Endoplasmic reticulum (ER) stress promotes tumor cell escape from immunosurveillance. However, the underlying mechanisms remain unknown. We hypothesized that ER stress induces hepatocellular carcinoma (HCC) cells to release exosomes, which attenuate antitumor immunity by modulating the expression of programmed death ligand 1 (PD‐L1) in macrophages. In this study, we demonstrated that expression of several ER stress markers (glucose‐regulated protein 78, activating transcription factor 6, protein kinase R–like ER kinase, and inositol‐requiring enzyme 1α) was up‐regulated in HCC tissues and negatively correlated with the overall survival and clinicopathological scores in patients with HCC. Expression of ER stress–related proteins positively correlated with CD68+ macrophage recruitment and PD‐L1 expression in HCC tissues. High‐throughput sequencing analysis identified miR‐23a‐3p as one of the most abundant microRNAs in exosomes derived from tunicamycin (TM)‐treated HCC cells (Exo‐TMs). miR‐23a‐3p levels in HCC tissues negatively correlated with overall survival. Treatment with Exo‐TMs up‐regulated the expression of PD‐L1 in macrophages in vitro and in vivo. Bioinformatics analysis suggests that miR‐23a‐3p regulates PD‐L1 expression through the phosphatase and tensin homolog (PTEN)–phosphatidylinositol 3‐kinase–protein kinase B (AKT) pathway. This notion was confirmed by in vitro transfection and coculture experiments, which revealed that miR‐23a‐3p inhibited PTEN expression and subsequently elevated phosphorylated AKT and PD‐L1 expression in macrophages. Finally, coculture of T cells with Exo‐TM–stimulated macrophages decreased CD8+ T‐cell ratio and interleukin‐2 production but increased T‐cell apoptosis in vitro. Conclusion: ER‐stressed HCC cells release exosomes to up‐regulate PD‐L1 expression in macrophages, which subsequently inhibits T‐cell function through an exosome miR‐23a–PTEN–AKT pathway. Our findings provide insight into the mechanism how tumor cells escape from antitumor immunity.

On December 31, 2019, several cases of pneumonia of unknown etiology have been reported in Wuhan, Hubei province, China [1][2][3]. On January 7, 2020, Chinese health authorities confirmed that these cases were associated with a novel coronavirus, which was subsequently named 2019 nCoV by WHO [4]. Previous study [5] reported that virus infection can cause several neurological complications, including polyneuritis, Guillain-Barre syndrome (GBS), meningitis, encephalomyelitis, and encephalopathy. We describe a rare case of 2019CoV infection and acute uni lateral isolated oculomotor nerve palsy. In this case, the diagnosis was made based on the chest computed CT mani festations and throat swab sample test.A 62yearold man was admitted to our department with a 5day history of persistent diplopia and a droopy left eyelid. During initial hospital assessment, he endorsed limb weak ness and poor spirit. He denied any fever, neck stiffness, headache, cough, shortness of breath, chest pain, or photo phobia. He had a history of alcohol and tobacco use, type II diabetes mellitus and hypertension (both well controlled by drugs), and lacunar infarction (without sequela).On examination, it revealed body temperature of 36.5 °C (97.7 °F), blood pressure of 142/72 mmHg, respiratory rate of 22 breaths per minute, pulse rate of 70 beats per minute and oxygen saturation of 95% while the patient was breath ing ambient air. There were coarse rales in the both lung field. The patient was alert and oriented to person, place, and time. His speech was fluent. Pupils were 3 mm and equally reactive to light. He had complete ptosis of the left eyelid, and his left eye was down and out at rest. The left eye was unable to adduct and look up. Left eyelid closure was weak. Both eyes were without orbital pain. Hearing was intact. No palate or tongue weakness/asymmetry was noted. Strength in upper and lower limbs was 5/5 throughout. Deep tendon reflexes were 2 + and symmetric throughout. Toes were downgoing bilaterally. Sensation to light touch, pinprick, and temperature was intact on the two sides. No pathologi cal reflection of Babinski's sign is induced. Romberg test was negative when eyes were open or close. The sign of meningeal irritation was negative. The laboratory results showed white blood cell count: 9.45 × 10 9 /L and neutrophil percentage: 69.6% were normal. Random blood glucose was 9.2 mmol/L (normal range 0-11.1 mmol/L) and hemoglobin A1C was 6.1% (normal range 0-6.2%). Respiratory patho gens test showed influenza A and B virus antigen, myco plasma pneumonia antigen, adenovirus antigen, and syncy tial virus were all negative. However, inflammatory markers were significantly elevated Creactive protein (142.21 mg/L; normal range 0-10 mg/L) and Serum amyloid A protein (300.00 mg/L; normal range 0-10 mg/L). Erythrocyte sedimentation rate was elevated (91.6 mm/h; normal range 0-15 mm/h). Magnetic resonance imaging (MRI) was not found new infarction, bleeding of brainstem or pituitary apo plexy, tumor, and multiple sclerosis (Figs. 1, 2). Ma...

Background Long noncoding RNAs (lncRNAs) play important roles in cancer development and therapeutic resistance. However, the role of small nucleolar RNA host gene 16 (SNHG16) in the development of hepatocellular carcinoma (HCC) remains largely unknown. Material/Methods In situ hybridization (ISH) staining was performed to detect the expression level of SNHG16 in HCC tissues and adjacent non-cancerous tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the level of SNHG16 in HCC samples, adjacent non-cancerous tissues and HCC cell lines. Transwell assay was performed to investigate the migration and invasion ability of HCC cells. Cell viability assays were performed to determine the ability of proliferation and sorafenib resistance of HCC cells. Results We found that SNHG16 was upregulated in HCC tissues and cell lines and that it was negatively correlated with survival time in HCC patients. Univariate and multivariate analyses revealed that SNHG16 was a significant and independent predictor for the overall survival of HCC patients. Furthermore, downregulation of SNHG16 inhibited proliferation, migration, invasion, and sorafenib resistance in hepatocellular carcinoma cell lines. Conclusions Our findings revealed that lncRNA SNHG16 could be used as an oncogene to predict the outcome of hepatocellular carcinoma.

Highlights This study showed high prevalence of psychological disorders and associated factors encompassed all phases of the Chinese COVID-19 epidemic, extending from early in the outbreak to the present remission for the first time. Our findings raise special concerns about public mental health, especially among non-HCWs involved at the remission stage of the COVID-19 epidemic.