Synthetic musks are used as additives in many household products.After absorption into the human body,they accumulate and their concentrations in human milk reflect both the mother and her infant＇s exposure level.Con...Synthetic musks are used as additives in many household products.After absorption into the human body,they accumulate and their concentrations in human milk reflect both the mother and her infant＇s exposure level.Concentrations of four synthetic musks,musk xylene（1-tert-butyl-2,6-dimethyl-2,4,6-trinitrobenzene,MX）,musk ketone（4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone,MK）,1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran（HHCB） and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4tetrahydronaphthalene（AHTN）,were determined in human milk samples collected from Shanghai,Wuxi,and Shaoxing in Eastern China.The four synthetic musks were found in most samples analyzed,with HHCB the dominant component followed by MX.The median（mean） values for HHCB,AHTN,MX and MK concentrations were 63（82）,5（12）,17（24） and 4（9） ng/g lipid weight,respectively.These data suggested the total synthetic musk contamination was low,and the distribution percentage was HHCB 〉 MX 〉 AHTN ≈ MK.The relative high ratio of nitro to polycylic musk indicated that nitro musks were still widely used.The musk concentrations in these cities were not significantly different from each other（p 〉 0.05）.Principal components score plots were obtained,which showed similar exposure sources.The amount of total synthetic musks in human milk were not associated with mother＇s age,although HHCB was significantly correlated with AHTN（p 〈 0.05）.Daily ingestion of HHCB,AHTN,MX and MK for infants from human milk were estimated as（2526 ± 2926）,（370 ± 524）,（7391 ± 832）,and（277 ± 462） ng/day,respectively.Those doses were 1-2 orders of magnitude below the provisional tolerable daily intakes.展开更多
Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Her...Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.展开更多
Since starch digestion in the small intestine provides more energy than digestion in the rumen of ru-minants,reducing dietary rumen degradable starch(RDS)content is beneficial for improving energy utilization of starc...Since starch digestion in the small intestine provides more energy than digestion in the rumen of ru-minants,reducing dietary rumen degradable starch(RDS)content is beneficial for improving energy utilization of starch in ruminants.The present study tested whether the reduction of rumen degradable starch by restricting dietary corn processing for growing goats could improve growth performance,and further investigated the possible underlying mechanism.In this study,twenty-four 12-wk-old goats were selected and randomly allocated to receive either a high RDS diet(HRDS,crushed corn-based concen-trate,the mean of particle sizes of corn grain=1.64 mm,n=12)or a low RDS diet(LRDS,non-processed corn-based concentrate,the mean of particle sizes of corn grain>8 mm,n=12).Growth performance,carcass traits,plasma biochemical indices,gene expression of glucose and amino acid transporters,and protein expression of the AMPK-mTOR pathway were measured.Compared to the HRDS,LRDS tended to increase the average daily gain(ADG,P=0.054)and decreased the feed-to-gain ratio(F/G,P<0.05).Furthermore,LRDS increased the net lean tissue rate(P<0.01),protein content(P<0.05)and total free amino acids(P<0.05)in the biceps femoris(BF)muscle of goats.LRDS increased the glucose concen-tration(P<0.01),but reduced total amino acid concentration(P<0.05)and tended to reduce blood urea nitrogen(BUN)concentration(P=0.062)in plasma of goats.The mRNA expression of insulin receptors(INSR),glucose transporter 4(GLUT4),L-type amino acid transporter 1(LAT1)and 4F2 heavy chain(4F2hc)in BF muscle,and sodium-glucose cotransporters 1(SGLT1)and glucose transporter 2(GLUT2)in the small intestine were significantly increased(P<0.05)in LRDS goats.LRDS also led to marked activation of p70-S6 kinase(S6K)(P<0.05),but lower activation of AMP-activated protein kinase(AMPK)(P<0.05)and eukaryotic initiation factor 2a(P<0.01).Our findings suggested that reducing the content of dietary RDS enhanced postruminal starch digestion and increased plasma glucose,thereby improving amino acid utilization and promoting protein synthesis in the skeletal muscle of goats via the AMPK-mTOR pathway.These changes may contribute to improvement in growth performance and carcass traits in LRDS goats.展开更多
Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which ar...Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.展开更多
Chromatic optical lenses have promising applications in three-dimensional imaging, which allows fast spectral tomography without mechanical moving parts. The scanning range of current chromatic optical lenses is limit...Chromatic optical lenses have promising applications in three-dimensional imaging, which allows fast spectral tomography without mechanical moving parts. The scanning range of current chromatic optical lenses is limited by their dispersion ability. The recent development in metasurfaces provides ideal blocks for optical wavefront manipulation and dispersion engineering of artificial materials at sub-wavelength scales. Hyper-dispersive metalenses can be realized by utilizing dispersive meta-atoms, which have enhanced dispersion compared to regular diffractive lenses. This is critical for increasing the imaging depth of fast spectral tomography. In this work, a hyper-dispersive metalens is realized with a chromatic dispersion 1.76 times greater than that of a regular diffractive metalens in the THz frequency range of 2.40–2.61 THz by simultaneously controlling the frequencydependent phase, group delay(GD), and GD dispersion of the metalens. This approach can also be extended to other optical spectra and improve the performance of spectral tomography.展开更多
Extracellular vesicles(EVs)are nanoscale substances produced by most cells,which were not fully understood in the early years.However,with the development of advanced techniques,researchers have discovered that EVs pl...Extracellular vesicles(EVs)are nanoscale substances produced by most cells,which were not fully understood in the early years.However,with the development of advanced techniques,researchers have discovered that EVs play an essential role in information exchange and signal transduction between cells.Nowadays,EVs are being used,modified,and developed as a natural drug carrier in various medical fields because of their high biocompatibility and natural affinity with the source body.Many studies have shown that multiple sources of EVs have been modified and utilized in cancer therapy to improve patients’treatment windows and effectively prolong patient survival.In this paper,we review the advances in the treatment of cancer based on EVs.We summarize the types of EVs loading therapy,the modes of drug loading and the latest therapeutic applications of multiple modes combined with EVs in cancer treatment.We conclude with a discussion of the current status,challenges,and prospects of EVs as a tool for tumor therapy.展开更多
Superoscillation metalenses have demonstrated promising prospects in breaking the theoretical diffraction limitations on the resolution of optical devices and systems. However, most reported superoscillation metalense...Superoscillation metalenses have demonstrated promising prospects in breaking the theoretical diffraction limitations on the resolution of optical devices and systems. However, most reported superoscillation metalenses have a very small field of view of several tenths of a degree, which greatly limits their applications in imaging and microscopy. Therefore, it is of critical importance to achieve absolute high resolution by increasing the numerical apertures(NAs) of optical devices and systems. Unfortunately, similar to the case in traditional optics, it is challenging to realize a large field of view at high NA, especially in the superoscillation regime. To date, no attempt has been made to achieve flat-field focusing in the superoscillation regime, to our knowledge. Here, we demonstrate a high-NA superoscillation metalens with an entrance aperture stop, which is optimized for superoscillation performance with a comparatively large field of view. The proposed flat-field superoscillation metalens has an effective NA as large as 0.89 and achieves superoscillation focusing within a field of view of 9°. Such a superoscillation metalens may offer a promising way toward superoscillation imaging and fast-scanning label-free farfield superoscillation microscopy.展开更多
Esophageal cancer(EC)is characterized by high morbidity and mortality,and chemotherapy has become an indispensable means for comprehensive treatment.However,due to the limitation of the effective in vitro disease mode...Esophageal cancer(EC)is characterized by high morbidity and mortality,and chemotherapy has become an indispensable means for comprehensive treatment.However,due to the limitation of the effective in vitro disease model,the development of chemotherapeutic agents still faces great challenges.In this paper,we present a novel tumor spheroid on a chip platform based on inverse opal hydrogel scaffolds to screen chemotherapeutic agents for EC treatment.With the microfluidic emulsion approach,the inverse opal hydrogel scaffolds were generated with tunable and organized pores,which could provide spatial confinement for cell growth.Thus,the suspended KYSE-70 cells could successfully form uniform cell spheroids on the inverse opal hydrogel scaffolds.It was demonstrated that the tumor cell spheroids could recapitulate 3D growth patterns in vivo and exhibited higher sensitivity to the chemotherapy agents compared with monolayer cells.Besides,by employing the scaffolds into a microfluidics to construct esophageal tumor on a chip,the device could realize high-throughput tumor cell spheroids generation and drug screening,indicating its promising role in chemotherapy drug development.展开更多
Exosomes are nanoscale membrane-enclosed extracellular vesicles secreted by various cells,which have enormous potential as disease biomarkers for clinical application.However,the isolation and detection of exosomes re...Exosomes are nanoscale membrane-enclosed extracellular vesicles secreted by various cells,which have enormous potential as disease biomarkers for clinical application.However,the isolation and detection of exosomes remain enormous challenges,which limits their further application.Herein,inspired by immunomagnetic beads,a magnetic nanoparticle conjugated aptamer was repurposed for the effective capture and detection of exosomes.The magnetic nanoparticles,composed of Fe 3 O 4 synthesized by the hydrothermal method as the core and coupled with gold nanoparticles(Fe 3 O 4@Au),provide a large specific surface area,making the resulting composite material an effective platform for exosome capture.Furthermore,the elution of captured exosomes with 1.0 M NaCl made downstream analysis of exosomes possible.The preliminary clinical application value of the composite in exosome analyses of serum from healthy individuals and patients with Alzheimer’s disease(AD)has also been verified,which could provide a promising platform for biomedical and clinical diagnosis.展开更多
Type 1 diabetes(T1D)is an autoimmune deficiency disease characterized by elevated blood sugar levels and insulin resistance,leading to various adverse health effects and complications,such as diabetic cardiomyopathy a...Type 1 diabetes(T1D)is an autoimmune deficiency disease characterized by elevated blood sugar levels and insulin resistance,leading to various adverse health effects and complications,such as diabetic cardiomyopathy and diabetic ketoacidosis.Currently,T1D is primarily treated through organoid transplantation and extracorporeal insulin injection.However,the clinical utility of these treatments is limited by increased systemic immunosuppression due to graft donor shortages and the side effects associated with exogenous insulin therapy.Recently,the emergence of bioengineered islet-like organs has opened up possibilities for constructing insulin-secreting cells in vitro to treat insulin-dependent diabetes.In this study,we developed a novel microsphere scaffold-based islet cell spheroid culture system that integrates islet organoids with 3D microsphere scaffolds,enabling the consistent generation of 3D islet cell spheroids.Following transplantation into the renal capsule of diabetic mice,these organoids demonstrated significant hypoglycemic effects,with detectable insulin secretion in the serum.On day 30 post-transplantation,β-cell marker expression was significantly increased in the grafts.We further investigated the glucose-related proteins that microsphere scaffold-based islet organoids may regulate.Our findings confirm that islet-like organoids can effectively secrete insulin and play a role in maintaining blood sugar stability.These results indicate that islet-like organs generated via microsphere scaffolds exhibit similar endocrine functions to those of natural islets,can survive in the host body for extended periods,and can effectively exert hypoglycemic effects,thereby providing a solid foundation for the application of islet-like organs in type 1 diabetes research.展开更多
基金supported by the National Basic Research Program(973) of China(No.2008CB418200)the National Natural Science Foundation of China(No. 40872204)the Key Subject of Shanghai Municipality (No.S30109)
文摘Synthetic musks are used as additives in many household products.After absorption into the human body,they accumulate and their concentrations in human milk reflect both the mother and her infant＇s exposure level.Concentrations of four synthetic musks,musk xylene（1-tert-butyl-2,6-dimethyl-2,4,6-trinitrobenzene,MX）,musk ketone（4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone,MK）,1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[γ]-2-benzopyran（HHCB） and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4tetrahydronaphthalene（AHTN）,were determined in human milk samples collected from Shanghai,Wuxi,and Shaoxing in Eastern China.The four synthetic musks were found in most samples analyzed,with HHCB the dominant component followed by MX.The median（mean） values for HHCB,AHTN,MX and MK concentrations were 63（82）,5（12）,17（24） and 4（9） ng/g lipid weight,respectively.These data suggested the total synthetic musk contamination was low,and the distribution percentage was HHCB 〉 MX 〉 AHTN ≈ MK.The relative high ratio of nitro to polycylic musk indicated that nitro musks were still widely used.The musk concentrations in these cities were not significantly different from each other（p 〉 0.05）.Principal components score plots were obtained,which showed similar exposure sources.The amount of total synthetic musks in human milk were not associated with mother＇s age,although HHCB was significantly correlated with AHTN（p 〈 0.05）.Daily ingestion of HHCB,AHTN,MX and MK for infants from human milk were estimated as（2526 ± 2926）,（370 ± 524）,（7391 ± 832）,and（277 ± 462） ng/day,respectively.Those doses were 1-2 orders of magnitude below the provisional tolerable daily intakes.
基金supported by the National Natural Science Foundation of China[52073216 and 51773130].
文摘Immune checkpoint blockade therapy provides a new strategy for tumor treatment;however,the insufficient infiltration of cytotoxic T cells and immunosuppression in tumor microenvironment lead to unsatisfied effects.Herein,we reported a lipid/PLGA nanocomplex(RDCM)co-loaded with the photosensitizer Ce6 and the indoleamine 2,3-dioxygenase(IDO)inhibitor 1MT to improve immunotherapy of colon cancer.Arginine–glycine–aspartic acid(RGD)as the targeting moiety was conjugated on 1,2-distearoyl-snglycero-3-phosphoethanolamine lipid via polyethylene glycol(PEG),and programmed cell death-ligand 1(PDL1)peptide inhibitor DPPA(sequence:CPLGVRGK-GGG-d(NYSKPTDRQYHF))was immobilized on the terminal group of PEG via matrix metalloproteinase 2 sensitive peptide linker.The Ce6 and 1MT were encapsulated in PLGA nanoparticles.The drug loaded nanoparticles were composited with RGD and DPPA modified lipid and lecithin to form lipid/PLGA nanocomplexes.When the nanocomplexes were delivered to tumor,DPPA was released by the cleavage of a matrix metalloproteinase 2-sensitive peptide linker for PD-L1 binding.RGD facilitated the cellular internalization of nanocomplexes via avβ3 integrin.Strong immunogenic cell death was induced by 1 O2 generated from Ce6 irradiation under 660 nm laser.1MT inhibited the activity of IDO and reduced the inhibition of cytotoxic T cells caused by kynurenine accumulation in the tumor microenvironment.The RDCM facilitated the maturation of dendritic cells,inhibited the activity of IDO,and markedly recruited the proportion of tumor-infiltrating cytotoxic T cells in CT26 tumor-bearing mice,triggering a robust immunological memory effect,thus effectively preventing tumor metastasis.The results indicated that the RDCM with dual IDO and PD-L1 inhibition effects is a promising platform for targeted photoimmunotherapy of colon cancer.
基金supported by the National Key Research and Development Program of China(grant number 2017YFD0500500).
文摘Since starch digestion in the small intestine provides more energy than digestion in the rumen of ru-minants,reducing dietary rumen degradable starch(RDS)content is beneficial for improving energy utilization of starch in ruminants.The present study tested whether the reduction of rumen degradable starch by restricting dietary corn processing for growing goats could improve growth performance,and further investigated the possible underlying mechanism.In this study,twenty-four 12-wk-old goats were selected and randomly allocated to receive either a high RDS diet(HRDS,crushed corn-based concen-trate,the mean of particle sizes of corn grain=1.64 mm,n=12)or a low RDS diet(LRDS,non-processed corn-based concentrate,the mean of particle sizes of corn grain>8 mm,n=12).Growth performance,carcass traits,plasma biochemical indices,gene expression of glucose and amino acid transporters,and protein expression of the AMPK-mTOR pathway were measured.Compared to the HRDS,LRDS tended to increase the average daily gain(ADG,P=0.054)and decreased the feed-to-gain ratio(F/G,P<0.05).Furthermore,LRDS increased the net lean tissue rate(P<0.01),protein content(P<0.05)and total free amino acids(P<0.05)in the biceps femoris(BF)muscle of goats.LRDS increased the glucose concen-tration(P<0.01),but reduced total amino acid concentration(P<0.05)and tended to reduce blood urea nitrogen(BUN)concentration(P=0.062)in plasma of goats.The mRNA expression of insulin receptors(INSR),glucose transporter 4(GLUT4),L-type amino acid transporter 1(LAT1)and 4F2 heavy chain(4F2hc)in BF muscle,and sodium-glucose cotransporters 1(SGLT1)and glucose transporter 2(GLUT2)in the small intestine were significantly increased(P<0.05)in LRDS goats.LRDS also led to marked activation of p70-S6 kinase(S6K)(P<0.05),but lower activation of AMP-activated protein kinase(AMPK)(P<0.05)and eukaryotic initiation factor 2a(P<0.01).Our findings suggested that reducing the content of dietary RDS enhanced postruminal starch digestion and increased plasma glucose,thereby improving amino acid utilization and promoting protein synthesis in the skeletal muscle of goats via the AMPK-mTOR pathway.These changes may contribute to improvement in growth performance and carcass traits in LRDS goats.
基金This work was financially supported by the National Science Foundation of China(Grant Nos.81873493 and 82170271 to DL.S.)Henan Thousand Talents Program(Grant Nos.204200510017to DL.S.).Thanks for the help of the research and innovation team project of the First Affiliated Hospital of Zhengzhou University。
文摘Acute myocardial infarction(AMI)induces a sterile inflammatory response,leading to cardiomyocyte damage and adverse cardiac remodeling.Interleukin-5(IL-5)plays an essential role in developing eosinophils(EOS),which are beneficial for the resolution of inflammation.Furthermore,the proangiogenic properties of IL-5 also contribute to tissue healing following injury.Therefore,targeted delivery of IL-5 is an innovative therapeutic approach for treating AMI.It has been shown that conventional IL-5 delivery can result in undesirable adverse effects and potential drug overdose.In this study,we successfully synthesized a biomimetic IL-5 nanoparticle by camouflaging the IL-5 nanoparticle in a neutrophilic membrane.The administration of neutrophil membrane-camouflaged nanoparticles(NM-NPIL-5)in the in vivo model showed that these nanoparticles promoted EOS accumulation and angiogenesis in the infarcted myocardium,thereby limiting adverse cardiac remodeling after AMI.Our results also demonstrated that the NM-NPIL-5 could serve as neutrophil“decoys”to adsorb and neutralize the elevated neutrophil-related cytokines in the injured heart by inheriting multiple receptors from their“parent”neutrophils.Finally,the targeted delivery of NM-NPIL-5 protected the cardiomyocytes from excessive inflammatory-induced apoptosis and maintained cardiac function.Our findings provided a promising cardiac detoxification agent for acute cardiac injury.
基金National Natural Science Foundation of China(61927818,61875220)National Key Research and Development Program of China(2013CBA01700)+5 种基金Fundamental Research Funds for the Central Universities(10611CDJXZ238826)Natural Science Foundation of Chongqing(cstc2019jcyj-msxmX0315,cstc2020jcyj-cxttX0005)“From 0 to 1”Innovation Program of Chinese Academy of Sciences(ZDBS-LY-JSC009)Scientific Instrument and Equipment Development Project of the Chinese Academy of Sciences(YJKYYQ20200032)National Science Fund for Excellent Young Scholar(62022084)Shanghai Outstanding Academic Leaders Plan(20XD1424700).
文摘Chromatic optical lenses have promising applications in three-dimensional imaging, which allows fast spectral tomography without mechanical moving parts. The scanning range of current chromatic optical lenses is limited by their dispersion ability. The recent development in metasurfaces provides ideal blocks for optical wavefront manipulation and dispersion engineering of artificial materials at sub-wavelength scales. Hyper-dispersive metalenses can be realized by utilizing dispersive meta-atoms, which have enhanced dispersion compared to regular diffractive lenses. This is critical for increasing the imaging depth of fast spectral tomography. In this work, a hyper-dispersive metalens is realized with a chromatic dispersion 1.76 times greater than that of a regular diffractive metalens in the THz frequency range of 2.40–2.61 THz by simultaneously controlling the frequencydependent phase, group delay(GD), and GD dispersion of the metalens. This approach can also be extended to other optical spectra and improve the performance of spectral tomography.
基金National Key Research and Development Program of China(2022YFE132800)National Natural Science Foundation of China(82101184)+2 种基金Shenzhen Science and Technology Program(JCYJ20210324102809024 and RCBS20210609103713045)Guangdong Basic and Applied Basic Research Foundation(2020A1515110780)Special Foundation for Basic Research Program of Higher Education Institutions of Henan Province(22ZX005).
文摘Extracellular vesicles(EVs)are nanoscale substances produced by most cells,which were not fully understood in the early years.However,with the development of advanced techniques,researchers have discovered that EVs play an essential role in information exchange and signal transduction between cells.Nowadays,EVs are being used,modified,and developed as a natural drug carrier in various medical fields because of their high biocompatibility and natural affinity with the source body.Many studies have shown that multiple sources of EVs have been modified and utilized in cancer therapy to improve patients’treatment windows and effectively prolong patient survival.In this paper,we review the advances in the treatment of cancer based on EVs.We summarize the types of EVs loading therapy,the modes of drug loading and the latest therapeutic applications of multiple modes combined with EVs in cancer treatment.We conclude with a discussion of the current status,challenges,and prospects of EVs as a tool for tumor therapy.
基金National Natural Science Foundation of China(61927818)Natural Science Foundation of Chongqing(cstc2019jcyj-msxm X0315)。
文摘Superoscillation metalenses have demonstrated promising prospects in breaking the theoretical diffraction limitations on the resolution of optical devices and systems. However, most reported superoscillation metalenses have a very small field of view of several tenths of a degree, which greatly limits their applications in imaging and microscopy. Therefore, it is of critical importance to achieve absolute high resolution by increasing the numerical apertures(NAs) of optical devices and systems. Unfortunately, similar to the case in traditional optics, it is challenging to realize a large field of view at high NA, especially in the superoscillation regime. To date, no attempt has been made to achieve flat-field focusing in the superoscillation regime, to our knowledge. Here, we demonstrate a high-NA superoscillation metalens with an entrance aperture stop, which is optimized for superoscillation performance with a comparatively large field of view. The proposed flat-field superoscillation metalens has an effective NA as large as 0.89 and achieves superoscillation focusing within a field of view of 9°. Such a superoscillation metalens may offer a promising way toward superoscillation imaging and fast-scanning label-free farfield superoscillation microscopy.
基金financially supported by the National Key Research and Development Program of China(2022YFE132800)Innovation Scientists and Technicians Troop Construction Projects of Henan Province(CXTD2017071)+1 种基金Key R&D Project of Henan Province(221111310600)Special Foundation for Basic Research Program of Higher Education Institutions of Henan Province(22ZX005).
文摘Esophageal cancer(EC)is characterized by high morbidity and mortality,and chemotherapy has become an indispensable means for comprehensive treatment.However,due to the limitation of the effective in vitro disease model,the development of chemotherapeutic agents still faces great challenges.In this paper,we present a novel tumor spheroid on a chip platform based on inverse opal hydrogel scaffolds to screen chemotherapeutic agents for EC treatment.With the microfluidic emulsion approach,the inverse opal hydrogel scaffolds were generated with tunable and organized pores,which could provide spatial confinement for cell growth.Thus,the suspended KYSE-70 cells could successfully form uniform cell spheroids on the inverse opal hydrogel scaffolds.It was demonstrated that the tumor cell spheroids could recapitulate 3D growth patterns in vivo and exhibited higher sensitivity to the chemotherapy agents compared with monolayer cells.Besides,by employing the scaffolds into a microfluidics to construct esophageal tumor on a chip,the device could realize high-throughput tumor cell spheroids generation and drug screening,indicating its promising role in chemotherapy drug development.
基金financially supported by the National Key Research and Development Program of China(2022YFE132800)National Natural Science Foundation of China(12105239)+1 种基金Key R&D project of Henan Province(221111310600)Special Foundation for Basic Research Program of Higher Education Institutions of Henan Province(22ZX005).
文摘Exosomes are nanoscale membrane-enclosed extracellular vesicles secreted by various cells,which have enormous potential as disease biomarkers for clinical application.However,the isolation and detection of exosomes remain enormous challenges,which limits their further application.Herein,inspired by immunomagnetic beads,a magnetic nanoparticle conjugated aptamer was repurposed for the effective capture and detection of exosomes.The magnetic nanoparticles,composed of Fe 3 O 4 synthesized by the hydrothermal method as the core and coupled with gold nanoparticles(Fe 3 O 4@Au),provide a large specific surface area,making the resulting composite material an effective platform for exosome capture.Furthermore,the elution of captured exosomes with 1.0 M NaCl made downstream analysis of exosomes possible.The preliminary clinical application value of the composite in exosome analyses of serum from healthy individuals and patients with Alzheimer’s disease(AD)has also been verified,which could provide a promising platform for biomedical and clinical diagnosis.
基金financially supported by the Key R&D project of Henan Province(221111310600)the Special Foundation for Basic Research Program of Higher Education Institutions of Henan Province(22ZX005)Joint Fund of Henan Province Science and Technology R&D Program(225200810020).
文摘Type 1 diabetes(T1D)is an autoimmune deficiency disease characterized by elevated blood sugar levels and insulin resistance,leading to various adverse health effects and complications,such as diabetic cardiomyopathy and diabetic ketoacidosis.Currently,T1D is primarily treated through organoid transplantation and extracorporeal insulin injection.However,the clinical utility of these treatments is limited by increased systemic immunosuppression due to graft donor shortages and the side effects associated with exogenous insulin therapy.Recently,the emergence of bioengineered islet-like organs has opened up possibilities for constructing insulin-secreting cells in vitro to treat insulin-dependent diabetes.In this study,we developed a novel microsphere scaffold-based islet cell spheroid culture system that integrates islet organoids with 3D microsphere scaffolds,enabling the consistent generation of 3D islet cell spheroids.Following transplantation into the renal capsule of diabetic mice,these organoids demonstrated significant hypoglycemic effects,with detectable insulin secretion in the serum.On day 30 post-transplantation,β-cell marker expression was significantly increased in the grafts.We further investigated the glucose-related proteins that microsphere scaffold-based islet organoids may regulate.Our findings confirm that islet-like organoids can effectively secrete insulin and play a role in maintaining blood sugar stability.These results indicate that islet-like organs generated via microsphere scaffolds exhibit similar endocrine functions to those of natural islets,can survive in the host body for extended periods,and can effectively exert hypoglycemic effects,thereby providing a solid foundation for the application of islet-like organs in type 1 diabetes research.
