Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this st...Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.展开更多
Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle e...Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle electrode system that protects against“electrical overload”by delivering medicinal hydrogel microspheres into the core regions.The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres,which are loaded into the threaded grooves,allowing for their stereoscopic release in the core regions.After the electrode is inserted,the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan,mitigating the electrical damage.Microspheres are designed to release alkylated vitamin B12 and vitamin E,providing antioxidant and cell protection effects upon in-situ activation,reducing reactive oxygen species(ROS)by 72.8%and cell death by 59.5%.In the model of peripheral nerve injury,the electrode system improves the overall antioxidant capacity by 78.5%and protects the surrounding cells.Additionally,it leads to an improved nerve conduction velocity ratio of 41.9%and sciatic nerve function index of 12.1%,indicating enhanced neuroregeneration.The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting“electrical overload”,potentially improving outcomes for tissue regeneration.展开更多
Objectives:Helicobacter pylori(H.pylori)infection is one of the most common infections,for which wellestablished medical treatments have been widely used,such as quadruple therapy and sequential therapy.However,some p...Objectives:Helicobacter pylori(H.pylori)infection is one of the most common infections,for which wellestablished medical treatments have been widely used,such as quadruple therapy and sequential therapy.However,some patients still suffer from the infection after multiple treatment.Traditional Chinese medicine(TCM)has been widely used to treat the H.pylori infection.Whether the combination of TCM therapy and antibiotic treatment is effective for these patients with repeated infection with H.pylori needs clinical observation.Methods:In this study,we reported two cases with refractory H.pylori infection.One is a 60-yearold Chinese woman with diagnoses of chronic atrophic gastritis and H.pylori infection,who has an uncomfortable feeling in her stomach with a poor appetite,depression and irregular defecations.The other is a Vietnamese woman aged 46,who had abdominal pain for 11 years.We treated the two patients with Chai Ping Decoction,combined with sequential therapy.Results:Both patients had pain relieved and H.pylori infection eradicated after treatment.Conclusion:TCM therapy may eliminate H.pylori infection well with sequential therapy.Based on the TCM theory,the patients who were diagnosed as spleen deficiency and dampness with abdominal uncomfortable symptoms could be well treated.展开更多
Correction:Advanced Fiber Materials,https://doi.org/10.1007/s42765-025-00513-0.The authors regret for the following corrections in the manuscript.The correction information is presented as following description.1.In t...Correction:Advanced Fiber Materials,https://doi.org/10.1007/s42765-025-00513-0.The authors regret for the following corrections in the manuscript.The correction information is presented as following description.1.In the published article(Fig.3c-m),the figures were corrected as the following Figure.2.In the Results and Discussion 2.2,the text was replaced with the following.展开更多
Precise regulation of intraosseous angiogenesis is essential for effectively repairing osteoporotic bone defects.However,the dual imbalance of redox homeostasis and the osteogenesis-angiogenesis coupling within the os...Precise regulation of intraosseous angiogenesis is essential for effectively repairing osteoporotic bone defects.However,the dual imbalance of redox homeostasis and the osteogenesis-angiogenesis coupling within the osteoporotic microenvironment poses significant challenges for bone regeneration.Here,we developed a poly-dopamine(PDA)-modified injectable short-fiber 3D scaffold(PSF@P-SLP)via short fibers homogenization to remodel the osteoporotic microenvironment and enhance bone healing.The scaffold surface was modified with PDA,which induced the in situ aggregation of short fibers into a porous 3D network,promoting directional cell migration and nutrient exchange.Moreover,parathyroid hormone[PTH(1-34)]loaded ROS-responsive thio-ether-phospholipid liposomes(P-SLP)were conjugated to the PDA coating through catechol groups,enabling sustained PTH release and efficient ROS scavenging via thioether oxidation.In vitro,PSF@P-SLP significantly reduced ROS levels,promoted osteogenic differentiation of mesenchymal stem cells,and enhanced the prolif-eration and migration of endothelial cells.In vivo,the scaffold facilitated both type H vessels formation and osteogenesis,accelerating the repair of osteoporotic bone defects.Collectively,this study presents a novel therapeutic strategy utilizing PTH(1-34)-loaded injectable short-fiber 3D scaffolds that modulate oxidative stress and restore osteogenesis-angiogenesis coupling within the osteoporotic niche,demonstrating strong translational potential for bone tissue engineering.展开更多
Abnormal mitochondrial division in microglia significantly impacts central nervous system(CNS)diseases.However,treating CNS diseases through microglial mitochondria presents several challenges:intracerebral de-livery ...Abnormal mitochondrial division in microglia significantly impacts central nervous system(CNS)diseases.However,treating CNS diseases through microglial mitochondria presents several challenges:intracerebral de-livery of drugs,microglial targeting,and mitochondrial regulation.Herein,a novel three-stage sequential tar-geted nasal drops delivery system that achieves precise drug delivery to the core of brain lesions through noninvasive nasal delivery,targeting microglia,and regulating mitochondria were developed.Firstly,dehy-droepiandrosterone(DHEA),identified from clinical data and transcriptomic analyses as a key neurosteroid regulating mitochondrial fission,was selected.Secondly,surface-positively charged hydrogel microspheres were prepared to adhere to the nasal mucosa,thereby avoiding rapid clearance and achieving the first stage of nasal mucosa targeting.Subsequently,targeted liposomes carrying cytotoxic T lymphocyte-associated protein-4 were constructed and modified into microspheres,which released liposomes through the nasal cavity to enter the brain and bound to the activated microglial surface receptors CD80/86 accomplishing the second stage of cell targeting.In the third stage,the system released DHEA in response to the microenvironment,precisely regulating dynamin-related protein 1 involved in mitochondrial membrane remodeling,which inhibited abnormal mito-chondrial division,stabilized mitochondrial morphology and function,inhibited microglial activation.This study demonstrated that three-stage sequential nasal drops efficiently traversed the nose-to-brain pathway via nasal mucosa in both murine(n=200)and porcine(n=16)models,while significantly ameliorating anesthesia/surgery-induced cognitive dysfunction in mice.Therefore,the three-stage sequential nasal drip is a promising method for the treatment of central nervous system diseases.展开更多
Neural cell senescence hinders spinal cord nerve function recovery,and existing therapies that target senescent cell clearance haven’t effectively addressed cellular senescence.In this study,injectable short fibers t...Neural cell senescence hinders spinal cord nerve function recovery,and existing therapies that target senescent cell clearance haven’t effectively addressed cellular senescence.In this study,injectable short fibers that accurately maintain genome homeostasis in real time were developed,which for the first time reversed neural cell senescence by blocking the excessive intervention of cell inspection points.First,the oxidization-sensitive hybrid liposomes were prepared by combining Bakuchiol(BAK),a natural plant extract with the ability of DNA protection,with the oxidization-sensitive phospholipid S-PC.Subsequently,the short fibers regulating the cell inspection points(ISN@n-BAK)were constructed by further complexing the oxidation-sensitive hybrid liposomes with short fibers throughπ–πconjugation and catechol groups mussel-stimulated polydopamine(PDA).In vitro experiments demonstrated that ISN@n-BAK promotes neural stem cell differentiation into neurons and has anti-aging effects across various aging stages.In vivo,ISN@n-BAK responded to excessive ROS by triggering oxidation-sensitive liposomes to release BAK,protecting against DNA damage,suppressing aging-related gene expression in Cdkn2a and Cdkn2c and inhibiting inspection point restrictions.Bioinformatics showed that ISN@n-BAK reversed neural cell senescence and aided spinal cord nerve regeneration by activating the endogenous cell cycle,downregulating the PI3K-Akt pathway and upregulating the Rap1 pathway.This study introduces a novel therapeutic approach using short fibers that inhibit inspection points intervention to rejuvenate injured spinal cords.展开更多
This study investigated the factors contributing to intravenous admixture preparation errors(IAPEs)within Pharmacy Intravenous Admixture Services(PIVAS).A retrospective analysis was conducted on IAPEs documented in th...This study investigated the factors contributing to intravenous admixture preparation errors(IAPEs)within Pharmacy Intravenous Admixture Services(PIVAS).A retrospective analysis was conducted on IAPEs documented in the PIVAS unit of a large multi-specialty hospital in China,which houses over 2000 beds,covering the period from January 1,2015 to December 31,2022.Drug preparation records were examined using a generalized linear mixed model(GLMM)to identify both univariate and multivariate factors associated with IAPE occurrences.A total of 824 IAPE cases were recorded during the study period,yielding an overall error rate of 0.018%.Univariate analysis identified drug categories(general drugs,anti-infective drugs,and antineoplastic drugs),preparation time(workdays),and years of work experience as significant determinants(P<0.05).Multivariate analysis further confirmed that drug categories(general and antineoplastic drugs),preparation time(workdays),and work experience remained statistically significant predictors of IAPE incidence(P<0.05).IAPEs in PIVAS were influenced by multiple factors,predominantly those related to personnel and drug characteristics.Targeted interventions,informed by multivariate analysis,are essential to mitigating these errors and enhancing medication safety.展开更多
Solar-driven interfacial desalination(SID)offers a sustainable route for freshwater production,yet its long-term performance is compromised by salt crystallization and microbial fouling under complex marine conditions...Solar-driven interfacial desalination(SID)offers a sustainable route for freshwater production,yet its long-term performance is compromised by salt crystallization and microbial fouling under complex marine conditions.Zwitterionic polymers offer promising nonfouling capabilities,but current zwitterionic hydrogel-based solar evaporators(HSEs)suffer from inadequate hydration and salt vulnerability.Inspired by the natural marine environmental adaptive characteristics of saltwater fish,we report a superhydrated zwitterionic poly(trimethylamine N-oxide,PTMAO)/polyacrylamide(PAAm)/polypyrrole(PPy)hydrogel(PTAP)with dedicated water channels for efficient,durable,and nonfouling SID.The directly linked N⁺and O⁻groups in PTMAO establish a robust hydration shell that facilitates rapid water transport while resisting salt and microbial adhesion.Integrated PAAm and PPy networks enhance mechanical strength and photothermal conversion.PTAP achieves a high evaporation rate of 2.35 kg m^(−2)h^(−1)under 1 kW m^(–2)in 10 wt%NaCl solution,maintaining stable operation over 100 h without salt accumulation.Furthermore,PTAP effectively resists various foulants including proteins,bacterial,and algal adhesion.Molecular dynamics simulations reveal that the exceptional hydration capacity supports its nonfouling properties.This work advances the development of nonfouling HSEs for sustainable solar desalination in real-world marine environments.展开更多
CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in bi...CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.展开更多
Cellular respiration can provide energy for wound healing.However,some of retarded healing processes in local hyperglycemic environment suffer from a decrease in cellular adaptation to oxygen,thus reducing in situ oxi...Cellular respiration can provide energy for wound healing.However,some of retarded healing processes in local hyperglycemic environment suffer from a decrease in cellular adaptation to oxygen,thus reducing in situ oxidative metabolism.Herein,a three-dimensional(3D)extracellular matrix(ECM)bionic short fibrous sponge was prepared for chronic diabetic wound healing and effectively regulated cellular respiration by enhancing cellular adaptation to oxygen and remolding the local tissue microenvironment.The 3D bionic sponge scaffold exhibited good cell adhesion,biocompatibility,bioactivity,and,most importantly,aggregated oxygen atoms on the graphene oxide(GO)surface.In an in vitro assay,the oxygen atom-concentrating short fibrous sponge activated monocyte chemoattractant protein-1(MCP-1),induced the expression of vascular endothelial growth factor(VEGF),and effectively promoted angiogenesis in a hyperglycemic environment.The sponge was also applied to diabetic wounds in vivo to verify its roles in the promotion of angiogenesis and collagen deposition.These experiments confirmed the synergistic effect of GO with adipose-derived stem cells(ADSCs),which could further promote diabetic wound healing.Therefore,oxygen atom-concentrating short fibrous sponges that regulate cellular respiration provide a new idea for the repair of poorly healing wounds by improving oxidative metabolism and have importantclinical significance.展开更多
The comparison between traditional Chinese medicine Jinzhen oral liquid(JZOL)and West-ern medicine in treating children with acute bronchitis(AB)showed encouraging outcomes.This trial eval-uated the efficacy and safet...The comparison between traditional Chinese medicine Jinzhen oral liquid(JZOL)and West-ern medicine in treating children with acute bronchitis(AB)showed encouraging outcomes.This trial eval-uated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB.480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days.The primary outcome was time-to-cough resolution.The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day.This random-ized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discom-fort symptoms.Combined with clinical trials,the mechanism of JZOL against AB was uncovered by network target analysis,it was found that the pathways in TRP channels like IL-1b/IL1R/TRPV1/TRPA1,NGF/TrkA/TRPV1/TRPA1,and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles.Animal ex-periments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.展开更多
There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel m...There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.展开更多
In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this wor...In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.展开更多
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(81930051 and 22105127)+1 种基金the Shanghai Municipal Health Commission(2022XD055 and 202140128)the Shanghai Jiao Tong University School of Medicine PhD Cultivation Fund for Science and Innovation(24KCPYYB005).
文摘Excessive uptake of purine and glucose can lead to hyperglycemia and hyperuricemia,mediated by specific intestinal transport proteins.Currently,there is a deficiency in targeted regulation of these proteins.In this study,we introduce an oral approach for targeted modulation using electrospun core–shell short-fibers that settle on the intestinal mucosa.These fibers,designed for the controlled in situ release of phlorizin—a multi-transporter inhibitor—are crafted through a refined electrospinning-homogenizing process using polylactic acid and gelatin.Phlorizin is conjugated via a phenyl borate ester bond.Furthermore,a calcium alginate shell ensures intestinal disintegration triggered by pH changes.These fibers adhere to the mucosa due to their unique structure,and phlorizin is released in situ post-ingestion through glucose-sensitive cleavage of the phenyl borate ester bond,enabling dual-target inhibition of intestinal transporter proteins.Both in vitro and in vivo studies confirm that the short-fibers possess intestine-settling and glucose-responsive properties,facilitating precise control over transport proteins.Using models of hyperuricemia and diabetes in mice,treatment with short-fibers results in reduc-tions of 49.6%in blood uric acid and 17.8%in glucose levels,respectively.Additionally,16S rRNA sequencing indicates an improved intestinal flora composition.In conclusion,we have developed an innovative oral strategy for the prevention of hyperglycemia and hyperuricemia.
基金supported by various grants,including the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China General Program(81930051,82205244)China Postdoctoral Science Foundation(2022M712135).
文摘Bioelectrical stimulation is a powerful technique used to promote tissue regeneration,but it can be hindered by an“electrical overload”phenomenon in the core region of stimulation.We develop a threaded microneedle electrode system that protects against“electrical overload”by delivering medicinal hydrogel microspheres into the core regions.The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres,which are loaded into the threaded grooves,allowing for their stereoscopic release in the core regions.After the electrode is inserted,the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan,mitigating the electrical damage.Microspheres are designed to release alkylated vitamin B12 and vitamin E,providing antioxidant and cell protection effects upon in-situ activation,reducing reactive oxygen species(ROS)by 72.8%and cell death by 59.5%.In the model of peripheral nerve injury,the electrode system improves the overall antioxidant capacity by 78.5%and protects the surrounding cells.Additionally,it leads to an improved nerve conduction velocity ratio of 41.9%and sciatic nerve function index of 12.1%,indicating enhanced neuroregeneration.The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting“electrical overload”,potentially improving outcomes for tissue regeneration.
基金This case report was supported by the National Natural Science Foundation of China(No.81774146)Beijing Nova Program(No.xxjh2015A093 and No.Z1511000003150125).
文摘Objectives:Helicobacter pylori(H.pylori)infection is one of the most common infections,for which wellestablished medical treatments have been widely used,such as quadruple therapy and sequential therapy.However,some patients still suffer from the infection after multiple treatment.Traditional Chinese medicine(TCM)has been widely used to treat the H.pylori infection.Whether the combination of TCM therapy and antibiotic treatment is effective for these patients with repeated infection with H.pylori needs clinical observation.Methods:In this study,we reported two cases with refractory H.pylori infection.One is a 60-yearold Chinese woman with diagnoses of chronic atrophic gastritis and H.pylori infection,who has an uncomfortable feeling in her stomach with a poor appetite,depression and irregular defecations.The other is a Vietnamese woman aged 46,who had abdominal pain for 11 years.We treated the two patients with Chai Ping Decoction,combined with sequential therapy.Results:Both patients had pain relieved and H.pylori infection eradicated after treatment.Conclusion:TCM therapy may eliminate H.pylori infection well with sequential therapy.Based on the TCM theory,the patients who were diagnosed as spleen deficiency and dampness with abdominal uncomfortable symptoms could be well treated.
文摘Correction:Advanced Fiber Materials,https://doi.org/10.1007/s42765-025-00513-0.The authors regret for the following corrections in the manuscript.The correction information is presented as following description.1.In the published article(Fig.3c-m),the figures were corrected as the following Figure.2.In the Results and Discussion 2.2,the text was replaced with the following.
基金supported by the National Natural Science Foundation of China(W2411085)Zhejiang Provincial Natural Science Foundation of China(LBZ24H060001)+5 种基金Undergraduate Training Program for Innovation and Entrepreneurship(202410285263Y)Health Talents Projects of Suzhou(GSWS2021023)Innovation and Entrepreneurship Training Program(202410285263Y)Suzhou Key R&D Program(Medical and Health Innovation)Project(SYW2025042)Suzhou‘National Mentor’Program for Young Core Healthcare Talents(Gngg2021008)Natural Science Foundation of Shandong Province(ZR2024MH091)。
文摘Precise regulation of intraosseous angiogenesis is essential for effectively repairing osteoporotic bone defects.However,the dual imbalance of redox homeostasis and the osteogenesis-angiogenesis coupling within the osteoporotic microenvironment poses significant challenges for bone regeneration.Here,we developed a poly-dopamine(PDA)-modified injectable short-fiber 3D scaffold(PSF@P-SLP)via short fibers homogenization to remodel the osteoporotic microenvironment and enhance bone healing.The scaffold surface was modified with PDA,which induced the in situ aggregation of short fibers into a porous 3D network,promoting directional cell migration and nutrient exchange.Moreover,parathyroid hormone[PTH(1-34)]loaded ROS-responsive thio-ether-phospholipid liposomes(P-SLP)were conjugated to the PDA coating through catechol groups,enabling sustained PTH release and efficient ROS scavenging via thioether oxidation.In vitro,PSF@P-SLP significantly reduced ROS levels,promoted osteogenic differentiation of mesenchymal stem cells,and enhanced the prolif-eration and migration of endothelial cells.In vivo,the scaffold facilitated both type H vessels formation and osteogenesis,accelerating the repair of osteoporotic bone defects.Collectively,this study presents a novel therapeutic strategy utilizing PTH(1-34)-loaded injectable short-fiber 3D scaffolds that modulate oxidative stress and restore osteogenesis-angiogenesis coupling within the osteoporotic niche,demonstrating strong translational potential for bone tissue engineering.
基金supported by the National Natural Science Foundation(52273133,52303190,82271223,82271220,82301369)Shanghai Municipal Health and Family Planning Commission(2022XD055)+3 种基金Shanghai Nat-ural Science Foundation(25ZR1402458)Shanghai Municipal Health Commission(20244Z0007)Shanghai Municipal Committee of Science and Technology(23XD1422900)Hongkou district Health Commission(Hongwei2401-03,HKLCFC202405,HKLCYQ2024-02,HKLCYQ2024-04).
文摘Abnormal mitochondrial division in microglia significantly impacts central nervous system(CNS)diseases.However,treating CNS diseases through microglial mitochondria presents several challenges:intracerebral de-livery of drugs,microglial targeting,and mitochondrial regulation.Herein,a novel three-stage sequential tar-geted nasal drops delivery system that achieves precise drug delivery to the core of brain lesions through noninvasive nasal delivery,targeting microglia,and regulating mitochondria were developed.Firstly,dehy-droepiandrosterone(DHEA),identified from clinical data and transcriptomic analyses as a key neurosteroid regulating mitochondrial fission,was selected.Secondly,surface-positively charged hydrogel microspheres were prepared to adhere to the nasal mucosa,thereby avoiding rapid clearance and achieving the first stage of nasal mucosa targeting.Subsequently,targeted liposomes carrying cytotoxic T lymphocyte-associated protein-4 were constructed and modified into microspheres,which released liposomes through the nasal cavity to enter the brain and bound to the activated microglial surface receptors CD80/86 accomplishing the second stage of cell targeting.In the third stage,the system released DHEA in response to the microenvironment,precisely regulating dynamin-related protein 1 involved in mitochondrial membrane remodeling,which inhibited abnormal mito-chondrial division,stabilized mitochondrial morphology and function,inhibited microglial activation.This study demonstrated that three-stage sequential nasal drops efficiently traversed the nose-to-brain pathway via nasal mucosa in both murine(n=200)and porcine(n=16)models,while significantly ameliorating anesthesia/surgery-induced cognitive dysfunction in mice.Therefore,the three-stage sequential nasal drip is a promising method for the treatment of central nervous system diseases.
基金supported by the National Nature Science Foundation of China(32000937,81871549 and 81971312)Science and Technology Commission of Shanghai Municipality(23015820800)Shanghai Municipal Health Commission(20204Y0355).
文摘Neural cell senescence hinders spinal cord nerve function recovery,and existing therapies that target senescent cell clearance haven’t effectively addressed cellular senescence.In this study,injectable short fibers that accurately maintain genome homeostasis in real time were developed,which for the first time reversed neural cell senescence by blocking the excessive intervention of cell inspection points.First,the oxidization-sensitive hybrid liposomes were prepared by combining Bakuchiol(BAK),a natural plant extract with the ability of DNA protection,with the oxidization-sensitive phospholipid S-PC.Subsequently,the short fibers regulating the cell inspection points(ISN@n-BAK)were constructed by further complexing the oxidation-sensitive hybrid liposomes with short fibers throughπ–πconjugation and catechol groups mussel-stimulated polydopamine(PDA).In vitro experiments demonstrated that ISN@n-BAK promotes neural stem cell differentiation into neurons and has anti-aging effects across various aging stages.In vivo,ISN@n-BAK responded to excessive ROS by triggering oxidation-sensitive liposomes to release BAK,protecting against DNA damage,suppressing aging-related gene expression in Cdkn2a and Cdkn2c and inhibiting inspection point restrictions.Bioinformatics showed that ISN@n-BAK reversed neural cell senescence and aided spinal cord nerve regeneration by activating the endogenous cell cycle,downregulating the PI3K-Akt pathway and upregulating the Rap1 pathway.This study introduces a novel therapeutic approach using short fibers that inhibit inspection points intervention to rejuvenate injured spinal cords.
基金The National Natural Science Foundation of China(Grant No.72474013)the Beijing Health Technology Promotion Project(Grant No.BHTPP2024007)。
文摘This study investigated the factors contributing to intravenous admixture preparation errors(IAPEs)within Pharmacy Intravenous Admixture Services(PIVAS).A retrospective analysis was conducted on IAPEs documented in the PIVAS unit of a large multi-specialty hospital in China,which houses over 2000 beds,covering the period from January 1,2015 to December 31,2022.Drug preparation records were examined using a generalized linear mixed model(GLMM)to identify both univariate and multivariate factors associated with IAPE occurrences.A total of 824 IAPE cases were recorded during the study period,yielding an overall error rate of 0.018%.Univariate analysis identified drug categories(general drugs,anti-infective drugs,and antineoplastic drugs),preparation time(workdays),and years of work experience as significant determinants(P<0.05).Multivariate analysis further confirmed that drug categories(general and antineoplastic drugs),preparation time(workdays),and work experience remained statistically significant predictors of IAPE incidence(P<0.05).IAPEs in PIVAS were influenced by multiple factors,predominantly those related to personnel and drug characteristics.Targeted interventions,informed by multivariate analysis,are essential to mitigating these errors and enhancing medication safety.
基金supported by National Natural Science Foundation of China(22209036,U23A20119)Hebei Provincial Natural Science Foundation,Excellent Youth Project(E2023202069)+1 种基金National Key R&D Program of China(2024YFF0506000,2024YFB4609100)Fundamental Research Foundation from Hebei University of Technology(424132016,282021485).
文摘Solar-driven interfacial desalination(SID)offers a sustainable route for freshwater production,yet its long-term performance is compromised by salt crystallization and microbial fouling under complex marine conditions.Zwitterionic polymers offer promising nonfouling capabilities,but current zwitterionic hydrogel-based solar evaporators(HSEs)suffer from inadequate hydration and salt vulnerability.Inspired by the natural marine environmental adaptive characteristics of saltwater fish,we report a superhydrated zwitterionic poly(trimethylamine N-oxide,PTMAO)/polyacrylamide(PAAm)/polypyrrole(PPy)hydrogel(PTAP)with dedicated water channels for efficient,durable,and nonfouling SID.The directly linked N⁺and O⁻groups in PTMAO establish a robust hydration shell that facilitates rapid water transport while resisting salt and microbial adhesion.Integrated PAAm and PPy networks enhance mechanical strength and photothermal conversion.PTAP achieves a high evaporation rate of 2.35 kg m^(−2)h^(−1)under 1 kW m^(–2)in 10 wt%NaCl solution,maintaining stable operation over 100 h without salt accumulation.Furthermore,PTAP effectively resists various foulants including proteins,bacterial,and algal adhesion.Molecular dynamics simulations reveal that the exceptional hydration capacity supports its nonfouling properties.This work advances the development of nonfouling HSEs for sustainable solar desalination in real-world marine environments.
基金This work was supported by the National Natural Science Foundation of China(91949203,22105127)Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT320001)+1 种基金Shanghai Pujiang Program(21PJD045)Clinical Research Project of Health Industry of Shanghai(202140128)。
文摘CRISPR/Cas9 is a revolutionary genome editing technology with the tremendous advantages such as precisely targeting/shearing ability,low cost and convenient operation,becoming an efficient and indispensable tool in biological research.As a disruptive technique,CRISPR/Cas9 genome editing has a great potential to realize a future breakthrough in the clinical bone and cartilage repairing as well.This review highlights the research status of CRISPR/Cas9 system in bone and cartilage repair,illustrates its mechanism for promoting osteogenesis and chondrogenesis,and explores the development tendency of CRISPR/Cas9 in bone and cartilage repair to overcome the current limitations.
基金support of the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China General Program(32000937)+2 种基金the Shanghai Municipal Health Commission(20204Y0354)the Youth Innovation Technology Project of Higher School in Shandong Province(20190919)the China Postdoctoral Science Foundation(2022T150426).
文摘Cellular respiration can provide energy for wound healing.However,some of retarded healing processes in local hyperglycemic environment suffer from a decrease in cellular adaptation to oxygen,thus reducing in situ oxidative metabolism.Herein,a three-dimensional(3D)extracellular matrix(ECM)bionic short fibrous sponge was prepared for chronic diabetic wound healing and effectively regulated cellular respiration by enhancing cellular adaptation to oxygen and remolding the local tissue microenvironment.The 3D bionic sponge scaffold exhibited good cell adhesion,biocompatibility,bioactivity,and,most importantly,aggregated oxygen atoms on the graphene oxide(GO)surface.In an in vitro assay,the oxygen atom-concentrating short fibrous sponge activated monocyte chemoattractant protein-1(MCP-1),induced the expression of vascular endothelial growth factor(VEGF),and effectively promoted angiogenesis in a hyperglycemic environment.The sponge was also applied to diabetic wounds in vivo to verify its roles in the promotion of angiogenesis and collagen deposition.These experiments confirmed the synergistic effect of GO with adipose-derived stem cells(ADSCs),which could further promote diabetic wound healing.Therefore,oxygen atom-concentrating short fibrous sponges that regulate cellular respiration provide a new idea for the repair of poorly healing wounds by improving oxidative metabolism and have importantclinical significance.
基金the National Key Research and Development Program of the Ministry of Science and Technology of China in 2018,“Research on Modernization of TCM”project,“Demonstration Study on Evidence-based Evaluation and Effect Mechanism of Ten Chinese Patent Medicines and Classic Famous Prescriptions in the Treatment of Major Diseases after marketed”(2018YFC1707400 and 2018YFC17074101,China)National Administration of Traditional Chinese Medicine(GZY-KJS-2024-03,China).
文摘The comparison between traditional Chinese medicine Jinzhen oral liquid(JZOL)and West-ern medicine in treating children with acute bronchitis(AB)showed encouraging outcomes.This trial eval-uated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB.480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days.The primary outcome was time-to-cough resolution.The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day.This random-ized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discom-fort symptoms.Combined with clinical trials,the mechanism of JZOL against AB was uncovered by network target analysis,it was found that the pathways in TRP channels like IL-1b/IL1R/TRPV1/TRPA1,NGF/TrkA/TRPV1/TRPA1,and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles.Animal ex-periments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.
基金funded by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(52103174,52273133,and 82202686)+4 种基金the Shanghai Pujiang Program(2021PJD044)the Shanghai Municipal Heaith and Family Planning Commission(2022XD055)the China Postdoctoral Science Foundation(2022T150420 and 2022M712100)the Shanghai Jiading District Health Committee(2022-QN-05)the GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine.
文摘There are stillchallenges in applying drug nanocarriers for in situ sustained macrophage targeting and regulation,due to the rapid clearance of nanocarriers and burst drug release invivo.Herein,a nanomicellehydrogel microsphere,characterized by its macrophage-targeted nanosized secondary structure that allows it to accurately bind to M1 macrophages through active endocytosis,is employed for in situ sustained macrophage targeting and regulation,and addresses the insufficient osteoarthritis therapeutic efficacy caused by rapid clearance of drug nanocarriers.The 3-dimensional structure of a microsphere can prevent the rapid escape and clearance of a nanomicelle,thus keeping it in joints,while the ligand-guided secondary structure can carry drugs to accurately target and enter M1 macrophages,and release drugs via the transition from hydrophobicity to hydrophilicity of nanomicelles under inflammatory stimulation inside the macrophages.
基金the National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(91949203 and 22105127)+4 种基金Shanghai Municipal Health Commission(202140128)Shanghai Pujiang Program(21PJD045)Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT320001)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20171906)GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine.
文摘In situ-activated therapy is a decent option for localized diseases with improved efficacies and reduced side effects,which is heavily dependent on the local conversion or activation of bioinert components.In this work,we applied a phospholipid-mimic artemisinin prodrug(ARP)for preparing an injectable nano/microsphere to first realize an in situ-activated therapy of the typical systemically administrated artemisinin-based medicines for a localized rheumatoid arthritis(RA)lesion.ARP is simultaneously an alternative of phospholipids and an enzyme-independent activable prodrug,which can formulate“drug-in-drug”co-delivery liposomes with cargo of partner drugs(e.g.,methotrexate).To further stabilize ARP/methotrexate“drug-in-drug”liposomes(MTX/ARPL)for a long-term intra-articular retention,a liposome-embedded hydrogel nano/microsphere(MTX/ARPL@MS)was prepared.After the local injection,the MTX/ARPL could be slowly released because of imine hydrolysis and targeted to RA synovial macrophages and fibroblasts simultaneously.ARP assembly is relatively stable before cellular internalization but disassembled ARP after lysosomal escape and converted into dihydroartemisinin rapidly to realize the effective in situ activation.Taken together,phospholipid-mimic ARP was applied for the firstly localized in situ-activated RA therapy of artemisinin-based drugs,which also provided a brand-new phospholipid-mimic strategy for other systemically administrated prodrugs to realize a remodeling therapeutic schedule for localized diseases.
