The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent...The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent heat treatment at 300,450,and 500°C.The material properties of the resulting samples were assessed through microstructural observation,tensile testing,electrical conductivity measurements,and electromagnetic shielding effectiveness(EMI-SE)testing.The influence of the Mg-8Li-3Y-2Zn alloy microstructure on its mechanical and electromagnetic shielding properties in different states was investigated.It was found that the as-cast alloy containsα-Mg,β-Li,Mg_(3)Zn_(3)Y_(2),and Mg_(12)ZnY phases.Following heat treatment at 500℃(HT500),the blockα-Mg phase transformedfine needle-shapes,its tensile strength increased to 263.7 MPa,and its elongation reached 45.3%.The mechanical properties of the alloy were significantly improved by the synergistic effects imparted by the needle-shapedα-Mg phase,solid solution strengthening,and precipitation strengthening.The addition of Y and Zn improved the EMI-SE of Mg-8Li-1Zn alloy,wherein the HT500 sample exhibits the highest SE,maintaining a value of 106.7–76.9 dB in the frequency range of 30–4500 MHz;this performance has rarely been reported for electromagnetically shielded alloys.This effect was mainly attributed to the multiple reflections of electromagnetic waves caused by the severe impedance mismatch of the abundant phase boundaries,which were in turn provided by the dual-phase(α/β)and secondary phases.Furthermore,the presence of nano-precipitation was also believed to enhance the absorption of electromagnetic waves.展开更多
Let G be a finite group.A generating set X of G is said to be minimal if no proper subset of X generates G.Let d(G)and m(G)denote the smallest size and the largest size of a minimal generating set of G,respectively.In...Let G be a finite group.A generating set X of G is said to be minimal if no proper subset of X generates G.Let d(G)and m(G)denote the smallest size and the largest size of a minimal generating set of G,respectively.In this paper we present a characterization for finite solvable groups G such that m(G)-d(G)=1 and m(G)≥m(G/N)+m(N)for any non-trivial normal subgroup N of G.展开更多
Regulating the precipitation behavior of Mg alloys to overcome the strength-ductility trade-off puzzle is a long-thought pursuit in the materials community.With this purpose,external stress has been recently applied d...Regulating the precipitation behavior of Mg alloys to overcome the strength-ductility trade-off puzzle is a long-thought pursuit in the materials community.With this purpose,external stress has been recently applied during aging and shows immense potential in affecting atomic diffusion,and regulating the coherence of the phase boundaries.In this study,elastic tensile(TSA)and compressive stress aging(CSA)of Mg-1.1Gd-0.6Zn-0.3Mn alloy are carried out and the competition of precipitation between multiple precipitates occurs during stress aging.A significant quantity ofβ’precipitates primarily distribute along grain boundaries in conventional peak aging alloy.Whereas high density ofγ’phases rather thanβ’phase precipitate in both TSA and CSA alloys.The first-principle calculations reveal that the application of external stress introduces shear strain,which decreases unstable stacking fault energies,and thereby promoting the precipitation ofγ’phase and impeding the precipitation ofβ’phase.Furthermore,the sequential transformation fromγ’phase to Long Period Stacking Ordered(LPSO)phase occurs in CSA sample,due to the release of elastic local strain at phase boundaries.After subjected to TSA treatment,the sample possesses an ultimate tensile strength of 356 MPa,a yield strength of 294 MPa,and a total elongation of~14.3%.The excellent strength-ductility synergy of TSA sample is primarily contributed to the profuseγ’precipitates hindering the motion of large number of pyramidal(c+a) dislocations during tensile deformation.This study offers new insights on regulating the precipitation behavior of Mg alloys containing multiple types of precipitates through the application of external stress,and extends the potential window for obtaining an excellent strength-ductility synergy in age-hardenable Mg alloys.展开更多
Objective:Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding.The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate ...Objective:Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding.The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation(RCA)combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis(IHD)treatment.Methods:Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments,and were randomly divided into RCA group and saline flushing group.In the RCA group,0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber.The sodium citrate was stopped after 3 h of dialysis,which was changed to sequential dialysis without anticoagulant.The hazard ratios for coagulation were according to baseline.Results:A total of 159 patients and 208 sessions were enrolled,including RCA group(80 patients,110 sessions)and saline flushing group(79 patients,98 sessions).The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group(3.64%vs.20.41%,P<0.001).The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group((238.34±9.33)min vs.(221.73±34.10)min,P<0.001).The urea clearance index(Kt/V)in the RCA group was similar to that in the saline flushing group with no statistically significant difference(1.12±0.34 vs.1.08±0.34,P=0.41).Conclusions:Compared with saline flushing,the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.展开更多
This study investigated the influence of aging prior to extrusion(APE)on the tensile strength and ductility of as-extruded Mg-8.32Sn-1.85Zn-0.17Mn alloy.Results demonstrated that APE treatment dramatically increased t...This study investigated the influence of aging prior to extrusion(APE)on the tensile strength and ductility of as-extruded Mg-8.32Sn-1.85Zn-0.17Mn alloy.Results demonstrated that APE treatment dramatically increased the volume fraction of recrystallized grains,thereby decreasing the grain size of the as-extruded alloy.This phenomenon was primarily attributed to the particle-stimulated nucleation and pinning effect induced by large amounts of small Mg 2 Sn precipitates produced by the APE treatment and dynamic precipitation.The tensile yield strength increased from 242.4 MPa to 256.5 MPa after APE treatment.The improved tensile strength can be attributed to the enhanced grain boundary strengthening and precipitation strengthening.The ductility of the as-extruded alloy also markedly increased from 7.1%to 13.5%after the APE treatment.The improved ductility of APE alloy was attributed to the texture randomization,the activity of pyramidal<c+a>slip and the suppressed formation of{10-11}contraction twins and coarse Mg 2 Sn phases.展开更多
Flue gas from coal combustion contains significant amounts of volatile selenium （Se）. The capture of Se in the flue gas desulfurization （FGD） scrubber unit has resulted in a generation of metal-laden residues. It ...Flue gas from coal combustion contains significant amounts of volatile selenium （Se）. The capture of Se in the flue gas desulfurization （FGD） scrubber unit has resulted in a generation of metal-laden residues. It is important to determine Se speciation to understand the environmental impact of its disposal. A simple method has been developed for selective inorganic Se（IV）, Se（VI） and organic Se determination in the liquid-phase FGD residues by hydride generation atomic fluorescence spectrometry （AFS）. It has been determined that Se（IV）, Se（VI） and organic Se can be accurately determined with detection limits （DL） of 0.05, 0.06 and 0.06 μg/L, respectively. The accuracy of the proposed method was evaluated by analyzing the certified reference material, NIST CRM 1632c, and also by analyzing spiked tap-water samples. Analysis indicates that the concentration of Se is high in FGD liquid residues and primarily exists in a reduced state as selenite （Se（IV））. The toxicity of Se（IV） is the strongest of all Se species. Flue gas desulfurization residues pose a serious environmental risk.展开更多
CeO2,Ce1–xZrxO2,and Ce1–xYxO2–δ(x=0.25,0.50,0.75,and 1.00)have been rapidly synthesized to estimate their catalytic behavior in decomposing CH3SH.The role of oxygen vacancies,and the relationship between the oxyge...CeO2,Ce1–xZrxO2,and Ce1–xYxO2–δ(x=0.25,0.50,0.75,and 1.00)have been rapidly synthesized to estimate their catalytic behavior in decomposing CH3SH.The role of oxygen vacancies,and the relationship between the oxygen species and catalytic properties of CeO2 and Zr‐doped and Y‐doped ceria‐based materials are investigated in detail.Combining the observed catalytic performance with the characterization results,it can be deemed that surface lattice oxygen plays a critical role in methanethiol catalytic conversion over cerium oxides.Ce0.75Zr0.25O2 shows higher catalytic activity for CH3SH decomposition due to the large amount of surface lattice oxygen,readily available oxygen species,and excellent redox properties.Ce0.75Y0.25O2–δdisplays better catalytic stability owing to the greater number of oxygen vacancies that would promote bulk lattice oxygen migration to the surface of the catalyst in order to replenish surface lattice oxygen.In addition,the results show that the difference in chemical valence between Ce and the heteroatoms would strongly influence the amount of surface lattice oxygen as well as the mobility of bulk‐phase oxygen in these catalysts,thus affecting their activity and stability.展开更多
The microstructure and thermal conductivity of four groups of Mg–rare earth（RE） binary alloys（Mg–Ce,Mg–Nd, Mg–Y and Mg–Gd） in as-cast and as-solutionized states were systematically studied. Thermal conductivi...The microstructure and thermal conductivity of four groups of Mg–rare earth（RE） binary alloys（Mg–Ce,Mg–Nd, Mg–Y and Mg–Gd） in as-cast and as-solutionized states were systematically studied. Thermal conductivity was measured on a Netzsch LFA457 using laser flash method at room temperature. Results indicated that for as-cast alloys, the volume fraction of second phases increased with the increase of alloying elements. After solutionizing treatment, a part or most of second phases were dissolved in α-Mg matrix, except for Mg–Ce alloys. The thermal conductivity of as-cast and as-solutionized Mg–RE alloys decreased with the increase of concentrations. The thermal conductivity of as-solutionized Mg–Nd,Mg–Y and Mg–Gd alloys was lower than that of as-cast alloys. Thermal conductivity of as-solutionized Mg–Ce alloys was higher than that of as-cast alloys, because of the elimination of lattice defects and fine dispersed particles during solutionizing treatment. Different RE elements have different influences on the thermal conductivity of Mg alloys in the following order： Ce 〈 Nd 〈 Y 〈 Gd. Ce has the minimum effect on thermal conductivity of Mg alloys, because of the very low solubility of Ce in the α-Mg matrix. The variations in the atomic radius of the solute elements with Mg atom（ r）, valence, configuration of extranuclear electron of the solute atoms, and the maximum solid solubility of elements in the α-Mg matrix were suggested to be the main reasons for the differences in thermal conductivity of resulting Mg–RE alloys.展开更多
Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effe...Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.展开更多
The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early de...The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.展开更多
Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methox...Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD, i.e., Averrhoa carambola extractive) liposomes(HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading(up to 83%)with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests,HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κ B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.展开更多
Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle di...Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.展开更多
The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary...The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.展开更多
The authors regret Fig.5C in the published article contained an incorrect image.Specifically,the image for the MHCC97H(pLVX-Puro)/DC group was mistakenly used during copying and pasting in the process of assembling th...The authors regret Fig.5C in the published article contained an incorrect image.Specifically,the image for the MHCC97H(pLVX-Puro)/DC group was mistakenly used during copying and pasting in the process of assembling the figure.This correction has no influence on the readers'understanding of the article.The original data of the figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.展开更多
The excellent strength-ductility combination of hetero-grained Mg alloys has been reported to stem from pronounced hetero-deformation induced(HDI)stress.This stress alters the internal stress state of various slip sys...The excellent strength-ductility combination of hetero-grained Mg alloys has been reported to stem from pronounced hetero-deformation induced(HDI)stress.This stress alters the internal stress state of various slip systems and triggers significant activity of non-basal slips.However,the HDI stress state of different slip systems,and the mechanisms underlying the selective activation between basal and non-basal slips remain unclear to date.This study develops a novel HDI stress partitioning framework that in-situ calculates the crystallographic parameters and geometrical information of each datapoint within grains,aiming to reveal the correlation between HDI stress partitioning on individual slip systems and localized deformation model in the case of bimodal-grained ZK60 alloy.The framework demonstrates that HDI stress shows a strong dependence on the density of geometrically necessary dislocations(GNDs)and slip-system-level grain size,while exhibiting a relatively weaker correlation with equivalent-circle size of the hetero-grains.Given the close relation between the stress partitioning and the physical parameters,the framework can accurately predict the single and multiple slip activity fields obtained from highresolution digital image correlation(HR-DIC).This holds even for slip systems with low Schmid factors,which are theoretically difficult to activate.Using this framework,it is found that HDI stress plays a more prominent role in diminishing the effective resolved shear stress(RSS)of basal<a>and prismatic<a>(i.e.,<a>component)dislocations,while having a negligible effect on pyramidal<c+a>slips.Benefiting from the increased ratio of RSS_(<c+a>)/RSS_(<a>),pyramidal<c+a>dislocations are extensively activated,leading to excellent strength-ductility combination in the bimodal-grained ZK60 alloy.展开更多
AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of...AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.展开更多
RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA...RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field.展开更多
The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a nove...The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a novel Ag/Bi2MoO6(Ag/BMO)nanozyme optimized by charge separation engineering with photoactivated sustainable peroxidase-mimicking activities and NIR-II photodynamic performance was synthesized by solvothermal reaction and photoreduction.The Ag/BMO nanozyme held satisfactory bactericidal performance against methicillin-resistant Staphylococcus aureus(MRSA)(~99.9%).The excellent antibacterial performance of Ag/BMO NPs was ascribed to the corporation of peroxidase-like activity,NIR-II photodynamic behavior,and acidity-enhanced release of Ag^(+).As revealed by theoretical calculations,the introduction of Ag to BMO made it easier to separate photo-triggered electronhole pairs for ROS production.And the conduction and valence band potentials of Ag/BMO NPs were favorable for the reduction of O_(2) to·O_(2)^(−).Under 1064 nm laser irradiation,the electron transfer to BMO was beneficial to the reversible change of Mo^(5+)/Mo^(6+),further improving the peroxidase-like catalytic activity and NIR-II photodynamic performance based on the Russell mechanism.In vivo,the Ag/BMO NPs exhibited promising therapeutic effects towards MRSA-infected wounds.This study enriches the nanozyme research and proves that nanozymes can be rationally optimized by charge separation engineering strategy.展开更多
Diabetic wounds have become a major clinical problem that cannot be ignored.Gases,such as hydrogen sulphide(H_(2)S),have demonstrated value in inducing angiogenesis and accelerating wound healing,while their effective...Diabetic wounds have become a major clinical problem that cannot be ignored.Gases,such as hydrogen sulphide(H_(2)S),have demonstrated value in inducing angiogenesis and accelerating wound healing,while their effective delivery is still challenging.Here,inspired by the continuous-independent hollow structure of bamboo,we propose novel gasotransmitter microfibres with septal H_(2)S bubbles using microfluidic spinning for diabetic wound healing.Benefitting from the exact control of microfluidics,gasotransmitter microfibres with different bubble sizes and morphologies could be generated successfully and continuously.Under the dual effects of drugs in the shell and gas in the core,the wound healing process could be accelerated.Furthermore,the controllable release of drugs could be achieved by adding responsive materials into the microfiber shell,which would promote continuous effects of contents on demand.Based on in vitro and in vivo stud-ies,we have proven that these gasotransmitter microfibres have a positive impact on inducing angiogenesis and promoting cell proliferation during wound healing.Thus,it is believed that the bamboo-inspired gasotransmitter microfibres will have important value in gasotransmitter research and clinical applications.展开更多
Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum...Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.展开更多
基金supported by the National Natural Sci-ence Foundation of China[No.51564032]Yunnan Provin-cial Department of Education Science Research Fund Project[KKPH202132005]the Analysis and Testing Founda-tion of Kunming University of Science and Technology[2022M20212130086].
文摘The performances of magnesium alloys remain insufficient to further enhance the application potential of ultralight magnesium alloys.In this work,a Mg-8Li-3Y-2Zn alloy was prepared through vacuum melting and subsequent heat treatment at 300,450,and 500°C.The material properties of the resulting samples were assessed through microstructural observation,tensile testing,electrical conductivity measurements,and electromagnetic shielding effectiveness(EMI-SE)testing.The influence of the Mg-8Li-3Y-2Zn alloy microstructure on its mechanical and electromagnetic shielding properties in different states was investigated.It was found that the as-cast alloy containsα-Mg,β-Li,Mg_(3)Zn_(3)Y_(2),and Mg_(12)ZnY phases.Following heat treatment at 500℃(HT500),the blockα-Mg phase transformedfine needle-shapes,its tensile strength increased to 263.7 MPa,and its elongation reached 45.3%.The mechanical properties of the alloy were significantly improved by the synergistic effects imparted by the needle-shapedα-Mg phase,solid solution strengthening,and precipitation strengthening.The addition of Y and Zn improved the EMI-SE of Mg-8Li-1Zn alloy,wherein the HT500 sample exhibits the highest SE,maintaining a value of 106.7–76.9 dB in the frequency range of 30–4500 MHz;this performance has rarely been reported for electromagnetically shielded alloys.This effect was mainly attributed to the multiple reflections of electromagnetic waves caused by the severe impedance mismatch of the abundant phase boundaries,which were in turn provided by the dual-phase(α/β)and secondary phases.Furthermore,the presence of nano-precipitation was also believed to enhance the absorption of electromagnetic waves.
基金Supported by China Scholarship Council(Grant No.202208360148)the National Natural Science Foundation of China(Grant Nos.12126415,12261042,12301026)the Natural Science Foundation of Jiangxi Province(Grant No.20232BAB211006).
文摘Let G be a finite group.A generating set X of G is said to be minimal if no proper subset of X generates G.Let d(G)and m(G)denote the smallest size and the largest size of a minimal generating set of G,respectively.In this paper we present a characterization for finite solvable groups G such that m(G)-d(G)=1 and m(G)≥m(G/N)+m(N)for any non-trivial normal subgroup N of G.
基金the financial supports from the University Natural Science Research Project of Anhui Province(No.2022AH050316)the National Natural Science Foundation of China,China(No.51901144)the Anhui Provincial Natural Science Foundation,China(No.2108085QE185)。
文摘Regulating the precipitation behavior of Mg alloys to overcome the strength-ductility trade-off puzzle is a long-thought pursuit in the materials community.With this purpose,external stress has been recently applied during aging and shows immense potential in affecting atomic diffusion,and regulating the coherence of the phase boundaries.In this study,elastic tensile(TSA)and compressive stress aging(CSA)of Mg-1.1Gd-0.6Zn-0.3Mn alloy are carried out and the competition of precipitation between multiple precipitates occurs during stress aging.A significant quantity ofβ’precipitates primarily distribute along grain boundaries in conventional peak aging alloy.Whereas high density ofγ’phases rather thanβ’phase precipitate in both TSA and CSA alloys.The first-principle calculations reveal that the application of external stress introduces shear strain,which decreases unstable stacking fault energies,and thereby promoting the precipitation ofγ’phase and impeding the precipitation ofβ’phase.Furthermore,the sequential transformation fromγ’phase to Long Period Stacking Ordered(LPSO)phase occurs in CSA sample,due to the release of elastic local strain at phase boundaries.After subjected to TSA treatment,the sample possesses an ultimate tensile strength of 356 MPa,a yield strength of 294 MPa,and a total elongation of~14.3%.The excellent strength-ductility synergy of TSA sample is primarily contributed to the profuseγ’precipitates hindering the motion of large number of pyramidal(c+a) dislocations during tensile deformation.This study offers new insights on regulating the precipitation behavior of Mg alloys containing multiple types of precipitates through the application of external stress,and extends the potential window for obtaining an excellent strength-ductility synergy in age-hardenable Mg alloys.
基金the 1.3.5 Project for Disciplines of Excellence from West China Hospital of Sichuan University(No.ZYGD18027)。
文摘Objective:Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding.The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation(RCA)combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis(IHD)treatment.Methods:Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments,and were randomly divided into RCA group and saline flushing group.In the RCA group,0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber.The sodium citrate was stopped after 3 h of dialysis,which was changed to sequential dialysis without anticoagulant.The hazard ratios for coagulation were according to baseline.Results:A total of 159 patients and 208 sessions were enrolled,including RCA group(80 patients,110 sessions)and saline flushing group(79 patients,98 sessions).The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group(3.64%vs.20.41%,P<0.001).The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group((238.34±9.33)min vs.(221.73±34.10)min,P<0.001).The urea clearance index(Kt/V)in the RCA group was similar to that in the saline flushing group with no statistically significant difference(1.12±0.34 vs.1.08±0.34,P=0.41).Conclusions:Compared with saline flushing,the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
基金The authors are grateful for the financial supports from the Sichuan Science and Technology Program(2019YJ0478)the Research Foundation for the introduction of talent of Sichuan University of Science and Engineering,China(Grant Nos.2017RCL18 and 2017RCL35)the Opening Project of Material Corrosion and Protection Key Laboratory of Sichuan Province,China(Grant Nos.2017CL05,2017CL06 and 2018CL06)。
文摘This study investigated the influence of aging prior to extrusion(APE)on the tensile strength and ductility of as-extruded Mg-8.32Sn-1.85Zn-0.17Mn alloy.Results demonstrated that APE treatment dramatically increased the volume fraction of recrystallized grains,thereby decreasing the grain size of the as-extruded alloy.This phenomenon was primarily attributed to the particle-stimulated nucleation and pinning effect induced by large amounts of small Mg 2 Sn precipitates produced by the APE treatment and dynamic precipitation.The tensile yield strength increased from 242.4 MPa to 256.5 MPa after APE treatment.The improved tensile strength can be attributed to the enhanced grain boundary strengthening and precipitation strengthening.The ductility of the as-extruded alloy also markedly increased from 7.1%to 13.5%after the APE treatment.The improved ductility of APE alloy was attributed to the texture randomization,the activity of pyramidal<c+a>slip and the suppressed formation of{10-11}contraction twins and coarse Mg 2 Sn phases.
基金supported by the National Natural Science Foundation of China (No.90410018)the Shanxi Nature Science Foundation (No.20051017)+1 种基金the Shanxi Returned Scholar Research Project (No.2005-21)the Programfor Changjiang Scholars and Innovative Research Team at University in MOE,China (No.IRT0517)
文摘Flue gas from coal combustion contains significant amounts of volatile selenium （Se）. The capture of Se in the flue gas desulfurization （FGD） scrubber unit has resulted in a generation of metal-laden residues. It is important to determine Se speciation to understand the environmental impact of its disposal. A simple method has been developed for selective inorganic Se（IV）, Se（VI） and organic Se determination in the liquid-phase FGD residues by hydride generation atomic fluorescence spectrometry （AFS）. It has been determined that Se（IV）, Se（VI） and organic Se can be accurately determined with detection limits （DL） of 0.05, 0.06 and 0.06 μg/L, respectively. The accuracy of the proposed method was evaluated by analyzing the certified reference material, NIST CRM 1632c, and also by analyzing spiked tap-water samples. Analysis indicates that the concentration of Se is high in FGD liquid residues and primarily exists in a reduced state as selenite （Se（IV））. The toxicity of Se（IV） is the strongest of all Se species. Flue gas desulfurization residues pose a serious environmental risk.
基金supported by the National Natural Science Foundation of China (21667016, 21267011, U1402233)~~
文摘CeO2,Ce1–xZrxO2,and Ce1–xYxO2–δ(x=0.25,0.50,0.75,and 1.00)have been rapidly synthesized to estimate their catalytic behavior in decomposing CH3SH.The role of oxygen vacancies,and the relationship between the oxygen species and catalytic properties of CeO2 and Zr‐doped and Y‐doped ceria‐based materials are investigated in detail.Combining the observed catalytic performance with the characterization results,it can be deemed that surface lattice oxygen plays a critical role in methanethiol catalytic conversion over cerium oxides.Ce0.75Zr0.25O2 shows higher catalytic activity for CH3SH decomposition due to the large amount of surface lattice oxygen,readily available oxygen species,and excellent redox properties.Ce0.75Y0.25O2–δdisplays better catalytic stability owing to the greater number of oxygen vacancies that would promote bulk lattice oxygen migration to the surface of the catalyst in order to replenish surface lattice oxygen.In addition,the results show that the difference in chemical valence between Ce and the heteroatoms would strongly influence the amount of surface lattice oxygen as well as the mobility of bulk‐phase oxygen in these catalysts,thus affecting their activity and stability.
基金co-supported by the National Natural Science Foundation of China (Grant No. 51474043)the Education Commission of Chongqing Municipality (Grant No. KJZH14101)the Chongqing Municipal Government (Grant No. CSTC2013JCYJC60001, Two River Scholar Project and The Chief Scientist Studio Project)
文摘The microstructure and thermal conductivity of four groups of Mg–rare earth（RE） binary alloys（Mg–Ce,Mg–Nd, Mg–Y and Mg–Gd） in as-cast and as-solutionized states were systematically studied. Thermal conductivity was measured on a Netzsch LFA457 using laser flash method at room temperature. Results indicated that for as-cast alloys, the volume fraction of second phases increased with the increase of alloying elements. After solutionizing treatment, a part or most of second phases were dissolved in α-Mg matrix, except for Mg–Ce alloys. The thermal conductivity of as-cast and as-solutionized Mg–RE alloys decreased with the increase of concentrations. The thermal conductivity of as-solutionized Mg–Nd,Mg–Y and Mg–Gd alloys was lower than that of as-cast alloys. Thermal conductivity of as-solutionized Mg–Ce alloys was higher than that of as-cast alloys, because of the elimination of lattice defects and fine dispersed particles during solutionizing treatment. Different RE elements have different influences on the thermal conductivity of Mg alloys in the following order： Ce 〈 Nd 〈 Y 〈 Gd. Ce has the minimum effect on thermal conductivity of Mg alloys, because of the very low solubility of Ce in the α-Mg matrix. The variations in the atomic radius of the solute elements with Mg atom（ r）, valence, configuration of extranuclear electron of the solute atoms, and the maximum solid solubility of elements in the α-Mg matrix were suggested to be the main reasons for the differences in thermal conductivity of resulting Mg–RE alloys.
基金supported by the National Natural Science Foundation of China(No.82072340)the Major National Science and Technology Projects–Major New Drug Creation(2019ZX09301-132)+1 种基金Changjiang Scholars and Innovative Research Team in University(No.IRT_15R13)Guangxi Science and Technology Base and Talent Special Project(No.AD17129003).
文摘Although great achievements have been made in the past decades in medicine,cancer remains a worldwide public health issue.Surgery is usually accompanied by shortcomings such as residual lesions and poor treatment effects,and the successive appearance of other treatment methods,such as radiotherapy and chemotherapy,has not changed the postoperative recurrence rate,toxicity,and side effects.However,the advent of photodynamic therapy has greatly improved this situation.Photodynamic therapy is an emerging tumor diagnosis and treatment technology with good application prospects,photodynamic therapy uses a specific wavelength of light to excite a photosensitizer to generate reactive oxygen species,damage tumor blood vessels and promote tumor cell apoptosis,exerting an anti-tumor effect.Photodynamic therapy has become a new clinical anti-tumor therapy due to its clear efficacy,few side effects,and easy use in combination with other therapies.In this review,we summarized the main mechanism,current challenges,and advancements of photodynamic therapy.
基金supported by the National Natural Science Foundation of China (No. 61775095)Natural Science Foundation of Jiangsu Province (No. BK20200092)+3 种基金Jiangsu Province Policy Guidance Plan (No. BZ2019014)Natural Science Foundation of Shandong Province (No. ZR2020KB018)‘Taishan scholars’ construction special fund of Shandong Provincethe High-Performance Computing Center in Nanjing Tech University for supporting the computational resources
文摘The small molecular second near-infrared(NIR-Ⅱ, 1000–1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-Ⅱ dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes.Herein, we report a novel molecular electron acceptor, boron difluoride formazanate(BDF). Based on BDF, a new small molecular NIR-Ⅱ dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-Ⅱ peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-Ⅱ fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-Ⅱ small molecular dyes for cancer phototheranostics.
基金funded by the Guangxi Key Laboratory of Biotargeting Theranostics(No.GXSWBX201804)the State Project for Essential Drug Research and Development(No.2019ZX09301132)+4 种基金Guangxi Science and Technology Bases and Talent Special Project(No.AD17129062)Guangxi Key Research and Development Project(No.AB20117001)Guangxi First-class Discipline Project for Pharmaceutical Sciences(No.GXFCDP-PS-2018)Natural Science Foundation of China(Nos.81760665,81460205)Guangxi Science and Technology Base and Talent Project(No.AD17195085)。
文摘Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione(DMDD, i.e., Averrhoa carambola extractive) liposomes(HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading(up to 83%)with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests,HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-κ B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.
基金supported by the Scientific and Technological Innovation Major Base of Guangxi (No. 2018–15-Z04)Guangxi Key Research and Development Project (No. AB20117001)+1 种基金Guangxi Science and Technology Bases and Talent Special Project (No. AD17129062)Guangxi Natural Science Foundation (No. 2018JJA140524)。
文摘Oncolytic virus is an emerging anti-cancer strategy. However, extracellular matrix(ECM), as a physical barrier, limits virus spread within the tumor. To overcome the obstacle, we constructed a recombinant Newcastle disease virus(NDV) expressing matrix metalloproteinase(MMP8)(NDV-MMP8) using with reverse genetic technology. In vitro, NDV-MMP8 was identified and verified by WB and ELISA. Cell viability was detected by CCK-8 assay. In vivo, we established two liver cancer xenograft models. NDV-MMP8 was injected into the tumor to observe the tumor volume and survival of mice. The changes in extracellular matrix were observed by Masson’s trichrome staining. Virus expression in tumor tissues was detected by immunofluorescence assay. The virus titer in tumor tissues was detected by TCID50. Histopathological changes were detected by hematoxylin and eosin(HE) and terminal deoxynucleotidyl transferase d UTP nick end labeling(TUNEL) staining. Intratumoral administration of NDV-MMP8 can effectively degrade ECM, promote the spread of the virus within the tumor, and reduce tumor growth rate. Therefore, the method of increasing intratumoral virus accumulation by degradation of the ECM to enhance the oncolytic effect has great potential for clinical application.
基金supported by the National Key Research and Development Program of China(2019YFA0112000 and 2018YFB1105600)the National Natural Science Foundation of China(81930051)+2 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906)Shanghai Jiao Tong University “Medical and Research”Program(ZH2018ZDA04)Foundation of National Facility for Translational Medicine(Shanghai)(TMSK-2020-117)。
文摘The immune response after implantation is a primary determinant of the tissue-repair effects of threedimensional(3D)-printed scaffolds.Thus,scaffolds that can subtly regulate immune responses may display extraordinary functions.Inspired by the angiogenesis promotion effect of humoral immune response,we covalently combined mesoporous silica micro rod(MSR)/polyethyleneimine(PEI)/ovalbumin(OVA)self-assembled vaccines with 3D-printed calcium phosphate cement(CPC)scaffolds for local antigen-specific immune response activation.With the response activated,antigen-specific CD4+T helper2(Th2)cells can be recruited to promote early angiogenesis.The silicon(Si)ions from MSRs can accelerate osteogenesis,with an adequate blood supply being provided.At room temperature,scaffolds with uniformly interconnected macropores were printed using a self-setting CPC-based printing paste,which promoted the uniform dispersion and structural preservation of functional polysaccharides oxidized hyaluronic acid(OHA)inside.Sustained release of OVA was achieved with MSR/PEI covalently attached to scaffolds rich in aldehyde groups as the vaccine carrier.The vaccine-loaded scaffolds effectively recruited and activated dendritic cells(DCs)for antigen presentation and promoted the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)in vitro.When embedded subcutaneously in vivo,the vaccine-loaded scaffolds increased the proportion of Th2 cells in the spleen and locally recruited antigenspecific T cells to promote angiogenesis in and around the scaffold.Furthermore,the result in a rat skull defect-repair model indicated that the antigen-specific vaccine-loaded scaffolds promoted the regeneration of vascularized bone.This method may provide a novel concept for patient-specific implant design for angiogenesis promotion.
文摘The authors regret Fig.5C in the published article contained an incorrect image.Specifically,the image for the MHCC97H(pLVX-Puro)/DC group was mistakenly used during copying and pasting in the process of assembling the figure.This correction has no influence on the readers'understanding of the article.The original data of the figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.
基金the National Natural Science Foundation of China(No.52305385,U23A20541,52471131,52201057)the University Natural Science Research Project of Anhui Province(No.2022AH050316).
文摘The excellent strength-ductility combination of hetero-grained Mg alloys has been reported to stem from pronounced hetero-deformation induced(HDI)stress.This stress alters the internal stress state of various slip systems and triggers significant activity of non-basal slips.However,the HDI stress state of different slip systems,and the mechanisms underlying the selective activation between basal and non-basal slips remain unclear to date.This study develops a novel HDI stress partitioning framework that in-situ calculates the crystallographic parameters and geometrical information of each datapoint within grains,aiming to reveal the correlation between HDI stress partitioning on individual slip systems and localized deformation model in the case of bimodal-grained ZK60 alloy.The framework demonstrates that HDI stress shows a strong dependence on the density of geometrically necessary dislocations(GNDs)and slip-system-level grain size,while exhibiting a relatively weaker correlation with equivalent-circle size of the hetero-grains.Given the close relation between the stress partitioning and the physical parameters,the framework can accurately predict the single and multiple slip activity fields obtained from highresolution digital image correlation(HR-DIC).This holds even for slip systems with low Schmid factors,which are theoretically difficult to activate.Using this framework,it is found that HDI stress plays a more prominent role in diminishing the effective resolved shear stress(RSS)of basal<a>and prismatic<a>(i.e.,<a>component)dislocations,while having a negligible effect on pyramidal<c+a>slips.Benefiting from the increased ratio of RSS_(<c+a>)/RSS_(<a>),pyramidal<c+a>dislocations are extensively activated,leading to excellent strength-ductility combination in the bimodal-grained ZK60 alloy.
基金supported by grants from National Natural Sciences Foundation of China(NSFC,Grant Nos.81273514,91539126 and81302827)grants from Innovation Engineering of Chinese Academy of Agricultural Sciences(No.125161015000150013)
文摘AMP-activated protein kinase(AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes.Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
基金supported by the National Natural Science Foundation of China(31871003,31901053)the Hunan Provincial Natural Science Foundation of China(2018JJ1019,2019JJ50196)+3 种基金the Hu-Xiang Young Talent Program(2018RS3094)the Fundamental Research Funds for the Central Universities(3052018065)the Beijing Institute of Technology Research Fund Program for Young Scholars.It was also supported,in part,by grants from the National Science and Technology Major Project of China(2019ZX09301-132)Program for Changjiang Scholars and Innovative Research Team in University of China(IRT_15R13).
文摘RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field.
基金NNSF of China(62120106002,52103166)Jiangsu Province Policy Guidance Plan(BZ2019014)+1 种基金Natural Science Foundation of Jiangsu Province(BK20200710)‘Taishan scholars’construction special fund of Shandong Province.
文摘The current feasibility of nanocatalysts in clinical anti-infection therapy,especially for drug-resistant bacteria infection is extremely restrained because of the insufficient reactive oxygen generation.Herein,a novel Ag/Bi2MoO6(Ag/BMO)nanozyme optimized by charge separation engineering with photoactivated sustainable peroxidase-mimicking activities and NIR-II photodynamic performance was synthesized by solvothermal reaction and photoreduction.The Ag/BMO nanozyme held satisfactory bactericidal performance against methicillin-resistant Staphylococcus aureus(MRSA)(~99.9%).The excellent antibacterial performance of Ag/BMO NPs was ascribed to the corporation of peroxidase-like activity,NIR-II photodynamic behavior,and acidity-enhanced release of Ag^(+).As revealed by theoretical calculations,the introduction of Ag to BMO made it easier to separate photo-triggered electronhole pairs for ROS production.And the conduction and valence band potentials of Ag/BMO NPs were favorable for the reduction of O_(2) to·O_(2)^(−).Under 1064 nm laser irradiation,the electron transfer to BMO was beneficial to the reversible change of Mo^(5+)/Mo^(6+),further improving the peroxidase-like catalytic activity and NIR-II photodynamic performance based on the Russell mechanism.In vivo,the Ag/BMO NPs exhibited promising therapeutic effects towards MRSA-infected wounds.This study enriches the nanozyme research and proves that nanozymes can be rationally optimized by charge separation engineering strategy.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Science Foundation of China(52073060 and 61927805)+2 种基金National Major New Drug Innovation Science and Technology Major Project(2019ZX09301132)Guangdong Basic and Applied Basic Research Foundation(2021B1515120054,2019A1515110925)the Shenzhen Fundamental Research Program(JCYJ20190813152616459 and JCYJ20210324133214038).
文摘Diabetic wounds have become a major clinical problem that cannot be ignored.Gases,such as hydrogen sulphide(H_(2)S),have demonstrated value in inducing angiogenesis and accelerating wound healing,while their effective delivery is still challenging.Here,inspired by the continuous-independent hollow structure of bamboo,we propose novel gasotransmitter microfibres with septal H_(2)S bubbles using microfluidic spinning for diabetic wound healing.Benefitting from the exact control of microfluidics,gasotransmitter microfibres with different bubble sizes and morphologies could be generated successfully and continuously.Under the dual effects of drugs in the shell and gas in the core,the wound healing process could be accelerated.Furthermore,the controllable release of drugs could be achieved by adding responsive materials into the microfiber shell,which would promote continuous effects of contents on demand.Based on in vitro and in vivo stud-ies,we have proven that these gasotransmitter microfibres have a positive impact on inducing angiogenesis and promoting cell proliferation during wound healing.Thus,it is believed that the bamboo-inspired gasotransmitter microfibres will have important value in gasotransmitter research and clinical applications.
基金supported by the National Key Research&Development Program of China(2021YFA1201000,2021YFC2302400,2023YFC2606004)the Guangxi Science and Technology Development Program(AB20117001)+5 种基金the National Natural Science Foundation of China(82204263,32171394,32001008)the Fundamental Research Funds for the Central Universities(3332022055,2022CX01013)the China Postdoctoral Science Foundation(2022M720438)the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(20220484207)We knowledge the Beijing Institute of Technology Research Fund Program for Young Scholars(XSQD-6120220072)We thank the Biological and Medical Engineering Core Facilities,and Analysis&Testing Center,Beijing Institute of Technology for supporting experimental equipment,and staffs for valuable help with technical support.
文摘Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.
