Publications by authors named "Xiaodong Liu"

619 Publications

Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer.

Front Mol Biosci 2021 21;8:675651. Epub 2021 May 21.

Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

To identify whether ferroptosis-related genes play predictive roles in bladder cancer patients and to develop a ferroptosis-related gene signature to predict overall survival outcomes. We downloaded the mRNA expression files and clinical data of 256 bladder samples (188 bladder tumour and 68 nontumour samples) from the GEO database and 430 bladder samples (411 bladder tumour and 19 nontumour samples) from the TCGA database. A multigene signature based on prognostic ferroptosis-related genes was constructed by least absolute shrinkage and selection operator Cox regression analysis in the GEO cohort. The TCGA cohort was used to validate the ferroptosis-related gene signature. Next, functional enrichment analysis, including both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses, was performed to elucidate the mechanism underlying the signature. The ssGSEA scores of 16 immune cells and 13 immune-related pathway activities between the high-risk and low-risk groups were also analysed in our study. Thirty-three (67.3%) ferroptosis-related genes were differentially expressed between bladder tumour samples and nontumour samples in the GEO cohort. The intersection of prognostic ferroptosis-related genes and differentially expressed genes identified four prognostic targets, including ALOX5, FANCD2, HMGCR and FADS2. The least absolute shrinkage and selection operator Cox regression successfully built a 4-gene signature: risk score value = e (each gene's normalized expression * each gene's coefficient). Univariate and multivariate Cox regression analyses were performed in both the GEO and TCGA cohorts to test the independent prognostic value of the 4-gene risk signature. Multivariate Cox regression analysis in the GEO cohort identified age ( < 0.001), grade ( = 0.129) and risk score ( = 0.016) as independent prognostic predictors for overall survival. Multivariate Cox regression analysis in the TCGA cohort also identified age ( = 0.002), stage ( < 0.001) and risk score ( = 0.006) as independent prognostic predictors for overall survival. The type II IFN response was determined to be significantly weakened in the high-risk group in both the GEO and TCGA cohorts. We successfully built a ferroptosis-related gene signature of significant predictive value for bladder cancer. These results suggest a novel research direction for targeted therapy of bladder cancer in the future.
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http://dx.doi.org/10.3389/fmolb.2021.675651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175978PMC
May 2021

Radiotherapy and Cytokine Storm: Risk and Mechanism.

Front Oncol 2021 20;11:670464. Epub 2021 May 20.

School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.

Radiotherapy (RT) shows advantages as one of the most important precise therapy strategies for cancer treatment, especially high-dose hypofractionated RT which is widely used in clinical applications due to the protection of local anatomical structure and relatively mild impairment. With the increase of single dose, ranging from 2~20 Gy, and the decrease of fractionation, the question that if there is any uniform standard of dose limits for different therapeutic regimens attracts more and more attention, and the potential adverse effects of higher dose radiation have not been elucidated. In this study, the immunological adverse responses induced by radiation, especially the cytokine storm and the underlying mechanisms such as DAMPs release, pro-inflammatory cytokine secretion and cGAS-STING pathway activation, will be elucidated, which contributes to achieving optimal hypofractionated RT regimen, improving the killing of cancer cells and avoiding the severe side effects.
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http://dx.doi.org/10.3389/fonc.2021.670464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173139PMC
May 2021

A Whole-Body Physiologically Based Pharmacokinetic Model Characterizing Interplay of OCTs and MATEs in Intestine, Liver and Kidney to Predict Drug-Drug Interactions of Metformin with Perpetrators.

Pharmaceutics 2021 May 11;13(5). Epub 2021 May 11.

Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.

Transmembrane transport of metformin is highly controlled by transporters including organic cation transporters (OCTs), plasma membrane monoamine transporter (PMAT), and multidrug/toxin extrusions (MATEs). Hepatic OCT1, intestinal OCT3, renal OCT2 on tubule basolateral membrane, and MATE1/2-K on tubule apical membrane coordinately work to control metformin disposition. Drug-drug interactions (DDIs) of metformin occur when co-administrated with perpetrators via inhibiting OCTs or MATEs. We aimed to develop a whole-body physiologically based pharmacokinetic (PBPK) model characterizing interplay of OCTs and MATEs in the intestine, liver, and kidney to predict metformin DDIs with cimetidine, pyrimethamine, trimethoprim, ondansetron, rabeprazole, and verapamil. Simulations showed that co-administration of perpetrators increased plasma exposures to metformin, which were consistent with clinic observations. Sensitivity analysis demonstrated that contributions of the tested factors to metformin DDI with cimetidine are gastrointestinal transit rate > inhibition of renal OCT2 ≈ inhibition of renal MATEs > inhibition of intestinal OCT3 > intestinal pH > inhibition of hepatic OCT1. Individual contributions of transporters to metformin disposition are renal OCT2 ≈ renal MATEs > intestinal OCT3 > hepatic OCT1 > intestinal PMAT. In conclusion, DDIs of metformin with perpetrators are attributed to integrated effects of inhibitions of these transporters.
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http://dx.doi.org/10.3390/pharmaceutics13050698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151202PMC
May 2021

Established Beta Amyloid Pathology Is Unaffected by TREM2 Elevation in Reactive Microglia in an Alzheimer's Disease Mouse Model.

Molecules 2021 May 4;26(9). Epub 2021 May 4.

Faculty of Medicine, School of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong.

Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer's disease (AD). However, findings on the effects of TREM2 on Aβ deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates Aβ pathology in TgCRND8 mice. We found that peripheral nerve injury resulted in a robust elevation of TREM2 exclusively in reactive microglia in the ipsilateral spinal cord of aged TgCRND8 mice at the age of 20 months. TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for at least 28 days. Compared to the contralateral side, neither amyloid beta plaque load nor soluble Aβ40 and Aβ42 levels were attenuated upon TREM2 induction. We further showed direct evidence that TREM2 elevation in reactive microglia did not affect amyloid-β pathology in plaque-bearing TgCRND8 mice by applying anti-TREM2 neutralizing antibody to selectively block TREM2. Our results question the ability of TREM2 to ameliorate established Aβ pathology, discouraging future development of disease-modifying pharmacological treatments targeting TREM2 in the late stage of AD.
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http://dx.doi.org/10.3390/molecules26092685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125360PMC
May 2021

N, P, and COD conveyed by urban runoff: a comparative research between a city and a town in the Taihu Basin, China.

Environ Sci Pollut Res Int 2021 Jun 1. Epub 2021 Jun 1.

School of Civil Engineering, Nanjing Forestry University, Nanjing, 210037, China.

Stormwater runoff containing various pollutants exerts adverse effects on receiving water bodies and deteriorates the urban aquatic environment. Although numerous studies have been conducted on runoff pollution, research comparing its characteristics in cities with those in towns is rare in the literature. To close this gap, the present study was conducted. The instantaneous concentrations of ammonia-N, TN, TP, and COD during the rainfall events in the town were higher than those in the city in most conditions. The outfall concentrations increased with the increase of rainfall intensity. EMCs (the average value of EMC) and CV (coefficient of variation) of TN and DTN in the town were higher than those in the city, which may lie in the differences of urban environment planning and management, road cleaning methods, garbage disposal methods, industrial enterprise, etc. On the one hand, EMCs and CV of TP in the city's industrial areas were lowest among three functional areas, while on the other hand, in the town it was in the commercial areas rather than the industrial areas that EMCs and CV were the lowest, which may be caused by the low level of economic development of small towns in China. The concentrations of COD in the town were generally higher than that in the city. Compared with the city, the correlation among COD and various forms of N was stronger in the town, which may illustrate a stronger similarity of pollutant sources in the town. According to the results, road runoff in the town contributed more to urban aquatic pollution; thus, further research should concentrate on this particular type of runoff.
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http://dx.doi.org/10.1007/s11356-021-14565-3DOI Listing
June 2021

Overexpression of Tumour Necrosis Factor-α-Induced Protein 8 is Associated with Prognosis in Colon Cancer.

Cancer Manag Res 2021 18;13:4055-4065. Epub 2021 May 18.

Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.

Purpose: The present study aimed to examine the association of tumour necrosis factor-α-induced protein 8 (TIPE) expression levels with clinicopathological features and prognosis of patients with colon cancer following surgery.

Patients And Methods: The present study included 200 patients with colon cancer who underwent colon resection between June 2011 and October 2012. All follow-ups were censored in July 2020, with a median follow-up time of 62.25 months. Kaplan-Meier survival curve analysis and Cox regression analysis were used to determine predictors for the overall survival rate.

Results: High expression of TIPE was associated with lymph node metastasis, higher Dukes' stage and right-sided colon cancer (RCC). An exploratory subgroup analysis found that high expression of TIPE was associated with age ≥65, lymphatic invasion and higher Dukes' stage only in the RCC group (<0.05), whereas no similar trend was observed in the left-sided colon cancer (LCC) subgroup. Age ≥65, differentiation, lymph node metastasis and TIPE expression levels were independent prognostic factors influencing the survival rate of patients with colon cancer following surgery in multivariate Cox analysis (<0.05). ROC curve analysis showed that the immunoreactive score of TIPE had good predictive value for five-year survival rates (AUC=0.727) and lymph node metastasis (AUC=0.760) among patients with RCC. Survival analysis revealed that the expression of TIPE had a significant impact on survival, and higher expression levels suggested a worse prognosis.

Conclusion: This study demonstrated that TIPE may be a novel biomarker for predicting the survival outcome and lymph node metastasis. TIPE was overexpressed in colon cancer tissue and significantly associated with poor patient survival, especially in patients with RCC.
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http://dx.doi.org/10.2147/CMAR.S297451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147554PMC
May 2021

Transcriptional signature in microglia associated with Aβ plaque phagocytosis.

Nat Commun 2021 05 21;12(1):3015. Epub 2021 May 21.

Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.

The role of microglia cells in Alzheimer's disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4) and non-containing (XO4) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4 microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4 microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4 microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4 microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
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http://dx.doi.org/10.1038/s41467-021-23111-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140091PMC
May 2021

The effect of concomitant chronic kidney disease on the recurrence of atrial fibrillation after catheter ablation: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 May;100(20):e25903

Department of Emergency, Suzhou Municipal Hospital, Anhui, China.

Background: Some new trials have reported the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation. Limited by small number of studies and insufficient outcomes, previous meta-analyses also failed to draw a consistent conclusion on this topic. We thus conducted a new meta-analysis to systematically analyze the effect of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation.

Methods: Two independent investigators followed The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to conduct the present meta-analysis. From the inception to June 2021, the EMBASE, PubMed, Web of Science, and Cochrane Library electronic databases were searched using the key phrases "atrial fibrillation," "chronic kidney disease," "catheter ablation," "renal failure," "renal function," "renal insufficiency," "end-stage renal disease," and "dialysis" for all relevant English-language trials. Observational or randomized controlled trial focusing on assessing the effectiveness of chronic kidney disease on recurrence of atrial fibrillation following catheter ablation was included. P < .05 was set as the significance level.

Results: Our hypothesis was that chronic kidney disease is associated with increased atrial fibrosis and a higher risk of arrhythmia recurrence and that restoration of normal rhythm through catheter ablation is associated with improved kidney function.

Registration Number: 10.17605/OSF.IO/3WJAE.
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http://dx.doi.org/10.1097/MD.0000000000025903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137086PMC
May 2021

Alterations of Cytochrome P450s and UDP-Glucuronosyltransferases in Brain Under Diseases and Their Clinical Significances.

Front Pharmacol 2021 21;12:650027. Epub 2021 Apr 21.

Center of Pharmacokinetics and Metabolism, School of Pharmacy, China Pharmaceutical University, Nanjing, China.

Cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) are both greatly important metabolic enzymes in various tissues, including brain. Although expressions of brain CYPs and UGTs and their contributions to drug disposition are much less than liver, both CYPs and UGTs also mediate metabolism of endogenous substances including dopamine and serotonin as well as some drugs such as morphine in brain, demonstrating their important roles in maintenance of brain homeostasis or pharmacological activity of drugs. Some diseases such as epilepsy, Parkinson's disease and Alzheimer's disease are often associated with the alterations of CYPs and UGTs in brain, which may be involved in processes of these diseases via disturbing metabolism of endogenous substances or resisting drugs. This article reviewed the alterations of CYPs and UGTs in brain, the effects on endogenous substances and drugs and their clinical significances. Understanding the roles of CYPs and UGTs in brain provides some new strategies for the treatment of central nervous system diseases.
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http://dx.doi.org/10.3389/fphar.2021.650027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097730PMC
April 2021

Metabolomics screening of serum biomarkers for occupational exposure of titanium dioxide nanoparticles.

Nanotoxicology 2021 May 7:1-18. Epub 2021 May 7.

Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China.

Although nanotoxicology studies have shown that respiratory exposure of titanium dioxide nanoparticles (TiO NPs) could induce adverse health effects, limited biomarkers associated with occupational exposure of TiO NPs were reported. The purpose of this study is to screen serum biomarkers among workers occupationally exposed to TiO NPs using metabolomics. Compared with the control group, a total of 296 serum metabolites were differentially expressed in the TiO NPs-exposed group, of which the relative expression of 265 metabolites increased, and the remaining 31 decreased. Three machine learning methods including random forest (RF), support vector machines (SVM), and boruta screened eight potential biomarkers and simultaneously selected a metabolite, Liquoric acid. Through multiple linear regression analysis to adjust the influence of confounding factors such as gender, age, BMI, smoking and drinking, occupational exposure to TiO NPs was significantly related to the relative expression of the eight potential biomarkers. Meanwhile, the receiver operating characteristic curves (ROCs) of these potential biomarkers had good sensitivity and specificity. These potential biomarkers were related to lipid peroxidation, and had biological basis for occupational exposure to TiO NPs. Therefore, it was demonstrated that the serum metabolites represented by Liquoric acid were good biomarkers of occupational exposure to TiO NPs.
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http://dx.doi.org/10.1080/17435390.2021.1921872DOI Listing
May 2021

pH-Controlled Release of Antigens Using Mesoporous Silica Nanoparticles Delivery System for Developing a Fish Oral Vaccine.

Front Immunol 2021 19;12:644396. Epub 2021 Apr 19.

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Science, Fujian Normal University, Fuzhou, China.

The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined . Further, the vaccine immune effects were evaluated in large yellow croaker oral administration. studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine could elicit innate and adaptive immune response, and provide good protection against challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.
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http://dx.doi.org/10.3389/fimmu.2021.644396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089398PMC
April 2021

Effect of dental malocclusion on cerebellar neuron activation via the dorsomedial part of the principal sensory trigeminal nucleus.

Eur J Oral Sci 2021 May 4:e12788. Epub 2021 May 4.

School of Stomatology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.

Occlusion has been proposed to play a role for body posture and balance, both of which are mediated mainly by the cerebellum. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) has direct projection to the cerebellum. The experimental unilateral anterior crossbite (UAC) has an impact on the motor nuclei in the brain stem via trigeminal mesencephalic nucleus (Vme). The current aim was to explore whether UAC has an impact on Vpdm-cerebellum circuit. The inferior alveolar nerve was injected into cholera toxin B subunit (CTb), the cerebellum was injected into fluoro-gold (FG), and the Vpdm was injected into biotinylated dextran amine (BDA) to identify the activation of Vpdm-cerebellum circuit by UAC. Data indicated that there were more neuronal nuclei (NeuN)/CTb/FG triple-labelled neurons and NeuN/CTb/vesicular glutamate transporter 1(VGLUT1) triple-labelled neurons in the Vpdm, and more NeuN/BDA/ VGLUT1 triple-labelled neurons in the cerebellum of rats with UAC than in control rats. The VGLUT1 expression in the Vpdm and cerebellum in the UAC group was higher than that in control rats. These findings indicate an excitatory impact of UAC on the Vpdm-cerebellum pathway and support the role of occlusion for body posture and balance.
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http://dx.doi.org/10.1111/eos.12788DOI Listing
May 2021

Outcomes of Graves' Disease Patients Following Antithyroid Drugs, Radioactive Iodine, or Thyroidectomy as the First-line Treatment.

Ann Surg 2021 Jun;273(6):1197-1206

Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background: The long-term outcomes of first-line choice among ATD, RAI, and thyroidectomy for GD patients remain unclear.

Objective: To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment.

Methods: A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments.

Results: Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality [hazard ratio (HR) = 0.363, 95% confidence interval (CI) = 0.332-0.396], CVD (HR = 0.216, 95% CI = 0.195-0.239), AF (HR = 0.103, 95% CI = 0.085-0.124), psychological disease (HR = 0.279, 95% CI = 0.258-0.301), diabetes (HR = 0.341, 95% CI = 0.305-0.381), and hypertension (HR = 0.673, 95% CI = 0.632-0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95% CI = 0.882-0.982), CVD (HR = 0.784, 95% CI = 0.742-0.828), AF (HR = 0.622, 95% CI = 0.578-0.67), and psychological disease (HR = 0.895, 95% CI = 0.855-0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower Charlson Comorbidity Index score than the other 2 groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively.

Conclusions: GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the 3 treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.
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http://dx.doi.org/10.1097/SLA.0000000000004828DOI Listing
June 2021

Author Correction: Water-flooding characteristics of lithologic reservoir in Ordos basin.

Sci Rep 2021 Apr 21;11(1):9083. Epub 2021 Apr 21.

State Key Laboratory of Continental Dynamics, Department of Geology, Northwest University, Xi'an, 710069, China.

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http://dx.doi.org/10.1038/s41598-021-88763-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060347PMC
April 2021

Randomized Controlled Trial Comparing the Short-term Outcomes of Enhanced Recovery After Surgery and Conventional Care in Laparoscopic Distal Gastrectomy (GISSG1901).

Ann Surg 2021 Apr 7. Epub 2021 Apr 7.

Affiliated Hospital of Qingdao University, Department of Gastrointestinal Surgery, China Shandong Provincial Hospital, Department of Gastrointestinal Surgery, China Qilu Hospital of Shandong University, Department of Gastrointestinal Surgery, China Yantai Yuhuangding Hospital, Department of Gastrointestinal Surgery, China Weihai Central Hospital, Department of Gastrointestinal Surgery, China Jining People's Hospital, Department of Gastrointestinal Surgery, China Dongying People's Hospital, Department of Gastrointestinal Surgery, China Qianfoshan Hospital of Shandong Province, Department of Gastrointestinal Surgery, China Second Hospital of Shandong University, Department of Gastrointestinal Surgery, China Qingdao Municipal Hospital, Department of Gastrointestinal Surgery, China Rizhao People's Hospital, Department of Gastrointestinal Surgery, China Weifang People's Hospital, Department of Oncological Surgery, China Weihai Municipal Hospital, Department of Gastrointestinal Surgery, China Section of Surgical Pathophysiology 7621, Rigshospitalet Copenhagen University, Denmark.

Objective: This study aimed to compare the effects of ERAS and conventional programs on short-term outcomes after laparoscopic distal gastrectomy (LDG).

Summary Background Data: Currently, the enhanced recovery after surgery (ERAS) program is broadly applied in surgical areas. Although several benefits of LDG with the ERAS program have been covered, high-level evidence is still limited, specifically in advanced gastric cancer (AGC).

Methods: The present study was designed as a randomized, multicenter, unblinded trial. The enrollment criteria included histologically confirmed cT2-4aN0-3M0 gastric adenocarcinoma. Postoperative complications, mortality, readmission, medical costs, recovery and laboratory outcomes were compared between the ERAS and conventional groups.

Results: Between April 2019 and May 2020, 400 consecutive patients who met the enrollment criteria were enrolled. They were randomly allocated to either the ERAS group (n = 200) or the conventional group (n = 200). After excluding patients who did not undergo surgery or gastrectomy, 370 patients were analyzed. The patient demographic characteristics were not different between the two groups. The conventional group had a significantly longer allowed day of discharge and postoperative hospital stay (6.96 vs 5.83 days, P<0.001; 8.85 vs 7.27 days, P<0.001); a longer time to first flatus, liquid intake and ambulation (3.37 vs 2.52 days, P<0.001; 3.09 vs 1.13 days, P<0.001; 2.85 vs 1.38 days, P<0.001, respectively); and higher medical costs (6826 vs 6328 $, P = 0.027) than the ERAS group. Additionally, patients in the ERAS group were more likely to initiate adjuvant chemotherapy earlier (29 vs 32 days, P = 0.035). There was no significant difference in postoperative complications or in the mortality or readmission rates. Regarding laboratory outcomes, the procalcitonin and C-reactive protein levels on postoperative day (POD) 3 were significantly lower and the hemoglobin levels on POD5 were significantly higher in the ERAS group than in the conventional group.

Conclusion: The ERAS program provides a faster recovery, a shorter postoperative hospitalization length, and lower medical costs after LDG without increasing complication and readmission rates. Moreover, enhanced recovery in the ERAS group enables early initiation of adjuvant chemotherapy.
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http://dx.doi.org/10.1097/SLA.0000000000004908DOI Listing
April 2021

A novel prognostic factor TIPE2 inhibits cell proliferation and promotes apoptosis in pancreatic ductal adenocarcinoma (PDAC).

Int J Med Sci 2021 11;18(9):2051-2062. Epub 2021 Mar 11.

Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People's Republic of China.

Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly discovered negative immune regulator. Studies have shown that TIPE2 causes significant malignant biological effects and is differentially expressed in various malignant tumors. However, the expression and roles of TIPE2 in pancreatic ductal adenocarcinoma (PDAC) are largely unknown. The expression of TIPE2 in PDAC tissues was assessed by immunohistochemistry, qPCR and western blot analysis and related clinicopathological parameters including survival time were analyzed. After overexpression of TIPE2, cell proliferation and apoptosis analysis were conducted, and the associated underlying molecular mechanism was also explored. In the present study, TIPE2 was upregulated in early PDAC tissues, and TIPE2 expression decreased as the tumor progressed (<0.001). TIPE2 expression was negatively associated with tumor size, TNM stage and metastasis of lymph nodes. Furthermore, as an independent risk factor, TIPE2 could be used to predict the survival of patients with PDAC (=0.035). TIPE2 overexpression significantly suppressed the viability, proliferation and induced apoptosis of PDAC cells by inhibiting survivin and increasing the activity of caspase3/7. For the first time, this study demonstrated that TIPE2 is an independent prognostic factor in PDAC. TIPE2 inhibited the proliferation and induced apoptosis via regulating survivin/caspase3/7 signaling pathway. These results indicated that TIPE2 is a potential biomarker for predicting the prognosis of PDAC patients and plays a pivotal role in the progression of PDAC.
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http://dx.doi.org/10.7150/ijms.51497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040395PMC
March 2021

High Chromosomal Stability and Immortalized Totipotency Characterize Long-Term Tissue Cultures of Chinese Ginseng ().

Genes (Basel) 2021 Mar 31;12(4). Epub 2021 Mar 31.

Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.

Chinese ginseng ( C. A. Meyer) is a highly cherished traditional Chinese medicine, with several confirmed medical effects and many more asserted health-boosting functions. Somatic chromosomal instability (CIN) is a hallmark of many types of human cancers and also related to other pathogenic conditions such as miscarriages and intellectual disabilities, hence, the study of this phenomenon is of wide scientific and translational medical significance. CIN also ubiquitously occurs in cultured plant cells, and is implicated as a major cause of the rapid decline/loss of totipotency with culture duration, which represents a major hindrance to the application of transgenic technologies in crop improvement. Here, we report two salient features of long-term cultured callus cells of ginseng, i.e., high chromosomal stability and virtually immortalized totipotency. Specifically, we document that our callus of ginseng, which has been subcultured for 12 consecutive years, remained highly stable at the chromosomal level and showed little decline in totipotency. We show that these remarkable features of cultured ginseng cells are likely relevant to the robust homeostasis of the transcriptional expression of specific genes (i.e., genes related to tissue totipotency and chromosomal stability) implicated in the manifestation of these two complex phenotypes. To our knowledge, these two properties of ginseng have not been observed in any animals (with respect to somatic chromosomal stability) and other plants. We posit that further exploration of the molecular mechanisms underlying these unique properties of ginseng, especially somatic chromosomal stability in protracted culture duration, may provide novel clues to the mechanistic understanding of the occurrence of CIN in human disease.
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http://dx.doi.org/10.3390/genes12040514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067114PMC
March 2021

Inverse hydrogen isotope fractionation indicates heterotrophic microbial production of long-chain n-alkyl lipids in desolate Antarctic ponds.

Geobiology 2021 Jul 2;19(4):394-404. Epub 2021 Apr 2.

Department of Earth, Environmental and Planetary Sciences, Brown University, Providence, RI, USA.

Long-chain (>C ) n-alkyl lipids have long been considered biomarkers for higher plant leaf waxes and widely applied for paleoclimate and paleoenvironmental reconstructions. However, recent experimental and lacustrine sediment studies suggest long-chain n-alkanes and n-alkanoic acids can also be produced by aerobic microbes, probably heterotrophic microbes based on carbon isotope data. Here we show that sedimentary long-chain n-alkanes and n-alkanoic acids in two desolate Antarctic ponds where vascular plants are absent in the surroundings display hydrogen isotopic values up to 300 per mil higher than those of lake water. It is the first time that such strongly inverse or reduced hydrogen isotopic fractionation of lipid biomarkers is observed in natural sediment samples. Based on recent extensive experimental data on microbial hydrogen isotopic fractionation, our data can only be explained by the predominant production of long-chain n-alkanes and n-alkanoic acids from heterotrophic micro-organisms. Together with preliminary 16S rRNA gene sequencing data, our results represent the first unambiguous example of predominant heterotrophic microbial production of long-chain n-alkyl waxes in a natural environment.
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http://dx.doi.org/10.1111/gbi.12441DOI Listing
July 2021

Multi-omic analysis suggests tumor suppressor genes evolved specific promoter features to optimize cancer resistance.

Brief Bioinform 2021 Mar 30. Epub 2021 Mar 30.

Chinese University of Hong Kong and a researcher at the CUHK-Shenzhen Research Institute, China.

Tumor suppressor genes (TSGs) exhibit distinct evolutionary features. We speculated that TSG promoters could have evolved specific features that facilitate their tumor-suppressing functions. We found that the promoter CpG dinucleotide frequencies of TSGs are significantly higher than that of non-cancer genes across vertebrate genomes, and positively correlated with gene expression across tissue types. The promoter CpG dinucleotide frequencies of all genes gradually increase with gene age, for which young TSGs have been subject to a stronger evolutionary pressure. Transcription-related features, namely chromatin accessibility, methylation and ZNF263-, SP1-, E2F4- and SP2-binding elements, are associated with gene expression. Moreover, higher promoter CpG dinucleotide frequencies and chromatin accessibility are positively associated with the ability of TSGs to resist downregulation during tumorigenesis. These results were successfully validated with independent datasets. In conclusion, TSGs evolved specific promoter features that optimized cancer resistance through achieving high expression in normal tissues and resistance to downregulation during tumorigenesis.
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http://dx.doi.org/10.1093/bib/bbab040DOI Listing
March 2021

Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus.

Front Neural Circuits 2021 12;15:638000. Epub 2021 Mar 12.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of Oral Anatomy and Physiology, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme-DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, < 0.05). Our findings demonstrated Vme-DMV circuit which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level.
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http://dx.doi.org/10.3389/fncir.2021.638000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994330PMC
March 2021

Clinical Significance of Lymph Node Micrometastasis in pN0 Gastric Cancer Patients.

Gastroenterol Res Pract 2021 3;2021:6854646. Epub 2021 Mar 3.

Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Purpose: To investigate the relationship between lymph node micrometastasis (LNMM) and clinicopathological factors and to evaluate the prognostic effects of LNMM in pN0 gastric cancer (GC) patients.

Methods: One hundred and seventy-two GC patients who received radical gastrectomy with D2 lymph node dissection were enrolled in the present study. 1371 negative lymph nodes from level 2 station confirmed by pathology were examined. The LNMM was diagnosed by telomeric repeat amplification protocol/enzyme-linked immunosorbent assay (TRAP-ELISA). The relationship between clinicopathological factors and LNMM was investigated by multivariate analysis. Survival analysis was performed to evaluate the effects of LNMM on prognosis.

Results: LNMM was detected in 423 lymph nodes from 72 patients. The results showed that invasion depth (OR = 3.755, = 0.004), TNM staging (OR = 3.152, = 0.002), lymphatic invasion (OR = 2.178, = 0.009), and tumor differentiation (OR = 1.266, = 0.013) were independent risk factors associated with LNMM. Survival analysis showed that patients with LNMM had significantly worse 5-year survival compared with those without LNMM (42% vs. 76.4%, < 0.05). Multivariate analysis demonstrated that LNMM, tumor size, Lauren type, invasion depth, and lymphatic invasion ( < 0.05) were independently factors associated with 5-year survival.

Conclusions: The findings showed that tumor invasion depth, TNM staging, lymphatic invasion, and tumor differentiation were independent risk factors associated with LNMM occurrence. Moreover, LNMM is a clinically negative prognostic factor in pN0 GC patients.
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http://dx.doi.org/10.1155/2021/6854646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946449PMC
March 2021

Impact of drinking Chinese green tea on postoperative short outcomes for gastric cancer: a randomized controlled trial.

Eur J Clin Nutr 2021 Mar 19. Epub 2021 Mar 19.

Department of Gastrointestinal Surgery of Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Early intake after surgery can decrease postoperative ileus. Several studies show coffee can stimulate bowel activity and be safe in patients after elective colectomy, mainly due to caffeine. It was postulated that drinking Chinese green tea as rich caffeine beverage after subtotal distal gastrectomy accelerates postoperative recovery in patients.

Method: This was a single-centre parallel open-label randomized trial. Patients with gastric cancer undergoing robotic or laparoscopic subtotal gastrectomy were randomly allocated to receive drinking Chinese green tea (GT group) or potable water (PW group) after surgery. The primary endpoint was the time to gastrointestinal function recovery and tolerance of solid food, and the secondary endpoints included the incidence of postoperative complications, symptoms of postoperative adverse reaction, length of stay, pain as assessed by analgesic consumption and a visual analogue scale, and fatigue as assessed by a fatigue score model.

Results: A total of 80 patients were recruited, 40 to each group. Patient characteristics were similar in both groups. The GT group showed significantly shorter time to gastrointestinal function recovery compared with PW group to first flatus (47.23 ± 13.46 vs. 76.96 ± 20.35, P < 0.001), first bowel motion (78.70 ± 25.77 vs. 125.76 ± 36.25, P < 0.001) and tolerance of solid food (62.20 ± 16.15 vs. 98.66 ± 20.15, P < 0.001).

Conclusion: Drinking Chinese green tea after robotic or laparoscopic subtotal gastrectomy is safe and promotes postoperative recovery of gastrointestinal function, also was an add method with strengthening analgesia and anti-inflammatory effect in the presence of the Enhance Recovery After Surgery (ERAS) program. Registration number: ChiCTR1800018294 ( http://www.chictr.org.cn ).
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http://dx.doi.org/10.1038/s41430-021-00868-8DOI Listing
March 2021

Modelling human blastocysts by reprogramming fibroblasts into iBlastoids.

Nature 2021 Mar 17;591(7851):627-632. Epub 2021 Mar 17.

Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia.

Human pluripotent and trophoblast stem cells have been essential alternatives to blastocysts for understanding early human development. However, these simple culture systems lack the complexity to adequately model the spatiotemporal cellular and molecular dynamics that occur during early embryonic development. Here we describe the reprogramming of fibroblasts into in vitro three-dimensional models of the human blastocyst, termed iBlastoids. Characterization of iBlastoids shows that they model the overall architecture of blastocysts, presenting an inner cell mass-like structure, with epiblast- and primitive endoderm-like cells, a blastocoel-like cavity and a trophectoderm-like outer layer of cells. Single-cell transcriptomics further confirmed the presence of epiblast-, primitive endoderm-, and trophectoderm-like cells. Moreover, iBlastoids can give rise to pluripotent and trophoblast stem cells and are capable of modelling, in vitro, several aspects of the early stage of implantation. In summary, we have developed a scalable and tractable system to model human blastocyst biology; we envision that this will facilitate the study of early human development and the effects of gene mutations and toxins during early embryogenesis, as well as aiding in the development of new therapies associated with in vitro fertilization.
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http://dx.doi.org/10.1038/s41586-021-03372-yDOI Listing
March 2021

Effect of myeloid ecotropic viral integration site (MEIS) family genes on tumor microenvironment remodeling and its potential therapeutic effect.

Transl Androl Urol 2021 Feb;10(2):594-608

Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Background: The myeloid ecotropic viral integration site (MEIS) family of genes is related to the occurrence, development, and outcome of many cancers. However, its role in the immune and tumor microenvironment (TME) is unclear. This study explored the relationship between the expression of MEIS genes and patient survival, immune subtypes, TME, tumor stem cell correlation, and drug sensitivity in cancer.

Methods: We used The Cancer Genome Atlas pan-cancer data to analyze the expression of the MEIS family genes. Kaplan-Meier analysis and univariate Cox proportional hazard regression model were used to detect the relationship between gene expression and overall survival. Analysis of variance was used to explore the relationship between the MEIS family and the immune components in the tumor, and the ESTIMATE algorithm was used to calculate the proportion and level of tumor-infiltrating immune cells. Spearman and Pearson's correlation tests were carried out to detect the relationship between and the characteristics of tumor stem cells and drug sensitivity.

Results: The MEIS family of genes shows different expression profiles in different cancers, with substantial inter- and intra-cancer heterogeneity. Among them, was upregulated in most cancers, whereas was downregulated. The change in gene expression was usually related to overall survival, but whether a member of the MEIS family was a risk factor or a protective factor was cancer-dependent. Immune component analysis suggested that the role of genes in promoting or inhibiting cancer may be related to different degrees of immune silencing. Further, there were varying degrees of correlation between gene expression and cancer cell stemness characteristics. It was also found that genes, especially and , may be related to chemotherapy resistance.

Conclusions: We explored the expression, prognostic relationship, molecular characteristics, and effects on immunity and TME of the gene family in cancer. Our results suggest that members should be studied as independent entities in different types of cancer. The gene family may be a potential target for cancer therapy, but further experiments are needed to confirm this.
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http://dx.doi.org/10.21037/tau-20-1163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947450PMC
February 2021

Early immune response in large yellow croaker (Larimichthys crocea) after immunization with oral vaccine.

Mol Cell Probes 2021 04 24;56:101708. Epub 2021 Feb 24.

Provincial University Key Laboratory of Cellular Stress Response and Metabolic Regulation, College of Life Sciences, Fujian Normal University, Fuzhou, 350117, China. Electronic address:

Mesoporous silica nanoparticles (MSNs) have been used in the field of biomedicine as antigen carriers and adjuvants for protective antigens. In the present study, an oral nanovaccine against Vibrio alginolyticus was prepared employing MSNs as carriers. The uptake of the dihydrolipoamide dehydrogenase (DLDH) antigens in the intestine of large yellow croaker was evaluated using an immunohistochemistry assay. Additionally, the effects of the nanovaccine on the early immune response in large yellow croaker were investigated via oral vaccination. The presence of the antigens was detected in the mucosa and lamina propria of the foregut, midgut, and hindgut of large yellow croaker at 3 h following oral immunization. The expression levels of cytokines (i.e., lysozyme, IFN-γ, IFITM, TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13) in the intestine, spleen, and head kidney tissues of large yellow croaker before and after the immune challenge were determined via RT-qPCR assay. The obtained results revealed that the expression levels of lysozyme, IFN-γ, IFITM, TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13 in the intestine and head kidney of the vaccinated large yellow croaker, as well as the expression of lysozyme, IL-1β, and IL-10 in the spleen, exhibited time-dependent oscillation regulation patterns. Notably, the nanovaccine immunization could induce early (6 h) and high expression of IFN-γ in the spleen and kidney tissues after the bacterial infection. The current study supplements the available data on the early immune response to fish nanovaccines. It also provides a valuable theoretical basis for the future development of large yellow croaker oral vaccines.
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http://dx.doi.org/10.1016/j.mcp.2021.101708DOI Listing
April 2021

High genetic diversity and low differentiation reflect the ecological versatility of the African leopard.

Curr Biol 2021 May 25;31(9):1862-1871.e5. Epub 2021 Feb 25.

Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark. Electronic address:

Large carnivores are generally sensitive to ecosystem changes because their specialized diet and position at the top of the trophic pyramid is associated with small population sizes. Accordingly, low genetic diversity at the whole-genome level has been reported for all big cat species, including the widely distributed leopard. However, all previous whole-genome analyses of leopards are based on the Far Eastern Amur leopards that live at the extremity of the species' distribution and therefore are not necessarily representative of the whole species. We sequenced 53 whole genomes of African leopards. Strikingly, we found that the genomic diversity in the African leopard is 2- to 5-fold higher than in other big cats, including the Amur leopard, likely because of an exceptionally high effective population size maintained by the African leopard throughout the Pleistocene. Furthermore, we detected ongoing gene flow and very low population differentiation within African leopards compared with those of other big cats. We corroborated this by showing a complete absence of an otherwise ubiquitous equatorial forest barrier to gene flow. This sets the leopard apart from most other widely distributed large African mammals, including lions. These results revise our understanding of trophic sensitivity and highlight the remarkable resilience of the African leopard, likely because of its extraordinary habitat versatility and broad dietary niche.
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http://dx.doi.org/10.1016/j.cub.2021.01.064DOI Listing
May 2021

Trend-Based Granular Representation of Time Series and Its Application in Clustering.

IEEE Trans Cybern 2021 Feb 26;PP. Epub 2021 Feb 26.

Granular computing has been an intense research area over the past two decades, focusing on acquiring, processing, and interpreting information granules. In this study, we focus on the granulation of time series and discover the overall structure of the original time series by clustering the granular time series. During the granulation process, when time series exhibit some trend (up trend, equal trend, or down trend) or consist of a variety of tendencies, the trend is essential to be involved to construct the granular time series. Following the principle of justifiable granularity, we propose to form a series of trend-based information granules to describe the original time series and effectively reduce its dimensionality. Then, the similarity measure between trend-based information granules is provided, and considering the dynamic feature of time-series data, dynamic time warping (DTW) distance is generalized to measure the distance for granular time series. In sum, we show here a novel way of forming trend-based granular time series and the corresponding similarity measure, then based on this, the hierarchical clustering of granular time series is realized. The proposed approach can capture the main essence of time series and help to reduce the computing overhead. Experimental results show that the designed approach can reveal meaningful trend-based information granules, and provide promising clustering results on UCR and real-world datasets.
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http://dx.doi.org/10.1109/TCYB.2021.3054593DOI Listing
February 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Lysosome activation in peripheral blood mononuclear cells and prognostic significance of circulating LC3B in COVID-19.

Brief Bioinform 2021 03;22(2):1466-1475

Shenzhen Center for Disease Control and Prevention, China.

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, causing significant mortality. There is a mechanistic relationship between intracellular coronavirus replication and deregulated autophagosome-lysosome system. We performed transcriptome analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and identified the aberrant upregulation of genes in the lysosome pathway. We further determined the capability of two circulating markers, namely microtubule-associated proteins 1A/1B light chain 3B (LC3B) and (p62/SQSTM1) p62, both of which depend on lysosome for degradation, in predicting the emergence of moderate-to-severe disease in COVID-19 patients requiring hospitalization for supplemental oxygen therapy. Logistic regression analyses showed that LC3B was associated with moderate-to-severe COVID-19, independent of age, sex and clinical risk score. A decrease in LC3B concentration <5.5 ng/ml increased the risk of oxygen and ventilatory requirement (adjusted odds ratio: 4.6; 95% CI: 1.1-22.0; P = 0.04). Serum concentrations of p62 in the moderate-to-severe group were significantly lower in patients aged 50 or below. In conclusion, lysosome function is deregulated in PBMCs isolated from COVID-19 patients, and the related biomarker LC3B may serve as a novel tool for stratifying patients with moderate-to-severe COVID-19 from those with asymptomatic or mild disease. COVID-19 patients with a decrease in LC3B concentration <5.5 ng/ml will require early hospital admission for supplemental oxygen therapy and other respiratory support.
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http://dx.doi.org/10.1093/bib/bbab043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929326PMC
March 2021