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There are no known approved pharmacotherapies for non‐alcoholic fatty liver disease (NAFLD) in the clinical setting. Although studies have provided substantial evidence that geranylgeranyl diphosphate synthase (GGPPS) is a potential therapeutic target for the treatment of NAFLD corresponding drug screening is rare. A GGPPS‐targeted inhibitor is identified using a structure‐based virtual small molecule screening method. The interaction of 4‐AZ and GGPPS is detected by microscale thermophoresis. 4‐AZ degradation of GGPPS by the ubiquitin‐proteasome pathway is detected by western blotting. The anti‐steatotic effect of 4‐AZ in vivo is detected by CT. Lipid‐related gene detection is detected by real‐time PCR both in primary hepatocytes and mice. The compound inhibits the accumulation of lipids in primary hepatocytes and decreases lipogenic gene expression through GGPPS. Pharmacological studies show that 4‐AZ can attenuate hepatic steatosis and improve liver injury in high‐fat diet‐induced mice. This data provides a novel application of 4‐AZ NAFLD therapy, proving that the inhibition of GGPPS is a novel strategy for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

(E) Two spEV protein biomarker for noninvasive differential diagnosis of azoospermia (NOA vs. However, the choices for high sensitivity and specificity in the noninvasive differential diagnosis of azoospermia are limited.3 Extracellular vesicles (EVs) are increasingly being considered as a promising source of novel diagnostic biomarkers due to their noninvasive nature and high reproducibility.4 In this study, we revealed that two proteins SLC5A12 and HIST1H2BA from human seminal plasma extracellular vesicle (spEV) could differentially diagnose azoospermia with high sensitivity and specificity. Dear Editor, Azoospermia, which accounts for about 10%-15% of infertile men, is generally classified as obstructive azoospermia (OA) due to male reproductive tract obstruction and nonobstructive azoospermia (NOA) due to testicular failure.1 NOA has three major forms: hypospermatogenesis (HS), germ cell arrest (MA), and Sertoli cell-only (SCO) based on the histopathological examination of testicular tissue.2 An accurate diagnosis of the subtype of azoospermia is crucial and mandatory, as the treatment approach differs between NOA and OA. Thus, significant decrease of spEV SLC5A12 is expected in OA patients, but not NOA patients. [Extracted from the article]