Publications by authors named "Lei Gao"

1,351 Publications

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Network-based analysis revealed significant interactions between risk genes of severe COVID-19 and host genes interacted with SARS-CoV-2 proteins.

Brief Bioinform 2021 Sep 17. Epub 2021 Sep 17.

Department of Bioinformatics, School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an 271099, Shandong, China.

Whether risk genes of severe coronavirus disease 2019 (COVID-19) from genome-wide association study could play their regulatory roles by interacting with host genes that were interacted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins was worthy of exploration. In this study, we implemented a network-based approach by developing a user-friendly software Network Calculator (https://github.com/Haoxiang-Qi/Network-Calculator.git). By using Network Calculator, we identified a network composed of 13 risk genes and 28 SARS-CoV-2 interacted host genes that had the highest network proximity with each other, with a hub gene HNRNPK identified. Among these genes, 14 of them were identified to be differentially expressed in RNA-seq data from severe COVID-19 cases. Besides, by expression enrichment analysis in single-cell RNA-seq data, compared with mild COVID-19, these genes were significantly enriched in macrophage, T cell and epithelial cell for severe COVID-19. Meanwhile, 74 pathways were significantly enriched. Our analysis provided insights for the underlying genetic etiology of severe COVID-19 from the perspective of network biology.
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http://dx.doi.org/10.1093/bib/bbab372DOI Listing
September 2021

Current status of group B infection in neonates: a multicenter prospective study.

Zhongguo Dang Dai Er Ke Za Zhi 2021 Sept 15;23(9):889-895

Department of Neonatology, Women and Children's Hospital, School of Medcine, Xiamen University/Xiamen Maternal and Child Care Hospital/Xiamen Key Laboratory of Perinatal-Neonatal Infection, Xiamen, Fujian 361003, China (Lin X-Z, Email: [email protected] 163. com).

Objectives: To investigate the incidence of maternal group B (GBS) colonization and neonatal early-onset GBS disease (GBS-EOD), and to study the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization.

Methods: A total of 16 384 pregnant women and 16 634 neonates delivered by them were enrolled prospectively who had medical records in Xiamen Maternal and Child Care Hospital, Beijing Obstetrics and Gynecology Hospital of Capital Medical University, and Zhangzhou Zhengxing Hospital from May 1, 2019 to April 30, 2020. Unified GBS screening time, culture method, and indication for intrapartum antibiotic prophylaxis (IAP) were adopted in the three hospitals. The incidence rates of maternal GBS colonization and neonatal GBS-EOD were investigated. A multivariate logistic regression analysis was used to identify the factors associated with the development of GBS-EOD in the offspring of pregnant women with GBS colonization.

Results: In these three hospitals, the positive rate of GBS culture among the pregnant women in late pregnancy was 11.29% (1 850/16 384), and the incidence rate of neonatal GBS-EOD was 0.96‰ (16/16 634). The admission rate of live infants born to the GBS-positive pregnant women was higher than that of those born to the GBS-negative ones (<0.05). The live infants born to the GBS-positive pregnant women had a higher incidence rate of GBS-EOD than those born to the GBS-negative ones [6.38‰ (12/1 881) vs 0.27‰ (4/14 725), <0.05]. The multivariate logistic regression analysis showed that placental swabs positive for GBS and positive GBS in neonatal gastric juice at birth were independent predictive factors for the development of GBS-EOD (<0.05), while adequate IAP was a protective factor (<0.05) in the offspring of pregnant women with GBS colonization.

Conclusions: GBS colonization of pregnant women in late pregnancy has adverse effects on their offspring. It is important to determine prenatal GBS colonization status of pregnant women and administer with adequate IAP based on the indications of IAP to reduce the incidence of neonatal GBS-EOD. .
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http://dx.doi.org/10.7499/j.issn.1008-8830.2105018DOI Listing
September 2021

A novel method of subxiphoid video-assisted thoracic surgery for thymectomy.

Ann Transl Med 2021 Aug;9(16):1339

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Background: With advances in thoracoscopic surgical instruments and techniques, subxiphoid video-assisted thoracic surgery (S-VATS) has become the main approach for anterior mediastinal tumor resection under thoracoscopy. However, the drawbacks of S-VATS, including it being a relatively unfixed surgical procedure, make it complicated and difficult for unexperienced surgeons to master.

Methods: This study retrospectively reviewed and analyzed consecutive patients with anterior mediastinal tumor or myasthenia gravis (MG) who underwent S-VATS at the Fujian Medical University Union Hospital, China, between March 2015 and April 2019.Patients were divided into the conventional group and the "four-zone one-way" group. Intraoperative and postoperative variables were compared between the groups. Cumulative sum (CUSUM) analysis was applied to determine the operation time (OT)-learning curve of the S-VATS "four-zone one-way" method.

Results: A total of 82 patients were included in this analysis, of which, 40 patients underwent the conventional method of S-VATS and 42 patients underwent the "four-zone one-way" method. Patients in the "four-zone one-way" group had significantly shorter OT (138.50±29.43 and 118.00±28.18 minutes, respectively; P=0.002) and significantly less blood loss (36.00±20.16 and 23.92±14.96 mL, respectively; P=0.003) compared with patients in the conventional group. Our data indicated that there was no difference of the efficacy of MG treatment between the 2 groups. The difference in the preoperative and postoperative quantitative MG scoring system score (QMG-score) and the dose reduction of cholinesterase inhibitors was comparable between patients in the 2 groups. According to the CUSUM analysis curve, after a steady improvement over phase I (cases 1-12 for the traditional method and cases 1-5 for the "four-zone one-way" method), the surgical procedure could be mastered. Phase III occurred after case 26 in the traditional group and case 28 in the "four-zone one-way" group, and is characterized by rapid improvements.

Conclusions: Compared with the conventional method of S-VATS, the "four-zone one-way" method significantly decreased OT and estimated blood loss. These results demonstrated the feasibility and safety of the "four-zone one-way" method of S-VATS.
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http://dx.doi.org/10.21037/atm-21-4070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422105PMC
August 2021

TPM3 mediates epithelial-mesenchymal transition in esophageal cancer via MMP2/MMP9.

Ann Transl Med 2021 Aug;9(16):1338

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Esophageal cancer (EC) is a malignant tumor with high mortality. Correlations have been found between the expression level of tropomyosin 3 (TPM3) and the depth of tumor invasion, lymph node metastasis, and the 5-year survival rate. However, the specific mechanisms underlying EC remain unclear.

Methods: Stably transfected TPM3-overexpresing and TPM3-knockdown esophageal squamous cell carcinoma (ESCC) cell lines (ECa109 and EC9706) were constructed, and the association between TPM3 and the proliferation, invasion, and migration of ESCC was investigated using molecular biology methods. The associations between TPM3 and matrix metalloproteinase (MMP)2/9 or epithelial-mesenchymal transition (EMT)-related proteins were verified, and the potential tumor-promoting mechanism was explored by Gelatin Zymography Experiment.

Results: TPM3 was found to promote the proliferation, migration, and metastatic potential of ESCC and in vitro, and stimulate the expression of MMP2/9 and certain EMT markers other than E-cadherin. The replenishment of MMP2/9 restored the malignant behavior of ESCC caused by TPM3. A gelatinase assay showed that the expression of TPM3 was related to the activity of MMP9.

Conclusions: TPM3 promoted proliferation, migration, and metastatic potential in EC cells. Additionally, TPM3 promoted the EMT process. This function may be achieved via the regulation the expression of MMP2/9.
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http://dx.doi.org/10.21037/atm-21-4043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422148PMC
August 2021

The Impact of FDI on Urban PM Pollution in China: The Mediating Effect of Industrial Structure Transformation.

Int J Environ Res Public Health 2021 Aug 29;18(17). Epub 2021 Aug 29.

School of Economics and Management, Beijing Forestry University, Beijing 100083, China.

With the rapid growth of foreign direct investment (FDI), PM pollution in Chinese cities is increasing. Based on panel data for 271 Chinese cities from 2003 to 2016, this paper uses the dynamic spatial fixed-effects Durbin model to analyze the correlation between FDI and PM pollution and the effect of FDI on urban PM concentrations, as mediated by industrial structure transformation, which is clarified using Stata/SE 16.0. The results showed that PM pollution in China has significant spatial spillover effects, and the pollution haven hypothesis is applicable to Chinese cities. The industrial structure partially mediates the relationship between FDI and PM. This paper proposes that local governments should promote the market-oriented reform of FDI to create a more convenient, legalized, and international environment for FDI and innovate the governance philosophy of only reducing the existing emissions. A top-level design and sound market supervision system of PM control are also needed.
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http://dx.doi.org/10.3390/ijerph18179107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430960PMC
August 2021

Gray matter asymmetry in asymptomatic carotid stenosis.

Hum Brain Mapp 2021 Sep 9. Epub 2021 Sep 9.

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan City, Hubei Province, China.

Even clinically "asymptomatic" carotid stenosis is associated with multidomain cognitive impairment, gray matter (GM) atrophy, and silent lesion. However, the links between them remain unclear. Using structural MRI data, we examined GM asymmetry index (AI) and white matter hyperintensity (WMH) in 24 patients with severe asymptomatic carotid stenosis (SACS), 24 comorbidity-matched controls, and independent samples of 84 elderly controls and 22 young adults. As compared to controls, SACS patients showed worse verbal memories, higher WMH burden, and right-lateralized GM in posterior middle temporal and mouth-somatomotor regions. These clusters extended to pars triangularis, lateral temporal, and cerebellar regions, when compared with young adults. Further, a full-path of WMH burden (X), GM volume (atrophy, M1), AI (asymmetry, M2), and neuropsychological variables (Y) through a serial mediation model was analyzed. This analysis identified that left-dominated GM atrophy and right-lateralized asymmetry in the posterior middle temporal cortex mediated the relationship between WMH burden and recall memory in SACS patients. These results suggest that the unbalanced hemispheric atrophy in the posterior middle temporal cortex is crucial to mediating relationship between WMH burden and verbal recall memories, which may underlie accelerated aging and cognitive deterioration in patients with SACS and other vascular cognitive impairment.
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http://dx.doi.org/10.1002/hbm.25645DOI Listing
September 2021

Galectin Trafficking Pathway-Enabled Color-Switchable Detection of Lysosomal Membrane Permeabilization.

Authors:
Lei Gao Shoufa Han

Anal Chem 2021 Sep 7. Epub 2021 Sep 7.

Department of Chemical Biology, College of Chemistry and Chemical Engineering, State Key Laboratory for Physical Chemistry of Solid Surfaces, the Key Laboratory for Chemical Biology of Fujian Province, and The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Xiamen University, Xiamen 361005, China.

Lysosomal membrane permeabilization (LMP) engaged in multiple human diseases is accompanied by relocation of cytosolic galectin into LMP lysosomes. We herein reported a galectin trafficking-targeted method to image LMP using two kinds of glyco-dendrimers, a sialic acid-terminated dendrimer labeled with pH-inert rhodamine and a lactose-terminated dendrimer labeled with fluorescein that becomes green-emissive in pH-elevated lysosomes. Albeit both accumulated in physiological lysosomes, the former is released from LMP lysosomes while the latter binds to galectin accumulated in LMP lysosomes and thus trapped in LMP lysosomes. Accordingly, LMP lysosomes exhibit loss of red fluorescence and turn-on green fluorescence due to loss of lysosomal acidity. This red-to-green color switch enables discernment of LMP lysosomes from physiological lysosomes and pH-elevated lysosomes and can be further utilized to detect LMP in distinct cell death pathways. These results suggest the utility of galectin trafficking pathway-integrated synthetic probes for detection of LMP, a key factor for diseased cells.
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http://dx.doi.org/10.1021/acs.analchem.1c02387DOI Listing
September 2021

Safety, Tolerability and Pharmacokinetics of the Serotonin 5-HT6 Receptor Antagonist, HEC30654, in Healthy Chinese Subjects.

Front Pharmacol 2021 19;12:726536. Epub 2021 Aug 19.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

HEC30654 is a selective 5-HT6 receptor antagonist that was safe and well-tolerated in preclinical models of Alzheimer's disease. The objective of this double-blind, randomized, placebo-controlled clinical trial was to evaluate the safety, tolerability, and pharmacokinetic profile of HEC30654 after single ascending doses in healthy Chinese subjects. Healthy volunteers received a single oral dose of HEC30654 (5, 10, 15, 30, 60 mg). Safety and tolerability assessments included adverse events, vital signs, and findings on electrocardiograms, electroencephalograms, physical examination, and clinical laboratory tests. Pharmacokinetic analysis of HEC30654 and its major metabolite HEC93263 were conducted in blood, urine, and fecal samples. Single doses of HEC30654 up to 30 mg were generally safe and well tolerated, but dose escalation was terminated early as the 60 mg HEC30654 treatment group met the pre-defined stopping rules specified in the protocol. Median t of HEC30654 was 6 h (range, 4-12 h), t of 10-60 mg HEC30654 ranged from 52.1 to 63.8 h. Exposure to HEC30654 across the dose range explored in this study increased more than in proportion to dose. Metabolism of HEC30654 to HEC93263 was slow (<10%), and HEC30654 was mainly eliminated unchanged through feces. Single doses of HEC30654 up to 30 mg were generally safe and well tolerated. Based on preclinical efficacy in various models of cognition, HEC30654 may represent a therapeutic option for symptomatic treatment of cognitive disorders.
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http://dx.doi.org/10.3389/fphar.2021.726536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416768PMC
August 2021

The Association Between Mycobacteria-Specific Antigen-Induced Cytokines and Host Response to Latent Tuberculosis Infection Treatment in a Chinese Population.

Front Microbiol 2021 13;12:716900. Epub 2021 Aug 13.

NHC Key Laboratory of Systems Biology of Pathogens, Center for Tuberculosis Research, Institute of Pathogen Biology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Objectives: Exploring biomarkers monitoring latent tuberculosis infection (LTBI) treatment effectiveness would benefit optimizing the therapeutic regimen. This study aims to identify potential mycobacteria-specific antigen-induced cytokines associated with host responses to preventive treatment.

Methods: Based on a randomized controlled trial on LTBI treatment among individuals with chest radiography abnormalities suggestive of prior tuberculosis (TB), the dynamically changed cytokine levels in QuantiFERON-TB Gold In-Tube (QFT) supernatants were estimated during the treatment by bead-based multiplex assays and enzyme-linked immunosorbent assay.

Results: In total, 63 treated participants and 32 untreated controls were included in the study. The levels of 13 background-corrected mycobacteria-specific antigen-stimulated cytokines [basic fibroblast growth factor (FGF), growth-regulated oncogene (GRO)-α, interleukin (IL)-1α, IL-1ra, IL-12 (p70), stem cell factor (SCF), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), IL-8, interferon (IFN)-α2, IL-5, IL-12 (p40), leukemia inhibitory factor (LIF), and IL-17A] were found to be statistically different between before and after treatment in treated participants, while no statistically differences were observed in untreated controls. Among these 13 cytokines, the level of IL-8 was significantly lower in the QFT reversed group than that in the non-reversed group ( = 0.028) among treated participants, while such a difference was not found for untreated controls ( = 0.292).

Conclusion: Our results suggested that the lower level of mycobacteria-specific antigen-induced IL-8 might be associated with the host's positive response to LTBI treatment.
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http://dx.doi.org/10.3389/fmicb.2021.716900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415003PMC
August 2021

Voxel-Wise Analysis of Structural and Functional MRI for Lateralization of Handedness in College Students.

Front Hum Neurosci 2021 13;15:687965. Epub 2021 Aug 13.

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China.

The brain structural and functional basis of lateralization in handedness is largely unclear. This study aimed to explore this issue by using voxel-mirrored homotopic connectivity (VMHC) measured by resting-state functional MRI (R-fMRI) and gray matter asymmetry index (AI) by high-resolution anatomical images. A total of 50 healthy subjects were included, among them were 13 left-handers, 24 right-handers, and 13 mixed-handers. Structural and R-fMRI data of all subjects were collected. There were significant differences in VMHC among the three groups in lateral temporal-occipital, orbitofrontal, and primary hand motor regions. Meanwhile, there were significant differences in AI that existed in medial prefrontal, superior frontal, and superior temporal regions. Besides, the correlation analysis showed that the closer the handedness score to the extreme of the left-handedness (LH), the stronger the interhemispheric functional connectivity, as well as more leftward gray matter. In general, left/mixed-handedness (MH) showed stronger functional homotopy in the transmodal association regions that depend on the integrity of the corpus callosum, but more variable in primary sensorimotor cortices. Furthermore, the group differences in VMHC largely align with that in AI. We located the specific regions for LH/MH from the perspective of structural specification and functional integration, suggesting the plasticity of hand movement and different patterns of emotional processing.
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http://dx.doi.org/10.3389/fnhum.2021.687965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414999PMC
August 2021

A combination of support vector machine and voxel-based morphometry in adult male alcohol use disorder patients with cognitive deficits.

Brain Res 2021 Aug 31:147644. Epub 2021 Aug 31.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510080, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510080, China. Electronic address:

Cognitive performance develops with drinking. However, the neural basis of cognitive deficits in AUD is still absent. Here we examined the relationship between overall drinking, brain structural alterations and cognitive deficits in middle-aged AUD men by mediation analysis. A total of 40 patients and 40 healthy controls (HC) underwent highresolution T1-weighted imaging scans and neuroimaging data were applied to voxelbased morphometry, support vector machine (SVM) classifications and mediation analysis. The patients demonstrated reduced gray matter (GM) volumes in different brain regions, including left amygdala, thalamus, hippocampus, precentral gyrus, cerebellum, calcarine, right supplementary motor area and bilateral superior temporal gyrus (all p values < 0.0001, FWE). Decreased GM volumes in the bilateral cerebellum (left r = 0.501, p = 0.001; right r = 0.519, p = 0.001) and thalamus (left r = 0. 442, p = 0.004; right r = 0.418, p = 0.007), left anterior medial temporal Lobe (r = 0.425, p = 0.006), left nucleus ambiguus+parahippocampus gyrus (r = 0.433, p = 0.005), left fusiform gyrus (r = 0.453, p = 0.003), left lingual gyrus (r = 0.455, p = 0.003), left hippocampus (r = 0.434, p = 0.005), right nucleus accumbens volume (r = 0.533, p < 0.001) had positive correlations with MoCA scores. The mediation analysis showed that left Crus 1 partially mediated the association of overall drinking and MoCA scores (standardized beta coefficient = -0.0003, s.e. = 0.0002, 95% CI = (-0.0006, 0.0000)). The SVM results could distinguish patients from HC with satisfactory classification results (0.8275). Our findings showed the altered GM volumes within the extended amygdala circuits and cognitive deficits in patients. The left Crus 1 may be an informative biomarker to predict the risk of AUD and a possible neural basis of cognitive deficits in middle-aged AUD men.
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http://dx.doi.org/10.1016/j.brainres.2021.147644DOI Listing
August 2021

The effect of WeChat-based training on improving the knowledge of tuberculosis management of rural doctors.

J Clin Tuberc Other Mycobact Dis 2021 Dec 11;25:100266. Epub 2021 Aug 11.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: In China, rural doctors played a crucial role in TB cases referral and management. The current study aimed to evaluate the effect of WeChat-based training program on improving the rural doctors' knowledge on TB management.

Methods: A One-year WeChat-based training was conducted among registered rural doctors from Zhongmu County, located in middle China, by means of releasing original contents (in forms of text, poster, video or cartoon) through WeChat subscription account (WeChat SA) once a week. Pre-and-post-training offline tests were hold using the same self-administered questionnaire to evaluate the training effect.

Results: A total of 467 rural doctor were included in the study. During the training, 60 original articles were posted through WeChat SA. With respect to the two tests, the median score increased from 50 (40.0-60.0) to 60 (53.0-70.0) (p < 0.001) after training. As compared with posters, the median readings were significantly higher for released contents in forms of text, video and cartoon (p < 0.001). Female's test performance improved better than male's. In addition, a positive relation was observed between education level and the test performance regardless of training.

Conclusions: Our results indicated that WeChat-based training improved the knowledge of rural doctors on TB management to a certain extent. It is worthy to explore more effective new media-based training methods to promote TB control in rural China.
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http://dx.doi.org/10.1016/j.jctube.2021.100266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379341PMC
December 2021

Examination of the differences between sulforaphane and sulforaphene in colon cancer: A study based on next-generation sequencing.

Oncol Lett 2021 Oct 1;22(4):690. Epub 2021 Aug 1.

Institute of Quality Standard and Testing Technology for Agro-Products, Shandong Academy of Agricultural Sciences, Jinan, Shandong 250100, P.R. China.

Sulforaphane and sulforaphene are isothiocyanate compounds derived from cruciferous vegetables that have demonstrated antiproliferative properties against colon cancer. However, the underlying mechanism of action of these two compounds has yet to be elucidated. The aim of the present study was to examine the effects of sulforaphane and sulforaphene on colon cancer using next-generation sequencing (NGS). The SW480 colon cancer cell line was cultured with 25 µmol/l sulforaphane or sulforaphene. Total RNA was extracted from the cells following 48 h of incubation with these compounds, and NGS was performed. Pearson's correlation and principal component analyses were performed on the NGS data in order to determine sample homogeneity followed by hierarchical clustering, chromosomal location, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 873 probes in the sulforaphene group were differentially expressed compared with the control group. Similarly, 959 probes in the sulforaphane group were differentially expressed compared with the control group. The differentially expressed genes were dispersed on the chromosomes, across 22 pairs of autosomes, as well as the X and Y chromosomes. GO and KEGG analyses demonstrated that both drugs affected the 'p53 signaling pathway', 'MAPK signaling pathway', 'FOXO signaling pathway' and 'estrogen signaling pathway', while 'Wnt signaling pathway' was enriched in the sulforaphane group, and 'ubiquitin mediated proteolysis' and 'estrogen signaling pathway' in the sulforaphene group. Thus, sulforaphane and sulforaphene exhibited similar biological activities on colon cancer cells. Sulforaphane and sulforaphene may be associated with Wnt and estrogen signaling, respectively.
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http://dx.doi.org/10.3892/ol.2021.12951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358736PMC
October 2021

Ternary Hybrid Perovskite Solid Solution Single Crystals: Growth, Composition Determination and Phase Stability in Highly Moist Atmosphere.

Chemistry 2021 Aug 25. Epub 2021 Aug 25.

Department of Chemistry, Tsinghua University, Beijing, 100084, China.

Ternary hybrid perovskite solid solutions have shown superior optoelectronic properties and better stability than their ABX simple perovskite counterparts under ambient conditions. However, crystal growth and identification of the accurate composition of these complex crystalline compounds remain challenging, and their stability under extreme conditions such as in highly moist atmosphere is unknown. Herein, large-size (up to 2 cm) single crystals of ternary perovskite 0.80FAPbI  ⋅ x'FAPbBr  ⋅ y'CsPbI (x'+y'=0.20) are grown. An elemental analysis method based on wavelength dispersive X-ray fluorescence is proposed to determine their accurate compositions. Among these single crystals, the composition with y'=0.12 shows the best moisture stability at 90 % relative humidity for 15 days. Other components with richer or poorer Cs ions undergo different phase segregation behaviours. The performance and stability of photodetectors based on these single crystals are tested. This work offers a deeper insight into phase stability of ternary hybrid perovskite solid solution crystals in highly moist atmosphere.
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http://dx.doi.org/10.1002/chem.202101655DOI Listing
August 2021

Intermetallic Compounds: Liquid-Phase Synthesis and Electrocatalytic Applications.

Chemistry 2021 Aug 24. Epub 2021 Aug 24.

Hunan University, College of Materials Science and Engineering, South Lushan Road 2#, 410082, China, 410082, Changsha, CHINA.

Characterized by long-range atomic ordering, well-defined stoichiometry, and controlled crystal structure, intermetallics have attracted increasing attention in the area of chemical synthesis and catalytic applications. Liquid-phase synthesis of intermetallics has arisen as the promising methodology due to its precise control over size, shape, and resistance toward sintering compared with the traditional metallurgy. This short review tends to provide perspectives on the liquid-phase synthesis of intermetallics in terms of both thermodynamics and methodology, as well as its applications in various catalytic reactions. Specifically, basic thermodynamics and kinetics in the synthesis of intermetallics will be first discussed, followed by discussing the main factors that will affect the formation of intermetallics during synthesis. The application of intermetallics in electrocatalysis will be demonstrated case by case at last. We conclude the review with perspectives on the future developments with respect to both synthesis and catalytic applications.
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http://dx.doi.org/10.1002/chem.202102500DOI Listing
August 2021

Tuberculosis infection screening in children with close contact: a hospital-based study.

BMC Infect Dis 2021 Aug 13;21(1):815. Epub 2021 Aug 13.

National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics, Capital Medical University, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.

Background: Identifying and prioritizing at-risk populations is critical for pediatric tuberculosis control. We aimed to identify a latent tuberculosis infection (LTBI) screening strategy that is appropriate for the Chinese context among children with different TB exposure levels and to explore its clinical importance.

Methods: During 2013-2015, we enrolled hospitalized children with suspected respiratory infectious disease (RID) for LTBI screening using the tuberculin skin test (TST) and interferon-γ release assay (IGRA) T-SPOT.TB as part of a work up for their RID. Participants with confirmed diagnosis were classified into three subgroups according to level of exposure to TB: no reported contact risk, with household contact risk, and with non-household contact risk.

Results: A total 6202 children (median age: 4.76 years; interquartile range: 1.0-8.0 years) were enrolled. Children with no reported contact risk had the lowest proportions of positive results for the IGRA (0.7%) and TST (3.3%). The proportion of positive results for each test was higher for household contacts than non-household contacts. The TST positive proportion was much higher than that for the IGRA in all three groups. Children with IGRA+/TST+ results had larger indurations than those with IGRA- /TST+  results (15 mm vs. 13 mm, P = 0.02). For IGRA, older age (> 5 years) and non-household or household contact risk were associated with a positive result.

Conclusions: Positive IGRA results in children with a contact risk can serve as a critical reference for LTBI management. IGRA can be used, in preference to TST, for Chinese children with a TB exposure risk.
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http://dx.doi.org/10.1186/s12879-021-06480-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364055PMC
August 2021

Comparative ribosome profiling reveals distinct translational landscapes of salt-sensitive and -tolerant rice.

BMC Genomics 2021 Aug 12;22(1):612. Epub 2021 Aug 12.

Guangdong Provincial Key Laboratory for Plant Epigenetics, Longhua Bioindustry and Innovation Research Institute, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China.

Background: Soil salinization represents a serious threat to global rice production. Although significant research has been conducted to understand salt stress at the genomic, transcriptomic and proteomic levels, few studies have focused on the translatomic responses to this stress. Recent studies have suggested that transcriptional and translational responses to salt stress can often operate independently.

Results: We sequenced RNA and ribosome-protected fragments (RPFs) from the salt-sensitive rice (O. sativa L.) cultivar 'Nipponbare' (NB) and the salt-tolerant cultivar 'Sea Rice 86' (SR86) under normal and salt stress conditions. A large discordance between salt-induced transcriptomic and translatomic alterations was found in both cultivars, with more translationally regulated genes being observed in SR86 in comparison to NB. A biased ribosome occupancy, wherein RPF depth gradually increased from the 5' ends to the 3' ends of coding regions, was revealed in NB and SR86. This pattern was strengthened by salt stress, particularly in SR86. On the contrary, the strength of ribosome stalling was accelerated in salt-stressed NB but decreased in SR86.

Conclusions: This study revealed that translational reprogramming represents an important layer of salt stress responses in rice, and the salt-tolerant cultivar SR86 adopts a more flexible translationally adaptive strategy to cope with salt stress compared to the salt susceptible cultivar NB. The differences in translational dynamics between NB and SR86 may derive from their differing levels of ribosome stalling under salt stress.
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http://dx.doi.org/10.1186/s12864-021-07922-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359061PMC
August 2021

Intestinal congestion and reperfusion injury: damage caused to the intestinal tract and distal organs.

Biosci Rep 2021 Sep;41(9)

Department of Tumor Surgery, Lanzhou University Second Hospital, Lanzhou, China.

In clinical practice, intestinal autologous diseases, ailments and organ transplants can cause severe congestive damage to the intestinal tract. However, after the etiological factor is gotten rid of and blood flow is free without any hinderance, further damage to the intestinal wall often occurs, causing other related organ dysfunctions. This ultimately results in intestinal congestion reperfusion injury (ICRI). When the structure and function of the intestine are destroyed, bacteria, metabolites and endotoxins in the intestinal tract perfuse and enter the portal vein through the already compromised intestinal mucosa, to the other organs via the liver. Nevertheless, this gives rise to further aggravation of the injury, and reperfusion injury syndrome occurs. ICRI is a very common complication encountered by clinicians, and its harm is more severe and serious as compared with that caused by ischemia-reperfusion. Quite a few number of studies on ICRI have been reported to date. The exact mechanism of the injury is still idiopathic, and effective treatment strategies are still limited. Based on recent studies, this article is aimed at reviewing the destruction, damage mechanisms resulting from ICRI to the intestinal anatomical sites and distant organs. It is geared towards providing new ideas for the prevention and therapeutic approaches of ICRI.
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http://dx.doi.org/10.1042/BSR20211560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421592PMC
September 2021

LaO modified MnO loaded biomass activated carbon and its enhanced performance for simultaneous abatement of NO and Hg.

Environ Sci Pollut Res Int 2021 Aug 7. Epub 2021 Aug 7.

School of Resources Environment and Safety Engineering, University of South China, Hengyang, 421001, People's Republic of China.

A battery of agricultural straw derived biomass activated carbons supported LaO modified MnO (LaMn/BACs) was prepared by a facile impregnation method and then tested for simultaneous abatement of NO and Hg. 15%LaMn/BAC manifested excellent removal efficiency of Hg (100%) and NO (86.7%) at 180 °C, which also exhibited splendid resistance to SO and HO. The interaction between Hg removal and NO removal was explored; thereinto, Hg removal had no influence on NO removal, while NO removal preponderated over Hg removal. The inhibitory effect of NH was greater than the accelerative effect of NO and O on Hg removal. The physicochemical characterization of related samples was characterized by SEM, XRD, BET, H-TPR, NH-TPD, and XPS. After incorporating suitable LaO into 15%Mn/BAC, the synergistic effect between LaO and MnO contributed to the improvement of BET surface area and total pore volume, the promotion of redox ability, surface active oxygen species, and acid sites, inhibiting the crystallization of MnO. 15%LaMn/BAC has the best catalytic oxidation activity at low temperature. That might be answerable for superior performance and preferable tolerance to SO and HO. The results indicated that 15%LaMn/BAC was a promising catalyst for simultaneous abatement of Hg and NO at low temperature.
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http://dx.doi.org/10.1007/s11356-021-15752-yDOI Listing
August 2021

Microcystin-LR induces ferroptosis in intestine of common carp (Cyprinus carpio).

Ecotoxicol Environ Saf 2021 Oct 5;223:112610. Epub 2021 Aug 5.

Key Laboratory of Aquatic Animal Diseases and Immune Technology of Heilongjiang Province, Heilongjiang River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Harbin 150070, China. Electronic address:

Previous studies provide comprehensive evidence of the environmental hazards and intestinal toxicity of microcystin-LR (MC-LR) exposure. However, little is known about the mechanisms underlying the injury of intestine exposed to MC-LR. Juvenile common carp (Cyprinus carpio) were exposed to MC-LR (0 and 10 μg/L) for 15 days. The results suggest that organic anion-transporting polypeptides 3a1, 4a1, 2b1, and 1d1 mediate MC-LR entry into intestinal tissues. Lesion morphological features (vacuolization, deformation and dilation of the endoplasmic reticulum [ER], absence of mitochondrial cristae in mid-intestine), up-regulated mRNA expressions of ER stress (eukaryotic translation initiation factor 2-alpha kinase 3, endoplasmic reticulum to nucleus signaling 1, activating transcription factor [ATF] 6, ATF4, DNA damage-inducible transcript 3), iron accumulation, and down-regulated activity of glutathione peroxidase (GPx) and glutathione (GSH) content were all typical characteristics of ferroptosis in intestinal tissue following MC-LR exposure. GSH levels in intestinal tissue corroborated as the most influential GSH/GPx 4- related metabolic pathway in response to MC-LR exposure. Verrucomicrobiota, Planctomycetes, Bdellovibrionota, Firmicutes and Cyanobacteria were correlated with the ferroptosis-related GSH following MC-LR exposure. These findings provide new perspectives of the ferroptosis mechanism of MC-LR-induced intestinal injury in the common carp.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112610DOI Listing
October 2021

Diversity and Biocontrol Potential of Cultivable Endophytic Bacteria Associated with Halophytes from the West Aral Sea Basin.

Microorganisms 2021 Jul 6;9(7). Epub 2021 Jul 6.

State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China.

Endophytes associated with halophytes may contribute to the host's adaptation to adverse environmental conditions through improving their stress tolerance and protecting them from various soil-borne pathogens. In this study, the diversity and antifungal activity of endophytic bacteria associated with halophytic samples growing on the shore of the western Aral Sea in Uzbekistan were investigated. The endophytic bacteria were isolated from the nine halophytic samples by using the culture-dependent method and identified according to their 16S rRNA gene sequences. The screening of endophytic bacterial isolates with the ability to inhibit pathogenic fungi was completed by the plate confrontation method. A total of 289 endophytic bacterial isolates were isolated from the nine halophytes, and they belong to , , and . The predominant genera of the isolated endophytic bacteria were , , and , accounting for 38.5%, 24.7%, and 12.5% of the total number of isolates, respectively. The comparative analysis indicated that the isolation effect was better for the sample S8, with the highest diversity and richness indices. The diversity index of the sample S7 was the lowest, while the richness index of samples S5 and S6 was the lowest. By comparing the isolation effect of 12 different media, it was found that the M7 medium had the best performance for isolating endophytic bacteria associated with halophytes in the western Aral Sea Basin. In addition, the results showed that only a few isolates have the ability to produce ex-enzymes, and eight and four endophytic bacterial isolates exhibited significant inhibition to the growth of and , respectively. The results of this study indicated that halophytes are an important source for the selection of microbes that may protect plant from soil-borne pathogens.
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http://dx.doi.org/10.3390/microorganisms9071448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303770PMC
July 2021

RiboNT: A Noise-Tolerant Predictor of Open Reading Frames from Ribosome-Protected Footprints.

Life (Basel) 2021 Jul 16;11(7). Epub 2021 Jul 16.

Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.

Ribo-seq, also known as ribosome profiling, refers to the sequencing of ribosome-protected mRNA fragments (RPFs). This technique has greatly advanced our understanding of translation and facilitated the identification of novel open reading frames (ORFs) within untranslated regions or non-coding sequences as well as the identification of non-canonical start codons. However, the widespread application of Ribo-seq has been hindered because obtaining periodic RPFs requires a highly optimized protocol, which may be difficult to achieve, particularly in non-model organisms. Furthermore, the periodic RPFs are too short (28 nt) for accurate mapping to polyploid genomes, but longer RPFs are usually produced with a compromise in periodicity. Here we present RiboNT, a noise-tolerant ORF predictor that can utilize RPFs with poor periodicity. It evaluates RPF periodicity and automatically weighs the support from RPFs and codon usage before combining their contributions to identify translated ORFs. The results demonstrate the utility of RiboNT for identifying both long and small ORFs using RPFs with either good or poor periodicity. We implemented the pipeline on a dataset of RPFs with poor periodicity derived from membrane-bound polysomes of seedlings and identified several small ORFs (sORFs) evolutionarily conserved in diverse plant species. RiboNT should greatly broaden the application of Ribo-seq by minimizing the requirement of RPF quality and allowing the use of longer RPFs, which is critical for organisms with complex genomes because these RPFs can be more accurately mapped to the position from which they were derived.
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http://dx.doi.org/10.3390/life11070701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307163PMC
July 2021

Rational design of West Nile virus vaccine through large replacement of 3' UTR with internal poly(A).

EMBO Mol Med 2021 Sep 5;13(9):e14108. Epub 2021 Aug 5.

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.

The genus Flavivirus comprises numerous emerging and re-emerging arboviruses causing human illness. Vaccines are the best approach to prevent flavivirus diseases. But pathogen diversities are always one of the major hindrances for timely development of new vaccines when confronting unpredicted flavivirus outbreaks. We used West Nile virus (WNV) as a model to develop a new live-attenuated vaccine (LAV), WNV-poly(A), by replacing 5' portion (corresponding to SL and DB domains in WNV) of 3'-UTR with internal poly(A) tract. WNV-poly(A) not only propagated efficiently in Vero cells, but also was highly attenuated in mouse model. A single-dose vaccination elicited robust and long-lasting immune responses, conferring full protection against WNV challenge. Such "poly(A)" vaccine strategy may be promising for wide application in the development of flavivirus LAVs because of its general target regions in flaviviruses.
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http://dx.doi.org/10.15252/emmm.202114108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422072PMC
September 2021

Structural and quantitative alterations of gut microbiota in experimental small bowel obstruction.

PLoS One 2021 4;16(8):e0255651. Epub 2021 Aug 4.

Graduate school of Tianjin Medical University, Tianjin, China.

Objective: To investigate structural and quantitative alterations of gut microbiota in an experimental model of small bowel obstruction.

Method: A rat model of small bowel obstruction was established by using a polyvinyl chloride ring surgically placed surrounding the terminal ileum. The alterations of gut microbiota were studied after intestinal obstruction. Intraluminal fecal samples proximal to the obstruction were collected at different time points (24, 48 and 72 hours after obstruction) and analyzed by 16s rDNA high-throughput sequencing technology and quantitative PCR (qPCR) for target bacterial groups. Furthermore, intestinal claudin-1 mRNA expression was examined by real-time polymerase chain reaction analysis, and serum sIgA, IFABP and TFF3 levels were determined by enzyme-linked immunosorbent assay.

Results: Small bowel obstruction led to significant bacterial overgrowth and profound alterations in gut microbiota composition and diversity. At the phylum level, the 16S rDNA sequences showed a marked decrease in the relative abundance of Firmicutes and increased abundance of Proteobacteria, Verrucomicrobia and Bacteroidetes. The qPCR analysis showed the absolute quantity of total bacteria increased significantly within 24 hours but did not change distinctly from 24 to 72 hours. Further indicators of intestinal mucosa damage and were observed as claudin-1 gene expression, sIgA and TFF3 levels decreased and IFABP level increased with prolonged obstruction.

Conclusion: Small bowel obstruction can cause significant structural and quantitative alterations of gut microbiota and induce disruption of gut mucosa barrier.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255651PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336877PMC
August 2021

Distribution and dispersion of heavy metals in the rock-soil-moss system of the black shale areas in the southeast of Guizhou Province, China.

Environ Sci Pollut Res Int 2021 Aug 3. Epub 2021 Aug 3.

College of Resources and Environment Engineering, Guizhou University, Guiyang, 550025, China.

Black shales are easily exposed due to human activities such as mining, road construction, and shale gas development, which results in several environmental issues including heavy metal (HM) pollution, soil erosion, and the destruction of vegetation. Mosses are widely used to monitor metal pollution in the atmosphere, but few studies on the distribution and dispersion of HMs in the rock-soil-moss system are available. Here, mosses (Pohlia flexuosa Harv. in Hook), growing soils, and corresponding parent rocks were collected from black shale areas. After appropriate pretreatment, samples were analyzed for multiple elemental concentrations by ICP-AES and ICP-MS. The results show that black shale parent rocks have elevated HM concentration and act as a source of multiple metals. The overlying soil significantly inherits and accumulates heavy metals released from black shale. Significant positive correlations between HMs in P. flexuosa and the growing soils indicate that HMs are mainly originating from geological source rather than atmospheric deposition. Differential accumulation of HMs is observed between rhizoids and stems in our study. Moreover, P. flexuosa is able to cope with high concentrations of toxic metals without any visible negative effect on its growth and development. Finally, the bioconcentration factor (BCF) for all the HMs in P. flexuosa is less than 1, indicating that it has a tolerance and exclusion mechanism for these metals, especially for the non-essential elements As and Pb. Therefore, the luxuriant and spontaneous growth of P. flexuosa could be used as a phytostabilization pioneer plant in the black shale outcrop where vascular plants are rare.
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http://dx.doi.org/10.1007/s11356-021-15335-xDOI Listing
August 2021

Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies.

Lancet HIV 2021 09 30;8(9):e531-e543. Epub 2021 Jul 30.

Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Background: Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality.

Methods: We did a systematic review for studies on anal HPV infection in men and a pooled analysis of individual-level data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), and HSIL or worse (HSIL+), were compared by use of adjusted prevalence ratios (aPRs) from generalised linear models.

Findings: The systematic review identified 93 eligible studies, of which 64 contributed data on 29 900 men to the pooled analysis. Among HIV-negative MSW anal HPV16 prevalence was 1·8% (91 of 5190) and HR-HPV prevalence was 6·9% (345 of 5003); among HIV-positive MSW the prevalences were 8·7% (59 of 682) and 26·9% (179 of 666); among HIV-negative MSM they were 13·7% (1455 of 10 617) and 41·2% (3798 of 9215), and among HIV-positive MSM 28·5% (3819 of 13 411) and 74·3% (8765 of 11 803). In HIV-positive MSM, HPV16 prevalence was 5·6% (two of 36) among those age 15-18 years and 28·8% (141 of 490) among those age 23-24 years (p=0·0091); prevalence was 31·7% (1057 of 3337) among those age 25-34 years and 22·8% (451 of 1979) among those age 55 and older (p<0·0001). HPV16 prevalence in HIV-negative MSM was 6·7% (15 of 223) among those age 15-18 and 13·9% (166 of 1192) among those age 23-24 years (p=0·0076); the prevalence plateaued thereafter (p=0·72). Similar age-specific patterns were observed for HR-HPV. No significant differences for HPV16 or HR-HPV were found by age for either HIV-positive or HIV-negative MSW. HSIL+ detection ranged from 7·5% (12 of 160) to 54·5% (61 of 112) in HIV-positive MSM; after adjustment for heterogeneity, HIV was a significant predictor of HSIL+ (aPR 1·54, 95% CI 1·36-1·73), HPV16-positive HSIL+ (1·66, 1·36-2·03), and HSIL+ in HPV16-positive MSM (1·19, 1·04-1·37). Among HPV16-positive MSM, HSIL+ prevalence increased with age.

Interpretation: High anal HPV prevalence among young HIV-positive and HIV-negative MSM highlights the benefits of gender-neutral HPV vaccination before sexual activity over catch-up vaccination. HIV-positive MSM are a priority for anal cancer screening research and initiatives targeting HPV16-positive HSIL+.

Funding: International Agency for Research on Cancer.
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http://dx.doi.org/10.1016/S2352-3018(21)00108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408042PMC
September 2021

Spectroscopic Perception of Trap States on the Performance of Methylammonium and Formamidinium Lead Iodide Perovskite Solar Cells.

Adv Mater 2021 Aug 2:e2102241. Epub 2021 Aug 2.

School of Physics and Key Laboratory of MEMS of the Ministry of Education, Southeast University, Nanjing, 211189, China.

To enhance the efficiency and stability of the organic-inorganic hybrid perovskite (OIHP) solar cells, doping has been demonstrated as a straightforward method. Nevertheless, the perception of trap states regulated by doping and their effects on the performance of solar cells is not in-depth. Herein, typical OIHPs (CH NH PbI and Cs FA MA Pb(I Br ) ) doped with RbI are employed to expound the doping mechanism in affecting the efficiency of devices. Systematic spectroscopic characterizations indicate that doping significantly influences the photocarrier dynamics via directly regulating the trap states. The results indicate that doping would reduce the trap density by passivating defects and induce extra trapping centers. This directly manipulates the transient transport of the photocarriers and finally influences the output of devices. The optimization of solar cell performance requires the tradeoff of competitive relation between the passivation and introduction of trapping centers. The results provide the spectroscopic perception on how doping concentration affects trap density, carrier dynamics, transport behavior, and ultimately the parameters of devices. It provides a straightforward guidance to the design and optimization of OIHP-based solar cells.
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http://dx.doi.org/10.1002/adma.202102241DOI Listing
August 2021

Identification and Validation of a Prognostic Signature for Prostate Cancer Based on Ferroptosis-Related Genes.

Front Oncol 2021 15;11:623313. Epub 2021 Jul 15.

Department of Urology, Shanghai Tenth People's Hospital, School of Medicine in Tongji University, Shanghai, China.

Ferroptosis, an iron-dependent form of selective cell death, is involved in the development of many cancers. However, ferroptosis related genes (FRGs) in prostate cancer (PCa) are not been well studied. In this study, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO, and multivariate Cox regression analyses were performed to construct a prognostic signature. Seven FRGs, , , , , , , and , were included to establish a risk model, which was validated in the MSKCC dataset. The results showed that the high-risk group was apparently correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immunotherapy, and bicalutamide response. Moreover, we found that overexpression induced the proliferation and invasion of PCa cell lines . These results demonstrate that this risk model can accurately predict prognosis, suggesting that FRGs are promising prognostic biomarkers and potential drug targets in PCa patients.
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http://dx.doi.org/10.3389/fonc.2021.623313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320699PMC
July 2021

Fast determination of 16 circulating neurotransmitters and their metabolites in plasma samples of spontaneously hypertensive rats intervened with five different Uncaria.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 14;1179:122856. Epub 2021 Jul 14.

Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai 201203, China; University of Chinese Academy of Sciences, No.19A Yuanquan Road, Beijing 100049, China. Electronic address:

This study aimed to establish a sensitive, reproducible, and rapid liquid chromatography method with tandem mass spectrometry detection to perform simultaneous quantitative analysis of 16 neurotransmitters and their metabolites in rat plasma, including levodopa, dopamine, norepinephrine, epinephrine, L-tryptophan, kynurenic acid, serotonin, melatonin, choline, acetylcholine, histamine, phenylethylamine, as well as excitatory (L-glutamic acid and L-aspartic acid) and inhibitory (γ-aminobutyric acid and L-glycine) neurotransmitters. These analytes were measured by ultra-high performance chromatography coupled with triple quadrupole mass spectrometry using a hydrophilic interaction chromatographic column (ethylene-bridged hybrid amide column). The internal standards of stable isotope labeling were used to improve the reliability of the results. Our method provided high linearity for all neurotransmitters (for all coefficients measured > 0.99), with inter- and intra-day accuracy from -14.82% to 17.49% and precision was between 0.89% and 17.70%. The method was subsequently verified in an animal study, where the intervention of five different Uncarias, the traditional Chinese medicine with hypotensive effects, was applied to the spontaneously hypertensive rats (SHRs). SHRs showed dysregulated plasma kynurenic acid, acetylcholine, and norepinephrine levels, and these neuroactive analytes were significantly restored by Uncaria treatment compared with the model group (SHR group). Compared with captopril, included as a positive control for its hypotensive effect, Uncaria had more effects on perturbing the levels of plasma neurotransmitters, which might indicate Uncaria's potential in treating symptoms related to the nervous system. These results suggested that the changes in the neurotransmitters and their metabolites in plasma may be related to the pathogenesis of hypertension. It also provided valuable information about the action mechanisms of Uncaria on its hypotensive effects.
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http://dx.doi.org/10.1016/j.jchromb.2021.122856DOI Listing
August 2021
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