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Hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) have robust self-renewal potential, which is responsible for sustaining normal and malignant hematopoiesis, respectively. Although considerable efforts have been made to explore the regulation of HSC and LSC maintenance, the underlying molecular mechanism remains obscure. Here, we observe that the expression of thymocyte-expressed, positive selection-associated 1 (Tespa1) is markedly increased in HSCs after stresses exposure. Of note, deletion of Tespa1 results in short-term expansion but long-term exhaustion of HSCs in mice under stress conditions due to impaired quiescence. Mechanistically, Tespa1 can interact with CSN subunit 6 (CSN6), a subunit of COP9 signalosome, to prevent ubiquitination-mediated degradation of c-Myc protein in HSCs. As a consequence, forcing c-Myc expression improves the functional defect of Tespa1-null HSCs. On the other hand, Tespa1 is identified to be highly enriched in human acute myeloid leukemia (AML) cells and is essential for AML cell growth. Furthermore, using MLL-AF9-induced AML model, we find that Tespa1 deficiency suppresses leukemogenesis and LSC maintenance. In summary, our findings reveal the important role of Tespa1 in promoting HSC and LSC maintenance and therefore provide new insights on the feasibility of hematopoietic regeneration and AML treatment.

In four studies, we tested whether higher trait self-objectification was associated with more strategic and less authentic self-presentation on social media among cisgender women, and whether these links could be attributed to heightened approval motivation among those having higher levels of self-objectification. Study 1 ( N = 167, Mage = 27.05) and Study 2 ( N = 149, Mage = 29.87), using self-reported measures, found that self-objectification was positively associated with strategic self-presentation on Tinder and Facebook. Study 3 ( N = 202, Mage = 28.07) replicated and extended the first two studies, using self-reported behavioral indicators of strategic self-presentation. The first three studies were conducted on Prolific with a nationwide sample of female participants. Study 4 ( Mage = 21.87) was a real-time behavioral study conducted on Zoom with 102 female U.K. university students using a tool by which actual photo editing was measured. The results confirmed a positive association between trait self-objectification and strategic self-presentation. Mediation analyses suggest that this relation may be attributed to a heightened approval motivation among those who self-objectify. Social media users and policy makers should be made aware of the potential downstream consequences associated with the frequent use of social media self-presentational techniques discussed in this research.

Hematopoietic stem cells (HSCs) possess the great self-renewal and multidirectional differentiation ability, which contributes to the continuous generation of various blood cells. Although many intrinsic and extrinsic factors have been found to maintain HSC homeostasis, how to precisely regulate hematopoiesis under stress conditions is poorly understood. In this study, we show that melanocortin receptor 5 (MC5R) is abundantly expressed in hematopoietic stem progenitor cells (HSPCs). Using a MC5R knockout (MC5R-/-) mouse model, we observe that it is not essential for steady-state hematopoiesis. Interestingly, the levels of α-melanocyte stimulating hormone (α-MSH), an important sub-type of melanocortin, are elevated in serum and bone marrow, and the expression of MC5R is upregulated in HSPCs from mice after irradiation. MC5R deficiency aggravates irradiation-induced myelosuppression due to the impairment in the proliferation and reconstitution function of HSCs. Further investigations exhibit that melanocortin/MC5R axis regulates the proliferation of HSCs through activating the PI3K/AKT and MAPK pathways. More importantly, α-MSH treatment can significantly accelerate the hematopoietic recovery in irradiated mice. In conclusion, our data demonstrate that melanocortin/MC5R axis plays a crucial role in regulating HSC proliferation under stress, thus providing a promising strategy to promote hematopoietic regeneration when suffering from injury.

Mitochondria are fundamental but complex determinants for hematopoietic stem cell (HSC) maintenance. However, the factors involved in the regulation of mitochondrial metabolism in HSCs and the underlying mechanisms have not been fully elucidated. Here, we identify sterol regulatory element binding factor-1c (Srebf1c) as a key factor in maintaining HSC biology under both steady-state and stress conditions. Srebf1c knockout (Srebf1c

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.

Hematopoietic stem cell (HSC) fate is tightly controlled by various regulators, whereas the underlying mechanism has not been fully uncovered due to the high heterogeneity of these populations. In this study, we identify tetraspanin CD63 as a novel functional marker of HSCs in mice. We show that CD63 is unevenly expressed on the cell surface in HSC populations. Importantly, HSCs with high CD63 expression (CD63(hi)) are more quiescent and have more robust self-renewal and myeloid differentiation abilities than those with negative/low CD63 expression (CD63(-/lo)). On the other hand, using CD63 knockout mice, we find that loss of CD63 leads to reduced HSC numbers in the bone marrow. In addition, CD63-deficient HSCs exhibit impaired quiescence and long-term repopulating capacity, accompanied by increased sensitivity to irradiation and 5-fluorouracil treatment. Further investigations demonstrate that CD63 is required to sustain TGFβ signaling activity through its interaction with TGFβ receptors I and II, thereby playing an important role in regulating the quiescence of HSCs. Collectively, our data not only reveal a previously unrecognized role of CD63 but also provide us with new insights into HSC heterogeneity.

Researchers have examined self-objectification—viewing oneself as an object rather than a subject—in terms of its impact on intrapersonal factors, such as mental health and cognitive performance. However, few have examined how self-objectification relates to interpersonal factors despite the importance of these factors for interpersonal outcomes. The present research addressed this gap by testing the impact of self-objectification on social approval motivation among women. Study 1 (N = 103) found that individual differences in self-objectification correlated positively with approval motivation. Study 2 (N = 94) replicated these results and found that women who reported higher self-objectification were more willing to modify their social media profile pictures unrealistically. In Study 3 (N = 100), higher self-objectifying women were more willing to unrealistically modify their profile pictures even if this exceeded normative levels, which was replicated in Study 4 (N = 199). These results suggest that women’s self-objectification is associated with a desire for approval from others and this desire manifests in a willingness to modify self-presentation.

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Backgroud: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated. Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation increased the proportions of G2/M phase and Caveolin-1 content in 4T1 breast cancer cells, contributing to an endocytic enhancement of PINPs@PM. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.

Rationale: The hematopoietic system and skeletal system have a close relationship, and megakaryocytes (MKs) may be involved in maintaining bone homeostasis. However, the exact role and underlying mechanism of MKs in bone formation during steady-state and stress conditions are still unclear. Methods: We first evaluated the bone phenotype with MKs deficiency in bone marrow by using c-Mpl-deficient mice and MKs-conditionally deleted mice. Then, osteoblasts (OBs) proliferation and differentiation and CD31hiEmcnhi tube formation were assessed. The expression of growth factors related to bone formation in MKs was detected by RNA-sequencing and enzyme-linked immunosorbent assays (ELISAs). Mice with specific depletion of TGF-β1 in MKs were used to further verify the effect of MKs on osteogenesis and angiogenesis. Finally, MKs treatment of irradiation-induced bone injury was tested in a mouse model. Results: We found that MKs deficiency significantly impaired bone formation. Further investigations revealed that MKs could promote OBs proliferation and differentiation, as well as CD31hiEmcnhi vessels formation, by secreting high levels of TGF-β1. Consistent with these findings, mice with specific depletion of TGF-β1 in MKs displayed significantly decreased bone mass and strength. Importantly, treatment with MKs or thrombopoietin (TPO) substantially attenuated radioactive bone injury in mice by directly or indirectly increasing the level of TGF-β1 in bone marrow. MKs-derived TGF-β1 was also involved in suppressing apoptosis and promoting DNA damage repair in OBs after irradiation exposure. Conclusions: Our findings demonstrate that MKs contribute to bone formation through coupling osteogenesis with angiogenesis by secreting TGF-β1, which may offer a potential therapeutic strategy for the treatment of irradiation-induced osteoporosis.

Five non-real time satellite-based precipitation products (SPPs), including TMPA 3B42V7, CMORPH CRT, PERSIANN-CDR, GSMaP_MVK and GSMaP_Gauge, were evaluated over the Xijiang Basin. By driving XAJ model with each of the SPPs and gauge-based interpolation precipitation data to compare the hydrological responses at Wuzhou Station during the period of 2010–2017, this study also evaluated the applicability of these SPPs in rainfall-runoff simulation over the Xijaing Basin. The results showed that: (1) GSMaP_Gauge had highest accuracy, then are CMORPH CRT and TMPA 3B42V7, respectively, and finally are PERSIANN-CDR and GSMaP_MVK; (2) Among the five SPPs, CMORPH CRT, GSMaP_Gauge and TMPA-3B42 V7 have comparable performance in rainfall-runoff simulation, with NSE value lower than that generated by driving gauge-based interpolation precipitation and obviously higher than that of PERSIANN-CDR, and the uncorrected SPP, i.e., GSMaP_MVK, performs worst because of large systematic errors.

The composition and origin of extrinsic cues required for hematopoietic stem cell (HSC) maintenance are incompletely understood. Here we identify renal Klotho and inorganic phosphate (Pi) as extrinsic factors that antagonistically regulate HSC maintenance in the bone marrow (BM). Disruption of the Klotho-Pi axis by renal Klotho deficiency or Pi excess causes Pi overload in the BM niche and Pi retention in HSCs, leading to alteration of HSC maintenance. Mechanistically, Pi retention is mediated by soluble carrier family 20 member 1 (SLC20A1) and sensed by diphosphoinositol pentakisphosphate kinase 2 (PPIP5K2) to enhance Akt activation, which then upregulates SLC20A1 to aggravate Pi retention and augments GATA2 activity to drive the expansion and megakaryocyte/myeloid-biased differentiation of HSCs. However, kidney-secreted soluble Klotho directly maintains HSC pool size and differentiation by restraining SLC20A1-mediated Pi absorption of HSCs. These findings uncover a regulatory role of the Klotho-Pi axis orchestrated by the kidneys in BM HSC maintenance.

Background Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. Methods The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. Results EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. Conclusion EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

Land use/cover change (LUCC) affects regional climate not only through its direct changes of land surface properties, but also through its further modifications of land-atmosphere interactions. Urban land expansion is a typical case of LUCC in highly populated areas, and has been widely discussed about its impacts on regional air temperature, notably known as urban heat island (UHI) effects. Besides air temperature, atmospheric humidity, as another key variable in hydrometeorology and climate, would be inevitably affected by LUCC as well. However, the impacts of LUCC on atmospheric humidity seem to have not been investigated as much as on temperature. We examined atmospheric humidity changes by trend analyses of humidity indicators in three representative urban agglomerations in the Yangtze River Economic Belt (YREB), China during 1965-2017, and found the evident urban dry island (UDI) effects which are characterized by significant humidity decrease and vapor pressure deficit increase. In different urban cores, the severity levels of UDI are different. Furthermore, strong positive correlations between humidity and evapotranspiration, and between evapotranspiration and leaf area were detected during 2001-2017 when cities entered the accelerated stage of land expansion, indicating that LUCC affects regional climate through an ecohydrological way. We speculated that the UDI effect will not appear until urban land expands to a certain scale. Besides, the UHI effect emerged in the early stage of urban expansion, about 5 years earlier than the UDI effect, and has not performed prominently in recent years. This implies that urbanization-induced LUCC may exert a larger influence on UDI than on UHI in the current later period of urban expansion.

Alcoholism is a severe threat to public health, and there are no adequate treatments for alcoholic liver disease. The aim of this study was to identify bioactive peptides derived from natural proteins that prevent acute alcohol-induced liver injury. We identified a peptide with the sequence Gly-Leu-hydroxyproline-Gly-Glu-Arg (GLpGER) from the hydrolysate of crucian carp swim bladder using size-exclusion chromatography and reversed-phase chromatography. The in vitro EC50 value of GLpGER to activate alcohol dehydrogenase (ADH) was 137.9 ± 9 µM. Molecular docking experiments indicated that the mechanism by which GLpGER activates ADH may be related to the formation of stable complexes with ADH active pockets through hydrogen bonding, and electrostatic and hydrophobic interactions. Oral administration of GLpGER one hour before acute alcohol ingestion significantly increased alcohol metabolism, manifesting as reduced incidence of the loss of righting reflex, increased alcohol tolerance time, shortened sobering time, and decreased blood alcohol concentration level. GLpGER restored liver ADH activity, maintained the typical morphology of hepatocytes, and reduced serum levels of alanine aminotransferase and aspartate aminotransferase. These findings suggest that GLpGER might reduce acute alcohol-induced liver injury and may have the potential to be developed as an anti-inebriation ingredient.

The cell cycle progression of hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML) cells is precisely controlled by multiple regulatory factors. However, the underlying mechanisms are not fully understood. Here, we find that cyclin-dependent kinase 19 (CDK19), not its paralogue CDK8, is relatively enriched in mouse HSCs, and its expression is more significantly increased than CDK8 after proliferative stresses. Furthermore, SenexinB (a CDK8/19 inhibitor) treatment impairs the proliferation and self-renewal ability of HSCs. Moreover, overexpression of CDK19 promotes HSC function better than CDK8 overexpression. Using CDK19 knockout mice, we observe that CDK19

Agricultural water productivity (AWP) model is an essential tool for irrigation water management that is highly dependent on soil water processes. Soil hydrological models based on numeric solution to the Richards’ equation are time-consuming and difficult to measure, and models based on soil water balance approach are favored especially for crop water simulation because of the less parameters requirement and higher operational efficiency. In most of the soil water balance models such as Williams-Ritchie water balance model, AquaCrop model and Hydrobal model, the under field-capacity redistribution (the redistribution during the period of soil water content below the field-capacity) is omitted and this treatment does not adequately simulate AWP for arid and semi-arid areas with deep groundwater. In these areas, AWP is the ratio between crop yield achieved and the sum of actual evapotranspiration and deep percolation at field scale. Since no more water supply for crop growth except for low frequency irrigation and tiny amount of precipitation, high evapotranspiration will aggravate an upward flow that can enhance transpiration and thus benefit crop growth while deep percolation not available for crop is sustainably accumulated to a considerable volume in under field-capacity redistribution process. To take into consideration the beneficial effects of upward flow on crop growth and the considerable under field-capacity deep percolation loss, a conceptual soil hydrological model considering under field-capacity redistribution (CSHMUR) is developed and coupled with the EPIC crop growth model. In CSHMUR model, soil water redistribution is characterized by two sequential water flows: downward flows affected by the gradient of gravitational potential and upward flows affected by the gradient of matric potential. These two flows are mainly used to simulate deep percolation occurring in redistribution processes and upward flows resulting from matric potential, respectively. The CSHMUR-EPIC model is calibrated and validated with field data for a typical arid area of northwestern China, and it is then applied for the simulation of seven irrigation scenarios. The study highlights that the upward flows aggravated by drought conditions and the under field-capacity deep percolation are remarkable enough and should not be neglected in the AWP estimation for arid and semi-arid areas with deep groundwater. The developed CSHMUR-EPIC model can effectively simulate upward flows and the under field-capacity deep percolation, and thus soil water content (SWC) both in lower and upper soil profiles, actual evapotranspiration and crop growth, resulting in an precise estimation of AWP. As upward flows and the under field-capacity deep percolation vary with irrigation schedule, the model is also helpful in exploring various irrigation schedule to obtain a sustainable agricultural water resources management.

A damage identification scheme combining impact-synchronous modal analysis (ISMA) and artificial neural network is developed in this study. The ISMA de-noising method makes it feasible to detect and classify the damage states with high accuracy when the machine is under operation. The feed-forward backprop network was utilized in this study. The input feature vector of the network consisted of the FRF changes in a selected vibrational mode frequency interval at several measurement points. The scheme was tested on a rectangular Perspex plate. It is proved that the trained network can successfully identify damage locations with the testing data collected by ISMA, which allows the damage detection to be carried out without shutting down the tested machine. For the plate structure in this study, an overall accuracy reached 100% when all five measurement points were used. With the input features optimized by mode shape assessment, 100% accuracy was also achieved with only two measurement points.

Natural killer (NK)–cell development and maturation is a well-organized process. The steroid receptor coactivator 3 (SRC-3) is a regulator of the hematopoietic and immune systems; however, its role in NK cells is poorly understood. Here, SRC-3 displayed increased nuclear translocation in NK cells during terminal differentiation and upon inflammatory cytokine stimulation. Targeted deletion of SRC-3 altered normal NK-cell distribution and compromised NK-cell maturation. SRC-3 deficiency led to significantly impaired NK-cell functions, especially their antitumor activity. The expression of several critical T-bet target genes, including Zeb2, Prdm1, and S1pr5, but not T-bet itself, was markedly decreased in NK cells in the absence of SRC-3. There was a physiologic interaction between SRC-3 and T-bet proteins, where SRC-3 was recruited by T-bet to regulate the transcription of the aforementioned genes. Collectively, our findings unmask a previously unrecognized role of SRC-3 as a coactivator of T-bet in NK-cell biology and indicate that targeting SRC-3 may be a promising strategy to increase the tumor surveillance function of NK cells.

Additional file 3. In vivo imaging of tumor-bearing mice at 12 h post injection of PINPs@PM.

Additional file 5. PM camouflage improves the antitumor ability of PINPs in vivo.

Additional file 1. TEM image of PINPs.

Merging gauge observation with a single original satellite-based precipitation product (SPP) is a common approach to generate spatial precipitation estimates. For the generation of high-quality precipitation maps, however, this common method has two drawbacks: (1) the spatial resolutions of original SPPs are still too coarse; and (2) a single SPP can’t capture the spatial pattern of precipitation well. To overcome these drawbacks, a two-step scheme consisting of downscaling and fusion was proposed to merge gauge observation with multiple SPPs. In both downscaling and fusion steps, the geographically weighted ridge regression (GWRR) method, which is a combination of the geographically weighted regression (GWR) method and the ridge regression method, is proposed and implemented to generate improved spatial precipitation estimates by overcoming the collinearity problem of the pure GWR method. The proposed two-step merging scheme was applied to Xijiang Basin of China for deriving daily precipitation estimates from the data of both gauge observation and four near real-time SPPs (i.e., TMPA-3B42RT, CMORPH, PERSIANN and GSMaP_NRT) during the period of 2010–2017. The results showed that: (1) the collinearity problem caused by GWR was not serious in downscaling but serious enough to prevent GWR from being directly used in the fusion; and (2) the proposed two-step merging scheme significantly improved the spatial resolution and accuracy of precipitation estimates over the original SPPs. Comparisons also showed that, in the second step (fusion) of the merging scheme, the use of multiple SPPs provided more reliable spatial precipitation estimates than using a single SPP.

Additional file 4. Thermal images of NaCl-treated tumor-bearing mice.

Additional file 2. 1-N-phenylnaph-thylamine (NPN)-uptake assay.

Ionizing radiation (IR) triggers the generation of reactive oxygen species (ROS), which shows potential roles in damaging the DNA and proteins at the nucleus, and eventually results in apoptosis and even cell death. Antioxidant agents can inhibit the generation of ROS after IR exposure. Tannic acid (TA), has an antioxidant activity involving in preventing cardiovascular and cerebrovascular diseases. However, little is known about the effects of TA on irradiation-induced apoptosis in megakaryocytes. Here, we evaluated the anti-radiation activity of TA in megakaryocytes. Our results showed that TA protected megakaryocytes from apoptosis induced by IR, attenuated IR-induced increases in the production of ROS, and inhibited the changes of mitochondrial membrane potential (MMP). Moreover, TA down-regulated NAPDH oxidase 1 (Nox1) expression, and decreased the phosphorylated levels of JNK and p38. Furthermore, JNK inhibitor could reduce apoptosis induced by X-irradiation in M07e cells. In vivo experiments confirmed that TA could promote the platelet recovery, reduce the percentage of apoptosis CD41+ megakaryocytes in bone marrow and raise survival during 30 days in mice by total body irradiation. In conclusion, TA can protecte the megakaryocytes from apoptosis caused by IR through inhibiting Nox1 expression to reduce ROS generation and repressing JNK/p38 MAPK pathway activation.

Essentials The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. We analyzed the role of anti-αvβ3 autoantibody in the pathogenesis of ITP in patients. Anti-αvβ3 autoantibody impeded megakaryocyte migration and adhesion to the vascular niche. Anti-αv β3 autoantibody potentially contributes to the pathogenesis of refractory ITP. Summary Background The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. Anti-αvβ3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti-αvβ3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti-αvβ3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti-αvβ3 antibody on megakaryocyte (MK) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MKs' distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti-αvβ3 autoantibody usually coexists with anti-αIIbβ3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In in vitro studies, we showed that the anti-αvβ3 antibody had no significant effect on the survival and proliferation of MKs, whereas it decreased formations of proplatelet significantly. Anti-αvβ3 antibody impeded stromal cell derived facor-1 alpha (SDF-1α)- mediated migration and inhibited the phosphorylation of protein kinase B. Anti-αvβ3 antibody significantly inhibited MKs' adhesion to endothelial cells and Fibrogen. The phosphorylation of focal adhesion kinase and proto-oncogene tyrosine-protein kinase Src induced by adhesion was inhibited when MKs were pretreated with anti-αvβ3 antibody. In in vivo studies, we showed that injection with anti-αv antibody delayed platelet recovery in a mouse model of ITP. Conclusions These findings demonstrate that the autoantibody against integrin αv β3 may aggravate thrombocytopenia in ITP patients by impeding MK migration and adhesion to the vascular niche, which provides new insights into the pathogenesis of ITP.

Backgroud: Cell membrane-based nanocarriers are promising candidates for delivering antitumor agents. The employment of a simple and feasible method to improve the tumor-targeting abilities of these systems is appealing for further application. Herein, we prepared a platelet membrane (PM)-camouflaged antitumor nanoparticle. The effects of irradiation pretreatment on tumor targeting of the nanomaterial and on its antitumor action were evaluated.Results: The biomimetic nanomaterial constructed by indocyanine green, poly(d,l-lactide-co-glycolide), and PM is termed PINPs@PM. A 4-Gy X-ray irradiation enabled the endocytic enhancement of PINPs@PM by 4T1 breast cancer cells. PINPs@PM produced hyperthermia and reactive oxygen species upon excitation by near-infrared irradiation, which were detrimental to the cytoplasmic lysosome and resulted in cell death. Irradiation pretreatment thus strengthened the antitumor activity of PINPs@PM in vitro. Mice experiments revealed that irradiation enhanced the tumor targeting capability of PINPs@PM in vivo. When the same dose of PINPs@PM was intravenously administered, irradiated mice had a better outcome than did mice without X-ray pretreatment. Conclusion: The study demonstrates an effective strategy combining irradiation pretreatment and PM camouflage to deliver antitumor nanoparticles, which may be instrumental for targeted tumor therapy.