Shengfang Ge

Bio: Shengfang Ge is an academic researcher from Shanghai Jiao Tong University. The author has contributed to research in topics: Medicine & Gene silencing. The author has an hindex of 29, co-authored 145 publications receiving 8159 citations.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

The novel roles of circRNAs in human cancer

Abstract: Covalently closed single-stranded circular RNAs (circRNAs) consist of introns or exons and are widely present in eukaryotic cells. CircRNAs generally have low expression levels and relatively stable structures compared with messenger RNAs (mRNAs), most of which are located in the cytoplasm and often act in cell type and tissue-specific manners, indicating that they may serve as novel biomarkers. In recent years, circRNAs have gradually become a hotspot in the field of RNA and cancer research, but the functions of most circRNAs have not yet been discovered. Known circRNAs can affect the biogenesis of cancers in diverse ways, such as functioning as a microRNA (miRNA) sponges, combining with RNA binding proteins (RBPs), working as a transcription factor and translation of proteins. In this review, we summarize the characteristics and types of circRNAs, introduce the biogenesis of circRNAs, discuss the emerging functions and databases on circRNAs and present the current challenges of circRNAs studies.

High prevalence of myopia and high myopia in 5060 Chinese university students in Shanghai.

Abstract: PURPOSE Myopia is an important cause of correctable visual impairment worldwide. Genetic and environmental factors contribute to its development. The population of Chinese university students consists of approximately 30 million young people characterized by academic excellence and similar ages. To date, little is known about their refractive status. Our study is designed to investigate the prevalence of myopia in this specific population. METHODS This is a cross-sectional study of myopia among university students in Shanghai, China; 5083 students from Donghua University were enrolled. All participants first responded to a detailed questionnaire, including questions on ethnicity, birth date, and family history, and then undertook a standardized ophthalmologic examination, including visual acuity, a slit-lamp examination, and non-cycloplegic autorefraction. RESULTS The mean spherical equivalent refraction (SER) of the university students was -4.1 diopters (D). Of the subjects 95.5% were myopic (SER < -0.50 D), 19.5% were highly myopic (SER < -6.0 D), and only 3.3% were emmetropic (-0.5 D ≤ SER ≤ 0.5 D). The postgraduates were more myopic than the undergraduates (96.9% and 94.9%, respectively). Being female (-4.1 ± 2.4 D in female versus -3.8 ± 2.4 D in male subjects), of Han ethnicity (-4.1 ± 2.4 D in Han versus -3.4 ± 2.2 D in minorities), and of older age were associated with a higher probability of myopia only in the undergraduate population. CONCLUSIONS The prevalence of myopia and high myopia in this university student population was high. The refractive status of this population deserves further attention.

Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancers by impairing the MDM2-p53 feedback loop.

Abstract: Dysregulated microRNAs (miRNAs) have an important role in many malignant tumors. However, elucidating the roles of miRNAs in cancer biology, especially in epithelial cancers, remains an ongoing process. In this study, we show that both miR-143 and miR-145, which belong to the same miRNA cluster, can negatively modulate expression of their target gene, MDM2. The miR-143 and miR-145 is posttranscriptionally activated by upregulated p53, thereby generating a short miRNAs-MDM2-p53 feedback loop. Re-expression of these miRNAs suppresses cellular growth and triggers the apoptosis of epithelial cancer, in vitro and in vivo, by enhancing p53 activity via MDM2 turnover. Moreover, the miRNA-dependent MDM2 turnover contributes to the equilibrium of repeated p53 pulses in response to DNA damage stress. These findings suggest that MDM2 dysregulation caused by downregulation of miR-143 and miR-145 contributes to epithelial cancer development and has a key role in regulating cellular proliferation and apoptosis. Re-expression of miR-143 and miR-145 may be a reasonable strategy for treatment of epithelial cancers.

Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene.

Abstract: Tumor suppressor microRNA miR-145 is commonly down-regulated in colon carcinoma tissues, but its specific role in tumors remains unknown. In this study, we identify the Friend leukemia virus integration 1 gene (Fli-1) as a novel target of miR-145. Fli-1 is involved in t(11;22)(q24:q12) reciprocal chromosomal translocation in Ewing sarcoma, and its expression appears to be associated with biologically more aggressive tumors. We demonstrate that miR-145 targets a putative microRNA regulatory element (MRE) in the 3′-UTR of Fli-1, and its abundance is reversely associated with Fli-1 expression in colon cancer tissues and cell lines. Using a luciferase/Fli-1 3′-UTR reporter system, we found that miR-145 down-regulated the reporter activity, and this down-regulation was reversed by anti-miR-145. Mutation of the miR-145 MRE sequence in the Fli-1 3′-UTR abolished the activity of miR-145. miR-145 decreased Fli-1 protein but not the Fli-1 mRNA, suggesting a mechanism of translational regulation. Furthermore, we demonstrate that miR-145 inhibited cell proliferation and sensitized LS174T cells to 5-fluorouracil-induced apoptosis. Taken together, these results suggest that miR-145 functions as a tumor suppressor by down-regulating oncogenic Fli-1 in colon cancer.

The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application.

Abstract: Using news reports and press releases from provinces, regions, and countries outside Wuhan, Hubei province, China, this analysis estimates the length of the incubation period of COVID-19 and its pu...

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Detection of SARS-CoV-2 in Different Types of Clinical Specimens.

Abstract: This study describes results of PCR and viral RNA testing for SARS-CoV-2 in bronchoalveolar fluid, sputum, feces, blood, and urine specimens from patients with COVID-19 infection in China to identify possible means of non-respiratory transmission.

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Abstract: Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China

Abstract: Objective An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods All COVID-19 cases reported through February 11, 2020 were extracted from China’s Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild/mild pneumonia (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic. Key words: 2019 Novel Coronavirus; Outbreak; Epidemiological characteristics