Focused oxidative stress of the specific organelles(e.g.,endoplasmic reticulum(ER)and mitochondrion)of cancer cells can boost the immunogenic cell death(ICD)effect for cancer immunotherapy.Herein,an ER-targeted biopro...Focused oxidative stress of the specific organelles(e.g.,endoplasmic reticulum(ER)and mitochondrion)of cancer cells can boost the immunogenic cell death(ICD)effect for cancer immunotherapy.Herein,an ER-targeted bioprobe with aggregationinduced emission(AIE)characteristics(TPE-PR-FFKDEL)was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide,which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke ICD.Compared with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer,TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed calreticulin,ATP secretion,and high-mobility group protein B1(HMGB1)and heat shock protein 70(HSP 70)expression.Furthermore,a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.展开更多
AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon can...AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 signifi cantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the fi rst time, that the TTYH2 gene expression is signifi cantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating andmetastatic potentials of colorectal cancer.展开更多
To achieve high power conversion efficiency(PCE) and long-term stability of perovskite solar cells(PSCs), a hole transport layer(HTL) with persistently high conductivity, good moisture/oxygen barrier ability, and adeq...To achieve high power conversion efficiency(PCE) and long-term stability of perovskite solar cells(PSCs), a hole transport layer(HTL) with persistently high conductivity, good moisture/oxygen barrier ability, and adequate passivation capability is important. To achieve enough conductivity and effective hole extraction, spiro-OMe TAD, one of the most frequently used HTL in optoelectronic devices, often needs chemical doping with a lithium compound(LiTFSI). However, the lithium salt dopant induces crystallization and has a negative impact on the performance and lifetime of the device due to its hygroscopic nature. Here, we provide an easy method for creating a gel by mixing a natural small molecule additive(thioctic acid, TA) with spiro-OMe TAD. We discover that gelation effectively improves the compactness of resultant HTL and prevents moisture and oxygen infiltration. Moreover, the gelation of HTL improves not only the conductivity of spiro-OMe TAD, but also the operational robustness of the devices in the atmospheric environment. In addition, TA passivates the perovskite defects and facilitates the charge transfer from the perovskite layer to HTL. As a consequence, the optimized PSCs based on the gelated HTL exhibit an improved PCE(22.52%) with excellent device stability.展开更多
The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized ...The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized that they have social interactions via signal molecules.In this work,we firstly discovered the well-known bacterial signal molecules play an adverse role in the cell morphology and metabolism in a model pathogen Trichosporon asahii.N-Tetradecanoyl-L-homoserine lactone(C14-HSL)was discovered to increase pathogen hazards of T.asahii,which limited mycelium by 52%,but enhanced cell aggregation by 93%.Higher fluorescence intensity of tryptophan(59%)and aromatic protein(2-fold)contents after the treatment of C14-HSL,indicating that aromatic proteins helped aggregate Trichosporon and showed hydrophobicity.Transcriptome analysis revealed that C14-HSL upregulated the shikimate pathway(above1-fold)located in downstream of tricarboxylic acid cycle,which contributed to the synthesis of more aromatic proteins and the formation of larger flocs.The limited mycelial growth of T.asahii attributed to the up-regulated expressions of cell cycle process.The fungal transboundary response to bacterial C14-HSL was controlled by signal transduction pathways.This study provides new insights into the co-evolution of bacterial and pathogenic fungi in microecosystems.展开更多
Accumulation and aggregation of β-amyloid（Aβ） peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer＇s disease. The self-assembled Aβ molecules form various intermediate aggregates incl...Accumulation and aggregation of β-amyloid（Aβ） peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer＇s disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.展开更多
The short term(hourly scale)variability of heterotrophic prokaryote(HP)vertical distribution and respiratory activity,was investigated in the north-western(NW)Mediterranean Sea.HP vertical distribution was determined ...The short term(hourly scale)variability of heterotrophic prokaryote(HP)vertical distribution and respiratory activity,was investigated in the north-western(NW)Mediterranean Sea.HP vertical distribution was determined on board by flow cytometry analysis of seawater samples collected by series of CTD casts.Cell counts and viability were determined for all samples.HP respiratory rates were determined later in the laboratory from filtered seawater samples(23 dm^(3))from 300-1150-m depth.The average cell viability was 94.8%±2.2%(n=240).There was no accumulation of dead cells,due to quick decay of damaged cells.In the epipelagic layer,three HP groups were distinguished,two(HNA1,HNA2)who se cells exhibited a high nucleic acid content and one(LNA)with low nucleic acid content cells.HNA2 was most populated at 50 m but not detected at 90 m and below,presumably aerobic anoxygenic photoheterotrophic bacteria(AAPs).The variability in HP abundance was mainly confined in the upper 80 m.A few secondary peaks of HP abundance were observed(80-150 m)in connection with abundance troughs in the surface layer.HP cells were continuously present in a wide layer around 500 m(mean 191×10^(3)cells/cm^(3)).Below this layer,HP abundance randomly exhibited peaks,coupled to respiratory rate peaks.The HP abundance and variability in the water column was suppressed during a strong wind event.The observed sporadic variability was tentatively interpreted through a pulsed carbon-export mechanism induced by the microorganism production of dissolved poly saccharide s,followed by flocculation and rapid sinking.This mechanism would thus contribute to(ⅰ)preventing organic matter accumulation in the epipelagic layer,(ⅱ)seeding the water column with live HP cells,and(ⅲ)supplying the aphotic water column with fre sh and labile organic matter.This important vertical flux mechanism needs further observations and modelling.展开更多
Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of or...Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of organisms.In the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and bioengineering.People have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological approaches.To date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell aggregation.So it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation manipulation.In this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell aggregation.We introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed.We expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.展开更多
基金supported by the National Natural Science Foundation of China(51873092,51961160730)the National Key R&D Program of China(Intergovernmental Cooperation Project,2017YFE0132200)+1 种基金Tianjin Science Fund for Distinguished Young Scholars(19JCJQJC61200)the Fundamental Research Funds for the Central Universities,Nankai University。
文摘Focused oxidative stress of the specific organelles(e.g.,endoplasmic reticulum(ER)and mitochondrion)of cancer cells can boost the immunogenic cell death(ICD)effect for cancer immunotherapy.Herein,an ER-targeted bioprobe with aggregationinduced emission(AIE)characteristics(TPE-PR-FFKDEL)was rationally designed and synthesized by integrating a new AIE photosensitizer with ER targeting peptide,which has been demonstrated to be able to efficiently induce ER oxidative stress to evoke ICD.Compared with the photosensitizer hypericin that is well-known as an ER-targeted ICD inducer,TPE-PR-FFKDEL can lead to more robust emission of immunostimulatory damage-associated molecular patterns such as surface-exposed calreticulin,ATP secretion,and high-mobility group protein B1(HMGB1)and heat shock protein 70(HSP 70)expression.Furthermore,a range of immune responses are activated to protect mice from the attack of cancer cells in vivo.
文摘AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 signifi cantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the fi rst time, that the TTYH2 gene expression is signifi cantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating andmetastatic potentials of colorectal cancer.
基金supported by the National Natural Science Foundation of China (21975028, U21A20172 and 22011540377)the Special Key Projects (2022-JCJQ-ZD-224-12)。
文摘To achieve high power conversion efficiency(PCE) and long-term stability of perovskite solar cells(PSCs), a hole transport layer(HTL) with persistently high conductivity, good moisture/oxygen barrier ability, and adequate passivation capability is important. To achieve enough conductivity and effective hole extraction, spiro-OMe TAD, one of the most frequently used HTL in optoelectronic devices, often needs chemical doping with a lithium compound(LiTFSI). However, the lithium salt dopant induces crystallization and has a negative impact on the performance and lifetime of the device due to its hygroscopic nature. Here, we provide an easy method for creating a gel by mixing a natural small molecule additive(thioctic acid, TA) with spiro-OMe TAD. We discover that gelation effectively improves the compactness of resultant HTL and prevents moisture and oxygen infiltration. Moreover, the gelation of HTL improves not only the conductivity of spiro-OMe TAD, but also the operational robustness of the devices in the atmospheric environment. In addition, TA passivates the perovskite defects and facilitates the charge transfer from the perovskite layer to HTL. As a consequence, the optimized PSCs based on the gelated HTL exhibit an improved PCE(22.52%) with excellent device stability.
基金the National Natural Science Foundation of China(Nos.52070036,U20A20322)the Fundamental Research Funds for the Central Universities(No.2412018ZD042)for their financial support。
文摘The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized that they have social interactions via signal molecules.In this work,we firstly discovered the well-known bacterial signal molecules play an adverse role in the cell morphology and metabolism in a model pathogen Trichosporon asahii.N-Tetradecanoyl-L-homoserine lactone(C14-HSL)was discovered to increase pathogen hazards of T.asahii,which limited mycelium by 52%,but enhanced cell aggregation by 93%.Higher fluorescence intensity of tryptophan(59%)and aromatic protein(2-fold)contents after the treatment of C14-HSL,indicating that aromatic proteins helped aggregate Trichosporon and showed hydrophobicity.Transcriptome analysis revealed that C14-HSL upregulated the shikimate pathway(above1-fold)located in downstream of tricarboxylic acid cycle,which contributed to the synthesis of more aromatic proteins and the formation of larger flocs.The limited mycelial growth of T.asahii attributed to the up-regulated expressions of cell cycle process.The fungal transboundary response to bacterial C14-HSL was controlled by signal transduction pathways.This study provides new insights into the co-evolution of bacterial and pathogenic fungi in microecosystems.
基金supported by the National Natural Science Foundation of China(91127043,31600803,and 21273051)
文摘Accumulation and aggregation of β-amyloid（Aβ） peptides result in neuronal death, leading to cognitive dysfunction in Alzheimer＇s disease. The self-assembled Aβ molecules form various intermediate aggregates including oligomers that are more toxic to neurons than the mature aggregates, including fibrils. Thus, one strategy to alleviate Aβ toxicity is to facilitate the conversion of Aβ intermediates to larger aggregates such as fibrils. In this study, we designed a peptide named A3 that significantly enhanced the formation of amorphous aggregates of Aβ by accelerating the aggregation kinetics. Thioflavin T fluorescence experiments revealed an accelerated aggregation of Aβ monomers, accompanying reduced Aβ cytotoxicity. Transgenic Caenorhabditis elegans over-expressing amyloid precursor protein exhibited paralysis due to the accumulation of Aβ oligomers, and this phenotype was attenuated by feeding the animals with A3 peptide. These findings suggest that the Aβ aggregation-promotion effect can potentially be useful for developing strategies to reduce Aβ toxicity.
基金Supported by the PROOF Grant provided by the INSU-CNRS and was part of the PECHE project“Production and exportation of carbon:control by heterotrophic organisms at small time scales”。
文摘The short term(hourly scale)variability of heterotrophic prokaryote(HP)vertical distribution and respiratory activity,was investigated in the north-western(NW)Mediterranean Sea.HP vertical distribution was determined on board by flow cytometry analysis of seawater samples collected by series of CTD casts.Cell counts and viability were determined for all samples.HP respiratory rates were determined later in the laboratory from filtered seawater samples(23 dm^(3))from 300-1150-m depth.The average cell viability was 94.8%±2.2%(n=240).There was no accumulation of dead cells,due to quick decay of damaged cells.In the epipelagic layer,three HP groups were distinguished,two(HNA1,HNA2)who se cells exhibited a high nucleic acid content and one(LNA)with low nucleic acid content cells.HNA2 was most populated at 50 m but not detected at 90 m and below,presumably aerobic anoxygenic photoheterotrophic bacteria(AAPs).The variability in HP abundance was mainly confined in the upper 80 m.A few secondary peaks of HP abundance were observed(80-150 m)in connection with abundance troughs in the surface layer.HP cells were continuously present in a wide layer around 500 m(mean 191×10^(3)cells/cm^(3)).Below this layer,HP abundance randomly exhibited peaks,coupled to respiratory rate peaks.The HP abundance and variability in the water column was suppressed during a strong wind event.The observed sporadic variability was tentatively interpreted through a pulsed carbon-export mechanism induced by the microorganism production of dissolved poly saccharide s,followed by flocculation and rapid sinking.This mechanism would thus contribute to(ⅰ)preventing organic matter accumulation in the epipelagic layer,(ⅱ)seeding the water column with live HP cells,and(ⅲ)supplying the aphotic water column with fre sh and labile organic matter.This important vertical flux mechanism needs further observations and modelling.
基金Nankai University,Grant/Award Number:63211050NationalNatural Science Foundation of China,Grant/Award Numbers:21874075,22074068,591859123。
文摘Cell–cell aggregation is one of the most well-known modes of intercellular communication.The aggregation also plays a vital role in the formation of multicellularity,thus manipulating the growth and development of organisms.In the past decades,cell–cell aggregation-related bioprocesses and molecular mechanisms have attracted enormous interest from scientists in biology,and bioengineering.People have developed a series of strategies to artificially regulate cell–cell aggregation through chemical–biological approaches.To date,not only the chemical reagents such as coordination compounds and polymers but also the biomacromolecules such as proteins and nucleic acids,are employed as the“cell glue”to achieve the control of the cell aggregation.So it is meaningful to review the recent advances of the chemical–biological approaches in cell–cell aggregation manipulation.In this review,we discuss the mechanisms and features of recently developed strategies to control cell–cell aggregation.We introduce molecules and designs relying on chemical reactions and biological conjugations respectively,and talk about their advantages and suitable applications.A perspective on the challenges in future applications in cell manipulation and cell-based therapy is also proposed.We expect this review could inspire innovative work on manipulating cell–cell aggregation and further modulate cell–cell interactions in the research of bio/chemical fields.
