Publications by authors named "Gen Li"

343 Publications

Mining TCGA Data for Key Biomarkers Related to Immune Microenvironment in Endometrial cancer by Immune Score and Weighted Correlation Network Analysis.

Front Mol Biosci 2021 26;8:645388. Epub 2021 Mar 26.

Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Endometrial cancer (EC) is one of the most lethal gynecological cancers around the world. The aim of this study is to identify the potential immune microenvironment-related biomarkers associated with the prognosis for EC. RNA-seq data and clinical information of EC patients were derived from The Genome Atlas (TCGA). The immune score of each EC sample was obtained by ESTIMATE algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify the interesting module and potential key genes concerning the immune score. The expression patterns of the key genes were then verified the GEPIA database. Finally, CIBERSORT was applied to evaluate the relative abundances of 22 immune cell types in EC. Immune scores were significantly associated with tumor grade and histology of EC, and high immune scores may exert a protective influence on the survival outcome for EC. WGCNA indicated that the black module was significantly correlated with the immune score. Function analysis revealed it mainly involved in those terms related to immune regulation and inflammatory response. Moreover, 11 key genes (APOL3, C10orf54, CLEC2B, GIMAP1, GIMAP4, GIMAP6, GIMAP7, GIMAP8, GYPC, IFFO1, TAGAP) were identified from the black module, validated by the GEPIA database, and revealed strong correlations with infiltration levels of multiple immune cell types, as was the prognosis of EC. In this study, 11 key genes showed abnormal expressions and strong correlations with immune infiltration in EC, most of which were significantly associated with the prognosis of EC. These findings made them promising therapeutic targets for the treatment of EC.
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http://dx.doi.org/10.3389/fmolb.2021.645388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048410PMC
March 2021

Prediction of Freezing of Gait in Parkinson's Disease Using a Random Forest Model Based on an Orthogonal Experimental Design: A Pilot Study.

Front Hum Neurosci 2021 22;15:636414. Epub 2021 Mar 22.

Department of Neurology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

Purpose: The purpose of this study was to introduce an orthogonal experimental design (OED) to improve the efficiency of building and optimizing models for freezing of gait (FOG) prediction.

Methods: A random forest (RF) model was developed to predict FOG by using acceleration signals and angular velocity signals to recognize possible precursor signs of FOG (preFOG). An OED was introduced to optimize the feature extraction parameters.

Results: The main effects and interaction among the feature extraction hyperparameters were analyzed. The false-positive rate, hit rate, and mean prediction time (MPT) were 27%, 68%, and 2.99 s, respectively.

Conclusion: The OED was an effective method for analyzing the main effects and interactions among the feature extraction parameters. It was also beneficial for optimizing the feature extraction parameters of the FOG prediction model.
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http://dx.doi.org/10.3389/fnhum.2021.636414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044955PMC
March 2021

Oxytocin receptor variant rs53576 genotype is associated with dysphoric arousal symptoms of DSM-5 posttraumatic stress disorder in Chinese earthquake survivors.

Chin J Traumatol 2021 Mar 28. Epub 2021 Mar 28.

Laboratory for Traumatic Stress Studies, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, 100101, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, 100049, China.

Purpose: Evidence suggests that the oxytocin receptor gene (OXTR) may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5).

Methods: This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscanKit were used to determine the OXTR rs53576. Multiple regression models were used to analyze the independent and interactive effects of OXTR rs53576 genotype and earthquake exposure on the severity of total PTSD symptoms and different dimensions of PTSD symptoms.

Results: The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (β = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (β = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05).

Conclusion: This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us understand the genetic basis of PTSD.
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http://dx.doi.org/10.1016/j.cjtee.2021.03.007DOI Listing
March 2021

Specific Microbial Taxa and Functional Capacity Contribute to Chicken Abdominal Fat Deposition.

Front Microbiol 2021 17;12:643025. Epub 2021 Mar 17.

Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, Foshan University, Foshan, China.

Genetically selected chickens with better growth and early maturation show an incidental increase in abdominal fat deposition (AFD). Accumulating evidence reveals a strong association between gut microbiota and adiposity. However, studies focusing on the role of gut microbiota in chicken obesity in conventional breeds are limited. Therefore, 400 random broilers with different levels of AFD were used to investigate the gut microbial taxa related to AFD by 16S rRNA gene sequencing of 76 representative samples, and to identify the specific microbial taxa contributing to fat-related metabolism using shotgun metagenomic analyses of eight high and low AFD chickens. The results demonstrated that the richness and diversity of the gut microbiota decrease as the accumulation of chicken abdominal fat increases. The decrease of Bacteroidetes and the increase of Firmicutes were correlated with the accumulation of chicken AFD. The Bacteroidetes phylum, including the genera , , and the species, , , and , were correlated to alleviate obesity by producing secondary metabolites. Several genera of Firmicutes phylum with circulating lipoprotein lipase activity were linked to the accumulation of chicken body fat. Moreover, the genera, and , might positively contribute to fat and energy metabolism, whereas the genus, , was possible to enhance energy capture, and associated to accumulate chicken AFD. These findings provide insights into the roles of the gut microbiota in complex traits and contribute to the development of effective therapies for the reduction of chicken fat accumulation.
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http://dx.doi.org/10.3389/fmicb.2021.643025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010200PMC
March 2021

Prediction of Lower Grade Insular Glioma Molecular Pathology Using Diffusion Tensor Imaging Metric-Based Histogram Parameters.

Front Oncol 2021 10;11:627202. Epub 2021 Mar 10.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Objectives: To explore whether a simplified lesion delineation method and a set of diffusion tensor imaging (DTI) metric-based histogram parameters (mean, 25th percentile, 75th percentile, skewness, and kurtosis) are efficient at predicting the molecular pathology status (MGMT methylation, IDH mutation, TERT promoter mutation, and 1p19q codeletion) of lower grade insular gliomas (grades II and III).

Methods: 40 lower grade insular glioma patients in two medical centers underwent preoperative DTI scanning. For each patient, the entire abnormal area in their b-non (b0) image was defined as region of interest (ROI), and a set of histogram parameters were calculated for two DTI metrics, fractional anisotropy (FA) and mean diffusivity (MD). Then, we compared how these DTI metrics varied according to molecular pathology and glioma grade, with their predictive performance individually and jointly assessed using receiver operating characteristic curves. The reliability of the combined prediction was evaluated by the calibration curve and Hosmer and Lemeshow test.

Results: The mean, 25th percentile, and 75th percentile of FA were associated with glioma grade, while the mean, 25th percentile, 75th percentile, and skewness of both FA and MD predicted IDH mutation. The mean, 25th percentile, and 75th percentile of FA, and all MD histogram parameters significantly distinguished TERT promoter status. Similarly, all MD histogram parameters were associated with 1p19q status. However, none of the parameters analyzed for either metric successfully predicted MGMT methylation. The 25th percentile of FA yielded the highest prediction efficiency for glioma grade, IDH mutation, and TERT promoter mutation, while the 75th percentile of MD gave the best prediction of 1p19q codeletion. The combined prediction could enhance the discrimination of grading, IDH and TERT mutation, and also with a good fitness.

Conclusions: Overall, more invasive gliomas showed higher FA and lower MD values. The simplified ROI delineation method presented here based on the combination of appropriate histogram parameters yielded a more practical and efficient approach to predicting molecular pathology in lower grade insular gliomas. This approach could help clinicians to determine the extent of tumor resection required and reduce complications, enabling more precise treatment of insular gliomas in combination with radiotherapy and chemotherapy.
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http://dx.doi.org/10.3389/fonc.2021.627202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988075PMC
March 2021

Comment on "COVID-19 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review of critically unwell children and the association with underlying comorbidities".

Eur J Pediatr 2021 Mar 25. Epub 2021 Mar 25.

Department of Pharmacy, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No.1314 Riyue Avenue, Qingyang District, Chengdu City, 610041, China.

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http://dx.doi.org/10.1007/s00431-021-04036-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990616PMC
March 2021

Highly efficient C-to-T and A-to-G base editing in a Populus hybrid.

Plant Biotechnol J 2021 Mar 20. Epub 2021 Mar 20.

Department of Plant Science and Landscape Architecture, University of Maryland, College Park, Maryland, USA.

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http://dx.doi.org/10.1111/pbi.13581DOI Listing
March 2021

Postoperative Pulmonary Complications' Association with Sugammadex versus Neostigmine.

Anesthesiology 2021 Mar 17. Epub 2021 Mar 17.

Background: Postoperative residual neuromuscular blockade related to nondepolarizing neuromuscular blocking agents may be associated with pulmonary complications. In this study, the authors sought to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications in comparison with neostigmine.

Methods: Adult patients from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who underwent general anesthesia procedures between January 2010 and July 2019 were included in an observational cohort study. In early 2017, a wholesale switch from neostigmine to sugammadex occurred at Vanderbilt University Medical Center. The authors therefore identified all patients receiving nondepolarizing neuromuscular blockades and reversal with neostigmine or sugammadex. An inverse probability of treatment weighting propensity score analysis approach was applied to control for measured confounding. The primary outcome was postoperative pulmonary complications, determined by retrospective chart review and defined as the composite of the three postoperative respiratory occurrences: pneumonia, prolonged mechanical ventilation, and unplanned intubation.

Results: Of 10,491 eligible cases, 7,800 patients received neostigmine, and 2,691 received sugammadex. A total of 575 (5.5%) patients experienced postoperative pulmonary complications (5.9% neostigmine vs. 4.2% sugammadex). Specifically, 306 (2.9%) patients had pneumonia (3.2% vs. 2.1%), 113 (1.1%) prolonged mechanical ventilation (1.1% vs. 1.1%), and 156 (1.5%) unplanned intubation (1.6% vs. 1.0%). After propensity score adjustment, the authors found a lower absolute incidence rate of postoperative pulmonary complications over time (adjusted odds ratio, 0.91 [per year]; 95% CI, 0.87 to 0.96; P < .001). No difference was observed on the odds of postoperative pulmonary complications in patients receiving sugammadex in comparison with neostigmine (adjusted odds ratio, 0.89; 95% CI, 0.65 to 1.22; P = 0.468).

Conclusions: Among 10,491 patients at a single academic tertiary care center, the authors found that switching neuromuscular blockade reversal agents was not associated with the occurrence of postoperative pulmonary complications.

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http://dx.doi.org/10.1097/ALN.0000000000003735DOI Listing
March 2021

Expression and Purification of a Recombinant Enterotoxin Protein Using Different E. coli Host Strains and Expression Vectors.

Protein J 2021 Apr 15;40(2):245-254. Epub 2021 Mar 15.

School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.

Infection by Enterotoxigenic Escherichia coli is a common cause of diarrhea in animals. The development of vaccines against enterotoxins can effectively control the infection. We have previously constructed a recombinant antigen SLS fused by STa, LTB and STb enterotoxin and it showed a high immunogenicity in mice. Herein, we evaluated the expression of SLS in three different E. coli cells with corresponding plasmids. SLS proteins expressed in E. coli BL21 (DE3) and Rosetta-gami B (DE3) were aggregated as inclusion bodies, and the proteins solubility were not obviously promoted in low temperature combined with adjustment of inducer concentration. In contrast, SLS protein with maltose-binding protein (MBP) yielded from TB1 (DE3) cells were partially soluble. After increasing the IPTG concentration in the medium up to 2 mM and incubating at 37 ℃ for 4 h, the soluble protein yield reached the highest level (4.533 mg/0.2 L culture), which was significantly higher than the expression of SLS protein in Rosetta-gami B (DE3) (P < 0.05). Therefore, the TB1-pMAL expression system can be used for mass extraction and purification of SLS antigen prior to measuring its immunogenicity in pregnant mammals.
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http://dx.doi.org/10.1007/s10930-021-09973-wDOI Listing
April 2021

Reductive C-N Coupling by P/P=O-Catalysis.

Trends Chem 2021 Jan 4;3(1):72-73. Epub 2020 Nov 4.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

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http://dx.doi.org/10.1016/j.trechm.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935090PMC
January 2021

A Ten-N-Methyladenosine (mA)-Modified Gene Signature Based on a Risk Score System Predicts Patient Prognosis in Rectum Adenocarcinoma.

Front Oncol 2020 17;10:567931. Epub 2021 Feb 17.

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Objectives: The study aims to analyze the expression of N-methyladenosine (mA)-modified genes in rectum adenocarcinoma (READ) and identify reliable prognostic biomarkers to predict the prognosis of READ.

Materials And Methods: RNA sequence data of READ and corresponding clinical survival data were obtained from The Cancer Genome Atlas (TCGA) database. N-methyladenosine (mA)-modified genes in READ were downloaded from the "m6Avar" database. Differentially expressed mA-modified genes in READ stratified by different clinicopathological characteristics were identified using the "limma" package in R. Protein-protein interaction (PPI) network and co-expression analysis of differentially expressed genes (DEGs) were performed using "STRING" and Cytoscape, respectively. Principal component analysis (PCA) was done using R. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to functionally annotate the differentially expressed genes in different subgroups. Univariate Cox regression analyses were conducted to identify the powerful independent prognostic factors in READ associated with overall survival (OS). A robust likelihood-based survival model was built using the "rbsurv" package to screen for survival-associated signature genes. The Support Vector Machine (SVM) was used to predict the prognosis of READ through the risk score of survival-associated signature genes. Correlation analysis were carried out using GraphPad prism 8.

Results: We screened 974 differentially expressed mA-modified genes among four types of READ samples. Two READ subgroups (group 1 and group 2) were identified by K means clustering according to the expression of DEGs. The two subgroups were significantly different in overall survival and pathological stages. Next, 118 differentially expressed genes between the two subgroups were screened and the expression of 112 genes was found to be related to the prognosis of READ. Next, a panel of 10 survival-associated signature genes including adamtsl1, csmd2, fam13c, fam184a, klhl4, olfml2b, pdzd4, sec14l5, setbp1, tmem132b was constructed. The signature performed very well for prognosis prediction, time-dependent receiver-operating characteristic (ROC) analysis displaying an area under the curve (AUC) of 0.863, 0.8721, and 0.8752 for 3-year survival rate, prognostic status, and pathological stage prediction, respectively. Correlation analysis showed that the expression levels of the 10 mA-modified genes were positively correlated with that of mA demethylase FTO and ALKBH5.

Conclusion: This study identified potential mA-modified genes that may be involved in the pathophysiology of READ and constructed a novel gene expression panel for READ risk stratification and prognosis prediction.
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http://dx.doi.org/10.3389/fonc.2020.567931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925823PMC
February 2021

The Dual Roles of Human γδ T Cells: Anti-Tumor or Tumor-Promoting.

Front Immunol 2020 16;11:619954. Epub 2021 Feb 16.

College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

γδ T cells are the unique T cell subgroup with their T cell receptors composed of γ chain and δ chain. Unlike αβ T cells, γδ T cells are non-MHC-restricted in recognizing tumor antigens, and therefore defined as innate immune cells. Activated γδ T cells can promote the anti-tumor function of adaptive immune cells. They are considered as a bridge between adaptive immunity and innate immunity. However, several other studies have shown that γδ T cells can also promote tumor progression by inhibiting anti-tumor response. Therefore, γδ T cells may have both anti-tumor and tumor-promoting effects. In order to clarify this contradiction, in this review, we summarized the functions of the main subsets of human γδ T cells in how they exhibit their respective anti-tumor or pro-tumor effects in cancer. Then, we reviewed recent γδ T cell-based anti-tumor immunotherapy. Finally, we summarized the existing problems and prospect of this immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2020.619954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921733PMC
February 2021

Rapid detection of porcine deltacoronavirus and porcine epidemic diarrhea virus using the duplex recombinase polymerase amplification method.

J Virol Methods 2021 Jun 15;292:114096. Epub 2021 Feb 15.

College of Veterinary Medicine of South China Agricultural University, Guangzhou, 510640, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou, 510640, China; Key Laboratory of Comprehensive Prevention and Control for Severe Clinical Animal Diseases of Guangdong Province, Guangzhou, 510640, China. Electronic address:

Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) have emerged and spread throughout the porcine industry in many countries and are economically important pathogens causing diarrhea in sows and acute death in newborn piglets. Therefore, a sensitive diagnostic method would be beneficial for the prevention and control of PEDV and PDCoV infection. However, traditional detection methods have a number of drawbacks. This research aimed to establish a rapid detection method of duplex recombinant enzyme-mediated thermostatic amplification (RT-RPA) for PEDV and PDCoV. In this study, eight pairs of primers were designed for each virus according to the conserved domains of both PEDV and PDCoV from the NCBI Genbank, and one pair of primers was selected for each virus following the test results. After optimization of the reaction time, reaction temperature and primer concentration ratio, the duplex RT-RPA assay amplified a 226-bp fragment specifically for PEDV and a 321-bp fragment specifically for PDCoV. Meanwhile, the specificity and sensitivity of the primers and clinical samples were tested to verify the establishment of the RT-RPA method. The sensitivities of the duplex RT-RPA method for PEDV and PDCoV were 1 × 10 copies/μL. The results were consistent with PCR results and showed that a detection method for PEDV and PDCoV duplex RT-RPA was successfully established. In summary, the duplex recombinase polymerase amplification method could offer a promising alternative to the duplex RT-qPCR for detection of PEDV and PDCoV.
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http://dx.doi.org/10.1016/j.jviromet.2021.114096DOI Listing
June 2021

Dynamic graph embedding for outlier detection on multiple meteorological time series.

Authors:
Gen Li Jason J Jung

PLoS One 2021 18;16(2):e0247119. Epub 2021 Feb 18.

Department of Computer Engineering, Chung-Ang University, Dongjak-gu, Seoul, Republic of Korea.

Existing dynamic graph embedding-based outlier detection methods mainly focus on the evolution of graphs and ignore the similarities among them. To overcome this limitation for the effective detection of abnormal climatic events from meteorological time series, we proposed a dynamic graph embedding model based on graph proximity, called DynGPE. Climatic events are represented as a graph where each vertex indicates meteorological data and each edge indicates a spurious relationship between two meteorological time series that are not causally related. The graph proximity is described as the distance between two graphs. DynGPE can cluster similar climatic events in the embedding space. Abnormal climatic events are distant from most of the other events and can be detected using outlier detection methods. We conducted experiments by applying three outlier detection methods (i.e., isolation forest, local outlier factor, and box plot) to real meteorological data. The results showed that DynGPE achieves better results than the baseline by 44.3% on average in terms of the F-measure. Isolation forest provides the best performance and stability. It achieved higher results than the local outlier factor and box plot methods, namely, by 15.4% and 78.9% on average, respectively.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247119PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891775PMC
February 2021

The chilly climate may increase the chance of infecting COVID-19.

J Infect 2021 Feb 8. Epub 2021 Feb 8.

College of Veterinary Medicine of South China Agricultural University, Guangzhou 510640, China; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, Guangzhou 510640, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.02.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868768PMC
February 2021

Identification of 6 gene markers for survival prediction in osteosarcoma cases based on multi-omics analysis.

Exp Biol Med (Maywood) 2021 Feb 9:1535370221992015. Epub 2021 Feb 9.

Department of Orthopaedics, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.

Multiple-omics sequencing information with high-throughput has laid a solid foundation to identify genes associated with cancer prognostic process. Multiomics information study is capable of revealing the cancer occurring and developing system according to several aspects. Currently, the prognosis of osteosarcoma is still poor, so a genetic marker is needed for predicting the clinically related overall survival result. First, Office of Cancer Genomics (OCG Target) provided RNASeq, copy amount variations information, and clinically related follow-up data. Genes associated with prognostic process and genes exhibiting copy amount difference were screened in the training group, and the mentioned genes were integrated for feature selection with least absolute shrinkage and selection operator (Lasso). Eventually, effective biomarkers received the screening process. Lastly, this study built and demonstrated one gene-associated prognosis mode according to the set of the test and gene expression omnibus validation set; 512 prognosis-related genes ( < 0.01), 336 copies of amplified genes ( < 0.05), and 36 copies of deleted genes ( < 0.05) were obtained, and those genes of the mentioned genomic variants display close associations with tumor occurring and developing mechanisms. This study generated 10 genes for candidates through the integration of genomic variant genes as well as prognosis-related genes. Six typical genes (i.e. MYC, CHIC2, CCDC152, LYL1, GPR142, and MMP27) were obtained by Lasso feature selection and stepwise multivariate regression study, many of which are reported to show a relationship to tumor progressing process. The authors conducted Cox regression study for building 6-gene sign, i.e. one single prognosis-related element, in terms of cases carrying osteosarcoma. In addition, the samples were able to be risk stratified in the training group, test set, and externally validating set. The AUC of five-year survival according to the training group and validation set reached over 0.85, with superior predictive performance as opposed to the existing researches. Here, 6-gene sign was built to be new prognosis-related marking elements for assessing osteosarcoma cases' surviving state.
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http://dx.doi.org/10.1177/1535370221992015DOI Listing
February 2021

Guideline-Discordant Preoperative Gentamicin Dosing and the Risk of Gentamicin Associated Nephrotoxicity in Urologic Surgery.

Urology 2021 Jan 29. Epub 2021 Jan 29.

Department of Urology, Columbia University Irving Medical Center, New York, NY. Electronic address:

Objective: To determine the rate of and predictors for guideline-discordant preoperative gentamicin dosing in urologic surgery and to assess the risk of nephrotoxicity in patients who receive the recommended high-dose prophylaxis.

Materials And Methods: We retrospectively reviewed all adult patients who received preoperative gentamicin for urologic surgery from January 1, 2017 - October 3, 2019. Doses were categorized as guideline-concordant or -discordant using a cutoff of 4.5 mg/kg dosing weight. We used multivariable logistic regression to identify predictors for guideline-discordant dosing. Postoperative kidney injury was assessed using RIFLE criteria.

Results: Among 2134 patients, 89% received a preoperative dose ≤ 4.5 mg/kg. Older age (70+ years) and endoscopic surgery were significant risk factors for guideline-discordant dosing (OR 2.54, P< 0.001; OR 6.21, P<0.001). Among 735 patients with complete data, there was no significant difference in the risk of kidney injury between those who received a dose less than 4.5 mg/kg and those who received a higher dose (OR 0.89, 95% CI: 0.26 - 2.99, P = 0.75).

Conclusion: Preoperative gentamicin is commonly administered at lower than recommended doses for urologic surgery. Older age and endoscopic surgery are significant predictors of guideline-discordant dosing. The risk of kidney injury following high-dose preoperative gentamicin for urologic procedures is likely comparable to the risk at lower doses.
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http://dx.doi.org/10.1016/j.urology.2021.01.037DOI Listing
January 2021

The factor structure of major depressive symptoms in a sample of Chinese earthquake survivors.

BMC Psychiatry 2021 Jan 28;21(1):59. Epub 2021 Jan 28.

Global and Community Mental Health Research Group, New York University (Shanghai), Pudong, Shanghai, China.

Background: Experiencing natural disasters is associated with common mental disorders including major depressive disorder (MDD). However, the latent structure of MDD is widely debated, and few studies tested the MDD factor structure in Chinese natural disaster survivors. Therefore, the aim of the current study was to evaluate the factorial validity of the Patient Health Questionnaire-9 (PHQ-9) for DSM-5 major depressive disorder (MDD) symptoms in Chinese earthquake survivors.

Method: Participants were 1058 Chinese earthquake survivors. Self-reported measures included the PHQ-9 and the Short-Form Health Survey (SF-36). Confirmatory factor analysis (CFA) and structural equation modelling (SEM) was used to examine the latent structure of MDD and the associations between latent factors of MDD and different domains of health-related quality of life (HRQoL), respectively.

Results: In the current sample, the model consisted of somatic and cognitive/affective (non-somatic) factors demonstrated significantly better fit than the other competing MDD models (χ = 173.89, df = 26, CFI = 0.986, TLI = 0.981, RMSEA = 0.073, BIC = 18,091.13). Further SEM analyses indicated that the non-somatic factor was significantly related to both physical (β = - 0.362, p < .01) and psychosocial HRQoL (β = - 0.773, p < .01), while the somatic factor was a uniquely predictor of physical HRQoL (β = - 0.336, p < .01). Furthermore, we found the somatic factor partially mediated the relationship between the cognitive/affective factor and physical HRQoL (all ps < .05).

Conclusions: The MDD symptoms was best captured by a two-factor model comprised of somatic and cognitive/affective factors in Chinese natural disaster survivors. The two MDD factors were differentially associated with physical and psychosocial HRQoL, and the cognitive/affective factor associated physical HRQoL partially through the somatic factor. The current findings increase our understanding of latent structure of MDD symptoms, and carry implications for assessment and intervention of post-disaster mental health problems.
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http://dx.doi.org/10.1186/s12888-020-02993-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841918PMC
January 2021

Research on the measurement of intracranial hemorrhage in rabbits by a parallel-plate capacitor.

PeerJ 2021 5;9:e10583. Epub 2021 Jan 5.

College of Biomedical Engineering, Third Military Medical University (Army Medical University), Chongqing, China.

Intracranial hemorrhage (ICH) carrying extremely high morbidity and mortality can only be detected by CT, MRI and other large equipment, which do not meet the requirements for bedside continuous monitoring and pre-hospital first aid. Since the biological tissues have different dielectric properties except the pure resistances, and the permittivity of blood is far larger than that of other brain tissues, here a new method was used to detect events of change at the blood/tissue volume ratio by measuring of the head permittivity. In this paper, we use a self-made parallel plate capacitor to detect the intracranial hemorrhage in rabbits by contactless capacitance measurement. The sensitivity of the parallel-plate capacitor was also evaluated by the physical solution measurement. The results of physical experiments show that the capacitor can distinguish between three solutions with different permittivity, and the capacitance increased with the increase of one solution between two plates. At the next step in the animal experiment, the capacitance changes caused by 2 ml blood injection into the rabbit brain were measured. The results of animal experiments show that the capacitance was almost unchanged before and after the blood injection, but increased with the increase of the blood injection volume. The increase of capacitance caused by blood injection was much larger than that before and after blood injection ( < 0.01). The experiments show that this method is feasible for the detection of intracranial hemorrhage in a non-invasive and contactless manner.
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http://dx.doi.org/10.7717/peerj.10583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792518PMC
January 2021

Temperature-Dependent Nanomechanical Properties of Adsorbed Poly-NIPAm Microgel Particles Immersed in Water.

Langmuir 2021 Feb 27;37(5):1902-1912. Epub 2021 Jan 27.

School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Chemistry, Division of Surface and Corrosion Science, KTH Royal Institute of Technology, Drottning Kristinas väg 51, SE-100 44 Stockholm, Sweden.

The temperature dependence of nanomechanical properties of adsorbed poly-NIPAm microgel particles prepared by a semibatch polymerization process was investigated in an aqueous environment via indentation-based atomic force microscopy (AFM) methods. Poly-NIPAm microgel particles prepared by the classical batch process were also characterized for comparison. The local mechanical properties were measured between 26 and 35 °C, i.e., in the temperature range of the volume transition. Two different AFM tips with different shapes and end radii were utilized. The nanomechanical properties measured by the two kinds of tips showed a similar temperature dependence of the nanomechanical properties, but the actual values were found to depend on the size of the tip. The results suggest that the semibatch synthesis process results in the formation of more homogeneous microgel particles than the classical batch method. The methodological approach reported in this work is generally applicable to soft surface characterization in situ.
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http://dx.doi.org/10.1021/acs.langmuir.0c03386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879429PMC
February 2021

The histone deacetylase inhibitor PCI-24781 impairs calcium influx and inhibits proliferation and metastasis in breast cancer.

Theranostics 2021 1;11(5):2058-2076. Epub 2021 Jan 1.

Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.

Histone deacetylases (HDACs) are involved in key cellular processes and have been implicated in cancer. As such, compounds that target HDACs or drugs that target epigenetic markers may be potential candidates for cancer therapy. This study was therefore aimed to identify a potential epidrug with low toxicity and high efficiency as anti-tumor agents. : We first screened an epigenetic small molecule inhibitor library to screen for an epidrug for breast cancer. The candidate was identified as PCI-24781 and was characterized for half maximal inhibitory concentration (IC), for specificity to breast cancer cells, and for effects on carcinogenesis and metastatic properties of breast cancer cell lines . A series of in silico and analyses were further performed of PCI-24781 to identify and understand its target. : Screening of an epigenetic inhibitor library in MDA-MB-231 cells, a malignant cancer cell line, showed that PCI-24781 is a potential anti-tumor drug specific to breast cancer. Ca related pathways were identified as a potential target of PCI-24781. Further analyses showed that PCI-24781 inhibited Gαq-PLCβ3-mediated calcium signaling by activating the expression of regulator of G-protein signaling 2 (RGS2) to reduce cell proliferation, metastasis, and differentiation, resulting in cell death in breast cancer. In addition, RGS2 depletion reversed anti-tumor effect and inhibition of calcium influx induced by PCI-24781 treatment in breast cancer cells. : We have demonstrated that PCI-24781 is an effective anti-tumor therapeutic agent that targets calcium signaling by activating RGS2. This study also provides a novel perspective into the use of HDAC inhibitors for cancer therapy.
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http://dx.doi.org/10.7150/thno.48314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797697PMC
January 2021

Modulation of phagosome phosphoinositide dynamics by a Legionella phosphoinositide 3-kinase.

EMBO Rep 2021 Mar 25;22(3):e51163. Epub 2021 Jan 25.

Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

The phagosome harboring the bacterial pathogen Legionella pneumophila is known to be enriched with phosphatidylinositol 4-phosphate (PtdIns4P), which is important for anchoring a subset of its virulence factors and potentially for signaling events implicated in the biogenesis of the Legionella-containing vacuole (LCV) that supports intracellular bacterial growth. Here we demonstrate that the effector MavQ is a phosphoinositide 3-kinase that specifically catalyzes the conversion of phosphatidylinositol (PtdIns) into PtdIns3P. The product of MavQ is subsequently phosphorylated by the effector LepB to yield PtdIns(3,4)P2, whose 3-phosphate is then removed by another effector SidF to generate PtdIns4P. We also show that MavQ is associated with the LCV and the ∆mavQ mutant displays phenotypes in the anchoring of a PtdIns4P-binding effector similar to those of ∆lepB or ∆sidF mutants. Our results establish a mechanism of de novo PtdIns4P biosynthesis by L. pneumophila via a catalysis axis comprised of MavQ, LepB, and SidF on the surface of its phagosome.
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http://dx.doi.org/10.15252/embr.202051163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926237PMC
March 2021

Spontaneous Agglomeration of Fluorinated Janus Particles and Its Effect on the Adsorption Behavior of Oil-Air Surfaces.

Front Chem 2020 8;8:602424. Epub 2021 Jan 8.

Department of Petroleum Engineering, Northeast Petroleum University, Daqing, China.

Based on the Pickering emulsion template method, two types of Janus particles with different relative amphiphilic areas for stabilizing non-aqueous foam were synthesized. In addition, particles with uniformly modified surface were synthesized for comparison. By adjusting oil mixtures, the behavior of particles on the oil-air surface was measured. Moreover, the role of particle agglomerates in surface adsorption process was investigated. Affected by the particle surface contact angle, the surface activity of Janus particles is not always greater than that of uniformly modified particles, which is reflected on delta surface tension and the volume of foam generated. The oil-surface adsorption process of synthesized Janus particles is not only occurred in the form of independent detached particles, but also in the form of particle agglomerates. The adsorption of the particles from the bulk phase to the surface requires the contact angle of the Cassie-Baxter composite surface of the particle agglomerates to be around 90°, but the inherent contact angle of the individual particles is <90°.
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http://dx.doi.org/10.3389/fchem.2020.602424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820900PMC
January 2021

Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15.

J Am Chem Soc 2021 Feb 19;143(4):1699-1721. Epub 2021 Jan 19.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

A growing number of organopnictogen redox catalytic methods have emerged-especially within the past 10 years-that leverage the plentiful reversible two-electron redox chemistry within Group 15. The goal of this Perspective is to provide readers the context to understand the dramatic developments in organopnictogen catalysis over the past decade with an eye toward future development. An exposition of the fundamental differences in the atomic structure and bonding of the pnictogens, and thus the molecular electronic structure of organopnictogen compounds, is presented to establish the backdrop against which organopnictogen redox reactivity-and ultimately catalysis-is framed. A deep appreciation of these underlying periodic principles informs an understanding of the differing modes of organopnictogen redox catalysis and evokes the key challenges to the field moving forward. We close by addressing forward-looking directions likely to animate this area in the years to come. What new catalytic manifolds can be developed through creative catalyst and reaction design that take advantage of the intrinsic redox reactivity of the pnictogens to drive new discoveries in catalysis?
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http://dx.doi.org/10.1021/jacs.0c12816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934640PMC
February 2021

Noninvasive real-time assessment of intracranial pressure after traumatic brain injury based on electromagnetic coupling phase sensing technology.

BMC Neurol 2021 Jan 18;21(1):26. Epub 2021 Jan 18.

Department of Neurosurgery, Southwest Hospital, Army Medical University, 29 Gaotanyan Street, Shapingba District, Chongqing, 400038, China.

Background: To investigate the feasibility of intracranial pressure (ICP) monitoring after traumatic brain injury (TBI) by electromagnetic coupling phase sensing, we established a portable electromagnetic coupling phase shift (ECPS) test system and conducted a comparison with invasive ICP.

Methods: TBI rabbits' model were all synchronously monitored for 24 h by ECPS testing and invasive ICP. We investigated the abilities of the ECPS to detect targeted ICP by feature extraction and traditional classification decision algorithms.

Results: The ECPS showed an overall downward trend with a variation range of - 13.370 ± 2.245° as ICP rose from 11.450 ± 0.510 mmHg to 38.750 ± 4.064 mmHg, but its change rate gradually declined. It was greater than 1.5°/h during the first 6 h, then decreased to 0.5°/h and finally reached the minimum of 0.14°/h. Nonlinear regression analysis results illustrated that both the ECPS and its change rate decrease with increasing ICP post-TBI. When used as a recognition feature, the ability (area under the receiver operating characteristic curve, AUCs) of the ECPS to detect ICP ≥ 20 mmHg was 0.88 ± 0.01 based on the optimized adaptive boosting model, reaching the advanced level of current noninvasive ICP assessment methods.

Conclusions: The ECPS has the potential to be used for noninvasive continuous monitoring of elevated ICP post-TBI.
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http://dx.doi.org/10.1186/s12883-021-02049-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812649PMC
January 2021

Burst-and-coast swimmers optimize gait by adapting unique intrinsic cycle.

Commun Biol 2021 Jan 14;4(1):40. Epub 2021 Jan 14.

Laboratoire de Physique et Mécanique des Milieux Hétérogènes (PMMH), CNRS UMR 7636, ESPCI Paris-PSL University, Sorbonne Université, Université de Paris, 75005, Paris, France.

This paper addresses the physical mechanism of intermittent swimming by considering the burst-and-coast regime of fish swimming at different speeds. The burst-and-coast regime consists of a cycle with two successive phases, i.e., a phase of active undulation powered by the fish muscles followed by a passive gliding phase. Observations of real fish whose swimming gait is forced in a water flume from low to high speed regimes are performed, using a full description of the fish kinematics and mechanics. We first show that fish modulate a unique intrinsic cycle to sustain the demanded speed by modifying the bursting to coasting ratio while maintaining the duration of the cycle nearly constant. Secondly, we show using numerical simulations that the chosen kinematics by correspond to optimized gaits for swimming speeds larger than 1 body length per second.
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http://dx.doi.org/10.1038/s42003-020-01521-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809443PMC
January 2021

SAAFEC-SEQ: A Sequence-Based Method for Predicting the Effect of Single Point Mutations on Protein Thermodynamic Stability.

Int J Mol Sci 2021 Jan 9;22(2). Epub 2021 Jan 9.

Department of Physics and Astronomy, Clemson University, Clemson, SC 29634, USA.

Modeling the effect of mutations on protein thermodynamics stability is useful for protein engineering and understanding molecular mechanisms of disease-causing variants. Here, we report a new development of the SAAFEC method, the SAAFEC-SEQ, which is a gradient boosting decision tree machine learning method to predict the change of the folding free energy caused by amino acid substitutions. The method does not require the 3D structure of the corresponding protein, but only its sequence and, thus, can be applied on genome-scale investigations where structural information is very sparse. SAAFEC-SEQ uses physicochemical properties, sequence features, and evolutionary information features to make the predictions. It is shown to consistently outperform all existing state-of-the-art sequence-based methods in both the Pearson correlation coefficient and root-mean-squared-error parameters as benchmarked on several independent datasets. The SAAFEC-SEQ has been implemented into a web server and is available as stand-alone code that can be downloaded and embedded into other researchers' code.
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http://dx.doi.org/10.3390/ijms22020606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7827184PMC
January 2021

A non-invasive real-time monitoring system for cytotoxic brain edema in postischemic stroke based on near-field coupling.

Technol Health Care 2020 Dec 28. Epub 2020 Dec 28.

College of Biomedical Engineering, Army Medical University, Chongqing, China.

Background: As a common secondary pathophysiological process in postischemic stroke (IS), cytotoxic brain edema (CBE) is an independent factor leading to poor prognosis of patients. Near-field coupling (NFC) technology has some advantages such as non-invasive, non-contact, and unimpeded penetration of the skull. In theory, it can reflect the difference between normal and edema tissues through the near-field coupling phase shift (NFCPS) in the electromagnetic wave transmission trait.

Methods: Combining NFC detection principle and computer programming, we established a high-performance real-time monitoring system with functions such as automatic setting of measurement parameters, data acquisition, real-time filtering and dynamic waveform display. To investigate the feasibility of this system to detect CBE, a saline simulation experiment and a 24-hour real-time monitoring experiment after middle cerebral artery occlusion (MCAO) in rats were carried out.

Results: The results of the saline simulation experiment showed that the change of NFCPS was proportional to the increase of the simulated edema solution, and the variation range of NFCPS was more than 9∘ after 5 ml injection. In the 24-hour monitoring after MCAO, the NFCPS of the experimental group showed an overall downward trend over time an average change of -17.7868 ± 1.6325∘ and the change rate gradually decreased. The 24-hour NFCPS in the control group fluctuates slightly around the initial value, which has no obvious upward or downward trend.

Conclusion: The intragroup and intergroup difference statistical analysis shows that NFCPS can effectively distinguish different intracranial pathophysiological states after IS. This work provides sufficient evidence and a technical basis for using NFCPS to monitor CBE in the future.
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http://dx.doi.org/10.3233/THC-202685DOI Listing
December 2020

Asparagine enhances LCK signalling to potentiate CD8 T-cell activation and anti-tumour responses.

Nat Cell Biol 2021 01 8;23(1):75-86. Epub 2021 Jan 8.

Tsinghua-Peking Center for Life Sciences, Beijing, China.

Nutrient availability is central for T-cell functions and immune responses. Here we report that CD8 T-cell activation and anti-tumour responses are strongly potentiated by the non-essential amino acid Asn. Increased Asn levels enhance CD8 T-cell activation and effector functions against tumour cells in vitro and in vivo. Conversely, restriction of dietary Asn, ASNase administration or inhibition of the Asn transporter SLC1A5 impairs the activity and responses of CD8 T cells. Mechanistically, Asn does not directly alter cellular metabolic fluxes; it instead binds the SRC-family protein tyrosine kinase LCK and orchestrates LCK phosphorylation at Tyr 394 and 505, thereby leading to enhanced LCK activity and T-cell-receptor signalling. Thus, our findings reveal a critical and metabolism-independent role for Asn in the direct modulation of the adaptive immune response by controlling T-cell activation and efficacy, and further uncover that LCK is a natural Asn sensor signalling Asn sufficiency to T-cell functions.
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http://dx.doi.org/10.1038/s41556-020-00615-4DOI Listing
January 2021