Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen re...Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.展开更多
The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-inf...The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.展开更多
To enhance the mechanical reliability of dental prostheses under long-term service conditions,this study aimed to evaluate the fracture behavior and energy dissipation characteristics of three commonly used prosthetic...To enhance the mechanical reliability of dental prostheses under long-term service conditions,this study aimed to evaluate the fracture behavior and energy dissipation characteristics of three commonly used prosthetic materials,namely,zirconia ceramics(ZrO_(2)),cobalt-chromium alloy(Co-Cr),and titanium-zirconium alloy(Ti-13Zr),under various crack configurations.A three-dimensional finite element model of a single-crown prosthesis incorporating predefined cracks was established,and both axial and oblique multidirectional loads were applied.Using LS-DYNA software,the deformation patterns,principal stress distribution,and energy release characteristics during crack propagation were systematically analyzed.The experimental results indicate that Ti-13Zr alloy exhibited the highest crack resistance,making it particularly suitable for patients with insufficient bone volume or limited implant space.Co-Cr alloy demonstrated favorable structural stability and mechanical performance under high-load conditions.In contrast,due to its inherent brittleness,ZrO_(2)was more prone to rapid fracture propagation in long-span or high-stress scenarios,although it remains a preferred option for anterior esthetic zones and patients with metal sensitivities.Furthermore,the simulation outcomes were theoretically validated using Griffith's energy-based fracture criterion,reinforcing the accuracy of failure predictions based on principal stress analysis.This study elucidates the differences in clinical applicability among prosthetic materials and reveals their distinct fracture mechanisms,thereby providing a theoretical foundation for optimizing material selection and structural design.The findings contribute to improving the long-term safety and functional stability of implant-supported dental restorations.展开更多
Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties ...Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties against neurodegenerative diseases).Nonhuman primates are ideal models for studying neurodegenerative diseases;however,existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels,nor recapitulate the impaired uric acid excretion observed in clinical hyperuricemic patients.Methods:First,we detected uricase expression in cynomolgus monkeys and compared it with that in mice.Then,we established a cynomolgus monkey hyperuricemia model by administering a mixture of potassium oxonate,hydrochlorothiazide,and adenine via fruits and vegetables.We further analyzed the regulatory effects of this model on uric acid metabolism(synthesis,degradation,and excretion)and the expression of uric acid transporter genes in the intestine and kidney.Results:Cynomolgus monkeys express functional uricase,but at a lower level than mice.The established model maintained stable,long-term hyperuricemia by three mechanisms:increasing intestinal and renal uric acid excretion load,inhibiting hepatic uric acid degradation,and promoting uric acid synthesis.Additionally,the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes,while upregulating uric acid-reabsorbing transporter genes.Conclusions:This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases,and will help clarify the mechanism by which serum uric acid influences cognitive function.展开更多
Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.I...Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.展开更多
Glioma,the most prevalent primary tumor of the central nervous system(CNS),is also the most lethal primary malignant tumor.Currently,there are limited chemotherapeutics available for glioma treatment,necessitating fur...Glioma,the most prevalent primary tumor of the central nervous system(CNS),is also the most lethal primary malignant tumor.Currently,there are limited chemotherapeutics available for glioma treatment,necessitating further research to identify and develop new chemotherapeutic agents.A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products(NPs)and optimizing their structures.Additionally,targeted drug delivery systems(TDDSs)are employed to enhance drug solubility and stability and overcome the blood-brain barrier(BBB).TDDSs can penetrate deep into the brain,increase drug concentration and retention time in the CNS,and improve the targeting efficiency of NPs,thereby reducing adverse effects and enhancing anti-glioma efficacy.This paper reviews the research progress of anti-glioma activities of NPs,including alkaloids,polyphenols,flavonoids,terpenoids,saponins,quinones,and their synthetic derivatives over the past decade.The review also summarizes anti-glioma mechanisms,such as suppression of related protein expression,regulation of reactive oxygen species(ROS)levels,control of apoptosis signaling pathways,reduction of matrix metalloproteinases(MMPs)expression,blocking of vascular endothelial growth factor(VEGF),and reversal of immunosuppression.Furthermore,the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined.The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.展开更多
The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst&...The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst's ability to adsorb and activate N_(2)and H_(2)O,while the ultrathin structure with maximized active crystal facets can maximize the enrichment of effective photogenerated electrons.This work employs a two-step synergistic method to fabricate ultrathin BiVO_(4)with oxygen vacancies and bismuth vacancies(2D-V_(Bi+O)-BVO,thickness<20 nm)for photocatalytic nitrogen reduction.Scanning electron microscopy,transmission electron microscopy(TEM),and atomic force microscopy characterization confirm the transformation of BiVO_(4)from bulk material(bulk-BVO,~1300 nm)to an ultrathin structure(~15 nm).TEM,X-ray photoelectron spectroscopy,electron paramagnetic resonance characterizations,and density functional theory(DFT)calculations verify the construction of oxygen and bismuth vacancies in the ultrathin BiVO_(4).Compared to bulk-BVO,the photocatalytic nitrogen fixation efficiency of 2D-V_(Bi+O)-BVO is increased by 4.7 times,with the highest activity reaching 158.73μmol·g^(-1)·h^(-1).N_(2)-temperature programmed desorption and DFT calculations demonstrate that the oxygen and bismuth vacancies in BiVO_(4),respectively,promote the adsorption/activation of N_(2)and H_(2)O,which is crucial for the overall nitrogen reduction reaction.Photo-deposition experiments prove that the(040)plane is the active surface for electrons.And the ultrathin structure maximizes the(040)facet of BiVO_(4),which is conducive to the high enrichment of electrons.Meanwhile,more active sites can be exposed for the activation of N_(2)and H_(2)O.In situ infrared spectroscopy confirms that N_(2)can be effectively adsorbed onto 2D-V_(Bi+O)-BVO,and the presence of NH_(2)-NH_(2)active species is consistent with the alternating reaction pathway.This study provides new insights into the development of green and efficient photocatalysts with dual vacancies and ultrathin structures.展开更多
Curcumin,a bioactive compound extracted from Curcuma longa.L.,demonstrates significant therapeutic potential in inflammatory diseases.This study aims to explore the effects of curcumin on hyperuricemia with acute gout...Curcumin,a bioactive compound extracted from Curcuma longa.L.,demonstrates significant therapeutic potential in inflammatory diseases.This study aims to explore the effects of curcumin on hyperuricemia with acute gout and associated renal dysfunction in a mouse model.The results show that curcumin treatment alleviates ankle joint swelling,reduces inflammatory cytokines IL-1βand TNF-α,and lowers serum uric acid concentrations.High-dose curcumin notably inhibits xanthine oxidase(XOD)activity,a key enzyme in uric acid production,while it enhances the renal expression of the urate transporter ABCG2,thereby promoting uric acid excretion.Furthermore,curcumin effectively mitigates renal injury as evidenced by reduced serum creatinineand blood urea nitrogen levels and suppresses renal inflammation.At the molecular level,curcumin exerts potent antioxidant effects by lowering reactive oxygen species(ROS)levels in both cultured HK-2 human renal tubular epithelial cells and RAW264.7 mouse macrophages.The curcumin-mediated effects are associated with the disruption of NEK7-NLRP3 complex formation,leading to the suppression of the ROS/NEK7-NLRP3 inflammasome pathway.This,in turn,inhibits pyroptosis and the subsequent release of mature IL-1β.These findings suggest that curcumin not only reduces uric acid production but also modulates inflammation through ROSscavenging properties and its ability to inhibit the NLRP3 inflammasome.展开更多
This study constructed an in vitro blood-brain barrier(BBB)transwell model to investigate the regulatory effects and mechanisms of the photothermal effects of gold nanorods(AuNRs)excited by the second near-infrared re...This study constructed an in vitro blood-brain barrier(BBB)transwell model to investigate the regulatory effects and mechanisms of the photothermal effects of gold nanorods(AuNRs)excited by the second near-infrared region(NIR-II)on BBB permeability.The experimental results showed that the photothermal effects of NIR-II t AuNRs significantly decreased trans-epithelial electrical resistance(TEER)and increased the permeability of fluorescein isothiocyanate(FITC)-dextran,indicating that it can effectively open the BBB.This effect was reversible,and the TEER and FITC permeability returned to baseline levels within 24 h after treatment.Mechanistic studies revealed that BBB opening did not rely on apoptosis,cytoskeletal disruption,mitochondrial dysfunction,or inflammation.The opening of the BBB was closely associated with a temporary decrease in the expression and conformational change of the tight junction protein occludin due to the photothermal effect.Molecular simulations and docking analysis revealed that the heat shock protein HSP70 could bind to the conformationally altered occludin,supporting the regulatory role of photothermal effects on tight junction proteins.In summary,NIR-II t AuNRs achieved safe and reversible opening of the BBB by regulating the conformation and expression of tight junction proteins,providing a deeper insight for further research on BBB and the treatment of neurological diseases.展开更多
Precise tumor targeting and therapy is a major trend in cancer treatment.Herein,we designed a tumor acidic microenvironment activatable drug loaded DNA nanostructure,in which,we made a clever use of the sequences of A...Precise tumor targeting and therapy is a major trend in cancer treatment.Herein,we designed a tumor acidic microenvironment activatable drug loaded DNA nanostructure,in which,we made a clever use of the sequences of AS1411 and i-motif,which can partially hybridize,and designed a simple while robust DNA D-strand nanostructure,in which,i-motif sequence was designed to regulate the binding ability of the AS1411 aptamer to target tumor.In the normal physiological environment,i-motif inhibits the targeting ability of AS1411.In the acidic tumor microenvironment,i-motif forms a quadruplex conformation and dissociates from AS1411,restoring the targeting ability of AS1411.Only when acidic condition and tumor cell receptor are present,this nanostructure can be internalized by the tumor cells.Moreover,the structure change of this nanostructure can realize the release of loaded drug.This drug loaded A-I-Duplex DNA structure showed cancer cell and spheroid targeting and inhibition ability,which is promising in the clinical cancer therapy.展开更多
Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belong...Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belonging to the same batch were randomly divided into 3 groups(n=10)using a random number table:Sham Surgery Control Group(Sham),Ischemia-Reperfusion(I/R)Group,and Ischemia-Reperfusion Group with Environmental Enrichment Intervention(I/R+EEI).The expression levels of brain-derived neurotrophic factor(BDNF)protein in the hippocampus region were measured and compared among different groups.Results:Compared with the Sham group,the I/R group showed significantly reduced learning and memory abilities,with notably lower BDNF levels(P<0.05).Compared to the I/R group,the I/R+EEI group exhibited significantly improved learning and memory abilities as well as increased BDNF protein levels(P<0.05).Conclusions:Abnormal BDNF protein secretion may be the molecular mechanism of cognitive dysfunction due to hippocampal neuronal damage in ischemia-reperfusion,and modifying this neurotransmitter’s secretion can effectively improve cognitive function in ischemia-reperfusion rats.展开更多
Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride ...Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride which is easily prepared,stable and user-friendly.The resulting donors exhibit exceptional shelf stability while can be readily activated to achieve high-yielding glycosylation,encompassing comprehensively aldosyl,ketosyl and ulosonyl donors,and both O-and N-glycosylation acceptors.Notably,the reactivity gradient across different generations of imidates,coupled with the accessible imidate acceptor from selective reaction of imidoyl fluoride at the anomeric hydroxyl group,enables a fully catalytic one-pot synthesis of oligosaccharides.展开更多
Due to its high sensitivity and non-destructive nature,Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development.Despite of the computational demands,data requiremen...Due to its high sensitivity and non-destructive nature,Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development.Despite of the computational demands,data requirements,or ethical considerations,artificial intelligence(AI)and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing,feature extraction,and model optimization,which not only improves the accuracy and efficiency of Raman spectroscopy detection,but also greatly expands its range of application.AI-guided Raman spectroscopy has numerous applications in biomedicine,including characterizing drug structures,analyzing drug forms,controlling drug quality,identifying components,and studying drug-biomolecule interactions.AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics,particularly in disease early diagnosis and treatment optimization.Therefore,AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics,offering new perspectives and tools for disease treatment and pharmaceutical process control.In summary,integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities,offering innovative approaches for research and clinical applications.展开更多
Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), p...Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.展开更多
Background: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples ...Background: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA. Methods: Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the pro ling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples. Results: Microarray pro ling showed that miR-30d-5p and miR-92a-3p were signi cantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were signi cantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling path- ways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a speci city of 60.5%. Conclusions: The levels of extracellular miR-30d-5p and miR-92a-3p in bile were signi cantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.展开更多
Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To p...Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.展开更多
Hydrogenations and air oxidations usually have low apparent reaction rate,generally controlled by mass transfer rate,and widely exist in the modern chemical manufacturing process.The key to increase the mass transfer ...Hydrogenations and air oxidations usually have low apparent reaction rate,generally controlled by mass transfer rate,and widely exist in the modern chemical manufacturing process.The key to increase the mass transfer rate is the reduction of the liquid film resistance 1/kLa.In this work,the original concept of microinterface intensification for mass transfer and then for these reactions has been proposed.We derived the regulation model and set up the mathematical calculation method of micron-scale gas-liquid interface structure on mass transfer and reaction,designed the mechanical energy exchange device that can produce gas-liquid microinterface system on a large scale,and established the OMIS system which is able on line to measure the diameter and distribution of millions of microbubbles,interface area a and mass transfer film thicknessδM,as well as developed a series of microinterface intensified reactor systems(MIRs)for the applications of hydrogenation and air oxidation processes.It is believed that this research will provide an up-to-date development for the intensification of hydrogenation and air oxidation reactions.展开更多
The hydrodynamic characteristics generated by the standard Rushton or 45°-upward pitched-blade-turbine (PBT) impellers in a baffled reactor are numerically simulated for different off-bottom clearances (C= 1/3H a...The hydrodynamic characteristics generated by the standard Rushton or 45°-upward pitched-blade-turbine (PBT) impellers in a baffled reactor are numerically simulated for different off-bottom clearances (C= 1/3H and 1/2H) and agitator speeds (100, 150, 200, 250 and 300r·min^-1) by using FLUENT code (Version 5.4). The results are compared with the experimental and simulated data in the published papers and good agreement is observed. The shapes of the profile of mean velocities seem independent to the speed of agitators under the experimental conditions (100-300r·min^-1).展开更多
The present article covers a simple approach to detect and subsequently identify in vivo metabolites of brodimoprim, using high performance liquid chromatography coupled to ion trap mass spectrometer（LC/ESI-MS）, whi...The present article covers a simple approach to detect and subsequently identify in vivo metabolites of brodimoprim, using high performance liquid chromatography coupled to ion trap mass spectrometer（LC/ESI-MS）, which is based on a data-dependent acquisition of isotope ions and result verified by full scan mass spectrum. The distinguished advantage of data-dependent scan is rapidness because it requires minimum sample preparation, and all the necessary data can be obtained in one chromatographic run. In addition, it is highly sensitive and selective, allowing detection of trace metabolites even in the presence of complex biomatrix. As a result, four phase-Ⅰ（M1--M4） and four Phase-Ⅱ（M5--M8） metabolites of brodimoprim were identified in urine after the oral administration of hrodimoprim to Wistar rats. Their chemical structures were proposed based on the interpretation of their CID fragmentation characterizations and the metabolic pathway was exhibited in this article.展开更多
AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 ...AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.展开更多
基金supported by the National Natural Science Foundation of China(22007008,22178048).
文摘Naphthalene,anthracene and pyridone endoperoxides are known to thermally release singlet oxygen.However,in the cycloreversion reaction,singlet oxygen is produced stoichiometrically;therefore,multiple singlet oxygen releasing modules are expected to be very useful in inducing apoptosis of cancer cells.Herein,we present a potential therapeutic agent presenting three-pyridone endoperoxide modules and a mitochondria targeting group.Compared to previously reported pyridone-based monofunctional endoperoxides,the triple endoperoxide is highly effective as evidenced by assays and fluorescence microscopy.
基金supported by the National Natural Science Foundation of China (No.22007008)the LiaoNing Revitalization Talents Program (No.XLYC1907021)the Fundamental Research Funds for the Central Universities (Nos.DUT23YG120,DUT19RC(3)009)。
文摘The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.
基金Funded by the National Key R&D Program of China(No.2023YFC2412300)the Technology Development Project of Shan-dong Weigao Orthopedic Materials Co.,Ltd.(No.20221h0074)the Independent Innovation Research Fund of Wuhan University of Technology(No.104972024ZHZXhp0027)。
文摘To enhance the mechanical reliability of dental prostheses under long-term service conditions,this study aimed to evaluate the fracture behavior and energy dissipation characteristics of three commonly used prosthetic materials,namely,zirconia ceramics(ZrO_(2)),cobalt-chromium alloy(Co-Cr),and titanium-zirconium alloy(Ti-13Zr),under various crack configurations.A three-dimensional finite element model of a single-crown prosthesis incorporating predefined cracks was established,and both axial and oblique multidirectional loads were applied.Using LS-DYNA software,the deformation patterns,principal stress distribution,and energy release characteristics during crack propagation were systematically analyzed.The experimental results indicate that Ti-13Zr alloy exhibited the highest crack resistance,making it particularly suitable for patients with insufficient bone volume or limited implant space.Co-Cr alloy demonstrated favorable structural stability and mechanical performance under high-load conditions.In contrast,due to its inherent brittleness,ZrO_(2)was more prone to rapid fracture propagation in long-span or high-stress scenarios,although it remains a preferred option for anterior esthetic zones and patients with metal sensitivities.Furthermore,the simulation outcomes were theoretically validated using Griffith's energy-based fracture criterion,reinforcing the accuracy of failure predictions based on principal stress analysis.This study elucidates the differences in clinical applicability among prosthetic materials and reveals their distinct fracture mechanisms,thereby providing a theoretical foundation for optimizing material selection and structural design.The findings contribute to improving the long-term safety and functional stability of implant-supported dental restorations.
基金The Yunnan“Xingdian Talent Program”Yunling Scholar Project,(Grant No.CA24129L025A)National Natural Science Foundation of China,Grant/Award Number:32160157 and 82160564Major Science and Technology Project of Yunnan Province(Grant No.202202AG050008)。
文摘Background:Chronic hyperuricemia is associated with complications such as gout and uric acid nephropathy,but uric acid also exhibits biological activities(e.g.,antioxidant effects,potential neuroprotective properties against neurodegenerative diseases).Nonhuman primates are ideal models for studying neurodegenerative diseases;however,existing nonhuman primate hyperuricemia models cannot sustain long-term elevated serum uric acid levels,nor recapitulate the impaired uric acid excretion observed in clinical hyperuricemic patients.Methods:First,we detected uricase expression in cynomolgus monkeys and compared it with that in mice.Then,we established a cynomolgus monkey hyperuricemia model by administering a mixture of potassium oxonate,hydrochlorothiazide,and adenine via fruits and vegetables.We further analyzed the regulatory effects of this model on uric acid metabolism(synthesis,degradation,and excretion)and the expression of uric acid transporter genes in the intestine and kidney.Results:Cynomolgus monkeys express functional uricase,but at a lower level than mice.The established model maintained stable,long-term hyperuricemia by three mechanisms:increasing intestinal and renal uric acid excretion load,inhibiting hepatic uric acid degradation,and promoting uric acid synthesis.Additionally,the model downregulated the expression of intestinal/renal uric acid-secreting transporter genes,while upregulating uric acid-reabsorbing transporter genes.Conclusions:This novel cynomolgus monkey hyperuricemia model provides a new tool for investigating the association between hyperuricemia and neurodegenerative diseases,and will help clarify the mechanism by which serum uric acid influences cognitive function.
基金supported by the Natural Science Foundation of Liaoning Province(2023-MSBA-020)the Fundamental Research Funds for Central Universities(DUT24MS020)Science and Technology Innovation Fund of Dalian(2022JJ13SN073).
文摘Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.
基金supported by the Project Program of Nature Science Foundation of Jiangsu Province of China(No.BK20201329)。
文摘Glioma,the most prevalent primary tumor of the central nervous system(CNS),is also the most lethal primary malignant tumor.Currently,there are limited chemotherapeutics available for glioma treatment,necessitating further research to identify and develop new chemotherapeutic agents.A significant approach to discovering anti-glioma drugs involves isolating antitumor active ingredients from natural products(NPs)and optimizing their structures.Additionally,targeted drug delivery systems(TDDSs)are employed to enhance drug solubility and stability and overcome the blood-brain barrier(BBB).TDDSs can penetrate deep into the brain,increase drug concentration and retention time in the CNS,and improve the targeting efficiency of NPs,thereby reducing adverse effects and enhancing anti-glioma efficacy.This paper reviews the research progress of anti-glioma activities of NPs,including alkaloids,polyphenols,flavonoids,terpenoids,saponins,quinones,and their synthetic derivatives over the past decade.The review also summarizes anti-glioma mechanisms,such as suppression of related protein expression,regulation of reactive oxygen species(ROS)levels,control of apoptosis signaling pathways,reduction of matrix metalloproteinases(MMPs)expression,blocking of vascular endothelial growth factor(VEGF),and reversal of immunosuppression.Furthermore,the functions and advantages of NP-based TDDSs in anti-glioma therapy are examined.The key information presented in this review will be valuable for the research and development of NP-based anti-glioma drugs and related TDDSs.
文摘The efficient utilization of photogenerated electrons and the effective activation of reactive molecules are among the major challenges in photocatalytic nitrogen reduction.Defect engineering can enhance the catalyst's ability to adsorb and activate N_(2)and H_(2)O,while the ultrathin structure with maximized active crystal facets can maximize the enrichment of effective photogenerated electrons.This work employs a two-step synergistic method to fabricate ultrathin BiVO_(4)with oxygen vacancies and bismuth vacancies(2D-V_(Bi+O)-BVO,thickness<20 nm)for photocatalytic nitrogen reduction.Scanning electron microscopy,transmission electron microscopy(TEM),and atomic force microscopy characterization confirm the transformation of BiVO_(4)from bulk material(bulk-BVO,~1300 nm)to an ultrathin structure(~15 nm).TEM,X-ray photoelectron spectroscopy,electron paramagnetic resonance characterizations,and density functional theory(DFT)calculations verify the construction of oxygen and bismuth vacancies in the ultrathin BiVO_(4).Compared to bulk-BVO,the photocatalytic nitrogen fixation efficiency of 2D-V_(Bi+O)-BVO is increased by 4.7 times,with the highest activity reaching 158.73μmol·g^(-1)·h^(-1).N_(2)-temperature programmed desorption and DFT calculations demonstrate that the oxygen and bismuth vacancies in BiVO_(4),respectively,promote the adsorption/activation of N_(2)and H_(2)O,which is crucial for the overall nitrogen reduction reaction.Photo-deposition experiments prove that the(040)plane is the active surface for electrons.And the ultrathin structure maximizes the(040)facet of BiVO_(4),which is conducive to the high enrichment of electrons.Meanwhile,more active sites can be exposed for the activation of N_(2)and H_(2)O.In situ infrared spectroscopy confirms that N_(2)can be effectively adsorbed onto 2D-V_(Bi+O)-BVO,and the presence of NH_(2)-NH_(2)active species is consistent with the alternating reaction pathway.This study provides new insights into the development of green and efficient photocatalysts with dual vacancies and ultrathin structures.
基金supported by the Fundamental Research Funds for the Central Universities(DUT24YG142).
文摘Curcumin,a bioactive compound extracted from Curcuma longa.L.,demonstrates significant therapeutic potential in inflammatory diseases.This study aims to explore the effects of curcumin on hyperuricemia with acute gout and associated renal dysfunction in a mouse model.The results show that curcumin treatment alleviates ankle joint swelling,reduces inflammatory cytokines IL-1βand TNF-α,and lowers serum uric acid concentrations.High-dose curcumin notably inhibits xanthine oxidase(XOD)activity,a key enzyme in uric acid production,while it enhances the renal expression of the urate transporter ABCG2,thereby promoting uric acid excretion.Furthermore,curcumin effectively mitigates renal injury as evidenced by reduced serum creatinineand blood urea nitrogen levels and suppresses renal inflammation.At the molecular level,curcumin exerts potent antioxidant effects by lowering reactive oxygen species(ROS)levels in both cultured HK-2 human renal tubular epithelial cells and RAW264.7 mouse macrophages.The curcumin-mediated effects are associated with the disruption of NEK7-NLRP3 complex formation,leading to the suppression of the ROS/NEK7-NLRP3 inflammasome pathway.This,in turn,inhibits pyroptosis and the subsequent release of mature IL-1β.These findings suggest that curcumin not only reduces uric acid production but also modulates inflammation through ROSscavenging properties and its ability to inhibit the NLRP3 inflammasome.
基金supported by the Fundamental Research Funds for the Central Universities(No.DUT24YG142).
文摘This study constructed an in vitro blood-brain barrier(BBB)transwell model to investigate the regulatory effects and mechanisms of the photothermal effects of gold nanorods(AuNRs)excited by the second near-infrared region(NIR-II)on BBB permeability.The experimental results showed that the photothermal effects of NIR-II t AuNRs significantly decreased trans-epithelial electrical resistance(TEER)and increased the permeability of fluorescein isothiocyanate(FITC)-dextran,indicating that it can effectively open the BBB.This effect was reversible,and the TEER and FITC permeability returned to baseline levels within 24 h after treatment.Mechanistic studies revealed that BBB opening did not rely on apoptosis,cytoskeletal disruption,mitochondrial dysfunction,or inflammation.The opening of the BBB was closely associated with a temporary decrease in the expression and conformational change of the tight junction protein occludin due to the photothermal effect.Molecular simulations and docking analysis revealed that the heat shock protein HSP70 could bind to the conformationally altered occludin,supporting the regulatory role of photothermal effects on tight junction proteins.In summary,NIR-II t AuNRs achieved safe and reversible opening of the BBB by regulating the conformation and expression of tight junction proteins,providing a deeper insight for further research on BBB and the treatment of neurological diseases.
基金funded by the National Natural Science Foundation of China(No.32271464)the Hunan Provincial Natural Science Foundation for Distinguished Young Scholars(No.2022JJ10086)+2 种基金the Innovation-Driven Project of Central South University(No.2020CX048)Hunan Provincial High-Level Health Talents(No.20240304088)Fund of the Hunan Provincial Natural Science Foundation and the Hunan Medical Products Administration(No.2023JJ60501)。
文摘Precise tumor targeting and therapy is a major trend in cancer treatment.Herein,we designed a tumor acidic microenvironment activatable drug loaded DNA nanostructure,in which,we made a clever use of the sequences of AS1411 and i-motif,which can partially hybridize,and designed a simple while robust DNA D-strand nanostructure,in which,i-motif sequence was designed to regulate the binding ability of the AS1411 aptamer to target tumor.In the normal physiological environment,i-motif inhibits the targeting ability of AS1411.In the acidic tumor microenvironment,i-motif forms a quadruplex conformation and dissociates from AS1411,restoring the targeting ability of AS1411.Only when acidic condition and tumor cell receptor are present,this nanostructure can be internalized by the tumor cells.Moreover,the structure change of this nanostructure can realize the release of loaded drug.This drug loaded A-I-Duplex DNA structure showed cancer cell and spheroid targeting and inhibition ability,which is promising in the clinical cancer therapy.
基金supported by 2023 Jiangsu Xuzhou Medical Higher Vocational School Natural Science Project(No.2023ZZX09)。
文摘Objective:Investigating the effects and molecular mechanisms of nursing interventions based on environmental enrichment on cognitive function in ischemic stroke rats.Methods:A total of 30 Sprague-Dawley(SD)rats belonging to the same batch were randomly divided into 3 groups(n=10)using a random number table:Sham Surgery Control Group(Sham),Ischemia-Reperfusion(I/R)Group,and Ischemia-Reperfusion Group with Environmental Enrichment Intervention(I/R+EEI).The expression levels of brain-derived neurotrophic factor(BDNF)protein in the hippocampus region were measured and compared among different groups.Results:Compared with the Sham group,the I/R group showed significantly reduced learning and memory abilities,with notably lower BDNF levels(P<0.05).Compared to the I/R group,the I/R+EEI group exhibited significantly improved learning and memory abilities as well as increased BDNF protein levels(P<0.05).Conclusions:Abnormal BDNF protein secretion may be the molecular mechanism of cognitive dysfunction due to hippocampal neuronal damage in ischemia-reperfusion,and modifying this neurotransmitter’s secretion can effectively improve cognitive function in ischemia-reperfusion rats.
基金the National Natural Science Foundation of China(No.21672147)Shanghai University of Traditional Chinese Medicine for financial support。
文摘Glycosyl imidates are among the pioneering donors for catalytic glycosylation.We report a new generation of imidates featuring the presence of a pentafluorophenyl group,introduced via substitution on imidoyl fluoride which is easily prepared,stable and user-friendly.The resulting donors exhibit exceptional shelf stability while can be readily activated to achieve high-yielding glycosylation,encompassing comprehensively aldosyl,ketosyl and ulosonyl donors,and both O-and N-glycosylation acceptors.Notably,the reactivity gradient across different generations of imidates,coupled with the accessible imidate acceptor from selective reaction of imidoyl fluoride at the anomeric hydroxyl group,enables a fully catalytic one-pot synthesis of oligosaccharides.
基金funded by Beijing Municipal Natural Science Foundation(Grant No.:KZ202210017025)Science and Technology Projects of Jiangsu Province(Grant No.:BE2021756).
文摘Due to its high sensitivity and non-destructive nature,Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development.Despite of the computational demands,data requirements,or ethical considerations,artificial intelligence(AI)and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing,feature extraction,and model optimization,which not only improves the accuracy and efficiency of Raman spectroscopy detection,but also greatly expands its range of application.AI-guided Raman spectroscopy has numerous applications in biomedicine,including characterizing drug structures,analyzing drug forms,controlling drug quality,identifying components,and studying drug-biomolecule interactions.AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics,particularly in disease early diagnosis and treatment optimization.Therefore,AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics,offering new perspectives and tools for disease treatment and pharmaceutical process control.In summary,integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities,offering innovative approaches for research and clinical applications.
基金supported by the National Natural Science Foundation of China(No.31371014)
文摘Danshensu [3-(3, 4-dihydroxyphenyl) lactic acid, DSS], one of the significant cardioprotective components, is extracted from the root of Salvia miltiorrhiza. In the present study, an ester prodrug of Danshensu(DSS), palmitoyl Danshensu(PDSS), was synthesized with the aim to improve its oral bioavailability and prolong its half-life. The in vitro experiments were carried out to evaluate the physicochemical properties and stability of PDSS. Although the solubility of PDSS in water was only 0.055 mg·mL^(-1), its solubility in Fa SSIF and Fe SSIF reached 4.68 and 9.08 mg·mL^(-1), respectively. Octanol-water partition coefficient(log P) was increased from-2.48 of DSS to 1.90 of PDSS. PDSS was relatively stable in the aqueous solution in pH range from 5.6 to 7.4. Furthermore, the pharmacokinetics in rats was evaluated after oral administration of PDSS and DSS. AUC and t1/2 of PDSS were enhanced up to 9.8-fold and 2.2-fold, respectively, compared to that of DSS. Cmax was 1.67 ± 0.11 μg·mL^(-1) for PDSS and 0.81 ± 0.06 μg·m L-1 for DSS. Thus, these results demonstrated that PDSS had much higher oral bioavailability and longer circulation time than its parent drug.
基金supported by grants from a Basic Science Re-search Program through the National Research Foundation of Ko-rea(NRF)funded by the Ministry of Education,Science and Tech-nology(2017R1A5A2015541 and 2019R1A2C1007401)’’+1 种基金supported by a grant from the National R&D Program for Cancer Control,Ministry of Health and Welfare,Republic of Ko-rea(1120330)a National Research Foundation of Korea grant funded by the Korea government(NRF-2013R 1A 1A 2063994)
文摘Background: Cholangiocarcinoma (CCA) is from cholangiocytes, and therefore bile is a potentially rich source of biomarkers for CCA. The aim of the study was to identify and validate microRNAs (miRNAs) in bile samples that are differentially expressed between benign biliary disease (BBD) and CCA. Methods: Bile samples from 106 patients with obstructive biliary disease were allocated consecutively to a discovery set (10 patients with BBD and 11 with CCA) and then a validation set (48 patients with BBD and 37 with CCA). An miRNA microarray platform was used to screen 1209 miRNAs in the discovery set. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the pro ling results in the discovery and validation sets. In addition, the levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were determined from patient serum samples. Results: Microarray pro ling showed that miR-30d-5p and miR-92a-3p were signi cantly upregulated in bile from the CCA group compared with those from the BBD group. qRT-PCR results indicated that the expression levels of miR-30d-5p and of miR-92a-3p were signi cantly upregulated in the CCA group compared to the BBD group, validating the miRNA microarray results. Pathway analysis suggested that putative target genes of miR-30d-5p and of miR-92a-3p were involved in CCA-associated signalling path- ways, such as Hippo, Wnt, p53, MAPK, and EGFR. Receiver operating curve analysis revealed that the areas under the curve for bile miR-30d-5p, miR-92a-3p, serum CA19-9, and CEA were 0.730, 0.652, 0.675, and 0.603, respectively, and bile miR-30d-5p showed the best diagnostic performance with a sensitivity of 81.1% and a speci city of 60.5%. Conclusions: The levels of extracellular miR-30d-5p and miR-92a-3p in bile were signi cantly higher in patients with CCA than those in patients with BBD. Bile-derived circulating extracellular miR-30d-5p and miR-92a-3p are potential biomarkers for discriminating CCA from BBD.
基金the National Natural Science Foundation of China(No.81872813,22108313,82273880)Natural Science Foundation of Jiangsu Province(No.BK 20200573,BK 20200576)+1 种基金Fundamental Research Funds for the Central Universities(No 2632022ZD16)the Scientific Research Fund of Hunan Provincial Education Department(No.22B0820).
文摘Amorphous solid dispersion(ASD)is one of the most effective approaches for delivering poorly soluble drugs.In ASDs,polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level.To prepare the solid dispersions,there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations.Polymer selection is of great importance because it influences the stability,solubility and dissolution rates,manufacturing process,and bioavailability of the ASD.This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers,formulation designs and preparation methods.Furthermore,considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.
基金the financial support of National Natural Science Foundation of China(No.91634104,21776122 and 22178391)National Key Research&Development Program of China(No.2018YFB0604605)Jiangsu Science and Technology Plan Project(No.BM2018007)。
文摘Hydrogenations and air oxidations usually have low apparent reaction rate,generally controlled by mass transfer rate,and widely exist in the modern chemical manufacturing process.The key to increase the mass transfer rate is the reduction of the liquid film resistance 1/kLa.In this work,the original concept of microinterface intensification for mass transfer and then for these reactions has been proposed.We derived the regulation model and set up the mathematical calculation method of micron-scale gas-liquid interface structure on mass transfer and reaction,designed the mechanical energy exchange device that can produce gas-liquid microinterface system on a large scale,and established the OMIS system which is able on line to measure the diameter and distribution of millions of microbubbles,interface area a and mass transfer film thicknessδM,as well as developed a series of microinterface intensified reactor systems(MIRs)for the applications of hydrogenation and air oxidation processes.It is believed that this research will provide an up-to-date development for the intensification of hydrogenation and air oxidation reactions.
基金Supported by the National Natural Science Foundation of China (No. 20028607).
文摘The hydrodynamic characteristics generated by the standard Rushton or 45°-upward pitched-blade-turbine (PBT) impellers in a baffled reactor are numerically simulated for different off-bottom clearances (C= 1/3H and 1/2H) and agitator speeds (100, 150, 200, 250 and 300r·min^-1) by using FLUENT code (Version 5.4). The results are compared with the experimental and simulated data in the published papers and good agreement is observed. The shapes of the profile of mean velocities seem independent to the speed of agitators under the experimental conditions (100-300r·min^-1).
基金the National Natural Science Foundation of China(Nos.30630075 and 20675056)Natural Science Founda-tion of Tianjin City,China(No.07JCYBJC01600)
文摘The present article covers a simple approach to detect and subsequently identify in vivo metabolites of brodimoprim, using high performance liquid chromatography coupled to ion trap mass spectrometer（LC/ESI-MS）, which is based on a data-dependent acquisition of isotope ions and result verified by full scan mass spectrum. The distinguished advantage of data-dependent scan is rapidness because it requires minimum sample preparation, and all the necessary data can be obtained in one chromatographic run. In addition, it is highly sensitive and selective, allowing detection of trace metabolites even in the presence of complex biomatrix. As a result, four phase-Ⅰ（M1--M4） and four Phase-Ⅱ（M5--M8） metabolites of brodimoprim were identified in urine after the oral administration of hrodimoprim to Wistar rats. Their chemical structures were proposed based on the interpretation of their CID fragmentation characterizations and the metabolic pathway was exhibited in this article.
基金Supported by Postdoctoral Science Foundation of China,No.20060390192,200801243research grant from Science and Technology Department of Gansu Province,China,No.0708NKCA128
文摘AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.
