The production scalability and increasing demand for nano-black phosphorus materials (nano-BPs) inevitably lead to their environmental leakage, thereby raising the risk of human exposure through inhalation, ingestion, dermal, and even intravenous pathways. Consequently, a systematic evaluation of their potential impacts on human health is necessary. This Review outlines recent progress in the understanding of various biological responses to nano-BPs. Attention is particularly given to the inconsistent toxicological findings caused by a wide variation of nano-BPs\' physicochemical properties, toxicological testing methods, and cell types examined in each study. Additionally, cellular uptake and intracellular trafficking, cell death modes, immunological effects, and other biologically relevant processes are discussed in detail, providing evidence for the potential health implications of nano-BPs. Finally, we address the remaining challenges related to the health risk evaluation of nano-BPs and propose a broader range of applications for these promising nanomaterials.

Electrical properties of single cells are important label-free biomarkers of disease and immunity. At present, impedance flow cytometry (IFC) provides important means for high throughput characterization of single-cell electrical properties. However, the accuracy of the spherical single-shell electrical model widely used in IFC has not been well evaluated due to the lack of reliable and reproducible single-shell model particles with true-value electrical parameters as benchmarks. Herein, a method is proposed to evaluate the accuracy of the single-cell electrical model with cell-sized unilamellar liposomes synthesized through double emulsion droplet microfluidics. The influence of three key dimension parameters (i.e., the measurement channel width w, height h, and electrode gap g) in the single-cell electrical model were evaluated through experiment. It was found that the relative error of the electrical intrinsic parameters measured by IFC is less than 10% when the size of the sensing zone is close to the measured particles. It further reveals that h has the greatest influence on the measurement accuracy, and the maximum relative error can reach ∼30%. Error caused by g is slightly larger than w. This provides a solid guideline for the design of IFC measurement system. It is envisioned that this method can advance further improvement of IFC and accurate electrical characterization of single cells.

Nanovaccines have attracted intense interests for efficient antigen delivery and tumor-specific immunity. It is challenging to develop a more efficient and personalized nanovaccine to maximize all steps of the vaccination cascade by exploiting the intrinsic properties of nanoparticles. Here, biodegradable nanohybrids (MP) composed of manganese oxide nanoparticles and cationic polymers are synthesized to load a model antigen ovalbumin to form MPO nanovaccines. More interestingly, MPO could serve as autologous nanovaccines for personalized tumor treatment taking advantage of in situ released tumor-associated antigens induced by immunogenic cell death (ICD). The intrinsic properties of MP nanohybrids including morphology, size, surface charge, chemical, and immunoregulatory functions are fully exploited to enhance of all steps of the cascade and induce ICD. MP nanohybrids are designed to efficiently encapsulate antigens by cationic polymers, drain to lymph nodes by appropriate size, be internalized by dendritic cells (DCs) by rough morphology, induce DC maturation through cGAS-STING pathway, and enhance lysosomal escape and antigen cross-presentation through the \"proton sponge effect\". The MPO nanovaccines are found to efficiently accumulate in lymph nodes and elicit robust specific T-cell immune responses to inhibit the occurrence of ovalbumin-expressing B16-OVA melanoma. Furthermore, MPO demonstrate great potential to serve as personalized cancer vaccines through the generation of autologous antigen depot through ICD induction, activation of potent antitumor immunity, and reversal of immunosuppression. This work provides a facile strategy for the construction of personalized nanovaccines by exploiting the intrinsic properties of nanohybrids.

Cell plasticity endows differentiated cells with competence to be reprogrammed to other lineages. Although extrinsic factors driving cell-identity conversion have been extensively characterized, it remains elusive which intrinsic epigenetic attributes, including high-order chromatin organization, delineate cell plasticity. By analysing the transcription-factor-induced transdifferentiation from fibroblasts to hepatocytes, we uncovered contiguous compartment-switchable regions (CSRs) as a unique chromatin unit. Specifically, compartment B-to-A CSRs, enriched with hepatic genes, possessed a mosaic status of inactive chromatin and pre-existing and continuous accessibility in fibroblasts. Pre-existing accessibility enhanced the binding of inducible factor Foxa3, which triggered epigenetic activation and chromatin interaction as well as hepatic gene expression. Notably, these changes were restrained within B-to-A CSR boundaries that were defined by CTCF occupancy. Moreover, such chromatin organization and mosaic status were detectable in different cell types and involved in multiple reprogramming processes, suggesting an intrinsic chromatin attribute in understanding cell plasticity.

Mechanical properties of single cells are important label-free biomarkers normally measured by expensive and complex imaging systems. To unlock this limit and allow mechanical properties comparable across different measurement platforms, camera-free intrinsic mechanical cytometry (CFIMC) is proposed for on-the-fly measurement of two major intrinsic mechanical parameters, that is, Young\'s modulus E and fluidity β, of single cells. CFIMC adopts a framework that couples the impedance electrodes with the constriction channel spatially, so that the impedance signals contain the dynamic deformability information of the cell squeezing through the constriction channel. Deformation of the cell is thus extracted from the impedance signals and used to derive the intrinsic mechanical parameters. With reasonably high throughput (>500 cells min-1 ), CFIMC can successfully reveal the mechanical difference in cancer and normal cells (i.e., human breast cell lines MCF-10A, MCF-7, and MDA-MB-231), living and fixed cells, and pharmacological perturbations of the cytoskeleton. It is further found that 1 µM level concentration of Cytochalasin B may be the threshold for the treated cells to induce a significant cytoskeleton effect reflected by the mechanical parameters. It is envisioned that CFIMC provides an alternative avenue for high-throughput and real-time single-cell intrinsic mechanical analysis.

Since the ferromagnetic (Fe3O4) nanoparticles were firstly reported to exert enzyme-like activity in 2007, extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies. As promising alternatives for natural enzymes, nanozymes have broadened the way toward clinical medicine, food safety, environmental monitoring, and chemical production. The past decade has witnessed the rapid development of metal- and metal oxide-based nanozymes owing to their remarkable physicochemical properties in parallel with low cost, high stability, and easy storage. It is widely known that the deep study of catalytic activities and mechanism sheds significant influence on the applications of nanozymes. This review digs into the characteristics and intrinsic properties of metal- and metal oxide-based nanozymes, especially emphasizing their catalytic mechanism and recent applications in biological analysis, relieving inflammation, antibacterial, and cancer therapy. We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

Phenolic carbon felt (PCF) is a three-dimensional material with a simple manufacturing process and low cost. To investigate the application of PCF as an anode material for use in microbial fuel cells (MFCs), we employed PCF as the anode material for the first time in MFCs that were carbonized at different temperatures. The relationship between the intrinsic characteristics and the electrochemical performance of different PCFs was also analyzed. Here, we obtained the best power generation with a power density of up to 2600 mW/m2 when PCF was heated to 900 °C (PCF-900); this power generation was much higher than that of the commercial carbon felts. From SEM images, we found that the biofilm growth of PCF-900 was quite uniform. This may result from the higher surface electropositivity of PCF-900 and increased electrostatic attraction between the microorganisms and PCF. We also analyzed the conductivity, specific surface area, functional groups, and surface charge of the PCF anode. Under the synergistic effect of these intrinsic properties, PCF-900 showed good biocompatibility for the adhesion of microorganisms and high electron transfer efficiency. In addition, PCF was easily prepared in different sizes. Thus, it could be a promising material for the application of scale-up MFCs.

Unilateral auditory deprivation results in lateralization changes in the central auditory system, interfering with the integration of binaural information and thereby leading to a decrease in binaural auditory functions such as sound localization. Principal neurons of the lateral superior olive (LSO) are responsible for computing the interaural intensity differences that are critical for sound localization in the horizontal plane. To investigate changes caused by unilateral auditory deprivation, electrophysiological activity was recorded from LSO principal neurons in control rats and rats with unilateral cochlear ablation. At one week after unilateral cochlear ablation, the excitability of LSO principal neurons on the side ipsilateral to the ablation (the ablated side) was greater than that on the side contralateral to the ablation (the intact side); however, the input resistance increased on both sides. Furthermore, by analysing the miniature inhibitory postsynaptic currents and miniature excitatory postsynaptic currents, we found that unilateral auditory deprivation weakened the inhibitory driving force on the intact side, whereas it strengthened the excitatory driving force on the ablated side. In summary, asymmetric changes in the electrophysiological activity of LSO principal neurons were found on both sides at postnatal day 19, one week after unilateral cochlear ablation.

Layer 2/3 (L2/3) excitatory neurons in the neocortex make major contributions to corticocortical connections and therefore function to integrate information across cortical areas and hemispheres. Recent evidence suggests that excitatory neurons in L2/3 can have different properties. Sparse evidence from previous studies suggests that L2 neurons located at the border between L1 and L2 (referred to as L2 marginal neurons, L2MNs), have a morphology distinct from a typical pyramidal neuron. However, whether the membrane properties and input/output properties of L2MNs are different from those of typical pyramidal neurons in L2/3 is unknown. Here we addressed these questions in a slice preparation of mouse temporal cortex. We found that L2MNs were homogeneous in intrinsic membrane properties but appeared diverse in morphology. In agreement with previous studies, L2MNs either had oblique apical dendrites or had no obvious apical dendrites. The tufts of both apical and basal dendrites of these neurons invaded L1 extensively. All L2MNs showed a regular firing pattern with moderate adaptation. Compared with typical L2/3 pyramidal neurons that showed regular spiking (RS) activity (neurons), L2MNs showed a higher firing rate, larger sag ratio, and higher input resistance. No difference in the amplitude of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively), evoked by stimulation of L1, was found between the two types of neurons, but the IPSPs in L2MNs had a slower time course than those in L2/3 RS cells. In paired recordings, unitary EPSPs showed no significant differences between synapses formed by L2MNs and those formed by L2/3 RS neurons. However, short-term synaptic depression (STSD) examined with a L2MN as the presynaptic neuron was greater when another L2MN was the postsynaptic neuron than when a L2/3 RS neuron was the postsynaptic neuron. The distinct morphological features of L2MNs found here have developmental implications, and the differences in electrophysiological properties between L2MNs and other L2/3 pyramidal neurons suggest that they play different functional roles in cortical networks.

The tree shrew, as a primate-like animal model, has been used for studying high brain functions such as social emotion and spatial learning memory. However, little is known about the excitatory synaptic transmission in cortical brain areas of the tree shrew. In the present study, we have characterized the excitatory synaptic transmission and intrinsic properties of pyramidal neurons in the anterior cingulate cortex (ACC) of the adult tree shrew, a key cortical region for pain perception and emotion. We found that glutamate is the major excitatory transmitter for fast synaptic transmission. Excitatory synaptic responses induced by local stimulation were mediated by AMPA and kainate (KA) receptors. As compared with mice, AMPA and KA receptor mediated responses were significantly greater. Interestingly, the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) in tree shrews was significantly less than that of mice. Moreover, both the ratio of paired-pulse facilitation (PPF) and the time of 50% decay for fast blockade of NMDA receptor mediated EPSCs were greater in the tree shrew. Finally, tree shrew neurons showed higher initial firing frequency and neuronal excitability with a cell type-specific manner in the ACC. Our studies provide the first report of the basal synaptic transmission in the ACC of adult tree shrew.