Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac.

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

A novel strategy to prepare high performance multifunctional composite films by combining electrostatic assembly, crosslinking, topology enhancement and sintering.

Currently, polymer-fiber composite films face the challenge of striking a balance between good mechanical properties and multi-functionalities. Here, aramid fibers (ANFs), chitosan (CS) dendritic particles, and silver nanowires (AgNWs) were used to create high-performance multifunctional composite films. AgNWs and polymer dendritic particles form an interpenetrating segregated network that ensures both a continuous conductive filler and a polymer network. Electrostatic assembly eliminates repulsion between negatively charged ANFs, cross-linked CS particles generate a stable three-dimensional network, and a "brick-mortar" structure composed of multiple materials contributes to topological enhancement. Sintering encourages local overlap and fusing of the AgNWs while reducing their internal flaws. Based on the above strategy, these films achieve a strength of 306.5 MPa, a toughness of 26.5 MJ m-3, and a conductivity of 392 S cm-1. Density functional theory (DFT) and Comsol simulations demonstrate that the introduction of CS thin layers leads to strong hydrogen bonds and three-dimensional continuous conductive networks. With its outstanding mechanical and electrical properties, the AgNW@ANF/CS-CH film demonstrates excellent electromagnetic shielding (22 879.1 dB cm2 g-1) and Joule heating (70 °C within 10 s) capabilities. This work presents a novel approach to fabricate high-performance conductive films and expand their potential applications in lightweight wearable electronics and electrothermal therapy.

Human pan-cancer analysis of the predictive biomarker for the CDKN3.

BACKGROUND: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3. METHODS: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways. RESULTS: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance. CONCLUSION: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.

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.

A pan-cancer analysis of TNFAIP8L1 in human tumors.

TNFAIP8L1, as a recently identified member in TNFAIP8 family, plays an important role in tumorigenesis. However, a pan-cancer analysis of TNFAIP8L1 in human tumors has not been conducted until now. The main purpose of study is to investigate TNFAIP8L1 during 33 different types of human tumors by using TCGA and GTEx. The pan-cancer analysis showed that TNFAIP8L1 was significantly over-expressed in 15 cancers and low-expressed in 9 cancers. There were distinct relations between TNFAIP8L1 expression and prognosis of patients with cancer. Furthermore, we also found that DNA methylation and RNA modification of TNFAIP8L1 were associated with many cancers. And then, we detected that TNFAIP8L1 level was positively associated with cancer-associated fibroblasts (CAFs) in many tumors. And, we obtained that TNFAIP8L1 expression was related with most of immune inhibitory and stimulatory genes in multiple types of tumors. We also found TNFAIP8L1 expression was correlated with most of chemokine, receptor, MHC, immunoinhibitor and immunostimulator gens in most of cancers. Moreover, we detected TNFAIP8L1 expression was associated with TMB and MSI in several tumors. Finally, TNFAIP8L1 gene had a significant positive association with 5 genes including BCL6B, DLL4, PCDH12, COL4A1 and DLL4 in the majority of tumors. GO enrichment and KEGG pathway analyses showed that TNFAIP8L1 in thepathogenesis of cancer may be related to "purine nucleoside binding," "purine ribonucleoside binding," "ECM-receptor interaction," etc. Our first pan-cancer study may provide a deep comprehending of TNFAIP8L1 in tumoeigenesis from different tumors.

Gradient heating induced better balance among water transportation, salt resistance and heat supply in a high performance multi-functional solar-thermal desalination device.

Solar-driven desalination (SDD) is a promising technology for addressing water scarcity. However, how to overcome the trade-off between water transportation and heat supply of the evaporator to achieve a high evaporation rate and good salt tolerance simultaneously remains a challenge. Here, a novel all-in-one multi-functional SDD evaporator undergoing gradient heating is used. This evaporator incorporates a hydrophilic PDA (polydopamine)@CNT(carbon nanotube)/PVA (polyvinyl alcohol) aerogel with vertically aligned structures as the water evaporation layer, enabling rapid water transportation. Surrounding the evaporation layer, there is a photothermal hydrophobic CCP (cotton/CNT/polydimethylsiloxane) film that serves as the heating layer, enhancing the heat supply to the evaporation layer. This innovative design strikes a favorable balance between water transportation and heat supply, facilitating high evaporation rates and good salt tolerance simultaneously, while also maximizing electricity generation. Due to the wettability difference between the evaporation layer (PVA aerogel) and heating layer (CCP film), a record stable temperature gradient of nearly 70 °C was formed between the CCP film and the PVA aerogel under 1 sun irradiation, so that heat on the high-temperature CCP film was continuously transferred to the low-temperature aerogel through its thermal conductive network, leading to a high evaporation rate of 6.96 kg m-2 h-1 under 1 sun irradiation in 5.0 wt% sodium chloride (NaCl) brine (higher than the world average seawater salinity (3.5 wt%)). Meanwhile, high flux directional flow of brine generated 130 mV stable voltage and 120 µA circuit current. Furthermore, the evaporator illustrates good stability for consecutive 7 days of testing and shows industry-leading comprehensive performance of SDD in actual use. More importantly, it was tested in real Bohai seawater under weak natural light, and fresh water generated can meet the recommended daily intake of water for 2.6 households and the simultaneously generated voltage reaches above 60 mV. In addition, the evaporator exhibits good adsorption capacity for heavy metals and dye molecules. This simple and universal solar evaporation structure is suitable for the assembly of gradient thermal structures for most solar thermal materials reported in the literature, which provides a new route for maximizing the use of solar energy for freshwater and electricity generation.

A pan-cancer analysis of the oncogenic role of YKT6 in human tumors.

YKT6, as a Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein with vesicle trafficking, plays an essential role in the development and progression of tumor. However, the gene of YKT6 has not been fully assessed in pan-cancer studies. We aim to investigate the gene of YKT6 across 33 different types of tumor by using the Cancer Genome Atlas, Gene Expression Omnibus database, and other several kinds of bioinformatic tools. YKT6 is significantly up-regulated in most tumors, and we found that overexpression of YKT6 is positively associated with poor prognosis of overall survival and poor disease-free survival prognosis in several tumors, such as Adrenocortical carcinoma, Bladder Urothelial Carcinoma, Head and Neck squamous cell carcinoma. We also detected distinct associations exist between YKT6 and tumor mutational burden or microsatellite instability with tumors. YKT6 expression was positively related to cancer-associated fibroblasts for TCGA tumors of colon adenocarcinoma and LGG. Furthermore, we discovered a significantly positively correlation between YKT6 expression and endothelial cell in tumors of colon adenocarcinoma, HNSC-HPV+, OV, READ and THCA. While a negative relationship was obtained between YKT6 expression and endothelial cell in KIRC. Moreover, "Syntaxin binding," "SNARE complex," "vesicle fusion" and "DNA replication" are involved in the influence of YKT6 on tumor pathogenesis. Our pan-cancer analysis offers a deep comprehending the gene of YKT6 in tumoeigenesis from viewpoint of clinical tumor samples.

Eltrombopag modulates the phenotypic evolution and potential immunomodulatory roles of monocytes/macrophages in immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. Loss of immune tolerance plays a crucial role in the pathogenesis of ITP. Monocytes and macrophages play an indispensable role in the pathophysiology of hematopoietic malignancies and have been implicated as key players in platelet destruction. Approximately 80% of adult patients with ITP exhibit corticosteroid treatment failure or become dependent, requiring novel therapy. Thrombopoietin (TPO) receptor agonists (TPO-RAs) have been used clinically to manage ITP effectively, however, little is known about the effect of TPO-RAs on monocyte and macrophage modulation in adult ITP. In this study, we investigated the phenotypic evolution and potential immunomodulatory roles of monocytes/macrophages in ITP patients receiving eltrombopag therapy. Results showed that the peripheral monocyte count positively correlated with IFN-γ/IL-4 ratio in ITP patients. Moreover, numerous phenotype-associated genes in ITP macrophages exhibited diverse responses, and ITP macrophages exhibited more M1-related characteristics. After eltrombopag therapy, the peripheral monocyte count and IFN-γ/IL-4 ratio significantly decreased in ITP patients. M1-related characteristics of ITP macrophages were partially reversed by eltrombopag. Therefore, this study revealed eltrombopag restored the monocyte dynamics and the associated Th1/Th2 imbalance, and partially reversed the M1-related characteristics of the ITP macrophages, which suggest the potential vital roles of TPO-RAs in regulating the monocyte/macrophage plasticity in ITP.

What is the context? Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease. Loss of immune tolerance plays a crucial role in the pathogenesis of ITP.Monocytes and macrophages play an indispensable role in the pathophysiology of hematopoietic malignancies and have been implicated as key players in platelet destruction.Approximately 80% of adult patients with ITP exhibit corticosteroid treatment failure or become dependent, requiring novel therapy. Thrombopoietin (TPO) receptor agonists (TPO-RAs) have been used clinically to manage ITP effectively, however, little is known about the effect of TPO-RAs on monocyte and macrophage modulation in ITP.What is new?In this study, we investigated the phenotypic evolution and potential immunomodula-tory roles of monocytes/macrophages in ITP patients receiving eltrombopag therapy.The expansion of peripheral monocytes positively correlated with IFN-γ/IL-4 ratio in ITP patients.ITP macrophages exhibited more M1-related characteristics.After eltrombopag therapy, the peripheral monocyte count and IFN-γ/IL-4 ratio significantly decreased in ITP patients.M1-related characteristics of ITP macrophages were partially reversed by eltrombopag.What is the impact?This study provides evidence that the potential vital roles of TPO-RAs in regulating the monocyte/macrophage plasticity in ITP.

[Research and Application of Seismic Performance of Medical Imaging Equipment].

In view of the shortage of research on the seismic performance of medical imaging equipment, this paper investigates and summarizes the seismic regulatory requirements and seismic tests of medical imaging equipment, and focuses on the parameter selection, detection steps, result evaluation and detection equipment requirements of seismic detection of medical imaging equipment. The seismic test data of medical imaging equipment with various installation modes are analyzed, and the seismic performance of medical imaging equipment is analyzed and summarized.

CircRNA circ_0000554 promotes ovarian cancer invasion and proliferation by regulating miR-567.

Circular RNAs (circRNAs) indicated potential modulating effects in tumor development. However, the specific role of circ_0000554 in ovarian tumor remains unknown. We found that circ_0000554 was overexpressed in ovarian tumor specimens and cells. Forced expression of circ_0000554 promoted cell growth, invasion, and epithelial to mesenchymal transition (EMT). We illustrated that miR-567 was downregulated in ovarian tumor specimens and cells. circ_0000554 was negatively correlated with miR-567 in ovarian tumor specimens. circ_0000554 sponged miR-567 expression in ovarian tumor. RIP assay showed that elevated expression of miR-567 could be enriched with circ_0000554. Luciferase reporter assay indicated that luciferase intensity was inhibited after treated with miR-567 mimic; however, the luciferase value of mut type was not decreased. Elevated expression of circ_0000554 suppressed miR-567 expression in HO8910 cell. circ_0000554 promoted ovarian tumor cell growth, invasion, and EMT via sponging miR-567. It suggested that circ_0000554 represent a potential therapy target for ovarian tumor.

Combined multiomics analysis reveals the mechanism of CENPF overexpression-mediated immune dysfunction in diffuse large B-cell lymphoma in vitro.

Diffuse large B-cell lymphoma (DLBCL) is one of the most common aggressive B-cell lymphomas with significant heterogeneity. More than half of patients are cured, but 40%-45% still face relapse or develop drug resistance, and the mechanism is not yet known. In this study, Centrimeric protein F (CENPF) overexpression was found in several DLBCL patients with relapsed or refractory disease compared to patients with complete remission. Thus, the human DLBCL cell line SU-DHL-4 was chosen for this study, and CENPF was upregulated in that cell line by using an adenovirus in vitro. Mass spectrometry-based quantitative proteome analysis was first performed, and the results showed that the expression levels of various proteins were increased when CENPF was upregulated, and these proteins are mainly involved in cellular processes, biological regulation, immune system processes and transcriptional regulator activity. Bioinformatics data analysis revealed that the main enriched proteins, including UBE2A, UBE2C, UBE2S, TRIP12, HERC2, PIRH2, and PIAS, were involved in various ubiquitin-related kinase activities and ubiquitination processes. Thus, ubiquitinome analysis was further performed, and the results demonstrated that proteins in many immune-related cellular pathways, such as natural killer cell-mediated cytotoxicity, the T-cell receptor signaling pathway and the B-cell receptor signaling pathway, were significantly deubiquitinated after CENPF was upregulated in DLBCL cells. Furthermore, TIMER2.0 was also used to reveal the association between CENPF and immune infiltration in DLBCL. The results showed that CENPF expression was positively correlated with CD8+ T cells, NK cells and B lymphocytes in DLBCL samples but negatively correlated with regulatory T cells. Aberrant activation of CENPF may induce immune dysregulation in DLBCL cells by mediating protein deubiquitination in various immune signaling pathways, which leads to tumor escape of DLBCL, but further experimental validation is still needed.

A metformin-based nanoreactor alleviates hypoxia and reduces ATP for cancer synergistic therapy.

Severe hypoxia in solid tumors limits the efficacy of oxygen (O2)-dependent photodynamic therapy (PDT). The overexpressed heat shock proteins (HSPs) in tumor cells hamper the effect of photothermal therapy (PTT). Herein, a tumor oxygenation-enhanced and ATP-reduced gelatin nanoreactor (MCGPD ∼ RGD NPs) for PDT/PTT-augmented combination cancer therapy is reported. In this nanosystem, the Arg-Gly-Asp (RGD) peptides of MCGPD ∼ RGD NPs can ensure accurate recognition and sufficient accumulation in the tumor site. After accumulation, doxorubicin (DOX) can be released from MCGPD ∼ RGD NPs in a mild acidic tumor microenvironment (TME) for highly efficient chemotherapy. Upon 808 nm laser irradiation, the overexpressed matrix metalloproteinase-2 (MMP-2) in the TME and the heat produced from the PDA coating trigger Gel NP degradation to expose chlorin e6 (Ce6) and Met from the cavity of MCGPD ∼ RGD NPs. The exposed Met elevates the O2 content and reduces ATP production in tumor sites to spur the successful O2-dependent PDT and HSP-mediated PTT. The heat generated by the PDA coating directly kills the tumor cells to ensure PTT and amplifies the chemotherapeutic effect. In vitro and in vivo assays indicate that MCGPD ∼ RGD NPs have excellent ability to promote cell apoptosis and to inhibit tumor growth. Overall, this smart responsive hydrogel nanosystem with hypoxia-relieving capacity and ATP-decreasing performance provides a promising strategy against cancer.

Characteristics of macrophages from myelodysplastic syndrome microenvironment.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplasms. The progression of malignancy is closely associated with immune regulation. Macrophages are indispensable tissue components and have been proposed to play a role in the pathophysiology of hematopoietic malignancies. However, the specific role of macrophages in the development of MDS remains unclear. Here, we investigated the characteristics and phenotypic evolution of macrophages from patients with MDS. Macrophages from patients with MDS expressed CD68, CD86 and CD163. Furthermore, MDS macrophages exhibited more M2-related characteristics. Moreover, a number of phenotype-associated genes in MDS macrophages exhibited diverse responses to iron overload or iron chelation upon stimulation by ferric chloride or deferoxamine (DFO, an iron chelator). Ferric chloride polarized MDS macrophages to exhibit more M1-related characteristics, a phenomenon that could be partially reversed by DFO. Therefore, this study reveals the characteristics and phenotypic evolution of MDS macrophages and broadens the knowledge of macrophage plasticity in hematopoietic malignancies.

Reinforcing the Induction of Immunogenic Cell Death Via Artificial Engineered Cascade Bioreactor-Enhanced Chemo-Immunotherapy for Optimizing Cancer Immunotherapy.

Traditional chemo-immunotherapy can elicit T cell immune response by inducing immunogenic cell death (ICD), however, insufficient ICD limits the lasting antitumor immunotherapeutic efficacy. Herein, tadpole-ovoid manganese-doped hollow mesoporous silica coated gold nanoparticles (Au@HMnMSNs) as biodegradable catalytic cascade nanoreactors are constructed to generate intratumoral high-toxic hydroxyl radicals combined with DOX and Aspirin (ASA) for enhancing the induction of ICD and maturation of dendritic cells (DCs). The released Mn2+ can catalyze endogenous H2 O2 to hydroxyl radicals, while internal gold nanoparticles mimetic glucose oxidase (GOx) converted glucose into H2 O2 to accelerate the generation of hydroxyl radicals. On the other hand, tadpole oval-structured Au@HMnMSNs can avoid the inactivation of gold nanoparticles due to strong protein adsorption. The introduction of ASA is to recruit DCs and cytotoxic T lymphocytes (CTLs) to tumor sites and restrain the intratumoral infiltration of immunosuppressive cells by decreasing the expression of prostaglandin E2 (PGE2 ). Accordingly, this work presents a novel insight to introduce GOx-like catalytic cascade ICD nano-inducer into antitumor immunotherapy for synergistic tumor therapy.

Factors Associated with Promoted Proliferation of Osteosarcoma by Peptidylarginine Deiminase 4.

Osteosarcoma is the most common type of bone malignancy, and the pathogenesis has not been entirely elucidated yet. An important deimination modification enzyme PADI4 (peptidylarginine deiminase 4) has attracted much attention in recent years for its important function in several kinds of human tumors. However, the role of PADI4 on osteosarcoma tumorigenesis remains largely unrevealed. Here, we first assessed the effect of PADI4 on osteosarcoma proliferation by the CCK8 method and colony formation assay. Ectopically expressing PADI4 positively regulates the colony formation capacity of both U2OS and Saos-2 cells. Furthermore, we explored the related mechanism and showed that PADI4 could stimulate Wnt/ß-catenin and MEK/ERK signaling in both U2OS and Saos-2 cells. Then, we detected expression of PADI4 in human tissues of osteosarcoma and revealed that differential expression of PADI4 was associated with tumorigenesis of osteosarcoma. Last, we performed the in vivo experiment in nude mice and results also showed PADI4 could affect the tumor growth. In conclusion, this work revealed that PADI4 could upregulate the proliferation of osteosarcoma, mainly via the Wnt/ß-catenin and MEK/ERK signaling pathway. This study gives us new insight into the regulation mechanism of osteosarcoma proliferation and highlights PADI4 as a promising target for osteosarcoma diagnosis and treatment.

The iron chelator deferoxamine decreases myeloma cell survival.

OBJECTIVE: This study evaluated serum ferritin (SF) levels and investigated their relationships with various clinical markers in patients with multiple myeloma (MM). Furthermore, the effects and molecular mechanism of deferoxamine (DFO) in myeloma cells were studied. METHODS: Clinical data from 84 patients with MM were collected to evaluate SF content and its relationship with several important clinical parameters. MM1S and MM1R myeloma cells were chosen to investigate the effects of iron and DFO on cell survival and apoptosis. RESULTS: Increased SF levels were detected in newly diagnosed patients, especially those with stage III disease or the κ isotype. SF content was positively correlated with ß2-microglobulin, interleukin-6, and lactate dehydrogenase expression. Furthermore, patients with progressive or relapsed disease had higher SF levels. Importantly, iron chelation with DFO efficiently inhibited myeloma cell survival and accelerated apoptosis by regulating apoptosis-related genes. CONCLUSIONS: The importance of SF for MM was highlighted. Additionally, it is suggested that DFO may be a good therapeutic option for MM.

Biodegradable copper-metformin nanoscale coordination polymers for enhanced chemo/chemodynamic synergistic therapy by reducing oxygen consumption to promote H2O2 accumulation.

Chemo/chemodynamic synergistic therapy is a promising strategy to improve the antitumor effect. However, hypoxia and a limited amount of hydrogen peroxide (H2O2) in the tumor microenvironment (TME) severely restrict the therapeutic efficacy of this combined treatment. Herein, we report biodegradable doxorubicin (Dox)-loaded copper-metformin (Met) nanoscale coordination polymers (Dox@Cu-Met NPs), which exert a chemo/chemodynamic synergistic therapeutic effect by reducing oxygen (O2) consumption to promote H2O2 accumulation in the tumor. Inside tumor cells, Met can inhibit the consumption of O2 to relieve tumor hypoxia by suppressing mitochondrial respiration. The alleviated-tumor hypoxia can not only elevate H2O2 content via the Dox-activated cascade reaction of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) and superoxide dismutase (SOD), but also improve the efficacy of Dox. More importantly, the depletion of glutathione (GSH) accompanies the whole treatment process, which can realize the conversion of Cu2+ to Cu+ and boost reactive oxygen species (ROS) accumulation to improve chemodynamic therapy (CDT) efficacy. Meanwhile, Met is expected to cut off the energy supply by inhibiting respiration, leading to starvation therapy. In vivo investigations demonstrate that tumor growth is significantly inhibited through the enhanced chemo/chemodynamic synergistic treatment. This work provides a new paradigm for cancer therapy using an economical and straightforward method to construct a synergistic nanomedicine platform.

Carborane-Containing Aromatic Polyimide Films with Ultrahigh Thermo-Oxidative Stability.

Carborane-containing aromatic polyimide (CPI) films with ultrahigh thermo-oxidative stability at 700 °C have been prepared by casting poly(amic acid) (PAA) resin solution on a glass surface, followed by thermal imidization at elevated temperatures. The PAA solution was prepared by copolymerization of an aromatic dianhydride and an aromatic diamine mixture, including carborane-containing aromatic diamine in an aprotic solvent. The CPI films showed excellent thermo-oxidative stability at 700 °C due to the multilayered protection layers formed on the film surface by thermal conversion of the carborane group into boron oxides. The boron oxide layer enhanced the degradation activation energy and suppressed the direct contact of inner polymer materials with oxygen molecules in a high-temperature environment, acting as a "self-healing" skin layer on the polyimide materials. The CPI-50 film was still flexible and maintained 50% retention of mechanical strength even after thermo-oxidative aging at 700 °C/5 min. The mechanism of thermo-oxidative degradation was proposed.

Effects of Deferoxamine on Leukemia In Vitro and Its Related Mechanism.

BACKGROUND This study aimed to investigate the effect of deferoxamine (DFO) on leukemia in vitro, and to explore the underlying molecular mechanism. MATERIAL AND METHODS K562 leukemia cells were treated with various concentrations of DFO (10, 50, and 100 µmol/l) with or without 10 µmol/l ferric chloride for 12 h. Then, total cellular iron was detected. CCK-8 kit and flow cytometry were used for cell viability and apoptosis detection. In addition, expression of apoptosis-related genes was determined by Western blotting and qRT-PCR, respectively. RESULTS The results suggested that DFO significantly inhibited K562 cell viability and induced cell apoptosis in a dose-dependent manner. We also found that the protein and mRNA levels of Bax, p53, and Fas dose-dependently increased in DFO-treated K562 cells, while the level of Bcl-2 markedly decreased in a dose-dependent manner. Moreover, the findings showed that ferric chloride eliminated these effects on K562 cells caused by DFO treatment. CONCLUSIONS Our results indicate that DFO plays a protective role in leukemia via inhibiting leukemia cell viability and inducing cell apoptosis by the regulation of apoptosis-related genes expression.

A rare case of multicentric castleman's disease transforms into multiple myeloma and its successful treatment.

Multicentric Castleman's disease (MCD) is a rare kind of lymphoproliferative disorder characterized by systemic problems such as frequent fever, fatigue and weight loss with angiofollicular lymph node hyperplasia. However, unlike unicentric Castleman's disease (UCD) with long-time survival by surgery and local radiotherapy, MCD remains poor prognosis due to no well-defined optimal treatment strategies and high risk of developing malignances especially lymphoma. We reported a case of MCD who received chemotherapy by ECHOP with unsatisfactory outcome and then oral administration with thalidomide combined with prednisone without disease progression after therapy. After 3 y, his MCD turned into multiple myeloma (MM) and accompanied by obvious response to combination of thalidomide with prednisone. Nowadays, there is no standard of therapy yet established for MCD. We successfully treated one such patient and found thalidomide based therapy may have a significant effect on MCD. We also proposed further researches with therapeutic potential about thalidomide for MCD.