A comprehensive understanding of the cellular heterogeneity and molecular mechanisms underlying the development, homeostasis, and disease of human intervertebral disks (IVDs) remains challenging. Here, the transcriptomic landscape of 108 108 IVD cells was mapped using single-cell RNA sequencing of three main compartments from young and adult healthy IVDs, including the nucleus pulposus (NP), annulus fibrosus, and cartilage endplate (CEP). The chondrocyte subclusters were classified based on their potential regulatory, homeostatic, and effector functions in extracellular matrix (ECM) homeostasis. Notably, in the NP, a PROCR+ resident progenitor population showed enriched colony-forming unit-fibroblast (CFU-F) activity and trilineage differentiation capacity. Finally, intercellular crosstalk based on signaling network analysis uncovered that the PDGF and TGF-β cascades are important cues in the NP microenvironment. In conclusion, a single-cell transcriptomic atlas that resolves spatially regulated cellular heterogeneity together with the critical signaling that underlies homeostasis will help to establish new therapeutic strategies for IVD degeneration in the clinic.

In this work, a dextran modified PDMS microfluidic ELISA device was fabricated. The dextran functionalization was conducted with a simple, economic and fast flow-through process in a fabricated PDMS microfluidic device, and demonstrated significant enhancement of hydrophilicity and efficient covalent immobilization of proteins on the PDMS microchannel surface. The device was used to simultaneously detect multiple important biomarker IL-5, HBsAg, and IgG, showing a limit of detection of 100 pg mL(-1) and a dynamic range of 5 orders of magnitude, which significantly improved the performance of the reported hydrophobic and plasma-treated hydrophilic PDMS flow-through immunoassay devices. The fabricated PDMS device demonstrated its capability for colorimetric detection of proteins through direct observation by human eyes. Thus, this work not only demonstrates great potential to fabricate an economical and sensitive lab-on-chip system for high throughput screening of various infectious diseases, but also provides an opportunity to develop a portable microfluidic ELISA device via human eye examination for heath point-of-care services.

The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.

Self-supported Bi 2 S 3 nanowire arrays with sizes up to several millimeters were prepared by a facile hydrothermal method. In our work, the oriented nanowire arrays were supported on a self-generated nanowire networked substrate. The as-prepared Bi 2 S 3 nanowire exhibited nonlinear current-voltage (I-V) characteristics and excellent photoresponse. It is suggested that the rectifying behavior comes from the Schottky contact between the Bi 2 S 3 nanowire and the Au electrodes. As the light source was switched on and off, the nanowire could be reversibly switched between low and high conductivity, indicating its potential applications in optoelectronic nanodevices.