► Removal of low-concentration formaldehyde (HCHO) in air by DC corona discharge plasma and plasma-catalysis was investigated. ► The positive DC corona discharge is much more effective in removing ...HCHO than the negative one. ► The discharge electrode configuration has limited effects on the HCHO conversion for a given discharge energy density. ► Increasing humidity has positive effects while coexisting toluene in the gas stream has adverse effects on the HCHO removal. ► The presence of downstream MnO
x
/Al
2O
3 catalyst significantly enhances the conversion of HCHO and reduces the emission of O
3.
The effects of discharge polarity, discharge electrode configuration, gas composition and downstream catalyst on the removal of low-concentration HCHO in air were systematically investigated in a link tooth wheel-cylinder plasma reactor energized by a DC power. Experimental results show that the positive DC corona discharge is much more effective in removing HCHO as compared to the negative one. The discharge electrode configuration significantly influences the energy input to the plasma reactor. For a given specific energy density (SED), longer reaction zone favors the HCHO conversion; however, the HCHO conversion is almost constant in spite of the different discharge electrode configurations within a fixed reaction zone. The conversion of HCHO increases with the increase of gas humidity, and decreases with increasing coexisting toluene in the gas stream. On the other hand, introduction of MnO
x
/Al
2O
3 catalyst downstream the plasma reactor significantly enhances the HCHO conversion and reduces the O
3 emission.
•Build a large-scale 3D shape retrieval benchmark that supports multi-modal queries.•Evaluate the 26 3D shape retrieval methods using 3 types of metrics.•Solicit and identify state-of-the-art methods ...and promising related techniques.•Perform detailed analysis on diverse methods w.r.t accuracy and efficiency.•Make benchmark and evaluation tools freely available to the community.
Large-scale 3D shape retrieval has become an important research direction in content-based 3D shape retrieval. To promote this research area, two Shape Retrieval Contest (SHREC) tracks on large scale comprehensive and sketch-based 3D model retrieval have been organized by us in 2014. Both tracks were based on a unified large-scale benchmark that supports multimodal queries (3D models and sketches). This benchmark contains 13680 sketches and 8987 3D models, divided into 171 distinct classes. It was compiled to be a superset of existing benchmarks and presents a new challenge to retrieval methods as it comprises generic models as well as domain-specific model types. Twelve and six distinct 3D shape retrieval methods have competed with each other in these two contests, respectively. To measure and compare the performance of the participating and other promising Query-by-Model or Query-by-Sketch 3D shape retrieval methods and to solicit state-of-the-art approaches, we perform a more comprehensive comparison of twenty-six (eighteen originally participating algorithms and eight additional state-of-the-art or new) retrieval methods by evaluating them on the common benchmark. The benchmark, results, and evaluation tools are publicly available at our websites (http://www.itl.nist.gov/iad/vug/sharp/contest/2014/Generic3D/, 2014, http://www.itl.nist.gov/iad/vug/sharp/contest/2014/SBR/, 2014).
Effects of relative humidity (30%, 50% and 80% RH) on the removal of low-concentration benzene, toluene and
p-xylene (BTX mixture) in air by non-thermal plasma (NTP) and the combination of NTP and ...MnO
x
/Al
2O
3 catalyst (CPC) were systematically investigated in a link tooth wheel-cylinder plasma reactor. A long-term (150
h) CPC experiment under 30% RH was also conducted to investigate the stability of the catalyst. Results show that increasing humidity inhibits the O
3 production in plasma and its decomposition over the catalyst. As for BTX conversion, increasing humidity suppresses the benzene conversion by both NTP and CPC; although higher humidity slightly promotes the toluene conversion by NTP, it negatively influences that by CPC; while the conversion of
p-xylene by both NTP and CPC is insensitive to the humidity levels. Irrespective of the RH, the introduction of MnO
x
/Al
2O
3 catalyst significantly promotes BTX conversion and improves the energy efficiency. On the other hand, CPC under 30% RH shows the best performance towards CO
x
formation during BTX oxidation processes. However, for a specific input energy of 10
J
L
−1 in this study, organic intermediates generated and accumulated over the catalyst surface, resulting in a slight deactivation of the MnO
x
/Al
2O
3 catalyst after 150-h reactions.
Modulating macrophages presents a promising avenue in tumor immunotherapy. However, tumor cells have evolved mechanisms to evade macrophage activation and phagocytosis. Herein, we introduced a ...bispecific antibody-based nanoengager to facilitate the recognition and phagocytosis of tumor cells by macrophages. Specifically, we genetically engineered two single chain variable fragments (scFv) onto cell membrane: anti-CD40 scFv for engaging with macrophages and anti-Claudin18.2 (CLDN18.2) scFv for interacting with tumor cells. These nanoengagers were further constructed by coating scFv-anchored membrane into PLGA nanoparticle core. Our developed nanoengagers significantly boosted immune responses, including increased recognition and phagocytosis of tumor cells by macrophages, enhanced activation and antigen presentation, and elevated cytotoxic T lymphocyte activity. These combined benefits resulted in enhancing antitumor efficacy against highly aggressive "cold" pancreatic cancer. Overall, this study offers a versatile nanoengager design for immunotherapy, achieved through genetically engineering to incorporate antibody-anchored membrane.
BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers worldwide. Despite the promising outcome of immune checkpoint inhibitors and agonist antibody therapies in ...different malignancies, PDAC exhibits high resistance due to its immunosuppressive tumor microenvironment (TME). Ameliorating the TME is thus a rational strategy for PDAC therapy. The intratumoral application of oncolytic herpes simplex virus-1 (oHSV) upregulates pro-inflammatory macrophages and lymphocytes in TME, and enhances the responsiveness of PDAC to immunotherapy. However, the antitumor activity of oHSV remains to be maximized. The aim of this study is to investigate the effect of the CD40L armed oHSV on the tumor immune microenvironment, and ultimately prolong the survival of the PDAC mouse model.MethodsThe membrane-bound form of murine CD40L was engineered into oHSV by CRISPR/Cas9-based gene editing. oHSV-CD40L induced cytopathic effect and immunogenic cell death were determined by microscopy and flow cytometry. The expression and function of oHSV-CD40L was assessed by reporter cell assay. The oHSV-CD40L was administrated intratumorally to the immune competent syngeneic PDAC mouse model, and the leukocytes in TME and tumor-draining lymph node were analyzed by multicolor flow cytometry. Intratumoral cytokines were determined by ELISA.ResultsIntratumoral application of oHSV-CD40L efficiently restrained the tumor growth and prolonged the survival of the PDAC mouse model. In TME, oHSV-CD40L-treated tumor accommodated more maturated dendritic cells (DCs), which in turn activated T helper 1 and cytotoxic CD8+ T cells in an interferon-γ-dependent and interleukin-12-dependent manner. In contrast, the regulatory T cells were significantly reduced in TME by oHSV-CD40L treatment. Repeated dosing and combinational therapy extended the lifespan of PDAC mice.ConclusionCD40L-armed oncolytic therapy endues TME with increased DCs maturation and DC-dependent activation of cytotoxic T cells, and significantly prolongs the survival of the model mice. This study may lead to the understanding and development of oHSV-CD40L as a therapy for PDAC in synergy with immune checkpoint blockade.
This study aimed to explore the prognostic and predictive value of autophagy-related lncRNAs in papillary thyroid carcinoma (PTC). The expression data of autophagy-related genes and lncRNAs of the ...PTC patients were obtained from TCGA database. Autophagy-related-differentially expressed lncRNAs (DElncs) were identified and used to establish the lncRNAs signature predicting patients’ progression-free interval (PFI) in the training cohort. Its performance was assessed in the training cohort, validation cohort, and entire cohort. Effects of the signature on I-131 therapy were also explored. We identified 199 autophagy-related-DElncs and constructed a novel six-lncRNAs signature was constructed based on these lncRNAs. This signature had a good predictive performance and was superior to TNM stages and previous clinical risk scores. I-131 therapy was found to be associated with favorable prognosis in patients with high-risk scores but not those with low-risk scores. Gene set enrichment analysis suggested that a series of hallmark gene sets were enriched in the high-risk subgroup. Single-cell RNA sequencing analysis suggested that the lncRNAs were mainly expressed in thyroid cells but not stromal cells. In conclusion, our study constructed a well-performed six-lncRNAs signature to predict PFI and I-131 therapy benefits in PTC.
Depletion of oocytes leads to ovarian aging-associated infertility, endocrine disruption and related diseases. Excitingly, unlimited oocytes can be generated by differentiation of primordial germ ...cell like cells (PGCLCs) from pluripotent stem cells. Nevertheless, development of oocytes and follicles from PGCLCs relies on developmentally matched gonadal somatic cells, only available from E12.5 embryos in mice. It is therefore imperative to achieve an in vitro source of E12.5 gonadal somatic cells.
We explored to identify small molecules, which can induce female embryonic stem cells (ESCs) into gonadal somatic cell like cells.
Using RNA-sequencing, we identified signaling pathways highly upregulated in E12.5_gonadal somatic cells (E12.5_GSCs). Through searching for the activators of these pathways, we identified small-molecule compounds Vitamin C (Vc) and AM580 in combination (V580) for inducing differentiation of female embryonic stem cells (ESCs) into E12.5_GSC-like cells (E12.5_GSCLCs). After V580 treatment for 6 days and sorted by a surface marker CD63, the cell population yielded a transcriptome profile similar to that of E12.5_GSCs, which promoted meiosis progression and folliculogenesis of primordial germ cells. This approach will contribute to the study of germ cell and follicle development and oocyte production and have implications in potentially treating female infertility.
ESCs can be induced into embryonic gonadal somatic cell like cells by small molecules.
•CRISPR/Cas9 system can improve the efficiency of HSV-1 genome editing.•CRISPR/Cas9 system successfully mediates the modification of therapeutic gene armed oncolytic herpes simplex virus ...(O-HSV1211).•IL12 and CXCL11 armed O-HSV1211 can significantly enhance the therapeutic outcome in Colorectal cancer.•The antitumor effect of IL12 and CXCL11 in O-HSV1211 is dependent on IFN-γ.
Oncolytic viruses are an emerging cancer treatment modality with promising results in clinical trials. The new generation of oncolytic viruses are genetically modified to enhance virus selectivity for tumor cells and allow local expression of therapeutic genes in tumors. The traditional technique for viral genome engineering based on homologous recombination using a bacterial artificial chromosome (BAC) system is laborious and time-consuming. With the advent of the CRISPR/Cas9 system, the efficiency of gene editing in human cells and other organisms has dramatically increased. In this report, we successfully applied the CRISPR/Cas9 technique to construct an HSV-based oncolytic virus, where the ICP34.5 coding region was replaced with the therapeutic genes murine interleukin 12 (IL12, p40-p35) and C-X-C motif chemokine ligand 11 (CXCL11), and ICP47 gene was deleted. The combination of IL12 and CXCL11 in oncolytic viruses showed considerable promise in colorectal cancer (CRC) treatment. Overall, our study describes genetic modification of the HSV-1 genome using the CRISPR/Cas9 system and provides evidence from principle studies for engineering of the HSV genome to express foreign genes.
Despite the promise in whole‐tumor cell vaccines, a key challenge is to overcome the lack of costimulatory signals. Here, agonistic‐antibody‐boosted tumor cell nanovaccines are reported by ...genetically engineered antibody‐anchored membrane (AAM) technology, capable of effectively activating costimulatory pathways. Specifically, the AAM can be stably constructed following genetic engineering of tumor cell membranes with anti‐CD40 single chain variable fragment (scFv), an agonistic antibody to induce costimulatory signals. The nanovaccines are versatilely designed and obtained based on the anti‐CD40 scFv‐anchored membrane and nanotechnology. Following vaccination, the anti‐CD40 scFv‐anchored membrane nanovaccine (Nano‐AAM/CD40) significantly facilitates dendritic cell maturation in CD40‐humanized transgenic mice and subsequent adaptive immune responses. Compared to membrane‐based nanovaccines alone, the enhanced antitumor efficacy in both “hot” and “cold” tumor models of the Nano‐AAM/CD40 demonstrates the importance of agonistic antibodies in development of tumor‐cell‐based vaccines. To expand the design of nanovaccines, further incorporation of cell lysates into the Nano‐AAM/CD40 to conceptually construct tumor cell‐like nanovaccines results in boosted immune responses and improved antitumor efficacy against malignant tumors inoculated into CD40‐humanized transgenic mice. Overall, this genetically engineered AAM technology provides a versatile design of nanovaccines by incorporation of tumor‐cell‐based components and agonistic antibodies of costimulatory immune checkpoints.
Biomimetic design of universal nanovaccine platform is introduced by taking advantage of tumor‐cell‐derived components and genetically engineered antibody‐anchored membrane. The nanovaccines can be cross‐presented on dendritic cells (DCs) to activate antigen‐specific T cells. The incorporation of agonistic antibody anti‐CD40 single chain variable fragment into the nanovaccines facilitates DC maturation, which in turn activates tumor‐specific CD8+ and CD4+ T cells.
The authors describe a flow cytometric immunoassay for aflatoxin B1 (AFB1). It has three distinct features: (a) Magnetic microspheres encoded with upconverting nanocrystals (UCNMMs) are used as ...fluorescent labels. These have the advantage of non-overlapping spectra and lacking crosstalk between the encoding signal and reporter signal via the low-energy near-infrared (NIR) light excitation; (b) phycoerythrin-labeled secondary antibodies are used to amplify the reporter signal; (c) The use of magnetic nanoparticles facilitates the rapid separation and specific purification of the analyte (AFB1). This assay has a detection limit of 9 pg·mL
−1
and a broad working range for AFB1, requires a 50 μL sample only, and can be completed within 2 h with good accuracy and high reproducibility. It is perceived that such multifluorescent UCNMMs, whose color depends on the kind of dopants (Yb, Er, Tm, Mn) in the NaYF
4
host lattice, represent a promising tool for the analysis of mycotoxins and other analytes.
Graphical abstract
Schematic of the UCNMM-based indirective competitive immunoassay for AFB1 using the flow cytometric analysis (FCA) technology. The UCNMMs are prepared by doping the upconversion nanocrystals and magnetic nanoparticles inside the mesoporous polystyrene microspheres as the self-healing encapsulation strategy.
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