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Marginal zone lymphoma (MZL) is an uncommon subtype of non-Hodgkin lymphoma (NHL). Combination of rituximab and cladribine (R-2CdA) is a potential option for indolent NHL (iNHL) and mantle cell lymphoma (MCL) patients. The goal of this multicenter retrospective study was to assess the efficacy and safety of R-2CdA in MZL to support consensus-reaching in first-line therapy in advanced-stage patients. We searched electronic medical records databases of eight centers in China. Between November 2014 and December 2019, 183 symptomatic advanced MZL patients (42 treated with R-2CdA and 141 with rituximab plus cyclophosphamide, adriamycin, vincristine, and prednisone [R-CHOP]) were identified. After propensity score matching (PSM) (1:1) to adjust for clinical characteristics, 39 patients from each treatment arm were selected. The overall response rate (ORR) (84.6% vs. 94.9%, P = 0.263) and complete response rate (59.0% vs. 66.7%, P = 0.487) were comparable between two protocols. Neither progression-free survival (PFS), including the 5-year PFS (67.7% vs. 56.1%, P = 0.352), nor overall survival was improved by R-2CdA versus R-CHOP. However, R-2CdA was more tolerable than R-CHOP in MZL patients regarding grade 3/4 hematological adverse events (odds ratio [OR] 0.565, 95% confidence interval [CI] neutropenic fever (OR 0.795, 95% CI 0.678-0.932), and infections (OR 0.800, 95% CI 0.640-1.000). Overall, our study demonstrated that R-2CdA is potentially as effective as but safer than R-CHOP in advanced MZL.

Low-cost UAV aerial photogrammetry and airborne lidar scanning have been widely used in forest biomass survey and mapping. However, the feature dimension after multisource remote sensing fusion is too high and screening key features to achieve feature dimension reduction is of great significance for improving the accuracy and efficiency of biomass estimation. In this study, UAV image and point cloud data were combined to estimate and map the biomass of subtropical forests. Firstly, a total of 173 dimensions of visible light vegetation index, texture, point cloud height, intensity, density, canopy, and topographic features were extracted as variables. Secondly, the Kendall Rank correlation coefficient and permutation importance (PI) index were used to identify the key features of biomass estimation among different tree species. The random forest (RF) model and XGBoost model finally were used to compare the accuracy of biomass estimation with different variable sets. The experimental results showed that the point cloud height, canopy features, and topographic factors were identified as the key parameters of the biomass estimate, which had a significant influence on the biomass estimation of the three dominant tree species in the study area. In addition, the differences in the importance of characteristics among the tree species were discussed. The fusion features combined with the PI index screening and RF model achieved the best estimation accuracy, the R2 of 0.7356, 0.8578, and 0.6823 were obtained for the three tree species, respectively.

Introduction: Chemoresistance is one of the major challenges for the acute myeloid leukemia (AML) treatment. Venetoclax (ABT-199), a selective small molecule BCL-2 inhibitor, is being clinically vetted and is an effective therapy for some B-cell lymphomas, yet many patients who initially respond to ABT-199 develop resistance. Thus, enhancing the sensitivity of resistant cells to chemotherapy is a great interest to clinical trial. Method: The resistant cell lines were generated by culturing in the medium containing ABT-199. CCK8 analysis was used to detect the cell viability. Flowcytometric analysis with Annexin-V/PI was used to test the apoptosis. CRISPR/Cas9 by lentivirus delivering well-validated shRNAs in pLKO.1 vector was used to knockout the expression of MTF1. Western blot with the antibodies was used to determine the expression of the molecules. Clonogenic growth assay was used to determine the growth of parental and DTEP cells. Results: Here we report that resistance to the BCL-2 targeting drug ABT-199 in AML cell lines evolves from outgrowth of persister clones harbor BCL2. Furthermore, persister status is generated via adaptive super-enhancer remodeling that reprograms transcription and offers opportunities for overcoming ABT-199 resistance. Notably, pharmacogenomic screens revealed that persisters are vulnerable to inhibition of metal regulatory transcription factor 1 (MTF1), which is essential for the transcriptional reprogramming that drives and sustains ABT-199 resistance. Conclusion: LOR-253, which is a MTF1-targeting agent, add novel insights to overcome ABT-199-resistance in B-cell lymphomas.

The formation of electroactive biofilm from activated sludge on electrode surface is a key step to construct a bio-electrochemical system, yet it is greatly limited by the poor affinity between the bacteria and the electrode interface. Herein, we report a new method to promote the formation of electroactive biofilm by regulating the extracellular polymeric substance (EPS) content in activated sludge with lysozyme. The investigation of the effect of lysozyme treatment on the content of extracellular polymers and the biofilm formation of electroactive bacteria suggests that lysozyme can improve the permeability of the positive bacterial cell membrane and thus increase the EPS content in the activated sludge. The characterizations of electrochemical activity, surface morphology and community structure of the anode biofilm indicate that increasing EPS content promotes the adhesion of the mixed bacteria in the activated sludge on the electrode and results in denser biofilms with better conductivities. The microbial fuel cell (MFC) inoculated with the sludge of high EPS content exhibits the power density up to 2.195 W/m

Background: This study was conducted to investigate the short-term efficacy and safety of rhTPO for the management of severe ITP in the elderly as first-line treatment. Methods: A total of 54 elderly patients with severe ITP were studied, including 39 patients treated with a combination regimen of rhTPO plus standard treatment (glucocorticoid; rhTPO group) and 15 patients treated with glucocorticoid treatment alone (control group). The response rate, time to initial response, peak platelet counts, and time to peak platelet counts were compared, and clinical characteristics correlated with the efficacy of rhTPO were analyzed. The efficacy of rhTPO in the elderly is comparable to the non-elderly in terms of the OR, CR, time to initial response, and peak platelet counts. Results: There were no differences in the overall response (OR) and the complete response (CR) in the rhTPO group compared to the control group. The time to initial response in the rhTPO group was shorter than that in the control group (p = 0.032). In patients without intravenous immunoglobulin (IVIg) and platelet transfusion, the peak platelet counts in the rhTPO group were higher than those in the control group (p = 0.003). Conclusions: Standard glucocorticoid treatment plus rhTPO effectively shortens the time to response and increases platelet counts in the elderly with severe ITP.

Exploration of feruloyl esterase (FAE) with the resistance to heat and alkali conditions in biobleaching process to improve the separation efficiency of lignocellulose is the key to achieving green papermaking. Herein, we expressed FAEB of C. thermophilum and obtained a thermostable alkaline FAE that can effectively promote the removal of lignin from pulp. The faeB gene was successfully obtained through genomic Blast strategy and high-efficiency expressed under the control of strong alcohol oxidase promoter in Pichia pastoris. The recombinant CtFAEB has an optimal temperature of 65 °C and pH of 7.0. After treated at 65 °C for 1 h, CtFAEB can still retain 63.21 % of its maximum activity, showing a good thermal stability. In addition, the recombinant CtFAEB has broad pH stability and can retain about 56 % of the maximum activity even at pH 11.0. Compared with the effect of mesophilic FAE, pretreatment with thermostable CtFAEB can promote the delignification by laccase and alkaline hydrogen peroxide from the pulp at 70 °C and pH 9.0. Alignment of the protein sequences of CtFAEB and mesophilic FAE suggested that the percentage of amino acids that easily form alpha helix in CtFAEB increases, which enhances its structural rigidity and thereby improves its thermal stability and alkali tolerance. Our study provides an effective method to obtain thermostable and alkaline FAEs, which will promote its application in biobleaching and other biorefining industries.

Objective Lymphoma, a malignant tumor, is mainly characterized by painless lymph node enlargement and hepatosplenomegaly. At present, lymphoma is mainly treated by radiation, chemical drugs, bone marrow transplantation and surgery. However, due to the high degree of heterogeneity, lymphomas are highly different in terms of treatment intensity and prognosis. This study is designed to investigate the function of tripartite motif-containing 11 (TRIM11) in lymphomas. Methods The expression of TRIM11 in lymphoma tissues and multiple lymphoma cell lines was respectively detected by microarray immunohistochemistry, real-time PCR and Western blotting. After TRIM11 knockdown, overexpression, or β-catenin inhibitor XAV939 treatment, proliferation, apoptosis and cell cycle progression, as well as expression of related-genes were detected. Next, Co-Immunoprecipitation (Co-IP) and ubiquitination detection were performed. Results Elevated expression of tripartite motif-containing 11 (TRIM11) was observed in lymphoma tissues and multiple lymphoma cell lines (Raji, Jurkat, U937 and Hut78). Knockdown of TRIM11 in lymphoma cells significantly suppressed cell proliferation and prevented cell cycle progression from entering S or G2 phase. Concurrently, the expression of β-catenin, Cyclin D1 and c-Myc proteins in TRIM11-silenced lymphoma cells was decreased, while Axin1 was increased. In addition, TRIM11 overexpression had an opposite effect to TRIM11 knockdown, and a β-catenin inhibitor, XAV939, potently attenuated the induction of TRIM11 on lymphoma cells. Co-IP assay showed the interaction of TRIM11 and Axin1, and TRIM11 knockdown inhibited Axin1 ubiquitination degradation. Conclusions Together all, the results suggested that TRIM11 may be an oncogene in lymphomas, which involving the activation of the β-catenin signaling and the ubiquitination degradation of Axin1.

Feruloyl esterases (FAEs) have great potential applications in paper and breeding industry. A new thermo-stable feruloyl esterase gene, TtfaeB was identified from the thermophilic fungus Thielavia terrestris h408. Deduced protein sequence shares the identity of 67% with FAEB from Neurospora crassa. The expression vector pPIC9K-TtfaeB was successfully constructed and electro-transformed into GS115 strain of Pichia pastoris. One transformant with high feruloyl esterase yield was obtained through plate screening and named TtFAEB1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of fermentation supernatant from transformant TtFAEB1 showed a distinct protein band appearing at the position of about 35-kDa, indicating that TtfaeB gene has been successfully expressed in P. pastoris. The recombinant TtFAEB was purified by affinity chromatography and the specific activity of purified TtFAEB was 6.06 ± 0.72 U/mg. The optimal temperature and pH for purified recombinant TtFAEB was 60 °C and 7.0, respectively. TtFAEB was thermostable, retaining 96.89 and 84.16% of the maximum activity after being treated for 1 h at 50 °C and 60 °C, respectively. Additionally, the enzyme was stable in the pH range 4.5–8.0. The homology model of TtFAEB showed that it consists of a single domain adopting a typical α/β-hydrolase fold and contains a catalytic triad formed by Ser117, Asp201, and His260. TtFAEB in association with xylanase from Trichoderma reesei could release 77.1% of FA from destarched wheat bran. The present results indicated that the recombinant TtFAEB with excellent enzymatic properties is a promising candidate for potential applications in biomass deconstruction and biorefinery.

Knockout of the N-hydroxybenzoate hydroxylase functional gene orf54 in the Streptomyces sp. 13580 gene cluster and its fermentation HPLC detection of its mutant strain. We identified the biosynthetic gene cluster from the strain Streptomyces sp. 13580 by genome sequencing, and finding genes for hydroxylase function through bioinformatics analysis. The cosmid Δorf54 deleting the N-hydroxybenzoate hydroxylase functional gene orf54 was constructed in Escherichia coli by PCR-targeting. Transfer of the mutant cosmid into Streptomyces sp. 13580. The orf54 gene sequence was knocked out by homologous recombination, and the double-crossover insertion-inactivated mutant 13580 Δorf54 was screened. The wild type strain Streptomyces sp. 13580 and its mutant 13580 Δorf54 were subjected to shake flask fermentation and then analyzed by high performance liquid chromatography (HPLC).

s Magnetic composite nanospheres carrying amino groups have attracted much interest due to their potential applications in the fields of catalysis, sensor, water purification, enzyme immobilization, DNA extraction, and drug delivery. In this paper, dedoped Fe 3 O 4 /polypyrrole (PPy) nanospheres with core–shell structure, high magnetization, superparamagnetism, and size meeting the demand of biorelated applications in vivo have been achieved by an in situ polymerization approach. The amount of the surface amino groups of Fe 3 O 4 /PPy is greatly enhanced by dedoping treatment due to liberation of the amino groups ever sheltered by the dopants, a situation that is responsible for facile conjugation of fluorescein and methotrexate (MTX) onto the magnetic composite through the EDC/NHS coupling chemistry to produce the desirable fluorescent Fe 3 O 4 /PPy/MTX targeting drug with a high MTX loading of ca. 109 μg mg −1 . The as-obtained magnetic targeting drug exhibits controlled drug release, enhanced intracellular drug retention, and specific targeting ability to HeLa cells, presenting a promising candidate for treatment of cancer cells overexpressing folate receptors.

Silica-coated magnetic microspheres present a promising candidate for applications in bioseparation, drug delivery, and catalysis. In this paper, we report on the synthesis of core–shell structured Fe 3 O 4 /SiO 2 microspheres via a modified Stober process. The magnetic composite microspheres exhibit superparamagnetism, high saturation magnetization, and good dispersion. The samples were characterized with XRD, FTIR, TEM, and VSM techniques, and further tested as adsorbents for purification of genomic DNA from Aspergillus niger NA1003 cells. The purified genomic DNA was analyzed by agarose gel electrophoresis and examined by polymerase chain reaction (PCR) amplification. The magnetic isolation protocol presents genomic DNA with PCR-ready quality and shows superior to the conventional phenol–chloroform extraction.

Magnetic separation with composite microspheres presents an alternative strategy for applications in biomedical and bioengineering fields. However, the synthesis of core-shell structured magnetic composites universally assumes the surfactant-directing and/or silica-assisting polymerization approach to modify and stabilize the magnetic cores. In this paper, we report on the surfactant-free synthesis of well-defined core-shell structured Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres with high magnetization. The temperature dependence of magnetization of the samples was examined as a function of temperature between 3 and 300 K in an applied field of 500 Oe. It was found that the blocking temperature (T(B)) values of the composite spheres are well above the room temperature. The small variation in magnetization as the temperature changes renders the composite spheres a suitable candidate when used at elevated temperatures. Also, the genomic DNA can be effectively isolated from Aspergillus niger (A. niger) cells with the composite microspheres, using a PEG-NaCl binding buffer and a phosphate eluting buffer. The magnetic isolation of genomic DNA with the composite microspheres was shown to be superior to the conventional phenol-chloroform extraction, which was confirmed by agarose gel eletrophoresis and polymerase chain reaction (PCR) diagnosis. The Fe(3)O(4)@PANI and Fe(3)O(4)@PPy microspheres presented here have great potential in enzyme immobilization, drug delivery, catalysis, and sensors.

As a well-known industrial fungus for cellulase production, the strain RUT-C30 of Trichoderma reesei was selected to produce the feruloyl esterase A (FAEA) by a random integration protocol. The strong promoter of cellobiohydrolase 1 (cbh1) gene was used to drive the expression of FAEA. Using double-joint PCR protocol, Pcbh1-faeA-TtrpC expression cassette was successfully constructed and co-transformed into RUT C30 strain of T. reesei. One transformant with high feruloyl esterase yield (3.44 ± 0.16 IU/mL) was obtained through plate screening and named TrfaeA1. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of fermentation supernatant from transformant TrfaeA1 showed a distinct protein band appearing at the position of about 34 kDa, indicating that faeA gene has been successfully expressed in T. reesei. Compared with that in original RUT C30 strain, β-glucosidase production in transformant TrfaeA1 was significantly increased by about 86.4%, reaching 63.2 IU/mL due to the random insertion of faeA. Moreover, the total secretion protein and filter paper activities of the transformant TrfaeA1 were also improved by up to 5.5 and 4.3%, respectively. The present results indicated that the random insertion strategy could be an effective and feasible method to improve and optimize the cellulase system of filamentous fungi.

Magnetic composite microspheres present a promising candidate for applications in bioseparation, drug delivery, and biocatalysis. We report here the synthesis of carboxyl-functionalized and core–shell structured Fe3O4/PS-PAA microspheres via a dispersion interfacial polymerization method, using styrene (St) and acrylic acid (AA) as monomers. The magnetic composite microspheres exhibit good dispersity, superparamagnetism, and high saturation magnetization. The samples were characterized with XRD, XPS, FTIR, FESEM, TEM, and VSM techniques, and further tested as adsorbents for purification of genomic DNA from Aspergillus niger NA1003 cells. Complexation mechanism of DNA with the adsorbent is discussed. The magnetic separation yields high-quality genomic DNA and satisfying productivity comparable to those isolated by the conventional phenol–chloroform extraction.

We have determined the trace element composition of three mushrooms of Basidiomycetes, used in traditional Chinese medicine using atomic absorption spectrophotometer (AAS). Metal concentrations in mushrooms were 203-401 mg/kg for iron, 22-51 mg/kg for manganese, 84-116 mg/kg for zinc, 24.1-41.3 mg/kg for copper, 1.6-5.6 mg/kg for lead, 3.3-4.4 mg/kg for chromium, 9.3-11.5 mg/kg for nickel, 0 mg/kg for vanadium, and 55.3-71 mg/kg for magnesium. The trace metal concentrations in mushrooms are hardly affected by the ecosystem and soil where they grew, as well as by the mushroom species and trace metal species. The results can be used to set new standards to control the quality of the three mushrooms of Basidiomycetes-Ganoderma lucidum, Coprinus comatus, and Grifola frondosa.

Objective Decidual macrophages (dMΦs) have been implicated in fetal tolerance, but little information is known regarding their differentiation capacity and interactions with T cells. The present study aimed to investigate the immunological characteristics of dMΦs at mid and term pregnancy. Methods The dMΦs were analyzed for their phenotypes and cytokine production by flow cytometry and ELISA, respectively. The transendothelial trafficking model was implemented to allow the dMΦs to differentiate. The differentiated cells from dMΦs were also measured for their phenotypes and cytokine production with same methods. The capacity of dMΦs or the differentiated cells from dMΦs to stimulate allogeneic T lymphocyte proliferation was evaluated by T lymphocyte stimulation assays. T cell differentiation was determined by flow cytometry. Results The dMΦs in the mid-pregnancy (Mid-dMΦs) resembled the M2 phenotype. The differentiated cells from Mid-dMΦs had little stimulatory capacity on T cell proliferation and favored regulatory T cell differentiation. The dMΦs at term differentiated into dendritic (DC)-like cells, stimulating T cell activation, proliferation, and differentiation into IFN-γ-producing T cellsdecidual Conclusions The present study suggests that the differences in phenotypes and cytokine production between Mid- and Term-dMΦs relate to their different roles in the homeostasis of the maternal–fetal interface. Mid-dMΦs differentiate into DC-like cells with immunosuppressive properties, playing an important role in maintaining homeostasis required for a successful pregnancy. Term-dMΦs differentiate into DC-like cells with immunostimulatory properties, likely involved in the activation of labor. The different differentiation capacities of dMΦs in the varied pregnancy stages may be due to the placental microenvironment.

To achieve the high-efficiency expression of feruloyl estrase gene (AnfaeA) from Aspergillus niger h408 in Pichia pastoris and characterize the recombinant feruloyl esterase (FAE).Using gene splicing by overlap extension (SOE), we cloned AnfaeA gene from A. niger h408 and subcloned into T vector for sequencing analysis. The expression vector pPIC9K-Anfae was constructed by the ligation of the Anfae A gene into the shuttle vector pPIC9K. The plasmid pPIC9K-Anfae was linearized and then electrotransformed into P. pastoris GS115. The recombinant strain with high level of FAE activity was obtained through plate screening. Effects of pH and temperature on recombinant FAE were determined by ultraviolet (UV) methods.We have successfully cloned and high-efficiently expressed the AnfaeA gene (GenBank: KF911349) from A. niger h408 in P. pastoris GS115. The sequencing result showed that the length of Anfae A was 783bp. The gene contained an Open Reading Frame encoding 260 amino acids and was similar to feruloyl esterase A from A. niger by homology analysis. The deduced amino acids contained a typical active lid and catalytic triad of lipase. The SDS-PAGE result indicated that molecular weight of the recombinant FAE was about 30 kDa and the activity of the recombinant enzyme was 24.72 U/mL. The specific activity of the recombinant FAE was 40.84 U/mg. Compared with A. niger h408, the recombinant enzyme activity increased about to 1100 times. The optimal temperature and pH for recombinant FAE was 50 degrees C and 5.0, respectively. Recombinant FAE showed nearly 80% of its maximal activity at 60 degrees C and was active in the pH range 4.0-9.0.The high-efficient expression of AnfaeA gene in P. pastoris provided a prerequisite for achieving industrial application in feed and paper-making industry. In addition, the results established the experimental basis for further improvement of recombinant feruloyl esterase by directed evolution.

We have determined the trace element composition of anti-influenza virus mushrooms using atomic absorption spectrophotometer. The elements present in greater concentration in Ganoderma lucidum samples are selenium, iron, and zinc, with selenium being the element with the highest concentration of all, at 416 ± 38.5 mg/kg; in Cordyceps militaris samples are iron, selenium, and zinc, with iron being the element with the highest concentration of all, at 291 ± 20.9 mg/kg; in Kuehneromyces mutabilis samples are selenium, iron, and manganese, with selenium being the element with the highest concentration of all, at 203 ± 9.8 mg/kg; in Inonotus hispidus samples are zinc, selenium, and iron, with zinc being the element with the highest concentration of all, at 194 ± 16.9mg/kg; in the Collybia maculata samples are iron, selenium, and zinc, with iron being the element with the highest concentration of all, at 274 ± 22.2 mg/kg, respectively. The average metal concentrations in mushrooms decreases in the order: selenium > iron > zinc > chromium > manganese > copper > magnesium > lead. After the mice were administered (orally) with mushroom extracts for 8 weeks and inoculated intranasally with viral suspension, element levels in serum were also measured. Highly significantly increased values of Se, Zn, and Mg in the serum of mice supplemented with anti-influenza virus mushrooms were a characteristic finding. Se, Zn, and Mg present in mushrooms may play a direct or indirect role in their anti-influenza virus nature. They may provide prophylactic protection against influenza infection via stimulation of host innate immune response.

A cellobiohydrolase 1 gene (cbh1) was cloned from Penicillium chrysogenum FS010 by a modified thermal asymmetric interlaced polymerase chain reaction (TAIL-PCR). DNA sequencing shows that cbh1 has an open reading frame of 1590 bp, encoding a putative protein of 529 amino acid residues. The deduced amino acid sequence revealed that CBHI has a modular structure with a predicted molecular mass of 56 kDa and consists of a fungal type carbohydrate binding module separated from a catalytic domain by a threonine rich linker region. The putative gene product is homologous to fungal cellobiohydrolases in Family 7 of the glycosyl hydrolases. A novel cbh1 promoter (1.3 kb) was also cloned and sequenced, which contains seven putative binding sites (5'-SYGGRG-3') for the carbon catabolite repressor CRE1. Effect of various carbon sources to the cbh1 transcription of P. chrysogenum was examined by Northern analysis, suggesting that the expression of cbh1 is regulated at transcriptional level. The cbh1 gene in cold-adaptive fungus P. chysogenum was expressed as an active enzyme in Saccharomyces cerevisiae H158. The recombinant CBHI accumulated intracellularly and could not be secreted into the medium.

Nearly monodisperse core–shell Fe3O4/SiO2 microspheres have been prepared via a glycol reduction method followed by a modified Stöber process. The thickness of the silica shells can be tuned in the range 33–53 nm by varying the amount of tetraethyl silicate (TEOS) during syntheses. The magnetic composite microspheres were characterized with XRD, XPS, FTIR, TEM, ICP–OES and VSM, and further tested as adsorbents for purification of plasmid DNA from Escherichia coli DH5α cells. The magnetic purification of plasmid DNA leads to satisfying integrity, yield and purity in comparison with those isolated by the traditional phenol–chloroform extraction.