)on prevention of tissue damage in testes of rats with experimental autoimmune orchitis(EAO)and on the contralateral testis in a model of prolonged testicular cord torsion(TCT).Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution(vehicle group).Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score.Mast cells(MC)were identified by histochemistry and quantified.In EAO model,KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group.KF also reduced the number of testicular MC compared to vehicle group.Similarly,in TCT model,multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium,seminiferous tubule atrophy,and interstitial edema.Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed.In contrast,sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features.A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals.In conclusion,we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models.The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.
文摘To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI). METHODSRats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined. RESULTSHistological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group. CONCLUSIONDMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.
文摘A comparison of voltammetric behavior of bisoprolol fumarate (BF) at edge and basal plane pyrolytic graphite electrodes (EPPGE/BPPGE) has been made with single wall carbon nanotube modified glassy carbon. The electrochemical properties are investigated exercising the cyclic voltammetry and square wave voltammetry (SWV). Enhanced peak current associated with bisoprolol fumarate oxidation at EPPGE is due to its better electron transfer property. Quantification of bisoprolol fumarate was carried out at pH 7.2 at both the pyrolytic graphite electrodes. Well-defined peak has been observed at ~ 792 and 954 mV at EPPGE and BPPGE respectively for bisoprolol fumarate oxidation. The detection limit is found to be 2.8 × 10–7 M and 7.3 × 10–7 M for EPPGE and BPPGE respectively. A comparison of common quantification parameters for bisoprolol at carbon nanotube modified glassy carbon electrode and bare BPPGE and EPPGE has been made and it is observed that carbon naotube modified glassy carbon exhibits sensitivity and detection limit close to that observed at bare basal plane pyrolytic graphite electrode. The method developed is applicable for determination of bisoprolol fumarate in pharmaceutical preparations and real samples.
基金supported by the College Science Technology Research Project of Hebei Province(Grant No:ZD20131002)
文摘Objective:To discuss the effect of dimethyl fumarate(DMF) on rats with L-arginine induced chronic pancreatitis(CP).Methods:Male Wistar rats were given DMF treatment(25 mg/kg) by oral lavage method;then Wistar rats were given the intraperitoneal injection of L-arginine for 5times(250 mg/100 kg,twice per time,each interval of 1 h) for building of CP model.Rats were divided into control group,CP group,DMF group and CP+DMF group.Rats in CP+DMF group were given the oral intragastric administration of DMF(25 mg/kg),while rats in control group and CP group were given the equal volume of normal saline.The weight of rats was evaluated and the intraperitoneal glucose tolerance test was performed(IPGTT,2 g/kg).The islet of rats was isolated and then flow cytometry was employed to evaluate the quality and activity of islets.Meanwhile,the histology of non-endocrine tissues and levels of myeloperoxidase(MPO) and malondialdchyde(MDA) were detected.Results:Compared with control group,the weight of rats in CP group was significantly reduced at week 2,4 and 6;the blood glucose significantly increased,AUC increased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration increased,levels of MDA and MPO increased,the islet equivalent and islet activity decreased at 0.30,60,120 and 180 min.Compared with CP group,the weight of rats in CP+DMF group significantly increased at week 2,4 and 6;the blood glucose significantly decreased.AUC decreased,the histopathological scores of pancreatic atrophy,acinar injury,edema and cellular infiltration decreased,levels of MDA and MPO decreased,the islet equivalent and islet activity increased at 0,30.60,120 and 180 min.Conclusions:DMF treatment can improve CP induced by L-argininc and islet function in rats.
文摘Metabolic rewiring underlies the effector functions of macrophages1-3,but the mechanisms involved remain incompletely defined.Here,using unbiased metabolomics and stable isotope-assisted tracing,we show that an inflammatory aspartate argininosuccinate shunt is induced following lipopolysaccharide stimulation.The shunt,supported by increased argininosuccinate synthase(ASS1)expression,also leads to increased cytosolic fumarate levels and fumarate-mediated protein succination.Pharmacological inhibition and genetic ablation of the tricarboxylic acid cycle enzyme fumarate hydratase(FH)further increases intracellular fumarate levels.
基金Project for Improving Basic Research Ability of Middle Aged and Young Teachers in Colleges and Universities of Guangxi in 2017(2017KY0284)Project of Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine(GXZYKF2019-7)+2 种基金Program of Key Laboratory for Extraction and Purification and Quality Analysis of TCM in 2017(J1700208)Project of Guangxi University of Chinese Medicine(YB14004)Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine([2013]No.20).
文摘[Objectives]To establish a new method for indirect determination of bisoprolol fumarate based on fluorescence quenching technology.[Methods]In ammonia water and ammonium chloride buffer solution at pH=9.2,whenλexcitation=277 nm andλemission=596 nm,with the increase of CCu2+,the fluorescence signal intensity of bisoprolol fumarate weakened,and the difference between the fluorescence intensity of bisoprolol fumarate itself and the fluorescence intensity of the test solution after the quencher Cu2+was added(ΔF)and Cbisoprolol fumarate showed a good linear relationship.[Results]In the range of 15.39-76.93μg/mL,ΔF=146.7 Cbisoprolol fumarate+482.1,r=0.9988,and the detection limit is 0.1391μg/mL.[Conclusions]The fluorescence quenching method has been applied to the determination of actual samples with a recovery rate of 99.9%and an RSD of 2.7%.The results are satisfactory.
文摘Symmetric, diesters of cis- or trans- bicyclo[2,2,1]hept-5-ene-2,3-dicarboxylate were prepared by aqueous Diels-Alder reaction of cyclopentadiene with symmetric diester of fumarate or maleate.
基金funded by Technical System of Modern Agricultural Industry (nycytx-50 )Agriculture Transfer Fund of Ministry of Science and Technology (03EFN213700155)+1 种基金Scientific and Technological Development Plan Project of Shandong Province (2010-2013)Taishan Scholar Post Fund about Aquatic Animal Nutrient and Feed of Shandong Province(HY201004)
文摘[ Objective] The study aimed to discuss the effects of ferrous fumarate on growth performance, blood biochemical parameters and content of trace element of Oncorhynchus mykiss. [ Method ] Juvenile rainbow trout with an initial weight of （89.2 ±0.2） g were fed with the basal fodder supplemented with different levels of ferrous fumarate （0, 20, 40, 80,160 and 480 mg/kg iron） for 60 d, and the six groups were named DO, D20, D40, D80, D160 and D480, wherein DO was as the control group, actually containing 62.60, 79.50, 99.60, 139.30, 215.20 and 538.40 mg/kg iron respectively. [ Result] The growth performance of juvenile rainbow trout was not affected by different dietary iron levels obviously （ P 〉 0.05）. With the increase of dietary iron level, hemoglobin （Hb） content and number of red blood cells（RBC） rose firstly and then leveled off. No significance was found in hematocrit （Hct） among the six groups （P 〉0.05）. Iron content in the whole body, vertebrae and muscle increased significantly with the improvement of dietary iron level（ P 〈0.05）, and iron concentration in the liver increased firstly and then leveled off in groups from D40 to D480. No significant difference in zinc content of the whole body was found among the six groups （ P〉0.05）, while zinc content in the vertebrae and muscle in control group was significantly higher than that of other groups （ P〈0.05）, and zinc concentration in the liver in groups DO and 1320 was significantly higher than that of other groups （ P 〈0.05）. Copper content in the whole body increased significantly with the increase of dietary iron level （P 〈 0.05 ）, while no significant difference was observed in the vertebrae （ P 〉0.05）, and copper concentration in the muscle in control group was significantly lower than that of other groups （ P 〈0.05）. Serum lysozyme （LZM） activity of group DO was significantly lower than that of other groups （ P 〈 0.05） except for group D480 （ P 〉 0.05）. Catalase （CAT） activity of serum enhanced significantly （ P 〈 0.05） from DO to EH0 and then decreased obviously （P 〈0.05）. [ Conclusion] Based on hemoglobin and iron content in the liver, the broken-line model analysis showed that the dietary iron level provided by ferrous fumarate for juvenile rainbow trout was estimated to be 99.8 and 100.4 mg/kg respectively in the experiment.
基金This study was supported by Natural Science Foundation of Gansu Province(No.20JR10RA727)。
文摘Objective:To evaluate the protective effect and mechanism of clemastine fumarate(CLE)on acute lung injury(ALI)in intestinal ischemia-reperfusion(I/R)mice.Methods:Twenty-four SPF Balb/c mice were randomly divided into sham operation group(sham group),ischemia-reperfusion group(I/R group),and clemastine fumarate pretreatment group(I/R+C group).In the I/R group,an intestinal ischemia-reperfusion model was established(ischemia for 40 minutes,reperfusion for 2 hours).In the I/R+C group,CLE 5 mg/kg was intraperitoneally injected before the operation.Lung tissue morphology was observed and scored by HE staining;and the ratios of wet weight to dry weight(W/D)were recorded.the levels of MDA,SOD,GSH-px,NF-κB and TNF-αin lung tissue of each group were determined by ELISA;Western blot method was used to determine the expression of TLR4 protein in lung tissue.Results:Compared with the Sham group,the I/R group had significantly higher lung tissue injury score and wet/dry ratio(P<0.05),increased lung tissue MDA level(P<0.05),decreased SOD and GSH-px levels(P<0.05),and increased NF-κB and TNF-αlevels,the expression of TLR4 protein in lung tissue increased(P<0.05);compared with the I/R group,the lung tissue injury score and wet/dry ratio of the I/R+C group decreased(P<0.05),the level of MDA in lung tissue decreased(P<0.05),the levels of SOD and GSH-px increased(P<0.05),and the levels of NF-κB and TNF-毩decreased(P<0.05),the expression of TLR4 protein in lung tissue decreased(P<0.05).Conclusion:Clemastine fumarate can alleviate acute lung injury after intestinal ischemia-reperfusion in mice,and the mechanism may be related to the inhibition of oxidative stress and inflammatory response in lung tissue.
文摘Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.
文摘Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm<sup>-1</sup> (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.
文摘Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease, and proton pump inhibitors (PPIs) have been recommended as the first-line treatment for GERD. In recent years, studies on vonoprazan fumarate in the treatment of GERD have attracted widespread attention. In this paper, we review the research progress of vonoprazan fumarate and proton pump inhibitors in the treatment of GERD in recent years, and compare and analyze the efficacy, safety, tolerability, and advantages and disadvantages of long-term application of both. By reviewing the relevant literature, we found that vonoprazan fumarate has similar performance with proton pump inhibitors in terms of efficacy and safety, but has potential advantages in terms of tolerability and long-term application. Therefore, we believe that vonoprazan fumarate may become a new option for GERD treatment, helping clinicians to develop more appropriate treatment plans for patients and providing new ideas and directions for research in related fields.
基金funded by Mr.Zheng Fang,Beijing Xianhe Transportation Technology Co.Ltd.Trees and Crops for the Future(TC4F)+2 种基金the Swedish Research Council for Environment,Agricultural Sciences and Spatial Planning(FORMASproject nos.219-2014-1172 and 2020-01327)NSFC Projects of International Cooperation and Exchanges,no.32011530117.Jia Hu obtained a stipend from the China Scholarship Council(file no.201708430115).
文摘Methane in rice paddies is mainly produced by methanogenic communities feeding on carbon from root exudates and debris.However,the dominant root secretion governing methane emissions is not yet identified after decades of studies,even though secreted carbohydrates and organic acids have been shown to contribute to methane emissions.In this study,we discovered that fumarate and ethanol are two major rice-orchestrated secretions and play a key role in regulating methane emissions.Fumarate released in the rhizosphere is metabolized by microorganisms,supporting the growth of methanogenic archaea that produce methane as an end carbon product,while ethanol mitigates methane emissions through inhibition of methanogenic activity and growth as well as reducing fumarate synthesis in the rice root.Furthermore,we elucidated the route of fumarate metabolism in the anoxic rhizospheric zone.We found that fumarate in the rice root is produced from acetate via propionate and succinate,and when released into soil directly is oxidized to propionate before conversion via acetate into methane as the end product.The knowledge on fumarate and ethanol metabolism in rice was then used for hybrid breeding of new rice varieties with the property of low methane emission.Cultivation of these novel rice lines or employing our findings for rice cultivation managements showed up to 70%reductions in methane production from seven paddy field sites during 3 years of cultivation trials.Taken together,these findings offer great possibilities for effective mitigation of the global climatic impact of rice cultivation.
基金supported by the National Key Research and Development Program of China (2022YFC2104700)the National Natural Science Foundation of China (52273003,51988102)。
文摘Poly(diethyl fumarate-co-methoxyethyl acrylate-co-vinyl chloroacetate)(PDEFMV),a novel bio-based elastomer with a saturated structure,was synthesized via redox emulsion polymerization.The glass-transition temperatures of PDEFMV,adjusted through the variation of the diethyl fumarate-to-methoxyethyl acrylate feeding ratio,ranged from-36.1 to-14.8 ℃.The number-average molecular weights of PDEFMV ranged from 384,000 to 46,000 g/mol.In designing the molecular structure,vinyl chloroacetate was used to provide active sites for subsequent vulcanization and crosslinking.The active chlorine groups within the PDEFMV chain reacted with the crosslinking agent trithiocyanuric acid under high temperature and pressure to form a nonsulfur crosslinked three-dimensional network structure.To achieve the desired properties,carbon black(CB,N330) was incorporated to reinforce PDEFMV,leading to the formation of PDEFMV/CB composites.A comprehensive study was conducted on the high-temperature oil resistance of PDEFMV/CB composites.Following immersion in IRM903 oil at temperatures of 150 and 200 ℃ for 72 h,the mass and volume changes in PDEFMV/CB were lower than those observed in commercially available acrylate rubber(AR)/CB,indicating that PDEFMV exhibited superior oil resistance.Furthermore,the aging characteristics and mechanisms of oil resistance in the PDEFMV/CB and AR/CB composites were investigated at different temperatures(150,200,and 250 ℃).The results provide insights into the operational temperature ranges suitable for PDEFMV/CB and offer valuable guidance for potential industrial applications.
基金supported by the Key Project of Hangzhou Science and Technology Bureau of Agriculture and Social Development Scientific Research(2022A04A02)Zhejiang Province Medical and Health Research Project(2018KY628)Hangzhou City Social Development Scientific Research Active Design Project(20172016A03).
文摘Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.
