Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temp...Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.展开更多
BACKGROUND Liver failure,particularly acute-on-chronic liver failure,is associated with high mortality(50%-90%).The plasma exchange(PE)mode of the artificial liver support system has been shown to improve clinical out...BACKGROUND Liver failure,particularly acute-on-chronic liver failure,is associated with high mortality(50%-90%).The plasma exchange(PE)mode of the artificial liver support system has been shown to improve clinical outcomes,although its efficacy may vary depending on the regenerative capacity of the liver.Alpha-fetoprotein(AFP),an oncofetal glycoprotein,is reactivated during liver regeneration and may serve as a prognostic biomarker.Previous studies have reported significantly higher post-PE AFP levels in survivors than in non-survivors(286.5 ng/mL vs 82.3 ng/mL at day 7).However,the predictive value of baseline AFP stratification and serial AFP kinetics during PE therapy remains unestablished.This study investigated whether serial AFP measurements predict clinical outcomes in liver failure patients receiving PE.AIM To evaluate the predictive value of serial AFP measurements in liver failure patients receiving PE.METHODS This retrospective study included 194 liver failure patients with complete AFP data,excluding those with tumors,bleeding disorders,allergies,or unstable conditions.Patients were stratified by baseline AFP into low-AFP(<100 ng/mL,n=60),medium-AFP(100-200 ng/mL,n=70),and high-AFP(>200 ng/mL,n=64)groups.AFP was measured before PE and on days 1,10,20,and 25.RESULTS Stratification by baseline AFP revealed significant gradients.The high-AFP group required fewer PE sessions than the low-AFP group(2.8±1.0 vs 4.2±1.5)but exhibited greater post-PE AFP elevation(75.1±20.3 ng/mL vs 33.1±10.2 ng/mL;P<0.001).The high-AFP group demonstrated optimal values,including the lowest ammonia,bilirubin,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transferase,and the highest albumin and prothrombin activity(all post hoc P<0.05 vs low-AFP).The medium-AFP group showed intermediate values except for prothrombin activity(35.2%±8.6%),which was significantly lower than in both other groups(P<0.001).The high-AFP group had a reduced incidence of spontaneous bacterial peritonitis(9.4%vs 25.0%;P=0.003),superior three-month survival(90.6%vs 56.7%;P<0.001),and a higher post-treatment three-month receiver operating characteristic area under the curve(0.8851 vs 0.7051).CONCLUSION AFP dynamics correlate with regenerative capacity and clinical outcomes in liver failure.Serial AFP monitoring may enhance risk stratification and support personalized therapeutic strategies.展开更多
Objective:To investigate the distribution of health literacy(HL)levels and the association of HL with proactive personality in patients with permanent colostomy.Methods:A cross-sectional study was conducted to measure...Objective:To investigate the distribution of health literacy(HL)levels and the association of HL with proactive personality in patients with permanent colostomy.Methods:A cross-sectional study was conducted to measure proactive personality and HL using validated scales.A total of 172 patients with permanent colostomy were selected from January 2021 to May 2022 in Yantai City,China.Descriptive statistics,t-test,ANOVA,Pearson correlation analysis,and multiple linear regression analysis techniques were used.Results:The results obtained from the study showed that the HL status of the participants was moderate.The correlation between participants’total HL scores and proactive personality scores was 0.417(P-value<0.001).In addition,HL showed statistically significant differences according to education level,place of residence,profession,and average monthly household income.Conclusions:This study showed that patients with higher proactive personality scores had higher HL.The key stakeholders require several positive strategies to improve the HL of patients with permanent colostomy by cultivating their proactive personalities,and these important policies will help to improve patient health and quality of life.展开更多
Acetaminophen(APAP)used as an antipyretic and analgesic agent can cause acute liver injury(AILI)under overdose.Sanghuangporous vaninii is an edible fungus with abundant metabolites exhibits excellent hepatoprotective ...Acetaminophen(APAP)used as an antipyretic and analgesic agent can cause acute liver injury(AILI)under overdose.Sanghuangporous vaninii is an edible fungus with abundant metabolites exhibits excellent hepatoprotective activities,but the effect for AILI is not yet fully understood.In this study,the polyphenol rich extract from S.vaninii(PSV)was prepared,with a total phenolic content of 75.72%and 34 compounds.The data of hepatoprotection indicated that PSV obviously alleviated the hepatocellular injury induced by APAP in vivo and in vitro.The protective mechanism of PSV against APAP-induced AILI might be attributed to the activating NRF2/GPX4 pathway.Based on network pharmacology analysis,the active components of PSV such as caffeic acid,osmundacetone and hispolone played a key role in hepatoprotection of PSV.Consequently,this study highlights the protection of PSV on AILI,which provides new insight into bioactivities of S.vaninii.展开更多
The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from me...The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.展开更多
Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants...Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines.In this study,we designed and formulated carrier-free double-adjuvant nanoparticles(FPC-NPs)by self-assembling of fluoroalkane-grafted polyethylenimide(PEI)(Toll-like receptor 4(TLR4)agonist)and cytosine-phosphateguanine(CpG)(TLR9 agonist),and then obtained personalized tumor vaccines(FPC-NPs@TAAs)by electrostatic adsorption of tumor-associated antigens(TAAs)on the surface of FPC-NPs.The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants,deliver antigens and adjuvants to the same antigen-presenting cell,which can effectively activate dendritic cells,encourage cross-presentation of antigens,and reduce the proportion of M2-type macrophages.Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles,showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy.展开更多
Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a pr...Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.展开更多
Elastic strain constitutes a decisive factor in determining the recoverable deformability of thermoelectric materials.Plastic deformation for microstructure engineering has been demonstrated as a viable approach to en...Elastic strain constitutes a decisive factor in determining the recoverable deformability of thermoelectric materials.Plastic deformation for microstructure engineering has been demonstrated as a viable approach to enhance the elastic strain.However,this approach is highly dependent on the material's plasticity,which is rather limited by the rigidity for the majority of inorganic semiconducting thermoelectric materials.Thermocouple materials,as metallic thermoelectric materials,possess a favorable plasticity,motivating this work to focus on the elastic bendability of a metallic thermoelectric generator that is composed of K-type thermocouple components,namely p-type Ni_(90)Cr_(10) and n-type Ni_(95)Al_(2)Mn_(2)Si.The cold-rolling process enables a large elastic modulus and a high yield strength,thanks to the texturized direction along<111>,and dense dislocations and refined grains,respectively,eventually resulting in a 400%increase in the elastic strain.Such superior elasticity ensures the preservation of the initial transport properties for the rolled films even after being bent 100000 times within a radius of~8 mm.A power output of~414μW is achieved in a ten-leg flexible thermoelectric device,suggesting its substantial potential for powering wearable electronics.展开更多
Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying m...Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.展开更多
Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatme...Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.展开更多
AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver inju...AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice.A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group(control group) and a Liuweiwuling tablet group.Mice were given Liuweiwuling tablets or a vehicle(PBS) orally prior to the administration of acetaminophen.Serum alanine aminotransferase(ALT) and aspartate aminotransaminase(AST) levels were measured at different time points within one week,and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury.Serum inflammatory cytokines,such as high mobility group box protein B1(HMGB1),tumor necrosis factor(TNF)-α and interleukin IL-1b,were detected using an ELISA method according to the manufacturer's instructions.Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining.Expression of proliferating cell nuclear antigen(PCNA) in liver tissue was determined by Western blot analysis.The m RNA levels of hepatocyte proliferation markers(PCNA,Cyclin D1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6,12 and 24 h compared to that of the control group(654.38 ± 120.87 vs 1566.17 ± 421.64,1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37,P < 0.01).Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group(23.49 ± 3.89 vs58.6 ± 3.65,61.62 ± 13.07 vs 27.32 ± 5.97,P < 0.01).Furthermore,serum TNF-α and IL-1b levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group(299.35 ± 50.61 vs 439.03 ± 63.59,57.42 ± 12.98 vs 160.07 ± 49.87,P < 0.01).Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury,but was almost abolished in the Liuweiwuling tablet group.The expression levels of PCNA and Cyclin D1 were up-regulated in liver tissue in the Liuweiwuling tablet group(321.08 ± 32.87 vs 157.91 ± 21.52,196.37 ± 25.39 vs 68.72 ± 11.27,P < 0.01); however,expression of p21 in liver tissue was downregulated compared to that of the control group(40.26 ± 9.97 vs 138.24 ± 13.66,P < 0.01).CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine(HMGB1,TNF-α and IL-1b) levels and promoting liver regeneration.展开更多
AIM: To investigate the effect of biliary drainage on inducible nitric oxide synthase (iNOS), CD14 and TGR5 expression in rats with obstructive jaundice (OJ). METHODS: Male adult Sprague-Dawley rats were randomly assi...AIM: To investigate the effect of biliary drainage on inducible nitric oxide synthase (iNOS), CD14 and TGR5 expression in rats with obstructive jaundice (OJ). METHODS: Male adult Sprague-Dawley rats were randomly assigned to four groups: OJ, sham operation (SH), internal biliary drainage (ID) and external biliary drainage (ED). Rat models were successfully established by two operations and succumbed for extraction of Kupffer cells (KCs) and liver tissue collection on the 8 th and 15 th day. KCs were isolated by in situ hepatic perfusion and digested with collagen Ⅳ, density gradient centrifuged by percoll reagent and purified by cell culture attachment. The isolated KCs were cultured with the endotoxin lipopolysaccharide (LPS) with and without the addition of ursodeoxycholic acid (UDCA). The expression of iNOS, CD14 and bile acid receptor-TGR5 protein in rat liver tissues was determined by immunohistochemistry. The expression of iNOS and CD14 messenger RNA (mRNA) on the isolated KCs was detected by reverse transcription polymerase chain reaction (PCR) and the TGR5 mRNA level in KCs was measured by real-time quantitative PCR. RESULTS: The iNOS protein was markedly expressed in the liver of OJ rats, but rare expressed in SH rats. After relief of OJ, the iNOS expression was decidedly suppressed in the ID group (ID vs OJ, P < 0.01), but obviously increased in rats of ED (ED vs OJ, P=0.004). When interfered only with LPS, the expression of iNOS mRNA by KCs was increased in the OJ group compared with the SH group (P=0.004). After relief of biliary obstruction, the iNOS mRNA expression showed slight changes in the ED group (ED vs OJ, P=0.71), but dropped in the ID group (ID vs OJ, P=0.001). Compared with the simple intervention with LPS, the expressions of iNOS mRNA were significantly inhibited in all four groups after interfered with both LPS and UDCA (P < 0.01, respectively). After bile duct ligation, the CD14 protein expression in rat liver was significantly strengthened (OJ vs SH, P < 0.01), but the CD14 mRNA level by KCs was not up-regulated (OJ vs SH, P=0.822). After relieving the OJ, the expression of CD14 protein was reduced in the ID group (ID vs OJ, P < 0.01), but not reduced in ED group (ED vs OJ, P=0.591). And then the CD14 mRNA expression was aggravated by ED (ED vs OJ, P < 0.01), but was not significantly different between the ID group and the SH and OJ groups (ID vs SH, P=0.944; ID vs OJ, P=0.513, respectively). The expression of TGR5 protein and mRNA increased significantly in OJ rats (OJ vs SH, P=0.001, respectively). After relief of OJ, ID could reduce the expression of TGR5 protein and mRNA to the levels of SH group (ID vs SH, P=0.22 and P=0.354, respectively), but ED could not (ED vs SH, P=0.001, respectively).CONCLUSION: ID could be attributed to the regulatory function of activation of KCs and release of inflammatory mediators.展开更多
Two-dimensional Ti_(3)C_(2)T_(x) flakes have great application potential in various areas due to their optical,electronic,electrochemical and mechanical properties,but their anti-corrosion and wear-resistance performa...Two-dimensional Ti_(3)C_(2)T_(x) flakes have great application potential in various areas due to their optical,electronic,electrochemical and mechanical properties,but their anti-corrosion and wear-resistance performance were not well understood.The difficulties in achieving good dispersity and interface interaction of inorganic additives in organic coatings hinder the incorporation of Ti_(3)C_(2)T_(x) into the epoxy coating.Here,few-layered Ti_(3)C_(2)T_(x) sheets with amino-functionalization were prepared,and as reinforced-additives were added into the waterborne epoxy coating.Anti-corrosion and tribological properties of as-prepared composite coatings were investigated in detail.The results reveal that the composite coating with 0.5 wt.%amino-functionalized Ti_(3)C_(2)T_(x) sheets shows excellent corrosion protection(the lowest frequency impedance was 3.12×10^(9) cm^(2))and wear resistance(wear rate was reduced by 72.74%).The greatly improving performance of composite coatings mainly depends on:(a)good dispersity and compatibility of amino-functionalized Ti_(3)C_(2)T_(x) in organic matrix,(b)high adhesion strength between coating and metal substrate and(c)the intrinsic properties of Ti3C2Tx sheets.The work provides a good path for applications of MXene as multifunctional additives.展开更多
Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial ce...Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018.展开更多
In the present work,a Pd/graphene/cordierite(Pd/Gr/Cor)composite was prepared as a monolithic catalyst for low-temperature combustion of toluene.We mainly focused on understanding the role of graphene coating through ...In the present work,a Pd/graphene/cordierite(Pd/Gr/Cor)composite was prepared as a monolithic catalyst for low-temperature combustion of toluene.We mainly focused on understanding the role of graphene coating through investigation of catalytic performance and adsorption behavior of the composite.Compared with the traditional Pd/Cor catalyst without graphene coating,Pd/Gr/Cor catalyst delivered much higher activity and stability for toluene catalytic combustion in both dry and moist conditions.Transmission electron microscopy(TEM)and hydrophobic characterizations indicated that graphene coating can considerably improve the dispersity of Pd nanoparticles and enhance the hydrophobicity of the cordierite support.The adsorption behavior of the above two catalysts,including adsorption isothermal,adsorption kinetics,and adsorption thermodynamics were carefully investigated.The simulation results indicated that a large amount of toluene was adsorbed on graphene surface through relatively weak interaction,whereas only a relatively small amount of toluene was adsorbed on Pd surface with strong affinity.The adsorption thermal calculation indicated that the adsorption of toluene on graphene was a process with reduced entropy,indicating highly-ordered assembly of toluene molecular on graphene.It is the significant concentration and affinity gap between graphene and Pd that ensures a simultaneously and rapid transfer of toluene during the reaction process.展开更多
The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signalin...The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.展开更多
Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility...Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.展开更多
Surface and interface engineering plays a crucial role in modulating the properties of materials,especially two-dimensional(2D)materials.Hence,a strategy,forming heterostructures with MoS_(2),is proposed to overcome t...Surface and interface engineering plays a crucial role in modulating the properties of materials,especially two-dimensional(2D)materials.Hence,a strategy,forming heterostructures with MoS_(2),is proposed to overcome the natural agglomeration of Ti_(3)C_(2)T_(x) MXene nanosheets.Most importantly,the interactions between Ti_(3)C_(2)Tx and MoS_(2) were elaborately investigated by first-principles calculations based on density functional theory(DFT)for the first time.The calculations demonstrate that van der Waals forces dominate the interface interactions of Ti_(3)C_(2)T_(x) and MoS_(2),rendering Ti_(3)C_(2)T_(x)@MoS_(2) heterostructures favorable stability.The Ti_(3)C_(2)T_(x)@MoS_(2) heterostructure composites were synthesized through a facile one-step hydrothermal method and exhibit a 2D hierarchical structure.Furthermore,the corrosion and tribological properties of epoxy composite coatings with varying proportions of Ti_(3)C_(2)T_(x)@MoS_(2) composites were studied in detail.As a result,the epoxy composite coating with 0.1 wt.%Ti_(3)C_(2)T_(x)@MoS_(2) composites(Ti_(3)C_(2)T_(x)@MoS_(2)-0.1)exhibits excellent corrosion protection and antiwear performances.The Ti_(3)C_(2)T_(x)@MoS_(2)-0.1 keeps the largest low-frequency impedance modulus(|Z|_(0.)01 Hz)and coating resistance(R_(c))during the whole immersion period.Its wear rate is 0.09μm^(3)/(Nμm)under the load of 10 N,one half of that of pure epoxy coating(EP).This work further broadens the application of MXene-based heterostructure composites.展开更多
AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute ...AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute liver failure(ALF).METHODS: Balb/c mice were randomly assigned to different groups,with ALF induced by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1(HMGB1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,IL-10,and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression of Sphk1 in liver tissue and PBMCs was upregulated in Gal N/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells,the resident macrophages of the liver. The survival rates of mice in the N,Ndimethylsphingosine(DMS,a specific inhibitor of Sph K1) treatment group were significantly higher than that of the control group(P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6,12,and 24 h compared with that of the control group(P < 0.01 for all). Serum HMGB1 levels at 6,12,and 24 h,as well as serum TNF-α,IL-6,and IL-1β levels at 12 h,were significantly lower in the DMS treatment group than in the control group(P < 0.01 for all). Furthermore,hepatic inflammation,necrosis,and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group(43.72% ± 5.51% vs 3.57% ± 0.83%,χ2 = 12.81,P < 0.01).CONCLUSION: Inhibition of Sph K1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells,and so might be a potential therapeutic strategy for this disease.展开更多
Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregul...Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.展开更多
基金supported by central government-guided major science and technology project of Hebei province 236Z7709G(M.C.Q.)Tangshan science and technology project 23130216E(M.C.Q.)+8 种基金key research projects of North China University of Science and Technology ZD-YG-202309(M.C.Q.)National Natural Science Foundations of China 82230030 and 81871492(Y.L.)Beijing International Science and Technology Cooperation Project Z221100002722003(Y.L.)Beijing Natural Science Foundation L234017(Y.L.)Peking University Medicine plus X Pilot Program-Key Technologies R&D Project 2024YXXLHGG004(Y.L.)Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)First-Class Discipline Team of Kunming Medical University 2024XKTDTS08(Y.L.)Innovative Research Team of High-level Local Universities in Shanghai SHSMU-ZLCX20212402(Y.L.)Postdoctoral Fellowship Program of CPSF under Grant Number GZB20240038(X.J.C.).
文摘Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.
基金Supported by National Natural Science Foundation of China,No.82160106.
文摘BACKGROUND Liver failure,particularly acute-on-chronic liver failure,is associated with high mortality(50%-90%).The plasma exchange(PE)mode of the artificial liver support system has been shown to improve clinical outcomes,although its efficacy may vary depending on the regenerative capacity of the liver.Alpha-fetoprotein(AFP),an oncofetal glycoprotein,is reactivated during liver regeneration and may serve as a prognostic biomarker.Previous studies have reported significantly higher post-PE AFP levels in survivors than in non-survivors(286.5 ng/mL vs 82.3 ng/mL at day 7).However,the predictive value of baseline AFP stratification and serial AFP kinetics during PE therapy remains unestablished.This study investigated whether serial AFP measurements predict clinical outcomes in liver failure patients receiving PE.AIM To evaluate the predictive value of serial AFP measurements in liver failure patients receiving PE.METHODS This retrospective study included 194 liver failure patients with complete AFP data,excluding those with tumors,bleeding disorders,allergies,or unstable conditions.Patients were stratified by baseline AFP into low-AFP(<100 ng/mL,n=60),medium-AFP(100-200 ng/mL,n=70),and high-AFP(>200 ng/mL,n=64)groups.AFP was measured before PE and on days 1,10,20,and 25.RESULTS Stratification by baseline AFP revealed significant gradients.The high-AFP group required fewer PE sessions than the low-AFP group(2.8±1.0 vs 4.2±1.5)but exhibited greater post-PE AFP elevation(75.1±20.3 ng/mL vs 33.1±10.2 ng/mL;P<0.001).The high-AFP group demonstrated optimal values,including the lowest ammonia,bilirubin,alanine aminotransferase,aspartate aminotransferase,γ-glutamyl transferase,and the highest albumin and prothrombin activity(all post hoc P<0.05 vs low-AFP).The medium-AFP group showed intermediate values except for prothrombin activity(35.2%±8.6%),which was significantly lower than in both other groups(P<0.001).The high-AFP group had a reduced incidence of spontaneous bacterial peritonitis(9.4%vs 25.0%;P=0.003),superior three-month survival(90.6%vs 56.7%;P<0.001),and a higher post-treatment three-month receiver operating characteristic area under the curve(0.8851 vs 0.7051).CONCLUSION AFP dynamics correlate with regenerative capacity and clinical outcomes in liver failure.Serial AFP monitoring may enhance risk stratification and support personalized therapeutic strategies.
文摘Objective:To investigate the distribution of health literacy(HL)levels and the association of HL with proactive personality in patients with permanent colostomy.Methods:A cross-sectional study was conducted to measure proactive personality and HL using validated scales.A total of 172 patients with permanent colostomy were selected from January 2021 to May 2022 in Yantai City,China.Descriptive statistics,t-test,ANOVA,Pearson correlation analysis,and multiple linear regression analysis techniques were used.Results:The results obtained from the study showed that the HL status of the participants was moderate.The correlation between participants’total HL scores and proactive personality scores was 0.417(P-value<0.001).In addition,HL showed statistically significant differences according to education level,place of residence,profession,and average monthly household income.Conclusions:This study showed that patients with higher proactive personality scores had higher HL.The key stakeholders require several positive strategies to improve the HL of patients with permanent colostomy by cultivating their proactive personalities,and these important policies will help to improve patient health and quality of life.
基金supported by the Shanghai Rising-Star Program(24QB2702300)Shanghai Municipal Commission of Science and Technology(22N51900100).
文摘Acetaminophen(APAP)used as an antipyretic and analgesic agent can cause acute liver injury(AILI)under overdose.Sanghuangporous vaninii is an edible fungus with abundant metabolites exhibits excellent hepatoprotective activities,but the effect for AILI is not yet fully understood.In this study,the polyphenol rich extract from S.vaninii(PSV)was prepared,with a total phenolic content of 75.72%and 34 compounds.The data of hepatoprotection indicated that PSV obviously alleviated the hepatocellular injury induced by APAP in vivo and in vitro.The protective mechanism of PSV against APAP-induced AILI might be attributed to the activating NRF2/GPX4 pathway.Based on network pharmacology analysis,the active components of PSV such as caffeic acid,osmundacetone and hispolone played a key role in hepatoprotection of PSV.Consequently,this study highlights the protection of PSV on AILI,which provides new insight into bioactivities of S.vaninii.
基金supported by the Nanjing Infectious Disease Clinical Medical Center,Innovation center for infectious disease of Jiangsu Province(NO.CXZX202232)the Leading Talent Project of Jiangsu Province Traditional Chinese Medicine(NO.SLJ0216)+4 种基金the Nanjing Health science and Technology Development Special fund Project(NO.YKK20102)the General Program of Jiangsu Commission of Health(NO.M2021088)the Nanjing Health science and Technology Development General Project(NO.YKK21121)the 2023 Nanjing Second Hospital Talent Support Project Grant(RCZD23003)the Jiangsu Province Postgraduate Research and Practice Innovation Program(KYCX24_2176).
文摘The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.
基金supported by Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0500800)National Natural Science Foundation of China(Nos.82302390,82172090 and 82072059)+4 种基金CAMS Innovation Fund for Medical Sciences(Nos.2021-I2M-1-058,2022-I2M-2-003 and 2023-I2M-2-008)China Postdoctoral Science Foundation(No.2022M720502)Tianjin Municipal Natural Science Foundation(Nos.22JCQNJC00070 and 24ZXZSSS00200)CAMS Union Young Scholars Support Program(No.2022051)Fundamental Research Funds for the Central Universities(No.2019PT320028).
文摘Immune adjuvants are extremely important in tumor vaccines,which can amplify antigen-specific immune responses and enhance anti-tumor efficacy.Nevertheless,well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines.In this study,we designed and formulated carrier-free double-adjuvant nanoparticles(FPC-NPs)by self-assembling of fluoroalkane-grafted polyethylenimide(PEI)(Toll-like receptor 4(TLR4)agonist)and cytosine-phosphateguanine(CpG)(TLR9 agonist),and then obtained personalized tumor vaccines(FPC-NPs@TAAs)by electrostatic adsorption of tumor-associated antigens(TAAs)on the surface of FPC-NPs.The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants,deliver antigens and adjuvants to the same antigen-presenting cell,which can effectively activate dendritic cells,encourage cross-presentation of antigens,and reduce the proportion of M2-type macrophages.Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles,showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy.
基金supported by the National Natural Science Foundation of China(81560059,81760058,8160042,and 31800891)。
文摘Patients with glioma have a very high mortality rate,thus improving the poor prognosis of glioma has been the goal in the therapeutic field.Searching for more effective drugs for gliomas from natural compounds is a promising strategy.In this study,both oleanonic acid and oleanolic acid inhibited proliferation of glioma cells and reduced expression of cyclin D1 and E1,but the former has a lower IC_(50)than the latter.Oleanonic acid reduced the expression of p-STAT3 but not p-STAT1 and 5,and also reducing the expression of STAT3 in the nucleus and its transcriptional activity in glioma cells.Furthermore,knockdown of STAT3 expression inhibited proliferation and migration of glioma cells.Next,the expressions of the upstream regulators such as SIRT6 and p-JAK2 but not SIRT1,p-ERK1/2,p300 were increased by oleanonic acid.The overexpression of SIRT6 not only reduced the expression of p-STAT3 and its transcriptional activity but also inhibited the proliferation and migration of glioma cells.In addition,the effects that oleanonic acid reduced the expression of p-STAT3 and its transcriptional activity and inhibited the proliferation and migration were attenuated by the knockdown of SIRT6.Furthermore,oleanonic acid effectively suppressed glioma growth and extended survival in nude mice bearing intracerebral U87 xenografts,but not in nude mice bearing intracerebral SIRT6-knockdown U87xenografts.In conclusion,oleanonic acid upregulates the expression of SIRT6 to inactivates STAT3 and then inhibits glioma growth.
基金supported by the National Key Research and Development Program of China(2023YFB3809400)the National Natural Science Foundation of China(Grant nos.T2125008,92163203,and 52371234)+1 种基金the Hong Kong,Macao,and Taiwan Science and Technology Cooperation Project for Science and Technology Innovation Plan of Shanghai(23520760600)the Fundamental Research Funds for the Central Universities.
文摘Elastic strain constitutes a decisive factor in determining the recoverable deformability of thermoelectric materials.Plastic deformation for microstructure engineering has been demonstrated as a viable approach to enhance the elastic strain.However,this approach is highly dependent on the material's plasticity,which is rather limited by the rigidity for the majority of inorganic semiconducting thermoelectric materials.Thermocouple materials,as metallic thermoelectric materials,possess a favorable plasticity,motivating this work to focus on the elastic bendability of a metallic thermoelectric generator that is composed of K-type thermocouple components,namely p-type Ni_(90)Cr_(10) and n-type Ni_(95)Al_(2)Mn_(2)Si.The cold-rolling process enables a large elastic modulus and a high yield strength,thanks to the texturized direction along<111>,and dense dislocations and refined grains,respectively,eventually resulting in a 400%increase in the elastic strain.Such superior elasticity ensures the preservation of the initial transport properties for the rolled films even after being bent 100000 times within a radius of~8 mm.A power output of~414μW is achieved in a ten-leg flexible thermoelectric device,suggesting its substantial potential for powering wearable electronics.
基金National Key Research and Development Program,Grant/Award Number:2022YFD1800505Hainan Province Science and Technology Special Fund,Grant/Award Number:ZDYF2024XDNY198+1 种基金Beijing Municipal Natural Science Foundation,Grant/Award Number:6232025Natural Science Foundation of China,Grant/Award Number:32272960。
文摘Background:Prion diseases(PrDs)are fatal transmissible neurodegenerative disorders caused by misfolded prion protein,which is highly expressed in the brain.Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.Methods:Drosophila transgenic for hamster prion protein(HaPrP)was generated by Valium20 transformation.Locomotion,longevity,protease resistance,and histology were assessed,and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.Results:The Drosophila model exhibited pan-neuronal expression of HaPrP,with expression levels increasing with age.Flies displayed reduced climbing ability,shortened lifespan,and vacuolar structures in the brain.Additionally,HaPrP expressed in older flies demonstrated resistance to digestion by 5μg/mL Proteinase K.The Drosophila model also displayed alterations in protein,lipid,and carbohydrate metabolism.We hypothesize that glutamate,N-acetylaspartate,ceramide,phosphatidylethanolamine,dihydroxyacetone phosphate,ribose-5-phosphate,and pyruvate are key metabolites potentially related to PrDs.Metformin improved locomotor activity,reduced PrP res formation,and ameliorated mitochondrial dysfunction in flies,which may be associated with alterations in succinate,pyruvate,choline,and sphingomyelin levels.Conclusions:We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals.Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the highthroughput screening of potential therapeutic compounds.
基金supported by the National Natural Science Foundation of China,Nos.81771271(to JF),31800898(to WL),81430025(to JYL),and U1801681(to JYL)Key Research and Development Program of Liaoning Province,No.2020JH2/10300047(to JF)+1 种基金the Key Field Research Development Program of Guangdong Province,No.2018B030337001(to JYL)the Outstanding Scientific Fund of Shengjing Hospital,No.M0475(to JF)。
文摘Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen species.These findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Therefore,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.
文摘AIM: To explore the mechanism of protection against acetaminophen-induced acute liver injury by Liuweiwuling tablets.METHODS: Intraperitoneal injections of acetaminophen(250 mg/kg) were used to induce acute liver injury in male C57BL/6 mice.A total of 24 healthy mice were randomly assigned to two groups: an acute liver injury group(control group) and a Liuweiwuling tablet group.Mice were given Liuweiwuling tablets or a vehicle(PBS) orally prior to the administration of acetaminophen.Serum alanine aminotransferase(ALT) and aspartate aminotransaminase(AST) levels were measured at different time points within one week,and pathological examinations of liver tissues were performed 36 h after induction of acute liver injury.Serum inflammatory cytokines,such as high mobility group box protein B1(HMGB1),tumor necrosis factor(TNF)-α and interleukin IL-1b,were detected using an ELISA method according to the manufacturer's instructions.Hepatic morphological changes at 36 h were assessed by hematoxylin and eosin staining.Expression of proliferating cell nuclear antigen(PCNA) in liver tissue was determined by Western blot analysis.The m RNA levels of hepatocyte proliferation markers(PCNA,Cyclin D1 and p21) were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS: The levels of ALT/AST in the Liuweiwuling tablet group were decreased significantly at 6,12 and 24 h compared to that of the control group(654.38 ± 120.87 vs 1566.17 ± 421.64,1154.18 ± 477.72 vs 4654.84 ± 913.71 and 935.13 ± 252.34 vs 4553.75 ± 727.37,P < 0.01).Serum HMGB1 levels at 6 and 12 h for the Liuweiwuling tablet group were significantly lower than those of the control group(23.49 ± 3.89 vs58.6 ± 3.65,61.62 ± 13.07 vs 27.32 ± 5.97,P < 0.01).Furthermore,serum TNF-α and IL-1b levels at 12 h in the Liuweiwuling tablet group were also significantly lower than those of the control group(299.35 ± 50.61 vs 439.03 ± 63.59,57.42 ± 12.98 vs 160.07 ± 49.87,P < 0.01).Centrilobular necrosis was evident in liver tissue of mice with acetaminophen-induced acute liver injury,but was almost abolished in the Liuweiwuling tablet group.The expression levels of PCNA and Cyclin D1 were up-regulated in liver tissue in the Liuweiwuling tablet group(321.08 ± 32.87 vs 157.91 ± 21.52,196.37 ± 25.39 vs 68.72 ± 11.27,P < 0.01); however,expression of p21 in liver tissue was downregulated compared to that of the control group(40.26 ± 9.97 vs 138.24 ± 13.66,P < 0.01).CONCLUSION: Liuweiwuling tablets can attenuate acute liver injury by decreasing inflammatory cytokine(HMGB1,TNF-α and IL-1b) levels and promoting liver regeneration.
基金Supported by National Natural Science Foundation of China,No. 30470790 and 30971355
文摘AIM: To investigate the effect of biliary drainage on inducible nitric oxide synthase (iNOS), CD14 and TGR5 expression in rats with obstructive jaundice (OJ). METHODS: Male adult Sprague-Dawley rats were randomly assigned to four groups: OJ, sham operation (SH), internal biliary drainage (ID) and external biliary drainage (ED). Rat models were successfully established by two operations and succumbed for extraction of Kupffer cells (KCs) and liver tissue collection on the 8 th and 15 th day. KCs were isolated by in situ hepatic perfusion and digested with collagen Ⅳ, density gradient centrifuged by percoll reagent and purified by cell culture attachment. The isolated KCs were cultured with the endotoxin lipopolysaccharide (LPS) with and without the addition of ursodeoxycholic acid (UDCA). The expression of iNOS, CD14 and bile acid receptor-TGR5 protein in rat liver tissues was determined by immunohistochemistry. The expression of iNOS and CD14 messenger RNA (mRNA) on the isolated KCs was detected by reverse transcription polymerase chain reaction (PCR) and the TGR5 mRNA level in KCs was measured by real-time quantitative PCR. RESULTS: The iNOS protein was markedly expressed in the liver of OJ rats, but rare expressed in SH rats. After relief of OJ, the iNOS expression was decidedly suppressed in the ID group (ID vs OJ, P < 0.01), but obviously increased in rats of ED (ED vs OJ, P=0.004). When interfered only with LPS, the expression of iNOS mRNA by KCs was increased in the OJ group compared with the SH group (P=0.004). After relief of biliary obstruction, the iNOS mRNA expression showed slight changes in the ED group (ED vs OJ, P=0.71), but dropped in the ID group (ID vs OJ, P=0.001). Compared with the simple intervention with LPS, the expressions of iNOS mRNA were significantly inhibited in all four groups after interfered with both LPS and UDCA (P < 0.01, respectively). After bile duct ligation, the CD14 protein expression in rat liver was significantly strengthened (OJ vs SH, P < 0.01), but the CD14 mRNA level by KCs was not up-regulated (OJ vs SH, P=0.822). After relieving the OJ, the expression of CD14 protein was reduced in the ID group (ID vs OJ, P < 0.01), but not reduced in ED group (ED vs OJ, P=0.591). And then the CD14 mRNA expression was aggravated by ED (ED vs OJ, P < 0.01), but was not significantly different between the ID group and the SH and OJ groups (ID vs SH, P=0.944; ID vs OJ, P=0.513, respectively). The expression of TGR5 protein and mRNA increased significantly in OJ rats (OJ vs SH, P=0.001, respectively). After relief of OJ, ID could reduce the expression of TGR5 protein and mRNA to the levels of SH group (ID vs SH, P=0.22 and P=0.354, respectively), but ED could not (ED vs SH, P=0.001, respectively).CONCLUSION: ID could be attributed to the regulatory function of activation of KCs and release of inflammatory mediators.
基金the National Natural Science Foundation of China(Nos.51705435 and 51575459)the Key Project of Sichuan Department of Science and Technology(Nos.2018JZ0048 and 2019YFG0292)。
文摘Two-dimensional Ti_(3)C_(2)T_(x) flakes have great application potential in various areas due to their optical,electronic,electrochemical and mechanical properties,but their anti-corrosion and wear-resistance performance were not well understood.The difficulties in achieving good dispersity and interface interaction of inorganic additives in organic coatings hinder the incorporation of Ti_(3)C_(2)T_(x) into the epoxy coating.Here,few-layered Ti_(3)C_(2)T_(x) sheets with amino-functionalization were prepared,and as reinforced-additives were added into the waterborne epoxy coating.Anti-corrosion and tribological properties of as-prepared composite coatings were investigated in detail.The results reveal that the composite coating with 0.5 wt.%amino-functionalized Ti_(3)C_(2)T_(x) sheets shows excellent corrosion protection(the lowest frequency impedance was 3.12×10^(9) cm^(2))and wear resistance(wear rate was reduced by 72.74%).The greatly improving performance of composite coatings mainly depends on:(a)good dispersity and compatibility of amino-functionalized Ti_(3)C_(2)T_(x) in organic matrix,(b)high adhesion strength between coating and metal substrate and(c)the intrinsic properties of Ti3C2Tx sheets.The work provides a good path for applications of MXene as multifunctional additives.
基金This study was supported by the National Natural Science Foundation of China(No.U1801681,to GC and No.31970906,to WL)Guangdong Science and Technology Department(‘Key technologies for treatment of brain disorders’,No.2018B030332001,to GC)+2 种基金the Natural Science Foundation of Guangdong Province of China(No.2020A1515011079,to WL and No.2020A1515010854,to QW)the internal funding from Jinan University(No.21616110,to GC)the Young Scientists Fund of the National Natural Science Foundation of China(No.31701291,to WL).
文摘Regenerating functional new neurons in the adult mammalian central nervous system has been proven to be very challenging due to the inability of neurons to divide and repopulate themselves after neuronal loss.Glial cells,on the other hand,can divide and repopulate themselves under injury or diseased conditions.We have previously reported that ectopic expression of NeuroD1 in dividing glial cells can directly convert them into neurons.Here,using astrocytic lineage-tracing reporter mice(Aldh1l1-CreERT2 mice crossing with Ai14 mice),we demonstrate that lineage-traced astrocytes can be successfully converted into NeuNpositive neurons after expressing NeuroD1 through adeno-associated viruses.Retroviral expression of NeuroD1 further confirms that dividing glial cells can be converted into neurons.Importantly,we demonstrate that for in vivo cell conversion study,using a safe level of adeno-associated virus dosage(10^10–10^12 gc/mL,1μL)in the rodent brain is critical to avoid artifacts caused by toxic dosage,such as that used in a recent bioRxiv study(2×10^13 gc/mL,1μL,mouse cortex).For therapeutic purpose under injury or diseased conditions,or for non-human primate studies,adeno-associated virus dosage needs to be optimized through a series of dose-finding experiments.Moreover,for future in vivo gliato-neuron conversion studies,we recommend that the adeno-associated virus results are further verified with retroviruses that mainly express transgenes in dividing glial cells in order to draw solid conclusions.The study was approved by the Laboratory Animal Ethics Committee of Jinan University,China(approval No.IACUC-20180330-06)on March 30,2018.
基金supported by the National Natural Science Foundation of China(21276284,21676303,21706292)~~
文摘In the present work,a Pd/graphene/cordierite(Pd/Gr/Cor)composite was prepared as a monolithic catalyst for low-temperature combustion of toluene.We mainly focused on understanding the role of graphene coating through investigation of catalytic performance and adsorption behavior of the composite.Compared with the traditional Pd/Cor catalyst without graphene coating,Pd/Gr/Cor catalyst delivered much higher activity and stability for toluene catalytic combustion in both dry and moist conditions.Transmission electron microscopy(TEM)and hydrophobic characterizations indicated that graphene coating can considerably improve the dispersity of Pd nanoparticles and enhance the hydrophobicity of the cordierite support.The adsorption behavior of the above two catalysts,including adsorption isothermal,adsorption kinetics,and adsorption thermodynamics were carefully investigated.The simulation results indicated that a large amount of toluene was adsorbed on graphene surface through relatively weak interaction,whereas only a relatively small amount of toluene was adsorbed on Pd surface with strong affinity.The adsorption thermal calculation indicated that the adsorption of toluene on graphene was a process with reduced entropy,indicating highly-ordered assembly of toluene molecular on graphene.It is the significant concentration and affinity gap between graphene and Pd that ensures a simultaneously and rapid transfer of toluene during the reaction process.
基金supported by Graduate Scientific Research Innovation Program of Jiangsu Province of China,No.KYCX192066(to WL)Project Funded by the Priority Academic Program Development(PAPD)of Jiangsu Higher Education institutions China,No.03081023(to GHJ)。
文摘The regulation of adult neural stem cells(NSCs) is critical for lifelong neurogenesis. MicroRNAs(miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, mi R-103-3 p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that mi R-103-3 p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, mi R-103-3 p negatively regulated Nud E neurodevelopment protein 1-like 1(Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3 a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel mi R-103-3 p target and that mi R-103-3 p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China(approval No. 20200826-003) on August 26, 2020.
文摘Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
基金financially supported by the National Natural Science Foundation of China(No.52075458)the Sichuan Science and Technology Program(No.2021JDRC0094)。
文摘Surface and interface engineering plays a crucial role in modulating the properties of materials,especially two-dimensional(2D)materials.Hence,a strategy,forming heterostructures with MoS_(2),is proposed to overcome the natural agglomeration of Ti_(3)C_(2)T_(x) MXene nanosheets.Most importantly,the interactions between Ti_(3)C_(2)Tx and MoS_(2) were elaborately investigated by first-principles calculations based on density functional theory(DFT)for the first time.The calculations demonstrate that van der Waals forces dominate the interface interactions of Ti_(3)C_(2)T_(x) and MoS_(2),rendering Ti_(3)C_(2)T_(x)@MoS_(2) heterostructures favorable stability.The Ti_(3)C_(2)T_(x)@MoS_(2) heterostructure composites were synthesized through a facile one-step hydrothermal method and exhibit a 2D hierarchical structure.Furthermore,the corrosion and tribological properties of epoxy composite coatings with varying proportions of Ti_(3)C_(2)T_(x)@MoS_(2) composites were studied in detail.As a result,the epoxy composite coating with 0.1 wt.%Ti_(3)C_(2)T_(x)@MoS_(2) composites(Ti_(3)C_(2)T_(x)@MoS_(2)-0.1)exhibits excellent corrosion protection and antiwear performances.The Ti_(3)C_(2)T_(x)@MoS_(2)-0.1 keeps the largest low-frequency impedance modulus(|Z|_(0.)01 Hz)and coating resistance(R_(c))during the whole immersion period.Its wear rate is 0.09μm^(3)/(Nμm)under the load of 10 N,one half of that of pure epoxy coating(EP).This work further broadens the application of MXene-based heterostructure composites.
基金Supported by the National Natural Science Foundation of ChinaNo.81160065
文摘AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute liver failure(ALF).METHODS: Balb/c mice were randomly assigned to different groups,with ALF induced by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1(HMGB1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,IL-10,and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western blot.RESULTS: The expression of Sphk1 in liver tissue and PBMCs was upregulated in Gal N/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells,the resident macrophages of the liver. The survival rates of mice in the N,Ndimethylsphingosine(DMS,a specific inhibitor of Sph K1) treatment group were significantly higher than that of the control group(P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6,12,and 24 h compared with that of the control group(P < 0.01 for all). Serum HMGB1 levels at 6,12,and 24 h,as well as serum TNF-α,IL-6,and IL-1β levels at 12 h,were significantly lower in the DMS treatment group than in the control group(P < 0.01 for all). Furthermore,hepatic inflammation,necrosis,and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment group compared to the control group(43.72% ± 5.51% vs 3.57% ± 0.83%,χ2 = 12.81,P < 0.01).CONCLUSION: Inhibition of Sph K1 ameliorates ALF by reducing HMGB1 cytoplasmic translocation in liver cells,and so might be a potential therapeutic strategy for this disease.
文摘Background The reversibility of pulmonary arterial hypertension(PAH)in congenital heart disease(CHD)is of great importance for the operability of CHD.Proteomics analysis found that transgelin was significantly upregulated in the lung tissue of CHD-PAH patients,especially in the irreversible group.However,how exactly it participated in CHD-PAH development is unknown.
