Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes were associated with distinct clinical features including age, sex, severity, and disease stages of COVID-19. SARS-CoV-2 RNAs were found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within viral positive cells. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and developing effective therapeutic strategies for COVID-19.

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Background/Aims: Anti-oxidation is an effective strategy for curing acute kidney injury (AKI). Herein, we suggest that extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) might play an anti-oxidative role by enhancing Nrf2/ARE activation in AKI. Methods: EVs isolated from the conditioned medium of human Wharton's Jelly mesenchymal stromal cells and human foreskin fibroblast were intravenously injected in rats immediately after 45 min of unilateral kidney ischemia. Animals were sacrificed 24 h after injury. Results: Results showed that renal tubular injury was alleviated and renal function was improved by MSC-EVs. Cell apoptosis and sNGAL levels, which reflect kidney cell injury, were reduced. Moreover, MSC-EVs decreased oxidative stress in injured kidney tissues and NRK-52E cells under hypoxia injury. Nrf2/antioxidant response element (ARE) enhancement and HO-1 up-regulation were further observed after MSC-EV treatment both in vivo and in vitro. Conclusions: MSC-EVs may protect against AKI possibly through anti-oxidation by enhancing Nrf2/ARE activation.

Heterogeneous network is a novel network architecture proposed in Long-Term-Evolution (LTE), which highly increases the capacity and coverage compared with the conventional networks. However, in order to provide the best services, appropriate resource management must be applied. In this paper, we consider the joint optimization problem of user association, subchannel allocation, and power allocation for downlink transmission in Multi-cell Multi-association Orthogonal Frequency Division Multiple Access (OFDMA) heterogeneous networks. To solve the optimization problem, we first divide it into two subproblems: 1) user association and subchannel allocation for fixed power allocation; 2) power allocation for fixed user association and subchannel allocation. Subsequently, we obtain a locally optimal solution for the joint optimization problem by solving these two subproblems alternately. For the first subproblem, we derive the globally optimal solution based on graph theory. For the second subproblem, we obtain a Karush-Kuhn-Tucker (KKT) optimal solution by a low complexity algorithm based on the difference of two convex functions approximation (DCA) method. In addition, the multi-antenna receiver case and the proportional fairness case are also discussed. Simulation results demonstrate that the proposed algorithms can significantly enhance the overall network throughput.

Niacin metal-organic frameworks (MOFs) encapsulated microcapsules with alginate shells and copper-/zinc-niacin framework cores were in situ synthesized by using a microfluidic electrospray approach for wound healing. As the alginate shells were bacteria-responsively degradable, the niacin MOFs encapsulated microcapsules could intelligently, controllably, and programmably release calcium, copper, and zinc ions, depending on the degree of infections. The released ions could not only kill microbes by destroying their membrane and inducing the outflow of nutrient substance, but also activate copper/zinc superoxide dismutase (Cu/Zn-SOD) to eliminate oxygen free radicals and rescue the cells from oxidative stress injury. Furthermore, the simultaneously released niacin could promote hemangiectasis and absorption of functional metal ions. Thus, the niacin MOFs encapsulated microcapsules were imparted with outstanding antibacterial, antioxidant, and angiogenesis properties. Based on an in vivo study, we have also demonstrated that the chronic wound healing process of an infected full-thickness skin defect model could be significantly enhanced by using the niacin MOFs encapsulated microcapsules as therapeutic agent. Therefore, the microfluidic electrospray niacin MOFs encapsulated microcapsules are potential for clinical applications.