Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule...Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule drug with aripiprazole as the active pharmaceutical ingredient） oral solution and die- thylenetriaminepentaacetic acid （DTPA） in Yervoy （a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient） intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions （Cu2＋, Fe3＋） which generate highly stable metallocom- plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in- volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de- termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids （APCAs） including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.展开更多
Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of ...Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict.展开更多
Capsaicin(CAP)is a major pungent component that has been widely studied in medical and pharmaceutical fields.CAP was used both orally and topically for pain relief.However,the extreme pungency and the water insolubili...Capsaicin(CAP)is a major pungent component that has been widely studied in medical and pharmaceutical fields.CAP was used both orally and topically for pain relief.However,the extreme pungency and the water insolubility of CAP lead to its restriction in the development of CAP as drug delivery system[1].Our previous study suggested that the computer software exhibited a beneficial role in the development of menthosomes for transdermal drug delivery[2].To confirm the reliability and reproducibility of simultaneous optimal formulations,the optimal ultraflexible liposomes(invasomes)estimated by the computer software(Design Expert?)were experimentally formulated and investigated.展开更多
Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference g...Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference gene and target gene would be degraded.As a result,it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation.This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment.Methods The new RNA was labeled with 5-ethyluridine(5-EU)instead of uracil,and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of“Click Chemistry”and magnetic bead screening.Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon(M.B.)and quantitative reverse transcription PCR(qRT-PCR).Results The bacterial nascent RNA captured by“Click Chemistry”screening can be used as a reverse transcription template to form cDNA.Combined with the fluorescent molecular beacon M.B.1,the synthesis rate of rRNA at 37℃is 1.2 times higher than that at 15℃.The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃and 16℃when analyzed with nascent RNA rather than total RNA,enabling accurate detection of RNA transcription rates.Conclusion Compared to other article reported experimental methods that utilize screening magnetic columns,the technical scheme employed in this study is more suitable for bacteria,and the operation steps are simple and easy to implement,making it an effective RNA capture method for researchers.展开更多
In this study, the adsorptive properties of L-menthol, moisture vapor transmission rate, and mechanical properties of poly (ethylene terephthalate) (PET), polypropylene (PP), and their blends were evaluated in contain...In this study, the adsorptive properties of L-menthol, moisture vapor transmission rate, and mechanical properties of poly (ethylene terephthalate) (PET), polypropylene (PP), and their blends were evaluated in containers fabricated by injection molding without a compatibilizing agent. These containers intended to hold pharmaceutical solutions containing lipophilic chemicals such as L-menthol. By the addition of a small amount of PP, the moisture barrier properties of PET were effectively improved, but its anti-adsorptive property was reduced. The strength of the PET/PP blends was reduced, but some PET/PP blends were still able to bear the experimental load required for application in eye-drop containers. PET/PP = 9/1 and PET/PP = 8/2 were found to be most applicable for using in the fabrication of containers for medicinal solutions.展开更多
Biomacromolecules derived from plant-based traditional Chinese medicines play a pivotal role in natural drug research.Ginseng,the root of Panax ginseng C.A.Meyer,has attracted significant attention due to its diverse ...Biomacromolecules derived from plant-based traditional Chinese medicines play a pivotal role in natural drug research.Ginseng,the root of Panax ginseng C.A.Meyer,has attracted significant attention due to its diverse pharmacological activities and broad therapeutic applications.This review focuses on specific active macromolecules obtained from ginseng,including pectin,exosomes,proteins,and dietary fibers.These components possess unique structural characteristics and biological activities that offer novel insights into the multifaceted applications of ginseng.To systematically assess this field,we reviewed literature published over the past 60 years and identified 119 relevant studies investigating the structural composition,pharmacological activity,and potential applications of P.ginseng biomacromolecules.By highlighting their crucial role in promoting health and enhancing disease resistance,this review synthesizes the latest research findings on ginseng’s pharmacological effects,providing new perspectives and strong theoretical support for clinical drug development.展开更多
Electromagnetic wave(EMW)absorbers with anti-corrosion property are highly desired to enhance the durability of military targets in harsh condition.Herein,cross-link NiAl-layered double hydroxide(NiAl-LDH)nanosheets o...Electromagnetic wave(EMW)absorbers with anti-corrosion property are highly desired to enhance the durability of military targets in harsh condition.Herein,cross-link NiAl-layered double hydroxide(NiAl-LDH)nanosheets on the inner/outer surfaces of carbon microtubes(CMTs)are ingeniously constructed through the combination of atomic layer deposition technique and a hydrothermal method.The obtained NiAl-LDH/CMT composite exhibits excellent EMW absorption and corrosion resistance performance.The large internal cavity of CMT significantly enhances impedance matching.The uniform distribution of NiAl-LDH nanosheets on both the inner and outer surfaces of CMT generates numerous heterogeneous inter-faces that induce substantial polarization loss.Consequently,at a filler rate of only 5 wt.%,the NiAl-LDH/CMT composite exhibits a minimum reflection loss of−60.2 dB and a maximum effective absorp-tion bandwidth of 5.9 GHz.In addition,the combined high impermeability of CMT and the effective Cl^(-)-trapping ability of NiAl-LDH endows NiAl-LDH/CMT composite with outstanding corrosion protection property in simulated seawater environment.Furthermore,the PO_(4)^(3-)anions are effectively incorporated into the NiAl-LDH interlayer via anion exchange,which can further enhance corrosion protection capac-ity through surface inactivation from slow-release PO_(4)^(3-)anions without reducing their EMW absorption performance.In summary,this work can give guidance for the development of efficient anti-corrosion EMW absorption materials.展开更多
Colistin serves as a crucial treatment for multidrugresistant(MDR)Gram-negative bacterial infections.However,its excessive use has contributed to an increase in colistin-resistant strains within livestock production(B...Colistin serves as a crucial treatment for multidrugresistant(MDR)Gram-negative bacterial infections.However,its excessive use has contributed to an increase in colistin-resistant strains within livestock production(Binsker et al.2022).The mobile colistin resistance gene,mcr,which reduces colistin affinity by incorporating phosphoethanolamine(pEtN)into the bacterial lipopolysaccharide,significantly compromises the effectiveness of colistin treatments(Liu et al.2016).展开更多
Background:Polygonum multiflorum-induced liver injury(PM-DILI)has significantly hindered its clinical application and development.Methods:This study investigates the variation in content and toxicity of dian-thrones,t...Background:Polygonum multiflorum-induced liver injury(PM-DILI)has significantly hindered its clinical application and development.Methods:This study investigates the variation in content and toxicity of dian-thrones,the toxic components of P.multiflorum,during different processing cycles.We employed the ultra-high-performance liquid chromatography triple quadrupole mass spectrometry method to quantify six dianthrones in raw P.multiflorum and formulations processed with a method called nine cycles of steaming and sunning.Additionally,toxicity assessments were conducted using human normal liver cell line L02 and zebrafish embryos.Results:Results indicate a gradual reduction in dianthrones content with increasing processing cycles.Processed formulations exhibited significantly reduced cytotoxic-ity in L02 cells and hepatotoxicity in zebrafish embryos.Conclusions:Our findings elucidate the relationship between processing cycles and P.multiflorum toxicity,providing theoretical support for its safe use.展开更多
Extensive use of avermectin(AVM)in agriculture can seriously contaminate fish in aquaculture.Ferulic acid(FA)is a strong antioxidant sourced from plants and is widely applied in food and medicine,but its protective fu...Extensive use of avermectin(AVM)in agriculture can seriously contaminate fish in aquaculture.Ferulic acid(FA)is a strong antioxidant sourced from plants and is widely applied in food and medicine,but its protective function on the immunological damage caused by AVM is still lacking.In this study,carp were chronically exposed to(1/1096 hr LC_(50))AVM for 30 day(s),with a dietary supplement of FA(400 mg/kg)to assess its effects on carp spleen.The experimental groups(n=10)included:control,AVM-exposed(2.404μg/L),FA+AVM co-treated,and FA alone.Long-term AVM exposure altered spleen tissue,reducing serum complement C3(p<0.01)and immunoglobulin M levels(p<0.001),and increasing proinflammatory tnf-α(p<0.001),il-6(p<0.001),il-1β(p<0.001),and inos mRNA levels,whilst down-regulating the anti-inflammatory tgf-β(p<0.05).Additionally,it disrupted the balance of oxidative stress indicators such asMDA(p<0.001),T-AOC,GSH,and CAT,leading to spleen tissue apoptosis(42.4%).However,the addition of FA reversed these conditions,elevated the anti-inflammatory factor,and improved spleen immune function following chronic exposure to AVMin carp.Moreover,the ability to restore oxidative homeostasis in carp by adjusting the Nrf2/NQO-1 axis protected the health of spleen tissues.This discovery also supports the development of fish feed for aquaculture.展开更多
Sepsis is an inflammatory disease resulting from a dysregulated host response to infection that may lead to multiple organ failure and is commonly observed in patients with severe trauma or infectious diseases.Sepsis ...Sepsis is an inflammatory disease resulting from a dysregulated host response to infection that may lead to multiple organ failure and is commonly observed in patients with severe trauma or infectious diseases.Sepsis has become a major global public health issue due to its high incidence and fatality.It not only causes an excessive inflammatory response,but also leads to immune system dysfunction[1].展开更多
Environmental residues of the fungicide difenoconazole(DFZ)have been shown to pose a threat to mammals.However,the risk assessment of DFZ for cultured carp remains unclear.The aim of this study was to investigate the ...Environmental residues of the fungicide difenoconazole(DFZ)have been shown to pose a threat to mammals.However,the risk assessment of DFZ for cultured carp remains unclear.The aim of this study was to investigate the adverse effects of DFZ on carp liver and their molecular mechanisms by simulating the environmental contamination concentrations of DFZ.Our results showed that DFZ induced structural damage in the liver,including edema,vacuolation,and congestion.In addition,DFZ residues were detected in liver tissues.Mechanistically,DFZ causes mitochondrial dysfunction by promoting Ca^(2+)transfer from the endoplasmic reticulum(ER)to mitochondria via IP3R,leading to the onset of ROS burst and apoptosis,and the inhibition of Nrf2 antioxidant function by DFZ also results in uncontrolled ROS.Mitophagy was also activated intracellularly to counteractmitochondrial damage.Interestingly,treatment with 2-APB alleviated mitochondrial dysfunction,restored the mitochondrial membrane potential,and inhibited apoptosis by blocking the translocation of Ca2+from the ER to the mitochondria.Metabolomic analysis revealed that DFZ disrupted energy metabolism in carp liver,whereas 2-APB reversed DFZ-induced metabolic alterations.In conclusion,the present study elucidates the threat of DFZ to carp liver and highlights the mechanism of damage,thereby helping to explain the impact of agriculture on the aquatic environment.展开更多
Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability ...Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability and validity of the DARS among Chinese individuals with major depressive disorder(MDD)and its treatment sensitivity in a prospective clinical study.Methods Data were from a multicentre,prospective clinical study(NCT03294525),which recruited both patients with MDD,who were followed for 8 weeks,and healthy controls(HCs),assessed at baseline only.The analysis included confirmatory factor analysis,validity and sensitivity to change.Results Patients’mean(standard deviation(SD))age was 34.8(11.0)years,with 68.7%being female.75.2%of patients with MDD had melancholic features,followed by 63.8%with anxious distress.Patients had experienced MDD for a mean(SD)of 9.2(18)months.DARS scores covered the full range of severity with no major floor or ceiling effects.Confirmatory factor analysis showed adequate fit statistics(comparative fit index 0.976,goodness-of-fit index 0.935 and root mean square error of approximation 0.055).Convergent validity with anhedonia-related measures was confirmed.While the correlation between the DARS and the Hamilton Depression Rating Scale was not strong(r=0.31,baseline),the DARS was found to differentiate between levels of depression.Greater improvements in DARS scores were seen with the Hamilton Rating Scale for Depression responder group(effect size 1.16)compared with the non-responder group(effect size 0.46).Conclusions This study comprehensively evaluated the measurement properties of the DARS using a Chinese population with MDD.Overall,the Chinese version of DARS demonstrates good psychometric properties and has been found to be responsive to change during antidepressant treatment.The DARS is a suitable scale for assessing patient-reported anhedonia in future clinical trials.展开更多
The purpose of the present study was to survey contents of trace elements of Cu, Mn, Fe, and Zn in the surface layer （0-20 cm） in the soil, pasture and serum of sheep in Huangcheng area of Qilian mountain grassland,...The purpose of the present study was to survey contents of trace elements of Cu, Mn, Fe, and Zn in the surface layer （0-20 cm） in the soil, pasture and serum of sheep in Huangcheng area of Qilian mountain grassland, China. Also the soil-plantanimal continuum was analyzed. Soil （n=300）, pasture （n=60）, and blood serum samples from sheep （n=480） were collected from Huangcheng area of Qilian mountain grassland, China. The contents of trace element in the samples were analyzed by atomic absorption spectrophotometer after digestion. The soil trace elements density distribution shows a ladder-like pattern distribution. Equations developed in the present study for prediction of Fe （R2=0.943） and Zn （R2=0.882） had significant R2 values.展开更多
Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicro...Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicrobial resistance in S. aureus cultured from bovine mastitis in Northwest China in 2014. A total of 44 S. aureus were isolated for antimicrobial resistance and resistance-related genes. Antimicrobial resistance was determined by disc diffusion and the corresponding resistance genes were detected by PCR. Phenotype indicated that S. aureus isolates were resistant to penicillin （84.09%）, erythromycin （20.45%）, tetracycline （15.91%）, gentamicin （9.09%）, tobramycin （6.82%）, kanamycin （6.82%） and methicillin （2.27%）. 9.09% of the S. aureus isolates were classified as multidrug resistant. In addition, genotypes showed that the isolates were resistant to rifampicin （100%, rpoB）, penicillin （95.45%, blaZ）, tetracycline （22.73%, tetK, tetM, alone or in combination）, erythromycin （22.73%, ermB or ermC）, gentamicin/tobramycin/kanamycin （2.27%, aacA-aphD）, methicillin （2.27%, mecA） and vancomycin （2.27%, vanA）. Resistance to tetracycline was attributed to the genes tetK and tetM （r=0.558, P〈0.001）. This study noted high-level geno- and phenotypic antimicrobial resistance in S. aureus isolates from bovine mastitis cases in Northwest China.展开更多
The objectives of this study were to investigate antimicrobial resistance of Streptococcus uberis and Streptococcus parauberis isolated from cows with bovine clinical mastitis in China and to examine the distribution ...The objectives of this study were to investigate antimicrobial resistance of Streptococcus uberis and Streptococcus parauberis isolated from cows with bovine clinical mastitis in China and to examine the distribution of resistance-and virulence-related gene patterns.Antimicrobial susceptibility was determined by the E-test.Genes encoding antimicrobial resistance and invasiveness factors were examined by PCR.A total of 27 strains were obtained from 326 mastitis milk samples.Streptococcus parauberis isolates(n=11)showed high resistance to erythromycin(90.9%),followed by tetracycline(45.5%),chloramphenicol(36.4%)and clindamycin(27.3%).Streptococcus uberis isolates(n=16)were highly resistant to tetracycline(81.3%)and clindamycin(62.5%).Both species were susceptible to ampicillin.The most prevalent resistance gene in S.uberis was tetM(80.0%),followed by blaZ(62.5%)and ermB(62.5%).However,tetM,blaZ,and ermB genes were only found in 27.3,45.5,and 27.3%,respectively,of S.parauberis.In addition,all of the isolates carried at least one selected virulence-related gene.The most prevalent virulence-associated gene pattern in the current study was sua+pauA/skc+gapC+hasC detected in 22.2%of the strains.One S.uberis strain carried 7 virulence-associated genes and belonged to the sua+pauA/skc+gapC+cfu+hasA+hasB+hasC pattern.More than 59.3%of analysed strains carried 4 to 7 virulence-related genes.Our findings demonstrated that S.parauberis and S.uberis isolated from clinical bovine mastitis cases in China exhibited diverse molecular ecology,and that the strains were highly resistant to antibiotics commonly used in the dairy cow industry.The data obtained in the current study contribute to a better understanding of the pathogenesis of bacteria in mastitis caused by these pathogens,and the findings are relevant to the development of multivalent vaccines and targeted prevention procedures.展开更多
Genetic transformation is an important technique for functional genomics study and genetic improvement of plants. Until now, Agrobacterium-mediated transformation methods using cotyledon as explants has been the major...Genetic transformation is an important technique for functional genomics study and genetic improvement of plants. Until now, Agrobacterium-mediated transformation methods using cotyledon as explants has been the major approach for cucumber, and its frequency has been up to 23%. For example, significantly enhancement of the transformation efficiency of this plant species was achieved from the cotyledon explants of the cultivar Poinsett 76 infected by Agrobacterium strains EHA105 with efficient positive selection system in lots of experiments. This review is to summarize some key factors influencing cucumber regeneration and genetic transformation, including target genes, selection systems and the ways of transgene introduction, and then to put forward some strategies for the increasing of cucumber transformation efficiency. In the future, it is high possible for cucumber to be potential bioreactor to produce vaccine and biomaterials for human beings.展开更多
Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to ...Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract.Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability.The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion.The prepared pellets show high drug loading capacity,and the drug loading up to 93%.Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR.The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets.The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size.All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors.展开更多
OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded lip...OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.展开更多
文摘Ion-pairing high-performance liquid chromatography-ultraviolet （HPLC-UV） methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid （EDTA） in Abilify （a small molecule drug with aripiprazole as the active pharmaceutical ingredient） oral solution and die- thylenetriaminepentaacetic acid （DTPA） in Yervoy （a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient） intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions （Cu2＋, Fe3＋） which generate highly stable metallocom- plexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation in- volving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the de- termination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids （APCAs） including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.
文摘Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict.
文摘Capsaicin(CAP)is a major pungent component that has been widely studied in medical and pharmaceutical fields.CAP was used both orally and topically for pain relief.However,the extreme pungency and the water insolubility of CAP lead to its restriction in the development of CAP as drug delivery system[1].Our previous study suggested that the computer software exhibited a beneficial role in the development of menthosomes for transdermal drug delivery[2].To confirm the reliability and reproducibility of simultaneous optimal formulations,the optimal ultraflexible liposomes(invasomes)estimated by the computer software(Design Expert?)were experimentally formulated and investigated.
文摘Objective Detection and quantification of RNA synthesis in cells is a widely used technique for monitoring cell viability,health,and metabolic rate.After exposure to environmental stimuli,both the internal reference gene and target gene would be degraded.As a result,it is imperative to consider the accurate capture of nascent RNA and the detection of transcriptional levels of RNA following environmental stimulation.This study aims to create a Click Chemistry method that utilizes its property to capture nascent RNA from total RNA that was stimulated by the environment.Methods The new RNA was labeled with 5-ethyluridine(5-EU)instead of uracil,and the azido-biotin medium ligand was connected to the magnetic sphere using a combination of“Click Chemistry”and magnetic bead screening.Then the new RNA was captured and the transcription rate of 16S rRNA was detected by fluorescence molecular beacon(M.B.)and quantitative reverse transcription PCR(qRT-PCR).Results The bacterial nascent RNA captured by“Click Chemistry”screening can be used as a reverse transcription template to form cDNA.Combined with the fluorescent molecular beacon M.B.1,the synthesis rate of rRNA at 37℃is 1.2 times higher than that at 15℃.The 16S rRNA gene and cspI gene can be detected by fluorescent quantitative PCR,it was found that the measured relative gene expression changes were significantly enhanced at 25℃and 16℃when analyzed with nascent RNA rather than total RNA,enabling accurate detection of RNA transcription rates.Conclusion Compared to other article reported experimental methods that utilize screening magnetic columns,the technical scheme employed in this study is more suitable for bacteria,and the operation steps are simple and easy to implement,making it an effective RNA capture method for researchers.
文摘In this study, the adsorptive properties of L-menthol, moisture vapor transmission rate, and mechanical properties of poly (ethylene terephthalate) (PET), polypropylene (PP), and their blends were evaluated in containers fabricated by injection molding without a compatibilizing agent. These containers intended to hold pharmaceutical solutions containing lipophilic chemicals such as L-menthol. By the addition of a small amount of PP, the moisture barrier properties of PET were effectively improved, but its anti-adsorptive property was reduced. The strength of the PET/PP blends was reduced, but some PET/PP blends were still able to bear the experimental load required for application in eye-drop containers. PET/PP = 9/1 and PET/PP = 8/2 were found to be most applicable for using in the fabrication of containers for medicinal solutions.
基金supported by the grants of the National Natural Science Foundation of China(Grant No.82474070)Jilin Science&Technology Development Plan(Grant No.20230204003YY).
文摘Biomacromolecules derived from plant-based traditional Chinese medicines play a pivotal role in natural drug research.Ginseng,the root of Panax ginseng C.A.Meyer,has attracted significant attention due to its diverse pharmacological activities and broad therapeutic applications.This review focuses on specific active macromolecules obtained from ginseng,including pectin,exosomes,proteins,and dietary fibers.These components possess unique structural characteristics and biological activities that offer novel insights into the multifaceted applications of ginseng.To systematically assess this field,we reviewed literature published over the past 60 years and identified 119 relevant studies investigating the structural composition,pharmacological activity,and potential applications of P.ginseng biomacromolecules.By highlighting their crucial role in promoting health and enhancing disease resistance,this review synthesizes the latest research findings on ginseng’s pharmacological effects,providing new perspectives and strong theoretical support for clinical drug development.
基金financially supported by the National Natu-ral Science Foundation of China(Nos.U24A20204,22168016,and 22278101)the Innovation Project for Scientific and Technological Talents in Hainan Province(No.KJRC2023C08)the Innovation Research Team in Hainan Province(No.525CXTD607).
文摘Electromagnetic wave(EMW)absorbers with anti-corrosion property are highly desired to enhance the durability of military targets in harsh condition.Herein,cross-link NiAl-layered double hydroxide(NiAl-LDH)nanosheets on the inner/outer surfaces of carbon microtubes(CMTs)are ingeniously constructed through the combination of atomic layer deposition technique and a hydrothermal method.The obtained NiAl-LDH/CMT composite exhibits excellent EMW absorption and corrosion resistance performance.The large internal cavity of CMT significantly enhances impedance matching.The uniform distribution of NiAl-LDH nanosheets on both the inner and outer surfaces of CMT generates numerous heterogeneous inter-faces that induce substantial polarization loss.Consequently,at a filler rate of only 5 wt.%,the NiAl-LDH/CMT composite exhibits a minimum reflection loss of−60.2 dB and a maximum effective absorp-tion bandwidth of 5.9 GHz.In addition,the combined high impermeability of CMT and the effective Cl^(-)-trapping ability of NiAl-LDH endows NiAl-LDH/CMT composite with outstanding corrosion protection property in simulated seawater environment.Furthermore,the PO_(4)^(3-)anions are effectively incorporated into the NiAl-LDH interlayer via anion exchange,which can further enhance corrosion protection capac-ity through surface inactivation from slow-release PO_(4)^(3-)anions without reducing their EMW absorption performance.In summary,this work can give guidance for the development of efficient anti-corrosion EMW absorption materials.
基金funded by theNational KeyR&DProgram of China(2023YFD1800800)the Basic Scientific Research Business Expenses of Central Public Welfare Scientific Research Institutes,China(Y2022YJ14)+1 种基金the Technology Innovation Project of Hubei Province,China(2022BEC033)the Innovation Program of Chinese Academy of Agricultural Sciences-Veterinary Natural Medicine and Antibiotic Replacement,China(25-LZIHPS-03).
文摘Colistin serves as a crucial treatment for multidrugresistant(MDR)Gram-negative bacterial infections.However,its excessive use has contributed to an increase in colistin-resistant strains within livestock production(Binsker et al.2022).The mobile colistin resistance gene,mcr,which reduces colistin affinity by incorporating phosphoethanolamine(pEtN)into the bacterial lipopolysaccharide,significantly compromises the effectiveness of colistin treatments(Liu et al.2016).
基金National Natural Science Foundation of China,Grant/Award Number:81973476Chinese Society of Toxicology,Grant/Award Number:CST2021CT101。
文摘Background:Polygonum multiflorum-induced liver injury(PM-DILI)has significantly hindered its clinical application and development.Methods:This study investigates the variation in content and toxicity of dian-thrones,the toxic components of P.multiflorum,during different processing cycles.We employed the ultra-high-performance liquid chromatography triple quadrupole mass spectrometry method to quantify six dianthrones in raw P.multiflorum and formulations processed with a method called nine cycles of steaming and sunning.Additionally,toxicity assessments were conducted using human normal liver cell line L02 and zebrafish embryos.Results:Results indicate a gradual reduction in dianthrones content with increasing processing cycles.Processed formulations exhibited significantly reduced cytotoxic-ity in L02 cells and hepatotoxicity in zebrafish embryos.Conclusions:Our findings elucidate the relationship between processing cycles and P.multiflorum toxicity,providing theoretical support for its safe use.
基金supported by the National Natural Science Foundation of China(No.81773968)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
文摘Extensive use of avermectin(AVM)in agriculture can seriously contaminate fish in aquaculture.Ferulic acid(FA)is a strong antioxidant sourced from plants and is widely applied in food and medicine,but its protective function on the immunological damage caused by AVM is still lacking.In this study,carp were chronically exposed to(1/1096 hr LC_(50))AVM for 30 day(s),with a dietary supplement of FA(400 mg/kg)to assess its effects on carp spleen.The experimental groups(n=10)included:control,AVM-exposed(2.404μg/L),FA+AVM co-treated,and FA alone.Long-term AVM exposure altered spleen tissue,reducing serum complement C3(p<0.01)and immunoglobulin M levels(p<0.001),and increasing proinflammatory tnf-α(p<0.001),il-6(p<0.001),il-1β(p<0.001),and inos mRNA levels,whilst down-regulating the anti-inflammatory tgf-β(p<0.05).Additionally,it disrupted the balance of oxidative stress indicators such asMDA(p<0.001),T-AOC,GSH,and CAT,leading to spleen tissue apoptosis(42.4%).However,the addition of FA reversed these conditions,elevated the anti-inflammatory factor,and improved spleen immune function following chronic exposure to AVMin carp.Moreover,the ability to restore oxidative homeostasis in carp by adjusting the Nrf2/NQO-1 axis protected the health of spleen tissues.This discovery also supports the development of fish feed for aquaculture.
基金supported by the National Natural Science Foundation of China(No.81773968)Priority Academic Program Development of Jiangsu Higher Education Institutions of China。
文摘Sepsis is an inflammatory disease resulting from a dysregulated host response to infection that may lead to multiple organ failure and is commonly observed in patients with severe trauma or infectious diseases.Sepsis has become a major global public health issue due to its high incidence and fatality.It not only causes an excessive inflammatory response,but also leads to immune system dysfunction[1].
基金supported by the 14th Five-Year Medical Key Talent Project(No.ZDRC013)the First People’s Hospital of Lianyungang Research Talent Program(No.2023RC23)+1 种基金the Open-end Funds of Jiangsu Key Laboratory of Marine Bioresources and Environment(No.SH20221203)the Priority Academic Program Development of Jiangsu Higher Education Institutions of China.
文摘Environmental residues of the fungicide difenoconazole(DFZ)have been shown to pose a threat to mammals.However,the risk assessment of DFZ for cultured carp remains unclear.The aim of this study was to investigate the adverse effects of DFZ on carp liver and their molecular mechanisms by simulating the environmental contamination concentrations of DFZ.Our results showed that DFZ induced structural damage in the liver,including edema,vacuolation,and congestion.In addition,DFZ residues were detected in liver tissues.Mechanistically,DFZ causes mitochondrial dysfunction by promoting Ca^(2+)transfer from the endoplasmic reticulum(ER)to mitochondria via IP3R,leading to the onset of ROS burst and apoptosis,and the inhibition of Nrf2 antioxidant function by DFZ also results in uncontrolled ROS.Mitophagy was also activated intracellularly to counteractmitochondrial damage.Interestingly,treatment with 2-APB alleviated mitochondrial dysfunction,restored the mitochondrial membrane potential,and inhibited apoptosis by blocking the translocation of Ca2+from the ER to the mitochondria.Metabolomic analysis revealed that DFZ disrupted energy metabolism in carp liver,whereas 2-APB reversed DFZ-induced metabolic alterations.In conclusion,the present study elucidates the threat of DFZ to carp liver and highlights the mechanism of damage,thereby helping to explain the impact of agriculture on the aquatic environment.
基金supported by the National Natural Science Foundation of China(No.82371530,82171529)the Capital Health Development Special Research Project(2022-1-4111)the National Key Technology R and D Program(No.2015BAI13B01).
文摘Background The patient-reported Dimensional Anhedonia Rating Scale(DARS)has been adapted into Chinese,so there is a need to evaluate its measurement properties in a Chinese population.Aims To evaluate the reliability and validity of the DARS among Chinese individuals with major depressive disorder(MDD)and its treatment sensitivity in a prospective clinical study.Methods Data were from a multicentre,prospective clinical study(NCT03294525),which recruited both patients with MDD,who were followed for 8 weeks,and healthy controls(HCs),assessed at baseline only.The analysis included confirmatory factor analysis,validity and sensitivity to change.Results Patients’mean(standard deviation(SD))age was 34.8(11.0)years,with 68.7%being female.75.2%of patients with MDD had melancholic features,followed by 63.8%with anxious distress.Patients had experienced MDD for a mean(SD)of 9.2(18)months.DARS scores covered the full range of severity with no major floor or ceiling effects.Confirmatory factor analysis showed adequate fit statistics(comparative fit index 0.976,goodness-of-fit index 0.935 and root mean square error of approximation 0.055).Convergent validity with anhedonia-related measures was confirmed.While the correlation between the DARS and the Hamilton Depression Rating Scale was not strong(r=0.31,baseline),the DARS was found to differentiate between levels of depression.Greater improvements in DARS scores were seen with the Hamilton Rating Scale for Depression responder group(effect size 1.16)compared with the non-responder group(effect size 0.46).Conclusions This study comprehensively evaluated the measurement properties of the DARS using a Chinese population with MDD.Overall,the Chinese version of DARS demonstrates good psychometric properties and has been found to be responsive to change during antidepressant treatment.The DARS is a suitable scale for assessing patient-reported anhedonia in future clinical trials.
基金The financial supports are greatly appreciated from the Central Public-interest Scientific Institution Basal Research Fund of China(1610322013003)the Agriculture Achievements Transformation Fund Project of the Ministry of Science and Technology of China(2010GB23260564)
文摘The purpose of the present study was to survey contents of trace elements of Cu, Mn, Fe, and Zn in the surface layer （0-20 cm） in the soil, pasture and serum of sheep in Huangcheng area of Qilian mountain grassland, China. Also the soil-plantanimal continuum was analyzed. Soil （n=300）, pasture （n=60）, and blood serum samples from sheep （n=480） were collected from Huangcheng area of Qilian mountain grassland, China. The contents of trace element in the samples were analyzed by atomic absorption spectrophotometer after digestion. The soil trace elements density distribution shows a ladder-like pattern distribution. Equations developed in the present study for prediction of Fe （R2=0.943） and Zn （R2=0.882） had significant R2 values.
基金supported by the Central Public-Interest Scientific Institution Basal Research Fund,China (1610322015007)the Key Technology R&D Program of China during the 12th Five-Year Plan period (2012BAD12B03)the Natural Science Foundation of Gansu Province,China (145RJYA311)
文摘Staphylococcus aureus is the most common etiological pathogen of bovine mastitis. The resistant strains make the disease difficult to cure. The aim of this study was to characterize the genetic nature of the antimicrobial resistance in S. aureus cultured from bovine mastitis in Northwest China in 2014. A total of 44 S. aureus were isolated for antimicrobial resistance and resistance-related genes. Antimicrobial resistance was determined by disc diffusion and the corresponding resistance genes were detected by PCR. Phenotype indicated that S. aureus isolates were resistant to penicillin （84.09%）, erythromycin （20.45%）, tetracycline （15.91%）, gentamicin （9.09%）, tobramycin （6.82%）, kanamycin （6.82%） and methicillin （2.27%）. 9.09% of the S. aureus isolates were classified as multidrug resistant. In addition, genotypes showed that the isolates were resistant to rifampicin （100%, rpoB）, penicillin （95.45%, blaZ）, tetracycline （22.73%, tetK, tetM, alone or in combination）, erythromycin （22.73%, ermB or ermC）, gentamicin/tobramycin/kanamycin （2.27%, aacA-aphD）, methicillin （2.27%, mecA） and vancomycin （2.27%, vanA）. Resistance to tetracycline was attributed to the genes tetK and tetM （r=0.558, P〈0.001）. This study noted high-level geno- and phenotypic antimicrobial resistance in S. aureus isolates from bovine mastitis cases in Northwest China.
基金This study was supported by the National Key Research and Development Project of China(2017YFD0502200)the National Natural Science Foundation of China(31802232)the International Science and Technology Cooperation Project of Gansu Province,China(17YF1WA169).
文摘The objectives of this study were to investigate antimicrobial resistance of Streptococcus uberis and Streptococcus parauberis isolated from cows with bovine clinical mastitis in China and to examine the distribution of resistance-and virulence-related gene patterns.Antimicrobial susceptibility was determined by the E-test.Genes encoding antimicrobial resistance and invasiveness factors were examined by PCR.A total of 27 strains were obtained from 326 mastitis milk samples.Streptococcus parauberis isolates(n=11)showed high resistance to erythromycin(90.9%),followed by tetracycline(45.5%),chloramphenicol(36.4%)and clindamycin(27.3%).Streptococcus uberis isolates(n=16)were highly resistant to tetracycline(81.3%)and clindamycin(62.5%).Both species were susceptible to ampicillin.The most prevalent resistance gene in S.uberis was tetM(80.0%),followed by blaZ(62.5%)and ermB(62.5%).However,tetM,blaZ,and ermB genes were only found in 27.3,45.5,and 27.3%,respectively,of S.parauberis.In addition,all of the isolates carried at least one selected virulence-related gene.The most prevalent virulence-associated gene pattern in the current study was sua+pauA/skc+gapC+hasC detected in 22.2%of the strains.One S.uberis strain carried 7 virulence-associated genes and belonged to the sua+pauA/skc+gapC+cfu+hasA+hasB+hasC pattern.More than 59.3%of analysed strains carried 4 to 7 virulence-related genes.Our findings demonstrated that S.parauberis and S.uberis isolated from clinical bovine mastitis cases in China exhibited diverse molecular ecology,and that the strains were highly resistant to antibiotics commonly used in the dairy cow industry.The data obtained in the current study contribute to a better understanding of the pathogenesis of bacteria in mastitis caused by these pathogens,and the findings are relevant to the development of multivalent vaccines and targeted prevention procedures.
基金financially supported by grants from the Biogreen 21 Program, RDA, Korea (PJ00810304)the Agricultural Science and Technology Innovation Program (ASTIP) of Chinese Academy of Agricultural Sciences (2014–2015)the Beijing Municipal Education Commission, China (KM200910011001)
文摘Genetic transformation is an important technique for functional genomics study and genetic improvement of plants. Until now, Agrobacterium-mediated transformation methods using cotyledon as explants has been the major approach for cucumber, and its frequency has been up to 23%. For example, significantly enhancement of the transformation efficiency of this plant species was achieved from the cotyledon explants of the cultivar Poinsett 76 infected by Agrobacterium strains EHA105 with efficient positive selection system in lots of experiments. This review is to summarize some key factors influencing cucumber regeneration and genetic transformation, including target genes, selection systems and the ways of transgene introduction, and then to put forward some strategies for the increasing of cucumber transformation efficiency. In the future, it is high possible for cucumber to be potential bioreactor to produce vaccine and biomaterials for human beings.
文摘Berberine chloride(BBR)is a pharmacokinetic profile of drug with poor bioavailability but good therapeutic efficacy,which is closely related to the discovery of BBR intestinal target.The major aim of this paper is to develop BBR intestinal retention type sustained-release pellets and evaluate their in vivo and in vitro behaviors base on the aspect of local action on intestinal tract.Here,wet milling technology is used to improve dissolution and dissolution rate of BBR by decreasing the particle size and increasing the wettability.The pellets are prepared by liquid layer deposition technology,and then the core pellets are coated with Eudragit~?L30 D-55 and Eudragit~?NE30 D aqueous dispersion.The prepared pellets show high drug loading capacity,and the drug loading up to 93%.Meanwhile,it possesses significant sustained drug release effect in purified water which is expected to improve the pharmacokinetic behavior of BBR.The pharmacokinetics results demonstrate that the halflife of BBR was increased significantly from 24 h to 36 h and the inter-and intra-subject variability are decreased compared to commercial BBR tablets.The retention test results indicate that the pellet size and Eudragit~?NE30 D plays an important role in retention time of the pellet,and it is found that the pellets with small particle size and high Eudragit~?NE30 D coating content can stay longer in the intestine than the pellets with large particle size.All in all,BBR intestinal retention type pellets are prepared successfully in this study,and the pellets show satisfactory in vivo and in vitro behaviors.
基金Supported by Overall Innovation Plan Projects of Science and Technology of Shaanxi Province in China(2015KTZDSF02-01-02)
文摘OBJECTIVE To determine the characterization,anti-tumor efficacy and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity.METHODS Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high pressure homogenization method.The particle size and zeta potential of the liposomes were determined by dynamic light scattering technique.The direct imaging of morphology of liposomes was charactered by transmission electron microscope.The content of bufalin in liposomes was analysed by HPLC method.The entrapment efficiency and the particle size was applied to assess the stability profile,after storage at 4℃ on day 0,7,15,30 and 90.The in-vitro release behaviours of bufalin from liposomes were conducted using dialysis bag technique at 37℃.In-vitro cytotoxicity studies were carried out using MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]assay on several kinds of tumor cel lines including SW620,PC-3,MDA-MB-231,A549,U251,U87 and HepG2.In-vivo pharmacokinetic study of bufalin liposomes was evaluated by HPLC method.RESULTS Their mean particle sizes were 127.6 nm and 155.0 nm,mean zeta potentials were 2.24 m V and-18.5 m V,entrapment efficiencies were 76.31%and 78.40%,respectively.In-vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that of bufalin-loaded liposomes.The cytotoxicity of blank liposomes has been found within acceptable range,whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity.In-vivo pharmacokinetics indicated that bufalinloaded PEGylated liposomes could extend eliminate half-life time of bufalin in plasma in rats.CONCLUSION The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.
