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The upregulated autophagy fuels the activation of hepatic stellate cells (HSCs) to promote hepatic fibrosis. However, the lack of specific inhibitors targeting autophagy and high requirements for cell targeting impede the application of antifibrotic therapy that targets autophagy. RNA interference (RNAi)-based short interfering RNA (siRNA) provides an approach to specifically inhibit autophagy. The therapeutic potential of siRNA, however, is far from being exploited due to the lack of safe and effective delivery vehicles. The cytoplasmic delivery of siRNA is essential for RNAi, and the intracellular trafficking pathway of vehicles determines the fate of siRNA. Unfortunately, the lysosomal degradation pathway, the intracellular fate of most gene vehicles, impedes RNAi efficiency. Inspired by the trafficking pathway of some viruses infecting cells, KDEL-grafted chondroitin sulfate (CK) was designed to alter the intracellular delivery fate of siRNA. The well-designed CD44–Golgi–ER trafficking pathway of CK was realized by triple cascade targeting including (1) CD44 targeting mediated by chondroitin sulfate, (2) Golgi apparatus targeting mediated by the caveolin-mediated endocytic pathway, and (3) endoplasmic reticulum (ER) targeting mediated by coat protein I (COP I) vesicles. CK was adsorbed on the complex of cationic liposomes (Lip) encapsulating siRNA targeting autophagy-related gene 7 (siATG7) to afford Lip/siATG7/CK. Lip/siATG7/CK functions as a drifting boat that follows the CD44–Golgi–ER flow and travels downstream to its destination (ER), bypassing the lysosomal degradation pathway and endowing HSCs with excellent RNAi efficiency. The efficient downregulation of ATG7 leads to an excellent antifibrotic effect both in vitro and in vivo.

Objectives This study aimed to assess the diagnostic value of human epididymal protein 4 (HE4), a potential novel biomarker for lung cancer, and its combined detection with five other conventional biomarkers in lung cancer diagnosis and subtyping.Methods In this retrospective study, 115 lung cancer patients, 50 patients with benign pulmonary disease, and 50 healthy controls were included. Serum HE4, progastrin-releasing peptide (ProGRP), squamous cell carcinoma (SCC) antigen, cytokeratin-19 fragment (CYFRA21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) were analyzed using the electrochemiluminescence immunoassay and chemiluminescence immunoassay. The receiver operating characteristic curve was performed to analyze the diagnostic efficacy of individual biomarkers in identifying both lung cancer and its histologic subtypes.Results All six biomarkers showed significantly elevated levels in the lung cancer group compared to both benign pulmonary disease and control groups (P < 0.05). Among the biomarkers evaluated, HE4 exhibited the highest diagnostic performance for lung cancer, lung adenocarcinoma, and lung squamous cell carcinoma with area under the curve (AUC) values of 0.921, 0.891, and 0.937, respectively. ProGRP was the optimal biomarker for small cell lung cancer with an AUC of 0.973. The combination of all six biomarkers yielded the largest AUCs in the diagnosis of lung cancer subtypes (0.937 for lung adenocarcinoma, 0.998 for lung squamous cell carcinoma, and 0.985 for small cell lung cancer). Furthermore, specific combinations, such as HE4 + CEA, HE4 + SCC, and ProGRP + HE4 + NSE, showed strong diagnostic performance in lung cancer.Conclusions HE4 and its combined detection held substantial clinical significance in the diagnosis of lung cancer and its histologic subtyping, especially for lung adenocarcinoma and lung squamous cell carcinoma.

A new TEMPO-catalyzed aminophosphinoylation of ethers with amines and H-phosphine oxides was developed for the synthesis of α-aminophosphine oxides. This metal-free aminophosphinoylation reaction could be conducted under mild conditions through tandem C(sp3)–H and C(sp3)–O bond cleavage. The present method offers a facile and efficient approach to broad range of α-aminophosphine oxide derivatives in moderate to good yields with excellent functional group tolerance.

As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a selective advantage for the survival and proliferation of cancer cells. Due to frequent aberration of upstream proto-oncogenes and tumor suppressors, hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent inducer of the Warburg effect. Here, we report that overexpression of a glycolytic enzyme, phosphoglyceric acid mutase-1 (PGAM1), is critical to oncogenic mTOR-mediated Warburg effect. mTOR stimulated PGAM1 expression through hypoxia-inducible factor 1α-mediated transcriptional activation. Blockage of PGAM1 suppressed mTOR-dependent glycolysis, cell proliferation, and tumorigenesis. PGAM1 expression and mTOR activity were positively correlated in non-small cell lung cancer (NSCLC) tissues and PGAM1 abundance was an adverse predictor for patient survival. PGAM1 is thus a downstream effector of mTOR signaling pathway and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg effect observed in cancer. We consider PGAM1 as a novel prognostic biomarker for NSCLC and a therapeutic target for cancer.

To help researchers selecting appropriate data mining models to provide better evidence for the clinical practice of Traditional Chinese Medicine (TCM) diagnosis and therapy.