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 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 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 cel...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,prolifera-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 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
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
Endometriosis,a heterogeneous,inflammatory,and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus,affects approximately 5-10%of reproduc...Endometriosis,a heterogeneous,inflammatory,and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus,affects approximately 5-10%of reproductive-age women,causing chronic pelvic pain and reduced fertility.Although the etiology of endometriosis is still elusive,emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris.Peritoneal macrophages and natural killer(NK)cells exhibit deficient cytotoxicity in the endometriotic microenvironment,leading to inefficient eradication of refluxed endometrial fragments.In addition,the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation,which contribute to endometriosis development.Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis,therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression.Here,we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment,focusing on their interactions with microbiota and endocrine and nervous systems,and how these interactions contribute to the etiology and symptomology of endometriosis.展开更多
Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic dat...Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.展开更多
Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream...Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream targets.A growing number of researches have demonstrated that p53 can influence tumor progression through the tumor microenvironment(TME).TME is involved in the process of tumor development and metastasis and affects the clinical prognosis of patients.p53 participates in host immunity and engages in the immune landscape of the TME,but the specific mechanisms remain to be investigated.This review briefly explores the interactions between different states of p53 and TME components and their mechanisms,as well as their effects on tumor progression.To understand the progress of drug development and clinical studies related to p53 and tumor microenvironment.展开更多
BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investig...BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.展开更多
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,prolifera-
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 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.
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 grants from the National Natural Science Foundation of China(Nos.82273255,81822034,81821002,and 81773119)National Key Research and Development Program of China(Nos.2022YFA1106600,2017YFA0106800,and 2018YFA0109200)+1 种基金Sichuan Science-Technology Project(Nos.22ZYZYTS0070 and 2019YFH0144)Direct Scientific Research Grants from West China Second Hospital,Sichuan University(Nos.KS021 and K1907)
文摘Endometriosis,a heterogeneous,inflammatory,and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus,affects approximately 5-10%of reproductive-age women,causing chronic pelvic pain and reduced fertility.Although the etiology of endometriosis is still elusive,emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris.Peritoneal macrophages and natural killer(NK)cells exhibit deficient cytotoxicity in the endometriotic microenvironment,leading to inefficient eradication of refluxed endometrial fragments.In addition,the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation,which contribute to endometriosis development.Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis,therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression.Here,we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment,focusing on their interactions with microbiota and endocrine and nervous systems,and how these interactions contribute to the etiology and symptomology of endometriosis.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82272008)The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2021KJ194)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.
基金supported by the Natural Science Foundation of Hunan Province(No.2021JJ30589)Hunan Provincial Natural Science Foundation Sector Joint Fund(No.2023JJ60049).
文摘Approximately half of all cancers have p53 inactivating mutations,in addition to which most malignancies inactivate the p53 pathway by increasing p53 inhibitors,decreasing p53 activators,or inactivating p53 downstream targets.A growing number of researches have demonstrated that p53 can influence tumor progression through the tumor microenvironment(TME).TME is involved in the process of tumor development and metastasis and affects the clinical prognosis of patients.p53 participates in host immunity and engages in the immune landscape of the TME,but the specific mechanisms remain to be investigated.This review briefly explores the interactions between different states of p53 and TME components and their mechanisms,as well as their effects on tumor progression.To understand the progress of drug development and clinical studies related to p53 and tumor microenvironment.
文摘BACKGROUND The peritumoral region possesses attributes that promote cancer growth and progression.However,the potential prognostic biomarkers in this region remain relatively underexplored in radiomics.AIM To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and surgically.Patients were divided into training(n=273)and validation(n=136)sets.Based on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve analyses.Risk stratification,Kaplan-Meier analysis,and permutation feature importance analysis were performed.RESULTS The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological feature.Notably,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their combinations.CONCLUSION Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in LARC.The comprehensive model may serve as a reliable tool for better stratification and management postoperatively.
