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As the desired sulfur host of lithium-sulfur battery, the strong polarity and fast electron migration capability are indispensable for achieving effective adsorption and conversion of lithium polysulfides (LiPSs), that is, restricting the shuttle effect. Herein a porous microdisk Ti4O7/TiN/C heterojunction with strong polar N-Ti-O covalent bonds is precisely constructed. Compared with O-Ti-O or N-Ti-N bond in single Ti4O7 or TiN, the N-Ti-O bond with stronger polarity could adsorb and bond with S and Li atoms in LiPSs, which is beneficial for LiPSs adsorption. Beside, the Ti4O7/TiN heterostructure favors the electron transfer, which could promote the conversion of LiPSs. The design strategy is to construct abundant polar N-Ti-O bonds at Ti4O7/TiN heterogeneous interface that would realize the associative process of LiPSs adsorption, trapping, and conversion, thereby restraining the shuttle effect efficiently. In the current study, as the host of the sulfur cathode, the porous microdisk TiN/Ti4O7/C heterojunction exhibits a high specific capacity of 1204.5 mAh g−1 at 0.2 C, and a high specific capacity of 616.5 mAh g−1 at an ultrahigh current density of 4 C. In addition, 86.4% and 116.9% capacity are retained over 1000 cycles at 1 C and 2 C, respectively. This strategy provides an insight into developing lithium-sulfur battery with extraordinary performance, and opens promising routes to design the next-generation electrochemical energy storage devices.

The high specific capacity of metal oxides cannot cover up their low electron and ion diffusion rate and large volume expansion as anodes of lithium-ion batteries.

Engineering MXene-based 2D heterostructures is a hot research topic for capacitive deionization (CDI) materials. Herein, MXene nanosheets were ingeniously integrated with metal-organic frameworks (MOFs)-derived carbons to generate the N, P-doped...

Although cobalt (Co) is indispensable for life, it is toxic to cells when accumulated in excess. The DmeRF system is a well-characterized metal-response system that contributes to Co and nickel resistance in certain bacterial species. The Vibrio parahaemolyticus RIMD 2210633 genome also harbors a dmeRF operon that encodes a multiple antibiotic resistance regulator family transcriptional regulator and a cation diffusion facilitator family protein. Quantitative real-time PCR, growth curves analysis, inductively coupled plasma-mass spectrometry, β-galactosidase activity assays, electrophoretic mobility shift assays, and a mouse infection experiment were performed to characterize the function of the DmeRF system in V. parahaemolyticus. Zinc, copper, and Co significantly increase dmeF expression, with Co inducing the greatest increase. DmeF promotes V. parahaemolyticus growth under high-Co conditions. Additionally, increased accumulation of cellular Co in the ΔdmeF mutant indicates that DmeF is potentially involved in Co efflux. Moreover, DmeR represses the dmeRF operon by binding directly to its promoter in the absence of Co. Finally, the DmeRF system was not required for V. parahaemolyticus virulence in mice. Collectively, our data indicate that the DmeRF system is involved in maintaining Co homeostasis in V. parahaemolyticus and DmeR functioning as a repressor of the operon.

An easy and delicate approach using cheap carbon source as conductive materials to construct 3D sequential porous structural Na3V2(PO4)3/C(NVP/C) with high performance for cathode materials of sodium ion battery is highly desired. In this paper, the NVP/C with 3D sequential porous structure is constructed by a delicate approach named as “cooking porridge” including evaporation and calcination stages. Especially, during evaporation, the viscosity of NVP/C precursor is optimized by controlling the adding quantity of citric acid, thus leading to a 3D sequential porous structure with a high specific surface area. Furthermore, the NVP/C with a 3D sequential porous structure enables the electrolyte to interior easily, providing more active sites for redox reaction and shortening the diffusion path of electron and sodium ion. Therefore, benefited from its unique structure, as cathode material of sodium ion batteries, the 3D sequential porous structural NVP/C exhibits high specific capacities(115.7, 88.9 and 74.4 mA·h/g at current rates of 1, 20 and 50 C, respectively) and excellent cycling stability (107.5 and 80.4 mA·h/g are remained at a current density of 1 C after 500 cycles and at a current density of 20 C after 2200 cycles, respectively).

Synchronously achieving high-capacity and high-rate sodium-ion storage is critical for large-scale energy stationary applications of sodium-ion batteries (SIB). Here we present a facile bottom-up strategy to covalently encapsulate sulfur chains into carbon-rich nanomaterials by knitting 3,4-ethylenedioxythiophene (EDOT) with external crosslinking reactants. Using a series of ex situ characterization studies, the synergistic effects of the covalent sulfur species (21.33 wt%) are demonstrated on both increasing reversible electrochemical active sites/structural defects and expanding interlayer spacing, which endow the elaborate anode material with a high capacity of 456 mA h g−1 @ 0.1 A g−1, a desirable rate capability as high as 253.2 mA h g−1 @ 5 A g−1 for sodium-ion storage, and an excellent long-cycling performance with almost no decay after 5000 cycles @ 5 A g−1. Significantly, dynamic investigation indicates that the sodium-ion storage process and transfer kinetics are closely related to the covalently encapsulated sulfur chains. This work furnishes a new and systemic insight into the rational design of sodium-ion anode materials, in which the covalent sulfur chemistry may play a crucial role in reaching the supreme performance of sodium-ion batteries.

Follicular lymphoma (FL) is characterized by t(14; 18)(q32; q21), leading to overexpression of the antiapoptotic molecule BCL2; however, a subset of FLs lack BCL2 rearrangement and BCL2 expression as analyzed by immunohistochemistry (IHC). In this study, we evaluated expression of antiapoptotic (MCL1 and BCL-XL) and proapoptotic proteins (BIM) by IHC in both BCL2(-) and BCL2(+) FLs. FLs diagnosed between 2009 and 2019 were reviewed to identify BCL2(-) cases by IHC (assessed by clone 124). Immunohistochemical analyses for BCL2 (EP36), MCL1, BIM, BCL-XL, and Ki-67 were performed on tissue microarrays or whole slides. BCL2 (EP36) was interpreted as positive (≥10%) or negative (10%). Ki-67 was interpreted on tumor cells in 10% increments. The remaining immunohistochemical analysis results were scored on tumor cells in 10% increments, and intensity was interpreted as weak, moderate, or strong to derive an H-score. Twenty-four BCL2(-) FLs were initially identified, but on further testing with BCL2(EP36) immunohistochemical staining, 5 of 24 were reclassified as BCL2(+), leaving 19 BCL2(-) FLs. Thirty-three BCL2(+) FLs were selected with sufficient tissue for additional immunohistochemical analyses. There was no significant difference in expression of antiapoptotic BCL-XL or MCL1 between BCL2(-) and BCL2(+) FLs (p = 0.75 and 0.28, respectively). However, proapoptotic BIM expression was significantly lower in BCL2(-) FLs than in BCL2(+) FLs (p = 0.002). In our study, 21% of putative BCL2(-) FLs were BCL2(+) when tested with alternative clones, supporting the practice of having more than one BCL2 clone in immunohistochemical laboratories. Decreased BIM expression in BCL2(-) FLs could have an overall antiapoptotic effect and represent an alternate mechanism for cell survival in BCL2(-) FLs.

Metal oxides/sulfides have been considered as promising anode candidates for use in next-generation lithium-ion batteries (LIBs), but the large volume changes and poor electron and ion conductivities limit their practical applications. Here, twin-born Fe3O4/FeS/carbon nanosheets (TB-FeOSC-NS) were precisely fabricated for the first time by using MIL-88b(Fe) as a self-sacrificing template. By adjusting the amount of citric acid and the annealing temperature, the structure and phase composition could be accurately controlled. Benefitting from its unique structure, TB-FeOSC-NS can provide an abundant contact interface with electrolytes and active sites for redox reactions, providing a short diffusion path for electrons and ions. Therefore, as an anode material for use in LIBs, the TB-FeOSC-NS electrode exhibits admirable electrochemical performance, including a high specific capacity, excellent cycling stability, and superior rate performance, with a high capacity of 400 mA h g−1 at an ultrahigh current density of 20 A g−1. More importantly, this work deepens our understanding of the precise synthesis of heterostructured materials for electrochemical energy storage and the synergistic modulation of morphologies, phase compositions, and interfaces.

The availability of efficient, low-cost and durable oxygen electrocatalyst for oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is the prerequisites for large-scale,practical application of rechargeable zinc (Zn)-air batteries. Thus, stable electrocatalysts with high oxygen electrocatalytic activity are in highly demand. Low-cost and metal-free carbon-based bifunctional oxygen electrocatalysts are regarded as promising alternatives to the commercially used noble metals which suffer from multiple drawbacks, including poor stability, high cost and susceptibility to methanol. Here, a facile and scalable strategy was introduced to fabricate porous carbon matrix doped with high content of active nitrogen species as efficient bifunctional oxygen electrocatalyst for superior Zn-air battery. Notably, the obtained electrocatalysts exhibit an ultrahigh surface area of 1200.3 ​m2 ​g−1 and abundant defects, both of which are capable to facilitate the accessibility and formation of catalytic sites. The as-fabricated Zn-air batteries achieve significantly large peak power density of ~160 ​mW ​cm−3 and excellent cycling performance (nearly 1000 cycles) with small voltage gap of 0.97 ​V. This research opens novel avenue for the design and fabrication of affordable high-performance oxygen electrocatalyst and durable energy storage systems.

Multi-wall Sn/SnO2 @carbon hollow nanofibers evolved from SnO2 nanofibers are designed and programable synthesized by electrospinning, polypyrrole coating, and annealing reduction. The synthesized hollow nanofibers have a special wire-in-double-wall-tube structure with larger specific surface area and abundant inner spaces, which can provide effective contacting area of electrolyte with electrode materials and more active sites for redox reaction. It shows excellent cycling stability by virtue of effectively alleviating pulverization of tin-based electrode materials caused by volume expansion. Even after 2000 cycles, the wire-in-double-wall-tube Sn/SnO2 @carbon nanofibers exhibit a high specific capacity of 986.3 mAh g-1 (1 A g-1 ) and still maintains 508.2 mAh g-1 at high current density of 5 A g-1 . This outstanding electrochemical performance suggests the multi-wall Sn/SnO2 @ carbon hollow nanofibers are great promising for high performance energy storage systems.

Capacitive deionization (CDI) provides a promising option for affordable freshwater while simultaneously storing energy, but its large-scale application is usually limited owing to the poor performance of conventional materials in natural (oxygenated) saline water. Herein, we report heterointerface optimization in a covalent organic framework (COF)-on-MXene heterostructure achieving a high CDI performance for desalination of oxygenated saline water. The 2D heterostructure with the optimal core-shell architecture inherits the high conductivity and reversible ion intercalation/deintercalation ability of MXene, and the hierarchical porous structure, large porosity, and extraordinary redox capacity of COFs. Thanks to the heterointerface optimization, the MXene@COF heterostructure exhibits a very stable cycling performance over 100 CDI cycles with a maximum NaCl adsorption capacity of 53.1 mg g

As a promising energy-storage and conversion anode material for high-power sodium-ion batteries operated at room temperature, the practical application of layered molybdenum disulfide (MoS

As a promising cathode material for high-power lithium-ion batteries, LiFePO4 (LFP) suffers from low lithium-ion diffusivity and poor electronic conductivity. In this work, hierarchically porous Ti3C2Tx MXene decorated LFP@C (LFP@C/MXene) composite was successfully synthesized by a facile and efficient electrostatic self-assemble method at room temperature with the help of CTAB to regulate charge state. The introduction of MXene sheets realized the formation of hierarchically porous structure and “dot-to-surface” conductive network, enabling the fast ion and electrons transfer for redox reactions, meanwhile, MXene will be partially oxidized into TiO2 and carbon during cycling, which further improved the diffusion of lithium-ion. Together with the optimized structure of LFP@C nanoplates, the resulting LFP@C/MXene exhibits robust high-rate capability (139 mAh·g−1 at 20 C) as well as a long-life cycling stability (156.6 mAh·g−1 at 1 C with superior capacity retention of 94.8% for 500 cycles). This ingenious design highlights the great potential of 2D MXene for facilely constructing multifunctional electrode materials for application in high-rate Li-ion batteries.

MCL-1 is one of the most frequently amplified genes in cancer, facilitating tumor initiation and maintenance and enabling resistance to anti-tumorigenic agents including the BCL-2 selective inhibitor venetoclax. The expression of MCL-1 is maintained via P-TEFb-mediated transcription, where the kinase CDK9 is a critical component. Consequently, we developed a series of potent small-molecule inhibitors of CDK9, exemplified by the orally active A-1592668, with CDK selectivity profiles that are distinct from related molecules that have been extensively studied clinically. Short-term treatment with A-1592668 rapidly downregulates RNA pol-II (Ser 2) phosphorylation resulting in the loss of MCL-1 protein and apoptosis in MCL-1-dependent hematologic tumor cell lines. This cell death could be attenuated by either inhibiting caspases or overexpressing BCL-2 protein. Synergistic cell killing was also observed between A-1592668 or the related analog A-1467729, and venetoclax in a number of hematologic cell lines and primary NHL patient samples. Importantly, the CDK9 inhibitor plus venetoclax combination was well tolerated in vivo and demonstrated efficacy superior to either agent alone in mouse models of lymphoma and AML. These data indicate that CDK9 inhibitors could be highly efficacious in tumors that depend on MCL-1 for survival or when used in combination with venetoclax in malignancies dependent on MCL-1 and BCL-2.

Metals are necessary elements for bacteria. Typically, vertebrate hosts restrict invading bacterial pathogens from accessing metals. Therefore, bacteria have evolved high-affinity metal importers to acquire metals. Streptococcus suis is a major swine pathogen and an emerging zoonotic agent that endangers the swine industry and human health worldwide. Herein, we aimed to identify the zinc acquisition systems in S. suis and evaluate their roles in bacterial virulence. Bioinformatic analyses revealed that S. suis encodes homologues of AdcA and AdcAII, two well-characterised Zn-binding lipoproteins in certain streptococci. Quantitative reverse transcription PCR (qRT-PCR) analysis revealed that the expressions of adcA and adcAII were significantly upregulated in response to Zn limitation, with a higher expression level of adcAII than adcA. Gene deletion mutants and complementation strains were constructed; their growth characteristics under Zn-deficient and Zn-replete conditions indicated that AdcA and AdcAII have overlapping functionality in Zn acquisition. A mouse infection model was used to evaluate the roles of AdcA and AdcAII in S. suis virulence. Mice infected with the double mutant ΔadcAΔadcAII exhibited a significantly higher survival rate, decreased bacterial burden, and lower production of inflammatory cytokines compared to those infected with the wild type (WT) strain. Furthermore, ΔadcAΔadcAII showed reduced competitiveness in infection establishment compared with the WT strain. RNA sequencing, qRT-PCR, and electrophoretic mobility shift assays revealed that AdcR negatively regulates the expressions of adcA and adcAII. Collectively, our results demonstrated that AdcA and AdcAII, which are negatively regulated by AdcR, contribute additively to zinc acquisition and virulence in S. suis.

Objectives Immunoglobulin M plasma cell myeloma (IgMPCM) is a rare entity that is difficult to distinguish from other IgM-related neoplasms. The study aims to characterize the clinicopathologic features of IgMPCM, including MYD88 L265P and CXCR4 mutations. Methods From our institutional archives, bone marrow biopsy specimens from January 1, 2008, to December 1, 2018, with monotypic plasma cells (PCs) expressing IgM that met current International Myeloma Working Group/World Health Organization criteria for PCM were included. Sanger sequencing was used to test for MYD88 L265P and WHIM-like CXCR4 mutations. Results Nine cases of IgMPCM were identified. Serum IgM paraproteins were detected in eight cases. CD138-positive PC burden averaged 41.9% (5%-80%). In four cases, PCs had lymphoplasmacytic morphology with cyclin D1 expression by immunohistochemistry. Three of four tested cases were positive for t(11;14) by fluorescence in situ hybridization, one with monosomy 13. The remaining case was positive for del13q14. All were negative for MYD88 L265P and WHIM-like CXCR4 mutations. Eight patients received immunochemotherapy, with four receiving autologous hematopoietic stem cell transplant. Median follow-up was 61 months (range, 11-120). All patients were alive except one. Conclusions Distinguishing IgMPCM from other IgM-related disorders requires correlation with clinical, laboratory, and radiologic findings. Exclusion of MYD88 L265P and WHIM-like CXCR4 mutations may be useful to diagnose IgMPCM.

Precisely carving of multi-shelled manganese-cobalt oxide hollow dodecahedra (Co/Mn-HD) with shell number up to three is achieved by a controlled calcination of the Mn-doped zeolitic imidazolate framework ZIF-67 precursor (Co/Mn-ZIF). The unique multi-shelled and polycrystalline structure not only provides a very large electrochemically active surface area (EASA), but also enhances the structural stability of the material. The residual C and N in the final structures might aid stability and increase their conductivity. When used in alkaline rechargeable battery, the triple-shelled Co/Mn-HD exhibits high electrochemical performance, reversible capacity (331.94 mAh g-1 at 1 Ag-1 ), rate performance (88 % of the capacity can be retained with a 20-fold increase in current density), and cycling stability (96 % retention over 2000 cycles).

Multishelled binary metal oxide, which can exert a synergetic effect of different oxides, is a promising electrochemical electrode material. However, it is challenging to synthesize this kind of binary metal oxide due to the severe hydrolysis and/or precipitation reactions of the precursors between cations and anions of different metals. Herein, by using citric acid as a chelating agent to inhibit hydrolysis and precipitation, a series of multishelled binary metal oxide hollow spheres (Fe2(MoO4)3, NiMoO4, MnMoO4, CoWO4, MnWO4, etc.) were obtained via coabsorption of negative and positive metal ions. In addition, the chelation between a metal ion and citric acid is systematically validated by NMR, MS, Raman, and UV–vis. In particular, multishelled Fe2(MoO4)3 hollow spheres show excellent electrochemical performance as cathode material for sodium-ion batteries benefited from their structural superiorities. Especially, the quintuple-shelled Fe2(MoO4)3 hollow sphere shows the highest specific capacity (99.03 ...

Layered double hydroxides (LDHs) with 3-dimentional (3D) hollow nanoarchitetures are highly desirable for energy related applications. In this study, Ni-Co-Mn LDH nanoflakes assembled hollow nanocages are constructed from bimetallic imidazolate framworks precursors. Benefiting from the 3D hierarchical porous strcuture and composition, the as-synthesized ternary Ni-Co-Mn LDH hollow nanocage, as a electrode for supercapacitor , demonstrates a remarkable electrochemical performance with a high specific capacitance of 2012.5 F g −1 at 1 A g−1 and a good rate capacity of 75.0% retention at 10 A g−1, significantly outperforming binary Ni-Co LDH (1266.2 F g−1 at 1 A g−1, 41.8% retention at 10 A g−1). This work demonstrates the construction of 3D hollow nanostructured LDH with multicomponent compositions for the first time, and can be simply extended to construct other hollow structured electrode materials for energy storage devices.

Introduction: Aggressive nature killer-cell leukemia (ANKL) is a rare, highly lethal and disseminated malignancy derived from NK cells. Patients are most commonly young to middle aged adults who present with constitutional symptoms and often have organomegaly, hemophagocytosis, and multiorgan failure. Most cases are refractory to therapy and the median survival is less than 2 months despite multiagent chemotherapy. Development model systems and novel targeted therapeutic agents remains an urgent issue. In this study we established a cell line and a NOD-scid IL2Rgammanull(NSG) mouse model of ANKL, which represented the primary malignant cells. We characterized the molecular features of this model and explored new targeted agents against it. Methods: Primary tumor cells were cultured ex vivo in the presence of human IL-2 and then injected into a NSG mouse. Flow cytometry, immunohistochemistry (IHC), CISH-EBER were used to confirm the engraftment and to compare the pathologic features of engrafted tumor cells with the primary sample. Karyotyping and oligonucleotide/single nucleotide polymorphism microarray analyses were performed to compare the established cell line CCANKL with primary tumor cells. Selective inhibitors targeting anti-apoptotic BCL-2 family members and a CD6-targeted antibody drug conjugate (ADC) were tested for their treatment efficacies in this model. Results: Leukemic peripheral blood from a 31-year old woman with relapsed ANKL demonstrated a hyperleukocytosis in which NK cells accounted for 88% of cells. Immunophenotyping showed the malignant cells expressed CD2, 7, 38, 45 and 56, and lacked CD3, 4, 5, 8, 10, 11b, 13, 14, 16, 19, 20, 22, 33, 34, 57, 64, 65, 117, HLADR and Kappa or Lambda immunoglobulin light chain. IHC of an involved lymph node showed the presence of EBV (EBER in situ hybridization) and a proliferative index of 70%. Isolated PBMC were cultured ex vivo and serially passaged as a cell line (CCANKL) in the presence of human IL2. CCANKL cells successfully engrafted in NSG mice and displayed splenomegaly. IHC and Immunophenotyping data confirmed both CCANKL cells and engrafted cells in NSG mice represented primary tumor cells. Both the primary PBMC and CCANKL cells had similar, abnormal karyotypes of 46,XX,dup(1)(q21q42), del(6)(q15q25)[1]/46,idem,der(20)t(7;20)(q11.2;q13.1)[9] and 46,XX,del(6)(q15q25),der(20)t(7;20)(q11.2;q13.1),add(22)(p11.1)[10], respectively. Microarray analysis of both primary tumor cells and CCANKL confirmed some of the karyotypic findings, but also revealed additional abnormalities, in particular for the CCANKL cell line. There were also some differences for the copy number changes and regions of loss of heterozygosity observed between the primary tumor cells and CCANKL. Abnormalities involving 1q, 6q and 7p have been reported in association with aggressive NK cell leukemia. Both immunoblotting and IHC revealed expression of anti-apoptotic proteins of BCL-xL, MCL-1 and pro-apoptotic BIM in CCANKL cells and NSG-engrafted tumors, while BCL-2 was positive in cultured cells by Western blotting but not detectable in engrafted tissue via IHC. Expression level of BCL-xl was stable but there were enhanced expression of MCL-1 and BIM during 72-hour starvation of IL2 in cultured CCANKL cells. Single agent of venetoclax, BCL-xl inhibitor (A-1331852), and CDK9 inhibitor (A-1592668), at range of 1 - 1000 nM, had no detectable (BCL-2), mild (BCL-xL), and strong (CDK9) killing activities against CCANKL cells. We further confirmed expression of CD6, a surface glycoprotein expressed on most T-cells and a subset of NK cells, by IHC and flow cytometry in CCANKL and also tested a novel CD6-targeted ADC. Compared to naked anti-CD6 IgG and isotype control, CD6-ADC was capable of inducing apoptosis in CCANKL cells. Administration of either anti-CD6 IgG or CD6-ADC (4 mg/kg) on the same day as inoculation of CCANKL cells in NSG mice blocked engraftment of these malignant cells in NSG mice. The 2 nd ANKL case tested by IHC showed positive of CD6 in malignant cells. Conclusion: A novel aggressive NK cell leukemia cell line and a NSG mouse model were established. The in vitro data support further investigation of the expression features of BCL-2 family proteins in ANKL cases and in vivo evaluation for the efficiency of anti-apoptotic protein inhibitors in this aggressive disease. Further studies targeting CD6 in ANKL is warranted. Disclosures Lin: Takeda Pharma: Consultancy, Research Funding. Phillips: AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Hsi: AbbVie Inc, Eli Lilly: Research Funding.

Metal sulfides with multi-shelled hollow structures are promising electrode materials for rechargeable alkaline batteries due to their abundant redox centers and electrochemically active sites. We designed and synthesized a high-performance electrode material of sulfide-rich metal sulfides with nanostructured multi-shelled hollow spheres. Using multi-shelled NiO hollow spheres as precursors, three types of nickel sulfide (Ni3S2, NiS, NiS2) with controlled valence were obtained by controlling the sulfurization conditions. When applied as electrode materials for rechargeable alkaline batteries, multi-shelled nickel sulfide hollow spheres exhibit excellent electrochemical performance. Interestingly, the hollow spheres with more shells deliver better performance than those hollow spheres with fewer shells, owing to their greater number of faradaic active sites, shorter diffusion path and better electrochemical stability. The quadruple-shelled NiS2 hollow spheres show a high specific capacity (216 mA h g−1 at 5 A g−1) and outstanding cycling performance (89.96% retention after 5000 cycles).

To evaluate the application of virtual reality technology in a dental implant training system. A 3-dimensional model of mandible was established by Mimics17.0 software based on the Digital Imaging and Communications in Medicine data obtained from cone beam computed tomography scanning of the patient in mandibular. Thirty physicians were divided into 2 groups. The virtual reality dental implant training system was used for group A, while conventional theoretical knowledge training and clinical demonstration were performed in group B. All young physicians have a 1-month study. After training, all the physicians in groups A and B would conduct a questionnaire survey according to the training situation, which was compared between the 2 groups. The success rate of the operation was also evaluated and compared. The median scores in the 5 dimensions of postoperative assessment of group A was 9/9/9/8/8, and of group B was 6/7/6/7/7. The scores of the 5 dimensions were significantly higher than those of group B (P

The Macrocystis pyrifera biomass residues (MPBRs) after extraction of algin could be applied in anaerobic fermentation. The effects of different pretreatment conditions, substrate concentrations and initial pH values on hydrogen and volatile fatty acid (VFA) production during the anaerobic fermentation of MPBRs were evaluated. The optimal pretreatment conditions, substrate concentration, initial pH values were determined as thermo-alkaline pretreatment at 100 °C with 0.1 mol/L NaOH, 40 g/L and 7.0, respectively. Under these conditions, the maximum hydrogen production was 11.38 mL/g (volatile solids, VS), which was approximately 23 times higher than that of untreated MPBRs. Furthermore, the maximum total volatile fatty acid (TVFA) yield was found to be 0.055 g/g (VS) and the VFA mainly consisted of acetic and butyric acids. The results indicate that the yield of TVFA is positively correlated with hydrogen production, and the MPBRs could produce hydrogen and TVFA simultaneously. In addition, thermo-alkaline pretreatment is proven to be the best method for hydrogen and VFA production.

Multi-wall Sn/SnO

Objectives: Mutations in CALR (calreticulin) have been discovered in 50% to 80% of JAK2 (Janus kinase 2) and MPL (myeloproliferative leukemia protein) wild-type patients with Philadelphia-negative myeloproliferative neoplasm (MPNs). We evaluate the performance of a monoclonal antibody for immunohistochemical detection of CALR mutations. Methods: A computerized archival search was performed for cases of non–chronic myeloid leukemia (CML) MPNs with available CALR and JAK2 V617F mutational analysis data. Bone marrow biopsy specimens were stained with monoclonal antibody CAL2, and the percentage of stained megakaryocytes was calculated. In select cases, double immunofluorescence staining was done with CAL2 and each of the following: CD61, myeloperoxidase, CD34, and glycophorin A. Results: We studied 38 bone marrow biopsy specimens of non-CML MPNs (primary myelofibrosis, n = 21; essential thrombocythemia, n = 15; and n = 2 post–polycythemia vera myelofibrosis) from 31 patients. All eight bone marrow biopsy specimens from patients with mutant CALR showed strong cytoplasmic staining of the megakaryocytes (83.5%; range, 50%-98%; median, 87%) with the CAL2 antibody. Double immunofluorescence staining of the small mononuclear cells seen in CALR mutant cases revealed them to be myeloid blasts. Conclusions: Immunohistochemistry in routinely processed bone marrow biopsy specimens for mutated CALR is feasible and accurately identifies mutated cases, including rare cases with additional driver mutations.

// Juraj Bodo 1 , Xiaoxian Zhao 1 , Lisa Durkin 1 , Andrew J. Souers 2 , Darren C. Phillips 2 , Mitchell R. Smith 3 , Eric D. Hsi 1 1 Department of Laboratory Medicine, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA 2 Oncology Discovery, AbbVie, Inc., Chicago, IL, USA 3 Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Correspondence to: Eric D. Hsi, email: hsie@ccf.org Keywords: venetoclax, resistance, follicular lymphoma Received: April 15, 2016 Accepted: August 10, 2016 Published: September 20, 2016 ABSTRACT The chromosomal translocation t ( 14;18 ) in follicular lymphoma (FL) is a primary oncogenic event resulting in BCL-2 over-expression. This study investigates activity of the BH3 mimetic venetoclax (ABT-199), which targets BCL-2, and mechanisms of acquired resistance in FL. The sensitivity of FL cells to venetoclax treatment correlated with BCL-2/BIM ratio. Cells with similar expression of anti-apoptotic proteins, but with higher levels of BIM were more sensitive to the treatment. Venetoclax induced dissociation of BCL-2/ BIM complex and a decrease in mitochondrial potential. Interestingly the population of cells that survived venetoclax treatment showed increased p-ERK1/2 and p-BIM (S69), as well as a decrease in total BIM levels. Venetoclax resistant cells initially showed elevated levels of p-AKT and p-Foxo1/3a, a dissociation of BIM/BCL-2/BECLIN1 complex, and a decrease in SQSTM1/p62 level (indicating increased autophagy) together with a slight decline in BIM expression. After stable resistant cell lines were established, a significant reduction of BCL-2 levels and almost total absence of BIM was observed. The acquisition of these resistance phenotypes could be prevented via selective ERK/AKT inhibition or anti-CD20 antibody treatment, thus highlighting possible combination therapies for FL patients.

In this study, oxygen tolerance of five photohydrogen-producing green algal species, Chlamydomonas moewusii, Chlorella fusca, Chlorella pyrenoidosa, Chlamydomonas reinhardtii and Scenedesmus obliquus, were first evaluated comparatively. These green algae varied in O2-tolerance. C. pyrenoidosa exhibited notable O2-tolerance and was investigated comparatively to that of C. reinhardtii. We used an improved O2-tolerance detection method to eliminate the effects of O2 dissolving rate. Results showed that the O2I50 values of C. pyrenoidosa cells (in vivo) and cell lysate (in vitro) were 139% and 61% higher than those of C. reinhardtii, respectively. Furthermore, owing to the higher O2-tolerance, C. pyrenoidosa cells could evolve hydrogen at a higher threshold of O2 content in the photobiological hydrogen production process and kept releasing H2 for more than 260 h under continuous illumination compared to 60 h in C. reinhardtii did under the same conditions.

The current standard of care for acute myeloid leukemia (AML) is largely ineffective with very high relapse rates and low survival rates, mostly due to the inability to eliminate a rare population of leukemic stem cells (LSCs) that initiate tumor growth and are resistant to standard chemotherapy. RNA-sequencing analysis on isolated LSCs confirmed C-type lectin domain family 12 member A (CLL1, also known as CLEC12A) to be highly expressed on LSCs but not on normal hematopoietic stem cells (HSCs) or other healthy organ tissues. Expression of CLL1 was consistent across different types of AML. We developed CLT030 (CLL1-ADC), an antibody-drug conjugate (ADC) based on a humanized anti-CLL1 antibody with 2 engineered cysteine residues linked covalently via a cleavable linker to a highly potent DNA-binding payload, thus resulting in a site-specific and homogenous ADC product. The ADC is designed to be stable in the bloodstream and to release its DNA-binding payload only after the ADC binds to CLL1-expressing tumor cells, is internalized, and the linker is cleaved in the lysosomal compartment. CLL1-ADC inhibits in vitro LSC colony formation and demonstrates robust in vivo efficacy in AML cell tumor models and tumor growth inhibition in the AML patient-derived xenograft model. CLL1-ADC demonstrated a reduced effect on differentiation of healthy normal human CD34+ cells to various lineages as observed in an in vitro colony formation assay and in an in vivo xenotransplantation model as compared with CD33-ADC. These results demonstrate that CLL1-ADC could be an effective ADC therapeutic for the treatment of AML.