We have developed a photoelectrochemical (PEC) cytosensor for ultrasensitive detection of RAW264.7 cells by the signal change of a TiO nanoneedles (NNs)@MoO array. For the first time, a TiO NNs@MoO array was adopted for the fabrication of the cytosensor for the signal output. The well-matched alignment of TiO NNs and MoO efficiently suppresses the recombination of photogenerated electron and hole (e/h) pairs for improved photon-to-current conversion efficiency. The RAW264.7 cell and F4/80 antibody could form the biocomplexes because of the specific recognition between each other. The constructed PEC cytosensor based on the TiO NNs@MoO array displayed good PEC property for detection of RAW264.7 cells. The numbers of RAW264.7 cells are directly detected through the decrement of photocurrent intensity, due to the increased steric hindrance when RAW264.7 cells are captured. The PEC cytosensor showed an ultrasensitive response to RAW264.7 cells with a linear range of 50-15 000 cells/mL and a detection limit of 50 cells/mL. The designed cytosensor based on a TiO NNs@MoO array offers an ideal platform to detect RAW264.7 cells with excellent stability, reproducibility, and selectivity and served as a model for the fabrication of cytosensors for other cells.

We herein report a self-powered and renewable cytosensing device based on ZnO nanodisks(NDs)@g-C3N4 quantum dots. The device features enhanced photoelectrochemical (PEC) activity compared to ZnO NDs or g-C3N4 QDs alone. The enhanced PEC ability is attributed to the synergistic effect of the high visible light sensitivity of g-C3N4 QDs and the staggered band alignment heterojunction structure with suitable band offset, which affords higher photoelectron transfer and separation efficiency. In addition, the hybridization of g-C3N4 QDs further accelerates interfacial electron transfer and blocks recombination between electron donors and photo-generated holes. The device was applied to the detection of CCRF-CEM cells. By conjugation to Sgc8c aptamer, which preferentially interacts with membrane-bound PTK7 on CCRF-CEM membranes, capture of target CCRF-CEM cells resulted in a decrease in apparent power output, which was then exploited for the ultrasensitive detection of the target cells. This decrease in power output can be recovered by simply increasing the temperature to release the cells, thus recycling the cytosensing performance. The device displayed a linear relationship between the change of power output and the logarithm of the cell concentration from 20 to 20,000 cell/mL (R2 = 0.9837) and a detection limit down to 20 cell/mL, as well as excellent selectivity and reproducibility. Thus, this ZnO NDs@g-C3N4 QDs-based device exhibits high potential for the detection of CCRF-CEM cells.

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The development of strategies to access 2,2′-diaminobiaryl derivatives via a transition-metal-catalyzed coupling reaction from protecting-group-free starting materials is a challenging task to accomplish, owing to the easy occurrence of undesired side reactions. The exploitation of Ni-catalyzed direct homocoupling of unprotected 2-haloaniline analogues to produce 2,2′-diaminobiaryls with a readily available and inexpensive bipyridine ligand has been described. This approach was highlighted by its high chemoselectivity, broad substrate scope, and functional group compatibility. The mechanistic and calculation studies indicated that Ni(0), Ni­(I), Ni­(II), and Ni­(III) species might be involved in the catalytic cycle.

Pediatric high-grade gliomas are the leading cause of brain cancer-related death in children. High-grade gliomas include clinically and molecularly distinct subtypes that stratify by anatomical location into diffuse midline gliomas (DMG) such as diffuse intrinsic pontine glioma (DIPG) and hemispheric high-grade gliomas. Neuronal activity drives high-grade glioma progression both through paracrine signaling(1,2) and direct neuron-to-glioma synapses(3-5). Glutamatergic, AMPA receptor-dependent synapses between neurons and malignant glioma cells have been demonstrated in both pediatric(3) and adult high-grade gliomas(4), but neuron-to-glioma synapses mediated by other neurotransmitters remain largely unexplored. Using whole-cell patch clamp electrophysiology, in vivo optogenetics and patient-derived glioma xenograft models, we have now identified functional, tumor-promoting GABAergic neuron-to-glioma synapses mediated by GABAA receptors in DMGs. GABAergic input has a depolarizing effect on DMG cells due to NKCC1 expression and consequently elevated intracellular chloride concentration in DMG tumor cells. As membrane depolarization increases glioma proliferation(3), we find that the activity of GABAergic interneurons promotes DMG proliferation in vivo. Increasing GABA signaling with the benzodiazepine lorazepam, a positive allosteric modulator of GABAA receptors commonly administered to children with DMG for nausea or anxiety, increases GABAA receptor conductance and increases glioma proliferation in orthotopic xenograft models of DMG. Conversely, levetiracetam, an anti-epileptic drug that attenuates GABAergic neuron-to-glioma synaptic currents, reduces glioma proliferation in patient-derived DMG xenografts and extends survival of mice bearing DMG xenografts. Concordant with gene expression patterns of GABAA receptor subunit genes across subtypes of glioma, depolarizing GABAergic currents were not found in hemispheric high-grade gliomas. Accordingly, neither lorazepam nor levetiracetam influenced the growth rate of hemispheric high-grade glioma patient-derived xenograft models. Retrospective real-world clinical data are consistent with these conclusions and should be replicated in future prospective clinical studies. Taken together, these findings uncover GABAergic synaptic communication between GABAergic interneurons and diffuse midline glioma cells, underscoring a tumor subtype-specific mechanism of brain cancer neurophysiology with important potential implications for commonly used drugs in this disease context.