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Background Multiple myeloma (MM) is an incurable hematological malignancy. Although proteasome inhibitors and immunomodulators have significantly improved patient outcomes, some patients respond poorly to treatment and almost all patients will relapse. Mechanisms of proteasome inhibitor resistance in multiple myeloma have not been fully elucidated. ZHX2 is a transcription regulator degraded via proteasome and presents both oncogenic or tumor suppressive effect in different cancers, however, it is still unknown that the role of ZHX2 in myeloma. In this study, we aim to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM. Methods GSE24080 gene expression profile datasets from Gene Expression Omnibus (GEO) were analyzed to evaluate the relationship between ZHX2 expression level and survival in MM. Expression of ZHX2 in human MM cell lines at baseline and after bortezomib (BTZ) treatment was determined by Western blotting (WB). The proliferation and apoptosis rate of MM cells treated with BTZ after the knockdown of ZHX2 were analyzed by flow cytometry. Nuclear translocation of NF‐κB after the knockdown of ZHX2 was evaluated by WB and immunofluorescence, and the expression of NF‐κB target genes was measured by real‐time quantitative PCR. Co‐immunoprecipitation (Co‐IP) and WB were used to detect the interaction of ZHX2 with NF‐κB. Results We found that higher ZHX2 expression was correlated with poorer clinical outcomes of patients. In addition, ZHX2 expression was relatively higher in RPMI‐8226 and MM.1S cell lines and the level of ZHX2 protein was upregulated after BTZ treatment. Knockdown of ZHX2 significantly enhanced the sensitivity of MM cells to BTZ, inhibited nuclear translocation of NF‐κB, and reduced mRNA expression of NF‐κB target genes. It was also revealed that ZHX2 directly binds to NF‐κB. Conclusion Our study showed that ZHX2 can promote proteasome inhibitor resistance in MM cells by regulating the nuclear translocation of NF‐κB., In this study, we aimed to demonstrate the effect and mechanism of ZHX2 on proteasome inhibitor resistance in MM. We found that ZHX2 can regulate the nuclear translocation of NF‐κB and is related to myeloma cell resistance to proteasome inhibitor.

The induction therapy containing ixazomib, an oral proteasome inhibitor, has shown favorable efficacy and safety in clinical trials, but its experience in real-life remains limited. In routine practice, few patients received ixazomib-based induction therapy due to reasons including (1) patients’ preference on oral regimens, (2) concerns on adverse events (AEs) of other intravenous/subcutaneous regimens, (3) requirements for less center visits, and (4) fears of COVID-19 and other infectious disease exposures. With the aim of assessing the real-life effectiveness and safety of ixazomib-based induction therapy, we performed this multi-center, observational study on 85 newly diagnosed multiple myeloma (NDMM) patients from 14 medical centers. Ixazomib-based regimens included ixazomib-lenalidomide-dexamethasone (IRd) in 44.7% of patients, ixazomib-dexamethasone (Id) in 29.4%, and Id plus another agent (doxorubicin, cyclophosphamide, thalidomide, or daratumumab) in 25.9%. Different ixazomib-based therapies were applied due to (1) financial burdens or limitations on local health insurance coverage, (2) concerns on treatment tolerance, and (3) drug accessibility issue. Ten patients received ixazomib maintenance. The median age was 67 years; 43.5% had ISS stage III disease; 48.2% had an Eastern Cooperative Oncology Group performance score ≥ 2; and 17.6% with high-risk cytogenetic abnormalities. Overall response rate for all 85 patients was 95.3%, including 65.9% very good partial response or better and 29.5% complete responses. The median time to response was 30 days. The response rate was similar across different ixazomib-based regimens. Median progression-free survival was not reached. Severe AEs (≥ grade 3) were reported in 29.4% of patients. No grade 3/4 peripheral neuropathy (PN) occurred. Patients received a median of 6 (range 1–20) cycles of ixazomib treatment; 56.6% remained on treatment at data cutoff; 15.3% discontinued treatment due to intolerable AEs. These results support that the ixazomib-based frontline therapy was highly effective with acceptable toxicity in routine practice and the ixazomib oral regimens could be good alternative options for NDMM patients.

A series of CeO2-graphene oxide (CeO2-GO) composites were systematically prepared and compared for the visible-light photocatalytic degradation of methylene blue (MB). The experimental results show that the as-prepared CeO2-GO (5.0 wt%) composite exhibits superior photocatalytic activity as compared to pure CeO2. An optimum weight ratio of GO to CeO2 not only causes a decrease in particle size of CeO2, but also leads to an increase in BET specific surface areas and favors an effective separation of the photogenerated electron-hole pairs, which should be responsible for the enhanced photocatalytic performance. More importantly, there is a direct correlation between the electrocatalytic activity of CeO2-GO and its photocatalytic activity for the visible-light photocatalytic degradation of MB. This fundamental research will provide guideline for exploring of highly efficient photocatalysts with many potential applications in future.

Photocatalysis is a well-established and green technique for degradation of antibiotics in wastewater. Hydroxyapatite (HAp) has excellent biocompatibility, biological activity, non-toxicity and low cost, and has many applications in biomaterials. Recently, HAp has been reported as an inexpensive green photocatalyst for cleaning some drug contaminations. However, its photocatalytic performance and chemical stability are far from practical applications. In this research, a series of porous hollow hydroxyapatite (HAp) microspheres decorated with small amounts of ultrathin graphitic carbon nitride (g-C3N4) were firstly and successfully fabricated by a facile hydrothermal procedure. The experimental results show that as-prepared g-C3N4/HAp photocatalysts exhibited evidently enhancement on the photocatalytic activities for the degradation of tetracycline (TC), compared with the corresponding ultrathin g-C3N4 and porous hollow HAp microspheres. Notably, g-C3N4 (1.5 wt.%)/HAp composite displayed a net high photocatalytic activity for TC degradation (almost 100% within 15 min). Moreover, the as-prepared g-C3N4 (1.5 wt.%)/HAp exhibited a good stability in the cyclic runs for the photocatalytic degradation of TC, demonstrating its promising potential as an efficient photocatalyst. An optimum decorating amount of ultrathin g-C3N4 onto porous hollow HAp microspheres favors an effective separation of photogenerated electron-hole pairs, which can be responsible for the enhanced photocatalytic performance. In addition, the photocatalytic degradation mechanism for TC was proposed. This fundamental research will provide a promising strategy for the development of highly efficient and compatible photocatalysts with many applications.

Most patients with multiple myeloma (MM) will eventually relapse and current treatments have limited effect. Herein, we demonstrate that succinate dehydrogenase subunit A (SDHA) was low expressed in MM patients, and patients with SDHA relatively high expression had long overall survival and progression-free survival. Furthermore, SDHA high expression inhibited proliferation and invasion in MM cell lines and enhanced the anti-tumor and synergistic effect of chemotherapeutics. More importantly, chidamide was proved effective in MM by targeting SDHA, and expression of SDHA was increased by chidamide through acetylating H3K27 site of SDHA. Collectively, high expression of SDHA, which was regulated by histone acetylation and targeted by chidamide, might become a good prognostic factor of MM patients.

Immunodeficiencies are widely becoming known as important features of multiple myeloma (MM) and may promote the proliferation of malignant cells as well as confer resistance to therapy. Few studies focus on the immunomodulatory effects of the complement system on MM. This study aims to explore the role of C1q in MM patients. Plasma C1q was found to be significantly reduced in MM patients, and the amount of C1q deposited around the CD138+ cells in bone marrow (BM) biopsy sections was observed to be much higher, especially in the subgroup with 1q21 amplification (Amp1q21). CD138+ cells expressed higher levels of C1q receptors (C1qRs) than CD138− cells. Patients with Amp1q21 expressed higher levels of globular C1qR (gC1qR), whereas patients without Amp21 expressed higher levels of collagen tail C1qR (cC1qR). Additionally, gC1qR was noted to suppress the MM-inhibiting role of C1q in H929, U266, and MM1S. gC1qR interacts with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), which also suppressed the function of C1q and regulated CDC28 protein kinase regulatory subunit 1B (CKS1B) mRNA. In summary, gC1qR suppressed the MM-inhibiting role of C1q and regulated CKS1B mRNA in promoting tumor proliferation via IGF2BP3 in 1q21-amplified MM. Our findings provide novel evidence on how MM cells evade the immune system and promote survival as well as suggest possible novel targets for future therapies of MM.

BackgroundThe outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV.MethodsSARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin.ResultsWe found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784).ConclusionThe results identify indomethacin as a potent inhibitor of SARS CoV-2.

Novel A- or B-sites substituted LaFeO 3 /silica fiber (SF) composites were prepared via a facile and efficient carbon nanofibers (CNFs) template-assisted alcohol-thermal route. The resulting samples were characterized by X-Ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), Brunauer-Emmett-Teller (BET) apparatus, and ultraviolet-visible (UV–vis) diffuse reflectance spectroscopy. Furthermore, their photocatalytic activities were evaluated by visible-light photocatalytic degradation of methylene blue (MB). Compared with powder LaFeO 3 , the obtained A- or B-sites substituted LaFeO 3 /SF composites showed enhanced degradation efficiencies to MB dyes under the identical conditions. Good stability was also observed in the cyclic runs for the degradation of MB. The enhanced photocatalytic performance should be relent with the following two factors: 1) the unique morphology and structure of A- or B-sites substituted LaFeO 3 /SF composites, and 2) the contribution of the secondary element doping either in A- or B-sites of LaFeO 3 /SF. The synthetic procedure is simple and could be applicable to other efficient and inexpensive photocatalytic materials.

In this work, MoS2/MnO2 synthesized by hydrothermal methods was employed to remove Hg0 in flue gas. Benefited from the growth of MnO2 on the surface of MoS2, the specific surface area of the Mm adsorbent has increased. Compared with pure MoS2, specific surface area of Mm-30 has increased by 26.0287 m2/g. The MoS2 modified with 30 w.t. % MnO2 revealed higher mercury removal performance at 120 °C, which reached 93%. The oxidation of mercury over Mm-30 is proposed to follow Mars-van Krevelen mechanism, whereby the lattice oxygen in the adsorbent is consumed. In presence of NO, HCl, O2 and SO2, the effect of different concentrations on mercury oxidation is observed. Mm-30 adsorbent reveals stable mercury removal performance in the presence of NO and HCl, while it also exhibited good sulfur resistance under the condition of 400 ppm SO2 + N2. This phenomenon indicates that the adsorbent can be applied in power plants with medium concentrations of SO2, which facilitated the application of Mm-30 as a potential mercury removal adsorbent for power plants.

The atomic interaction between elemental mercury in the flue gas and defective carbonaceous surface is studied by the first-principles calculation. The defective carbonaceous surface is modeled by a nine-fused benzene cluster with two adjacent atomic vacancies. The results indicate that vacancies can increase the activity of their neighboring carbon atoms. However, the vacant sites present the decrease in mercury removal capacity, which is different from the behavior of the defective carbonaceous surface with only one atomic vacancy. In addition, flue gas molecules (FGMs) including CO, CO2, NO, NO2, SO2 and H2O, are examined to evaluate the influence on the mercury removal of the defective carbonaceous surface. The calculated results demonstrate that different adsorption behaviors for Hg0 occur on the defective carbonaceous surface due to the presence of FGMs. It can be found that CO may enhance the mercury removal capacity of the defective carbonaceous surface when its concentration is higher than that of Hg0. Meanwhile, SO2 presents the remarkable positive effect on the mercury removal efficiency at the vacancy. On the contrary, the presence of CO2, NO, NO2 and H2O leads to the increase in the adsorption energies of mercury on the defective carbonaceous surface.

At the front end of the Electrostatic precipitator (ESP), activated carbon injection is a common method to remove mercury from flue gas, but the high cost, low efficiency and non-recyclability limit the practical application of activated carbon. MoS2, a transition metal sulfide with a two-dimensional layered structure, was found to have favourable performances in removing contaminant. In this work, Fe3O4 was successfully grown on the surface of flower-like MoS2 by two-steps hydrothermal methods. The experimental results showed that the specific surface area of MoS2/Fe3O4 (MF) was the largest when the ratio is 10 wt% (MF-10). Compared with pure MoS2, the specific surface area of MF-10 increased by 6.7467 m2/g, which was attributed to the growth of Fe3O4. At the same time, the introduction of Fe3O4 made the MF possess superparamagnetism to facilitate its retrievability under an external magnetic field. In addition, MF-10 also showed a mercury removal efficiency of almost 100%. Although the efficiency of the MF-10 has decreased after 5 cycles and 24 h, it could still maintain about 90%, revealing a stable cycle life. Due to its mercury removal performance and recyclability, MF can be considered as a favorable adsorbent for removing elemental mercury.

Nanoparticle system with the composition xEu2O3-(1-x)α-Fe2O3 (x = 0.1 and 0.5) was successfully synthesized by mechanochemical activation of Eu2O3 and a-Fe2O3 mixtures for 0-12 hours of ball milling time. The study is of relevance to catalysis, biomedical, sensing and energy-related applications. 57Fe and 151Eu Mossbauer spectroscopy were used to investigate the phase evolution, solid solution formation and hyperfine parameters of xEu2O3-(1-x)α-Fe2O3 nanoparticle system under the mechanochemical activation process. The 57Fe Mossbauer studies showed that the spectrum of the ball milled samples evolved from a sextet for hematite to sextets and a doublet upon duration of the milling process with europium oxide. This indicated the formation of the EuFeO3 perovskite for large x values and long milling times. The 151Eu Mossbauer investigations showed that the isomer shift decreased with increasing milling time for all molar concentrations employed.

In this paper, we used coprecipitation method to prepare different ratios of Mn / γ - Fe 3 O 4 to remove Hg0. Different ratios of Mn and Fe could affect the mercury removal efficiency of M n / γ - F e 3 O 4 . The mechanism of Hg0 adsorption on the surface of M n / γ - F e 3 O 4 matches the Mars-van Krevelen reaction mechanism. The catalytic oxidation of mercury on the surface of the sample is related to Fe and Mn. We also performed a pseudo-first-order kinetic model and an improved pseudo-n-order kinetic model. In addition, the external magnetic field has a certain promoting effect on the mercury removal.

Photocatalysis is a well-established and green technique in environmental pollutant remediation. In the present study, a novel and green red phosphorus (5.0 wt%)/hollow hydroxyapatite microsphere photocatalyst was fabricated and applied forthe degradation of rifampicin, tetracycline, and levofloxacin. The as-prepared material exhibits outstanding photocatalytic activity and stability, and has universal application for degradation of each antibiotic. Notably, tetracycline, rifampicin, andlevofloxacin can be completely degraded within 10 min, 20 min, and 50 min, respectively, under a 300 W Xe lamp with full spectrum illumination, where the optimal conditions were an initial pH of 6.0 and a photocatalyst dosage of 1.0 g/L. In addition, a plausible photocatalytic reaction mechanism was proposed. The low-cost, highly efficient, and green red phosphorus (5.0 wt%)/hollow hydroxyapatite microsphere photocatalyst is a promising candidate for the removal of many hazardous pollutants.

x Eu 2 O 3 –(1− x )α-Fe 2 O 3 ( x =0.1, 0.3, 0.5, and 0.7) nanoparticle system was successfully synthesized by mechanochemical activation of Eu 2 O 3 and α-Fe 2 O 3 mixtures for 0–12 h of ball milling time. The investigations aimed at exploring the formation of magnetic ceramic nanostructures, which are of crucial importance for catalysis and sensing applications. X-ray powder diffraction (XRD),as well as 57 Fe and 151 Eu Mossbauer spectroscopy and thermal analysis by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) was used to study the phase evolution of x Eu 2 O 3 –(1− x )α−Fe 2 O 3 nanoparticle system under the mechanochemical activation process. Rietveld refinement of the XRD patterns yielded the values of the particle size as a function of composition and milling times and indicated the formation of the EuFeO 3 perovskite for large x values and long milling times. The 57 Fe Mossbauer studies showed that the spectrum of the mechanochemically activated composites evolved from a sextet for hematite to sextets and a doublet upon duration of the milling process with europium oxide. The 151 Eu Mossbauer investigations showed that the isomer shift decreased with increasing milling time for all molar concentrations employed. These results correlate well with the DSC/TGA analysis, which shows the consumption of hematite and the formation of EuFeO 3 in the system under investigation.

x Li 2 O–(1− x )α-Fe 2 O 3 ( x =0.1, 0.3, 0.5, and 0.7) nanoparticle systems were successfully synthesized by mechanochemical activation of Li 2 O and α-Fe 2 O 3 mixtures for 0–12 h of ball milling time. The study aims at exploring the formation of magnetic oxide semiconductors at the nanoscale, which is of crucial importance for catalysis, sensing and electrochemical applications. X-ray powder diffraction (XRD), Mossbauer spectroscopy and magnetic measurements were used to study the phase evolution of x Li 2 O–(1− x )α-Fe 2 O 3 nanoparticle systems under the mechanochemical activation process. Rietveld refinement of the XRD patterns yielded the values of the particle size as function of composition and milling times and indicated the presence of Li-substituted hematite and tetra lithium iron oxide LiFeO 2 , along with the formation of multiple phases for large x values and long milling times. The Mossbauer studies showed that the spectrum of the mechanochemically activated composites evolved from a sextet for hematite to sextets and a doublet upon duration of the milling process with lithium oxide. Magnetic measurements recorded at 5 K to room temperature (RT) in an applied magnetic field of 50,000 Oe showed that the magnetization of the milled samples is larger at low temperatures than at RT and increases with decreasing particle size. Zero field cooling measurements made possible the determination of the blocking temperatures of the specimens as function of ball milling time and evidenced the occurrence of superparamagnetism in the studied samples. This result correlates well with the observed presence of a quadrupole-split doublet in the Mossbauer spectra.

J Li, L Bao, ZJ Xia and KY Ding contributed equally to this study. Background: Based on the promising results shown in the phase 3 trial (TOURMALINE-MM1, NCT01564537) and the China Continuation Study of MM1, the oral proteasome inhibitor (PI) ixazomib (ixa) was approved in China in April of 2018, in combination with lenalidomide (len) and dexamethasone (dex) (IRd), for patients (pts) with relapsed/refractory multiple myeloma (RRMM). Data on the efficacy and safety of ixa-based therapy in Chinese pts with MM in real-life practice is rather limited. A large national, multi-center, real-world study involving 14 centers from different areas of China was performed to investigate the current status of ixa usage in China and to evaluate the efficacy and safety in routine clinical practice. A total of 246 ixa-treated MM pts was enrolled, with 163 (66.3%) RRMM, 60 (24.4%) newly diagnosed MM and 23 (9.4%) pts received ixa as maintenance. Herein, we reported the data of RRMM in this study. Methods: Medical records, including demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs) and survival, of ixa-treated (at least one cycle completed with response evaluation result) RRMM pts were analyzed. Results: A total of 149 evaluable pts (out of 163 RRMM pts) treated from April 2018, to July 2019 were included in analysis. Baseline features and prior treatment are summarized in Table 1. Patients were categorized into MM1 trial-eligible/-ineligible groups according to the inclusion and exclusion criteria of MM1 study. Median age was 62 years (range 33 - 87) with 52 (34.9%) ≥65 years. Most pts (75.2%) had ISS stage II-III disease. High-risk cytogenetic abnormalities (including del 17p, t (4;14), and/or t (14;16)) were detected in 19 patients (21.1%, among 90 patients with FISH results). Fifty-two (34.9%) pts had a ECOG PS ≥2. Overall, ixa-based regimens were used as the 2nd/3rd/4th/≥5th-line therapy in 29.7%, 33.1%, 16.2% and 17.4% of the pts, respectively. Prior treatment included bortezomib (91.9%), len (52.0%) and thalidomide (58.8%). More than half pts (54.7%) were refractory to previous bortezomib treatment, and 32.2% pts were len-refractory. MM-1 trial-ineligible pts had more advanced ISS stage, higher ECOG PS, more severe anemia, more lines of prior therapy and more refractory diseases. Treatment, outcome and survival were listed in Table 2. Ixa-based regimens included IRd in 70 (47.0%) patients, ixa-dex (Id) in 31 (20.8%) patients and Id plus chemotherapeutics/other agents (44, 29.5%; including cyclophosphamide in 14 pts, thalidomide in 12 pts, adriamycin in 6 pts, melphalan in 5 pts and daratumumab in 3 pts) in 20 (33.3%). (Table 2). One patient received stem cell transplantation (SCT) during follow-up. The best confirmed ORR (≥PR) for all 149 patients was 53.7% (80/149), including 28.2% of patients with ≥VGPR and 7.4% with a CR, with a median time to response of 41.5 days. Surprisingly, ixa-based regimens demonstrated efficacy in pts with PI/len refractory diseases, with an ORR and ≥VGPR rate of 44.4% and 19.9% for PI-refractory pts, and an ORR and ≥VGPR rate of 30.6% and 12.2% for len-refractory pts. Pts eligible for MM1 study shown comparable ORR (76.7%) with that reported in MM1 (ORR 78%). No significant difference in response between different ixa-based regimens was observed. The median PFS of the whole cohort, pts with standard/high cytogenetic risks, pts refractory to bortezomib/len and pts eligible/ineligible for MM1 trial was 8.2, 8.2, 6.8, 6.7, 5.9months, not reached and 6.6months respectively. The median overall survival (OS) of the whole cohort and every subgroup was not reached. Adverse events (AEs) of grade 3/4, reported in 40 (27.2%) patients, included 10.1% thrombocytopenia, 5.4% anemia, 3.4% diarrhea and 6.0% pneumonia. Only 3 (2.01%) pts had a grade 3/4 peripheral neuropathy during follow-up. Discussion and conclusion: Our results show that ixa-based therapy demonstrated good efficacy with limited toxicity for pts with RRMM in real-life clinical practice. Moreover, in pts with PIs- or len- refractory diseases, ixa-based therapy still showed acceptable effectiveness (ORR: 44.4% and 30.6%; mPFS: 6.7 months and 5.9 months). Although 70.5% pts in our real-life cohort were ineligible for MM1 trial, the efficacy and safety profile is similar to that reported in MM1 China Continuation Study. Ixa-based therapy is a reasonable choice for Chinese RRMM pts. Disclosures No relevant conflicts of interest to declare.

Jing Li, Li Bao and Zhong-jun Xia contributed equally to this study. Background: Ixazomib (ixa) is the first oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM) in > 60 countries. In a recently reported long-term result of a phase 1/2 study (NCT01217957), the all-oral triplet regimen of ixazomib plus Rd (IRd) demonstrated favorable efficacy with acceptable toxicity in patients with newly diagnosed MM (NDMM). Meanwhile, a large phase 3 trial (TOURMALINE-MM2, NCT01850524) evaluating IRd in stem-cell transplantation (SCT) ineligible NDMM patients is ongoing. However, outcomes and toxicity profiles of novel-agent-based MM therapies in real world practice often differ from data reported in clinical trials and data of the efficacy of ixa-based treatment in NDMM in routine practice is currently missing. Aims and Methods: To assess the efficacy and safety profile of ixa-based frontline therapy in NDMM patients in routine practice, we performed a large national, multi-center, observational study enrolling ixa-treated (at least one cycle completed) NDMM patients from 14 China centers. Clinical records on demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs), and treatment discontinuations and survival were collected and analyzed. Results: A total of 60 NDMM patients treated with ixa-based regimens were included. Ixa-based regimens included IRd in 23 (38.3%) patients, the ixa and dexamethaxone (Id) in 17 (28.3%) patients and Id plus chemotherapeutics/other agents (Adriamycin in 12 patients, cyclophosphamide in 5 patients, and thalidomide in 3 patients) in 20 (33.3%). None of the patients included received SCT during follow-up. Median age was 69 years (range 35 - 85) with 33 (55.0%) ≥65 years. At initial diagnosis, ISS stage I/II/III disease were presented in 21.7%/28.3%/50.0% patients at initial diagnosis; high-risk cytogenetic abnormalities (including del 17p, t(4;14), and/or t(14;16) detected by fluorescence in situ hybridization) were detected in 9 patients (19.6%, among 46 patients with FISH results). Twenty-six (43.4%) patients had a ECOG PS ≥2 and 5 patients (8.3%) had extramedullary disease. Eighteen patients were not eligible for ixa phase 1/2 study (NCT01217957) according to its inclusion and exclusion criteria, and even more patients (36, 60%) were not eligible for TOURMALINE-MM2 study. (Table1). The best confirmed ORR (partial response or better) for all 60 patients was 93.3% (56/60), including 63.3% of patients with ≥VGPR and 20.0% with a CR. The median time to response was 41 days. Similar response was observed among different subgroups: the ORR in Ixa phase1/2 study-eligible/ineligible group, MM2 trial- eligible/ineligible group and patients with standard/high-risk cytogenetics was 95.2%, 88.9%, 91.7%, 94.4%, 91.9% and 100.0%, respectively. And no significant difference in response between different ixa-based regimens was observed. After a median follow-up of 137.5 days after the first dose of ixazomib treatment (range, 28 - 372), median overall survival (mOS) and progression-free survival (mPFS) were not reached. (Table2) Adverse events (AEs) of grade 3 or higher were uncommon, reported in 14 (23.3%) patients, including thrombocytopenia (4 patients, 6.7%), diarrhea (5 patients, 8.3%), pneumonia (3 patients, 5.0%) and hypokalemia (1, 1.7%). No drug-related grade 3/4 peripheral neuropathy was recorded. Median cycles of ixa received were 4 cycles (range 1-11); 50 (83.3%) were still on treatment at data cut-off; 6 (10.0%) patients discontinued ixa due to intolerable AEs and 4 (6.7%) stop treatment for other reasons (mostly economic concerns). Discussion and conclusion: Here we reported the first real world, multi-center data on the efficacy and safety profile of ixa-based frontline therapy in patients with NDMM. Our results show that the ixa-based frontline therapy in real-life clinical practice is highly effective and fast in response, with an efficacy data (ORR 93.3%, ≥VGPR rate 63.3%) even better than that reported in NCT01217957 trial (ORR 88.0%, ≥VGPR rate 58.8%). Given the fact that no patients received SCT during follow-up in our cohort, our results maybe more comparable to the ongoing MM2 trial assessing SCT-ineligible NDMM. Ixa-based frontline therapy is well tolerated in NDMM patients treated in routine clinical practice. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ixazomib is an oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM). Here in this abstract, I will present data on real-life practice of the use of ixazomib in newly diagnosed multiple myeloma.

Three types of nanostructured systems: x NbO·(1− x )α-Fe 2 O 3 , x NbO 2 ·(1− x )α-Fe 2 O 3 , and x Nb 2 O 5 ·(1− x )α-Fe 2 O 3 were synthesized by ball milling at different molar concentrations ( x =0.1, 0.3, 0.5, and 0.7). The effect of Nb valence and milling time on mechanochemical activation of these systems were studied by X-ray diffraction and the Mossbauer spectroscopy measurements. In general, Nb-substituted hematite was obtained at lower molar concentrations for all Nb oxides. For the NbO–Fe 2 O 3 system the favorable substitution of Fe 2+ for Nb 2+ in the octahedral sites in the NbO lattice was observed after 12 h milling for x =0.7. In the case of the NbO 2 –Fe 2 O 3 and Nb 2 O 5 –Fe 2 O 3 systems a formation of orthorhombic FeNbO 4 compound was observed, in which Fe 3+ cations were detected. For the highest concentration of NbO 2 ( x =0.7) iron was completely incorporated into the FeNbO 4 phase after 12 h milling. The molar concentrations of x =0.3 and 0.5 were the most favorable for the formation of ternary FeNbO 4 compound in the Nb 2 O 5 –Fe 2 O 3 system. Influence of ball milling on thermal behavior of the powders was investigated by simultaneous DSC–TG measurements up to 800 °C.

Single phase, a FeVO4 triclinic crystalline structure was successfully synthesized by annealing the mechanochemically milled xV2O5·(1-x)α-Fe2O3 composites (x = 0.5) at 550 °C for 1 h. X-ray powder diffraction (XRD) and Mössbauer spectroscopy were combined for a detailed study of the assisting role of the mechanochemical milling process. Mechanochemical milling homogeneously mixed the starting materials of α-Fe2O3 and V2O5 and substantially decreased their average grain sizes. The partially V5+-substituted α-Fe2O3 phase and Fe3+-substituted V2O5 could be the important intermediate phases in the production of FeVO4 single phase. In addition, xV2O3·(1-x)α-Fe2O3 (x = 0.1, 0.3, 0.5, and 0.7) solid solutions were successfully synthesized by mechanochemical activation of V2O3 and α-Fe2O3 mixtures. Complete solid solutions exist after 12 h ball-milling time for all studied x values. The synthesized xV2O3·(1-x)α-Fe2O3 solid solutions with x = 0.5 and 0.7 were mainly paramagnetic at room temperature. The study demonstrates that the transformation pathway is related to the valence state of the metallic specie of the oxide used in connection with hematite.

LaFeO3 perovskite was synthesized mechanochemically through ball milling of La2O3 and Fe2O3 in stoichiometric ratio. X-ray powder diffraction (XRPD), simultaneous differential scanning calorimetry and thermogravimetry analysis (DSC–TGA), Mossbauer spectroscopy, scanning electron microscopy (SEM), and optical diffuse reflectance spectroscopy were combined for a detailed study of the growth mechanism of LaFeO3 perovskite during the ball milling process. The XRPD results showed that La2O3 is unstable when exposed to air. Both La2O3 and La(OH)3 phases coexist under the ball milling process, indicating that La2O3 or La(OH)3 can be used to produce LaFeO3. The formation of LaFeO3 perovskite was evident after only 2 h of milling and the amount of LaFeO3 gradually increased with the increase of ball milling time. After 12 h of ball milling, single phase LaFeO3 was formed. The Mossbauer spectroscopy studies show that the spectrum of the formed LaFeO3 phase consists of three sextets and one doublet, indicating the wide distribution of LaFeO3 particle sizes and some of the smaller particles having superparamagnetic properties. This is in good agreement with the SEM images, which show that the formed LaFeO3 phase consists of nanometer-sized particles and micrometer-sized agglomerates. The formation of LaFeO3 phase was mainly caused by the La3+ substitution of Fe3+ in Fe2O3 lattice. Optical diffuse reflectance spectroscopy studies show that the formed LaFeO3 phase has semiconductor properties, with the band gap energy ~2.67 eV.

Intermetallics of the Nd 3 Fe 27− x Co x V 2 ( x = 0, 2 and 4) system with monoclinic type structure and their hydrides were prepared by arc melting and exposed to hydrogenation. The effects of Co substitution of Fe on the magnetic hyperfine fields of intermetallic compound Nd 3 Fe 27 V 2 , as well as the effects of interstitial hydrogen additions on the symmetry and local magnetic properties in these systems were studied. The investigations were performed by powder X-ray diffraction, Mossbauer spectroscopy and simultaneous TGA-DSC. Both site populations and magnetic hyperfine field strength were analyzed in order to discriminate between the Co and H contributions to the local atomic environments in these systems. The values of magnetic hyperfine fields corresponding to inequivalent lattice sites were found to be enhanced after the increase in Co content and hydrogenation. Slight changes in the relative site occupancies were observed. Simultaneous TGA-DSC studies showed that the amount of hydrogen insertion decreased slightly with the increase of Co contents, while the enthalpy associated with hydrogen desorption decreased sharply under heat treatment. The Nd 3 Fe 27− x Co x V 2 ( x = 0, 2 and 4) and their hydrides are not stable under treatment and two exothermic peaks are observed in the DSC curves, corresponding to the decomposition of the monoclinic phase with the precipitation of α-Fe phase.

Indium oxide-doped hematite xIn2O3*(1-x)α-Fe2O3 (molar concentration x = 0.1–0.7) solid solutions were synthesized using mechanochemical activation by ball milling. XRD patterns yield the dependence of lattice parameters and grain size as function of milling time. After 12 h of milling, the completion of In3 + substitution of Fe3 + in hematite lattice occurs for x = 0.1. For x = 0.3, 0.5 and 0.7, the substitutions between In3 + and Fe3 + into hematite and respectively, In2O3 lattices occur simultaneously. The lattice parameters of α-Fe2O3 (a and c) and In2O3 (a) vary with milling time. For x = 0.1, Mossbauer spectra were fitted with one, two, or three sextets versus milling time, corresponding to gradual substitution of In3 + for Fe3 + in hematite lattice. For x = 0.3, Mossbauer spectra after milling were fitted with three sextets and two quadrupole-split doublets, representing In3 + substitution of Fe3 + in hematite lattice and Fe3 + substitution of In3 + in two different sites of In2O3 lattice. For x = 0.5 and 0.7, Mossbauer spectra fitting required two sextets and one quadrupole-split doublet, representing coexistence of In3 + substitution of Fe3 + in hematite lattice and Fe3 + substitution of In3 + in indium oxide lattice. The recoilless fraction studied versus milling time for each molar concentration exhibited low values, consistent with the occurrence of nanoparticles in the system. SEM/EDS measurements revealed that the mechanochemical activation by ball milling produced xIn2O3*(1-x)α-Fe2O3 solid solution system with a wide range of particle size distribution, from nanometer to micrometer, but with a uniform distribution of Fe, In, and O elements.

Indium oxide-doped hematite xIn2O3·(1 − x)α-Fe2O3 (x = 0.1–0.7) nanostructure system was synthesized using mechanochemical activation by ball milling and characterized by XRD, simultaneous DSC–TGA, and UV/Vis/NIR. The microstructure and thermal behavior of as obtained system were dependent on the starting In2O3 molar concentration x and ball milling time. XRD patterns yielded the dependence of lattice parameters and grain size as a function of ball milling time. After 12 h of ball milling, the completion of In3+ substitution of Fe3+ in hematite lattice occurs for x = 0.1, indicating that the solid solubility of In2O3 in hematite lattice is extended. For x = 0.3, 0.5, and 0.7, the substitutions between In3+ and Fe3+ into hematite and In2O3 lattice occur simultaneously. The lattice parameters a and c of hematite and lattice parameter a of indium oxide vary as a function of ball milling time. The changes of these parameters are due to ion substitutions between In3+ and Fe3+ and the decrease in the grain sizes. Ball milling has a strong effect on the thermal behavior and band gap energy of the as-obtained system. The hematite decomposition is enhanced due to the smaller hematite grain size. The crystallization of hematite and In2O3 was suppressed, with drops of enthalpy values due to the stronger solid–solid interactions after ball milling, which caused gradual In3+–Fe3+ substitution in hematite/In2O3 lattices. The band gap for hematite shifts to higher energy value, while that of indium oxide shifts to lower energy value after ball milling.

High energy ball-milling methods were employed in the synthesis of anatase-doped hematite xTiO2(a) · (1−x)α-Fe2O3 (x = 0.1, 0.5, and 0.9) ceramic system. The thermal behavior of as obtained ceramic system was characterized by simultaneous DSC–TG. The pure anatase phase was found to be stable below 800 °C, but there is a 10.36% mass loss due to the water content. Two exothermic peaks on DSC curves of pure anatase indicate the different crystallization rates. The pure hematite partially decomposed upon heating under argon atmosphere. Ball-milling has a strong effect on the thermal behaviors of both anatase and hematite phases. For x = 0.1 and 0.5, there is gradual Ti substitution of Fe in hematite lattice, and the decomposition of hematite is enhanced due to the smaller particle size after ball-milling. The crystallization of hematite was suppressed as the enthalpy values decreased due to the anatase-hematite solid–solid interaction. For x = 0.9, most of the anatase phase converted to rutile phase after long milling time. The thermal behavior of xTiO2(a) · (1−x)α-Fe2O3 showed smaller enthalpy value of the hematite transformation to magnetite and anatase crystallization due to the small fraction of hematite phase in the system and hematite–anatase interaction, while the mass loss upon heating increased as a function of milling time due to more water content absorbed by the smaller particle size.

Gallium nitride single crystals with 2 µm diameters and lengths up to several millimeters were grown in supercritical ammonia. The colorless transparent hexagonal nitride crystals were grown at 600 °C for 4 days with a vertical temperature gradient of 150 °C. Several amide catalysts and temperature gradients were studied. The wurtzite structure (space group P63mc) of the crystals was confirmed by X-ray powder diffraction. The chemical mechanisms of the nitride growth and the transport in supercritical ammonia are discussed. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The stability of gamma alumina with respect to phase transitions and loss of surface area can be greatly improved by digestion of the aluminium hydroxide precursor. Pseudoboehmite (aluminium hydroxide) was formed by precipitating aluminium nitrate with ammonium hydroxide at pH 6. The freshly precipitated gel has a very low surface area, but the surface area increases after digestion of the hydroxide in the mother liquour. Digestion leads to a ‘drier’ hydroxide as shown by thermogravimetry. After calcination to 500°C, the resulting alumina has a surface area of 230 to 310 m 2 g −1 , depending on the length of digestion of the hydroxide. Aluminas prepared from aged precursors have better thermal stability than those prepared without the digestion step. The digested alumina was able to withstand calcination to 1200°C for 12 h, and maintained a surface area of ∼68 m 2 g −1 . The transformation to the alpha phase is delayed in the digested samples. The effect of digestion on the surface area and improved thermal stability are explained on the basis of a reduction in the number of defect sites responsible for surface diffusion.

High-surface-area zirconia was obtained by digestion of hydrous oxide precipitated with ammonia and sodium hydroxide. The acidity of digested and undigested samples was compared by ammonia temperature-programmed desorption and pyridine adsorption. Undigested zirconia showed only Lewis acid sites but digested samples have Bronsted sites as well. The acid strength of the digested samples was higher than that of undigested samples. This is attributed to the smaller crystallite size, which results in a larger number of highly uncoordinated zirconium ions. Samples prepared from sodium hydroxide contained sodium ions in a surface layer that reduces the acidity of the samples.

X-ray powder diffraction, simultaneous DSC/TGA and Mössbauer spectroscopy. Structural, thermal and magnetic properties. Cation distributions derived from isomer shifts. The xFe2TiO4-(1−x)Fe3O4 pseudo-binary systems (0≤x≤1) of ulvöspinel component were synthesized by solid-state reaction between ulvöspinel Fe2TiO4 precursors and commercial Fe3O4 powders in stochiometric proportions. Crystalline structures were determined by X-ray powder diffraction (XRD) and it was found that the as-obtained titanomagnetites maintain an inverse spinel structure. The lattice parameter a of synthesized titanomagnetite increases linearly with the increase in the ulvöspinel component. 57Fe room temperature Mössbauer spectra were employed to evaluate the magnetic properties and cation distribution. The hyperfine magnetic field is observed to decrease with increasing Fe2TiO4 component. The fraction of Fe2+ in both tetrahedral and octahedral sites increases with the increase in Ti4+ content, due to the substitution and reduction of Fe3+ by Ti4+ that maintains the charge balance in the spinel structure. For x in the range of 0 ≤x≤0.4, the solid solution is ferrimagnetic at room temperature. However, it shows weak ferrimagnetic and paramagnetic behavior for x in the range of 0.40.70, it only shows paramagnetic behavior, with the appearance of quadrupole doublets in the Mössbauer spectra. Simultaneous differential scanning calorimetry and thermogravimetric analysis (DSC–TGA) studies showed that magnetite is not stable, and thermal decomposition of magnetite occurs with weight losses accompanying with exothermic processes under heat treatment in inert atmosphere. The work at Duquesne was supported by the National Science Foundation under grant DMR-0854794. Peerreview

Indium oxide-doped hematite xIn2O3·(1-x)α-Fe2O3 (x = 0.1-0.7) solid solution systems were synthesized using mechanochemical activation. The microstructures, magnetic and thermal properties of the system were dependent on In2O3 molar concentration x and ball milling time. XRD results showed that the completion of In3+ substitution of Fe3+ in hematite lattice occurs after 12 h ball milling for x = 0.1. For x = 0.3, 0.5 and 0.7, the substitutions between In3+ and Fe3+ into hematite and In2O3 lattices occur simultaneously. The lattice parameters of hematite and In2O3 vary as a function of ball milling time. The change in these parameters was due to ions substitution between In3+and Fe3+ and the decrease in grain sizes. Mössbauer spectra of the system with x = 0.3 were fitted with three sextets and two quadrupole-split doublets after milling, representing In3+ substitution of Fe3+ in hematite lattice and Fe3+ substitution of In3+ in two different sites of In2O3 lattice. TGA results showed that the hematite decomposition is enhanced due to the smaller hematite grain size. The crystallization of hematite and In2O3 was suppressed with the drops of enthalpy values due to the stronger solid-solid interactions after ball milling. These caused gradual In3+-Fe3+ substitution in hematite/In2O3 lattices.