Highlights d 11,394 proteins are quantified in autopsy samples from 7 organs in 19 COVID-19 patients d Elevated expression of cathepsin L1 is detected in the COVID-19 lung tissue d Dysregulation of angiogenesis, coagulation, and fibrosis is detected in multiple organs d Systemic metabolic dysregulation is detected in multiple organs

Decoration of phytochemicals contributes to the majority of metabolic diversity in nature, whereas how this process alters the biological functions of their precursor molecules remains to be investigated. Flavones, an important yet overlooked subclass of flavonoids, are most commonly conjugated with sugar moieties by UDP-dependent glycosyltransferases (UGTs). Here, we report that the natural variation of rice flavones is mainly determined by OsUGT706D1 (flavone 7-O-glucosyltransferase) and OsUGT707A2 (flavone 5-O-glucosyltransferase). UV-B exposure and transgenic evaluation demonstrate that their allelic variation contributes to UV-B tolerance in nature. Biochemical characterization of over 40 flavonoid UGTs reveals their differential evolution in angiosperms. These combined data provide biochemical insight and genetic regulation into flavone biosynthesis and additionally suggest that adoption of the positive alleles of these genes into breeding programs will likely represent a potential strategy aimed at producing stress-tolerant plants.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.

Flavonoids are widely distributed in plants and play important roles in many biological processes. Citrus fruits are rich dietary sources of flavonoids. However, there have been very few reports about the comprehensive metabolic profile and natural diversity of flavonoids in different tissues of various Citrus cultivars. In this study, based on the 7416 metabolic signals detected with non-targeted metabolomics approach, Principal Component Analysis revealed the flavedo has the largest differences from other tissues in metabolite levels; as many as 198 flavonoid signals were then detected in 62 Citrus germplasms from 5 species mainly cultivated worldwide, while 117 flavonoids were identified, including 39 polymethoxylated flavonoids (PMFs), 7 flavones, 10 C-O-glycosylflavonoids, 44 O-glycosylflavonoids, 10 C-glycosylflavonoids and 7 newly annotated O-glycosylpolymethoxylated flavonoids. Tissue-specific accumulations were observed: O-glycosylated flavonoids were abundant in all fruit tissues, while PMFs were accumulated preferentially in the flavedo. Among different species, mandarins had the highest levels of PMFs and O-glycosylpolymethoxylated flavonoids, followed by sweet oranges. Based on the flavonoid profiles, 62 germplasms could be clearly grouped into five distinct clusters via hierarchical clustering analysis, which were perfectly matched with their species, with sweet oranges and mandarins clustering closely and being further away from other three species.

Aims: Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been deemed as a global pandemic by World Health Organization. While diffuse alveolar damage (DAD) is recognized to be the primary manifestation COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest due to growing concerns regarding the potential long-term complications in prolonged survivors. Methods: Here we report a detailed histopathologic study of thirty autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February to March, 2020. Results: The mean age was 69 years, with twenty (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median=42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organizing (25%), and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (p=0.034) and they had a longer duration of illness (p=0.033), hospitalization (p=0.037) and mechanical ventilation (p=0.014) compared to those with acute DAD. Patients with organizing DAD had a longer duration of illness (p=0.032) and hospitalization (p=0.023) compared to those with acute DAD. Conclusions: COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiologic follow-up studies.