<b><i>Background:</i></b> Primary liver cancer, around 90% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. <b><i>Summary:</i></b> Since the publication of <i>Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2017 Edition)</i> in 2018, additional high-quality evidence has emerged with relevance to the diagnosis, staging, and treatment of liver cancer in and outside China that requires the guidelines to be updated. The new edition <i>(2019 Edition)</i> was written by more than 70 experts in the field of liver cancer in China. They reflect the real-world situation in China regarding diagnosing and treating liver cancer in recent years. <b><i>Key Messages:</i></b> Most importantly, the new guidelines were endorsed and promulgated by the Bureau of Medical Administration of the National Health Commission of the People’s Republic of China in December 2019.

Emerging evidence suggests that 17β-estradiol (E2) and estrogen receptor (ER) signaling are protective against hepatocellular carcinoma (HCC). In our previous study, we showed that E2 suppressed the carcinogenesis and progression of HCC by targeting NLRP3 inflammasome activation, whereas the molecular mechanism by which the NLRP3 inflammasome initiated cancer cell death was not elucidated. The present study aimed to investigate the effect of NLRP3 inflammasome activation on cell death pathways and autophagy of HCC cells. First, we observed an increasing mortality in E2-treated HCC cells, and then apoptotic and pyroptotic cell death were both detected. The mortality of HCC cells was largely reversed by the caspase 1 antagonist, YVAD-cmk, suggesting that E2-induced cell death was associated with caspase 1-dependent pyroptosis. Second, the key role of the NLRP3 inflammasome in autophagy of HCC cells was assessed by E2-induced activation of the NLRP3 inflammasome, and we demonstrated that autophagy was inhibited by the NLRP3 inflammasome via the E2/ERβ/AMPK/mTOR pathway. Last, the interaction of pyroptosis and autophagy was confirmed by flow cytometry methods. We observed that E2-induced pyroptosis was dramatically increased by 3-methyladenine (3-MA) treatment, which was abolished by YVAD-cmk treatment, suggesting that caspase 1-dependent pyroptosis was negatively regulated by autophagy. In conclusion, E2-induced activation of the NLRP3 inflammasome may serve as a suppressor in HCC progression, as it triggers pyroptotic cell death and inhibits protective autophagy.

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SummaryThe guard cell chloroplast is the site of perception of blue light and of photosynthetically active radiation, and of at least one of the mechanisms sensing CO 2 in the guard cell. The guard cell chloroplast has been the focus of intense controversy over its capacity for light sensing and photosynthetic carbon fixation, and the osmoregulatory mechanisms mediating stomatal movements. It is argued here that a primary reason behind these long-lived controversies is the remarkable plasticity of the guard cell, which has resulted in responses being generalized as basic properties when opposite responses appear to be the norm under different environmental or experimental conditions. Examples of guard cell plasticity are described, including variation of chlorophyll fluorescence transients over a daily course, acclimation of the guard cell responses to blue light and CO 2 , the shift from potassium to sucrose in daily courses of osmoregulation and the transduction of red light into different osmoregulatory pathways. Recent findings on the properties of the guard cell chloroplast are also presented, including the role of the chloroplastic carotenoid, zeaxanthin, in blue light photoreception, the blue-green reversibility of stomatal movements, and the involvement of phytochrome in the stomatal response to light in the orchid, Paphiopedilum .© New Phytologist (2002 ) 153 : 415 -424

The purpose of this study was to investigate the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Shanghai Children's Hospital in China. Twenty-two non-duplicate CRKP strains were collected from pediatric patients between March and June in 2014. Antimicrobial susceptibility testing was conducted by the agar dilution method. Beta-lactamases were characterized by polymerase chain reaction (PCR) and DNA sequencing. The transferability of bla NDM-1 was investigated by conjugation experiment. The plasmids bearing antibiotic resistance genes were characterized by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization. Clonal relatedness was evaluated by PFGE and multilocus sequence typing (MLST). The clinical data of patients were retrospectively reviewed. The 22 CRKP strains were resistant to most of the antimicrobial agents tested, except tigecycline and colistin. Overall, 59, 77, and 100 % of these strains were resistant to imipenem, meropenem, and ertapenem, respectively. The bla NDM-1 was positive in 77.3 % (17/22) of the CRKP strains, of which the 16 isolates from inpatients were designated as ST37 (n = 9) and ST76 (n =7) and one isolate from an outpatient belonged to ST846. The 17 bla NDM-1-positive isolates belonged to PFGE type A (n = 9), type C (n = 7), or type B (n = 1). The plasmids bearing bla NDM-1 could be transferred into recipient Escherichia coli J53 through conjugation in 88.2 % (15/17) of the strains. The hybridization results showed that the plasmids carrying the bla NDM-1 gene were approximately 50-240 kb in size. This is the first report of an outbreak caused by NDM-1-producing K. pneumoniae ST76 and ST37 among neonates.

A recent study has discovered that mesenchymal stem cells (MSCs) are recruited into tumors and MSC-derived exosomes in a novel mechanism of cell-to-cell communication in human cancers. Here, in this study, we explore the impact of the microRNA-208a (miR-208a)-enriched exosomes derived from bone marrow-derived mesench- ymal stem cells (BMSCs) on osteosarcoma cells. Human osteosarcoma cells MG-63and Saos-2 were exposed to BMSCs-derived exosomes treated with either miR-208a mimic or inhibitor. The MTT assay, transwell migration assay, and soft agar colony formation assay were used to evaluate the viability, migration, and clonogenicity of osteosarcoma cells. Bioinformatics analysis and dual-luciferase reporter gene assays validated the targeted relationship between miR-208a and PDCD4. Western blot assay was used to detect the expression of PDCD4 and related proteins in the ERK1/2 pathway in osteosarcoma cells. BMSCs communicated with osteosarcoma cells via exosomes. Ectopic expression of miR-208a was shown to increase the viability, migration, and clonogenicity of osteosarcoma cells. Analysis of the exosomal content identified miR-208a as a mediator of the exosomal effects on osteosarcoma cells in part via downregulation of PDCD4 and activating the ERK1/2 pathway. In summary, our study illuminates that BMSC-derived exosomal miR-208a enhances the progression of osteosarcoma. K E Y W O R D Sbone marrow-derived mesenchymal stem cells, exosome, microRNA-208a, osteosarcoma, PDCD4

The Arabidopsis mutant npq1, which cannot accumulate zeaxanthin because of a defective violaxanthin deepoxidase, was used to investigate the role of zeaxanthin in the stomatal response to blue light. Neither dark-adapted nor light-treated guard cells or mesophyll cells of the npq1 mutant contained detectable zeaxanthin. In contrast, wild-type guard cells had a significant zeaxanthin content in the dark and accumulated large amounts of zeaxanthin when illuminated. The well-documented red light enhancement of blue light-stimulated stomatal opening, in which increasing fluence rates of background red light result in increased response to blue light, was used to probe the specific blue light response of Arabidopsis stomata. Stomata from the npq1 mutant did not have a specific blue light response under all fluence rates of background red light tested. On the other hand, stomata from leaves of hy4 (cry 1), an Arabidopsis mutant lacking blue light-dependent inhibition of hypocotyl elongation, had a typical enhancement of the blue light response by background red light. The lack of a specific blue light response in the zeaxanthinless npq1 mutant provides genetic evidence for the role of zeaxanthin as a blue light photoreceptor in guard cells.

To investigate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer, gastric cancer AGS cells were treated with luteolin and/or other chemotherapeutic agents. Cell growth was assessed by MTT assay, cell cycle and apoptosis were assessed by flow-cytometric analysis, and the expression of major proteins regulating cell cycle and apoptosis was also detected. The results showed that luteolin inhibited the growth of gastric cancer cells in a dose- and time-dependent manner. Flow cytometry revealed that the percentage of cells at G2/M phase increased dose-dependently. The protein levels of Cdc2, Cyclin B1 and Cdc25C were reduced and p21/cip1 was up-regulated after the treatment with luteolin. Furthermore, luteolin induced apoptosis in gastric cancer AGS cells. Western blotting showed that luteolin treatment significantly increased the levels of pro-apoptotic proteins, including Caspase-3, 6, 9, Bax, and p53, and decreased the levels of anti-apoptotic protein Bcl-2, thus shifting the Bax/Bcl ratio in favor of apoptosis. It was also demonstrated that a combinational treatment of cisplatin and luteolin induced more effectively cell growth inhibition, compared to cisplatin treatment alone. These findings indicate the anti-proliferative and chemosensitizing effects of luteolin on human gastric cancer AGS cells and luteolin may be a promising candidate agent used in the treatment of gastric cancer.