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Chronic adipose tissue inflammation accompanied by macrophage accumulation and activation is implicated in the pathogenesis of insulin resistance and type 2 diabetes in humans. The transcriptional coregulator CREBZF is a key factor in hepatic metabolism, yet its role in modulating adipose tissue inflammation and type 2 diabetes remains elusive. The present study demonstrates that overnutrition‐induced CREBZF links adipose tissue macrophage (ATM) proinflammatory activation to insulin resistance. CREBZF deficiency in macrophages, not in neutrophils, attenuates macrophage infiltration in adipose, proinflammatory activation, and hyperglycemia in diet‐induced insulin‐resistant mice. The coculture assays show that macrophage CREBZF deficiency improves insulin sensitivity in primary adipocytes and adipose tissue. Mechanistically, CREBZF competitively inhibits the binding of IκBα to p65, resulting in enhanced NF‐κB activity. In addition, bromocriptine is identified as a small molecule inhibitor of CREBZF in macrophages, which suppresses the proinflammatory phenotype and improves metabolic dysfunction. Furthermore, CREBZF is highly expressed in ATM of obese humans and mice, which is positively correlated with proinflammatory genes and insulin resistance in humans. This study identifies a previously unknown role of CREBZF coupling ATM activation to systemic insulin resistance and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Bronchoscopic TransParenchymal Nodule Access (BTPNA) technology is mainly used for sampling or ablative treatment of lung parenchymal lesions that cannot be reached by bronchoscopy and its appendages, generally for palliative treatment of some lung tumors. We used BTPNA to treat a 32‐year‐old young woman with pulmonary tuberculosis and successfully perforated her occluded left main bronchus. Her left atelectasis was recovered, and a silicone stent was inserted to preserve the shape of the left main bronchus. [ABSTRACT FROM AUTHOR]

Diterpenoids, including more than 18,000 compounds, represent an important class of metabolites that encompass both phytohormones and some industrially relevant compounds. These molecules with complex, diverse structures and physiological activities, have high value in the pharmaceutical industry. Most medicinal diterpenoids are extracted from plants. Major advances in understanding the biosynthetic pathways of these active compounds are providing unprecedented opportunities for the industrial production of diterpenoids by metabolic engineering and synthetic biology. Here, we summarize recent developments in the field of diterpenoid biosynthesis from medicinal herbs. An overview of the pathways and known biosynthetic enzymes is presented. In particular, we look at the main findings from the past decade and review recent progress in the biosynthesis of different groups of ringed compounds. We also discuss diterpenoid production using synthetic biology and metabolic engineering strategies, and draw on new technologies and discoveries to bring together many components into a useful framework for diterpenoid production. [ABSTRACT FROM AUTHOR]

Background: Data on clinical, laboratory, and radiographic characteristics and risk factors for in‐hospital mortality of lung cancer patients with COVID‐19 are scarce. Here, we aimed to characterize the early clinical features of lung cancer patients with COVID‐19 and identify risk factors associated with in‐hospital mortality. Methods: All consecutive lung cancer patients with laboratory‐confirmed COVID‐19 admitted to 12 hospitals in Hubei province, China, from 3 January to 6 May 2020 were included in the study. Patients without definite clinical outcomes during the period were excluded. Data on initial clinical, laboratory and radiographic findings were compared between survivors and nonsurvivors. Univariable and multivariable logistic regression analyses were used to explore the risk factors associated with in‐hospital mortality. Results: Of the 45 lung cancer patients (median [interquartile range] age, 66 [58–74] years; 68.9% males) included, 34 (75.6%) discharged and 11 (24.4%) died. Fever (73.3%) and cough (53.3%) were the dominant initial symptoms, and respiratory symptoms were common. Lung cancer patients also presented atypical appearances of COVID‐19. In the multivariable analysis, prolonged prolongation prothrombin time (PT) (OR = 2.1, 95% CI: 1.00–4.41, P = 0.0497) and elevated high sensitivity cardiac troponin I (hs‐TNI) (OR = 7.65, 95% CI: 1.24–47.39, P = 0.0287) were associated with an increased risk of in‐hospital mortality. Conclusions: Lung cancer patients with COVID‐19 have high in‐hospital mortality. Prolonged PT and elevated hs‐TNI are independent risk factors for in‐hospital mortality of lung cancer patients with COVID‐19. Key points: Significant findings of the study: Lung cancer patients with COVID‐19 have atypical early symptoms and imaging features.The prolonged prothrombin time and elevated high sensitivity cardiac troponin I are independent risk factors for in‐hospital mortality of lung cancer patients with COVID‐19. What this study adds: This study characterizes the early clinical features of lung cancer patients with COVID‐19 in China, and identifies the risk factors associated with in‐hospital mortality of lung cancer patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Prenylated compounds are pharmacologically attractive natural products that are widely distributed in nature. Prenyltransferases (PTs) could catalyze the transfer of prenyl moieties to aromatic acceptors and increase the structural diversity and biological activity of natural products. In this work, a permissive O‐prenyltransferase AcaPT was discovered from Antrodia camphorata, a precious medicinal mushroom in Taiwan. AcaPT exhibited robust O‐prenylation capability toward structurally diverse drug‐like phenolic compounds, including antrodins, flavonoids, and coumarins. In total, 23 O‐prenylated products were obtained by scaled‐up enzymatic synthesis. AcaPT could be used as an efficient biocatalyst to synthesize O‐prenylated derivatives for drug discovery. [ABSTRACT FROM AUTHOR]

Background and Purpose: Berberine, a compound from rhizome coptidis, is traditionally used to treat gastrointestinal infections, such as bacterial diarrhoea. Recently, berberine was shown to have hypoglycaemic and hypolipidaemic effects. We investigated the mechanisms by which berberine regulates hepatic lipid metabolism and energy expenditure in mice.Experimental Approach: Liver-specific SIRT1 knockout mice and their wild-type littermates were fed a high-fat, high-sucrose (HFHS) diet and treated with berberine by i.p. injection for five weeks. Mouse primary hepatocytes and human HepG2 cells were treated with berberine and then subjected to immunoblotting analysis and Oil Red O staining.Key Results: Berberine attenuated hepatic steatosis and controlled energy balance in mice by inducing autophagy and FGF21. These beneficial effects of berberine on autophagy and hepatic steatosis were abolished by a deficiency of the nutrient sensor SIRT1 in the liver of HFHS diet-fed obese mice and in mouse primary hepatocytes. SIRT1 is essential for berberine to potentiate autophagy and inhibit lipid storage in mouse livers in response to fasting. Mechanistically, the berberine stimulates SIRT1 deacetylation activity and induces autophagy in an autophagy protein 5-dependent manner. Moreover, the administration of berberine was shown to promote hepatic gene expression and circulating levels of FGF21 and ketone bodies in mice in a SIRT1-dependent manner.Conclusions and Implications: Berberine acts in the liver to regulate lipid utilization and maintain whole-body energy metabolism by mediating autophagy and FGF21 activation. Hence, it has therapeutic potential for treating metabolic defects under nutritional overload, such as fatty liver diseases, type 2 diabetes and obesity. [ABSTRACT FROM AUTHOR]