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
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
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
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
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
The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment...The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection.However,their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity.Herein,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin(ISL)loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug(ISL-G2)bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized oligochitosan.The obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr)binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs.The NPs maintained their negatively charged surface,thus prolonging the blood circulation time.In response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the biofilms.Sequentially,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA.An in vivo study was performed on a MRSA biofilm infected wound model.This phytochemical-based system led to~2log CFU(>99%)reduction of biofilm MRSA as compared to untreated wound(P<0.001)with negligible biotoxicity in mice.This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.展开更多
Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treat...Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.展开更多
This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses...This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses and modulated key indicators of antioxidant capacity.Moreover,the down-regulation of critical proteins of the Nrf2 pathway induced by Pb could be reversed after NCVP intervention.In addition,NCVP maintained the diversity of gut bacteriobiota and restored the relative abundance of f_Prevotellaceae,g_Alloprevotella,and f_Eubacterium_coprostanoligenes_group reduced by Pb.Also,NCVP regulated the diversity and abundance of gut mycobiota affected by Pb.Specifically,Pb decreased the proportion of pathogenic species(g_Fusarium,p_Basidiomycota,g_Alternaria,g_Aspergillus,and g_Candida)while NCVP increased the abundance of probiotics species(g_Kazachstania and p_Ascomycota).Furthermore,the metabolomic analysis found that NCVP significantly altered a range of microbial metabolites,including porphobilinogen,cromakalim,salidroside,and trichostatin A,which has significant associations with specific gut bacteriobiota or mycobiota.These altered metabolites are involved in primary bile acid biosynthesis,metabolism of xenobiotics by cytochrome P450,lysine degradation,and other metabolic pathways.Overall,our findings indicate that NCVP might be an excellent natural product for eliminating Pb-induced hepatorenal toxicity,possibly by regulating gut bacteriome,mycobiome and metabolome.展开更多
Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiom...Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or regions.Here,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe.Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig populations.Furthermore,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions.Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,respectively.Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,respectively.Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs.The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.展开更多
The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra hou...The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.展开更多
The threat to information security from electromagnetic pollution has sparked widespread interest in the development of microwave absorption materials(MAMs).Although considerable progress has been made in high-perform...The threat to information security from electromagnetic pollution has sparked widespread interest in the development of microwave absorption materials(MAMs).Although considerable progress has been made in high-performance MAMs,little attention was paid to their absorption frequency regulation to respond to variable input frequencies and their stability and durability to cope with complex environments.Here,a highly compressible polyimide-packaging carbon nanocoils/carbon foam(PI@CNCs/CF)fabricated by a facile vacuum impregnation method is reported to be used as a dynamically frequency-tunable and environmentally stable microwave absorber.PI@CNCs/CF exhibits good structural stability and mechanical properties,which allows precise absorption frequency tuning by simply changing its compression ratio.For the first time,the tunable effective absorption bandwidth can cover the whole test frequency band(2−18 GHz)with the broadest effective absorption bandwidth of 10.8 GHz and the minimum reflection loss of−60.5 dB.Moreover,PI@CNCs/CF possesses excellent heat insulation,infrared stealth,self-cleaning,flame retardant,and acid-alkali corrosion resistance,which endows it high reliability even under various harsh environments and repeated compression testing.The frequency-tunable mechanism is elucidated by combining experiment and simulation results,possibly guiding in designing dynamically frequency-tunable MAMs with good environmental stability in the future.展开更多
To tackle the increasing electromagnetic pollution,new and efficient electromagnetic wave absorption(EWA)and shielding(EWS)materials are urgently needed.Multi-component synergism and complex microstructure design are ...To tackle the increasing electromagnetic pollution,new and efficient electromagnetic wave absorption(EWA)and shielding(EWS)materials are urgently needed.Multi-component synergism and complex microstructure design are effective measures to improve the EWA and EWS properties.However,how to implement the above designs still faces huge challenges.Herein,multi-interface carbon-coated FeCoNi nanoneedles grown on carbon cloth(FeCoNi@C/CC)were synthesized by a combination of hydrothermal process and chemical vapor deposition(CVD)technology with the concept of“green synthesis”.Using acetylene as the carbon source and atmosphere,the FeCoNi ternary hydroxide can be transformed into a multiple magnetic component(Fe3O4,Ni,and Co metals)by simple annealing.Simultaneously,a uniform carbon layer is formed on the surface,resulting in a composite system with a variety of heterogeneous interfaces and loss mechanisms.Additionally,the dielectric and magnetic loss capacities can be effectively adjusted by changing the temperature of CVD.The optimized FeCoNi@C/CC as filler exhibits remarkable EWA performance with a minimum reflection loss of69.3 dB at a thickness of 1.82 mm and a maximum effective absorption bandwidth of 6.80 GHz.Moreover,the composites as an integrated component also show a fascinating electromagnetic interference shielding efficiency of 42.2 dB.This work provides a guide for the structural design of high-performance electromagnetic protection materials with multiheterogeneous interfaces.展开更多
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.
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.
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 National Natural Science Foundation of China(No.3210190403)the Natural Science Foundation of Heilongjiang Province(No.YQ2022C016)+2 种基金the China Postdoctoral Science Foundation(2022T150104and 2020M670877)the Postdoctoral Science Foundation of Heilongjiang Province(LBH-TZ2104 and LBH-Z20039)the China Agriculture Research System of MOF and MARA(No.CARS-35)。
文摘The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections.Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection.However,their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity.Herein,we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin(ISL)loading content for effective treatment of MRSA biofilm.A dimeric ISL prodrug(ISL-G2)bearing a lipase responsive ester bond was synthesized,and then encapsulated into the amphiphilic quaternized oligochitosan.The obtained ISL-G2loaded NPs possessed positively charged surface,which allowed cis-aconityl-D-tyrosine(CA-Tyr)binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs.The NPs maintained their negatively charged surface,thus prolonging the blood circulation time.In response to low pH in the biofilms,the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive,which enhanced the accumulation and penetration of NPs in the biofilms.Sequentially,the pH-triggered release of D-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA.An in vivo study was performed on a MRSA biofilm infected wound model.This phytochemical-based system led to~2log CFU(>99%)reduction of biofilm MRSA as compared to untreated wound(P<0.001)with negligible biotoxicity in mice.This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
基金supported by the National Natural Science Foundation of China(Grant No.:82074104)the Research Project of Clinical Toxicology Transformation from the Chinese Society of Toxicology,China(Grant No.:CST2021CT101)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences,China(Grant Nos.:2017-I2M-1-011 and 2022-I2M-2-002).
文摘Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.
基金supported by the Program of the National Natural Science Foundation of China(31872519)General Project of Jilin Provincial Department of Science and Technology(20230101247JC)the Open Research Fund of Engineering Research Center of Bioreactor and Pharmaceutical Development,Ministry of Education.(KF202002).
文摘This study aimed to explore the protective effect and potential mechanism of Nostoc commune Vauch.polysaccharide(NCVP)on lead(Pb)-poisoning mice.NCVP improved Pb-induced hepatorenal toxicity and inflammatory responses and modulated key indicators of antioxidant capacity.Moreover,the down-regulation of critical proteins of the Nrf2 pathway induced by Pb could be reversed after NCVP intervention.In addition,NCVP maintained the diversity of gut bacteriobiota and restored the relative abundance of f_Prevotellaceae,g_Alloprevotella,and f_Eubacterium_coprostanoligenes_group reduced by Pb.Also,NCVP regulated the diversity and abundance of gut mycobiota affected by Pb.Specifically,Pb decreased the proportion of pathogenic species(g_Fusarium,p_Basidiomycota,g_Alternaria,g_Aspergillus,and g_Candida)while NCVP increased the abundance of probiotics species(g_Kazachstania and p_Ascomycota).Furthermore,the metabolomic analysis found that NCVP significantly altered a range of microbial metabolites,including porphobilinogen,cromakalim,salidroside,and trichostatin A,which has significant associations with specific gut bacteriobiota or mycobiota.These altered metabolites are involved in primary bile acid biosynthesis,metabolism of xenobiotics by cytochrome P450,lysine degradation,and other metabolic pathways.Overall,our findings indicate that NCVP might be an excellent natural product for eliminating Pb-induced hepatorenal toxicity,possibly by regulating gut bacteriome,mycobiome and metabolome.
基金supported by the Foundation for the National Key R&D Program(2022YFD1800400)Innovative Research Groups of the National Natural Science Foundation of China(32121004)Natural Science Foundation of Guangdong Province of China(2021A1515011159)。
文摘Monitoring the prevalence of antimicrobial resistance genes(ARGs)is vital for addressing the global crisis of antibiotic-resistant bacterial infections.Despite its importance,the characterization of ARGs and microbiome structures,as well as the identification of indicators for routine ARG monitoring in pig farms,are still lacking,particularly concerning variations in antimicrobial exposure in different countries or regions.Here,metagenomics and random forest machine learning were used to elucidate the ARG profiles,microbiome structures,and ARG contamination indicators in pig manure under different antimicrobial pressures between China and Europe.Results showed that Chinese pigs exposed to high-level antimicrobials exhibited higher total and plasmid-mediated ARG abundances compared to those in European pigs(P<0.05).ANT(6)-Ib,APH(3')-IIIa,and tet(40)were identified as shared core ARGs between the two pig populations.Furthermore,the core ARGs identified in pig populations were correlated with those found in human populations within the same geographical regions.Lactobacillus and Prevotella were identified as the dominant genera in the core microbiomes of Chinese and European pigs,respectively.Forty ARG markers and 43 biomarkers were able to differentiate between the Chinese and European pig manure samples with accuracies of 100%and 98.7%,respectively.Indicators for assessing ARG contamination in Chinese and European pigs also achieved high accuracy(r=0.72-0.88).Escherichia flexneri in both Chinese and European pig populations carried between 21 and 37 ARGs.The results of this study emphasize the importance of global collaboration in reducing antimicrobial resistance risk and provide validated indicators for evaluating the risk of ARG contamination in pig farms.
基金the National Natural Science Foundation of China(32273062,31973005)。
文摘The use of Chinese herbal medicines can replace antibiotics that cause drug-resistance problems,which are currently necessary for disease control.In this paper,a traditional Chinese medicine compound named Ephedra houttuynia granule for the treatment of Mycoplasma galliscepticum(MG)infection was prepared.Furthermore,its action mechanism was explored through network pharmacology.The optimal extraction and granulation processes of the compound were determined by high performance liquid chromatography(HPLC)method and L9 orthogonal test,and in the treatment experiment,Ephedra houttuynia granule showed a significant therapeutic effect on MG infection.In the study of network pharmacology,the results showed that the core targets of Ephedra houttuynia granule against MG infection were vascular endothelial growth factor(VEGFA),fos proto-oncogene(FOS),prepro-coagulation factor II(F2),etc.,the gene ontology/kyoto encyclopedia of genes and genomes(GO/KEGG)analysis results indicated that the signaling pathways of neuroactive ligand receptor interaction,cAMP,IL-17,T cell receptor,and tumor necrosis factor(TNF)might involve in anti-MG infection.In conclusion,this study would provide a new idea for elucidating the action mechanism of other diseases in veterinary clinic,which had a certain guiding significance.
基金supported by the National Natural Science Foundation of China(grants 22278101,22068010,and 52365044)the Natural Science Foundation of Hainan Province(grants 120RC454 and 519QN176)the Innovation Project for Scientific and Technological Talents in Hainan Province(grant KJRC2023C08)。
文摘The threat to information security from electromagnetic pollution has sparked widespread interest in the development of microwave absorption materials(MAMs).Although considerable progress has been made in high-performance MAMs,little attention was paid to their absorption frequency regulation to respond to variable input frequencies and their stability and durability to cope with complex environments.Here,a highly compressible polyimide-packaging carbon nanocoils/carbon foam(PI@CNCs/CF)fabricated by a facile vacuum impregnation method is reported to be used as a dynamically frequency-tunable and environmentally stable microwave absorber.PI@CNCs/CF exhibits good structural stability and mechanical properties,which allows precise absorption frequency tuning by simply changing its compression ratio.For the first time,the tunable effective absorption bandwidth can cover the whole test frequency band(2−18 GHz)with the broadest effective absorption bandwidth of 10.8 GHz and the minimum reflection loss of−60.5 dB.Moreover,PI@CNCs/CF possesses excellent heat insulation,infrared stealth,self-cleaning,flame retardant,and acid-alkali corrosion resistance,which endows it high reliability even under various harsh environments and repeated compression testing.The frequency-tunable mechanism is elucidated by combining experiment and simulation results,possibly guiding in designing dynamically frequency-tunable MAMs with good environmental stability in the future.
基金supported by the National Natural Science Foundation of China(Grant Nos.22168016,22278101,and 22068010)the Natural Science Foundation of Hainan Province(Grant Nos.120RC454 and 519QN176)the Innovation Project for Scientific and Technological Talents in Hainan Province(Grant No.KJRC2023C08).
文摘To tackle the increasing electromagnetic pollution,new and efficient electromagnetic wave absorption(EWA)and shielding(EWS)materials are urgently needed.Multi-component synergism and complex microstructure design are effective measures to improve the EWA and EWS properties.However,how to implement the above designs still faces huge challenges.Herein,multi-interface carbon-coated FeCoNi nanoneedles grown on carbon cloth(FeCoNi@C/CC)were synthesized by a combination of hydrothermal process and chemical vapor deposition(CVD)technology with the concept of“green synthesis”.Using acetylene as the carbon source and atmosphere,the FeCoNi ternary hydroxide can be transformed into a multiple magnetic component(Fe3O4,Ni,and Co metals)by simple annealing.Simultaneously,a uniform carbon layer is formed on the surface,resulting in a composite system with a variety of heterogeneous interfaces and loss mechanisms.Additionally,the dielectric and magnetic loss capacities can be effectively adjusted by changing the temperature of CVD.The optimized FeCoNi@C/CC as filler exhibits remarkable EWA performance with a minimum reflection loss of69.3 dB at a thickness of 1.82 mm and a maximum effective absorption bandwidth of 6.80 GHz.Moreover,the composites as an integrated component also show a fascinating electromagnetic interference shielding efficiency of 42.2 dB.This work provides a guide for the structural design of high-performance electromagnetic protection materials with multiheterogeneous interfaces.
