A generalized Udwadia-Kalaba control design for uncertain belt conveyor systems with inequality constraints.

Uncertainty can lead to jitter or overshoot in mechanical systems, necessitating the design of multiple constraints to stabilize them. This paper proposes a control structure based on the generalized Udwadia-Kalaba equation to address these constraints simultaneously. An uncertain dynamical model is developed, incorporating both equality and inequality constraints. By integrating diffeomorphism theory, a robust control strategy is designed to ensure compliance with these constraints. Utilizing the Lyapunov approach, the uniform boundedness and uniform ultimate boundedness of the dynamical system are demonstrated. Finally, the feasibility of the proposed control method is validated through its application to a belt conveyor system.

Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS.

Systemic iron overload is a common clinical challenge leading to significantly serious complications in patients with acute myeloid leukemia (AML), which affects both the quality of life and the overall survival of patients. Symptoms can be relieved after iron chelation therapy in clinical practice. However, the roles and mechanisms of iron overload on the initiation and progression of leukemia remain elusive. Here we studied the correlation between iron overload and AML clinical outcome, and further explored the role and pathophysiologic mechanism of iron overload in AML by using two mouse models: an iron overload MLL-AF9-induced AML mouse model and a nude xenograft mouse model. Patients with AML had an increased ferritin level, particularly in the myelomonocytic (M4) or monocytic (M5) subtypes. High level of iron expression correlated with a worsened prognosis in AML patients and a shortened survival time in AML mice. Furthermore, iron overload increased the tumor load in the bone marrow (BM) and extramedullary tissues by promoting the proliferation of leukemia cells through the upregulation of FOS. Collectively, our findings provide new insights into the roles of iron overload in AML. Additionally, this study may provide a potential therapeutic target to improve the outcome of AML patients and a rationale for the prospective evaluation of iron chelation therapy in AML.

miR-2765 Modulates the Seasonal Polyphenism in Cacopsylla chinensis by Targeting a Novel Cold Rreceptor CcTRPC3.

Polyphenism is a beneficial way in organisms to better cope with changing circumstances and is a hot topic in entomology, evolutionary biology, and ecology. Until now, this phenomenon has been proven to be season-, density-, and diet-dependent; however, there are very few reports on temperature regulation. Cacopsylla chinensis showed seasonal polyphenism, namely as summer- and winter-form, with obvious diversity in phenotypic characteristics in response to seasonal variation. Previous studies have found that low temperature in autumn is an extremely important element in inducing summer-form change to winter-form, but the underlying regulatory mechanism is still a mystery. Herein, we provided the initial evidence that the third instar of the summer-form is the critical period for developing to the winter-form, and 10 °C induces this transition by affecting the total pigment, chitin level, and thickness of the cuticle. Second, CcTPRC3 was proven to function as a novel cold receptor to control this seasonal polyphenism. Moreover, miR-2765 was found to mediate seasonal polyphenism by inhibiting CcTRPC3 expression. Last, we found that cuticle binding proteins CcCPR4 and CcCPR9 function as the downstream signals of CcTRPC3 to regulate the seasonal polyphenism in C. chinensis. In conclusion, our results displayed a novel signal pathway of miR-2765 and CcTRPC3 for the regulation of seasonal polyphenism in C. chinensis. These findings provide insights into the comprehensive analysis of insect polyphenism and are useful in developing potential strategies to block the phase transition for the pest control of C. chinensis.

miR-252 targeting temperature receptor CcTRPM to mediate the transition from summer-form to winter-form of Cacopsylla chinensis.

Temperature determines the geographical distribution of organisms and affects the outbreak and damage of pests. Insects seasonal polyphenism is a successful strategy adopted by some species to adapt the changeable external environment. Cacopsylla chinensis (Yang & Li) showed two seasonal morphotypes, summer-form and winter-form, with significant differences in morphological characteristics. Low temperature is the key environmental factor to induce its transition from summer-form to winter-form. However, the detailed molecular mechanism remains unknown. Here, we firstly confirmed that low temperature of 10 °C induced the transition from summer-form to winter-form by affecting the cuticle thickness and chitin content. Subsequently, we demonstrated that CcTRPM functions as a temperature receptor to regulate this transition. In addition, miR-252 was identified to mediate the expression of CcTRPM to involve in this morphological transition. Finally, we found CcTre1 and CcCHS1, two rate-limiting enzymes of insect chitin biosyntheis, act as the critical down-stream signal of CcTRPM in mediating this behavioral transition. Taken together, our results revealed that a signal transduction cascade mediates the seasonal polyphenism in C. chinensis. These findings not only lay a solid foundation for fully clarifying the ecological adaptation mechanism of C. chinensis outbreak, but also broaden our understanding about insect polymorphism.

Sox13 and M2-like leukemia-associated macrophages contribute to endogenous IL-34 caused accelerated progression of acute myeloid leukemia.

Interleukin 34 (IL-34) mainly plays physiologic and pathologic roles through the sophisticated multi-ligand signaling system, macrophage colony-stimulating factor (M-CSF, CSF-1)/IL-34-CSF-1R axis, which exhibits functional redundancy, tissue-restriction and diversity. This axis is vital for the survival, differentiation and function of monocytic lineage cells and plays pathologic roles in a broad range of diseases. However, the role of IL-34 in leukemia has not been established. Here MLL-AF9 induced mouse acute myeloid leukemia (AML) model overexpressing IL-34 (MA9-IL-34) was used to explore its role in AML. MA9-IL-34 mice exhibited accelerated disease progression and short survival time with significant subcutaneous infiltration of AML cells. MA9-IL-34 cells showed increased proliferation. In vitro colony forming assays and limiting dilution transplantation experiments demonstrated that MA9-IL-34 cells had elevated leukemia stem cell (LSC) levels. Gene expression microarray analysis revealed a panel of differential expressed genes including Sex-determining region Y (SRY)-box 13 (Sox13). Furthermore, a positive correlation between the expressions of IL-34 and Sox13 was detected human datasets. Knockdown of Sox13 rescued the enhanced proliferation, high LSC level and subcutaneous infiltration in MA9-IL-34 cells. Moreover, more leukemia-associated macrophages (LAMs) were detected in MA9-IL-34 microenvironment. Additionally, those LAMs showed M2-like phenotype since they expressed high level of M2-associated genes and had attenuated phagocytic potential, suggesting that LAMs should also contribute to IL-34 caused adverse phenotypes. Therefore, our findings uncover the intrinsic and microenvironmental mechanisms of IL-34 in AML and broadens the knowledge of M-CSF/IL-34-CSF-1R axis in malignancies.

Molecular identification of carboxylesterase genes and their potential roles in the insecticides susceptibility of Grapholita molesta.

Grapholita molesta is one of the most damaging pests worldwide in stone and pome fruits. Application of chemical pesticides is still the main method to control this pest, which results in resistance to several types of insecticides. Carboxylesterase (CarE) is one of the important enzymes involved in the detoxification metabolism and tolerance of xenobiotics and insecticides. However, the roles of CarEs in insecticides susceptibility of G. molesta are still unclear. In the present study, the enzyme activity of CarEs and the mRNA expression of six CarE genes were consistently elevated after treatment with three insecticides (emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole). According to spatio-temporal expression profiles, six CarE genes expressed differently in different developmental stages, and highly expressed in some detoxification metabolic organs. RNAi-mediated knockdown of these six CarE genes indicated that the susceptibility of G. molesta to all these three insecticides were obviously raised after GmCarE9, GmCarE14, GmCarE16, and GmCarE22 knockdown, respectively. Overall, these results demonstrated that GmCarE9, GmCarE14, GmCarE16, and GmCarE22 play a role in the susceptibility of G. molesta to emamectin benzoate, lambda-cyhalothrin, and chlorantraniliprole treatment. This study expands our understanding of CarEs in insects, that the same CarE gene could participate in the susceptibility to different insecticides.

Fbxw11 impairs the repopulation capacity of hematopoietic stem/progenitor cells.

BACKGROUND: The ubiquitin-proteasome system plays important roles in maintaining the self-renewal and differentiation of stem and progenitor cells through highly ordered degradation of cellular proteins. Fbxw11, an E3 ligase, participates in many important biological processes by targeting a broad range of proteins. However, its roles in hematopoietic stem/progenitor cells (HSPCs) have not been established. METHODS: In this study, the effects of Fbxw11 on HSPCs were studied in vitro and in vivo by an overexpression strategy. Real-time PCR was performed to detect the expression of Fbxw11 in hematopoietic subpopulations. Colony-forming assays were performed to evaluate the in vitro function of Fbxw11 on HSPCs. Hoechst 33342 and Ki67 staining was performed to determine the cell-cycle distribution of HSPCs. Competitive transplantation experiments were used to evaluate the effect of Fbxw11 on the reconstitution potential of HSPCs. Single-cell RNA sequencing (scRNA-seq) was employed to reveal the transcriptomic alterations in HSPCs. RESULTS: The expression of Fbxw11 was higher in Lin-c-Kit+Sca-1+ (LSK) cells and myeloid progenitors than in lymphoid progenitors. Fbxw11 played negative roles in colony-forming and quiescence maintenance of HSPCs in vitro. Furthermore, serial competitive transplantation experiments revealed that Fbxw11 impaired the repopulation capacity of HSPCs. The proportion of granulocytes (Gr-1+CD11b+) in the differentiated mature cells was significantly higher than that in the control group, T cells and B cells were lower. Moreover, scRNA-seq revealed seven cell clusters in HSPCs. In addition, Fbxw11 downregulated the expression of Cebpa, Myc and Arid5b, which are significant regulators of HSPC activity, in most cell clusters. CONCLUSION: Our data demonstrate that Fbxw11 plays a negative role in the maintenance of HSPCs in vitro and repopulation capacity in vivo. Our data also provide valuable transcriptome references for HSPCs in homeostasis.

Microrheological Phenomenon and Mechanical Properties of High-Aspect-Ratio Microgroove Injection Moulding of Kaolin/PP Composites.

The microrheological phenomenon of kaolin-filled polypropylene (kaolin/PP) composites was investigated for the first time. The microviscosity of kaolin/PP composites was studied by changing the melt temperature and shear rate. Then, injection moulding experiments of rectangular microgrooves with different aspect ratios using kaolin/PP composites and mechanical property tests of the samples were carried out. The results showed that with increasing kaolin content, the microviscosity of the kaolin/PP composites gradually increases. The shear rate had the greatest influence on the microviscosity, and the kaolin content had the least influence. When the aspect ratio of rectangular microgrooves is small, with an increasing kaolin content, the microgroove filling rate increases, and the microstructured sample geometric shape replication effect is good; however, when the aspect ratio reaches 10:1, the microgroove filling rate decreases with an increasing kaolin content. The microstructured sample geometric shape replication effect is also poor, and size effects appear. Different factors control the microrheological morphology of composites with different aspect ratios, including the shear deformation and viscous flow of composites. The increase in kaolin content leads to a decrease in the friction coefficient and an increase in the wear resistance of the composites. We concluded that the best composite formulation for kaolin/PP composites in microinjection is the 7KL/PP composite with 7% kaolin. When the aspect ratio is 5:1, the reproduction of the microstructured sample geometry is the best, and the comprehensive mechanical properties of the sample are the best.

Loss of IRF7 accelerates acute myeloid leukemia progression and induces VCAM1-VLA-4 mediated intracerebral invasion.

Interferon regulatory factor 7 (IRF7) is widely studied in inflammatory models. Its effects on malignant progression have been documented mainly from the perspective of the microenvironment. However, its role in leukemia has not been established. Here we used MLL-AF9-induced acute myeloid leukemia (AML) mouse models with IRF7 knockout or overexpression and xenograft mouse models to explore the intrinsic effects of IRF7 in AML. AML-IRF7-/- mice exhibited accelerated disease progression with intracerebral invasion of AML cells. AML-IRF7-/- cells showed increased proliferation and elevated leukemia stem cell (LSC) levels. Overexpression of IRF7 in AML cells decreased cell proliferation and LSC levels. Furthermore, overexpression of transforming growth-interacting factor 1 (TGIF1) rescued the enhanced proliferation and high LSC levels caused by IRF7 deficiency. Moreover, upregulation of vascular cell adhesion molecule 1 (VCAM1), which correlated with high LSC levels, was detected in AML-IRF7-/- cells. In addition, blocking VCAM1-very late antigen 4 (VLA-4) axis delayed disease progression and attenuated intracerebral invasion of AML cells. Therefore, our findings uncover the intrinsic effects of IRF7 in AML and provide a potential strategy to control central nervous system myeloid leukemia.

Study on the Strength and Micro Characteristics of Grouted Specimens with Different Superfine Cement Contents.

To provide the most effective comprehensive performance grouting material ratio, in this experimental investigation, a total of eight grouted specimens with two water-cement ratios (0.45:1, 0.55:1) and four different superfine cement contents (0%, 30%, 70%, 100%) were evaluated. Based on a uniaxial compression test, the fractal dimension of the fragments, a mercury injection test, and scanning electron microscopy, the effects of the superfine cement content on the strength characteristics and microscopic characteristics of the grouted specimens were studied. The results showed that increasing the superfine cement content could enhance the compressive and tensile strength of the grouted specimens and reduce the fractal dimension of the fragments and the porosity of the grouted specimens. The superfine cement content increased from 0% to 70% when the water-cement ratio was 0.45:1. The compressive strength of the grouted specimens increased from 16.7 MPa to 26.3 MPa, and the fractal dimension decreased from 1.8645 to 1.2301. When the water-cement ratio was 0.55:1, the compressive strength of the grouted specimens increased from 10.5 MPa to 20.6 MPa, and the fractal dimension value decreased from 2.2955 to 1.4458. When the superfine cement content increased from 0% to 100%, the water-cement ratio was 0.45:1. The porosity of the grouted specimens was reduced from 28.41% to 21.62%. When the water-cement ratio was 0.55:1, the porosity of the grouted specimens was reduced from 33.33% to 29.46%.

MiR-451a enhances the phagocytosis and affects both M1 and M2 polarization in macrophages.

Leukemia associated macrophages (LAMs), which are different from tumor-associated macrophages as well as classical M1 and M2 macrophages, are specifically activated by leukemic microenvironment. We have reported the heterogeneity of gene expression profiles in LAMs. However, the expression profiles of microRNA (miRNA) in LAMs and their regulatory mechanisms have not been established. Here, the expression profiles of miRNA in LAMs from bone marrow and spleen of acute myeloid leukemia mice were analyzed. Then, the effects of miR-451a, which was upregulated in LAMs, on macrophages were studied by transfecting miRNA mimic to peritoneal macrophages. The results showed that overexpression of miR-451a altered the morphology, enhanced the phagocytic ability of macrophages, and promotes the expression of differentiation marker CD11b in macrophages. Furthermore, miR-451a increased the proliferation capacity of both M1- and M2-polarized macrophages, but not M0 macrophages. Moreover, miR-451a further enhanced the expression of iNOS upon M1 activation. Therefore, our results reveal the miRNA expression profiles in LAMs, and broaden the knowledge about miRNA regulation in macrophages.

Overall Structure Construction of an Intervertebral Disk Based on Highly Anisotropic Wood Hydrogel Composite Materials with Mechanical Matching and Buckling Buffering.

Natural intervertebral disks (IVDs) exhibit distinctive anisotropic mechanical support and dissipation performances due to their well-developed special microstructures. As the intact IVD structure degrades, the absence of function will lead to severe backache. However, the complete simulation for the characteristic structure and function of native IVD is unattainable using current methods. In this work, by overall construction of the two-phase structure of native IVD (extraction of the naturally aligned cellulose framework and in situ polymerization of the nanocomposite hydrogel), a complete wood framework IVD (WF-IVD) is manufactured containing elastic nanocomposite hydrogel-based nucleus pulposus (NP) and anisotropic wood cellulose hydrogel-based annulus fibrosus (AF). In addition to the imitation and construction of the natural structure, WF-IVD also achieves favorable mechanical matching and good biocompatibility and possesses unique mechanical buckling buffer characteristics owing to the aligned fiber bundles. This study offers a promising strategy for the mimicking and construction of complex native tissues.

Fabrication of multi-functional carbon dots based on "one stone, three birds" strategy and their applications for the dual-mode Fe3+ detection, effective promotion on cell proliferation and treatment on ferric toxicosis in vitro.

The ingenious design of multi-functional materials to simultaneously achieve the accurate detection of targets and effective treatment of target-related diseases is of great significance for both practical and clinical applications. Accordingly, based on their advantages of facile synthesis and function designability, functional nanomaterials have become promising candidates for integrating multi-functionality into one platform, especially carbon dot (CD)-based materials. Herein, deferoxamine (DFO)-inspired CDs with integrated "sense and treatment" potential were elaborately designed and fabricated via a one-pot hydrothermal synthesis by employing l-aspartic acid (Asp) and 2,5-diaminobenzenesulfonic acid (DABSA) as the reactants. A series of characterization results distinctly confirmed that the synthesized CDs possessed a unique chemical composition, uniform spherical morphology (diameter of around 5 nm) and good dispersibility in aqueous solution, exhibiting excellent fluorescence stability under different conditions. Owing to the complexation interaction between Fe3+ and the functional groups of CDs, the selective and sensitive detection of Fe3+ could be successfully realized through fluorescent and colorimetric dual-mode detection based on the statistic quenching in the initial stage, and subsequently the FRET process. Furthermore, these CDs could be utilized for cellular imaging and effective Fe3+ detection due to their outstanding biocompatibility and cytoplasmatic distribution. More significantly, these DFO-inspired CDs could remarkably promote the proliferation of various mammalian cells. Particularly, the results in this work obviously indicated that this type of CDs could weaken the damage of Fe3+ towards the physiological behaviors of cells, helping the cells to regain their capability of differentiation after ferric toxicosis. Therefore, this work presents an original approach for the design and fabrication of multi-functional materials according to the "one stone, three birds" strategy, which may be an optional solution to develop various multi-functional platforms for disease diagnosis and corresponding clinical treatment.

DDIT4 mediates the proliferation-promotive effect of IL-34 in human monocytic leukemia cells.

Interleukin 34 (IL-34) is a cytokine that shares the receptor with colony-stimulating factor 1 (CSF-1). IL-34 is involved in a broad range of pathologic processes including cancer. We previously demonstrated that IL-34 promoted the proliferation and colony formation of human acute monocytic leukemia (AMoL) cells. However, the mechanism has not been elucidated. Here, by analyzing the gene profiles of Molm13 and THP1 cells overexpressing IL-34 (Molm13-IL-34 and THP1-IL-34), upregulation of the DNA damage-inducible transcript 4 (DDIT4) was detected in both series. Knockdown of DDIT4 effectively inhibited the proliferation, promoted apoptosis and colony formation in Molm13-IL-34 and THP1-IL-34 cells. Our results suggest that DDIT4 mediates the proliferation-promotive effect of IL-34 whereas does not mediate the promotive effect of IL-34 on colony formation in AMoL cells.

Fabrication of fluorescent hybrid nanomaterials based on carbon dots and its applications for improving the selective detection of Fe (III) in different matrices and cellular imaging.

Considering that detection on cations or ions still meets some challenges in achieving the effectivity and selectivity just by employing one platform, the ingenious fabrication of nanomaterials exhibits an increasing research interests for the preponderance in improving or integrating the performance of single platform. Herein, a fluorescent hybrid nanomaterials based on an organic dye 4-methylumbelliferone (4-MU) as modifier and D-arginine as carbon cores has been developed via a facile one-step hydrothermal synthesis, forming carbon dots (CDs)/4-MU hybrid nanomaterials (CDs-4-MU). This kind of nanomaterials can improve the sensitive and selective detection of single CDs towards Fe3+ ions in different matrices. The detection mechanism of CDs-4-MU towards Fe3+ can be attributed to an electron transfer process between CDs-4-MU and Fe3+, leading to the fluorescence quenching. The limit of detection (LOD) and corresponding linear range in tris-HCl buffer solution are 0.68 µM and 2.29-200 µM, respectively. Furthermore, this nanomaterial can also achieve a detection of Fe3+ ions in real samples such as tap water, culture medium and fetal bovine serum. In particular, CDs-4-MU exhibits a good biocompatibility and can be uptaken by MC3T3 cells, thus can be applied for Fe3+ ions detection in cellular level and cellular imaging. Therefore, this work provides a versatile strategy for the synthesis of CDs-based hybrid nanomaterials and opens a new pathway for improving the ion detection in real samples, which is of significance in practical applications.

Biomimetic synthesis of chondroitin sulfate-analogue hydrogels for regulating osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells.

As a typical representative of crucial glycosaminoglycans (GAGs), chondroitin sulfate (CS) with sulfonated polysaccharide in structures extensively exists in the extracellular matrix (ECM) and exhibits peculiar bioactivity on the regulation of cells behaviors and fates (e.g. proliferation and differentiation) in organisms. Nevertheless, some intrinsic disadvantages of natural CS mainly ascribe to the intricate structure and inhomogeneous composition (especially the uncontrollable sulfonate degrees), resulting in overt restrictions on its physiological functions and applications. Although recent bionic synthesis of artificial GAGs analogues at the molecular level have already provides an efficient strategy to reconstruct GAG for regulating the cellular behaviors and fates, it still remains great challenges to rationally design and synthesize GAGs analogues with special composition and structure for precisely mimicking ECM. Simultaneously, the relevant regulation process of GAG analogues on cell fate needs to be further studied as well. Herein, chondroitin sulfate-analogue (CS-analogue) hydrogels with diverse contents of saccharide and sulfonate units in the networks were fabricated through photo-polymerization and then characterized by Fourier transform infrared (FT-IR) spectroscopy, zeta potential and scanning electron microscope (SEM). Additionally, CS-analogue hydrogels with proper mechanical properties exhibited favorable swelling, degradation performance and prominent cytocompatibility. According to cell cultivation results, CS-analogue hydrogel with a certain proportion of saccharide and sulfonate units presented preferable promotion on the adhesion, spreading, proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), shedding light on the significance of saccharide and sulfonate units in regulating cell behaviors. Furthermore, BMSCs cultivated with CS-analogue hydrogels under different culture conditions were also systematically investigated, revealing that with the help of cultivation environment CS-analogue hydrogels owned the remarkable capacity of directing either chondrogenic or osteogenic differentiation of BMSCs. Therefore, it is envisioned that versatile CS-analogue hydrogels would have promising application prospects in the biomedical and clinical fields.

All-Polycarbonate Thermoplastic Elastomers Based on Triblock Copolymers Derived from Triethylborane-Mediated Sequential Copolymerization of CO2 with Various Epoxides.

Various oxirane monomers including alkyl ether or allyl-substituted ones such as 1-butene oxide, 1-hexene oxide, 1-octene oxide, butyl glycidyl ether, allyl glycidyl ether, and 2-ethylhexyl glycidyl ether were anionically copolymerized with CO2 into polycarbonates using onium salts as initiator in the presence of triethylborane. All copolymerizations exhibited a "living" character, and the monomer consumption was monitored by in situ Fourier-transform infrared spectroscopy. The various polycarbonate samples obtained were characterized by 1H NMR, GPC, and differential scanning calorimetry. In a second step, all-polycarbonate triblock copolymers demonstrating elastomeric behavior were obtained in one pot by sequential copolymerization of CO2 with two different epoxides, using a difunctional initiator. 1-Octene oxide was first copolymerized with CO2 to form the central soft poly(octene carbonate) block which was flanked by two external rigid poly(cyclohexene carbonate) blocks obtained through subsequent copolymerization of cyclohexene oxide with CO2. Upon varying the ratio of 1-octene oxide to cyclohexene oxide and their respective ratios to the initiator, three all-polycarbonate triblock samples were prepared with molar masses of about 350 kg/mol and 22, 26, and 29 mol % hard block content, respectively. The resulting triblock copolymers were analyzed using 1H NMR, GPC, thermogravimetric analysis, differential scanning calorimetry, and atomic force microscopy. All three samples demonstrated typical elastomeric behavior characterized by a high elongation at break and ultimate tensile strength in the same range as those of other natural and synthetic rubbers, in particular those used in applications such as tissue engineering.

Monocyte-Derived Leukemia-Associated Macrophages Facilitate Extramedullary Distribution of T-cell Acute Lymphoblastic Leukemia Cells.

Macrophages play important roles in both physiologic and pathologic processes and arise from successive waves of embryonic and adult hematopoiesis. Monocyte-derived macrophages (MOMF) exert distinct functions under pathologic conditions, and leukemia-associated macrophages (LAM) show considerable diversities in activation and functional phenotype. However, their origin and pathologic roles have not been well elucidated. Here we used wild-type and CCR2-/- mice to study the pathologic roles of monocyte-derived LAM in extramedullary tissues in models of Notch1-induced T-cell acute lymphoblastic leukemia (T-ALL). MOMF existed in the resting liver and spleen. In the spleen, Ly6C+ monocytes gave rise to the Ly6C+ macrophage subset. Furthermore, an increase of monocyte-derived LAM, including the Ly6C+ subset, was detected in the extramedullary tissues in leukemic mice. More monocyte-derived LAM, including Ly6C+ LAM, was detected in the spleens of leukemic mice transplanted with exogeneous mononuclear cells. Moreover, Ly6C+ LAM exhibited increased M1-related characteristics and contributed to sterile inflammation. In CCR2-/- leukemic mice, reduced Ly6C+ LAM, relieved sterile inflammation, and reduced distribution of leukemia cells were detected in extramedullary tissues. In addition, monocyte-derived Ly6C+ LAM expressed high levels of CCL8 and CCL9/10. Blocking CCR1 and CCR2 relieved hepatosplenomegaly and inhibited the extramedullary distribution of leukemia cells in T-ALL mice. Collectively, our findings reveal the multifaceted pathologic roles of monocyte-derived LAM in T-ALL progression. SIGNIFICANCE: This study links monocyte-derived leukemia-associated macrophages with noninfectious inflammation and extramedullary distribution of leukemia cells during leukemia progression, providing new insight into macrophage-based immunotherapy in leukemia.

Hyaluronic acid bioinspired polymers for the regulation of cell chondrogenic and osteogenic differentiation.

As the simplest glycosaminoglycan (GAG) in extracellular matrix, hyaluronic acid (HA) takes part in several important biological processes, such as regulating cell proliferation, differentiation, and migration. In this work, a series of HA-inspired polymers with different saccharide and carboxylate units (HA-analogue polymers) are synthesized by free radical polymerization, and characterized using Fourier transform infrared spectroscopy (FT-IR), gel permeation chromatography (GPC) and nuclear magnetic resonance spectrometer (NMR), Moreover, cell experiments demonstrate that HA-analogue polymers with a certain proportion of saccharide and carboxylate (PM1G1) units shows a positive effect on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, HA-analogue polymers have prominent cartilage inductive capacity in chondrogenic induction medium (CIM) and brilliant bone inductive capacity in osteogenic induction medium (OIM) toward BMSCs. Therefore, it is confirmed that the HA-analogue polymers can effectively mimic the functions of HA and have broad potential application prospects in the biomedical and clinical fields.