The coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in December 2019 and has subsequently spread worldwide. Currently, there is no effective method to cure COVID‐19. Mesenchymal stromal cells (MSCs) may be able to effectively treat COVID‐19, especially for severe and critical patients. Menstrual blood‐derived MSCs have recently received much attention due to their superior proliferation ability and their lack of ethical problems. Forty‐four patients were enrolled from January to April 2020 in a multicenter, open‐label, nonrandomized, parallel‐controlled exploratory trial. Twenty‐six patients received allogeneic, menstrual blood‐derived MSC therapy, and concomitant medications (experimental group), and 18 patients received only concomitant medications (control group). The experimental group was treated with three infusions totaling 9 × 10 7 MSCs, one infusion every other day. Primary and secondary endpoints related to safety and efficacy were assessed at various time points during the 1‐month period following MSC infusion. Safety was measured using the frequency of treatment‐related adverse events (AEs). Patients in the MSC group showed significantly lower mortality (7.69% died in the experimental group vs 33.33% in the control group; P = .048). There was a significant improvement in dyspnea while undergoing MSC infusion on days 1, 3, and 5. Additionally, SpO 2 was significantly improved following MSC infusion, and chest imaging results were improved in the experimental group in the first month after MSC infusion. The incidence of most AEs did not differ between the groups. MSC‐based therapy may serve as a promising alternative method for treating severe and critical COVID‐19.

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Soil microbes provide important ecosystem services. Though the effects of changes in nutrient availability due to fertilization on the soil microbial communities in the topsoil (tilled layer, 0–20 cm) have been extensively explored, the effects on communities and their associations with soil nutrients in the subsoil (below 20 cm) which is rarely impacted by tillage are still unclear. 16S rRNA gene amplicon sequencing was used to investigate bacterial and archaeal communities in a Pup-Calric-Entisol soil treated for 32 years with chemical fertilizer (CF) and CF combined with farmyard manure (CFM), and to reveal links between soil properties and specific bacterial and archaeal taxa in both the top- and subsoil. The results showed that both CF and CFM treatments increased soil organic carbon (SOC), soil moisture (MO) and total nitrogen (TN) while decreased the nitrate_N content through the profile. Fertilizer applications also increased Olsen phosphorus (OP) content in most soil layers. Microbial communities in the topsoil were significantly different from those in subsoil. Compared to the CF treatment, taxa such as Nitrososphaera, Nitrospira, and several members of Acidobacteria in topsoil and Subdivision 3 genera incertae sedis, Leptolinea, and Bellilinea in subsoil were substantially more abundant in CFM. A co-occurrence based network analysis demonstrated that SOC and OP were the most important soil parameters that positively correlated with specific bacterial and archaeal taxa in topsoil and subsoil, respectively. Hydrogenophaga was identified as the keystone genus in the topsoil, while genera Phenylobacterium and Steroidobacter were identified as the keystone taxa in subsoil. The taxa identified above are involved in the decomposition of complex organic compounds and soil carbon, nitrogen, and phosphorus transformations. This study revealed that the spatial variability of soil properties due to long-term fertilization strongly shapes the bacterial and archaeal community composition and their interactions at both high and low taxonomic levels across the whole soil profile.

management philosophy, mission-driven organization, identification, sensemaking, individual outcomes, job involvement, organizational citizenship behavior,

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Background Platinum‐based chemotherapy is effective in inducing shrinkage of primary lung cancer lesions; however, it shows finite therapeutic efficacy in patients suffering from brain metastasis (BM). The intrinsic changes of BM cells, which contribute to the poor results remain unknown. Methods Platinum drug‐sensitivity was assessed by utilizing a preclinical BM model of PC9 lung adenocarcinoma cells in vitro and in vivo. High consumption of glutathione (GSH) and two associated upregulated proteins (GPX4 and GSTM1) in BM were identified by integrated metabolomics and proteomics in cell lines and verified by clinical serum sample. Gain‐of‐function and rescue experiments were implemented to reveal the impact and mechanism of GPX4 and GSTM1 on the chemosensitivity in BM. The interaction between GPX4 and GSTM1 was examined by immunoblotting and immunoprecipitation. The mechanism of upregulation of GPX4 was further uncovered by luciferase reporter assay, immunoprecipitation, and electrophoretic mobility shift assay. Results The derivative brain metastatic subpopulations (PC9‐BrMs) of parental cells PC9 developed obvious resistance to platinum. Radically altered profiles of BM metabolism and protein expression compared with primary lung cancer cells were described and GPX4 and GSTM1 were identified as being responsible for the high consumption of GSH, leading to decreased chemosensitivity by negatively regulating ferroptosis. Besides, GSTM1 was found regulated by GPX4, which was transcriptionally activated by the Wnt/NR2F2 signaling axis in BM. Conclusions Collectively, our findings demonstrated that Wnt/NR2F2/GPX4 promoted acquired chemoresistance by suppressing ferroptosis with high consumption of GSH. GPX4 inhibitor was found to augment the anticancer effect of platinum drugs in lung cancer BM, providing novel strategies for lung cancer patients with BM.

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