Due to the lack of inversion,mirror or other roto-inversion symmetries,chiral crystals possess a well-defined handedness which,when combined with time-reversal symmetry breaking from the application of magnetic fields...Due to the lack of inversion,mirror or other roto-inversion symmetries,chiral crystals possess a well-defined handedness which,when combined with time-reversal symmetry breaking from the application of magnetic fields,can give rise to directional dichroism of the electrical transport phenomena via the magnetochiral anisotropy.In this study,we investigate the nonreciprocal magneto-transport in microdevices of NbGe_(2),a superconductor with structural chirality.A giant nonreciprocal signal from vortex motions is observed during the superconducting transition,with the ratio of nonreciprocal resistance to the normal resistanceγreaching 6×10^(5)T^(-1)·A^(-1).Interestingly,the intensity can be adjusted and even sign-reversed by varying the current,the temperature,and the crystalline orientation.Our findings illustrate intricate vortex dynamics and offer ways of manipulation on the rectification effect in superconductors with structural chirality.展开更多
Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment.Ho...Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment.However,developing multifunctional biodegradable,biocompatible,low-toxic but highly efficient,and clinically available transformed nano-immunostimulants remains a challenge and is in great demand.Herein,we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid(BA),a water-soluble chitosan oligosaccharide(COS),and a low toxic photosensitizer chlorin e6(Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy.We show that the designed nanodrugs harbored a smart and distinctive“dormancy”characteristic in chemotherapeutic effect with desired lower cytotoxicity,and multiple favorable therapeutic features including improved^(1)O_(2)generation induced by the reduced energy gap of Ce6,pH-responsiveness,good biodegradability,and biocompatibility,ensuring a highly efficient,synergistic photochemotherapy.Moreover,when combined with anti-PD-L1 therapy,both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy(PDT)could effectively activate antitumor immunity when treating primary or distant tumors,opening up potentially attractive possibilities for clinical immunotherapy.展开更多
Oral drug delivery,which requires surviving the harsh environment in the gastrointestinal(Gl)tract and penetrating the intestinal epithelium,has not bee n achieved using simple formulatio n nan oparticles(NPs).Medici ...Oral drug delivery,which requires surviving the harsh environment in the gastrointestinal(Gl)tract and penetrating the intestinal epithelium,has not bee n achieved using simple formulatio n nan oparticles(NPs).Medici nal natural products(MNPs)have bee n widely used in traditi onal medicine for disease management through oral consumption.However,most pharmacologically active compounds within MNPs do not have the properties suitable for oral applicatio ns.We hypothesize that some MNPs contain n atural nano materials that can convert those compounds into oral formulations by forming NPs.After screening 66 MNPs,we identified five classes of small molecules that form NPs,many of which are capable of efficient drug encapsulation and Gl penetration.We show that one of them,dehydrotrametenolic acid(DTA),is capable of mediating oral delivery for effective disease treatment.We determined that DTA NPs assemble through hydrogen bonding and penetra怕the Gl tract via apical sodium-depe ndent bile acid tran sporter.Our study reveals a no vel class of single comp orient,small molecule-assembled NPs for oral drug delivery,and suggests a n ovel approach to modernizi ng MNPs through nano material discovery.展开更多
Natural products,as a gift of nature to humanity,have long been used as drugs or pharmacological actives to help people cure various diseases.Yet we still know comparatively little about their ability to be materials....Natural products,as a gift of nature to humanity,have long been used as drugs or pharmacological actives to help people cure various diseases.Yet we still know comparatively little about their ability to be materials.In recent years,some small molecule natural products isolated from traditional Chinese medicines have been found to have new features,namely,self-assembly to form gels(i.e.,natural product gels,NPG).However,the application development of these natural products is seriously lacking,which greatly weakens their practical value and delays the maturity of the field.Here,a series of selfassembled triterpenoid natural products are used as materials(gel scaffolds)to construct drug delivery systems.Surprisingly,these NPG not only exhibit the excellent self-healing,controlled gelation,good safety and sustained release,but also achieve synergistic treatment of tumors through bioactive natural products.Compared with non-bioactive gel scaffolds,NPG scaffolds show great advantages in tumor therapy,including optimal tumor inhibition,preferable health,better body recovery,stronger immune function,less toxic side effects and longer survival.The successful construction of NPG scaffolds not only takes full advantage of the self-assembled natural products,but also takes an important step in the development of new applications for natural products.展开更多
High-energy diets and lipid metabolism can lead to high levels of total cholesterol,a decrease in antioxidant,enzyme activity,and an increase in oxidative stress and dyslipidemia biomarker.In this study,the in vivo an...High-energy diets and lipid metabolism can lead to high levels of total cholesterol,a decrease in antioxidant,enzyme activity,and an increase in oxidative stress and dyslipidemia biomarker.In this study,the in vivo antihyperlipidemic and antioxidant effects of 1,3-dioleoyl-2-palmitoyl triglyceride(OPO)using a high fat-diet model were investigated.The mice were divided into groups including high-fat model group(HF),auxiliary group(AG),positive Control group(PC),low OPO dose group(LO),medium OPO dose group(MO)and high OPO.OPO was administrated to 60 hyperlipidemia induced male Kunming mice at the dosage of 200,400 and 800 mg/kg•d body weight,for 35 days.The results showed that the administration of OPO decreased the body weight from 43.92 g in HF to 37.74 g in HO group,liver index from 3.94%in HF to 3.43 in HO group and kidney index from 1.38 in HF%to 1.17%in HO group.The administration of OPO significantly decreased hyperlipidemia mice's serum triglyceride,total cholesterol,and low-density lipoprotein cholesterol levels at P<0.05.High-density lipoprotein cholesterol levels were increased with reductions of visceral hypertrophy and fat accumulation in model mice.Furthermore,in the HO group,superoxide dismutase,catalase and glutathione peroxidase levels increased significantly by 27.39,38.33 and 22.90%at(P<0.05),respectively.OPO also significantly reduced the enzyme activity of aspartate aminotransferase and alanine aminotransferase in serum at P<0.05.These findings suggested that OPO has potential use in hyperlipidemia treatment and other health-related complications.展开更多
基金Project supported by the National Key R&D Program of China(Grant No.2022YFA1403603)the National Natural Science Foundation of China(Grant Nos.U2032213,12104461,12374129,and 12304156)+1 种基金Chinese Academy of Sciences(Grant Nos.YSBR-084,and JZHKYPT-2021-08)A portion of this work was supported by the High Magnetic Field Laboratory of Anhui Province.
文摘Due to the lack of inversion,mirror or other roto-inversion symmetries,chiral crystals possess a well-defined handedness which,when combined with time-reversal symmetry breaking from the application of magnetic fields,can give rise to directional dichroism of the electrical transport phenomena via the magnetochiral anisotropy.In this study,we investigate the nonreciprocal magneto-transport in microdevices of NbGe_(2),a superconductor with structural chirality.A giant nonreciprocal signal from vortex motions is observed during the superconducting transition,with the ratio of nonreciprocal resistance to the normal resistanceγreaching 6×10^(5)T^(-1)·A^(-1).Interestingly,the intensity can be adjusted and even sign-reversed by varying the current,the temperature,and the crystalline orientation.Our findings illustrate intricate vortex dynamics and offer ways of manipulation on the rectification effect in superconductors with structural chirality.
基金the financial support from the National Natural Science Foundation of China(No.31972040,81760708)Jiangxi Provincial Natural Science Foundation Key Project(No.20192ACBL20028,China)。
文摘Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment.However,developing multifunctional biodegradable,biocompatible,low-toxic but highly efficient,and clinically available transformed nano-immunostimulants remains a challenge and is in great demand.Herein,we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid(BA),a water-soluble chitosan oligosaccharide(COS),and a low toxic photosensitizer chlorin e6(Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy.We show that the designed nanodrugs harbored a smart and distinctive“dormancy”characteristic in chemotherapeutic effect with desired lower cytotoxicity,and multiple favorable therapeutic features including improved^(1)O_(2)generation induced by the reduced energy gap of Ce6,pH-responsiveness,good biodegradability,and biocompatibility,ensuring a highly efficient,synergistic photochemotherapy.Moreover,when combined with anti-PD-L1 therapy,both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy(PDT)could effectively activate antitumor immunity when treating primary or distant tumors,opening up potentially attractive possibilities for clinical immunotherapy.
基金This work was supported by NIH(Nos.NS095817(J.Z.)and 18TPA34170180(J.Z.))the National Natural Science Foundation of China(NSFC)(Nos.31770614(C.M.),21233003(L.F.),and 21573019(L.F.)).
文摘Oral drug delivery,which requires surviving the harsh environment in the gastrointestinal(Gl)tract and penetrating the intestinal epithelium,has not bee n achieved using simple formulatio n nan oparticles(NPs).Medici nal natural products(MNPs)have bee n widely used in traditi onal medicine for disease management through oral consumption.However,most pharmacologically active compounds within MNPs do not have the properties suitable for oral applicatio ns.We hypothesize that some MNPs contain n atural nano materials that can convert those compounds into oral formulations by forming NPs.After screening 66 MNPs,we identified five classes of small molecules that form NPs,many of which are capable of efficient drug encapsulation and Gl penetration.We show that one of them,dehydrotrametenolic acid(DTA),is capable of mediating oral delivery for effective disease treatment.We determined that DTA NPs assemble through hydrogen bonding and penetra怕the Gl tract via apical sodium-depe ndent bile acid tran sporter.Our study reveals a no vel class of single comp orient,small molecule-assembled NPs for oral drug delivery,and suggests a n ovel approach to modernizi ng MNPs through nano material discovery.
基金supported by the National Natural Science Foundation of China,Nos.31972040 and 31571798Heilongjiang provincial financial support project(Xin Yang)Harbin Special Foundation for Excellent Academic Leader Project,No.2014RFXXJ113,China
文摘Natural products,as a gift of nature to humanity,have long been used as drugs or pharmacological actives to help people cure various diseases.Yet we still know comparatively little about their ability to be materials.In recent years,some small molecule natural products isolated from traditional Chinese medicines have been found to have new features,namely,self-assembly to form gels(i.e.,natural product gels,NPG).However,the application development of these natural products is seriously lacking,which greatly weakens their practical value and delays the maturity of the field.Here,a series of selfassembled triterpenoid natural products are used as materials(gel scaffolds)to construct drug delivery systems.Surprisingly,these NPG not only exhibit the excellent self-healing,controlled gelation,good safety and sustained release,but also achieve synergistic treatment of tumors through bioactive natural products.Compared with non-bioactive gel scaffolds,NPG scaffolds show great advantages in tumor therapy,including optimal tumor inhibition,preferable health,better body recovery,stronger immune function,less toxic side effects and longer survival.The successful construction of NPG scaffolds not only takes full advantage of the self-assembled natural products,but also takes an important step in the development of new applications for natural products.
基金the financial support received from the National Key Research and Development projects(2017YFD0400200).
文摘High-energy diets and lipid metabolism can lead to high levels of total cholesterol,a decrease in antioxidant,enzyme activity,and an increase in oxidative stress and dyslipidemia biomarker.In this study,the in vivo antihyperlipidemic and antioxidant effects of 1,3-dioleoyl-2-palmitoyl triglyceride(OPO)using a high fat-diet model were investigated.The mice were divided into groups including high-fat model group(HF),auxiliary group(AG),positive Control group(PC),low OPO dose group(LO),medium OPO dose group(MO)and high OPO.OPO was administrated to 60 hyperlipidemia induced male Kunming mice at the dosage of 200,400 and 800 mg/kg•d body weight,for 35 days.The results showed that the administration of OPO decreased the body weight from 43.92 g in HF to 37.74 g in HO group,liver index from 3.94%in HF to 3.43 in HO group and kidney index from 1.38 in HF%to 1.17%in HO group.The administration of OPO significantly decreased hyperlipidemia mice's serum triglyceride,total cholesterol,and low-density lipoprotein cholesterol levels at P<0.05.High-density lipoprotein cholesterol levels were increased with reductions of visceral hypertrophy and fat accumulation in model mice.Furthermore,in the HO group,superoxide dismutase,catalase and glutathione peroxidase levels increased significantly by 27.39,38.33 and 22.90%at(P<0.05),respectively.OPO also significantly reduced the enzyme activity of aspartate aminotransferase and alanine aminotransferase in serum at P<0.05.These findings suggested that OPO has potential use in hyperlipidemia treatment and other health-related complications.