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Background & aims Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment. Methods We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin. Results Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021). Conclusions More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

The bone marrow microenvironment is composed primarily of immune and stromal cells that play important roles in fracture healing. Although immune cells have been identified in mouse bone marrow, variations in their numbers and type during the fracture healing process remain poorly defined. In this study, single-cell RNA sequencing was used to identify immune cells in fracture tissues, including neutrophils, monocytes, T cells, B cells, and plasma cells. The number of B cells decreased significantly in the early stage of fracture healing. Furthermore, B cells in mice fracture models decreased significantly during the epiphyseal phase and then gradually returned to normal during the epiphyseal transformation phase of fracture healing. The B-cell pattern was opposite to that of bone formation and resorption activities. Notably, B-cell–derived exosomes inhibited bone homeostasis in fracture healing. In humans, a decrease in the number of B cells during the epiphyseal phase stimulated fracture healing. Then, as the numbers of osteoblasts increased during the callus reconstruction stage, the number of B cells gradually recovered, which reduced additional bone regeneration. Thus, B cells are key regulators of fracture healing and inhibit excessive bone regeneration by producing multiple osteoblast inhibitors.

Isatidis Radix, the dried root of Isatidis indigotica Fort, is a traditional heat-clearing and detoxicating herb, which has the antiviral and anti-inflammatory activity and immune regulation. It has been widely used to treat cold, fever, sore throat, mumps, and tonsillitis in clinics. A previous study demonstrated that the acidic fraction of Isatidis Radix (RIAF) had strong anti-inflammatory activity, but the mechanism of action was not well elucidated. Lipopolysaccharide- (LPS-) induced RAW264.7 cells were employed to observe the anti-inflammatory activity of RIAF. The level of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL-6) was determined by enzyme-linked immunosorbent assay kits. Western blot was performed to quantify the expression of extracellular signal-regulated kinase (ERK) 1/2, c-jun NH2-termianl kinase (JNK), p38, inducible NO synthetase (iNOS), cyclooxygenase (COX)-2, andnuclear factor-κB (NF-κB). Immunofluorescence assay and electrophoretic mobility shift assay (EMSA) were used to quantify the translocation and the binding-DNA activity of NF-κB. RIAF could inhibit the secretion of inflammatory cytokines (PGE2, IL-6, IL-1β, and NO, other than TNF-α) in a dose-dependent manner. Further investigation showed that the expression of iNOS and COX-2 induced by LPS were downregulated by treatment with RIAF. Meanwhile, data from the signal pathway exhibited that RIAF significantly suppressed the phosphorylation of ERK1/2, JNK, and p38 and reduced the translocation of NF-κB from the cytoplasm to nucleus, as well as the binding-DNA activity. The anti-inflammatory mechanism of action of RIAF was to reduce inflammation-associated gene expression (iNOS, COX-2, IL-1β, IL-6) by regulating the phosphorylation of the mitogen-activated protein kinases (MAPK) pathway and interventing the activation of the NF-κB pathway, which partly illustrated the basis of treatment of Isatidis Radix on cold, fever, sore throat, mumps, and tonsillitis in clinics.

Baicalin is a natural flavonoid glycoside that confers protection against myocardial ischemia/reperfusion (I/R) injury. However, its mechanism has not been fully understood. This study focused on elucidating the role of ferroptosis in baicalin-generated protective effects on myocardial ischemia/reperfusion (I/R) injury by using the myocardial I/R rat model and oxygen–glucose deprivation/reoxygenation (OGD/R) H9c2 cells. Our results show that baicalin improved myocardial I/R challenge–induced ST segment elevation, coronary flow (CF), left ventricular systolic pressure , infarct area, and pathological changes and prevented OGD/R-triggered cell viability loss. In addition, enhanced lipid peroxidation and significant iron accumulation along with activated transferrin receptor protein 1 (TfR1) signal and nuclear receptor coactivator 4 (NCOA4)-medicated ferritinophagy were observed in in vivo and in vitro models, which were reversed by baicalin treatment. Furthermore, acyl-CoA synthetase long-chain family member 4 (ACSL4) overexpression compromised baicalin-generated protective effect in H9c2 cells. Taken together, our findings suggest that baicalin prevents against myocardial ischemia/reperfusion injury via suppressing ACSL4-controlled ferroptosis. This study provides a novel target for the prevention of myocardial ischemia/reperfusion injury.

The aim of this study is to investigate the role of microRNA-499 (miR-499) in hepatocellular carcinoma tumor growth and the underlying molecular mechanisms. The expression of miR-499 was significantly decreased in hepatocellular carcinoma tissues compared with that in adjacent normal tissues. Furthermore, miR-499 overexpression in HEPG2 cell was related to the tumor growth in nude mice xenograft models. Likewise, miR-499 mimic or inhibitor decreased or accelerated cell proliferation, respectively. Mechanistically, miR-499 directly targeted the 3′- untranslated region of astrocyte elevated gene-1 and downregulate astrocyte elevated gene-1 expression. Restoration of astrocyte elevated gene-1 expression in hepatocellular carcinoma cells reversed the inhibitory effect of miR-499 on cell growth. In addition, astrocyte elevated gene-1 and miR-499 expression were inversely correlated in human and mice hepatocellular carcinoma tissues. Our study identified miR-499 as a tumor-suppressive miR in hepatocellular carcinoma, thus providing a candidate therapeutic target for the future diagnosis or treatment of hepatocellular carcinoma.

The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31hiendomucinhi (CD31hiEMCNhi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31hi EMCNhi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31hiEMCNhi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31hiEmcnhi vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.

It is generally known that the large formation amount of calcium ferrite is favorable for the iron ore sintering. The effects of sintering temperature and O2 content of inlet gas on the calcium ferrite formation characteristic of typical iron ores, including hematite, limonite, specularite and magnetite, were investigated. And the effect of O2 content on the microstructure of the roasted briquettes was also studied in detail. The results show the amount of calcium ferrite initially increases then decreases with the increase of the sintering temperature. The temperature of maximum calcium ferrite generation amount is determined as follows: for hematite and limonite it is 1275 °C, whereas for specularite and magnetite, 1250 °C. The maximum contents of calcium ferrite for hematite, limonite, specularite and magnetite under the optimal sintering temperature are 73%, 82%, 67% and 63%, respectively. Increasing O2 content of the airflow is advantageous to the formation of calcium ferrite. Relatively, the effect of O2 content on the calcium ferrite formation of magnetite is the most pronounced, while O2 content of inlet gas has little effect on the calcium ferrite formation of limonite.