Publications by authors named "Nan Hu"

618 Publications

Digitally predesigned positioning tray and custom restoration shell for immediate implantation prothesis: a digital workflow.

Int J Comput Dent 2021 Sep;24(3):293-302

The present article introduces a new digital workflow for the fabrication of an immediate implantation prothesis. With this technique, based on the surgical planning, the positioning tray and the restoration shell are predesigned and premanufactured together with the implant guide before the physical surgery. After implantation, the restoration shell is placed and bonded with a temporary abutment guided by the positioning tray, which acts as a type of tooth-borne device to guide the placement and bonding of the immediate restoration. The restoration shell acts as a type of hollowed out restoration in the tissue surface to improve the implantation error tolerance.
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September 2021

Cognition effectiveness of continuous positive airway pressure treatment in obstructive sleep apnea syndrome patients with cognitive impairment: a meta-analysis.

Exp Brain Res 2021 Sep 21. Epub 2021 Sep 21.

Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, 8 Sanjiaohu Road, Wuhan, 430056, Hubei, China.

Obstructive sleep apnea (OSA) is a common respiratory disorder characterized by recurrent pharyngeal collapses during sleep leading to intermittent hypoxia and sleep disruption. Cognitive challenges and high risks of cognitive impairment, including Alzheimer's disease (AD), are closely associated with OSA. Currently, continuous positive airway pressure (CPAP) is widely used in the treatment of OSA. However, whether CPAP benefits cognitive functions in patients with OSA remains elusive. Here, we identified published studies through a systematic review of PubMed, Cochrane Library, Embase, Wanfang Data, CBM, and CNKI from January 1, 1970, to July 1, 2020. 288 patients from 7 articles (one was excluded in the meta-analysis for it was a follow-up study) were included in the present study. It revealed that cognitive functions of OSA patients with mild cognitive impairment (MCI) or AD were mildly but significantly improved after CPAP treatment (SMD 0.49, 95% CI 0.11-0.86), especially long-term CPAP treatment (SMD 0.56, 95% CI 0.10-1.02, p = 0.02), as measured by Mini-Mental State Examination (MMSE) (SMD 0.49, 95%CI 0.11-0.86). However, no significant cognition benefits were detected by the Montreal Cognitive Assessment (SMD 0.43, 95% CI 0.85-1.72). In terms of heterogeneity, cognitive improvements by CPAP were detectable on OSA patients either at a younger age or over longer periods of CPAP treatment. Therefore, our findings highlight the partial efficiency of CPAP treatment in cognition improvement of OSA patients with MCI or AD.
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http://dx.doi.org/10.1007/s00221-021-06225-2DOI Listing
September 2021

Integrated printed BDNF/collagen/chitosan scaffolds with low temperature extrusion 3D printer accelerated neural regeneration after spinal cord injury.

Regen Biomater 2021 Oct 12;8(6):rbab047. Epub 2021 Aug 12.

Tianjin Key Laboratory of Brain Science and Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.

Recent studies have shown that 3D printed scaffolds integrated with growth factors can guide the growth of neurites and promote axon regeneration at the injury site. However, heat, organic solvents or cross-linking agents used in conventional 3D printing reduce the biological activity of growth factors. Low temperature 3D printing can incorporate growth factors into the scaffold and maintain their biological activity. In this study, we developed a collagen/chitosan scaffold integrated with brain-derived neurotrophic factor (3D-CC-BDNF) by low temperature extrusion 3D printing as a new type of artificial controlled release system, which could prolong the release of BDNF for the treatment of spinal cord injury (SCI). Eight weeks after the implantation of scaffolds in the transected lesion of T10 of the spinal cord, 3D-CC-BDNF significantly ameliorate locomotor function of the rats. Consistent with the recovery of locomotor function, 3D-CC-BDNF treatment could fill the gap, facilitate nerve fiber regeneration, accelerate the establishment of synaptic connections and enhance remyelination at the injury site.
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http://dx.doi.org/10.1093/rb/rbab047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417565PMC
October 2021

Fully Convolutional Network and Visual Saliency-Based Automatic Optic Disc Detection in Retinal Fundus Images.

J Healthc Eng 2021 31;2021:3561134. Epub 2021 Aug 31.

School of Information and Control Engineering, Shenyang Jianzhu University, Shenyang 110168, China.

We present in this paper a novel optic disc detection method based on a fully convolutional network and visual saliency in retinal fundus images. Firstly, we employ the morphological reconstruction-based object detection method to locate the optic disc region roughly. According to the location result, a 400 × 400 image patch that covers the whole optic disc is obtained by cropping the original retinal fundus image. Secondly, the Simple Linear Iterative Cluster approach is utilized to segment such an image patch into many smaller superpixels. Thirdly, each superpixel is assigned a uniform initial saliency value according to the background prior information based on the assumption that the superpixels located on the boundary of the image belong to the background. Meanwhile, we use a pretrained fully convolutional network to extract the deep features from different layers of the network and design the strategy to represent each superpixel by the deep features. Finally, both the background prior information and the deep features are integrated into the single-layer cellular automata framework to gain the accurate optic disc detection result. We utilize the DRISHTI-GS dataset and RIM-ONE r3 dataset to evaluate the performance of our method. The experimental results demonstrate that the proposed method can overcome the influence of intensity inhomogeneity, weak contrast, and the complex surroundings of the optic disc effectively and has superior performance in terms of accuracy and robustness.
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http://dx.doi.org/10.1155/2021/3561134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424246PMC
August 2021

DNA Methylation and RNA-Sequencing Analysis Show Epigenetic Function During Grain Filling in Foxtail Millet ( L.).

Front Plant Sci 2021 27;12:741415. Epub 2021 Aug 27.

College of Biology and Food Engineering, Anyang Institute of Technology, Anyang, China.

Grain filling is a crucial process for crop yield and quality. Certain studies already gained insight into the molecular mechanism of grain filling. However, it is unclear whether epigenetic modifications are associated with grain filling in foxtail millet. Global DNA methylation and transcriptome analysis were conducted in foxtail millet spikelets during different stages to interpret the epigenetic effects of the grain filling process. The study employed the whole-genome bisulfite deep sequencing and advanced bioinformatics to sequence and identify all DNA methylation during foxtail millet grain filling; the DNA methylation-mediated gene expression profiles and their involved gene network and biological pathway were systematically studied. One context of DNA methylation, namely, CHH methylation, was accounted for the largest percentage, and it was gradually increased during grain filling. Among all developmental stages, the methylation levels were lowest at T2, followed by T4, which mainly occurred in CHG. The distribution of differentially methylated regions (DMR) was varied in the different genetic regions for three contexts. In addition, gene expression was negatively associated with DNA methylation. Evaluation of the interconnection of the DNA methylome and transcriptome identified some stage-specific differentially expressed genes associated with the DMR at different stages compared with the T1 developmental stage, indicating the potential function of epigenetics on the expression regulation of genes related to the specific pathway at different stages of grain development. The results demonstrated that the dynamic change of DNA methylation plays a crucial function in gene regulation, revealing the potential function of epigenetics in grain development in foxtail millet.
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http://dx.doi.org/10.3389/fpls.2021.741415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429616PMC
August 2021

Circ-Klhl8 overexpression increased the therapeutic effect of EPCs in diabetic wound healing via the miR-212-3p/SIRT5 axis.

J Diabetes Complications 2021 Aug 11:108020. Epub 2021 Aug 11.

Department of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, #321 Zhongshan Road, Nanjing, 210008 Jiangsu, China. Electronic address:

Previous studies found that hypoxic pretreatment of endothelial progenitor cells (EPCs) prior to transplantation had a greater therapeutic effect than untreated EPCs in promoting diabetic wound healing. However, the exact mechanism is uncertain. Here, circRNA expression in EPCs after hypoxic treatment was investigated. High-throughput sequencing was used to assess abnormal expression by EPCs of circular RNAs (circRNAs) following hypoxic pretreatment. Additionally, an in vivo full-thickness skin defect mouse model was used to assess the effects of transplanted EPCs on diabetic wound closure. Subsequently, the regulatory mechanism and targets were studied. The results showed that circ-Klhl8 overexpression suppressed hyper glucose-induced endothelial cell damage by activating autophagy. MiR-212-3p and SIRT5 were identified as the downstream targets of circ-Klhl8. Circ-Klhl8 overexpression promoted skin wound healing by regulating SIRT5-mediated autophagy. In conclusion, the study found that circ-Klhl8 overexpression increased the EPC therapeutic effect in promoting diabetic wound healing by targeting the miR-212-3p/SIRT5 axis.
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http://dx.doi.org/10.1016/j.jdiacomp.2021.108020DOI Listing
August 2021

Black Phosphorus Nanosheet Encapsulated by Zeolitic Imidazole Framework-8 for Tumor Multimodal Treatments.

ACS Appl Mater Interfaces 2021 Sep 8;13(37):43855-43867. Epub 2021 Sep 8.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education of China, Tianjin University of Science and Technology, Tianjin 300457, China.

Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 ([email protected]) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared [email protected] with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the [email protected] with high drug loading amount (1353.3 mg g). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted [email protected] an ideal candidate for tumor multimodal treatments.
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http://dx.doi.org/10.1021/acsami.1c04001DOI Listing
September 2021

Disrupted homeostasis of synovial hyaluronic acid and its associations with synovial mast cell proteases of rheumatoid arthritis patients and collagen-induced arthritis rats.

Immunol Res 2021 Sep 4. Epub 2021 Sep 4.

School of Pharmacy, School of Medicine, Changzhou University, Changzhou, 213164, Jiangsu, China.

Hyaluronic acid (HA) is the main component of the extracellular matrix (ECM) of joints, and it is important for a lubricating joint during body movement. Degradation is the main metabolic process of HA in vivo. Hyaluronidases (HAase) were known for HA degradation. The inflammation-induced HA rapid-metabolism can reduce HA viscosity and concentration in joints. Mast cells (MC) containing their specific proteases were found in synovium tissue. It is unclear if MC-proteases could be involved in HA degradation pathways. This study aims to explore the correlations between HA concentration vs mast cell proteases, or matrix metalloproteinase-2/9 (MMP-2/9) and to investigate the association of MC-specific proteases with disrupted synovial HA homeostasis in rheumatoid arthritis (RA) or collagen-induced arthritis rats. The synovial fluid samples from no-RA and RA patients were collected; the collagen-induced arthritis (CIA) rat model was established; HA concentration and the activities of MC-protease and MMP-2/9 in the samples were detected, and the correlations were analyzed. In vitro interaction experiment was carried out by mixing MC-proteases with HA to observe the degradation speed. The HA concentrations in synovial fluids were decreased in RA patients and CIA rats compared with those in no-RA subjects or normal rats respectively. The activities of mast cell proteases in synovial fluids were increased and positively correlated with MMP-9, but negatively correlated with HA concentrations. In vitro study, the addition of MC-chymase and tryptase promoted the speed in HA degradation. MC-proteases may influence HA degradation pathway.
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http://dx.doi.org/10.1007/s12026-021-09231-2DOI Listing
September 2021

School academic performance of children hospitalised with a chronic condition.

Arch Dis Child 2021 Sep 2. Epub 2021 Sep 2.

Population Child Health Research Team, School of Women's and Children's Health, University of New South Wales, Randwick, New South Wales, Australia.

Objective: To examine academic outcomes among children hospitalised with a chronic health condition.

Design: Population-level birth cohort.

Setting: New South Wales, Australia.

Participants: 397 169 children born 2000-2006 followed up to 2014.

Intervention/exposure: Hospitalisations with a chronic condition.

Main Outcome Measures: Academic underperformance was identified as 'below the national minimum standard' (BNMS) in five literacy/numeracy domains using the national assessment (National Assessment Program-Literacy and Numeracy) data. Multivariable logistic regression assessed the adjusted ORs (aORs) of children performing BNMS in each domain at each grade (grades 3, 5 and 7, respectively).

Results: Of children hospitalised with a chronic condition prior to National Assessment Program-Literacy and Numeracy (NAPLAN) (16%-18%), 9%-12% missed ≥1 test, with a maximum of 37% of those hospitalised ≥7 times, compared with 4%-5% of children not hospitalised. Excluding children who missed a NAPLAN test, more children hospitalised with a chronic condition performed BNMS across all domains and grades, compared with children not hospitalised (eg, for BNMS in reading at grade 3: n=2588, aOR 1.35 (95% CI 1.28 to 1.42); for BNMS in numeracy at grade 3: n=2619, aOR 1.51 (95% CI 1.43 to 1.59)). Increasing frequency and bed-days of hospitalisation were associated with 2-3 fold increased odds of performing BNMS across all domains and grades. Children hospitalised with mental health/behavioural conditions had the highest odds of performing BNMS across all domains at each grade.

Conclusions: Children hospitalised with a chronic condition underperform academically across literacy/numeracy domains at each school grade. Health and educational supports are needed to improve these children's academic outcomes.
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http://dx.doi.org/10.1136/archdischild-2020-321285DOI Listing
September 2021

Predation risk and the evolution of a vertebrate stress response: Parallel evolution of stress reactivity and sexual dimorphism.

J Evol Biol 2021 Aug 31. Epub 2021 Aug 31.

Department of Biological Sciences, W.M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, NC, USA.

Predation risk is often invoked to explain variation in stress responses. Yet, the answers to several key questions remain elusive, including the following: (1) how predation risk influences the evolution of stress phenotypes, (2) the relative importance of environmental versus genetic factors in stress reactivity and (3) sexual dimorphism in stress physiology. To address these questions, we explored variation in stress reactivity (ventilation frequency) in a post-Pleistocene radiation of live-bearing fish, where Bahamas mosquitofish (Gambusia hubbsi) inhabit isolated blue holes that differ in predation risk. Individuals of populations coexisting with predators exhibited similar, relatively low stress reactivity as compared to low-predation populations. We suggest that this dampened stress reactivity has evolved to reduce energy expenditure in environments with frequent and intense stressors, such as piscivorous fish. Importantly, the magnitude of stress responses exhibited by fish from high-predation sites in the wild changed very little after two generations of laboratory rearing in the absence of predators. By comparison, low-predation populations exhibited greater among-population variation and larger changes subsequent to laboratory rearing. These low-predation populations appear to have evolved more dampened stress responses in blue holes with lower food availability. Moreover, females showed a lower ventilation frequency, and this sexual dimorphism was stronger in high-predation populations. This may reflect a greater premium placed on energy efficiency in live-bearing females, especially under high-predation risk where females show higher fecundities. Altogether, by demonstrating parallel adaptive divergence in stress reactivity, we highlight how energetic trade-offs may mould the evolution of the vertebrate stress response under varying predation risk and resource availability.
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http://dx.doi.org/10.1111/jeb.13918DOI Listing
August 2021

Exosomal long non-coding RNA LIPCAR derived from oxLDL-treated THP-1 cells regulates the proliferation of human umbilical vein endothelial cells and human vascular smooth muscle cells.

Biochem Biophys Res Commun 2021 Oct 25;575:65-72. Epub 2021 Aug 25.

Department of Cardiothoracic and Vascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, 430030, China. Electronic address:

Background: It has been reported that long non-coding RNA (lncRNA) LIPCAR is involved in the progression of atherosclerosis. However, the mechanism underlying the effects of LIPCAR on regulating the occurrence and development of atherosclerosis remains unclear.

Methods: Reverse transcription-quantitative PCR was performed to detect the levels of LIPCAR in the plasma of patients with atherosclerosis and in THP-1 macrophages. THP-1 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) to induce foam cell formation. Furthermore, Transwell assay was carried out to evaluate the migration ability of vascular smooth muscle cells (VSMCs).

Results: The expression of LIPCAR in the plasma of patients with atherosclerosis was significantly higher compared with that in healthy subjects, while LIPCAR knockdown notably reversed ox-LDL-induced THP-1 cell apoptosis. In addition, LIPCAR was upregulated in exosomes derived from THP-1 cells treated with ox-LDL (THP-1/ox-LDL Exo). Furthermore, THP-1/ox-LDL Exo significantly increased the expression levels of CDK2 and proliferative cell nuclear antigen in human VSMCs, while these effects were reversed following LIPCAR silencing.

Conclusion: The results of the present study suggested that exosomal lncRNA LIPCAR derived from ox-LDL modified THP-1 cells could promote the progression of atherosclerosis. Therefore, LIPCAR may be considered as a novel biomarker for the development of new strategies to treat atherosclerosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.08.053DOI Listing
October 2021

Celastrol Exerts Cardioprotective Effect in Rheumatoid Arthritis by Inhibiting TLR2/HMGB1 Signaling Pathway-Mediated Autophagy.

Int Arch Allergy Immunol 2021 Aug 24:1-10. Epub 2021 Aug 24.

Department of Rheumatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Objective: Rheumatoid arthritis (RA) is a kind of chronic inflammatory disease characterized by the release of inflammatory cytokines and cardiomyocyte apoptosis, which lead to increased riskfor heart diseases. This study aims to explore the possible effect and mechanism of Celastrol on RA induced cardiac impairments in rats.

Methods: Collagen induced RA wistar rat models (CIA) were established for the measurement on secondary foot swelling degree, polyarthritis index score, spleen and thymus index. Pathological morphology was observed using H&E staining. Heart fibrosis was measured after Sirius red staining, while cell apoptosis was determined by TUNEL staining. For in vitro experiments, rat cardiomyocytes were isolated to determine the inflammatory cytokine secretion and cell apoptosis using ELISA and flow cytometry, respectively. Protein expressions of related index and autophagy were detected by Western blot and immunofluorescence.

Results: CIA rat model was successfully established and characterized by severe secondary foot swelling degree, and increased polyarthritis index score and spleen and thymus index. Synovial hyperplasia, disordered cardiomyocytes, cell infiltration and fibrosis were also observed in CIA rat model. Compared with CIA model, Celastrol treatment could suppress the release of inflammatory cytokines, including TNF-α, IL-6, IL-1β, as well as inhibiting the expressions of Bax, cleaved caspase3, collagen I, collagen III and α-SMA. In addition to that, Celastrol treatment can attenuate cell apoptosis and fibrosis of cardiomyocytes and elevate Bcl-2 expression. RA induced cell autophagy can be suppressed by Celastrol through inhibiting the activation of TLR2/HMGB1 signal pathway.

Conclusion: Celastrol can regulate TLR2/HMGB1 signal pathway to suppress autophagy and therefore exert cardioprotective effect in RA.
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http://dx.doi.org/10.1159/000517185DOI Listing
August 2021

SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.

Neoplasma 2021 Aug 25. Epub 2021 Aug 25.

Department of Neurosurgery, The Fifth Affiliated Hospital, Zhengzhou University, ZhengZhou, China.

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.
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http://dx.doi.org/10.4149/neo_2021_210327N410DOI Listing
August 2021

Cullin-5 (CUL5) as a potential prognostic marker in a pan-cancer analysis of human tumors.

Bioengineered 2021 12;12(1):5348-5360

Department of Neurosurgery, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.

There is some evidence supporting an association between Cullin-5 (CUL5) and cancer, but no research using pan-cancer analysis has been conducted previously. We therefore investigated the oncogenic role of CUL5 in 33 tumors from the Gene Expression Omnibus and The Cancer Genome Atlas databases. Many cancers reduce CUL5 levels, and the prognosis of certain cancers is vitally linked with CUL5 expression. CUL5 expression is associated with CD8 + T-cell infiltration levels in uveal melanomas and head and neck squamous cell carcinomas, and we observed a positive relationship between CUL5 and Tcm (T central memory) cells, and a negative relationship between T helper (Th) cells and pDC (plasmacytoid DC). CUL5 had negative associations with NK cells, NK CD56 cells, NK CD56 cells, Tregs, cytotoxic cells, and Th17 cells. Functions relating to protein processing and ubiquitin were included in the CUL5 functional mechanisms. The top 100 genes that are most strongly related to CUL5 were identified, and enrichment analysis indicated that the biological process with the closest relationship was neddylation, related pathways included the TGF-beta signaling pathway and intracellular receptor signaling pathway. CUL5 is related to biological cell behaviors such as chromosome segregation and positive regulation of chromosome organization. As the first study to perform a pan-cancer analysis of CUL5, the present findings will improve the understanding of the oncogenic role of CUL5 in different tumors.
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http://dx.doi.org/10.1080/21655979.2021.1940042DOI Listing
December 2021

Identification and validation of tumor microenvironment-related lncRNA prognostic signature for uveal melanoma.

Int J Ophthalmol 2021 18;14(8):1151-1159. Epub 2021 Aug 18.

Department of Ophthalmology, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China.

Aim: To investigate the role of tumor microenvironment (TME)-related long non-coding RNA (lncRNA) in uveal melanoma (UM), probable prognostic signature and potential small molecule drugs using bioinformatics analysis.

Methods: UM expression profile data were downloaded from the Cancer Genome Atlas (TCGA) and bioinformatics methods were used to find prognostic lncRNAs related to UM immune cell infiltration. The gene expression profile data of 80 TCGA specimens were analyzed using the single sample Gene Set Enrichment Analysis (ssGSEA) method, and the immune cell infiltration of a single specimen was evaluated. Finally, the specimens were divided into high and low infiltration groups. The differential expression between the two groups was analyzed using the R package 'edgeR'. Univariate, multivariate and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analyses were performed to explore the prognostic value of TME-related lncRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were also performed. The Connectivity Map (CMap) data set was used to screen molecular drugs that may treat UM.

Results: A total of 2393 differentially expressed genes were identified and met the criteria for the low and high immune cell infiltration groups. Univariate Cox analysis of lncRNA genes with differential expression identified 186 genes associated with prognosis. Eight prognostic markers of TME-included lncRNA genes were established as potentially independent prognostic elements. Among 269 differentially expressed lncRNAs, 69 were up-regulated and 200 were down-regulated. Univariate Cox regression analysis of the risk indicators and clinical characteristics of the 8 lncRNA gene constructs showed that age, TNM stage, tumor base diameter, and low and high risk indices had significant prognostic value. We screened the potential small-molecule drugs for UM, including W-13, AH-6809 and Imatinib.

Conclusion: The prognostic markers identified in this study are reliable biomarkers of UM. This study expands our current understanding of the role of TME-related lncRNAs in UM genesis, which may lay the foundations for future treatment of this disease.
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http://dx.doi.org/10.18240/ijo.2021.08.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342279PMC
August 2021

The Threshold Effects of Low-Dose-Rate Radiation on miRNA-Mediated Neurodevelopment of Zebrafish.

Radiat Res 2021 Aug 16. Epub 2021 Aug 16.

School of Public Health, University of South China, Hengyang 421001, PR China.

The biological effects and regulatory mechanisms of low-dose and low-dose-rate radiation are still rather controversial. Therefore, in this study we investigated the effects of low-dose-rate radiation on zebrafish neurodevelopment and the role of miRNAs in radiation-induced neurodevelopment. Zebrafish embryos received prolonged gamma-ray irradiation (0 mGy/h, 0.1 mGy/h, 0.2 mGy/h, 0.4 mGy/h) during development. Neurodevelopmental indicators included mortality, malformation rate, swimming speed, as well as the morphology changes of the lateral line system and brain tissue. Additionally, spatiotemporal expression of development-related miRNAs (dre-miR-196a-5p, dre-miR-210-3p, dre-miR-338) and miRNA processing enzymes genes (Dicer and Drosha) were assessed by qRT-PCR and whole mount in situ hybridization (WISH). The results revealed a decline in mortality, malformation and swimming speed, with normal histological and morphological appearance, in zebrafish that received 0.1 mGy/h; however, increased mortality, malformation and swimming speed were observed, with pathological changes, in zebrafish that received 0.2 mGy/h and 0.4 mGy/h. The expression of miRNA processing enzyme genes was altered after irradiation, and miRNAs expression was downregulated in the 0.1 mGy/h group, and upregulated in the 0.2 mGy/h and 0.4 mGy/h groups. Furthermore, ectopic expression of dre-miR-210-3p, Dicer and Drosha was also observed in the 0.4 mGy/h group. In conclusion, the effect of low-dose and low-dose-rate radiation on neurodevelopment follows the threshold model, under the regulation of miRNAs, excitatory effects occurred at a dose rate of 0.1 mGy/h and toxic effects occurred at a dose rate of 0.2 mGy/h and 0.4 mGy/h.
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http://dx.doi.org/10.1667/RADE-20-00265.1DOI Listing
August 2021

Ginsenoside Rb1 induces a pro-neurogenic microglial phenotype via PPARγ activation in male mice exposed to chronic mild stress.

J Neuroinflammation 2021 Aug 9;18(1):171. Epub 2021 Aug 9.

School of Life Science and Technology, Mental Health Center of Chengdu, University of Electronic Science and Technology of China, Chengdu, 610054, China.

Background: Anti-inflammatory approaches are emerging as a new strategy for the treatment of depressive disorders. Ginsenoside Rb1 (GRb1), a major component of Panax ginseng, can inhibit inflammatory cascade and alleviate depressive-like behaviors. Microglia can promote or inhibit adult hippocampal neurogenesis according to their functional phenotypes. Here, we examine whether GRb1 may exert antidepressant effects by promoting a pro-neurogenic phenotype of microglia and thereby increasing neurogenesis.

Methods: The antidepressant effects of GRb1 or the licensed antidepressant imipramine (IMI) were assessed in chronic mild stress (CMS)-exposed male mice. The depressive-like behaviors of mice were evaluated by sucrose preference test, forced swimming test (FST), and tail suspension test (TST). The microglial phenotypes were identified by pro- and anti-inflammatory cytokine expression and morphological properties, analyzed by RT-qPCR, western blotting, and immunofluorescence staining. The effect of GRb1-treated microglia on adult hippocampal neurogenesis in vivo and in vitro was detected using immunofluorescence staining.

Results: Behavioral assessment indicated that GRb1 or IMI treatment alleviated depressive-like behaviors in CMS-exposed mice. Immunofluorescence examination demonstrated that GRb1 induced a pro-neurogenic phenotype of microglia via activating PPARγ in vivo and in vitro, which were effectively reversed by the PPARγ inhibitor GW9662. In addition, GRb1-treated microglia increased the proliferation and differentiation of neural precursor cells.

Conclusions: These findings demonstrated that GRb1 alleviated depressive-like behaviors of CMS-exposed male mice mainly through PPARγ-mediated microglial activation and improvement of adult hippocampus neurogenesis.
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http://dx.doi.org/10.1186/s12974-021-02185-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353817PMC
August 2021

Virtual Reality-Assisted Percutaneous Transluminal Angioplasty for Interventional Treatment of Lower-Extremity Arteriosclerosis Obliterans.

J Healthc Eng 2021 27;2021:9975583. Epub 2021 Jul 27.

Department of Vascular Surgery, The Affiliated Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing City 210000, China.

This study was to evaluate the biomechanical characteristics of the vascular wall during virtual reality- (VR-) assisted percutaneous transluminal angioplasty (PTA) and its effect on the treatment of lower-extremity arteriosclerosis obliterans (LEAO). In this study, a three-dimensional (3D) model and a finite-element model of arteries were constructed first, and various fluid mechanics were analyzed. Then, the virtual expansion simulation (VES) of individualized PTA was performed based on the ABAQUS/Explicit module to analyze the interaction between the balloon and the blood vessel at different times and the changes in the vascular shape and structural stress distribution. Finally, an LEAO animal model was constructed. Based on conventional PTA (PTA group) and VR-assisted PTA (VR-PTA) treatment, the morphological changes of vascular lumen of the two animal models were evaluated. The results showed that the normal, stenotic blood vessels and blood models were successfully constructed; the pressure of the stenotic blood vessel at the stenosis decreased obviously and the shear stress of blood vessel wall increased compared with that of the normal blood vessels, and there may be a blood reflux area in the poststenosis stage. The simulation results of the VES showed that the maximum principal stress value at 3 mm of the marginal vessel was much lower than that at 5 mm (about 10% lower), so the maximum principal stress change within 2 mm of the balloon-expanded vessel was the most obvious. The treatment results of the animal model showed that the VR-PTA group showed an obvious increase in the diameter of the vascular lumen, a decrease in the intima and media area, and a decrease in the thickness of the vessel wall in contrast to the PTA group ( < 0.05), which had an important effect on the reconstruction and expansion of the vascular lumen. The VR-PTA treatment on LEAO was realized in this study, which provided critical reference for the follow-up application of VR technology in the evaluation of surgical plan and research on biomechanical mechanisms of restenosis after PTA.
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http://dx.doi.org/10.1155/2021/9975583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8331279PMC
July 2021

Safety, Tolerability, and Pharmacokinetics of High-Volume Subcutaneous Crenezumab, With and Without Recombinant Human Hyaluronidase in Healthy Volunteers.

Clin Pharmacol Ther 2021 Aug 4. Epub 2021 Aug 4.

Genentech, Inc., South San Francisco, California, USA.

Compared with intravenous formulations, subcutaneous (s.c.) formulations of therapeutic monoclonal antibodies may provide increased patient access and more convenient administration options, although historically high-volume s.c. administration (> 10-15 mL) has been challenging. We report results from two phase I studies in healthy participants (GP29523 and GP40201) that evaluated s.c. crenezumab, an anti-Aβ monoclonal antibody in development for individuals at risk for autosomal-dominant Alzheimer's disease. GP29523 assessed safety, tolerability, and pharmacokinetics (PK) in 68 participants (aged 50-80 years) who received single ascending doses (600-7,200 mg) of crenezumab or placebo (4-40 mL). GP40201 assessed safety, tolerability, and PK in 72 participants (aged 18-80 years) who received different combinations of dose (1,700-6,800 mg), infusion volume (10-40 mL), and flow rate (2-4 mL/minute), with/without recombinant human hyaluronidase (rHuPH20). There were no serious or dose-limiting adverse events in either study. There were no meaningful differences in pain scores among reference placebo (4 mL), test placebo (4-40 mL), or crenezumab (600-7,200 mg) in GP29523, or across treatments with varying infusion volume, flow rate, dose, or rHuPH20 co-administration or concentration in GP40201. Transient erythema was the most common infusion site reaction in both studies. In GP40201 at volumes of ≥ 20 mL, rHuPH20 co-administration appeared to reduce infusion site swelling incidence, but, in some cases, was associated with larger areas of infusion site erythema. Crenezumab exhibited approximately dose-proportional PK, and s.c. bioavailability was 66% and independent of dose or rHuPH20 co-administration. High-dose, high-concentration, high-volume s.c. crenezumab formulated with/without rHuPH20 was well-tolerated in healthy participants, with an acceptable safety profile.
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http://dx.doi.org/10.1002/cpt.2385DOI Listing
August 2021

Perirenal Perivascular Epithelioid Cell Tumor (PEcoma) with Pulmonary Micro Invasive Adenocarcinoma: A Case Report and Literature Review.

Onco Targets Ther 2021 21;14:4255-4260. Epub 2021 Jul 21.

Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People's Republic of China.

Perivascular epithelioid cell tumor (PEComa) is a rare type of mesenchymal neoplasm, which occurs most commonly in uterus and gastrointestinal tract. PEComa with perirenal manifestation is an extremely rare entity. To the best of our knowledge, only four cases have been reported up to now. In this case, we reported a patient with both a pulmonary mass and a perirenal mass. Two resections were performed successively and postoperative pathology suggested pulmonary micro invasive adenocarcinoma (MIA) and perirenal PEComa. This is the first case of perirenal PEComa with pulmonary MIA. Combining the present case and prior literature, we summarized the crucial role of immunohistochemistry in the diagnosis and consider that complete operation might be conducive to patients with perirenal PEComa that presents a benign phenotype, regardless of complications with other tumors.
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http://dx.doi.org/10.2147/OTT.S317777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313374PMC
July 2021

Split hand in amyotrophic lateral sclerosis: A systematic review and meta-analysis.

J Clin Neurosci 2021 Aug 21;90:293-301. Epub 2021 Jun 21.

Department of Neurology, Peking Union Medical College Hospital, Beijing 100730, China. Electronic address:

Objective: To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS).

Methods: PubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AA was calculated by AA = APB/ADM and split-hand index (SI) was calculated by SI = (APB × FDI)/ADM. The mean differences (MD) in APB/ADM and SI between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SI.

Results: Pooled results of five studies including 339 patients showed that 50% (95%CI: 35%-65%) of patients with ALS presented split hand. APB/ADM in patients with ALS was significantly lower than healthy population (MD: -0.38, 95%CI: -0.48, -0.28). SI in patients with ALS was significantly lower than healthy controls (MD: -5.87, 95%CI: -6.28, -5.46) and neuromuscular controls (MD: -5.60, 95%CI: -5.78, -5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SI. The sensitivity and specificity for SI were 78% and 81% (cut-off value: 5.2-11.8), respectively.

Conclusion: Half of ALS patients might show split hand sign. SI could be a potential biomarker in the diagnosis of ALS.
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http://dx.doi.org/10.1016/j.jocn.2021.06.015DOI Listing
August 2021

PET evidence of preclinical cerebellar amyloid plaque deposition in autosomal dominant Alzheimer's disease-causing Presenilin-1 E280A mutation carriers.

Neuroimage Clin 2021 4;31:102749. Epub 2021 Jul 4.

Banner Alzheimer's Institute, Phoenix, AZ, USA; Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Arizona State University, Tempe, AZ, USA; University of Arizona, Tucson, AZ, USA; Translational Genomics Research Institute, Phoenix, AZ, USA. Electronic address:

Background: In contrast to sporadic Alzheimer's disease, autosomal dominant Alzheimer's disease (ADAD) is associated with greater neuropathological evidence of cerebellar amyloid plaque (Aβ) deposition. In this study, we used positron emission tomography (PET) measurements of fibrillar Aβ burden to characterize the presence and age at onset of cerebellar Aβ deposition in cognitively unimpaired (CU) Presenilin-1 (PSEN1) E280A mutation carriers from the world's largest extended family with ADAD.

Methods: F florbetapir and C Pittsburgh compound B (PiB) PET data from two independent studies - API ADAD Colombia Trial (NCT01998841) and Colombia-Boston (COLBOS) longitudinal biomarker study were included. The tracers were selected independently by the respective sponsors prior to the start of each study and used exclusively throughout. Template-based cerebellar Aβ-SUVR (standard-uptake value ratios) using a known-to-be-spared pons reference region (cerebellar SUVR_pons), to a) compare 28-56-year-old CU carriers and non-carriers; b) estimate the age at which cerebellar SUVR_pons began to differ significantly in carrier and non-carrier groups; and c) characterize in carriers associations with age, cortical SUVR_pons, delayed recall memory, and API ADAD composite score.

Results: Florbetapir and PiB cerebellar SUVR_pons were significantly higher in carriers than non-carriers (p < 0.0001). Cerebellar SUVR_pons began to distinguish carriers from non-carriers at age 34, 10 years before the carriers' estimated age at mild cognitive impairment onset. Florbetapir and PiB cerebellar SUVR_pons in carriers were positively correlated with age (r = 0.44 & 0.69, p < 0.001), cortical SUVR_pons (r = 0.55 & 0.69, p < 0.001), and negatively correlated with delayed recall memory (r = -0.21 & -0.50, p < 0.05, unadjusted for cortical SUVR_pons) and API ADAD composite (r = -0.25, p < 0.01, unadjusted for cortical SUVR_pons in florbetapir API ADAD cohort).

Conclusion: This PET study provides evidence of cerebellar Aβ plaque deposition in CU carriers starting about a decade before the clinical onset of ADAD. Additional studies are needed to clarify the impact of using a cerebellar versus pons reference region on the power to detect and track ADAD changes, even in preclinical stages of this disorder.
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http://dx.doi.org/10.1016/j.nicl.2021.102749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278433PMC
September 2021

Impact of breast cancer risk factors on clinically relevant prognostic biomarkers for primary breast cancer.

Breast Cancer Res Treat 2021 Sep 29;189(2):483-495. Epub 2021 Jun 29.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH), Bethesda, USA.

Purpose: In addition to impacting incidence, risk factors for breast cancer may also influence recurrence and survival from the disease. However, it is unclear how these factors affect combinatorial biomarkers for aiding treatment decision-making in breast cancer.

Methods: Patients were 8179 women with histologically confirmed invasive breast cancer, diagnosed and treated in a large cancer hospital in Beijing, China. Individual clinicopathological (tumor size, grade, lymph nodes) and immunohistochemical (IHC: ER, PR, HER2, KI67) markers were used to define clinically relevant combinatorial prognostic biomarkers, including the Nottingham Prognostic Index (NPI: combining size, grade, nodes) and IHC4 score (combining ER, PR, HER2, KI67). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between breast cancer risk factors and quartiles (Q1-Q4) of NPI and IHC4 were assessed in multivariable polytomous logistic regression models.

Results: Overall, increasing parity (OR(95% CI) = 1.20(1.05-1.37);P = 0.007), overweight (OR(95% CI) = 1.60(1.29-1.98)), and obesity (OR(95% CI)  = 2.12(1.43-3.14)) were associated with higher likelihood of developing tumors with high (Q4) versus low (Q1) NPI score. Conversely, increasing age (OR(95% CI) = 0.75(0.66-0.84);P < 0.001) and positive family history of breast cancer (FHBC) (OR(95% CI) = 0.66(0.45-0.95)) were inversely associated with NPI. Only body mass index (BMI) was associated with IHC4, with overweight (OR(95% CI)  = 0.82(0.66-1.02)) and obese (OR(95% CI)  = 0.52(0.36-0.76)) women less likely to develop high IHC4 tumors. Notably, elevated BMI was associated with higher NPI irrespective of hormone receptor-expression status.

Conclusions: Our findings indicate that factors affecting breast cancer incidence, particularly age, parity, FHBC, and BMI, may impact clinically relevant prognostic biomarkers with implications for surveillance, prognostication, and counseling.
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http://dx.doi.org/10.1007/s10549-021-06294-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357643PMC
September 2021

Factor VIII replacement prophylaxis in patients with hemophilia A transitioning to adults: a systematic literature review.

Orphanet J Rare Dis 2021 06 26;16(1):287. Epub 2021 Jun 26.

Medical Affairs, Pharmaceuticals, Bayer Healthcare Company Ltd, Beijing, 100020, China.

Background: Despite the advantages of prophylactic treatment for hemophilia, patients tend to discontinue or not adhere to it because of several challenges such as long-term use, high cost, young patients transitioning to adolescents, and switch to self-infusion or self-care. The goal of this systematic literature review is to emphasize adherence to and efficiency of prophylactic treatment in adults.

Methods: A literature review was conducted in PubMed, Embase, and Cochrane databases until April 2021 according to PRISMA guidelines, and the protocol was registered with PROSPERO (CRD42020220085). Studies evaluating the efficacy of prophylaxis in enhancing the quality of life were included.

Results: A total of 31 articles involving 2379 patients with hemophilia were included in this systematic review. Of these, 26 studies were observational, questionnaire-based studies, and 5 were randomized controlled trials. The majority of studies reported lower annualized bleeding rates in patients receiving prophylaxis compared with those receiving on-demand treatment or those who discontinued prophylaxis. Standard-dose prophylaxis was reported to be effective in most of the studies. In developing countries like China, data suggest that low doses were administered because of limited available resources. However, standard dose or individualized prophylaxis should be provided to prevent joint damage in the long term. Compared with adults, greater adherence to treatment was observed in patients aged < 16 years.

Conclusion: This systematic review emphasizes the importance of adherence to prophylaxis among young adults transitioning from childhood. In countries like China, low-dose prophylaxis can help in preventing joint bleeds in the short term, but in the long term, standard-dose therapy has shown high adherence among young adults and better joint health, in turn improving the quality of life.
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http://dx.doi.org/10.1186/s13023-021-01919-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236177PMC
June 2021

Long Non-coding RNA 332443 Inhibits Preadipocyte Differentiation by Targeting Runx1 and p38-MAPK and ERK1/2-MAPK Signaling Pathways.

Front Cell Dev Biol 2021 8;9:663959. Epub 2021 Jun 8.

National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Long non-coding RNAs (lncRNAs) have emerged as integral regulators of pathophysiological processes, but their specific roles and mechanisms in adipose tissue development remain largely unknown. Here, through microarray analysis, co-expression, and tissue specific analysis of adipocyte tissues after fasting for 72 h, we found that expression was dramatically decreased, as well as the expression of . The UCSC database and Ensembl database indicated that is the antisense lncRNA of . and are highly enriched in adipose tissue and downregulated during adipogenic differentiation. Adipose tissue-specific knockdown of increased fat mass , and specific knockdown of in 3T3-L1 preadipocytes promoted adipogenic differentiation. In this process, expression was decreased when was downregulated in adipocytes or 3T3-L1 preadipocytes, and vice versa, when was upregulated, the expression of was increased. However, overexpression of decreased the expression of the adipocyte cell marker genes γ, α and significantly, while not affected the expression of Mechanistically, positively regulates expression in mouse adipocytes and suppresses adipocyte differentiation by attenuating the phosphorylation of MAPK-p38 and MAPK-ERK1/2 expression. Thus, this study indicated that inhibits adipogenesis and which might be a drug target for the prevention and treatment of obesity.
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http://dx.doi.org/10.3389/fcell.2021.663959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217766PMC
June 2021

Hypofractionated Intensity Modulated Radiation Therapy With Concurrent Chemotherapy in Locally Advanced Non-Small Cell Lung Cancer: A Phase II Prospective Clinical Trial (GASTO1011).

Pract Radiat Oncol 2021 Sep-Oct;11(5):374-383. Epub 2021 Jun 20.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou; Lung Cancer Institute of Sun Yat-sen University, Guangzhou; Guangdong Association Study of Thoracic Oncology, Guangzhou. Electronic address:

Purpose: We aimed to explore the efficacy and toxicity of split-course hypofractionated radiation therapy with concurrent chemotherapy (HRT-CHT) in patients with locally advanced non-small cell lung cancer (LANSCLC) in this single-arm, phase II study.

Methods And Materials: Patients with LANSCLC were considered eligible if their forced expiratory volume in 1 second/forced vital capacity (FEV/FVC%) and carbon monoxide diffusing capacity (DLCO%) were ≥40% and ≥45%, respectively. HRT-CHT using the intensity modulated radiation therapy technique was administered with 51 Gy in 17 fractions as the first course followed by a break. Patients without disease progression or persistent ≥grade 2 toxicities had an HRT-CHT of 15 to 18 Gy in 5 to 6 fractions as a boost. The primary endpoint was progression-free survival, and the secondary endpoint was overall survival (OS).

Results: Eighty-nine patients were enrolled and analyzed. The median follow-up was 29.5 months for all patients and 35.3 months for the survivors. The objective response rate was 97.8%; the median progression-free survival and OS were 11.0 and 27.0 months, respectively. Grade 3 acute esophagitis/pneumonitis occurred in 15 (16.9%)/7 (7.9%) patients. Grade 3/5 late pneumonitis occurred in 2 (2.2%)/1 (1.1%) patients. Of the 78 (87.6%) who completed the split-course HRT-CHT per protocol, patients with better FEV/FVC% and DLCO% after the break had significantly better OS (for the FEV/FVC1% ≥ 80% vs 60%-79% vs 41%-59% groups, 2-year OS values were 57.2% vs 56.9% vs 0%, respectively, P = .024; for the DLCO% ≥ 80% vs 60%-79% vs 45%-59% groups, 2-year OS values were 70.4% vs 48.4% vs 37.5%, respectively, P = .049).

Conclusions: Split-course HRT-CHT achieved a promising response rate and survival with tolerable toxicity in LANSCLC. Pulmonary function tests are necessary indicators for radiation treatment planning and dose escalation.
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http://dx.doi.org/10.1016/j.prro.2021.06.004DOI Listing
September 2021

The nearly complete genome of Ginkgo biloba illuminates gymnosperm evolution.

Nat Plants 2021 06 14;7(6):748-756. Epub 2021 Jun 14.

The Southern Modern Forestry Collaborative Innovation Center, the Key Lab of Tree Genetics and Biotechnology of Educational Department of China and the Key Lab of Tree Genetics and Silvicultural Sciences of Jiangsu Province, Nanjing Forestry University, Nanjing, China.

Gymnosperms are a unique lineage of plants that currently lack a high-quality reference genome due to their large genome size and high repetitive sequence content. Here, we report a nearly complete genome assembly for Ginkgo biloba with a genome size of 9.87 Gb, an N50 contig size of 1.58 Mb and an N50 scaffold size of 775 Mb. We were able to accurately annotate 27,832 protein-coding genes in total, superseding the inaccurate annotation of 41,840 genes in a previous draft genome assembly. We found that expansion of the G. biloba genome, accompanied by the notable extension of introns, was mainly caused by the insertion of long terminal repeats rather than the recent occurrence of whole-genome duplication events, in contrast to the findings of a previous report. We also identified candidate genes in the central pair, intraflagellar transport and dynein protein families that are associated with the formation of the spermatophore flagellum, which has been lost in all seed plants except ginkgo and cycads. The newly obtained Ginkgo genome provides new insights into the evolution of the gymnosperm genome.
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http://dx.doi.org/10.1038/s41477-021-00933-xDOI Listing
June 2021

Enhanced effects and mechanisms of Syngonium podophyllum-Peperomia tetraphylla co-planting on phytoremediation of low concentration uranium-bearing wastewater.

Chemosphere 2021 Sep 18;279:130810. Epub 2021 May 18.

Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Heng Yang, 421001, Hunan, PR China. Electronic address:

To improve the remediation efficiency of plants on low concentration uranium-bearing wastewater and clarify its strengthening mechanism, Syngonium podophyllum-Peperomia tetraphylla co-planting system was established, the enhanced effects of plants interaction on uranium removal were investigated, the chemical forms, valence states, and subcellular distribution of uranium in plants were confirmed, and the mechanisms of alleviating uranium stress by plants interaction were revealed. In Syngonium podophyllum-Peperomia tetraphylla co-planting system, the total amount of ethanol-extracted uranium and deionized water-extracted uranium with higher toxicity in their roots were reduced by 10.30% and 7.17%, respectively, which reduced the toxicity of uranium to plants. Plants interaction can inhibit the reduction of U(VI) in the root of Peperomia tetraphylla, which is conducive to the transport of uranium from roots to shoots. In addition, uranium in plants mainly existed in the cell wall (54.44%-66.52%) and the soluble fraction (23.85%-32.89%). These results indicated that Syngonium podophyllum and Peperomia tetraphylla co-planting can enhance their effects of uranium removal by alleviating uranium stress with the cell wall immobilization and vacuole compartmentation, improving biomass of plants, increasing bioaccumulation factor and translocation factor of uranium.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130810DOI Listing
September 2021

Epidemiological and clinical features of functional dyspepsia in a region with a high incidence of esophageal cancer in China.

Chin Med J (Engl) 2021 Jun 4;134(12):1422-1430. Epub 2021 Jun 4.

Department of Gastroenterology, Peking University Third Hospital, Beijing 100191, China.

Background: Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population.

Methods: A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses.

Results: A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028-4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251-0.741).

Conclusions: The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire.

Trial Registration: ClinicalTrials.gov, NCT01688908; https://clinicaltrials.gov/ct2/show/record/NCT01688908.
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http://dx.doi.org/10.1097/CM9.0000000000001584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213306PMC
June 2021

Worldwide prevalence of early repolarization pattern in general population and physically active individuals: A meta-analysis.

Medicine (Baltimore) 2021 Jun;100(22):e25978

Department of General Practice, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China.

Background: The early repolarization pattern (ERP) has recently been associated with cardiac events such as ventricular arrhythmias and sudden cardiac death. However, estimates of the prevalence of ERP vary widely, especially between the general population and physically active individuals. We performed this systematic review and meta-analysis to quantitatively evaluate the worldwide prevalence of ERP in the general population and physically active individuals.

Methods: We thoroughly searched the PubMed, EMBASE, Web of science, the Cochrane Library, and Scopus databases for relevant studies published until December 20, 2020. Studies in which prevalence was presented or could be estimated from eligible data were included. The pooled prevalence was analyzed using a random-effect model.

Results: Finally, we included 29 studies (182,135 subjects) in the general population and 14 studies (8087 subjects) in the physically active individuals. The worldwide pooled prevalence of ERP in the general population was 11.6% (95% confidence interval [CI]: 10.0%-13.3%). The incidence of ERP was 17.0% and 6.2% in men and women, respectively. The prevalence was 20.9% in blacks, 13.4% in Asians, and 10.1% in Caucasians. Additionally, the prevalence of ERP in physically active individuals was 33.9% (95% CI: 25.3%-42.6%).

Conclusion: A significant difference in the worldwide prevalence of ERP is revealed in this study. The ERP is highly prevalent in men, blacks, and physically active individuals.
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http://dx.doi.org/10.1097/MD.0000000000025978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183793PMC
June 2021
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