Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—com...Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.展开更多
The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy ...The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy that synergistically combines pH regulation and micelle-assisted treatment to create an optimized microenvironment for impurity removal.Under mechanical grinding conditions,this approach enhances the rheological properties of the phosphogypsumslurries and facilitates the dissolution and removal of impurity ions.Experimental results demonstrate that the synergistic method achieves a remarkable 64.01%increase in whiteness while significantly reducing soluble phosphorus and fluoride content in a single-step process.This technique not only achieves high purification efficiency but also offers a practical pathway for the high-value utilization of phosphogypsum.These findings suggest that this method has substantial potential for enhancing sustainable resource management and enabling broader industrial applications of purified phosphogypsum.展开更多
The development of new carbon dots(CDs)for fluorescence-based cancer diagnosis has recently attracted extensive attention.Diagnosis methods based on ligand-receptor fluorescence suffer from the heterogeneity of recept...The development of new carbon dots(CDs)for fluorescence-based cancer diagnosis has recently attracted extensive attention.Diagnosis methods based on ligand-receptor fluorescence suffer from the heterogeneity of receptor expression.Changes in the microenvironments of cancer cells provide opportunities for accurate and broad-spectrum cancer diagnosis.The lysosomes in cancer cells have lower polarity and higher viscosity than normal cells.Based on these two key microenvironmental parameters,dual-responsive CDs with inherent lysosome-targeting ability were synthesized via one-step hydrothermal treatment.The CDs exhibit many advantageous properties including facile synthesis,good water solubility,pH-independent emission,excellent photostability,good biocompatibility,and wash-free imaging ability.The CDs were successfully employed in the fluorescence-based discrimination of a broad spectrum of cancer cells from normal cells with high contrast.The CDs are promising candidates for use in the field of cancer diagnosis.展开更多
Biomaterial acts as artificial extracellular matrix for providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to regulate cell behaviors,such as cell ...Biomaterial acts as artificial extracellular matrix for providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to regulate cell behaviors,such as cell adhesion,migration.展开更多
Biomaterials play essential role in regenerative medicine and tissue engineering,which providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to guide ...Biomaterials play essential role in regenerative medicine and tissue engineering,which providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to guide cellular performance[1].It thus spatially and temporally regulates complex cellular process of tissue formation,function and regeneration.展开更多
In modern medicine,bone and dental loss and defects are common and widespread morbidities,for which regenerative therapy has shown great promise.Mesenchymal stem cells,obtained from various sources and playing an esse...In modern medicine,bone and dental loss and defects are common and widespread morbidities,for which regenerative therapy has shown great promise.Mesenchymal stem cells,obtained from various sources and playing an essential role in organ development and postnatal repair,have exhibited enormous potential for regenerating bone and dental tissue.Currently,mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering.Nevertheless,the efficacy of MSCbased regeneration is not always fulfilled,especially in diseased microenvironments.Specifically,the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs,both as donors and recipients.Accordingly,approaches targeting a diseased microenvironment have been established,including improving the diseased niche to restore endogenous MSCs,enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies.Moreover,the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy.In this review,we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment,emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.展开更多
Korean pine（Pinus koraiensis） and broadleaved mixed forest in Northeast China has been changed regressively into secondary forest with almost no conifers.Planting Korean pine trees under the canopy of secondary fore...Korean pine（Pinus koraiensis） and broadleaved mixed forest in Northeast China has been changed regressively into secondary forest with almost no conifers.Planting Korean pine trees under the canopy of secondary forest is a feasible approach for recovering Korean pine and broadleaved mixed forest.For establishing an effective growth promotion method for under-canopy planted young Korean pine trees,two stands were selected as the experiment plots,Stand A（planted in 1989） and Stand B（planted in 1982）,and an experiment of microenvironment regulation was conducted relying mainly on Opening degree（K=1,K=1.5,K=2,CK） in 2004.The results were shown that the adjustment had promoted growth of diameter and height of Korean pine planted in Stand A and Stand B,and had a significant influence on the growth rate of basal diameter,diameter at breast height and height in the two growth stands.The four years periodic increment of mean diameter and height of Korean pine planted in 1989 and in 1982 after regulation in K=1 level were 63.4%（D0） and 82.7%（H）,64.8%（D1.3） and 69.7%（H） higher than that of control respectively.Quantitative regulation had significant influence on specific leaf area of Korean pine planted in 1989,and the current year specific leaf area（SLA） was lager than perennial year SLA.Quality indexes of natural pruning capacity,normal form quotient and crown size was not significantly changed but shown a positive tendency.The regulation scheme of Opening degree K=1 might be proper for adjusting the microenvironment of Korean pine trees planted under the canopy of secondary forest when the Korean pine trees were in the growth period of 15 to 26 years old in the experiment region.展开更多
Colorectal cancer(CRC)is a major health problem causing significant morbidity and mortality.Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment,emphasizing the com...Colorectal cancer(CRC)is a major health problem causing significant morbidity and mortality.Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment,emphasizing the complex interacting network between cancer cells and nearby host cells,which triggers diverse signaling pathways to promote the growth and spread ofcancer cells.The CCN family proteins share a uniform modular structure,mediating a variety of physiological functions,including proliferation,apoptosis,migration,adhesion,differentiation,and survival.Furthermore,CCN proteins are also involved in CRC initiation and development.Many studies have shown that CCN members,such as CCN1,CCN2,CCN3,Wnt-induced secreted protein(WISP)-1,WISP-2,and WISP-3,are dysregulated in CRC,which implies potential diagnostic markers or therapeutic targets clinically.In this review,we summarize the research findings on the role of CCN family proteins in CRC initiation,development,and progression,highlighting their potential for diagnosis,prognosis,and therapeutic application.展开更多
Rationally,engineering a favorable physicochemical microenvironment for enzymes has recently emerged as an effective strategy to improve their catalytic performance.In this review,we discuss four microenvironmental ef...Rationally,engineering a favorable physicochemical microenvironment for enzymes has recently emerged as an effective strategy to improve their catalytic performance.In this review,we discuss four microenvironmental effects according to the mechanism of action:localizing and excluding reactants and regulators,regulating microenvironmental pH,creating a water-like microenvironment,and increasing the local temperature.These mechanisms are enzyme-independent and can in principle be used in combination to tailor enzyme behaviors,offering new approaches to enabling,enhancing,and regulating enzyme catalysis in diverse applications without the need for genetic engineering.展开更多
Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemor...Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.展开更多
Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2...Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CDS, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Results Significant differences in 11 factors （age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8＋ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum l^2-microglobulin） were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index （IPI）, revised IPI, and NCCN-IPI models] （P 〈 0.05）. Concordance rates were high （81.4%-100.0%） when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. Conclusion We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.展开更多
It is envisaged that the creation of cellular environments at multiple length scales, that recapitulate in vivo bioactive and structural roles, may hold the key to creating functional, complex tissues in the laborator...It is envisaged that the creation of cellular environments at multiple length scales, that recapitulate in vivo bioactive and structural roles, may hold the key to creating functional, complex tissues in the laboratory. This review considers recent advances in biofabrication and bioprinting techniques across different length scales. Particular focus is placed on 3D printing of hydrogels and fabrication of biomaterial fibres that could extend the feature resolution and material functionality of soft tissue constructs. The outlook from this review discusses how one might create and simulate microenvironmental cues in vitro. A fabrication platform that integrates the competencies of different biofabrication technologies is proposed. Such a multi-process, multiscale fabrication strategy may ultimately translate engineering capability into an accessible life sciences toolkit, fulfilling its potential to deliver in vitro disease models and engineered tissue implants.展开更多
The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we develope...The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we developed standard chronologies for earlywood width(EWW),late-wood width(LWW),and total ring width(TRW)of P.massoniana at two sampling sites on slopes with different orientations,then analyzed characteristics of the chronolo-gies and their correlations with climate variables from five stations in the region and with a regional normalized differ-ence vegetation index(NDVI).Statistical results showed that the TRW/EWW/LWW chronology consistency and charac-teristics(mean sensitivity,signal to noise ratio,expressed population signal)for trees growing on the southeastern slope were much higher than for trees on the northeastern slope.Correlations indicated that temperature in current March and August has a significant positive effect on TRW/EWW/LWW formation,and the effect on the northeastern slope was weaker than on the southeastern slope.Compared to temperature,precipitation has more complicated effects on tree growth,but the effect on the northeastern slope was also generally weaker than on the southeastern slope.Step-wise linear regression analyses showed that temperature in August was the main limiting factor at the two sampling sites.Similarly,the response of tree growth on the southeast-ern slope as determined by the NDVI is better than on the northeastern slope,and the TRW/EWW/LWW chronologies for the southeastern slope explained over 50%of the total NDVI variances in June.Overall,the results indicate that the difference in the climate response of P.massoniana at two sampling sites is clearly caused by differences in the microenvironment,and such differences should be properly considered in future studies of forest dynamics and climate reconstructions.展开更多
The complex mechanism of degenerative diseases and the non-specific modulation of regenerative targets aretopics that need to be elucidated in order to advance the use of stem cells in improvement of neurodegenerative...The complex mechanism of degenerative diseases and the non-specific modulation of regenerative targets aretopics that need to be elucidated in order to advance the use of stem cells in improvement of neurodegenerative diseases.From pre-transplantation through post-transplantation, there are many changes in the conditions, both inside andoutside of the stem cells that have not been carefully considered. This has hindered development in the field of celltherapy and regeneration. This viewpoint highlights the potential implications of intracellular and extracellularalterations of stem cells in transplanted areas at risk of neurodegenerative disease.展开更多
The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centros...The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.展开更多
The interaction between hematopoietic stem and progenitor cell(HSPC)and its vascular niche is essential for supporting the homeostasis and reconstitution of hematopoietic system in adult bone marrow(BM),but a comprehe...The interaction between hematopoietic stem and progenitor cell(HSPC)and its vascular niche is essential for supporting the homeostasis and reconstitution of hematopoietic system in adult bone marrow(BM),but a comprehensive atlas covering this HSPC-vascular niche crosstalk in multiple developmental stages and species is lacking.Here,we integrated single-cell transcriptomic data of HSPC and its vascular niches from fetal liver until aged BM,covering two species,two organs,and six developmental time points.Comparative analyses revealed dramatic differences in the gene expression,enriched pathway,and cell–cell communication between human fetal and adult BM.Notably,many of these differences were conserved between humans and mice.Multi-timepoint profiling of murine BM vascular niches revealed a stepwise maturation of gene expression,including critical niche factors such as SCF and CXCL12.Furthermore,analysis of this dynamic vascular niche atlas highlighted organ-specific features between fetal liver and BM niches,significant transcriptional changes in aged BM endothelial cells,and identified midkine as a previously unknown niche factor.Functional validation showed that transplanting HSPC into midkine knockout mice or treating with a midkine inhibitor(iMDK)enhanced hematopoietic reconstitution.In contrast,recombinant midkine suppressed HSPC differentiation.Together,our work presents a cross-species and multi-stage atlas of HSPC–vascular niche interactions,offering valuable insights into the dynamic changes of vascular niche through lifelong HSPC development and a platform to identify unknown niche factors.展开更多
Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism k...Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism known as stress erythropoiesis.This crucial physiological process results in increased erythrocyte production,particularly in extramedullary sites such as the spleen and liver,to restore adequate oxygen levels.Unlike steady-state erythropoiesis,which primarily occurs in the bone marrow,stress erythropoiesis depends on distinct progenitor cells and signaling pathways within a specialized erythroid niche in adult spleen and liver.This niche provides essential support for the proliferation,differentiation,and maturation of erythroid progenitors during anemic stress.The dynamics within this niche under stress conditions involve complex interactions between progenitor and niche cells.These interactions are regulated by specific molecular signals that adapt to the body’s physiological demands,ensuring an appropriate response to stress.This review explores the cellular and molecular mechanisms governing these processes,highlighting the extrinsic pathways and cellular interactions during stress erythropoiesis.In addition,it underscores the need for future research to translate findings from murine models into therapeutic strategies for treating anemia-related diseases.展开更多
Low-oxygen(O_(2))environments are essential in various research and application fields,yet traditional methods like nitrogen flushing or chemical O_(2) absorbers face challenges in high equipment cost and low controll...Low-oxygen(O_(2))environments are essential in various research and application fields,yet traditional methods like nitrogen flushing or chemical O_(2) absorbers face challenges in high equipment cost and low controllability.This study introduces a novel electrochemical oxygen removal(EOR)controller,offering a lightweight,low-cost,and precise low-O_(2) control solution.The self-powered EOR controller uses a sacrificial anode to drive the cathodic oxygen reduction reaction(ORR),efficiently consuming environmental O_(2) to reduce its level,thus eliminating the requirements of external gas or power sources.By integrating a single-atom ORR catalyst and flexible design,the device achieves a substantial reduction in weight and cost.The incorporation of electronic components for the EOR controller,including a switch for reaching targeted O_(2) concentration and a fixed resistor for O_(2) removal rate regulation,enables multi-dimensional O_(2) removal control.The system also realizes the O_(2) concentration estimation in real-time with±1%accuracy(within the 21%-1% range)by calculating electron transfers.The EOR controller's effectiveness is validated in plant hypoxia stress experiments,demonstrating precise O_(2) level adjustments and its potential across various applications requiring controlled hypoxic conditions.展开更多
Upper Andean tropical forests are renowned for their extraordinary biodiversity and heterogeneous environmental conditions.Despite the critical role of litter decomposition in carbon and nutrient cycles,its dynamics i...Upper Andean tropical forests are renowned for their extraordinary biodiversity and heterogeneous environmental conditions.Despite the critical role of litter decomposition in carbon and nutrient cycles,its dynamics in this region remains unexplored at finer scales.This study investigates how micro site conditions influence litter decomposition of 15 upper Andean species over time.A reciprocal translocation field experiment was conducted over 18 months in 14 permanent plots within four sites in Colombian Andean mountain forests.Each plot contained three litterbeds(microsites),each with the 15 species,harvested at 3,6,12 and 18 months,totaling 2520 litterbags.Different forest variables,including canopy openness,leaf area index,slope and depth of litter,were measured in each litterbed.ANOVAs and linear mixed models were used to assess variation between sites and plots respectively,while multiple linear regression analyses evaluated the effects of forest variables on decay rates over time at the micro site scale.Results showed differences in absolute decay rates between sites but consistent relative decay rates,indicating varying magnitudes of decomposition,yet maintaining the same order based on their litter quality.Decay rates varied between species,with more variation in labile species compared to recalcitrant ones.Despite substantial variation in forest characteristics within sites,their influence on litter decomposition was minimal and declined over time.This suggests that,at finer spatial scales,the forest microenvironment plays a lesser role in litter decomposition,with litter quality emerging as the primary driver.This study is a step towards understanding the fine-scale dynamics of litter decomposition in upper Andean tropical forests,highlighting the intricate interplay between microenvironmental factors and decomposition processes.展开更多
The microenvironmental effects of β-cyclodextrin (β-CD) on the twisted intramolecular charge transfer (TICT) of ρ-N, N-dimethylaminobenzaldehyde (DMABA) are investigated using fluorescence spectroscopy. The typical...The microenvironmental effects of β-cyclodextrin (β-CD) on the twisted intramolecular charge transfer (TICT) of ρ-N, N-dimethylaminobenzaldehyde (DMABA) are investigated using fluorescence spectroscopy. The typical TICT dual fluorescence of DMABA is observed in pure water and aqueous β-CD solution, and β-CD has s remarkable influence on the TICT fluorescence characteristics of DMABA. A linear dependence of the ratio of intensity of TICT fluorescence band (a band) to that of normal fluorescence band (b band) on DMABA concentration is also observed and the introduction of β-CD increases the linear slope. Combined with the results of absorption spectroscopy, fluorescence polarization, and peculiar salt effects, the properties of TICT state of DMABA, the interaction of DMABA with β-CD, and the intrinsic traits of the microenvironmental effects of β-CD are discussed in detail.展开更多
基金funded by the Italian Ministry of Health through the grant“PRIN 2022 PNRR”entitled“Landscape ANalyses of immune CEll signatures associated with early Liver metastatic cOlorecTal cancer”(LANCELOT),P2022N3NC4,which has received funding from European Commission—NextGeneration for the salary of the researcher Candela Cives-Losada.
文摘Colorectal cancer(CRC)is the second deadliest cancer worldwide,being the presence of metastasis,mainly in the liver,a major contributor to high mortality rates in affected patients.The tumor microenvironment(TME)—comprised of interacting endothelial,stromal,and immune cells—plays a critical role in creating a supportive niche for tumor cell colonization and immune evasion and,thus,the establishment of metastases.The liver’s intrinsic nature further facilitates the development of immune tolerance,mediated by regulatory T cells,myeloid-derived suppressor cells,and soluble factors such as anti-inflammatory cytokines,which together dampen antitumor immune responses.This immunosuppressive milieu contributes significantly to resistance to immune checkpoint inhibitors,limiting the efficacy of immunotherapy in metastatic CRC.Deciphering the complex crosstalk between metastatic CRC cells and TME within the liver is essential for developing novel,effective immunotherapeutic approaches.Several strategies to overcome this lack of response are under research,including combination therapies,novel compounds,and approaches that target TME components.The scope of this review is to synthesize recent advances in the characterization of the hepatic metastatic microenvironment and emerging therapeutic approaches aimed at overcoming immune resistance in CRC liver metastases.
基金financially supported by the Key Research and Development Program of Hubei Province(No.2022BCA082 and No.2022BEC013).
文摘The presence of impurities in phosphogypsum has long impeded its effective utilization,highlighting the need for energy-efficient and sustainable purification methods.This study proposes a novel purification strategy that synergistically combines pH regulation and micelle-assisted treatment to create an optimized microenvironment for impurity removal.Under mechanical grinding conditions,this approach enhances the rheological properties of the phosphogypsumslurries and facilitates the dissolution and removal of impurity ions.Experimental results demonstrate that the synergistic method achieves a remarkable 64.01%increase in whiteness while significantly reducing soluble phosphorus and fluoride content in a single-step process.This technique not only achieves high purification efficiency but also offers a practical pathway for the high-value utilization of phosphogypsum.These findings suggest that this method has substantial potential for enhancing sustainable resource management and enabling broader industrial applications of purified phosphogypsum.
基金supported by the National Natural Science Foundation of China(Nos.21974125,21708035)Program for Innovative Research Team(in Science and Technology)in University of Henan Province(No.22TRTSTHN002)+1 种基金the 111 Project of Henan Province(No.CXJD2021001)National 111 Project(No.D20003).
文摘The development of new carbon dots(CDs)for fluorescence-based cancer diagnosis has recently attracted extensive attention.Diagnosis methods based on ligand-receptor fluorescence suffer from the heterogeneity of receptor expression.Changes in the microenvironments of cancer cells provide opportunities for accurate and broad-spectrum cancer diagnosis.The lysosomes in cancer cells have lower polarity and higher viscosity than normal cells.Based on these two key microenvironmental parameters,dual-responsive CDs with inherent lysosome-targeting ability were synthesized via one-step hydrothermal treatment.The CDs exhibit many advantageous properties including facile synthesis,good water solubility,pH-independent emission,excellent photostability,good biocompatibility,and wash-free imaging ability.The CDs were successfully employed in the fluorescence-based discrimination of a broad spectrum of cancer cells from normal cells with high contrast.The CDs are promising candidates for use in the field of cancer diagnosis.
基金support by China Ministry of Science and Technology(973 Project No2009CB930000)Natural Science Foundation of Chongqing Municipal Government(2007BA4004)+1 种基金Program for New Century Excellent Talents in University(NCET-07-0904)"111 project"(B06023)
文摘Biomaterial acts as artificial extracellular matrix for providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to regulate cell behaviors,such as cell adhesion,migration.
基金support by Natural Science Foundation of China and Chongqing 50603032 and 2007BA4004Foundation of Chongqing Municipal Government 2007BA4004+2 种基金China Ministry of Science and Technology 973 Project No.2009CB930000Program for New Century Excellent Talents in University NCET-07-0904"111 project"B06023
文摘Biomaterials play essential role in regenerative medicine and tissue engineering,which providing a provisional three-dimensional(3D)microenvironments to interact biophysically and/or biochemically with cells to guide cellular performance[1].It thus spatially and temporally regulates complex cellular process of tissue formation,function and regeneration.
基金supported by the National Key Research and Development Program of China (2016YFC1101400 to Y.J.)the National Natural Science Foundation of China (31800817 to S.L., 31870970 to J.Z.)
文摘In modern medicine,bone and dental loss and defects are common and widespread morbidities,for which regenerative therapy has shown great promise.Mesenchymal stem cells,obtained from various sources and playing an essential role in organ development and postnatal repair,have exhibited enormous potential for regenerating bone and dental tissue.Currently,mesenchymal stem cells (MSCs)-based bone and dental regeneration mainly includes two strategies: the rescue or mobilization of endogenous MSCs and the application of exogenous MSCs in cytotherapy or tissue engineering.Nevertheless,the efficacy of MSCbased regeneration is not always fulfilled,especially in diseased microenvironments.Specifically,the diseased microenvironment not only impairs the regenerative potential of resident MSCs but also controls the therapeutic efficacy of exogenous MSCs,both as donors and recipients.Accordingly,approaches targeting a diseased microenvironment have been established,including improving the diseased niche to restore endogenous MSCs,enhancing MSC resistance to a diseased microenvironment and renormalizing the microenvironment to guarantee MSC-mediated therapies.Moreover,the application of extracellular vesicles (EVs) as cell-free therapy has emerged as a promising therapeutic strategy.In this review,we summarize current knowledge regarding the tactics of MSC-based bone and dental regeneration and the decisive role of the microenvironment,emphasizing the therapeutic potential of microenvironment-targeting strategies in bone and dental regenerative medicine.
基金supported by the Project of AGRFUND from Ministry of Science and Technology of the People's Republic of China (Project No. 2007GB24320427)
文摘Korean pine（Pinus koraiensis） and broadleaved mixed forest in Northeast China has been changed regressively into secondary forest with almost no conifers.Planting Korean pine trees under the canopy of secondary forest is a feasible approach for recovering Korean pine and broadleaved mixed forest.For establishing an effective growth promotion method for under-canopy planted young Korean pine trees,two stands were selected as the experiment plots,Stand A（planted in 1989） and Stand B（planted in 1982）,and an experiment of microenvironment regulation was conducted relying mainly on Opening degree（K=1,K=1.5,K=2,CK） in 2004.The results were shown that the adjustment had promoted growth of diameter and height of Korean pine planted in Stand A and Stand B,and had a significant influence on the growth rate of basal diameter,diameter at breast height and height in the two growth stands.The four years periodic increment of mean diameter and height of Korean pine planted in 1989 and in 1982 after regulation in K=1 level were 63.4%（D0） and 82.7%（H）,64.8%（D1.3） and 69.7%（H） higher than that of control respectively.Quantitative regulation had significant influence on specific leaf area of Korean pine planted in 1989,and the current year specific leaf area（SLA） was lager than perennial year SLA.Quality indexes of natural pruning capacity,normal form quotient and crown size was not significantly changed but shown a positive tendency.The regulation scheme of Opening degree K=1 might be proper for adjusting the microenvironment of Korean pine trees planted under the canopy of secondary forest when the Korean pine trees were in the growth period of 15 to 26 years old in the experiment region.
文摘Colorectal cancer(CRC)is a major health problem causing significant morbidity and mortality.Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment,emphasizing the complex interacting network between cancer cells and nearby host cells,which triggers diverse signaling pathways to promote the growth and spread ofcancer cells.The CCN family proteins share a uniform modular structure,mediating a variety of physiological functions,including proliferation,apoptosis,migration,adhesion,differentiation,and survival.Furthermore,CCN proteins are also involved in CRC initiation and development.Many studies have shown that CCN members,such as CCN1,CCN2,CCN3,Wnt-induced secreted protein(WISP)-1,WISP-2,and WISP-3,are dysregulated in CRC,which implies potential diagnostic markers or therapeutic targets clinically.In this review,we summarize the research findings on the role of CCN family proteins in CRC initiation,development,and progression,highlighting their potential for diagnosis,prognosis,and therapeutic application.
基金supported by the National Science Foundation of USA under Award Number NSF-ENG 1844149。
文摘Rationally,engineering a favorable physicochemical microenvironment for enzymes has recently emerged as an effective strategy to improve their catalytic performance.In this review,we discuss four microenvironmental effects according to the mechanism of action:localizing and excluding reactants and regulators,regulating microenvironmental pH,creating a water-like microenvironment,and increasing the local temperature.These mechanisms are enzyme-independent and can in principle be used in combination to tailor enzyme behaviors,offering new approaches to enabling,enhancing,and regulating enzyme catalysis in diverse applications without the need for genetic engineering.
文摘Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.
基金supported by the National Natural Science Foundation of China(81170467 and 81270569)Major Project of PLA Medical S&T Foundation(AWS11C004)Medical Science Research Foundation of Chongqing Health and Family Planning Committee(2015MSXM224)
文摘Objective To investigate the risk stratification of aggressive B cell lymphoma using the immune microenvironment and clinical factors. Methods A total of 127 patients with aggressive B cell lymphoma between 2014 and 2015 were enrolled in this study. CD4, Foxp3, CDS, CD68, CD163, PD-1, and PD-L1 expression levels were evaluated in paraffin-embedded lymphoma tissues to identify their roles in the risk stratification. Eleven factors were identified for further evaluation using analysis of variance, chi-square, and multinomial logistic regression analysis. Results Significant differences in 11 factors （age, Ann Arbor stage, B symptom, ECOG performance status, infiltrating CD8＋ T cells, PD-L1 expression, absolute blood monocyte count, serum lactate dehydrogenase, serum iron, serum albumin, and serum l^2-microglobulin） were observed among patient groups stratified by at least two risk stratification methods [International Prognostic Index （IPI）, revised IPI, and NCCN-IPI models] （P 〈 0.05）. Concordance rates were high （81.4%-100.0%） when these factors were used for the risk stratification. No difference in the risk stratification results was observed with or without the Ann Arbor stage data. Conclusion We developed a convenient and inexpensive tool for use in risk stratification of aggressive B cell lymphomas, although further studies on the role of immune microenvironmental factors are needed.
文摘It is envisaged that the creation of cellular environments at multiple length scales, that recapitulate in vivo bioactive and structural roles, may hold the key to creating functional, complex tissues in the laboratory. This review considers recent advances in biofabrication and bioprinting techniques across different length scales. Particular focus is placed on 3D printing of hydrogels and fabrication of biomaterial fibres that could extend the feature resolution and material functionality of soft tissue constructs. The outlook from this review discusses how one might create and simulate microenvironmental cues in vitro. A fabrication platform that integrates the competencies of different biofabrication technologies is proposed. Such a multi-process, multiscale fabrication strategy may ultimately translate engineering capability into an accessible life sciences toolkit, fulfilling its potential to deliver in vitro disease models and engineered tissue implants.
基金This study was supported by National Key Research and Development Program of China(No.2018YFA0605601)National Natural Science Foundation of China(No.42077417 and41671042).
文摘The Tongbai Mountains is an ecologically sensi-tive region and the northern boundary of Pinus massoniana Lamb.To analyze the effect of different microenvironments on tree growth response to climate factors,we developed standard chronologies for earlywood width(EWW),late-wood width(LWW),and total ring width(TRW)of P.massoniana at two sampling sites on slopes with different orientations,then analyzed characteristics of the chronolo-gies and their correlations with climate variables from five stations in the region and with a regional normalized differ-ence vegetation index(NDVI).Statistical results showed that the TRW/EWW/LWW chronology consistency and charac-teristics(mean sensitivity,signal to noise ratio,expressed population signal)for trees growing on the southeastern slope were much higher than for trees on the northeastern slope.Correlations indicated that temperature in current March and August has a significant positive effect on TRW/EWW/LWW formation,and the effect on the northeastern slope was weaker than on the southeastern slope.Compared to temperature,precipitation has more complicated effects on tree growth,but the effect on the northeastern slope was also generally weaker than on the southeastern slope.Step-wise linear regression analyses showed that temperature in August was the main limiting factor at the two sampling sites.Similarly,the response of tree growth on the southeast-ern slope as determined by the NDVI is better than on the northeastern slope,and the TRW/EWW/LWW chronologies for the southeastern slope explained over 50%of the total NDVI variances in June.Overall,the results indicate that the difference in the climate response of P.massoniana at two sampling sites is clearly caused by differences in the microenvironment,and such differences should be properly considered in future studies of forest dynamics and climate reconstructions.
基金This work was supported by the National Research Foundation of Korea(NRF)Grant Funded by the Korea Government(MSIT)(NRF-2020R1C1C1013535).
文摘The complex mechanism of degenerative diseases and the non-specific modulation of regenerative targets aretopics that need to be elucidated in order to advance the use of stem cells in improvement of neurodegenerative diseases.From pre-transplantation through post-transplantation, there are many changes in the conditions, both inside andoutside of the stem cells that have not been carefully considered. This has hindered development in the field of celltherapy and regeneration. This viewpoint highlights the potential implications of intracellular and extracellularalterations of stem cells in transplanted areas at risk of neurodegenerative disease.
文摘The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.
基金supported by the National Key R&D Program of China(2024YFC3405600)the Fundamental Research Funds for the Central Universities(2024ZYGXZR077)+6 种基金National Natural Science Foundation of China(32270866,32300693,32471155,32470868)Guangzhou basic and applied basic research funding(2024A04J6259,2025A04J7029)The Pearl River Talent Recruitment Program(2023ZT10Y154,2021ZT09Y233,2023QN10Y147)South China University of Technology(D6241240)Supported by Major Research Project and Basic Research Project of Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences(GIBHMRP25-01,GIBHBRP23-02,GIBHBRP24-01)Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences.(KLRB202305,YHJ2024001)partially supported by Science and Technology Planning Project of Guangdong Province,China(2023B1212060050,2023B1212120009).
文摘The interaction between hematopoietic stem and progenitor cell(HSPC)and its vascular niche is essential for supporting the homeostasis and reconstitution of hematopoietic system in adult bone marrow(BM),but a comprehensive atlas covering this HSPC-vascular niche crosstalk in multiple developmental stages and species is lacking.Here,we integrated single-cell transcriptomic data of HSPC and its vascular niches from fetal liver until aged BM,covering two species,two organs,and six developmental time points.Comparative analyses revealed dramatic differences in the gene expression,enriched pathway,and cell–cell communication between human fetal and adult BM.Notably,many of these differences were conserved between humans and mice.Multi-timepoint profiling of murine BM vascular niches revealed a stepwise maturation of gene expression,including critical niche factors such as SCF and CXCL12.Furthermore,analysis of this dynamic vascular niche atlas highlighted organ-specific features between fetal liver and BM niches,significant transcriptional changes in aged BM endothelial cells,and identified midkine as a previously unknown niche factor.Functional validation showed that transplanting HSPC into midkine knockout mice or treating with a midkine inhibitor(iMDK)enhanced hematopoietic reconstitution.In contrast,recombinant midkine suppressed HSPC differentiation.Together,our work presents a cross-species and multi-stage atlas of HSPC–vascular niche interactions,offering valuable insights into the dynamic changes of vascular niche through lifelong HSPC development and a platform to identify unknown niche factors.
文摘Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism known as stress erythropoiesis.This crucial physiological process results in increased erythrocyte production,particularly in extramedullary sites such as the spleen and liver,to restore adequate oxygen levels.Unlike steady-state erythropoiesis,which primarily occurs in the bone marrow,stress erythropoiesis depends on distinct progenitor cells and signaling pathways within a specialized erythroid niche in adult spleen and liver.This niche provides essential support for the proliferation,differentiation,and maturation of erythroid progenitors during anemic stress.The dynamics within this niche under stress conditions involve complex interactions between progenitor and niche cells.These interactions are regulated by specific molecular signals that adapt to the body’s physiological demands,ensuring an appropriate response to stress.This review explores the cellular and molecular mechanisms governing these processes,highlighting the extrinsic pathways and cellular interactions during stress erythropoiesis.In addition,it underscores the need for future research to translate findings from murine models into therapeutic strategies for treating anemia-related diseases.
基金This work was supported by China Ministry of Science and Technology(No.2021YFA1600800)the National Natural Science Foundation of China(Nos.92261105,22221003,and 22401194)+6 种基金the Joint Funds of the National Natural Science Foundation of China(No.U23A2081)China Postdoctoral Science Foundation funded project(No.2022M712178)the Anhui Provincial Natural Science Foundation(Nos.2108085UD06 and 2208085UD04)the Anhui Provincial Key Research and Development Project(Nos.2023z04020010 and 2022a05020053)the Fundamental Research Funds for the Centre Universities(No.WK9990000155)the Joint Funds from Hefei National Synchrotron Radiation Laboratory(Nos.KY2060000180 and KY2060000195)the USTC Research Funds of the Double First-Class Initiative(No.YD2060006005).
文摘Low-oxygen(O_(2))environments are essential in various research and application fields,yet traditional methods like nitrogen flushing or chemical O_(2) absorbers face challenges in high equipment cost and low controllability.This study introduces a novel electrochemical oxygen removal(EOR)controller,offering a lightweight,low-cost,and precise low-O_(2) control solution.The self-powered EOR controller uses a sacrificial anode to drive the cathodic oxygen reduction reaction(ORR),efficiently consuming environmental O_(2) to reduce its level,thus eliminating the requirements of external gas or power sources.By integrating a single-atom ORR catalyst and flexible design,the device achieves a substantial reduction in weight and cost.The incorporation of electronic components for the EOR controller,including a switch for reaching targeted O_(2) concentration and a fixed resistor for O_(2) removal rate regulation,enables multi-dimensional O_(2) removal control.The system also realizes the O_(2) concentration estimation in real-time with±1%accuracy(within the 21%-1% range)by calculating electron transfers.The EOR controller's effectiveness is validated in plant hypoxia stress experiments,demonstrating precise O_(2) level adjustments and its potential across various applications requiring controlled hypoxic conditions.
基金supported by the Universidad del Rosario(Small grant ID:IV-FPD003)。
文摘Upper Andean tropical forests are renowned for their extraordinary biodiversity and heterogeneous environmental conditions.Despite the critical role of litter decomposition in carbon and nutrient cycles,its dynamics in this region remains unexplored at finer scales.This study investigates how micro site conditions influence litter decomposition of 15 upper Andean species over time.A reciprocal translocation field experiment was conducted over 18 months in 14 permanent plots within four sites in Colombian Andean mountain forests.Each plot contained three litterbeds(microsites),each with the 15 species,harvested at 3,6,12 and 18 months,totaling 2520 litterbags.Different forest variables,including canopy openness,leaf area index,slope and depth of litter,were measured in each litterbed.ANOVAs and linear mixed models were used to assess variation between sites and plots respectively,while multiple linear regression analyses evaluated the effects of forest variables on decay rates over time at the micro site scale.Results showed differences in absolute decay rates between sites but consistent relative decay rates,indicating varying magnitudes of decomposition,yet maintaining the same order based on their litter quality.Decay rates varied between species,with more variation in labile species compared to recalcitrant ones.Despite substantial variation in forest characteristics within sites,their influence on litter decomposition was minimal and declined over time.This suggests that,at finer spatial scales,the forest microenvironment plays a lesser role in litter decomposition,with litter quality emerging as the primary driver.This study is a step towards understanding the fine-scale dynamics of litter decomposition in upper Andean tropical forests,highlighting the intricate interplay between microenvironmental factors and decomposition processes.
基金Project supported by the Natural Science Foundation of Fujian Province, China.
文摘The microenvironmental effects of β-cyclodextrin (β-CD) on the twisted intramolecular charge transfer (TICT) of ρ-N, N-dimethylaminobenzaldehyde (DMABA) are investigated using fluorescence spectroscopy. The typical TICT dual fluorescence of DMABA is observed in pure water and aqueous β-CD solution, and β-CD has s remarkable influence on the TICT fluorescence characteristics of DMABA. A linear dependence of the ratio of intensity of TICT fluorescence band (a band) to that of normal fluorescence band (b band) on DMABA concentration is also observed and the introduction of β-CD increases the linear slope. Combined with the results of absorption spectroscopy, fluorescence polarization, and peculiar salt effects, the properties of TICT state of DMABA, the interaction of DMABA with β-CD, and the intrinsic traits of the microenvironmental effects of β-CD are discussed in detail.
