Checkpoint blockade antibodies have been approved as immunotherapy for multiple types of cancer, but the response rate and efficacy are still limited. There are few immunogenic cell death ...(ICD)-inducing drugs available that can kill cancer cells, enhance tumor immunogenicity, increase the in vivo immune infiltration, and thereby boosting a tumor response to immunotherapy. So far, the ICD markers have been identified as the few immuno-stimulating characteristics of dead cells, but whether the presence of such ICD markers on tumor cells translates into enhanced antitumor immunity in vivo is still investigational. To identify anticancer drugs that could induce tumor cell death and boost T cell response, we performed drug screenings based on both an ICD reporter assay and T cell activation assay. We identified that teniposide, a DNA topoisomerase II inhibitor, could induce high mobility group box 1 (HMGB1) release and type I interferon signaling in tumor cells, and teniposide-treated tumor cells could activate antitumor T cell response both in vitro and in vivo. Mechanistically, teniposide induced tumor cell DNA damage and innate immune signaling including NF-κB activation and STING-dependent type I interferon signaling, both of which contribute to the activation of dendritic cells and subsequent T cells. Furthermore, teniposide potentiated the antitumor efficacy of anti-PD1 on multiple types of mouse tumor models. Our findings showed that teniposide could trigger tumor immunogenicity, and enabled a potential chemo-immunotherapeutic approach to potentiate the therapeutic efficacy of anti-PD1 immunotherapy.
The first controllable, regioselective radical amination of allenes with N‐fluoroarylsulfonimide is described to proceed under very mild reaction conditions. With this methodology, a general and ...straightforward route for the synthesis of both allenamides and fluorinated tetrasubstituted alkenes was realized from a wide range of terminal and internal allenes.
Radical highway: By employing N‐fluoroarylsulfonimide as a nitrogen source, a facile, mild, and highly regioselective copper‐catalyzed oxidative radical amination of various allenes was developed. In addition, a protocol involving nitrogen radical addition/fluorine‐atom transfer affords fluorinated tetrasubstituted alkenes by using silver as catalyst.
Electrochemical advanced oxidation processes (EAOPs) are effective and environmentally friendly for the treatment of refractory organic pollutants. Among EAOPs, heterogeneous electro-Fenton (EF) ...process with in-situ formation of hydrogen peroxide (H2O2) is an eco-friendly, cost-effective and easy-operable technology to generate hydroxyl radicals (•OH) with high redox potential. The generation of •OH is determined by the synergistic H2O2 formation and activation. The surface catalytic mechanisms for H2O2 activation in the heterogeneous EF process were discussed. Some required features such as heteroatom doping and oxygen groups for H2O2 formation via selective two-electron oxygen reduction reaction (ORR) with carbonaceous electrode are summarized. The solid Fenton catalysts and integrated functional cathodes that widely used in heterogeneous EF for wastewater treatment are grouped into few classes. And the brief discussion on catalytic activity and stability of materials over different experimental conditions are given. In addition, the application of heterogeneous EF process on the remediation of emerging contaminants is provided. The challenges and future prospects of the heterogeneous EF processes about catalytic fall-off and multi-step/complex techniques for water purification are emphasized.
This manuscript reviewed the recent advances and achievements in heterogeneous electro-Fenton and their applications in the remediation of emerging contaminants. Display omitted
One-dimensional hollow-structured NiCoP nanorods are synthesized via Kirkendall effect resulting from different diffusion rates of Ni and Co ions at 350 °C, using NaH2PO2 as a phosphorization agent. ...Various techniques were used to study the formation mechanism of hollow NiCoP nanorods which structure and crystallinity could be effectively tuned by adjusting phosphorization time. Capacitance of NiCoP reaches 273.4 μAh cm−2 at a current density of 30 mA cm−2 with a rate retention of 85.6%. Specific capacitance of an asymmetric supercapacitor cell (ASC) where NiCoP sample was used together with activated carbon reached 264.6 μAh cm−2 at 2 mA cm−2 and decreased to 213.2 μAh cm−2 with current density rising to 30 mA cm−2. The ASC possesses quite high energy- and power densities, compared to previously reported results, which demonstrates applicability of hollow NiCoP nanorods for electrochemical energy storage.
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•1D hollow-structured NiCoP nanorods were synthesized via phosphorization.•Formation of void space in NiCoP nanorods results from Kirkendall effect.•NiCoP supercapacitor cathode showed an energy density of 68 Wh kg−1 at 9594 W kg−1.
A mild and efficient approach for highly regio- and enantioselective copper-catalyzed hydroboration of 1,1-diaryl substituted alkenes with bis(pinacolato)diboron (B2Pin2) was developed for the ...first time, providing facile access to a series of valuable β,β-diaryl substituted boronic esters with high enantiomeric purity. Moreover, this approach could also be suitable for hydroboration of α-alkyl styrenes for the synthesis of enantioenriched β,β-arylalkyl substituted boronic esters. Gram-scale reaction, stereospecific derivatizations, and the application of important antimuscarinic drug (R)-tolterodine for concise enantioselective synthesis further highlighted the attractiveness of this new approach.
With the rise in popularity of autonomous driving, the speed and accuracy of surrounding objects' detection by in-vehicle sensing technology is becoming increasingly important for autonomous ...vehicles. Building on CenterNet, this paper proposes CenterNet-Auto, a new anchor-free detection network for driving scenes that can satisfy the detection speed requirements while ensuring detection accuracy. The network's backbone uses the RepVGG model transformed through structural re-parameterization technology. Features of different scales are fused, and feature pyramids and deformable convolution are added after the backbone to accurately detect objects of different sizes. To solve the occlusion problem in the driving scene, this paper proposes the Average Border Model, which supports locating the object using the boundary feature information. The test results demonstrate that the proposed algorithm outperforms CenterNet regarding speed and accuracy on the BDD dataset. The accuracy reaches 55.6%, and the speed reaches 30 FPS, meeting the speed and accuracy requirements in a driving scene.
In this study, both nanofibrillated cellulose (NFC) and graphene oxide (GO) as dispersant and binder, were employed to effectively disperse and assemble carbon nanotube (CNT) via ultrasonic ...dispersion. A NFC/rGO (reduced graphene oxide)/CNT conductive composite membrane was prepared via a low-temperature and efficient hot pressing treatment with the synergistic effect of drying, reduction, and densification, which exhibited good conductivity, mechanical performance, and thermal stability. After the composite membrane (mass ratio of NFC:GO:CNT was 2:4:4) was hot pressed under 3 MPa at 170 °C for 30 min, its sheet resistance reduction rate reached to 61.1% (decreased from 19.8 ± 3.1 Ω sq.−1 to 7.7 ± 1.1 Ω sq.−1), while its Young's modulus increased from 1496.3 ± 250.9 MPa to 3178.3 ± 356.2 MPa. Hot pressing at the low temperature can reduce oxygen-containing groups on GO, by which the carbon-to‑oxygen ratio was increased from 2.28 to 5.05. The presented controllable method helps to construct a conductive network in the composite membrane, and provides a new strategy to enhance performance of the low-dimensional carbon composite membrane.
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•A stable and flexible NFC/rGO/CNT conductive composite membrane was prepared via a low-temperature hot pressing process.•The hot pressing process simultaneously attained the reduction of GO, densification and drying of the composite membranes.•Both NFC and GO with good dispersibility were used to synergistically drive the dispersion of CNT.•The presented design for the process is efficient and environmentally friendly to the manufacture of the composite membranes.
To solve the competition problem of acidophilic bacteria and sulfate-reducing bacteria in the practical application of mine tailing bioremediation, research into the mechanisms of using different ...nutrients to adjust the microbial community was conducted. Competition experiments involving acidophilic bacteria and sulfate-reducing bacteria were performed by supplementing the media with yeast extract, tryptone, lactate, and glucose. The physiochemical properties were determined, and the microbial community structure and biomass were investigated using MiSeq sequencing and qRT-PCR, respectively. Four nutrients had different remediation mechanisms and yielded different remediation effects. Yeast extract and tryptone (more than 1.6 g/L) promoted sulfate-reducing bacteria and inhibited acidophilic bacteria. Lactate inhibited both sulfate-reducing and acidophilic bacteria. Glucose promoted acidophilic bacteria more than sulfate-reducing bacteria. Yeast extract was the best choice for adjusting the microbial community and bioremediation, followed by tryptone. Lactate kept the physiochemical properties stable or made slight improvements; however, glucose was not suitable for mine tailing remediation. Different nutrients had significant effects on the abundance of the second enzyme of the sulfate-reducing pathway (p < 0.05), which is the rate-limiting step of sulfate-reducing pathways. Nutrients changed the remediation effects effectively by adjusting the microbial community and the abundance of the sulfate-reducing rate-limiting enzyme.
Hyperactive mevalonate (MVA) metabolic activity is often observed in cancer cells, and blockade of this pathway inhibits tumor cell lipid synthesis and cell growth and enhances tumor immunogenicity. ...How tumor cell MVA metabolic blockade promotes antitumor immune responses, however, remains unclear. Here we show that inhibition of the MVA metabolic pathway in tumor cells elicits type 1 classical dendritic cells (cDC1)-mediated tumor recognition and antigen cross-presentation for antitumor immunity. Mechanistically, MVA blockade disrupted prenylation of the small GTPase Rac1 and induced cancer cell actin filament exposure, which was recognized by CLEC9A, a C-lectin receptor specifically expressed on cDC1s, in turn activating antitumor T cells. MVA pathway blockade or Rac1 knockdown in tumor cells induced CD8
T-cell-mediated antitumor immunity in immunocompetent mice but not in
mice lacking CLEC9A
dendritic cells. These findings demonstrate tumor MVA metabolic blockade stimulates a cDC1 response through CLEC9A-mediated immune recognition of tumor cell cytoskeleton, illustrating a new immune surveillance mechanism by which dendritic cells monitor tumor metabolic dysregulation and providing insight into how MVA pathway inhibition may potentiate anticancer immunity. SIGNIFICANCE: These findings suggest that mevalonate blockade in cancer cells disrupts Rac1 prenylation to increase recognition and cross-presentation by conventional dendritic cells, suggesting this axis as a potential target for cancer immunotherapy.
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