Allelopathic plants are important resources for the discovery of bioherbicides.Rosebay willowherb[Chamaenerion angustifolium(L.)Scop.syn.Epilobium angustifolium L.]widely distributes in Western Asia,Europe,and North A...Allelopathic plants are important resources for the discovery of bioherbicides.Rosebay willowherb[Chamaenerion angustifolium(L.)Scop.syn.Epilobium angustifolium L.]widely distributes in Western Asia,Europe,and North America,and behaves as a dominant species within the community due to the production of substances that restrict growth of other plants.This study aims at investigating the allelopathic potential of rosebay willowherb by evaluation of the effects of aqueous extracts from different parts on seed germination and seedling growth in lettuce(Lactuca sativa L.),as well as measuring the accumulation of reactive oxygen species and structural analysis of root tips via scanning electron and transmission electron microscopy.It was observed that the aqueous extracts from the leaves of rosebay willowherb had the strongest inhibitory effect on the germination index,germination energy and total germination of lettuce seeds,followed by capsular fruits and flowers,and the inhibition effect of stems was the weakest.All aqueous extracts(100 mg/mL)showed a significant inhibitory effect on radicle elongation of lettuce seedlings.Additionally,after treatment with the aqueous extract of rosebay willowherb leaves,accumulation of reactive oxygen species increased in columella cells,which correlated with disruption of root tip structure.展开更多
Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor...Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.展开更多
Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target ...Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.展开更多
Episodes of drought-induced decline in tree growth and mortality are becoming more frequent as a result of climate warming and enhanced water stress in semi-arid areas.However,the ecophysiological mechanisms under-lyi...Episodes of drought-induced decline in tree growth and mortality are becoming more frequent as a result of climate warming and enhanced water stress in semi-arid areas.However,the ecophysiological mechanisms under-lying the impact of drought on tree growth remains unre-solved.In this study,earlywood and latewood tree-ring growth,δ^(13)C,andδ^(18)O chronologies of Picea mongolica from 1900 to 2013 were developed to clarify the intra-and inter-annual tree-ring growth responses to increasingly fre-quent droughts.The results indicate that annual basal area increment residuals(BAI_(res)),which removed tree age and size effects,have significantly decreased since 1960.How-ever,the decreasing trend of earlywood BAI_(res) was higher than that of latewood.Climate response analysis suggests that the dominant parameters for earlywood and latewood proxies(BAI_(res),δ^(13)C andδ^(18)O)were drought-related climate variables(Palmer drought severity index,temperature,rela-tive humidity,and vapor pressure deficit).The most signifi-cant period of earlywood and latewood proxies’responses to climate variables were focused on June-July and July-August,respectively.BAI_(res),andδ^(13)C were significantly affected by temperature and moisture conditions,whereasδ^(18)O was slightly affected.Decreasing stomatal conduct-ance due to drought outweighed the influence of increasing CO_(2) on intrinsic water use efficiency(iWUE),and ultimately led to a decline in BAI_(res).Compared to latewood,the faster decreasing BAI_(res) and smaller increasing iWUE of early-wood suggested trees were more vulnerable to water stress in the early growing season.Our study provides insights into the inter-and intra-annual mechanisms of tree-ring growth in semi-arid regions under rising CO_(2) and climate change.展开更多
Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exer...Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exerting therapeutic actions,which requires to quickly reach the minimum valid concentrations of free drugs.Fortunately,we find that a natural compound(BL-193)selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin(PPT)at ineffective dose concentrations.Based on this,we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT.Specifically,a redox-sensitive prodrug(PSSF)of PPT is synthesized by coupling 9-fluorenyl-methanol(Fmoc-OH)with PPT linked via disulfide bond.Intriguingly,PSSF with aπ-conjugated structure readily co-assembles with BL-193 into stable nanoassembly.Significantly,BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic windowfor PPT.Moreover,prodrug design and precise hybrid nanoassembly well manage off-target toxicity.As expected,such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses.This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.展开更多
Nickel-manganese binary layered oxides with high working potential and low cost are potential candidates for sodium-ion batteries,but their electrochemical properties are highly related to compositional diversity.Dive...Nickel-manganese binary layered oxides with high working potential and low cost are potential candidates for sodium-ion batteries,but their electrochemical properties are highly related to compositional diversity.Diverse composite materials with various phase structures of P3,P2/P3,P2,P2/O3,and P2/P3/O3 were synthesized by manipulating the sodium content and calcination conditions,leading to the construction of a synthetic phase diagram for Na_(x)Ni_(0.25)Mn_(0.75)O_(2)(0.45≤x≤1.1).Then,we compared the electrochemical characteristics and structural evolution during the desodiation/sodiation process of P2,P2/P3,P2/03,and P2/P3/O3-Na_(x)Ni_(0.25)Mn_(0.75)O_(2).Among them,P2/P3-Na0.75Ni0.25Mn0.75O2exhibits the best rate capability of 90.9 mA h g^(-1)at 5 C,with an initial discharge capacity of 142.62 mA h g^(-1)at 0.1 C and a capacity retention rate of 78.25%after 100 cycles at 1 C in the voltage range of 2-4.3 V.The observed superior sodium storage performance of P2/P3 hybrids compared to other composite phases can be attributed to the enhanced Na^(+)transfer dynamic,reduction of the Jahn-teller effect,and improved reaction reversibility induced by the synergistic effect of P2 and P3 phases.The systematic research and exploration of phases in Na_(x)Ni_(0.25)Mn_(0.75)O_(2)provide new sights into high-performance nickel-manganese binary layered oxide for sodium-ion batteries.展开更多
Terahertz heterodyne receivers with high sensitivity and spectral resolution are crucial for various applications.Here,we present a room-temperature atomic terahertz heterodyne receiver that achieves ultrahigh sensiti...Terahertz heterodyne receivers with high sensitivity and spectral resolution are crucial for various applications.Here,we present a room-temperature atomic terahertz heterodyne receiver that achieves ultrahigh sensitivity and frequency resolution.At a signal frequency of 338.7 GHz,we obtain a sensitivity of 2.88±0.09V·cm^(−1)·Hz^(−1/2) for electric field measurements.The calibrated linear dynamical range spans approximately 89 dB,ranging from−110 dBV/cm to−21 dBV/cm.We demodulate a 400 symbol stream encoded in 4-state phase-shift keying,demonstrating excellent phase detection capability.By scanning the frequency of the local oscillator,we realize a terahertz spectrometer with Hz level frequency resolution.This resolution is more than two orders of magnitude higher than that of existing terahertz spectrometers.The demonstrated terahertz heterodyne receiver holds promising potential for working across the entire terahertz spectrum,significantly advancing its practical applications.展开更多
Objective:To explore the effect of King’s Theory of Goal Attainment combined with teach-back method on improving the standardization rate of eye drop use in patients.Methods:A total of 200 patients who used more than...Objective:To explore the effect of King’s Theory of Goal Attainment combined with teach-back method on improving the standardization rate of eye drop use in patients.Methods:A total of 200 patients who used more than two types of eye drops in the Department of Ophthalmology of our hospital were selected as the research subjects,and were randomly divided into an observation group and a control group.The control group was given routine health education,while the observation group was given King’s Theory of Goal Attainment combined with teach-back method on the basis of the control group.The standardization rate of eye drop use,knowledge awareness rate,and nursing satisfaction were compared between the two groups before and after the intervention.Results:After the intervention,the standardization rate of eye drop use,the awareness rate of eye drop knowledge,and the nursing satisfaction of the observation group were significantly higher than those of the control group(P<0.05).Conclusion:King’s Theory of Goal Attainment combined with teach-back method can effectively improve the standardization rate of eye drop use in patients,increase their awareness of eye drop knowledge,and improve nursing satisfaction,which is worthy of clinical application.展开更多
Mepiquat chloride(MC)priming alleviates the effects of salt stress during seed germination in cotton(Gossypium hirsutum L.),but the mechanisms underlying its effects are unknown.We found that MC priming increases salt...Mepiquat chloride(MC)priming alleviates the effects of salt stress during seed germination in cotton(Gossypium hirsutum L.),but the mechanisms underlying its effects are unknown.We found that MC priming increases salt tolerance,as evidenced by marked increases in seed vigor and germination rates,and alleviated salt toxicity by reducing Cl^(−)accumulation in germinating seeds.Consistently,electrophysiological experiments revealed that the seeds with MC priming displayed superior Cl^(−)exclusion ability in the root apex.These beneficial effects of MC priming were abolished by the abscisic acid(ABA)-synthesis blocker fluridone under salt stress.MC priming induced an early response to acclimatization and stress,as indicated by rapidly increasing ABA content during initial exposure to salt stress.Transcriptome analyses revealed that MC priming induced an array of differentially expressed genes(DEGs)in germinating seeds.The most noticeable changes in germinating seeds were MC priming-induced increases in the expression of DEGs encoding components of ABA biosynthesis,ABA catabolism,and ABA signaling pathways under salt stress.MC priming also increased the expression of some DEGs encoding Cl^(−)ion transporters(e.g.CCC,SLAC1/SLAH1/SLAH3,CLC,and ALMT9)in germinating seeds.These results indicate that MC priming-induced ABA contributes to Cl^(−)homeostasis in tissues and acts as a positive regulator of salt tolerance via regulation of Cl^(−)transporters(particularly CCC and SLAC1/SLAH1/SLAH3).Taken together,these findings shed light on the molecular mechanism underlying MC-mediated tolerance to salt stress during seed germination.展开更多
This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of...This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.展开更多
The defect chemistry is successfully modulated on free-standing and binder-free carbon cathodes for highly efficient Li-S redox reactions.Such rationally regulated defect engineering realizes the synchronization of io...The defect chemistry is successfully modulated on free-standing and binder-free carbon cathodes for highly efficient Li-S redox reactions.Such rationally regulated defect engineering realizes the synchronization of ion/electron-conductive and defect-rich networks on the threedimension carbon cathode,leading to its tunable activity for both relieving the shuttle phenomenon and accelerating the sulfur redox reaction kinetics.As expected,the defective carbon cathode harvests a high rate capacity of 1217.8 mAh g^(-1)at 0.2 C and a superior capacity retention of61.7%at 2 C after 500 cycles.Even under the sulfur mass loading of 11.1 mg cm^(-2),the defective cathode still holds a remarkable areal capacity of 8.5 mAh cm^(-2).展开更多
In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sus...In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with EudragitNE30D were similar to Herbesser,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesserwas 98.536.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.展开更多
The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three...The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.展开更多
A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was car...A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was carried out by gradient elution using an Agilent C8 column(4.6 mm×250 mm,5 mm)which was maintained at 25℃.The mobile phase composed of solvent A(methanol)and solvent B(solution consisting 0.02 mmol/l monopotassium phosphate and 0.025 mmol/l sodium hydroxide)was at a flow rate of 1.0 ml/min.The samples were detected and quantified at 237 nm using an ultraviolet absorbance detector.Calibration curves of all analytes from 0.5 to 3.5 mg/ml were good linearity(r≥0.9990)and recovery was greater than 99.5% for each analyte.The lower limit of detection(LLOD)and quantification(LOQ)of this analytical method were 10 ng/ml and 25 ng/ml for all impurities,respectively.The stress studies indicated that the degradation products could not interfere with the detection of ilaprazole and its related impurities and the assay can thus be considered stability-indicating.The method precisions were in the range of 0.41-1.21 while the instrument precisions were in the range of 0.38-0.95 in terms of peak area RSD% for all impurities,respectively.This method is considered stabilityindicating and is applicable for accurate and simultaneous measuring of the ilaprazole and its related impurities in commercial enteric-coated tablets.展开更多
A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine,...A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.展开更多
Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） r...Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） receptor remains unclear. This study presumed that intrathecal injection of butorphanol has an analgesic effect on formalin-induced inflammatory pain in rats, and its analgesic effect is associated with inhibition of NMDA receptors. Concurrently, ketamine was injected into the intrathecal space, which is a non-competitive NMDA receptor antagonist, to determine the analgesic mechanism of butorphanol. The total reflection time in phase 1 and phase 2 of rat hind paws carding action was reduced when the butorphanol dose was increased to 25 μg, or a low dose of butorphanol was combined with ketamine. Intrathecal injection of a high dose of butorphanol alone or a low dose of butorphanol combined with ketamine can remarkably reduce NMDA receptor expression in the Ls spinal dorsal hom of formalin-induced pain rats. The results suggest that intrathecal injection of butorphanol has analgesic effects on formalin-induced inflammatory pain, and remarkably reduces NMDA receptor expression in the rat spinal dorsal horn Ketamine strengthens this analgesic effect. The analgesic mechanism of intrathecal injection of butorphanol is associated with inhibition of NMDA receptor activation.展开更多
A two-moment bulk stratiform microphysics scheme, including recently developed physically-based droplet activation/ice nucleation parameterizations has been implemented into the Grid-point Atmospheric Model of IAP LA...A two-moment bulk stratiform microphysics scheme, including recently developed physically-based droplet activation/ice nucleation parameterizations has been implemented into the Grid-point Atmospheric Model of IAP LASG （GAMIL） as an effort to enhance the model＇s capability to simulate aerosol indirect effects. Unlike the previous one-moment cloud microphysics scheme, the new scheme produces a reasonable rep- resentation of cloud particle size and number concentration. This scheme captures the observed spatial variations in cloud droplet number concentrations. Simulated ice crystal number concentrations in cirrus clouds qualitatively agree with in situ observations. The longwave and shortwave cloud forcings are in better agreement with observations. Sensitivity tests show that the column cloud droplet number concentrations calculated from two different droplet activation parameterizations are similar. However, ice crystal number concentration in mixed-phased clouds is sensitive to different heterogeneous ice nucleation formulations. The simulation with high ice crystal number concentration in mixed-phase clouds has less liquid water path and weaker cloud forcing. ~rthermore, ice crystal number concentration in cirrus clouds is sensitive to different ice nucleation parameterizations. Sensitivity tests also suggest that the impact of pre-existing ice crystals on homogeneous freezing in old clouds should be taken into account.展开更多
基金This research was funded by Shandong Provincial Natural Science Foundation,China,Grant No.ZR2018BD030Guangdong Key Laboratory of Marine Material Medica,Grant No.LMM2020-6.
文摘Allelopathic plants are important resources for the discovery of bioherbicides.Rosebay willowherb[Chamaenerion angustifolium(L.)Scop.syn.Epilobium angustifolium L.]widely distributes in Western Asia,Europe,and North America,and behaves as a dominant species within the community due to the production of substances that restrict growth of other plants.This study aims at investigating the allelopathic potential of rosebay willowherb by evaluation of the effects of aqueous extracts from different parts on seed germination and seedling growth in lettuce(Lactuca sativa L.),as well as measuring the accumulation of reactive oxygen species and structural analysis of root tips via scanning electron and transmission electron microscopy.It was observed that the aqueous extracts from the leaves of rosebay willowherb had the strongest inhibitory effect on the germination index,germination energy and total germination of lettuce seeds,followed by capsular fruits and flowers,and the inhibition effect of stems was the weakest.All aqueous extracts(100 mg/mL)showed a significant inhibitory effect on radicle elongation of lettuce seedlings.Additionally,after treatment with the aqueous extract of rosebay willowherb leaves,accumulation of reactive oxygen species increased in columella cells,which correlated with disruption of root tip structure.
基金supported by the National Natural Science Foundation of China (3207269732030102)+2 种基金CARS-PIG-35R&D Programmes of Guangdong Province (2018B020203003)Laboratory of Lingnan Modern Agriculture Project (NZ2021006)。
文摘Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat production.Insulin-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat thickness.This favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig breeds.To improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) pigs.Results We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote adipogenesis.Conclusions We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling pathways.Our study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2023A1515010969)Natural Science Foundation of Top Talent of SZTU(GDRC202305).
文摘Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.
基金This study was supported by the National Natural Science Foundation of China(42277448,41971104 and 41807431)the National Science Foundation of Shaanxi Province(2019JQ-325)the Fundamental Research Funds for the Central Universities(GK201903068 and GK202206032).
文摘Episodes of drought-induced decline in tree growth and mortality are becoming more frequent as a result of climate warming and enhanced water stress in semi-arid areas.However,the ecophysiological mechanisms under-lying the impact of drought on tree growth remains unre-solved.In this study,earlywood and latewood tree-ring growth,δ^(13)C,andδ^(18)O chronologies of Picea mongolica from 1900 to 2013 were developed to clarify the intra-and inter-annual tree-ring growth responses to increasingly fre-quent droughts.The results indicate that annual basal area increment residuals(BAI_(res)),which removed tree age and size effects,have significantly decreased since 1960.How-ever,the decreasing trend of earlywood BAI_(res) was higher than that of latewood.Climate response analysis suggests that the dominant parameters for earlywood and latewood proxies(BAI_(res),δ^(13)C andδ^(18)O)were drought-related climate variables(Palmer drought severity index,temperature,rela-tive humidity,and vapor pressure deficit).The most signifi-cant period of earlywood and latewood proxies’responses to climate variables were focused on June-July and July-August,respectively.BAI_(res),andδ^(13)C were significantly affected by temperature and moisture conditions,whereasδ^(18)O was slightly affected.Decreasing stomatal conduct-ance due to drought outweighed the influence of increasing CO_(2) on intrinsic water use efficiency(iWUE),and ultimately led to a decline in BAI_(res).Compared to latewood,the faster decreasing BAI_(res) and smaller increasing iWUE of early-wood suggested trees were more vulnerable to water stress in the early growing season.Our study provides insights into the inter-and intra-annual mechanisms of tree-ring growth in semi-arid regions under rising CO_(2) and climate change.
基金supported by the Basic Research Projects of Liaoning Provincial Department of Education(LJKZZ20220109)the Shenyang Youth Science and Technology Innovation Talents Program(No.RC210452)+1 种基金the National Natural Science Foundation of China(No.82204317)the Natural Science Foundation of Liaoning Province(No.2022-BS-162).
文摘Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery.However,prodrug activation remains a rate-limiting step for exerting therapeutic actions,which requires to quickly reach the minimum valid concentrations of free drugs.Fortunately,we find that a natural compound(BL-193)selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin(PPT)at ineffective dose concentrations.Based on this,we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT.Specifically,a redox-sensitive prodrug(PSSF)of PPT is synthesized by coupling 9-fluorenyl-methanol(Fmoc-OH)with PPT linked via disulfide bond.Intriguingly,PSSF with aπ-conjugated structure readily co-assembles with BL-193 into stable nanoassembly.Significantly,BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic windowfor PPT.Moreover,prodrug design and precise hybrid nanoassembly well manage off-target toxicity.As expected,such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses.This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.
基金supported by project from the National Natural Science Foundation of China(21805018)by the Sichuan Science and Technology Program(2022ZHCG0018,2023NSFSC0117,2023ZHCG0060)+1 种基金the Yibin Science and Technology Program(2022JB005)project funded by the China Postdoctoral Science Foundation(2022M722704)。
文摘Nickel-manganese binary layered oxides with high working potential and low cost are potential candidates for sodium-ion batteries,but their electrochemical properties are highly related to compositional diversity.Diverse composite materials with various phase structures of P3,P2/P3,P2,P2/O3,and P2/P3/O3 were synthesized by manipulating the sodium content and calcination conditions,leading to the construction of a synthetic phase diagram for Na_(x)Ni_(0.25)Mn_(0.75)O_(2)(0.45≤x≤1.1).Then,we compared the electrochemical characteristics and structural evolution during the desodiation/sodiation process of P2,P2/P3,P2/03,and P2/P3/O3-Na_(x)Ni_(0.25)Mn_(0.75)O_(2).Among them,P2/P3-Na0.75Ni0.25Mn0.75O2exhibits the best rate capability of 90.9 mA h g^(-1)at 5 C,with an initial discharge capacity of 142.62 mA h g^(-1)at 0.1 C and a capacity retention rate of 78.25%after 100 cycles at 1 C in the voltage range of 2-4.3 V.The observed superior sodium storage performance of P2/P3 hybrids compared to other composite phases can be attributed to the enhanced Na^(+)transfer dynamic,reduction of the Jahn-teller effect,and improved reaction reversibility induced by the synergistic effect of P2 and P3 phases.The systematic research and exploration of phases in Na_(x)Ni_(0.25)Mn_(0.75)O_(2)provide new sights into high-performance nickel-manganese binary layered oxide for sodium-ion batteries.
基金supported by the National Key Research and Development Program of China(Grant No.2021YFA1402004)the Key-Area Research and Development Program of Guangdong Province,China(Grant Nos.2019B030330001 and 2020B0301030008)+2 种基金the National Natural Science Foundation of China(Grant Nos.12225405,12204182,and U20A2074)the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0301705)the Natural Science Foundation of Guangdong Province,China(Grant No.2022A1515012026).
文摘Terahertz heterodyne receivers with high sensitivity and spectral resolution are crucial for various applications.Here,we present a room-temperature atomic terahertz heterodyne receiver that achieves ultrahigh sensitivity and frequency resolution.At a signal frequency of 338.7 GHz,we obtain a sensitivity of 2.88±0.09V·cm^(−1)·Hz^(−1/2) for electric field measurements.The calibrated linear dynamical range spans approximately 89 dB,ranging from−110 dBV/cm to−21 dBV/cm.We demodulate a 400 symbol stream encoded in 4-state phase-shift keying,demonstrating excellent phase detection capability.By scanning the frequency of the local oscillator,we realize a terahertz spectrometer with Hz level frequency resolution.This resolution is more than two orders of magnitude higher than that of existing terahertz spectrometers.The demonstrated terahertz heterodyne receiver holds promising potential for working across the entire terahertz spectrum,significantly advancing its practical applications.
基金Maoming Science and Technology Plan Project(2022182)。
文摘Objective:To explore the effect of King’s Theory of Goal Attainment combined with teach-back method on improving the standardization rate of eye drop use in patients.Methods:A total of 200 patients who used more than two types of eye drops in the Department of Ophthalmology of our hospital were selected as the research subjects,and were randomly divided into an observation group and a control group.The control group was given routine health education,while the observation group was given King’s Theory of Goal Attainment combined with teach-back method on the basis of the control group.The standardization rate of eye drop use,knowledge awareness rate,and nursing satisfaction were compared between the two groups before and after the intervention.Results:After the intervention,the standardization rate of eye drop use,the awareness rate of eye drop knowledge,and the nursing satisfaction of the observation group were significantly higher than those of the control group(P<0.05).Conclusion:King’s Theory of Goal Attainment combined with teach-back method can effectively improve the standardization rate of eye drop use in patients,increase their awareness of eye drop knowledge,and improve nursing satisfaction,which is worthy of clinical application.
基金This work was supported by the National Natural Science Foundation of China(31801312)the National Key Research and Development Program of China(2017YFD0101600)+1 种基金Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences,the China Agriculture Research System(CARS-18-05)Xinjiang Production and Construction Corps Science&Technology NOVA Program(2020CB029).
文摘Mepiquat chloride(MC)priming alleviates the effects of salt stress during seed germination in cotton(Gossypium hirsutum L.),but the mechanisms underlying its effects are unknown.We found that MC priming increases salt tolerance,as evidenced by marked increases in seed vigor and germination rates,and alleviated salt toxicity by reducing Cl^(−)accumulation in germinating seeds.Consistently,electrophysiological experiments revealed that the seeds with MC priming displayed superior Cl^(−)exclusion ability in the root apex.These beneficial effects of MC priming were abolished by the abscisic acid(ABA)-synthesis blocker fluridone under salt stress.MC priming induced an early response to acclimatization and stress,as indicated by rapidly increasing ABA content during initial exposure to salt stress.Transcriptome analyses revealed that MC priming induced an array of differentially expressed genes(DEGs)in germinating seeds.The most noticeable changes in germinating seeds were MC priming-induced increases in the expression of DEGs encoding components of ABA biosynthesis,ABA catabolism,and ABA signaling pathways under salt stress.MC priming also increased the expression of some DEGs encoding Cl^(−)ion transporters(e.g.CCC,SLAC1/SLAH1/SLAH3,CLC,and ALMT9)in germinating seeds.These results indicate that MC priming-induced ABA contributes to Cl^(−)homeostasis in tissues and acts as a positive regulator of salt tolerance via regulation of Cl^(−)transporters(particularly CCC and SLAC1/SLAH1/SLAH3).Taken together,these findings shed light on the molecular mechanism underlying MC-mediated tolerance to salt stress during seed germination.
基金supported by grants from the Medical Scientific Fund and Intensive Research of Nanjing Military Area Command of Chinese PLA, No.Nan2007-13 and Nan 08Z003the Medical Scientific Fund and Research of Chinese PLA during the 12th Five-Year Plan Period,No.CWS11J260
文摘This study established a dog model of acute multiple cauda equina constriction by experimental constriction injury （48 hours） of the lumbosacral central processes in dorsal root ganglia neurons. The repair effect of intrathecal injection of brain-derived neurotrophic factor with 15 mg encapsulated biodegradable poly（lactide-co-glycolide） nanoparticles on this injury was then analyzed. Dorsal root ganglion cells （LT） of all experimental dogs were analyzed using hematoxylin-eosin staining and immunohistochemistry at 1,2 and 4 weeks following model induction. Intrathecal injection of brain-derived neurotrophic factor can relieve degeneration and inflammation, and elevate the expression of brain-derived neurotrophic factor in sensory neurons of compressed dorsal root ganglion Simultaneously, intrathecal injection of brain-derived neurotrophic factor obviously improved neurological function in the dog model of acute multiple cauda equina constriction. Results verified that sustained intraspinal delivery of brain-derived neurotrophic factor encapsulated in biodegradable nanoparticles promoted the repair of histomorphology and function of neurons within the dorsal root ganglia in dogs with acute and severe cauda equina syndrome.
基金supported by the National Natural Science Foundation of China(52172239)Project of State Key Laboratory of Environment-Friendly Energy Materials+2 种基金Southwest University of Science and Technology(Grant Nos.21fksy24 and 18ZD320304)Chongqing Talents:Exceptional Young Talents Project(Grant No.CQYC201905041)Natural Science Foundation of Chongqing China(Grant No.cstc2021jcyj-jqX0031)。
文摘The defect chemistry is successfully modulated on free-standing and binder-free carbon cathodes for highly efficient Li-S redox reactions.Such rationally regulated defect engineering realizes the synchronization of ion/electron-conductive and defect-rich networks on the threedimension carbon cathode,leading to its tunable activity for both relieving the shuttle phenomenon and accelerating the sulfur redox reaction kinetics.As expected,the defective carbon cathode harvests a high rate capacity of 1217.8 mAh g^(-1)at 0.2 C and a superior capacity retention of61.7%at 2 C after 500 cycles.Even under the sulfur mass loading of 11.1 mg cm^(-2),the defective cathode still holds a remarkable areal capacity of 8.5 mAh cm^(-2).
文摘In this study,diltiazem hydrochloride(DTZ)pellets were prepared successfully by extrusionespheronization method.Then methacrylic acid and ethylcellulose coating formulations were employed to make the DTZ pellets sustained release.The pellets with different coatings were investigated by in vitro dissolution tests.At last,the pellets with the best coating copolymer were subjected to pharmacokinetic studies in beagle dogs.The dissolution profiles of pellets coated with EudragitNE30D were similar to Herbesser,one of the marketed sustained release capsules.In the bioavailability study,the principal pharmacokinetic parameters of self-made pellets and the marketed ones were comparable;the relative bioavailability of DTZ sustained release capsules compared with Herbesserwas 98.536.4%.All the data indicated self-made sustained pellets could prolong the release of DTZ,decrease the fluctuation of drug level in vivo,and increase the compliance of patients.
基金This work was financially supported from the National Nature Science Foundation of China(No.81173009).
文摘The pharmacokinetics of oxiracetam and its degraded substance(4-hydroxy-2-oxo-1-pyrrolidine acetic acid,HOPAA)after oral and intravenous administration in rats were studied using an established UPLC-MS/MS method.Three groups of rats after an overnight fasted received 10 g/kg(n=6)oxiracetam suspensions orally,and 2 g/kg(n=6)normal or degraded oxiracetam injections intravenously via a caudal tail vein,respectively.Before the pharmacokinetic experiment,a simple safety evaluation testwas conducted on the degraded oxiracetam injections containing 16.16% HOPAA in mice.There was no mortality by a single intravenous dose of 2 g/kg of degraded oxiracetam injections within twoweeks,demonstrating that HOPAA was non-toxic in mice.Following intravenous administration of the normal injections,the plasma concentration-time curves of oxiracetam and HOPAA both showed a rapid elimination phase.The values of t_(1/2)were 3.1±1.5 h for oxiracetamand 0.8±0.2 h for HOPAA,andthemean residencetimes(MRT)were 1.2±0.1h and 0.8±0.1h,respectively.Oxiracetam and HOPAA after intravenous administration of the degraded oxiracetam injections presented elimination patterns similar to those observed in the normal injections.Oral pharmacokinetic results showed that the Tmax was less than 1.5 h for the two analytes,and both had a longer t_(1/2) and MRT than those of intravenous administration.Contents of HOPAA in three groupswere calculated based on AUC_(0-t) values of the two analytes.The quantitative change of HOPAA in vivo was also evaluated by comparing the plasma concentrations of HOPAA and oxiracetamat the same time for every group.Additionally,the values of absolute bioavailability of oxiracetam were about 8.0%and 7.4%calculated by the normal or degraded oxiracetam injections,whichwere far less than the value of 75%reported in literature,indicating the necessity of further study.
文摘A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was carried out by gradient elution using an Agilent C8 column(4.6 mm×250 mm,5 mm)which was maintained at 25℃.The mobile phase composed of solvent A(methanol)and solvent B(solution consisting 0.02 mmol/l monopotassium phosphate and 0.025 mmol/l sodium hydroxide)was at a flow rate of 1.0 ml/min.The samples were detected and quantified at 237 nm using an ultraviolet absorbance detector.Calibration curves of all analytes from 0.5 to 3.5 mg/ml were good linearity(r≥0.9990)and recovery was greater than 99.5% for each analyte.The lower limit of detection(LLOD)and quantification(LOQ)of this analytical method were 10 ng/ml and 25 ng/ml for all impurities,respectively.The stress studies indicated that the degradation products could not interfere with the detection of ilaprazole and its related impurities and the assay can thus be considered stability-indicating.The method precisions were in the range of 0.41-1.21 while the instrument precisions were in the range of 0.38-0.95 in terms of peak area RSD% for all impurities,respectively.This method is considered stabilityindicating and is applicable for accurate and simultaneous measuring of the ilaprazole and its related impurities in commercial enteric-coated tablets.
基金the financial support from the National Natural Science Foundation of China (No. 81173009)Technology Bureau in Shenyang (No. ZCJJ2013402)+2 种基金the financial support from Project for New Century Excellent Talents of Ministry of Education (No.NCET-12-1015)Specific Science Foundation of Shenyang Pharmaceutical University (No. ZCJJ2014409)National Undergraduate Training Program for Innovation and Entrepreneurship (2016)
文摘A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative(2’-deoxy-2’, 2’-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated.The conventional plasma sample preparation method of nucleoside analogues is solidphase extraction(SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation(LLOQ)of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.
基金a Grant from Department of Science and Technology of Hunan Prov-ince, No. 2009SK3112a Grant from Department of Health of Hunan Province, No. C2008005
文摘Clinical and animal experiments have proved that intrathecal injection of butorphanol has an analgesic effect. However, whether the analgesic effect is associated with activation of the N-methyI-D-aspartate （NMDA） receptor remains unclear. This study presumed that intrathecal injection of butorphanol has an analgesic effect on formalin-induced inflammatory pain in rats, and its analgesic effect is associated with inhibition of NMDA receptors. Concurrently, ketamine was injected into the intrathecal space, which is a non-competitive NMDA receptor antagonist, to determine the analgesic mechanism of butorphanol. The total reflection time in phase 1 and phase 2 of rat hind paws carding action was reduced when the butorphanol dose was increased to 25 μg, or a low dose of butorphanol was combined with ketamine. Intrathecal injection of a high dose of butorphanol alone or a low dose of butorphanol combined with ketamine can remarkably reduce NMDA receptor expression in the Ls spinal dorsal hom of formalin-induced pain rats. The results suggest that intrathecal injection of butorphanol has analgesic effects on formalin-induced inflammatory pain, and remarkably reduces NMDA receptor expression in the rat spinal dorsal horn Ketamine strengthens this analgesic effect. The analgesic mechanism of intrathecal injection of butorphanol is associated with inhibition of NMDA receptor activation.
基金supported by the National Natural Science Funds of China(Grant No.41205071)the Ministry of Science and Technology of China for the National Basic Research Program of China(973 Program:Grant No.2011CB309704)the funding support from the U.S.Department of Energy(DOE),Office of Science,Earth System Modeling Program
文摘A two-moment bulk stratiform microphysics scheme, including recently developed physically-based droplet activation/ice nucleation parameterizations has been implemented into the Grid-point Atmospheric Model of IAP LASG （GAMIL） as an effort to enhance the model＇s capability to simulate aerosol indirect effects. Unlike the previous one-moment cloud microphysics scheme, the new scheme produces a reasonable rep- resentation of cloud particle size and number concentration. This scheme captures the observed spatial variations in cloud droplet number concentrations. Simulated ice crystal number concentrations in cirrus clouds qualitatively agree with in situ observations. The longwave and shortwave cloud forcings are in better agreement with observations. Sensitivity tests show that the column cloud droplet number concentrations calculated from two different droplet activation parameterizations are similar. However, ice crystal number concentration in mixed-phased clouds is sensitive to different heterogeneous ice nucleation formulations. The simulation with high ice crystal number concentration in mixed-phase clouds has less liquid water path and weaker cloud forcing. ~rthermore, ice crystal number concentration in cirrus clouds is sensitive to different ice nucleation parameterizations. Sensitivity tests also suggest that the impact of pre-existing ice crystals on homogeneous freezing in old clouds should be taken into account.
