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Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2 + TMPRSS2 + cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

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Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

Stretchable strain sensors with high sensitivity or gauge factor (GF), large stretchability, and long-term durability are highly demanded in human motion detection, artificial intelligence, and electronic skins. Nevertheless, to develop high-sensitive sensors without sacrificing the stretchability cannot be realized using simple device configurations. In this work, an acid-interface engineering (AIE) method was proposed to develop a stretchable strain sensor with high GF and large stretchability. The AIE generates a layer of SiO x at the interface between the carbon nanotube (CNT) film and Ecoflex, playing a key role in enhancing the sensor’s GF. Compared to devices without AIE (GF = 2.4), the ones with AIE are significantly improved. At an AIE time of 10 min, the GF up to 1665.9 is achieved without sacrificing the stretchability (>100%). The AIE-generated cracks are found to modulate the electrical behaviors and enhance the GFs of sensors with AIE through the crack-induced rapid reduction in the electrical conduction pathway, which is manipulated by the CNTs bridging over the cracks. The device with AIE proves its high mechanical durability through a cycling test (>10 000 cycles) at a high strain up to ∼80%, further paving its practical applications in various human motion detections.

Background: Although N6-methyladenosine (m6A) plays a very important role in different biological processes, its function in the brain has not been fully explored. Thus, we investigated the roles of the RNA demethylases Alkbh5/Fto in cerebral ischemia-reperfusion injury. Methods: We used a rat model and primary neuronal cell culture to study the role of m6A and Alkbh5/Fto in the cerebral cortex ischemic penumbra after cerebral ischemia-reperfusion injury. We used Alkbh5-shRNA and Lv-Fto ( in vitro) to regulate the expression of Alkbh5/Fto to study their regulation of m6A in the cerebral cortex and to study brain function after ischemia-reperfusion injury. Results: We found that RNA m6A levels increased consecutive to the increase of Alkbh5 expression in both the cerebral cortex of rats after middle cerebral artery occlusion, and in primary neurons after oxygen deprivation/reoxygenation. In contrast, Fto expression decreased after these perturbations. Our results suggest that knocking down Alkbh5 can aggravate neuronal damage. This is due to the demethylation of Alkbh5 and Fto, which selectively demethylate the Bcl2 transcript, preventing Bcl2 transcript degradation and enhancing Bcl2 protein expression. Conclusion: Collectively, our results demonstrate that the demethylases Alkbh5/Fto co-regulate m6A demethylation, which plays a crucial role in cerebral ischemia-reperfusion injury. The results provide novel insights into potential therapeutic mechanisms for stroke.

Stromal cell-derived factor 1 (SDF-1) is a critical regulator of endothelial progenitor cells (EPCs) mediated physiological and pathologic angiogenesis. It was considered to act via its unique receptor CXCR4 for a long time. CXCR7 is a second, recently identified receptor for SDF-1, and its role in human EPCs is unclear. In present study, CXCR7 was found to be scarcely expressed on the surface of human EPCs derived from cord blood, but considerable intracellular CXCR7 was detected, which differs from that on EPCs derived from rat bone marrow. CXCR7 failed to support SDF-1 induced human EPCs migration, proliferation, or nitric oxide (NO) production, but mediated human EPCs survival exclusively. Besides that, CXCR7 mediated EPCs tube formation along with CXCR4. Blocking CXCR7 with its antagonist CCX733 impaired SDF-1/CXCR4 induced EPCs adhesion to active HUVECs and trans-endothelial migration. Those results suggested that CXCR7 plays an important role in human cord blood derived EPCs in response to SDF-1.

Background and purpose: To compare 68 Ga-fibroblast activation protein inhibitor (FAPI) and 18 F-FDG PET/ CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68 Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18 F-FDG PET/CT. Materials and methods: Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18 F-FDG and 68 Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTV CT ), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded. Results: The 68 Ga-FAPI PET showed significantly higher radiotracer uptake than 18 F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI Â20%, 30%, 40%, and FDG Â40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTV CT demonstrated the largest volume (median: 48.80 mm 3 , range: 14.83-162.23 mm 3 ) than PET-based GTVs. For PET/CT-guided complementary contouring of GTV CT , four patients (19%) were increased by FAPI Â20% and 30%, two patients (9.5%) were increased by FAPI Â40%, and only one patient was increased by FDG Â40%. Furthermore, the volume of GTV based on CE-CT plus FAPI Â20%, 30%, and 40% showed no significant difference with GTV CT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard. Conclusion:The 68 Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses.