Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID‐19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation‐related cytokines, we found significantly altered cytokine profiles in severe COVID‐19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL‐10, IL‐6, IL‐10, IL‐12, and TNF‐α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL‐10 and TNF‐α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up‐regulated expression levels of inflammatory cytokines and surface markers with IL‐6 in monocytes through STAT3 and NF‐κB signaling pathways. Collectively, our results suggest that overweight COVID‐19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID‐19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.

We aimed to investigate changes in pulmonary function and computed tomography (CT) findings in patients with coronavirus disease 2019 (COVID-19) during the recovery period. COVID-19 patients underwent symptom assessment, pulmonary function tests, and high-resolution chest CT 6 months after discharge from the hospital. Of the 54 patients enrolled, 31 and 23 were in the moderate and severe group, respectively. The main symptoms 6 months after discharge were fatigue and exertional dyspnea, experienced by 24.1% and 18.5% of patients, respectively, followed by smell and taste dysfunction (9.3%) and cough (5.6%). One patient dropped out of the pulmonary function tests. Of the remaining 54 patients, 41.5% had pulmonary dysfunction. Specifically, 7.5% presented with restrictive ventilatory dysfunction (forced vital capacity <80% of the predicted value), 18.9% presented with small airway dysfunction, and 32.1% presented with pulmonary diffusion impairment (diffusing capacity for carbon monoxide <80% of the predicted value). Of the 54 patients enrolled, six patients dropped out of the chest CT tests. Eleven of the remaining 48 patients presented with abnormal lung CT findings 6 months after discharge. Patients with residual lung lesions were more common in the severe group (52.6%) than in the moderate group (3.4%); a higher proportion of patients had involvement of both lungs (42.1% vs. 3.4%) in the severe group. The residual lung lesions were mainly ground-glass opacities (20.8%) and linear opacities (14.6%). Semiquantitative visual scoring of the CT findings revealed significantly higher scores in the left, right, and both lungs in the severe group than in the moderate group. COVID-19 patients 6 months after discharge mostly presented with fatigue and exertional dyspnea, and their pulmonary dysfunction was mostly characterized by pulmonary diffusion impairment. As revealed by chest CT, the severe group had a higher prevalence of residual lesions than the moderate group, and the residual lesions mostly manifested as ground-glass opacities and linear opacities.

Development of chemoresistance is the main reason for failure of clinical management of multiple myeloma (MM), but the genetic and epigenetic aberrations that interact to confer such chemoresistance remains unknown. In the present study, we find that high steroid receptor coactivator-3 (SRC-3) expression is correlated with relapse/refractory and poor outcomes in MM patients treated with bortezomib (BTZ)-based regimens. Furthermore, in immortalized cell lines, high SRC-3 enhances resistance to proteasome inhibitor (PI)-induced apoptosis. Overexpressed histone methyltransferase NSD2 in patients bearing a t(4;14) translocation or in BTZ-resistant MM cells coordinates elevated SRC-3 by enhancing its liquid–liquid phase separation to supranormally modify histone H3 lysine 36 dimethylation (H3K36me2) modifications on promoters of anti-apoptotic genes. Targeting SRC-3 or interference of its interactions with NSD2 using a newly developed inhibitor, SI-2, sensitizes BTZ treatment and overcomes drug resistance both in vitro and in vivo. Taken together, our findings elucidate a previously unrecognized orchestration of SRC-3 and NSD2 in acquired drug resistance of MM and suggest that SI-2 may be efficacious for overcoming drug resistance in MM patients.

Stimuli-responsive nanoparticles (NPs), so-called "smart" NPs, possess great potentials in drug delivery. Presently, the intelligence of smart NPs is mainly based on their chemical or physical changes to stimuli, which are usually "mechanical" and fundamentally different from biological intelligence. Inspired by mitochondria (MT), a biosmart nanoparticle with microenvironment targeting and self-adaptive capacity (MTSNP) was fabricated for ischemic tissue repair. The nanoparticles were designed as shell@circular DNA@ shell@core. The double shells were like the two-layered membranes of MT, the melatonin-loaded cores corresponded to the MT matrix, and the circular DNA corresponded to MTDNA. In function, melatonin-loaded cores simulated the cell-protective mechanism of MT, which naturally synthesized melatonin to resist ischemia, while circular DNA was constructed to mimic the biological oxygen-sensing mechanism, synthesizing VEGF for vascularization according to oxygen level, like the ATP supply by MT according to microenvironment demand. At the acute stage of ischemia, melatonin was rapidly released from MTSNP to scavenge reactive oxygen species and activated melatonin receptor I on MT to prevent cytochrome c release, which would activate apoptosis. During the chronic stage, circular DNA could sense hypoxia and actively secrete VEGF for revascularization as a response. Importantly, circular DNA could also receive feedback of revascularization and shut down VEGF secretion as an adverse response. Then, the therapeutic potentials of the MTSNP were verified in myocardial ischemia by the multimodality of the methods. Such nanoparticles may represent a promising intelligent nanodrug system.