Search

Photodynamic therapy (PDT) is a novel and non-invasive treatment that induces apoptosis and autophagy. Autophagy could play a pro-survival role, thus inhibiting autophagic activity might be a promising method to enhance the effectiveness of PDT for tumors. In the present study, photosensitizer Chlorin e6 (Ce6) was found to mainly locate in endoplasmic reticulum, and to a lesser extent in mitochondria and lysosome. Chlorin e6 photodynamic therapy (Ce6-PDT) could kill human colon cancer SW620 cells by inducing apoptotic cell death, and autophagy also induced by Ce6-PDT in colon cancer cells. More importantly, autophagy played a pro-survival role. Its inhibition enhanced Ce6-PDT-associated apoptotic cell death because cells pretreated with the typical autophagy inhibitor 3-methyladenine exhibited higher cytotoxicity and apoptotic cell death.

Multiple myeloma (MM) is an aggressive malignancy characterized by terminally differentiated plasma cells accumulation in the bone marrow (BM). MM BM exhibits elevated MΦs (macrophages) numbers relative to healthy BM. Current evidence indicates that MM-MΦs (MM-associated macrophages) have pro-myeloma functions, and BM MM-MΦs numbers negatively correlate with patient survival. Here, we found that BMI1, a polycomb-group protein, modulates the pro-myeloma functions of MM-MΦs, which expressed higher BMI1 levels relative to normal MΦs. In the MM tumor microenvironment, hedgehog signaling in MΦs was activated by MM-derived sonic hedgehog, and BMI1 transcription subsequently activated by c-Myc. Relative to wild-type MM-MΦs, BMI1-KO (BMI1 knockout) MM-MΦs from BM cells of BMI1-KO mice exhibited reduced proliferation and suppressed expression of angiogenic factors. Additionally, BMI1-KO MM-MΦs lost their ability to protect MM cells from chemotherapy-induced cell death. In vivo analysis showed that relative to wild-type MM-MΦs, BMI1-KO MM-MΦs lost their pro-myeloma effects. Together, our data show that BMI1 mediates the pro-myeloma functions of MM-MΦs.

Engineered bacteria are promising bioagents to synthesize antitumor drugs at tumor sites with the advantages of avoiding drug leakage and degradation during delivery. Here, we report an optically controlled material-assisted microbial system by biosynthesizing gold nanoparticles (AuNPs) on the surface of

Purpose: The aim of this study was to investigate the symptom clusters and associated clinical factors in ambulatory multiple myeloma patients undergoing medication therapy. We also aim to determine the correlations between symptom clusters and the patients’ quality of life. Methods: A total of 174 multiple myeloma patients hospitalized in the hematology day unit were included in this study. A cross-sectional survey aimed to examine the symptoms and quality of life was conducted. The symptoms were assessed by the Chinese version of Condensed Memorial Symptom Assessment Scale. The quality of life was measured with the Functional Assessment of Cancer Therapy-General. Principal component analysis was used to identify symptom clusters. Independent-Samples t test and Chi-square test were used for comparisons between groups. Spearman’s Rank Correlation Analysis was used to identify correlations.Results: We identified three symptom clusters in multiple myeloma patients: psychological, pain-dry mouth-difficulty sleep, and fatigue symptom cluster. For each symptom cluster, the patients could be categorized in severe-symptom group or mild-symptom group based on the distress of the symptoms. The patients in each group exhibited differential demographic and clinical features. The distress of each symptom cluster was adversely correlated with patients’ quality of life.Conclusions: The ambulatory multiple myeloma patients undergoing medication therapy experience multiple symptoms, which can be categorized into three symptom clusters. The distress of each symptom cluster was associated with patients’ demographic and clinical characteristics. The presence and distress of these symptom clusters have adverse impact on patient’s quality of life.

Weight loss and muscle wasting can have devastating impacts on survival and quality of life of patients with cancer cachexia. Here, we have established a hybrid mouse of ApcMin/+ mice and MMP12 knockout mice (ApcMin/+; MMP12-/-) and found that knockout MMP12 can suppress the weight and muscle loss of ApcMin/+ mice. In detail, we found that interleukin 6 was highly upregulated in the serum of cancer patients and MMP12 was increased in muscle of tumor-bearing mice. Interestingly, the interleukin 6 secreted by tumor cells led to MMP12 overexpression in the macrophages, which further resulted in degradation of insulin and insulin-like growth factor 1 and interruption of glycolipid metabolism. Notably, depletion of MMP12 prevented weight loss of ApcMin/+ mice. Our study uncovers the critical role of MMP12 in controlling weight and highlights the great potential of MMP12 in the treatment of cancer cachexia.

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

Background Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM. Patients and Methods Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS). Results A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P Conclusion These data support the use of D-Vd in Chinese patients with RRMM.

Background: Ibrutinib is an oral covalent Bruton’s tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies. Some studies have found an increased risk of bleeding with ibrutinib. Some studies, however, found no significant differences in the risk of major bleeding between patients treated with ibrutinib and those with other regimens. So, a systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to estimate the risk of bleeding associated with ibrutinib in patients with B-cell malignancies.Methods: A systematic search of PUBMED, EMBASE, Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from January 2000 to February 2020 to identify RCTs by comparing ibrutinib with other agents or placebo in B-cell malignancies. The RevMan software (version 5.3) was used to carry out this analysis, and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI).Results: There were 11 eligible RCTs (4,288 patients). All studies reported major bleeding, and seven studies reported overall bleeding (any-grade bleeding). Ibrutinib was associated with a significantly increased risk of bleeding (overall bleeding and major bleeding) in patients with B-cell malignancies [RR = 2.56, 95% CI 1.68–3.90, p < 0.0001 and RR = 2.08, 95% CI 1.36–3.16, p = 0.0006, respectively]. The bleeding (overall bleeding and major bleeding) risk in patients with CLL was more obvious [RR = 3.08, 95% CI 2.07–4.58, p < 0.00001 and RR = 2.46, 95% CI 1.37–4.41, p = 0.003, respectively]. There were no statistically significant differences for risk of bleeding between the subgroups based on dose and treatment setting.Conclusion: Ibrutinib was associated with a significantly higher risk of bleeding (both overall bleeding and major bleeding) in patients with B-cell malignancies, especially in CLL.

Epidermal growth factor receptor (EGFR) is widely accepted in cancer diagnosis and targeted therapy. Shkbp1 is an upstream molecule of EGFR, which prevents EGFR degradation. However, the role of Shkbp1 in tumor remains to be clarified. Herein we induced tumor in the lungs of Shkbp1 knockout mice with chemical drugs to investigate the function of Shkbp1. Compared with wild-type mice, tumors in the lungs were significantly fewer in Shkbp1 knockout mice. To further explore the biological characteristics and functions of Shkbp1 in cancer cells, we established cell lines with overexpression and low expression of Shkbp1, respectively. Results from our experiments showed that low expression of Shkbp1 in lung cancer remarkably inhibited cancer cell migration and invasion, while overexpression of Shkbp1 promoted their migration and invasion, which indicated that Shkbp1 was closely related with tumor migration and invasion. The mRNA expression analysis of 494 matched tumor and adjacent non-tumor tissues (data derived from TCGA database) revealed that Shkbp1 was associated with the clinic TNM staging. Furthermore, immunohistochemistry (IHC) analysis of tissue microarrays showed that Shkbp1 was also correlated with lymphatic metastasis. Mechanistically, we observed that Shkbp1 was associated with epithelial-mesenchymal transition (EMT) marker. More interestingly, Shkbp1 was also expressed in a variety of immune cells, and we hereby used a subcutaneous transplantation tumor model and a metastasis model created by tail vein injection to explore whether Shkbp1 could impact tumor growth. The results showed that Shkbp1 knockout reduced tumor growth in both tumor models. In general, our results suggest that knocking out Shkbp1 in either immune cells or tumor cells could suppress tumor growth and metastasis.

Two new dibenzyl derivatives, dendrocandins V-W (

Background Anemia is a common complication of multiple myeloma (MM). Recombinant human erythropoietin (rhEPO) and blood transfusions are two general treatments for anemia. Methods In a retrospective study, we compared the efficacy and treatment response of rhEPO to those of blood transfusions on anemia and sought to determine its prognostic value in for these patients. The 94 patients who received rhEPO were divided into high-dose (≥160,000 U/month) and low-dose (P

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979

Background Idiopathic thrombocytopenic purpura (ITP) especially refractory and (or) relapsed ITP, is a serious and global health burden and its clinical treatment is far from being satisfied. Hetrombopag is a novel, small-molecule thrombopoietin receptor agonist for the treatment of chronic idiopathic thrombocytopenic purpura (CITP). Objectives This first-in-patient study aimed to investigate the safety, pharmacokinetics, and anticipated therapeutic dose of hetrombopag in CITP patients. Methods In this multicenter, first-in-patient study, CITP patients received hetrombopag in a dose escalation (2.5 mg/day, 5 mg/day, or 7.5 mg/day) cohort. All patients received hetrombopag in fasting condition once daily for 2 weeks. Results Of 44 patients screened, 32 were enrolled and treated. Most adverse events were graded 1 to 2 (ie, mild to moderate), and the incidence and severity were similar for three study cohorts. The pharmacokinetics of hetrombopag were found to be nonlinear with greater than dose-proportional: 12.5% of patients (1/8) in the 2.5 mg/d cohort, 58.3% of patients (7/12) in the 5 mg/d cohort, 66.7% of patients (8/12) in the 7.5 mg/d cohort reached the primary study endpoint of a platelet count exceeding 50 × 109 /L on day 28. Conclusion Hetrombopag was well tolerated and preliminarily efficacious. Efficacy, safety, and pharmacokinetic data suggest that 7.5 mg hetrombopag once daily was the anticipated therapeutic dose of hetrombopag in CITP patients and has been recommended for investigation in a later confirmatory clinical study of hetrombopag.

As an important industry of the national economy, the development of furniture manufacturing industry is very rapid. In particular, with the development of panel furniture industry, wood-based panels have become a necessary choice for furniture material for modern families in recent years. As a new particleboard material, in order to be more widely used in the furniture industry, it is not enough to have the characteristics of environmental protection. The material should also have excellent appearance and dimensional stability, so as to change people&rsquo, s dependence on traditional wood-based panels. In this study, the rice straw particleboard (RSP) substrate was veneered by Betula sp. and Cyclobalanopsis glauca. In the process of veneering, different RSP specimens were treated by different sanding thicknesses and moisture contents of the RSP substrate, glue spread, species and thickness of veneer. The dimensional stability of different RSP specimens after veneering was analyzed. Based on the same variables, the change in the panel dimension and warp degree of the specimens of RSP which the sanding thickness was 0.2 mm were higher than the specimens with a sanding thickness of 0.6 mm. The dimensional stability of specimens of Cyclobalanopsis glauca veneer was better than that of Betula sp. veneer. A certain degree of change within the appropriate moisture content had a little effect on dimensional stability of veneered RSP. The greater of the amount of glue, the worse the dimensional stability of veneered RSP. The thinner the veneer, the worse was the dimensional stability of the veneered RSP.

The development of social economy has promoted the rise of Internet financial information service industry in China, and the diversified service revenue recognition of this industry has brought certain difficulties to the audit work. The article starts from the difficulty of revenue recognition in the Internet financial information service industry. Taking the auditing failure case of DZH as an example, it focuses on analyzing the problems in the revenue recognition and the fault of Shu Lun Pan, and exploring the problems that CPAs should pay attention to when auditing the income of the Internet financial information service industry. Analysis found that CPAs should maintain professional cautiousness, be alert to audit risks, optimize audit procedures, standardize audit work, and clarify audit scope, obtain adequate and appropriate audit evidence, based on understanding the difficulties in revenue recognition in the industry to improve the audit quality of revenue recognition in the Internet financial information service industry.

Chromosome copy-number variations are a hallmark of cancer. Among them, the prevalent chromosome 17p deletions are associated with poor prognosis and can promote tumorigenesis more than TP53 loss. Here, we use multiple functional genetic strategies and identify a new 17p tumor suppressor gene (TSG), plant homeodomain finger protein 23 (PHF23). Its deficiency impairs B-cell differentiation and promotes immature B-lymphoblastic malignancy. Mechanistically, we demonstrate that PHF23, an H3K4me3 reader, directly binds the SIN3–HDAC complex through its N-terminus and represses its deacetylation activity on H3K27ac. Thus, the PHF23–SIN3–HDAC (PSH) complex coordinates these two major active histone markers for the activation of downstream TSGs and differentiation-related genes. Furthermore, dysregulation of the PSH complex is essential for the development and maintenance of PHF23-deficient and 17p-deleted tumors. Hence, our study reveals a novel epigenetic regulatory mechanism that contributes to the pathology of 17p-deleted cancers and suggests a susceptibility in this disease. Significance: We identify PHF23, encoding an H3K4me3 reader, as a new TSG on chromosome 17p, which is frequently deleted in human cancers. Mechanistically, PHF23 forms a previously unreported histone-modifying complex, the PSH complex, which regulates gene activation through a synergistic link between H3K4me3 and H3K27ac. This article is highlighted in the In This Issue feature, p. 1

Under the background of the Internet, discussions are conducted in this paper on the teaching practice of political and ideological curriculum in materials disciplines from teaching idea, teaching design, teaching process and teaching based evaluation mechanism, which can effectively improve the students' ideological and political participation and satisfaction. As a result, it improves the teaching effect on ideological and political theory, providing certain references for other educational reform in ideology and politics. As a result, it brings new opportunities for the development of material specialty.

Tumor cells obtain energy supply from different metabolic pathways to maintain survival. In this study, a tumor acidity-responsive spherical nanoparticle (called as LMGC) was designed by attaching glucose oxidase (GOx) and mineralizing calcium carbonate on the surface of liquid metal nanoparticles to integrate the synergistic effect of adenosine triphosphate (ATP) generation inhibition and photothermal therapy (PTT) for enhanced tumor therapy. After GOx catalysis, the process of glycolysis was inhibited, and the increased H

Ethnopharmacological relevance Euonymus alatus (Thunb.) Siebold (family Celastraceae) is a deciduous woody shrub that is recorded in ShenNong BenCaoJing. It has been widely used for diabetes in traditional Chinese medicine. AIM OF THE STUDY: This study aimed to identify the most effective extract of Euonymus alatus (EA) against high glucose-induced endothelial cells in vitro, evaluate its pharmacological effect on retinopathy in diabetic mice and explore its underlying mechanism by RNA sequencing. Methods Retinal vascular endothelial cells (RF/6A) were treated with normal glucose (5.5 mmol/L glucose), high glucose (25 mmol/L glucose) or high glucose plus methanol extracts of EA (MEA), ethyl acetate extracts of EA (EEA) or water extracts of EA (WEA). The cytotoxicity and cell viability were determined by Cell Counting Kit-8 (CCK-8) assay. Cell migration was examined using the Transwell assay, and tube formation ability was measured using the Matrigel assay. Then, the KK-Ay mice were administered WEA or water for 12 weeks. The velocities of ocular blood flow were determined by Doppler ultrasound. RNA sequencing and reverse transcription quantitative PCR (RT–qPCR) were performed on WEA-stimulated RF/6A cells to reveal the underlying mechanism. Results The cytotoxicity assay found that 30 μg/mL MEA, 20 μg/mL EEA and 30 μg/mL WEA had no toxic effect on RF/6A cells. The cell viability results showed that MEA, EEA and WEA all decreased cell viability. Compared with the high-glucose group, both MEA and WEA decreased the number of migrated cells, while the inhibition rate of WEA was higher. The Matrigel results showed that 30 μg/mL WEA effectively reduced the total tube length. Moreover, WEA improved the haemodynamics of the central retinal artery. RNA sequencing coupled with RT–qPCR verified that WEA regulated angiogenesis-related factors in high glucose-stimulated RF/6A cells. Conclusions WEA inhibits the migration and tube formation of RF/6A cells and improves diabetic retinopathy (DR) by mediating angiogenesis.

Polarized structure oxides have unique advantages in photovoltaic field with internal electric field, but it is difficult to make full use of them with visible light in general due to their large band gap. The stability and electronic structure properties of a novel R3c polarization structure MgSnX3 (X O, S and Se) have been calculated by first-principles method. The calculated results show that the elastic coefficients and phonon frequencies of R3c-MgSnX3 (X O, S and Se) satisfy the mechanical stability conditions. R3c-MgSnX3 (S and Se) maintains a higher theoretical ferroelectric polarization strength than R3c-MgSnO3, and at the same time reduces the band gap obviously. Spectroscopic Limited Maximum Efficiency calculation also shows that MgSnS3 has high photoelectric conversion efficiency and is a potential ferroelectric photovoltaic material with high efficiency.

Periventricular white matter injury (PWMI) is very common in survivors of premature birth, and the final outcomes are a reduction in myelinated neurons leading to white matter hypomyelination. How and (or) why the oligodendrocyte lineage develops abnormally and myelination is reduced is a hot topic in the field. This study focuses on the effect of intrauterine inflammation on the proliferation of oligodendrocyte lineage cells and the underlying mechanisms. Lipopolysaccharide (LPS) (300 μg/kg) was intraperitoneally injected into pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish a rat model of intrauterine infection-induced white matter injury. Corpus callosum tissues were collected at postnatal day 14 (P14) to quantify the number of oligodendrocytes, the number and proliferation of oligodendrocyte precursor cells (OPCs), and the expression of myelin proteins (MBP and PLP). Furthermore, the expression of Wnt and Notch signaling-related proteins was analyzed. The results showed that the number of oligodendrocytes in the corpus callosum tissues of LPS-treated rats was reduced, and the expression levels of myelinating proteins were down-regulated. Further analysis showed that the Notch signaling pathway was down-regulated in the LPStreated group. These results indicate that intrauterine LPS may inhibit the proliferation of OPCs by down-regulating the Notch rather than the Wnt signaling pathway, leading to hypomyelination of white matter.

Osteolytic lesion (OL) and bone damage are common complications in multiple myeloma (MM). This study aimed to analyze the occurrence of OL in MM patient groups of different ages and genders.We performed a retrospective study of 762 MM patients admitted to West China Hospital from 2009 to 2014 to investigate the association between OL occurrence with patients' ages and genders. The presence or absence of OL was confirmed by X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) examination. We also downloaded MM patients' published gene expression profiles and performed microarray-based analyses to identify differentially regulated genes and signaling pathways. Finally, we examined target gene expressions in MM bone marrow (BM) biopsies through immunohistochemistry (IHC).We calculated the frequency of OL in female and male MM patients with different age cut-offs. From West China Hospital data, we found that in young female MM patients aged under 55, the frequency of OL was 16.67%, significantly lower than the frequencies in other groups of patients (young males: 34.38%; old males: 31.04%; old females: 29.24%; p .05). The same was true in another independent MM cohort. Microarray-based analyses showed that Microtubule Associated Serine/Threonine Kinase Family Member 4 (MAST4), an estrogen-responsive gene, expression was up-regulated in MM patients without OL and in young female MM patients (p .05). The expression of MAST4 in MM BM was confirmed by IHC. The perspective of cell signaling network suggested that MAST4 might interact with phosphatase and tensin homolog (PTEN) and control the expression of a panel of osteoclast-regulatory cytokines, such as TNFSF11 and CCL2.Young female (55 years) MM patients have significantly lower OL frequency than other groups. MAST4 gene expression is thought to be associated with this phenomenon.

It is believed that the alteration of tissue microenvironment would affect cancer initiation and progression. However, little is known in terms of the underlying molecular mechanisms that would affect the initiation and progression of breast cancer. In the present study, we use two murine mammary tumor models with different speeds of tumor initiation and progression for whole genome expression profiling to reveal the involved genes and signaling pathways. The pathways regulating PI3K-Akt signaling and Ras signaling were activated in Fvb mice and promoted tumor progression. Contrastingly, the pathways regulating apoptosis and cellular senescence were activated in Fvb.B6 mice and suppressed tumor progression. We identified distinct patterns of oncogenic pathways activation at different stages of breast cancer, and uncovered five oncogenic pathways that were activated in both human and mouse breast cancers. The genes and pathways discovered in our study would be useful information for other researchers and drug development.

The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P

Tissue engineering is a promising strategy to repair spinal cord injury (SCI). However, a bioscaffold with mechanical properties that match those of the pathological spinal cord tissue and a pro-regenerative matrix that allows robust neurogenesis for overcoming post-SCI scar formation has yet to be developed. Here, we report that a mechanically enhanced decellularized spinal cord (DSC) scaffold with a thin poly (lactic-co-glycolic acid) (PLGA) outer shell may fulfill the requirements for effective in situ neuroengineering after SCI. Using chemical extraction and electrospinning methods, we successfully constructed PLGA thin shell-ensheathed DSC scaffolds (PLGA-DSC scaffolds) in a way that removed major inhibitory components while preserving the permissive matrix. The DSCs exhibited good cytocompatibility with neural stem cells (NSCs) and significantly enhanced their differentiation toward neurons in vitro. Due to the mechanical reinforcement, the implanted PLGA-DSC scaffolds showed markedly increased resilience to infiltration by myofibroblasts and the deposition of dense collagen matrix, thereby creating a neurogenic niche favorable for the targeted migration, residence and neuronal differentiation of endogenous NSCs after SCI. Furthermore, PLGA-DSC presented a mild immunogenic property but prominent ability to polarize macrophages from the M1 phenotype to the M2 phenotype, leading to significant tissue regeneration and functional restoration after SCI. Taken together, the results demonstrate that the mechanically matched PLGA-DSC scaffolds show promise for effective tissue repair after SCI.

Two-dimensional ferromagnetic van der Waals (2D vdW) heterostructures have opened new avenues for creating artificial materials with unprecedented electrical and optical functions beyond the reach of isolated 2D atomic layered materials, and for manipulating spin degree of freedom at the limit of few atomic layers, which empower next-generation spintronic and memory devices. However, to date, the electronic properties of 2D ferromagnetic heterostructures still remain elusive. Here, we report an unambiguous magnetoresistance behavior in CrI3/graphene heterostructures, with a maximum magnetoresistance ratio of 2.8%. The magnetoresistance increases with increasing magnetic field, which leads to decreasing carrier densities through Lorentz force, and decreases with the increase of the bias voltage. This work highlights the feasibilities of applying two-dimensional ferromagnetic vdW heterostructures in spintronic and memory devices.

Dickkopf-1 (DKK1) is an ideal target for the immunotherapy of multiple myeloma. Heat Shock protein70 (HSP70) is a class of important molecular chaperone to promote antigen presentation. Homologous xenogeneic antigens can enhance immunogenicity and induce stronger anti-tumor immune response than that of allogeneic ones. Therefore, we constructed human DKK1 and human HSP70 DNA fusion vaccine (hDKK1-hHSP70), and then determined its anti-tumor immuno- genicity and anti-tumor effects on immunizing BALB/c mice already inoculated with NS-1 murine multiple myeloma cells in prophylactic and therapeutic models using cytotoxic T lymphocytes, enzyme-lined immunosorbent assay, flow cytometry, immunohistochemistry and Hochest staining. The side effects of vaccines were also monitored. We found that hDKK1-hHSP70 fusion vaccine could significantly inhibit tumor growth and prolonged the survival of the mice, whether prophylactic or therapeutic immunotherapy in vivo, by eliciting both humoral and cellular tumor-specific immune responses. A significant decrease of proliferation and increase of apoptosis were also observed in the tumor tissues injected with hDKK1-hHSP70 vaccine. These findings showed the xenogeneic homologous vaccination had stronger immunogenicity and minimal toxicity. Our study may provide an effective and safety immonutheraphy strategy for multiple myeloma.

Hematologic malignancies (HMs) are blood diseases that have a great threat on human health, including all kinds of leukemia, lymphoma and myeloma. Chemotherapy is the basic and effective treatment. However, the side effects, relapse and drug resistance of the HMs remain a clinical challenge. Dox is an effective anthracycline drug for the HMs therapy, but the application is limited due to the adverse effects, especially the cardiotoxicity. Nanomedicine is an effective means to solve the problems that chemotherapeutics are facing, including reduction of the side effect, possessing targeting actions, enhancement of the antitumor activities, increasing the circulation time and so on. Recently many types of nanomedicines have been developed, including the liposomes, micelles, nanoparticles etc. This review aims to provide an overview of the recent progress of Dox nanomedicine in hematologic malignancies.

Current disjunct patterns can result from long‐distance dispersal or postglacial contraction. We herein investigate the evolutionary history of Triplostegia to elucidate the disjunction between the Himalaya–Hengduan Mountain region (HHM) and Taiwan (TW). Genetic structure of Triplostegia was investigated for 48 populations using sequences from five chloroplast loci and the ribosomal nuclear internal transcribed spacer. Divergence time estimation, ancestral area reconstruction, and species distribution modeling (SDM) were employed to examine the biogeographic history of Triplostegia. Substantial genetic differentiation among populations from southwestern China (SW), Central China (CC), and TW was detected. Triplostegia was inferred to have originated in SW, and diversification began during the late Miocene; CC was colonized in the mid‐Pliocene, and TW was finally colonized in the early Pleistocene. SDM suggested an expansion of climatically suitable areas during the Last Glacial Maximum and range contraction during the Last interglacial in Triplostegia. Disjunction between HHM and TW in Triplostegia is most likely the consequence of topographic isolation and postglacial contraction. The potential climatic suitability areas for Triplostegia by 2070s (2061–2080) are predicted to slightly shrink and move northward. With continued global warming and human‐induced deforestation, extinction risk may increase for the cold‐adapted species, and appropriate strategies should be employed for ecosystem conservation.

Object To study the outcomes of GnRHa on final adult height in Chinese idiopathic central precocious puberty (ICPP) girls and the involved factor(s) that can predict height gain. Methods We conducted a retrospective analysis on 10 years of data obtained from three clinical hospitals from January 2005 to March 2015, and 101 girls with ICPP, who received GnRHa therapy for more than six months and already reached their adult height were enrolled. Results Height, bone age, midparent height, HtSDS, sexual development, therapy duration and predicted adult height(PAH)at start and end of GnRHa, and the final adult height(FAH) were recorded and calculated. Their PAH significantly increased at end of GnRHa (158.4±6.00cm), compared to that at the start of GnRHa(153.1±5.37cm) (P0.05). After GnRHa therapy, most of the ICPP girls reached their midparent height compared to that at start of GnRHa(P0.05). The percentage of adult short stature decreased and those reached midparent height significantly increased after GnRHa therapy, compared to that at start of GnRHa(60.6% vs.30.4% and 67.85% vs. 94.64%, respectively, P

To retrospectively validate the prognostic value of the latest Chinese disseminated intravascular coagulation (DIC) scoring system (CDSS) in hematological malignancies, 260 patients with confirmed hematological malignancies and suspected DIC in West China Hospital between 2011 and 2015 were included in this study. We evaluated via univariate and multivariate analyses the diagnostic biomarkers, and the cutoff levels used in the CDSS, except those for fibrinogen, were found to be valid. In subgroup analyses, the value of fibrinogen was found to be mainly unfit for the acute promyelocytic leukemia group. Forty-six patients (17.7%) had elevated fibrinogen levels (>4 g/L) and tended to have a poor prognosis, and thus we redetermined the cutoff value of fibrinogen (4 g/L was defined as abnormal). As a result, all of the markers used in the CDSS had prognostic value (including for the promyelocytic leukemia group); meanwhile, this modification also resulted in a larger area under the receiver operating characteristic curve compared to the CDSS and the International Society on Thrombosis and Haemostasis score. We believe that, with regard to prognosis prediction, this cutoff value modification for fibrinogen is preferable for DIC patients with a tendency toward severe hypofibrinogenemia. However, a multicenter, prospective study is needed to validate this possibility.

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome triggered by EBV infection. It often becomes relapsed or refractory (r/r), given that etoposide-based regimens cannot effectively clear the virus. r/r EBV-HLH is invariably lethal in adults without allogeneic hematopoietic stem cell transplantation. Here, we performed a retrospective analysis of 7 r/r EBV-HLH patients who were treated with nivolumab on a compassionate-use basis at West China Hospital. All 7 patients tolerated the treatment and 6 responded to it. Five of them achieved and remained in clinical complete remission with a median follow-up of 16 months (range, 11.4-18.9 months). Importantly, both plasma and cellular EBV-DNAs were completely eradicated in 4 patients. Single-cell RNA-sequencing analysis showed that HLH syndrome was associated with hyperactive monocytes/macrophages and ineffective CD8 T cells with a defective activation program. Nivolumab treatment expanded programmed death protein-1–positive T cells and restored the expression of HLH-associated degranulation and costimulatory genes in CD8 T cells. Our data suggest that nivolumab, as a monotherapy, provides a potential cure for r/r EBV-HLH, most likely by restoring a defective anti-EBV response.

In our previous study, we identified a class of 4-substituted coumarins as a powerful microtubule inhibitors binding to the colchicine site of

Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clinical trials from PUBMED, EMBASE, and The Cochrane Library. For safety analysis, the incidence and exhibition of any grade and grade ≥3 adverse events (AEs) were evaluated. Overall response rate (ORR), 6-month progression-free survival (PFS) and 6-month overall survival (OS) were calculated for efficacy analysis. Results: Overall ten studies and 718 patients (114 non-Hodgkin lymphomas, 604 Hodgkin lymphomas) were enrolled, including 4 phase I studies and 6 phase II studies. The pooled incidences of any grade and grade ≥3 adverse events (AEs) were 74 and 24%, respectively. Drug-related deaths occurred in two patients. The most common any grade AEs were fatigue (14.91%), rash (14.8%), hypothyroidism (13.77%), platelet count decreased (13.54%), pyrexia (13%). The most common grade ≥3 AEs were neutropenia (4.79%), pneumonitis (3.58%), rash (3.38%), and leukopenia (3.31%). Fatigue (p = 0.0072) and rash (p = 0.0078) in any grade AEs were less observed in patients treated with pembrolizumab than nivolumab. The pooled ORR, PFS rate and OS rate were 58, 73, and 96%, respectively. The ORR in patients with Hodgkin lymphomas (HL) was higher than patients with non-Hodgkin lymphomas (NHL) (69.08 vs. 30.77%, p < 0.0001). However, there was no significant difference of efficacy between nivolumab and pembrolizumab. Conclusions: Nivolumab and pembrolizumab have promising outcomes with tolerable AEs and drug-related deaths in patients with relapsed or refractory lymphoma. Pembrolizumab caused less any grade AEs like fatigue and rash than nivolumab. Patients with HL got better response than NHL.

UTX (also known as KDM6A), a histone 3 lysine 27 demethylase, is among the most frequently mutated epigenetic regulators in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recent studies have suggested that UTX mutations promote MDS and AML by blocking the differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we performed an epigenetic drug library screening for small molecules able to release the differentiation block on HSPCs induced by UTX deficiency. We found that SP2509, a selective inhibitor of LSD1, specifically promoted the differentiation of Utx-null HSPCs while sparing wild-type HSPCs. Transcriptome profiling showed that Utx loss reduced the expression of differentiation-related and tumor suppressor genes, correlating with their potential roles in HSPC self-renewal and leukemogenesis. In contrast, SP2509 treatment reversed these changes in gene expression in Utx-null HSPCs. Accordingly, Utx loss decreased H3K4 methylation level probably through the COMPASS-like complex, while LSD1 inhibition by SP2509 partially reversed the reduction of H3K4 methylation in Utx-deficient HSPCs. Further, SP2509 promoted the differentiation of Utx-null AML cells in vitro and in vivo and, therefore, extended the survival of these leukemic mice. Thus, our study identified a novel strategy to specifically target both premalignant and malignant cells with Utx deficiency for differentiation therapy and provided insights into the molecular mechanisms underlying the role of Utx in regulating HSPCs and related diseases., Cancer: Restoring differentiation A small molecule that restores the differentiation of hematopoietic stem and progenitor cells (HSPCs) extends the survival of mice with leukemia. Mutations that impair the activity of UTX, a protein that mediates heritable changes in gene expression by removing methyl groups from histones, prevent the production of blood cells in the bone marrow and have been associated with leukemia. Yu Liu and colleagues at Sichuan University, China, carried out a screen for compounds that target epigenetic regulators and found that SP2509, an LSD1 inhibitor, promoted HSPC differentiation and tumor suppressor gene expression in cells lacking UTX activity. The ability of SP2509 to stop the progression of leukemia in mice suggests that it could be a potential treatment strategy for cancers driven by UTX mutations.

The p53 gene is well known as a key tumor suppressor gene; it is vital for hematopoietic stem cell differentiation and growth. In the present study, the change of platelets (PLTs) in p53 knockout mice (p53-/- mice) was investigated. The peripheral blood cell subsets and PLT parameters in p53-/-mice were compared with those in age-matched p53+/+ mice. Bleeding time as well as the alteration of PLT levels, were analyzed with the PLT marker CD41 antibody using flow cytometry. The results revealed that the number of PLTs in p53-/- mice was significantly lower than that in p53+/+ mice. Bleeding time was prolonged in the peripheral blood of p53-/- mice compared with that of p53+/+ mice. Furthermore, the related gene expression of the PI3K signaling pathway in the bone marrow of p53-/- mice was shown to be associated with plateletogenesis. PI3K inhibitor (LY294002) was also used to treat p53-/- mice, and the results demonstrated that LY294002 revert the change of PLTs in these mice. In summary, PLTs were altered in p53-/- mice, and the PI3K signaling pathway was involved in that process, suggesting that the p53-dependent PI3K signaling pathway is involved in thrombocytopenia or PLT diseases. PLT number is reduced in p53 deficiency; however, this reduction could be reverted by inhibiting the PI3K pathway.

This study was to perform preclinical evaluation of a novel class I and IIb HDAC-selective inhibitor, purinostat mesylate, for the treatment of PhBiochemical assays were used to test enzymatic activity inhibition of purinostat mesylate. PhPurinostat mesylate, a class I and IIb HDAC highly selective inhibitor, exhibited robust antitumor activity in hematologic cancers. Purinostat mesylate at low nanomolar concentration induced apoptosis, and downregulated BCR-ABL and c-MYC expression in PhPurinostat mesylate provides a new therapeutic strategy for patients with Ph

Purpose: The resistance to differentiation therapy and early death caused by fatal bleeding endangers the health of a significant proportion of patients with acute promyelocytic leukemia (APL). This study aims to investigate the molecular mechanisms of all-trans retinoic acid (ATRA) resistance and uncover new potential therapeutic strategies to block the rapid progression of early death. Experimental Design: The important role of TWIST1 in APL leukemogenesis was first determined by gain- and loss-of-function assays. We then performed in vivo and in vitro experiments to explore the interaction of TWIST1 and TRIB3 and develop a potential peptide-initiated therapeutic opportunity to protect against early death and induction therapy resistance in patients with APL. Results: We found that the epithelial–mesenchymal transition (EMT)-inducing transcription factor TWIST1 is highly expressed in APL cells and is critical for leukemic cell survival. TWIST1 and TRIB3 were highly coexpressed in APL cells compared with other subtypes of acute myeloid leukemia cells. We subsequently demonstrated that TRIB3 could bind to the WR domain of TWIST1 and contribute to its stabilization by inhibiting its ubiquitination. TRIB3 depletion promoting TWIST1 degradation reverses resistance to induction therapy and improves sensitivity to ATRA. On the basis of a detailed functional screen of synthetic peptides, we discovered a peptide analogous to the TWIST1 WR domain that specifically represses APL cell survival by disrupting the TRIB3/TWIST1 interaction. Conclusions: Our data not only define the essential role of TWIST1 as an EMT-TF in patients with APL but also suggest that disrupting the TRIB3/TWIST1 interaction reverses induction therapy resistance and blocks rapid progression of APL early death. See related commentary by Peeke and Gritsman, p. 6018

A series of 7H-pyrrolo[2,3-d]pyrimidine derivatives were designed and synthesized as reversible BTK inhibitors, and evaluated their kinase selectivity, anti-proliferation against the B-cell lymphoma cell lines (Ramos, Jeko-1) and cell line BTK enhanced (Daudi) in vitro. Among them, compound 28a exhibited the most excellent potency (IC50 = 3.0 nM against BTK enzyme, 8.52 μM, 11.10 μM and 7.04 μM against Ramos, Jeko-1, Daudi cells, respectively), good kinase selectivity and inhibited BTK Y223 auto-phosphorylation and PLCγ2 Tyr1217 phosphorylation. Importantly, 28a showed efficacy anti-arthritic effect on collagen-induced arthritis (CIA) model in vivo. 28a 60 mg/kg dose level once a day group displayed markedly reduced joint damage and cellular infiltration without any bone and cartilage morphology change.

Background: The prognosis of nasal type advanced-stage or relapsed extranodal NK/T cell lymphoma (ENKTL) is poor even with intensive multi-agent chemotherapy. It is therefore critical to develop more effective treatment strategies to improve outcomes and prognosis of ENKTL patients. Methods: We conducted a multi-center, prospective study to evaluate the efficacy and safety of a new treatment strategy: induction chemotherapy with gemcitabine, L-asparaginase or PEG-asparaginase, ifosfamide, dexamethasone and etoposide (GLIDE) followed by upfront autologous hematopoietic stem cell transplantation (ASCT) conditioning with either carmustine, etoposide, cytarabine, and melphalan (BEAM) or chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Findings: A total of 64 eligible patients were enrolled. After a maximum of 6 cycles of GLIDE, 43 patients (70·5%) achieved complete response, including 31 (50·8%) who achieved complete response after 2 cycles. With median follow-up of 23.8 months, estimated 5-year progression-free survival and overall survival of the whole cohort was 54·0% and 68.9% respectively. Among 50 chemo-sensitive patients (patients in complete or partial remission) , 27 underwent upfront ASCT, and they showed a significantly higher rate of 5-year progression-free survival than chemosensitive patients who did not receive upfront ASCT (78·8% vs. 36·0%, p=0·0004) as well as a significantly higher rate of 5-year overall survival (87·2% vs. 55·4%, p=0·0035). Interpretation: GLIDE chemotherapy showed a high efficacy in disease control for the patients with advance-staged or relapsed ENTKL, and in whom achieved partial or complete response, GLIDE followed by upfront ASCT may be a more effective treatment strategy than GLIDE alone. Trial Registration Information: The study was registered at the Chinese Clinical Trial Registry (Chictr.org.cn, Chicrt-TNC-10000782). Funding Statement: This work was supported by a grant from Science and Technology Fund of Sichuan Province, China, NO.18ZDYF2063. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital, Sichuan University. Written informed consent was obtained from all patients.

Fe-TiB2 composite cathode materials were prepared by cold pressing sintering in which metal Fe was added as sintering aids. The electrolysis performance was studied in a 20 A electrolysis test, and the composition phase analyses of the composite cathode materials before and after the electrolysis test were carried out by using an energy spectrometer (EDS), and the migration behavior of various elements in the electrolysis process was studied. The results showed that the Fe could effectively fill the gap between the aggregate during the sintering process and improve the sintering density of the composite cathode material significantly. The voltage of the 20 A electrolysis test is stable. The impurity of the aluminum is 0.81%. The surface of the composite cathode is wetted obviously by the aluminum liquid. In the process of electrolysis, the alkali metal is main. In the permeation of the liquid electrolyte into the cathode material, the permeation of K element was more deeply than that of Na element; the Al produced on the cathode surface and the Fe in the cathode material will diffuse to each other until the relative equilibrium is reached.

Since X-linked chronic granulomatosis disease (X-CGD) exhibits no specific clinical symptoms at an early stage, early diagnosis is difficult and depends predominantly on neonatal screening. Therefore, the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis. The cases of 10 children with X-CGD diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized. Serum biomarkers and clinical symptoms at acute infection were organized. A total of 132 children with X-CGD were enrolled in this study. For 55.8% of the patients, the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested. Children with X-CGD at an acute infection stage showed three recurrent signs in terms of serum biomarkers: (1) the total number of white blood cells (especially N%) was increased significantly, accompanied by anemia in some cases; (2) C-reactive protein (CRP) levels were increased significantly; and (3) most of the patients exhibited very high serum IgG levels (>12 g/L). Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features. Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers, which can provide clues for early diagnosis.

This study was designed to investigate the anti-inflammatory activity of the pure compound gentiopicroside (Gent) on dextran sulfate sodium (DSS)-induced colitis in a mouse model and to explore the possible related mechanisms. Experimental colitis was induced in ICR mice by dissolving 5% DSS in their drinking water for 7days. Gent (200, 100, and 50mg/kg) and 5-aminosalicylic acid (5-ASA, 100mg/kg) were oral administrated once a day for 7days. Anti-inflammatory effects were evaluated by comparing extend of colonic mucosal injury assessed by disease activity index (DAI), colon length, histopathological examination, and biochemical test. The possible mechanisms of Gent activities were explored by evaluating expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 using real-time fluorogenic PCR and expression levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) using Western blotting. The results showed that oral administration of Gent significantly attenuated DSS-induced loss of body weight, diarrhea, shortening of colon length and histological changes, associated with the decrease in the activity of myeloperoxidase (MPO) in the colon. In addition, the mRNA expression of TNF-α, IL-1β, IL-6 and the overexpression of COX-2 and iNOS proteins in the colon were down-regulated by Gent treatment. To our knowledge, this is the first study to demonstrate that Gent treatment can exert anti-inflammatory effects on experimental acute colitis through attenuating the expression levels of TNF-α, IL-1β, IL-6, iNOS and COX-2, and it may present the therapeutic potential in the treatment of colitis.

To investigate the antioxidative effect of astaxanthin on Nω-nitro-L-arginine methyl ester (L-NAME)-induced preeclamptic rats. Cell survival, the level of reactive oxygen species (ROS) and the changes in mitochondrial membrane potential (MMP) were examined in astaxanthin and H2O2-treated human umbilical vein endothelial cells (HUVECs). The preeclamptic Sprague-Dawley (SD) rat model was established by injection of L‑NAME and treatment with astaxanthin. The activities of malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide synthase (NOS) in serum were analyzed. Pathological changes were examined by hematoxylin and eosin (H&E) staining. The expression of nuclear factor (NF)‑κB, Rho‑associated protein kinase II (ROCK II), heme oxygenase‑1 (HO‑1) and caspase 3 in preeclamptic placentas were examined by immunohistochemistry. Astaxanthin significantly reduced H2O2‑induced HUVEC cell death, decreased ROS and increased MMP. Astaxanthin significantly reduced blood pressure and the content of MDA, but significantly increased the activity of SOD in preeclamptic rats. The urinary protein and the level of NO and NOS were also decreased. H&E staining revealed that the thickness of the basilar membrane was increased, while the content of trophoblast cells and spiral arteries were reduced following astaxanthin treatment. Immunohistochemistry results showed that the expression of NF‑κB, ROCK II and caspase 3 in preeclamptic placentas was significantly decreased after astaxanthin treatment, while HO‑1 expression was increased. In conclusion, astaxanthin inhibited H2O2‑induced oxidative stress in HUVECs. Astaxanthin treatment significantly improved L‑NAME‑induced preeclamptic symptoms and reduced the oxidative stress and inflammatory damages in preeclamptic placentas. Astaxanthin treatment may effectively prevent and treat preeclampsia.

The deactivations of Cu–Co alloy nanoparticles supported on ZrO 2 for higher alcohols synthesis from syngas were investigated. The catalysts after reaction for 200 and 1500 h were compared and characterized by using N 2 adsorption and desorption, X-ray diffraction, transmission electron microscopy, energy dispersive spectrometer, inductively coupled plasma mass spectrometry and thermo gravimetric analysis techniques. The characterization results showed that the deactivation of the Cu–Co/ZrO 2 catalyst in the reaction period of 200–1500 h was mainly attributed to cobalt volatilization in the form of its carbonyl at the reaction temperature. Sintering of the Cu–Co alloy and coke deposited on the catalyst surface could hardly be observed, meaning that sintering and coke deposition are not responsible for the deactivation of the catalyst. At the same time, the formation of Co 2 C on the surface of Cu–Co alloy might play a protective role for the decomposition of Cu–Co alloy and the volatilization of carbonyl cobalt. According to the results, some possible recommendations were proposed for the design of Cu–Co-based catalysts.

We reconstructed a phylogenetic tree of Chinese vascular plants (Tracheophyta) using sequences of the chloroplast genes atpB, matK, ndhF, and rbcL and mitochondrial matR. We produced a matrix comprising 6098 species and including 13 695 DNA sequences, of which 1803 were newly generated. Our taxonomic sampling spanned 3114 genera representing 323 families of Chinese vascular plants, covering more than 93% of all genera known from China. The comprehensive large phylogeny supports most relationships among and within families recognized by recent molecular phylogenetic studies for lycophytes, ferns (monilophytes), gymnosperms, and angiosperms. For angiosperms, most families in Angiosperm Phylogeny Group IV are supported as monophyletic, except for a paraphyletic Dipterocarpaceae and Santalaceae. The infrafamilial relationships of several large families and monophyly of some large genera are well supported by our dense taxonomic sampling. Our results showed that two species of Eberhardtia are sister to a clade formed by all other taxa of Sapotaceae, except Sarcosperma. We have made our phylogeny of Chinese vascular plants publically available for the creation of subtrees via SoTree (http://www.darwintree.cn/flora/index.shtml), an automated phylogeny assembly tool for ecologists.

In the present study, a series of novel histone deacetylase (HDAC) inhibitors using the morpholinopurine as the capping group were designed and synthesized. Several compounds demonstrated significant HDAC inhibitory activities and antiproliferative effects against diverse human tumor cell lines. Among them, compound 10o was identified as a potent class I and class IIb HDAC inhibitor with good pharmaceutical profile and druglike properties. Western blot analysis further confirmed that 10o more effectively increased acetylated histone H3 than panobinostat (LBH-589) and vorinostat (SAHA) at the same concentration in vitro. In in vivo efficacy evaluations of HCT116, MV4-11, Ramos, and MM1S xenograft models, 10o showed higher efficacy than SAHA or LBH-589 without causing significant loss of body weight and toxicity. All the results indicated that 10o could be a suitable candidate for treatment of both solid and hematological cancer.