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The exploration of photosensitizers with aggregation-induced emission (AIE PSs) for efficient visualization and broad-spectrum photodynamic killing of pathogenic microbes is a significant task. Herein, two far-red/near-infrared AIE-active PSs (TBTPy and TBTCy) were attained to show efficient Type I and Type II ROS generation, benefiting from the efficient ISC processes. The attained AIE PSs, especially TBTPy with bright emission, showed advantages in discriminating G

Supplementary Figure legends

Purpose:Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP).Patients and Methods:In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups.Results:The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm.Conclusions:Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644.See related commentary by Müller, p. 3

AEs of interest and laboratory abnormalities: Forest plot comparing rate differences (all grades) for flumatinib and imatinib. AEs were assessed according to the Common Terminology Criteria for Adverse. Events (NCI-CTCAE version 4.03). Abbreviation: QTc, Electrocardiogram QT corrected interval.

Background The efficacy of hetrombopag in Chinese patients with immune thrombocytopenia (ITP) has been demonstrated in a randomized, double-blind, placebo-controlled, multicenter, phase III trial (NCT03222843). Objective This study aimed to report comprehensive data on a ≤6-week dose tapering to withdrawal (Stage 3) and an additional 24-week long-term extension period (Stage 4) in this phase III trial. Patients/methods Patients who fulfilled the screening criteria were eligible to enter Stage 3 or 4. During Stage 3, hetrombopag was gradually tapered to withdrawal. During Stage 4, hetrombopag treatment was initiated at 2.5, 3.75, 5, or 7.5 mg once daily. The efficacy endpoints during Stage 3 or 4 and the safety profile during the entire treatment period were reported. Results Among 194 patients who entered Stage 3, 171 (88.1%) relapsed. The median time to the first relapse since the start of Stage 3 was 15.0 days (95% CI, 14.0-16.0). In Stage 4, 144 (42.5%) patients responded at ≥75% of their assessments and 254 (74.9%) patients achieved platelet count ≥30×109 /L at least once, which was at least twice their baseline platelet count in the hetrombopag group (n=339). The most common adverse events were upper respiratory tract infection (53.1%), thrombocytopenia (27.1%), and urinary tract infection (21.2%) in the hetrombopag group. Conclusion The majority of patients who experienced dose tapering to withdrawal experienced a relapse. Long-term treatment with hetrombopag was effective in increasing and maintaining platelet count within the desired range in Chinese adults with ITP. Hetrombopag was well tolerated.

The biological sulfur cycle is closely related to iron corrosion in the natural environment. The effect of the sulfur-oxidising bacterium Ectothiorhodospira sp., named PHS-Q, on the metal corrosion behaviour rarely has been investigated. In this study, the corrosion mechanism of Q235 carbon steel in a PHS-Q-inoculated medium is discussed via the characterization of the morphology and the composition of the corrosion products, the measurement of local corrosion and the investigation of its electrochemical behaviour. The results suggested that, initially, PHS-Q assimilates sulfate to produce H2S directly or indirectly in the medium without sulfide. H2S reacts with Fe2+ to form an inert film on the coupon surface. Then, in localised areas, bacteria adhere to the reaction product and use the oxidation of FeS as a hydrogen donor. This process leads to a large cathode and a small anode, which incurs pitting corrosion. Consequently, the effect of PHS-Q on carbon steel corrosion behaviour is crucial in an anaerobic environment.

A photo-bio cascade strategy was explored to synthesize enantiocomplementary vicinal fluoro alcohols from styrenes, with high efficiency and stereoselectivity.

PURPOSE A combination of anti–B-cell maturation antigen (BCMA) and anti-CD19 chimeric antigen receptor (CAR) T cells induced high response rates in patients with relapsed or refractory (R/R) multiple myeloma (MM), but long-term outcomes have not been assessed yet. PATIENTS AND METHODS In this single-arm, phase II trial, patients with R/R MM received a combination of anti-BCMA CAR T cells and anti-CD19 CAR T cells at a dose of 1 × 106 cells/kg, after receiving a conditioning chemotherapy consisting of cyclophosphamide and fludarabine. The overall response, long-term outcomes, and safety were assessed, as were their associations with clinical and disease characteristics. RESULTS Of 69 enrolled patients, 62 received the combined infusion of anti-BCMA and anti-CD19 CAR T cells with a median follow-up of 21.3 months. The overall response rate was 92% (57/62), and complete response or better was observed in 37 patients (60%). Minimal residual disease–negativity was confirmed in 77% (43/56) of the patients with available minimal residual disease detection. The estimated median duration of response was 20.3 months (95% CI, 9.1 to 31.5). The median progression-free survival was 18.3 months (95% CI, 9.9 to 26.7), and the median overall survival was not reached. Patients with extramedullary disease had significantly inferior survival. Fifty-nine patients (95%) had cytokine release syndrome, with 10% grade 3 or higher. Neurotoxic events occurred in seven patients (11%), including 3% grade 3 or higher. Late adverse effects were rare, except for B-cell aplasia, hypogammaglobulinemia, and infections. CONCLUSION The combination of anti-BCMA and anti-CD19 CAR T cells induced durable response in patients with R/R MM, with a median progression-free survival of 18.3 months and a manageable long-term safety profile.

The present study was focused on comparison of four typical fungicides in ginseng field to evaluate the impact of the different fungicides on the soil bacterial and fungal communities’ composition and diversity by using high-throughput sequencing. Five treatments were designed comprising carbendazim (D), dimethyl disulfide (E), dazomet (M), calcium cyanamide (S), and control (C). The application of fungicide obviously altered the distribution of dominant fungal and bacterial communities and remarkably decreased the diversity (1099-763 and 6457-2245). The most abundant Proteobacteria obviously degenerate in fungicide-treated soil and minimum in E (0.09%) compared to control (25.72%). The relative abundance of Acidobacteria was reduced from 27.76 (C) to 7.14% after applying fungicide and minimum in E. The phylum Actinobacteria are both decomposers of organic matter and enemies of soil-borne pathogens, elevated from 11.62 to 51.54% and are high in E. The fungi community mainly distributed into Ascomycota that enriched from 66.09 to 88.21% and highin M and E (88.21 and 85.10%), and Basidiomycota reduced from 21.13 to 3.23% and low in M and E (5.27 and 3.23%). Overall, environmentally related fungicides decreased the diversity and altered the composition of bacterial and fungal communities, highest sensitivity present in dimethyl disulfide-treated soil., Graphical abstract

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder which characterizes with platelet production impairment and platelet destruction increment. CD4+CD25+ Foxp3+ Treg cells (Tregs) are involved in the immune pathogenesis of ITP. MicroRNAs (miRNAs) are also involved in ITP and their loss of function is shown to facilitate immune disorders. Thus, the miRNA expression profile in Tregs from ITP was analyzed in this study. We assessed the genome-wide miRNA expression profile of three newly diagnosed adult patients with ITP and three healthy controls using microarray analysis of CD4+CD25+CD127dim/− Tregs that were sorted using an immune magnetic bead kit. The miRNA microarray chip was based on miRBase 18.0 and Volcano Plot filtering software used to analyze the miRNA profile in Tregs. Distinct miRNA expression was further validated by fluorescence-based real-time quantitative PCR (qPCR). We found that 502 human miRNAs were differentially expressed (244 upregulated and 258 downregulated) in patients with ITP compared with healthy donors. We identified 37 miRNAs expressed significantly, including 26 upregulated and 11 downregulated. Among the deregulated miRNAs, three downregulated miRNAs including miR-155–5p, miR-146b-5p, and miR-142–3p were selected for qPCR verification. We confirmed that miR-155–5p, miR-146b–5p, and miR-142–3p were significantly decreased in Tregs from patients with ITP compared with healthy controls. Compared with the healthy controls, miRNAs expressed differentially in the Tregs of patients with ITP. The levels of expression of miR-155–5p, miR-146b-5p, and miR-142–3p were significantly decreased. Therefore, the deregulation of miRNAs may affect the function of Tregs in the course of ITP.

The development of long-wavelength emission carbon dots as a label-free sensing platform for the direct detection of glutathione (GSH) is still of great challenge. Herein, novel rose-red fluorescence carbon dots (wCDs) with a long-wavelength emission of 654 nm were successfully synthesized by a one-step microwave-solvothermal treatment of biomass Wedelia trilobata. The biomass-based wCDs could sensitively respond to copper ions (Cu2+) with a limit of detection (LOD) of 0.22 μM, which could be utilized as the fluorescence turn off-on sensor for the detection of GSH through recovering their fluorescence quenched by Cu2+. Moreover, the label-free wCDs with abundant active functional groups could be used to construct a direct quenching platform for the sensitive and selective detection of GSH by the dynamic quenching effect within 20 s without further modification, displaying a good linear range of 0-3.0 mM with a LOD of 35 μM that fits well with the GSH content in living cells (0.5-10 mM). Additionally, confocal imaging of living cells indicates that as-prepared wCDs with high photobleaching resistance and favorable biocompatibility possess the capacity for real-time monitoring of the variations of intracellular Cu2+ and GSH levels, and distinguishing cancerous cells from normal cells owing to the overexpression of GSH in cancerous cells. This study opens a new vision for developing an efficient and sensitive fluorescent sensor for the detection of GSH, and demonstrates the great prospects for wCDs in ion/molecule tracking, bioimaging and cancer diagnosis.

The primary purpose of this study was to develop an innovative chitosan (CS) modified polylactic acid (PLA) nanospheres for enhancing the bioavailability of 1, 2-benzisothiazolin-3-one (BIT). The cellular uptake efficiency was corresponded positively to the quantity of CS coated on BIT-PLA nanospheres against E. coli and S. aureus. The membrane potentials of E.coli and S. aureus treated with BIT-PLA, BIT-PLA-0.1%CS and BIT-PLA-0.5%CS were reduced with the extension of incubation time and the ratio of coated CS. The enhancement of CS modified on BIT-PLA nanospheres was reduced antioxidase activities and generated excessive reactive oxygen species. The lowest EC50 value of the modified BIT-PLA-0.5%CS suggested that its toxicity index was around 2.95-fold and 2.11-fold that of non-modified BIT-PLA against E. coli and S. aureus, respectively. These results revealed that the CS modified BIT-PLA nanospheres had a bright prospect in antibacterial formulation delivery system and improving the bioavailability.

This work demonstrates that the effective use of antimicrobial agents (CQDs-TiO2: carbon quantum dot-decorated titanium dioxide) and natural resources, such as sunlight, is able to improve the ability of sustainable degradation of bacteria. The CQDs-TiO2 nanomaterials, prepared using the hydrothermal method, were characterized by X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Scanning electron microscope (SEM) and Transmission electron microscope (TEM). The CQDs-TiO2 properties and their antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus were systematically evaluated. The antibacterial efficiency reached 90.9% and 92.8% toward E. coli and S. aureus, respectively, with 1 μg/mL CQDs-TiO2 under visible light for 24 h. Under visible light irradiation, CQDs-TiO2 greatly improved absorption of visible light and increased the content of free radicals. These free radicals directly attack the bacterial cells, degrade organic matter within the cells and finally break down bacteria. Seven cycles of antimicrobial experiments using recycled materials demonstrated that the ability of CQDs-TiO2 to sustainably degrade bacteria was stronger than pure titanium dioxide (TiO2). It is noteworthy that carbon quantum dots (CQDs) not only prevent TiO2 from agglomerating, but also attract bacteria and carry TiO2 to the cell. In addition, CQDs-TiO2 showed very low cytotoxicity and can be applied to medical and human health fields.

The diagnostic hallmark of acute promyelocytic leukemia (APL) is the reciprocal translocation t(15;17), resulting in the characteristic PML-RARA fusion; however, patients occasionally have masked PML-RARArearrangements. We report an APL case with no evidence of t(15;17) or PML-RARA rearrangement by karyotype or commercial reverse transcription polymerase chain reaction analyses. Fluorescence in situ hybridization detected a small RARA insertion signal within PML. mRNA sequencing identified a novel PML-RARA transcript generated from the juxtaposition of PMLIIa (exons 1–4, 6, and 7ab) and RARA exons (3–9), with novel breakpoints in PML exon 7b and RARA exon 3. The patient achieved molecular remission after the second consolidation chemotherapy and remains in complete remission 22 months after initial presentation. This is the first report of an APL case presenting with submicroscopic ins(15;17) and simultaneous novel breakpoints in both PML and RARA. This case highlights the importance of sequence analysis to confirm APL diagnosis and for subsequent monitoring of minimal residual disease.

Three novel copper(ii) complexes, Cu(L1)2 (1), Cu(L2)2·2DMF (2), and Cu(L3)2·2DMF (3), were synthesized using three aroylhydrazone ligands, (E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL1), (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2) and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL3). The complexes were characterized by elemental analysis, infrared (IR), and Ultraviolet-visible light (UV-vis) spectroscopy. The X-ray crystal structures of the complexes all possess a distorted octahedral coordination geometry. Both an absorption spectral titration and a competitive binding assay (ethidium bromide, 4',6-diamidino-2-phenylindole (DAPI), and methyl green) revealed that complexes 2 and 3 bind readily to calf thymus DNA (ctDNA) through intercalative and minor groove binding modes. Complexes 2 and 3 also exhibited oxidative cleavage of supercoiled plasmid DNA (pUC19) in the presence of ascorbic acid as an activator. Cytotoxicity studies showed that complexes 2 and 3 possessed high cytotoxicities toward the HeLa human cervical cancer cell line, but weak toxicities toward the L929 normal mouse fibroblast cell line. We therefore have reason to believe that complexes 2 and 3 both show potential as promising anticancer candidate drugs.

Nano-antibacterial calcium phosphate (CaP) has attracted intense attention with regard to its wide variety of medical and biological applications. The γ-polyglutamic acid and copper cosynthesized hydroxyapatite (γ-PGA/CuxHAp) was synthesized using the wet method. Structural and chemical characterizations demonstrate that copper was quantitatively incorporated into the hydroxyapatite structure, and the degree of Cu substitution was up to 20 mol % in the synthesized nanocrystals. Morphology characterization showed that the size of the γ-PGA/CuxHAp nanoparticles decreases with the increased copper content. γ-PGA/CuxHAp exhibited a steady release of Cu ions. Two experimental protocols were applied to compare the antibacterial activity of the γ-PGA/CuxHAp samples. A positive correlation was observed between Cu content and the inhibition of bacterial growth. The study also showed that nanoparticles with smaller particle sizes exhibited higher antibacterial activities than the larger particles. Endothelial and osteoblast cells rapidly proliferated on γ-PGA/CuxHAp, whereas high concentrations (20 mol %) of Cu ions reduced cell proliferation. In the rat calvarial defect model, some γ-PGA/CuxHAp samples such as γ-PGA/CuxHAp (x = 8, 16) showed efficient bone regeneration capacities at 12 weeks post implantation. Thus, the multibiofunctional γ-PGA/CuxHAp nanocomposite exhibited degradative, angiogenic, bactericidal and bone regenerative properties, providing a potential means to address some of the critical challenges in the field of bone tissue engineering.

Additional file 1: Table S1. Investigators per site. Table S2. Dose adjustments of hetrombopag during the double-blind treatment period and open-label treatment period. Table S3. Dose adjustments of eltrombopag for patients in the Placebo-eltrombopag group during the double-blind treatment period and open-label treatment period. Table S4. Platelet responses (platelet counts ≥ 50 × 109/L at week 8) were observed across all subgroups of baseline platelet counts, sex, age, and splenectomy status. Table S5. Proportion of responders at different time points within 8 weeks after treatment.

Starting from primary amine bearing cyclic carbonate tert-butyl-(2-oxo-1,3-dioxan-5-yl) carbamate (TBODC) and caprolactone (CL), amphiphilic poly(caprolactone-ran-amino trimethyl carbonate)s (P(CL-ran-ATC)s) random copolymers with controlled molecular weight and composition were synthesized via ring opening polymerization (ROP) and deprotection, using stannous octoate (Sn(Oct)2) as catalyst and benzyl alcohol (BnOH) as initiator. Therefore, hydrophilic/lipophilic ratio (HLR) of the P(CL-ran-ATC)s copolymers can be finely adjusted by the feed ratio of TBODC and CL. The antimicrobial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) of P(CL-ran-ATC)s were proportional to HLR, and P(CL-ran-ATC)s presented more vigorous bactericidal activity towards S. aureus. The minimum inhibitory concentration (MIC) values of P(CL-ran-ATC 50.9%) are 2000 &mu, g mL&minus, 1 and 3000 &mu, 1 for S. aureus and E. coli. While P(CL-ran-ATC 50.9%) exhibited deficient hemolytic activity as 1.41%. In addition, the P(CL-ran-ATC)s showed extremely low cytotoxicity towards fibroblast L929 cells.

Anthracycline chemotherapy is commonly used in the treatment of diffuse large B-cell lymphoma (DLBCL). Treatment-related cardiotoxicity (TRC) is defined as when the patient is identified to have one of the following clinical manifestations: Symptomatic heart failure, cardiac death, arrhythmia, infarction, a decrease in left ventricular ejection fraction (LVEF) of >15% from baseline or a decrease in LVEF of >10 to 1 for predicting TRC after anthracycline chemotherapy (P

Antibiotics are frequently used for clinical treatment and by the farming industry, and most of these are eventually released into the surrounding environment. The impact of these antibiotic pollutants on environmental microorganisms is a concern. The present study showed that after Pseudomonas putida entered the logarithmic growth phase, tetracycline strongly stimulated its biofilm formation in a dose-dependent manner. This was supported by the increased expression of the key adhesin gene lapA in response to tetracycline treatment. Tetracycline treatment also changed the expression levels of the exopolysaccharide gene clusters alg, bcs and pea and the adhesin gene lapF. However, these genes did not participate in the tetracycline-induced biofilm formation. When a biofilm had been established, the P. putida population became more tolerant to tetracycline. Confocal laser scanning microscopic images showed that the interior of the biofilm provided favorable conditions that protected bacterial cells from tetracycline. Besides, biofilm formation of P. putida was also promoted by several other antibiotics, including oxytetracycline, fluoroquinolones, rifampicin, and imipenem, but not aminoglycosides. Susceptibility tests suggested that biofilm conferred a higher tolerance on P. putida cells to specific antibiotics (e.g., tetracyclines and fluoroquinolones). These antibiotics exerted a stronger inducing effect on biofilm formation. Together, our results indicate that P. putida actively forms robust biofilms in response to antibiotic stress, and the biofilms improve the survival of bacterial population under such stress.

Background: Anthracycline chemotherapy is commonly used in the treatment of diffuse large B-cell lymphoma (DLBCL) patients. Treatment-related cardiotoxicity (TRC) may be observed during treatment and may induce severe cardiac failure or cardiac arrhythmia as the main cause of death, even several years after chemotherapy implementation. Herein, we performed a study to investigate the prognostic value of gated myocardial perfusion imaging (G-MPI) summed rest score (SRS) for the early detection of TRC caused by anthracycline chemotherapy in DLBCL patients.Methods: A total of 36 DLBCL patients were enrolled, and a series of parameters from the same individual patient were compared between baseline and after the end of the 6th R-CHOP chemotherapeutic regimen. According to whether TRC occurred during the observation period, the patients were divided into two groups, and parameters related to cardiac function were compared.Results: SRS in G-MPI and QTc interval in electrocardiogram were significantly different before and after chemotherapy (P = 0.012 and P = 0.015, respectively).By comparing parameters related to cardiac function between the TRC group (n = 22) and the no-TRC group (n = 14), only SRS was significantly different (P = 0.012). Multivariate logistic regression analysis showed that the SRS level was the only independent predicator for TRC (P = 0.018, HR = 6.053, 95% CI: 1.364-26.869). Receiver operating characteristic curve analysis identified an optimal SRS cutoff of >1for predicting TRC after anthracycline chemotherapy (P＜ 0.001).Conclusion: The G-MPI SRS level was an early indicator for TRC surveillance in DLBCL patients after anthracycline chemotherapy, thus contributing to early treatment and a subsequent decrease in mortality caused by such cardiovascular complications.

Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups. Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Müller, p. 3

In this work, three aroylhydrazone ligands ((E)-2-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL1; (E)-3-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL2; and (E)-4-hydroxy-N'-(1-(pyrazin-2-yl)ethylidene)benzohydrazide, HL3) and their complexes with nickel (Ni(L1)2, NiL1; Ni(L2)2∙2DMF, NiL2; Ni(L3)2∙2DMF, NiL3) were prepared. The single crystal X-ray structures analysis of three compounds showed that they were neutral. The ligand adopts tridentate chelating mode. The nickel ion is six-coordinate with two O atoms and four N atoms from two ligands, and forms an octahedral arrangement. The investigation of DNA binding ability by ultraviolet and fluorescence titrations showed that NiL2 and NiL3 exhibit moderate binding affinity toward calf Thymus DNA. Spectroscopy, molecular docking, and molecular dynamics simulation indicated that NiL2 and NiL3 bind at the minor groove of DNA through intercalation.

In this work, γ-valerolactone (GVL) pretreatment using FeCl3 as a catalyst under mild temperature (120 °C) to facilitate efficient deconstruction and saccharification of Chinese silvergrass (CS) was reported. The pretreatment resulted in significant xylan and lignin removal of CS and the highest xylan and lignin removal reaching 84.3 % and 68.7 % at FeCl3 concentration of 100 mM. No obvious change in the crystalline structure of cellulose was observed under the mild pretreatment condition. X-ray photoelectron spectroscopy analysis indicated that the FeCl3-catalyzed GVL pretreatment caused poorer lignin but richer carbohydrates on the CS surface due to the increased O/C ratio in CS (increased from 0.23 to 0.63). The results indicated that the pretreatment could facilitate the decrease of non-productive adsorption of enzyme and was beneficial for the enzymatic saccharification of pretreated CS, and a high glucose yield of 99.7 % was achieved by cellulases and Tween 80.

3D flower-like MoS2/NiCo(OH)2CO3 (MoS2/NiCoHC) composites are synthesized by a hydrothermal method using MoS2 nanospheres as precursors. The microstructure of the composite is characterized by X-ray diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy and X-ray photoelectron spectroscopy. The MoS2 nanospheres are served as nucleating agent to trigger the formation of NiCoHC nanosheets, which self-assemble into 3D flower-like MoS2/NiCoHC particles. The MoS2/NiCoHC composites exhibit a high supercapacitive performance with a specific capacity of 583 C g−1 (1296 F g−1) at 1 A g −1 and a long-term cycling stability by retaining 94.3% after 2000 cycles in 2 M KOH. Moreover, the asymmetric supercapacitor of MoS2/NiCoHC as the positive electrode and commercial active carbon as the negative electrode achieves a high power density of 375 W kg−1 at 16.4 Wh kg−1. The enhanced performance of the MoS2/NiCoHC composite can be attributed to the larger surface area provided by 3D flower-like structure and the synergy of the two hybrids.

This study aimed to investigate clinical characteristics and prognostic significance of activation-induced cytidine deaminase (AID) gene, miR-181b and miR-155 expression in de novo adult B-cell acute lymphoblastic leukemia (B-ALL) patients. Results showed that AID and miR-155 expression were higher in B-ALL patients than healthy controls, while miR-181b expression was lower in B-ALL patients. In addition, Ph+ B-ALLs had higher AID expression than Ph- B-ALLs, and its high expression was associated with BCR-ABL. Moreover, B-ALL patients with AIDhigh or miR-181blow expression had a shorter overall survival (OS). AIDhigh with miR-181blow, AIDhigh with miR-155low, miR-181blow, miR-155low, AIDhigh with miR-181blow and miR-155low expression were associated with shorter OS. Combination of the three molecules are more accurate predictors for unfavorable OS compared with univariate group. Therefore, AID, miR-181b and miR-155 provide clinical prognosis of adult de novo B-ALL patients and may refine their molecular risk classification.

The diagnostic hallmark of acute promyelocytic leukemia (APL) is the reciprocal translocation t(15;17), resulting in the characteristic PML-RARA fusion; however, patients occasionally have masked PML-RARArearrangements. We report an APL case with no evidence of t(15;17) or PML-RARA rearrangement by karyotype or commercial reverse transcription polymerase chain reaction analyses. Fluorescence in situ hybridization detected a small RARA insertion signal within PML. mRNA sequencing identified a novel PML-RARA transcript generated from the juxtaposition of PMLIIa (exons 1-4, 6, and 7ab) and RARA exons (3-9), with novel breakpoints in PML exon 7b and RARA exon 3. The patient achieved molecular remission after the second consolidation chemotherapy and remains in complete remission 22 months after initial presentation. This is the first report of an APL case presenting with submicroscopic ins(15;17) and simultaneous novel breakpoints in both PML and RARA. This case highlights the importance of sequence analysis to confirm APL diagnosis and for subsequent monitoring of minimal residual disease.

Erbin has been shown to have significant effects on the development of solid tumors. However, little is known about its function and regulatory mechanism in hematological malignancies. The biological function of Erbin on cell proliferation was measured in vitro and in vivo. The predicted target of Erbin was validated by dual-luciferase reporter assay and rescue experiment. We found that overexpression of Erbin could inhibit the cell proliferation and promote the cell differentiation of acute myeloid leukemia (AML) cells, whereas depletion of Erbin could enhance the cell proliferation and block the cell differentiation in AML cells in vitro and in vivo. Besides, miR-183-5p was identified as the upstream regulator that negatively regulated the Erbin expression. The results were confirmed by dual-luciferase reporter and RNA pull-down assay. Furthermore, we found that miR-183-5p negatively regulated Erbin, resulting in enhanced cell proliferation of AML cells via activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways. The activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways was mediated by Erbin interacting with Grb2. These results were also validated by rescue experiments in vitro and in vivo. All above-mentioned findings indicated that the miR-183-5p/Erbin signaling pathway might represent a novel prognostic biomarker or therapeutic target for treatment of AML., Regulation mechanism of Erbin in hematological malignancy especially in leukemia remains unexplored. In this issue of Molecular Therapy, Zheng et al. report that the miR-183-5p/Erbin pathway modulates proliferation and differentiation of acute myeloid leukemia cells and may be served as a novel therapeutic target.

Nanocomposites composed of Ag and γ-Fe