The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

Viral infection triggers the formation of mitochondrial antiviral signaling protein ( MAVS ) aggregates, which potently promote immune signaling. Autophagy plays an important role in controlling MAVS ‐mediated antiviral signaling; however, the exact molecular mechanism underlying the targeted autophagic degradation of MAVS remains unclear. Here, we investigated the mechanism by which RNF 34 regulates immunity and mitophagy by targeting MAVS . RNF 34 binds to MAVS in the mitochondrial compartment after viral infection and negatively regulates RIG ‐I‐like receptor ( RLR )‐mediated antiviral immunity. Moreover, RNF 34 catalyzes the K27‐/K29‐linked ubiquitination of MAVS at Lys 297, 311, 348, and 362 Arg, which serves as a recognition signal for NDP 52‐dependent autophagic degradation. Specifically, RNF 34 initiates the K63‐ to K27‐linked ubiquitination transition on MAVS primarily at Lys 311, which facilitates the autophagic degradation of MAVS upon RIG ‐I stimulation. Notably, RNF 34 is required for the clearance of damaged mitochondria upon viral infection. Thus, we elucidated the mechanism by which RNF 34‐mediated autophagic degradation of MAVS regulates the innate immune response, mitochondrial homeostasis, and infection.

The aim of the study is to investigate the changes of serum leptin and kisspeptin levels in children and adolescents with different pubertal stages and nutritional states. A total of 647 Chinese children and adolescents were recruited, and serum estradiol, testosterone, pituitary gonadotropins, leptin, and kisspeptin levels were measured. The results showed that serum leptin levels of boys in T2 stage were the highest among the five stages, while they showed a gradual increase from T1 to T5 stage in girls and reached the highest in T5 stage (P < 0.05). Conversely, serum kisspeptin levels of boys were higher in T4 and T5 stages than those in T1 stage, while its levels of girls were the highest in T2 stage, 21.4% higher than those in T1 stage (P < 0.05). Both leptin and kisspeptin levels were positively correlated with BMI, WC, and weight in all boys and girls (all P < 0.05). In conclusion, kisspeptin levels were firstly found to be notably changed in pubertal stages and nutritional status in Chinese children and adolescents with a significant sexual dimorphism. Obese/overweight girls had higher kisspeptin levels, and there was a positive correlation between kisspeptin and FSH and LH and obesity-related parameters in all boys and girls.