Publications by authors named "Huadong Wang"

103 Publications

Hub Long Noncoding RNAs with m6A Modification for Signatures and Prognostic Values in Kidney Renal Clear Cell Carcinoma.

Front Mol Biosci 2021 6;8:682471. Epub 2021 Jul 6.

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

N6-methyladenosine (m6A)-modified long noncoding RNAs (m6A-lncRNAs) have been proven to be involving in regulating tumorigenesis, invasion, and metastasis for a variety of tumors. The present study aimed to screen lncRNAs with m6A modification and investigate their biological signatures and prognostic values in kidney renal clear cell carcinoma (KIRC). lncRNA-seq, miRNA-seq, and mRNA-seq profiles of KIRC samples and the clinical characteristics of corresponding patients were downloaded from The Cancer Genome Atlas (TCGA). The R package "edgeR" was utilized to perform differentially expressed analysis on these profiles to gain DElncRNAs, DEmiRNAs, and DEmRNAs, respectively. The results of intersection of DElncRNAs and m6A-modified genes were analyzed by the weighted gene co-expression network analysis (WGCNA) to screen hub m6A-lncRNAs. Then, WGCNA was also used to construct an lncRNA-miRNA-mRNA (ceRNA) network. The Cox regression analysis was conducted on hub m6A-lncRNAs to construct the m6A-lncRNAs prognostic index (m6AlRsPI). Receiver operating characteristic (ROC) curve was used to assess the predictive ability of m6AlRsPI. The m6AlRsPI model was tested by internal and external cohorts. The molecular signatures and prognosis for hub m6A-lncRNAs and m6AlRsPI were analyzed. The expression level of hub m6A-lncRNAs in KIRC cell lines were quantified by qRT-PCR. A total of 21 hub m6A-lncRNAs associated with tumor metastasis were identified in the light of WGCNA. The ceRNA network for 21 hub m6A-lncRNAs was developed. The Cox regression analysis was performed on the 21 hub m6A-lncRNAs, screening two m6A-lncRNAs regarded as independent prognostic risk factors. The m6AlRsPI was established based on the two m6A-lncRNAs as follows: (0.0006066 × expression level of LINC01820) + (0.0020769 × expression level of LINC02257). The cutoff of m6AlRsPI was 0.96. KM survival analysis for m6AlRsPI showed that the high m6AlRsPI group could contribute to higher mortality. The area under ROC curve for m6AlRsPI for predicting 3- and 5-year survival was 0.760 and 0.677, respectively, and the m6AlRsPI was also tested. The mutation and epithelial-mesenchymal transition (EMT) analysis for m6AlRsPI showed that the high m6AIRsPI group had more samples with gene mutation and had more likely caused EMT. Finally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for mRNAs interacted with the two m6A-lncRNAs, showing they were involved in the process of RNA splicing and regulation of the mRNA surveillance pathway. qRT-PCR analysis showed that the two m6A-lncRNAs were upregulated in KIRC. In the present study, hub m6A-lncRNAs were determined associated with metastasis in KIRC, and the ceRNA network demonstrated the potential carcinogenic regulatory pathway. Two m6A-lncRNAs associated with the overall survival were screened and m6AlRsPI was constructed and validated. Finally, the molecular signatures for m6AlRsPI and the two m6A-lncRNAs were analyzed to investigate the potential modulated processes in KIRC.
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http://dx.doi.org/10.3389/fmolb.2021.682471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290079PMC
July 2021

GAN-CL: Generative Adversarial Networks for Learning From Complementary Labels.

IEEE Trans Cybern 2021 Jul 16;PP. Epub 2021 Jul 16.

Learning from complementary labels (CLs) is a useful learning paradigm, where the CL specifies the classes that the instance does not belong to, instead of providing the ground truth as in the ordinary supervised learning scenario. In general, although it is less laborious and more efficient to collect CLs compared with ordinary labels, the less informative signal in the complementary supervision is less helpful to learn competent feature representation. Consequently, the final classifier's performance greatly deteriorates. In this article, we leverage generative adversarial networks (GANs) to derive an algorithm GAN-CL to effectively learn from CLs. In addition to the role in original GAN, the discriminator also serves as a normal classifier in GAN-CL, with the objective constructed partly with the complementary information. To further prove the effectiveness of our schema, we study the global optimality of both generator and discriminator for the GAN-CL under mild assumptions. We conduct extensive experiments on benchmark image datasets using deep models, to demonstrate the compelling improvements, compared with state-of-the-art CL learning approaches.
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http://dx.doi.org/10.1109/TCYB.2021.3089337DOI Listing
July 2021

Erratum: usDSM: a novel method for deleterious synonymous mutation prediction using undersampling scheme.

Brief Bioinform 2021 Jun 15. Epub 2021 Jun 15.

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China.

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http://dx.doi.org/10.1093/bib/bbab247DOI Listing
June 2021

BnA1.CER4 and BnC1.CER4 are redundantly involved in branched primary alcohols in the cuticle wax of Brassica napus.

Theor Appl Genet 2021 Jun 12. Epub 2021 Jun 12.

National Key Laboratory of Crop Genetic Improvement, National Center of Rapeseed Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Key Message: The mutations BnA1.CER4 and BnC1.CER4 produce disordered wax crystals types and alter the composition of epidermal wax, causing increased cuticular permeability and sclerotium resistance. The aerial surfaces of land plants are coated with a cuticle, comprised of cutin and wax, which is a hydrophobic barrier for preventing uncontrolled water loss and environmental damage. However, the mechanisms by which cuticle components are formed are still unknown in Brassica napus L. and were therefore assessed here. BnA1.CER4 and BnC1.CER4, encoding fatty acyl-coenzyme A reductases localizing to the endoplasmic reticulum and highly expressed in leaves, were identified and functionally characterized. Expression of BnA1.CER4 and BnC1.CER4 cDNA in yeast (Saccharomyces cerevisiae) induced the accumulation of primary alcohols with chain lengths of 26 carbons. The mutant line Nilla glossy2 exhibited reduced wax crystal types, and wax composition analysis showed that the levels of branched primary alcohols were decreased, whereas those of the other branched components were increased. Further analysis showed that the mutant had reduced water retention but enhanced resistance to Sclerotinia sclerotiorum. Collectively, our study reports that BnA1.CER4 and BnC1.CER4 are fatty acyl-coenzyme A reductase genes in B. napus with a preference for branched substrates that participate in the biosynthesis of anteiso-primary alcohols.
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http://dx.doi.org/10.1007/s00122-021-03879-yDOI Listing
June 2021

usDSM: a novel method for deleterious synonymous mutation prediction using undersampling scheme.

Brief Bioinform 2021 Apr 19. Epub 2021 Apr 19.

GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China.

Although synonymous mutations do not alter the encoded amino acids, they may impact protein function by interfering with the regulation of RNA splicing or altering transcript splicing. New progress on next-generation sequencing technologies has put the exploration of synonymous mutations at the forefront of precision medicine. Several approaches have been proposed for predicting the deleterious synonymous mutations specifically, but their performance is limited by imbalance of the positive and negative samples. In this study, we firstly expanded the number of samples greatly from various data sources and compared six undersampling strategies to solve the problem of the imbalanced datasets. The results suggested that cluster centroid is the most effective scheme. Secondly, we presented a computational model, undersampling scheme based method for deleterious synonymous mutation (usDSM) prediction, using 14-dimensional biology features and random forest classifier to detect the deleterious synonymous mutation. The results on the test datasets indicated that the proposed usDSM model can attain superior performance in comparison with other state-of-the-art machine learning methods. Lastly, we found that the deep learning model did not play a substantial role in deleterious synonymous mutation prediction through a lot of experiments, although it achieves superior results in other fields. In conclusion, we hope our work will contribute to the future development of computational methods for a more accurate prediction of the deleterious effect of human synonymous mutation. The web server of usDSM is freely accessible at http://usdsm.xialab.info/.
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http://dx.doi.org/10.1093/bib/bbab123DOI Listing
April 2021

A mitochondria-localized pentatricopeptide repeat protein is required to restore hau cytoplasmic male sterility in Brassica napus.

Theor Appl Genet 2021 May 16;134(5):1377-1386. Epub 2021 Mar 16.

National Key Laboratory of Crop Genetic Improvement, National Centre of Rapeseed Improvement, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.

Key Message: A mitochondria-localized pentatricopeptide repeat protein was identified by positional cloning and transferred into the hau CMS line, where it successfully restored fertility Cytoplasmic male sterility (CMS) is a maternally inherited trait that can be controlled by restorer-of-fertility (Rf) genes present in the nucleus. The hau CMS was identified as a new form of CMS associated with the mitochondrial transcript orf288; however, a lack of a restorer gene has limited its utilization in Brassica crops. Here, the combination of Brassica 60 K array with bulk segregant analysis and map-based cloning was used to delimit the Rfh locus to an 82.2-kb region on chromosome A09. A candidate gene encoding a mitochondria-localized pentatricopeptide repeat (PPR) protein was identified and transferred into the hau CMS line, where it successfully restored the fertility of the hau CMS plants. Furthermore, the expression analysis showed that Rfh was highly expressed in the flower buds, and the sequence analysis results implied that functional divergence between RFH and rfh could be due to 59 amino acid residue differences in the deduced protein sequences. In addition, a co-separated molecular marker was developed based on the divergent sequences between the dominant and recessive alleles. These results will help enable the heterosis of Brassica crops in the future.
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http://dx.doi.org/10.1007/s00122-021-03777-3DOI Listing
May 2021

Immobilization of Ni (Ⅱ) at three levels of contaminated soil by rhamnolipids modified nano zero valent iron ([email protected]): Effects and mechanisms.

Chemosphere 2021 Aug 2;276:130139. Epub 2021 Mar 2.

State Key Laboratory of Bioreactor Engineering, School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China. Electronic address:

A kind of biosurfactant rhamnolipid modified zero-valent iron nanoparticles have been synthesized and applied to evaluate the immobilization efficiency of Ni (Ⅱ) contaminated soil at three concentration levels (200Ni, 600Ni and 1800Ni). The results of SEM and XRD were clearly indicative of the well-attached phenomenon of rhamnolipid on the nZVI, featuring better stability and dispersity, and FTIR analysis proposed the interactions between rhamnolipid and nZVI through monodentate chelating between carboxylate groups and nZVI or hydrogen bonding with Fe-O groups on the surface. Sequential extraction procedures (SEP) analysis illustrated that the majority of labile fractions had been transformed into less accessible fractions (Fe-Mn oxide-bound fractions and residual fractions) after 28 days of incubation. And for low-concentrations polluted soil, soil self-remediation played a dominant role, while [email protected] exhibited a more significant stabilizing effect for medium and high-concentrations pollution. Furthermore, XPS and XRD analyses of Ni-adsorbed [email protected] identified the formation of NiO, Ni(OH) and revealed the possible interaction mechanisms including reduction, adsorption and precipitation/co-precipitation. These results confirmed that [email protected] presented a promising prospect for the immobilization of Ni polluted soil.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130139DOI Listing
August 2021

High-generation near-isogenic lines combined with multi-omics to study the mechanism of polima cytoplasmic male sterility.

BMC Plant Biol 2021 Mar 5;21(1):130. Epub 2021 Mar 5.

National Key Laboratory of Crop Genetic Improvement, National Center of Rapeseed Improvement, Huazhong Agricultural University, Wuhan, 430070, China.

Background: Cytoplasmic male sterility (CMS), which naturally exists in higher plants, is a useful mechanism for analyzing nuclear and mitochondrial genome functions and identifying the role of mitochondrial genes in the plant growth and development. Polima (pol) CMS is the most universally valued male sterility type in oil-seed rape. Previous studies have described the pol CMS restorer gene Rfp and the sterility-inducing gene orf224 in oil-seed rape, located in mitochondria. However, the mechanism of fertility restoration and infertility remains unknown. Moreover, it is still unknown how the fecundity restorer gene interferes with the sterility gene, provokes the sterility gene to lose its function, and leads to fertility restoration.

Result: In this study, we used multi-omics joint analysis to discover candidate genes that interact with the sterility gene orf224 and the restorer gene Rfp of pol CMS to provide theoretical support for the occurrence and restoration mechanisms of sterility. Via multi-omics analysis, we screened 24 differential genes encoding proteins related to RNA editing, respiratory electron transport chain, anther development, energy transport, tapetum development, and oxidative phosphorylation. Using a yeast two-hybrid assay, we obtained a total of seven Rfp interaction proteins, with orf224 protein covering five interaction proteins.

Conclusions: We propose that Rfp and its interacting protein cleave the transcript of atp6/orf224, causing the infertility gene to lose its function and restore fertility. When Rfp is not cleaved, orf224 poisons the tapetum cells and anther development-related proteins, resulting in pol CMS mitochondrial dysfunction and male infertility. The data from the joint analysis of multiple omics provided information on pol CMS's potential molecular mechanism and will help breed B. napus hybrids.
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http://dx.doi.org/10.1186/s12870-021-02852-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934456PMC
March 2021

Computational study and optimization experiment of nZVI modified by anionic and cationic polymer for Cr(VI) stabilization in soil: Kinetics and response surface methodology (RSM).

Environ Pollut 2021 May 14;276:116745. Epub 2021 Feb 14.

Shanghai Institute of Pollution Control and Ecological Security, Shanghai, 200092, China; School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

Nanoscale zero-valent iron (nZVI) modified by cationic polyquaternium-7 (M550-nZVI) or anionic carboxymethyl cellulose (CMC-nZVI) were freshly synthesized, and followed by the successful applicability for the stabilization of Cr(VI) in soil. Scanning electron microscope (SEM) showed that the sizes of M550-nZVI and CMC-nZVI were 42-170 nm and 66-200 nm, respectively. X-ray diffraction (XRD) confirmed the presence of Fe and FeC in the as-synthesized composites. The kinetics were well fitted with pseudo-second order model (R > 0.99), indicating that the process was principally chemical reduction. Additionally, we observed that M550-nZVI had better resistance to oxidation than that of CMC-nZVI. Besides, RSM experiments showed that acetate ion (AA) could promote the Cr(VI) removal but humic acid ion (HA) and carbonate ion (CA) resulted in negative effects. Moreover, the modeling predication revealed that the optimum Cr(VI) removal of 92.44% by CMC-nZVI was available, being 22.52% higher than that of M550-nZVI. In conclusion, this work demonstrated that the inoxidizability of M550-nZVI had a dominant advantage, while CMC-nZVI had the more excellent reactivity than M550-nZVI. We believe that our conducted research work will open the new avenues for effective removal of heavy metals from the soil.
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http://dx.doi.org/10.1016/j.envpol.2021.116745DOI Listing
May 2021

Magnesium-Based Whitlockite Bone Mineral Promotes Neural and Osteogenic Activities.

ACS Biomater Sci Eng 2020 10 16;6(10):5785-5796. Epub 2020 Sep 16.

Department of Orthopedics, the Fourth Medical Centre, Chinese PLA General Hospital, Beijing, 100048, China.

Nerves spread throughout human bone minerals and play an important role in regulating osteogenic homeostasis. However, whether the distributive nerves can sense bone minerals and the role of bone minerals in nerve outgrowth are still unclear. We hypothesized that a natural magnesium-containing bone mineral, whitlockite (WH), the second most abundant bone mineral in the human body, could simultaneously promote both osteogenic and neural activities. To verify the hypothesis, both WH and hydroxyapatite (HAP) nanoparticles were synthesized, and their characterization was completed by Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). The effect of WH on neural differentiation of mesenchymal stem cells (MSCs) and neural progenitor cells (NPCs) in 2D and 3D culture was examined by immunostaining and quantitative real-time polymerase chain reaction (qRT-PCR). The secretion of calcitonin gene-related polypeptide (CGRP) was examined by enzyme-linked immunosorbent assay (ELISA). The neural and osteogenic differentiation in a preosteoblasts and NPCs coculture system was examined by immunostaining and qRT-PCR. The results showed that WH promotes the gene and protein expression of neuronal specific marker (MAP-2 and βIII-tubulin) in 2D and 3D culture systems. In addition, the neurite length in the WH group was significantly longer than in other groups. Furthermore, both neural differentiation and osteogenic differentiation were simultaneously enhanced in the WH group in the coculture system. Thus, this study demonstrated the simultaneous stimulatory effect of WH bone mineral on neural and osteogenic activities, which provided WH as a valuable material for bone regeneration.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00852DOI Listing
October 2020

[Application of high frequency color Doppler ultrasonography combined with microvascular stapler in maxillofacial defect repair].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2020 Dec;34(12):1102-1107

Oral and Maxillofacial Surgery,Nanchong Central Hospital,Second Clinical Medical College of North Sichuan Medical College,Nanchong,Sichuan Province,637000,China.

To evaluate the clinical application value of high frequency color Doppler ultrasound(HFCUS) combined with microvascular stapler in the repair of oral and maxillofacial defects with the anterolateral thigh perforator flap. Forty maxillofacial malignant tumor patients were divided into HFCUS+stapler group(23 cases) and control group(17 cases). All of cases used anterolateral thigh flap without fascia lata to repair the soft tissue defect in the operative area. One artery and two veins were anastomosed during the operation. The flaps were harvested from 6.0 cm×7.0 cm to 10.0 cm×12.0 cm, and the donor sites were closed and sutured at the same time. In group HFCUS+stapler, HFCUS was used to locate the perforating vessels and mark the location on the body surface the operation, and the vein was anastomosed intraoperatively with a stapler. In the control group, only iliac patella line was fixed before operation, and the vein was manually sutured during operation. The clinical data of 2 groups was evaluated by comparing the time consumption of flap harvest, the vascular anastomosis, the incidence of postoperative venous crisis, and the long-term survival rate of flap. In the HFCUS+stapler group, a total of 27 perforators were found before the operation, 24 perforators within 1.0 cm from the preoperative marker were actually detected during the operation, and the remaining 3 perforators were about 1.7 cm, 2.0 cm and 2.5 cm from the marker respectively, with an accuracy rate of 88.9%. HFCUS+stapler group used (63.17±7.80) min to harvest the flap, while the control group used (85.47±7.41) min HFCUS+stapler group took significantly less time than the control group(<0.001). The arterial anastomat time in the HFCUS+stapler group was (9.48±1.20) min and it was (9.18±1.13) min in the control group. The difference between the two groups was not statistically significant(=0.426). The total anastomosis time of the two veins was (14.87±2.62) min in the HFCUS+stapler group and (33.06±3.86) min in the control group. The HFCUS+stapler group had significantly less anastomosing time than the control group(<0.001). In HFCUS+stapler group, no arteriovenous crisis occurred after operation, and all flaps survived well 15 days after operation. In the control group, 2 cases had venous crisis after operation(=0.091). HFCUS combined with iliac patellar line can improve the accuracy of anatomical perforated vessels, reduce the time of flap harvesting, and reduce the possibility of accidental injury of perforated vessels. The use of microvascular stapler for vein anastomosis can reduce the operation time and improve the survival rate of flap. The combination of the two can significantly reduce the operation time of microsurgical repairing maxillofacial soft tissue defect, improve the operation quality, and has higher clinical application value.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2020.12.011DOI Listing
December 2020

Anatomical evidence for the efferent pathway from the hypothalamus to autonomic innervation in the anterior chamber structures of eyes.

Exp Eye Res 2021 01 21;202:108367. Epub 2020 Nov 21.

Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.
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http://dx.doi.org/10.1016/j.exer.2020.108367DOI Listing
January 2021

Predicting Hot Spot Residues at Protein-DNA Binding Interfaces Based on Sequence Information.

Interdiscip Sci 2021 Mar 17;13(1):1-11. Epub 2020 Oct 17.

Key Laboratory of Intelligent Computing and Signal Processing of Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, 230601, Anhui, China.

Hot spot residues at protein-DNA binding interfaces are hugely important for investigating the underlying mechanism of molecular recognition. Currently, there are a few tools available for identifying the hot spot residues in the protein-DNA complexes. In addition, the three-dimensional protein structures are needed in these tools. However, it is well known that the three-dimensional structures are unavailable for most proteins. Considering the limitation, we proposed a method, named SPDH, for predicting hot spot residues only based on protein sequences. Firstly, we obtained 133 features from physicochemical property, conservation, predicted solvent accessible surface area and structure. Then, we systematically assessed these features based on various feature selection methods to obtain the optimal feature subset and compared the models using four classical machine learning algorithms (support vector machine, random forest, logistic regression, and k-nearest neighbor) on the training dataset. We found that the variability of physicochemical property features between wild and mutative types was important on improving the performance of the prediction model. On the independent test set, our method achieved the performance with AUC of 0.760 and sensitivity of 0.808, and outperformed other methods. The data and source code can be downloaded at https://github.com/xialab-ahu/SPDH .
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http://dx.doi.org/10.1007/s12539-020-00399-zDOI Listing
March 2021

High-brightness anterograde transneuronal HSV1 H129 tracer modified using a Trojan horse-like strategy.

Mol Brain 2020 01 13;13(1). Epub 2020 Jan 13.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China.

Neurotropic viral transsynaptic tracing is an increasingly powerful technique for dissecting the structure and function of neural circuits. Herpes simplex virus type 1 strain H129 has been widely used as an anterograde tracer. However, HSV tracers still have several shortcomings, including high toxicity, low sensitivity and non-specific retrograde labeling. Here, we aimed to construct high-brightness HSV anterograde tracers by increasing the expression of exogenous genes carried by H129 viruses. Using a Trojan horse-like strategy, a HSV/AAV (adeno-associated virus) chimaera termed H8 was generated to enhance the expression of a fluorescent marker. In vitro and in vivo assays showed that the exogenous gene was efficiently replicated and amplified by the synergism of the HSV vector and introduced AAV replication system. H8 reporting fluorescence was brighter than that of currently available H129 tracers, and H8 could be used for fast and effective anterograde tracing without additional immunostaining. These results indicated that foreign gene expression in HSV tracers could be enhanced by integrating HSV with AAV replication system. This approach may be useful as a general enhanced expression strategy for HSV-based tracing tools or gene delivery vectors.
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http://dx.doi.org/10.1186/s13041-020-0544-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958791PMC
January 2020

[Predictive value of serum procalcitonin and hypersensitive C-reactive protein levels in patients with acute cerebral infarction complicated with infection].

Authors:
Huadong Wang

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2019 Aug;31(8):962-966

Department of Critical Care Medicine, Feicheng Mining Center Hospital, Feicheng 271608, Shandong, China. Corresponding author: Wang Huadong, Email:

Objective: To analyze the changes of early procalcitonin (PCT) and hypersensitive C-reactive protein (hs-CRP) in patients with acute cerebral infarction, and to explore the predictive value of both for acute cerebral infarction with infection.

Methods: 206 acute cerebral infarction patients admitted to the department of neurology of Feicheng Mining Center Hospital from May 2014 to May 2019 were enrolled. Clinical data of patients and serum PCT and hs-CRP levels at 24, 48 and 72 hours after onset were collected. Patients were divided into infected group (n = 69) and non-infected group (n = 137) according to whether infection occurred within 5 days after onset. And 60 healthy people in the same period were selected as the healthy control group. The trends of serum PCT and hs-CRP levels in each group were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the values of serum PCT and hs-CRP levels in identifying acute cerebral infarction with infection.

Results: The serum level of PCT at 24, 48 and 72 hours in the infected group and the non-infected group were significantly higher than those in the healthy control group, and the serum level of PCT at 48 hours and 72 hours in the infected group were significantly higher than those in the non-infected group (μg/L: 0.28±0.08 vs. 0.19±0.03, 0.31±0.07 vs. 0.15±0.06, both P < 0.05). Compared with 24 hours, the serum PCT level in the infected group at 48 hours and 72 hours were significantly increased, but decreased in the non-infected group. The serum hs-CRP level in the infected group at 24, 48 and 72 hours were significantly higher than those in the non-infected group and the healthy control group (mg/L: 5.86±1.73 vs. 5.45±1.08, 5.25±1.33; 8.01±2.41 vs. 5.67±2.13, 5.25±1.33; 14.25±2.19 vs. 12.30±1.87, 5.25±1.33; all P < 0.05). And the serum hs-CRP level in the non-infected group at 72 hours was significantly higher than that in the healthy control group. Compared with 24 hours, the serum hs-CRP level in the infected group and non-infected group at 48 hours and 72 hours were significantly increased. It was shown by ROC curve analysis that serum PCT and hs-CRP levels at 24 hours had no predictive value for infection in patients with acute cerebral infarction [area under ROC curve (AUC) was 0.440, 0.576 respectively, both P > 0.05]. At 48 hours, the AUC of serum PCT in diagnosis of acute cerebral infarction with infection was 0.850 [95% confidence interval (95%CI) = 0.784-0.916], the sensitivity and specificity were 66.7% and 97.8% when the cut-off of PCT was 0.25 μg/L; the AUC of serum hs-CRP was 0.759 (95%CI = 0.689-0.830), the sensitivity and specificity were 66.7% and 76.6% when the cut-off of hs-CRP was 6.80 mg/L; the AUC of PCT combined with hs-CRP was 0.911 (95%CI = 0.859-0.964), the sensitivity was 90.5%, the specificity was 86.9%. At 72 hours, the AUC of serum PCT in diagnosis of acute cerebral infarction with infection was 0.952 (95%CI = 0.916-0.989), the sensitivity and specificity were 89.9% and 93.4% when the cut-off of PCT was 0.23 μg/L; the AUC of serum hs-CRP was 0.753 (95%CI = 0.678-0.828), the sensitivity and specificity were 60.9% and 83.2% when the cut-off of hs-CRP was 14.01 mg/L; the AUC of PCT combined with hs-CRP was 0.954 (95%CI = 0.918-0.991), the sensitivity was 97.1%, and the specificity was 89.8%. The results showed that the diagnostic value of serum PCT at 48 hours and 72 hours were higher than those of hs-CRP, and the predictive value of PCT combined with hs-CRP was higher than those of single index.

Conclusions: Acute cerebral infarction itself has an effect on serum PCT level; serum PCT level above 0.23 μg/L at 72 hours after onset and reference to serum hs-CRP level have a high predictive value for the diagnosis of infection in patients with acute cerebral infarction.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2019.08.010DOI Listing
August 2019

Proteomics Analysis Identifies IRSp53 and Fascin as Critical for PRV Egress and Direct Cell-Cell Transmission.

Proteomics 2019 12 7;19(23):e1900009. Epub 2019 Oct 7.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.

Pseudorabies virus (PRV) has been widely used as a live trans-synaptic tracer for mapping neuronal circuits. Systematically identifying mature PRV virion proteomes and defining co-purified host proteins are necessary to fully understand the detailed mechanism underlying PRV transmission processes. Here, a PRV virion purification strategy based on sorting with flow cytometry is developed and the mature extracellular and intracellular PRV virion proteomes using LC coupled with MS/MS are characterized. In addition to viral proteins, a large number of host proteins are also identified, including proteins related to actin cytoskeletal dynamics and membrane protrusion. How many of these host proteins are true virion components are unknown and the majority of these may not be. Through functional analysis, it is found that IRSp53 and fascin are critical for the egress process and play a role in direct cell-cell transmission. Moreover, it is shown that CDC42 and Rac1 are also involved in the production of mature extracellular virions. The results suggest that the formation of the filopodia-like cytoskeleton and the rearrangement of the membrane, which are both associated with IRSp53 and fascin, may be important for the transmission of viruses used in neuronal tracing.
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http://dx.doi.org/10.1002/pmic.201900009DOI Listing
December 2019

Exogenous Promoter Triggers APETALA3 Silencing through RNA-Directed DNA Methylation Pathway in .

Int J Mol Sci 2019 Sep 11;20(18). Epub 2019 Sep 11.

National Key Laboratory of Crop Genetic Improvement, National Center of Rapeseed Improvement, Huazhong Agricultural University, Wuhan 430070, China.

The development of floral organs plays a vital role in plant reproduction. In our research, the () promoter-transgenic lines showed abnormal developmental phenotypes in stamens and petals. The aim of this study is to understand the molecular mechanisms of the morphological defects in transgenic plants. By performing transgenic analysis, it was found that the -promoted genes and the vector had no relation to the morphological defects. Then, we performed the expression analysis of the class A, B, and C genes. A dramatic reduction of transcript levels of class B genes ( and ) was observed. Additionally, we also analyzed the methylation of the promoters of class B genes and found that the promoter of was hypermethylated. Furthermore, combining mutations in , , and with the -silencing lines rescued the abnormal development of stamens and petals. The expression of was reactivated and the methylation level of promoter was also reduced in RdDM-defective -silencing lines. Our results showed that the RdDM pathway contributed to the transcriptional silencing in the transgenic -silencing lines. Moreover, the results revealed that fact that the exogenous fragment of a promoter could trigger the methylation of homologous endogenous sequences, which may be ubiquitous in transgenic plants.
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http://dx.doi.org/10.3390/ijms20184478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770043PMC
September 2019

[Analysis and Improvement Suggestions on Change of Medical Devices Licensing Items].

Zhongguo Yi Liao Qi Xie Za Zhi 2019 Jul;43(4):297-299

Henan Provincial Food and Drug Evaluation Inspection Center, Zhengzhou, 450018.

Based on the statistics of 350 technical evaluations of changes in licensing items of class Ⅱ passive and active medical devices completed in Henan province from July 2017 to November 2018, this paper summarized and analysed the common problems and requirements listed in the correction notifications of the technical evaluation, and put forward relevant countermeasures or suggestions, with a view to further speeding up the evaluation and approval of medical devices.
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http://dx.doi.org/10.3969/j.issn.1671-7104.2019.04.017DOI Listing
July 2019

Evaluation of retrograde labeling profiles of HSV1 H129 anterograde tracer.

J Chem Neuroanat 2019 10 23;100:101662. Epub 2019 Jul 23.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, China; Center for Brain Science, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address:

Herpes simplex virus type 1 H129 strain has been widely used as a useful anterograde neuronal circuit tracing tool. However, whether H129 is a rigorous anterograde tracer and undergoes anterograde-only spreading are questions of significant interest. In the present study, we evaluated the retrograde labeling efficiency of H129 using a TK and ICP34.5 dual deleted H129 recombinant (named as H306) which was replication-deficient in non-dividing postmitotic neurons. The novel tracer was tested in vitro and in vivo for evaluating its invasion properties and tracing capacities. The results demonstrated that H306 could efficiently label the neurons following intracerebral injection. Notably, H306 could also efficiently infect upstream innervating neurons through axon terminal uptake and displayed obvious retrograde labeling phenotype, regardless of 3 days or 10 days of tracing. The data implied that replication-competent, trans-multisynaptic H129 tracing results might be a mixed neural networks from two types of starter cells, because the retrogradely infected neurons would also replicate H129 and spread virus anterogradely through their axon collaterals (ectopic starter sites), as the local infected neurons in the injection site (true starter site). Therefore, the interpretation of the anterogradely tracing neural networks by current H129 tools at longer post-inoculation intervals need to be cautious, and effective modification strategies are needed to avoid or block the axon terminal invasion process of H129, which is important for rigorous anterograde H129 tracer.
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http://dx.doi.org/10.1016/j.jchemneu.2019.101662DOI Listing
October 2019

Construction of restorer lines and molecular mapping for restorer gene of hau cytoplasmic male sterility in Brassica napus.

Theor Appl Genet 2019 Sep 4;132(9):2525-2539. Epub 2019 Jun 4.

National Key Laboratory of Crop Genetic Improvement, National Center of Rapeseed Improvement in Wuhan, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan City, 430070, People's Republic of China.

Key Message: Successfully constructing restorer lines for the hau CMS line and molecular mapping of Rfh to a 94 kb candidate region on chromosome A03 in Brassica napus. Cytoplasmic male sterility is a general phenomenon in almost 200 species, and the interaction between chimeric genes in mitochondria and restorer genes in nucleus may be responsible for restoration of male fertility. Orf288 has been identified as a CMS-associated gene in the hau CMS line of Brassica napus and Brassica juncea; however, the restorer lines/genes have not been found yet. We therefore have successfully constructed two restorer lines in B. napus by extensive testcrossing and have mapped a major restorer gene Rfh to a physical distance of 94 kb on chromosome A03 by whole-genome resequencing and molecular markers. We found that the restorer line is indeed restored to male fertility at histological level. Comparative genomics and collinearity analysis between close relatives revealed that rearrangements and recombination may have happened and thus caused the production of Rfh or components of the restoration of fertility complex. Meanwhile, nuclear backgrounds with multiple loci and temperature were related to the variation and instability of restoration of fertility in three different populations. Our study provides new sights into the coevolution between restorer genes and CMS-associated genes as well as the cultivation of superior hybrids via molecular breeding.
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http://dx.doi.org/10.1007/s00122-019-03368-3DOI Listing
September 2019

USP8 ameliorates cognitive and motor impairments via microglial inhibition in a mouse model of sepsis-associated encephalopathy.

Brain Res 2019 09 7;1719:40-48. Epub 2019 May 7.

Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou 510632, PR China. Electronic address:

Sepsis-associated encephalopathy (SAE) is a common and serious complication of sepsis, which is thought to be caused by neuroinflammation. In our previous study, ubiquitin-specific protease 8 (USP8), was reported to regulate inflammation in vitro. In the current study, we investigated whether increased USP8 expression would ameliorate the cognitive and motor impairments induced by cecal ligation and puncture (CLP) in mice, a model of SAE. Male adult mice were randomly divided into four groups: control, sham, CLP, and CLP + USP8 groups. The CLP + USP8 mice showed reduced weight loss on day 4 post-CLP, with a slight increase noted on day 7. The mortality rate in the CLP group was 70% 48 h after CLP; however, USP8 significantly improved survival after CLP. USP8 modulated the neurobehavioral scores in CLP mice. Our results also indicate that USP8 attenuated the CLP-induced cognitive and motor impairments, based on the performance of mice in the Morris water maze (MWM), pole-climbing, and wire suspension tests. USP8 suppressed the release of pro-inflammatory mediators, including prostaglandin E(PGE) in the serum and nitric oxide (NO) in brain tissue, as well as levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) in brain tissue. Immunofluorescence experiments revealed that USP8 inhibited CLP-induced increases in microglial size and density in the hippocampus, and protected hippocampal neurons. Our findings indicate that neuroinflammation occurs in the brains of CLP mice, and that USP8 exerts protective effects against CLP-induced neuroinflammation and cognitive and motor impairments, which may aid in the development of novel therapeutic strategies for SAE.
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http://dx.doi.org/10.1016/j.brainres.2019.05.009DOI Listing
September 2019

Structural Characterization of a Boron(III) η-σ-Silane-Complex.

J Am Chem Soc 2019 May 8;141(20):8358-8363. Epub 2019 May 8.

Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials , Fudan University , Songhu Road 2005 , Shanghai 200438 , China.

Coordination of H-E (E = H, C, Si, etc.) σ-bonds to unsaturated element centers, forming η-σ-complexes, is a crucial step in H-E bond activations which are involved in numerous chemical transformations. Structural characterization of σ-complexes has provided invaluable insight into the σ-bond activation process. While numerous η-σ-complexes of low-oxidation-state transition metals have been isolated and thoroughly studied, those based on d metals or high-oxidation-state main group elements still remain elusive, despite their suggested role as key intermediates in σ-bond metathesis. Here we report the synthesis of a highly electrophilic o-carboranyl-substituted hydroborenium and its η-σ-(H-Si)-complex, the latter of which was characterized by X-ray analysis. Unlike previous known σ-(H-Si)-complexes in which back-donation contributes significantly to their stability, our computational studies revealed that no back-donation takes place between the borenium and silane moieties, and the key factors for the stability of this silane-borenium complex are (1) the strong interaction between the empty p orbital of the boron center and the bonding σ orbital of H-Si and (2) steric accessibility of the boron center due to the presence of a hydrogen substituent.
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http://dx.doi.org/10.1021/jacs.9b03213DOI Listing
May 2019

Detection of neural connections with ex vivo MRI using a ferritin-encoding trans-synaptic virus.

Neuroimage 2019 08 22;197:133-142. Epub 2019 Apr 22.

State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China; Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, 430074, PR China; Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, Shanghai, 200031, PR China. Electronic address:

The elucidation of neural networks is essential to understanding the mechanisms of brain functions and brain disorders. Neurotropic virus-based trans-synaptic tracing tools have become an effective method for dissecting the structure and analyzing the function of neural-circuitry. However, these tracing systems rely on fluorescent signals, making it hard to visualize the panorama of the labeled networks in mammalian brain in vivo. One MRI method, Diffusion Tensor Imaging (DTI), is capable of imaging the networks of the whole brain in live animals but without information of anatomical connections through synapses. In this report, a chimeric gene coding for ferritin and enhanced green fluorescent protein (EGFP) was integrated into Vesicular stomatitis virus (VSV), a neurotropic virus that is able to spread anterogradely in synaptically connected networks. After the animal was injected with the recombinant VSV (rVSV), rVSV-Ferritin-EGFP, into the somatosensory cortex (SC) for four days, the labeled neural-network was visualized in the postmortem whole brain with a T2-weighted MRI sequence. The modified virus transmitted from SC to synaptically connected downstream regions. The results demonstrate that rVSV-Ferritin-EGFP could be used as a bimodal imaging vector for detecting synaptically connected neural-network with both ex vivo MRI and fluorescent imaging. The strategy in the current study has the potential to longitudinally monitor the global structure of a given neural-network in living animals.
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http://dx.doi.org/10.1016/j.neuroimage.2019.04.039DOI Listing
August 2019

Bacteria-released outer membrane vesicles promote disseminated intravascular coagulation.

Thromb Res 2019 Jun 28;178:26-33. Epub 2019 Mar 28.

Department of Hematology, The 3rd Xiangya Hospital, Central South University, Changsha, PR China; State Key Laboratory of Medical Genetics, School of Biological Science and Technology, Central South University, Changsha, Hunan Province, PR China; Department of Pathophysiology, School of Basic Medical Science, Jinan University, Guangzhou, Guangdong Province, PR China; Key Laboratory of Non-resolving Inflammation and Cancer of Hunan Province, The 3rd Xiangya Hospital, Central South University, Changsha, PR China. Electronic address:

Introduction: Sepsis is frequently complicated by disseminated intravascular coagulation (DIC), which promotes multiple organ dysfunctions and significantly increase the mortality of patients with sepsis. How bacteria cause DIC is not fully understood. Outer membrane vesicles (OMVs) are membrane-enclosed microvesicles released by variety of bacteria. The aim of this study is to determine whether OMVs contribute to the pathogenesis of DIC during bacterial infection.

Methods: Wild-type (WT) or Toll-like receptor 4 (TLR4) knock-out mice were intraperitoneally injected with purified Escherichia coli (E.coli) derived OMVs, or with either wild type E.coli or E.coli with genetic deletion of ypjA, which is critical for OMV's production. Blood samples, liver and lung tissues were collected. The development of DIC was assessed in terms of the occurrence of coagulopathy, the thrombi deposition in livers and lungs, the multiple organ injuries, and the lethality.

Results: Genetic deletion of ypjA significantly attenuated E.coli-induced coagulopathy, intravascular thrombi deposition, multiple organ injuries and mortality, whereas injection of purified E.coli-derived OMVs resulted in the development of DIC in a TLR4-dependent manner.

Conclusions: OMVs importantly contribute to the pathogenesis of DIC during Gram-negative bacterial infection. These findings might open a new avenue to prevent infection-associated coagulopathy by targeting OMVs production.
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http://dx.doi.org/10.1016/j.thromres.2019.03.019DOI Listing
June 2019

Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine.

Emerg Microbes Infect 2019 ;8(1):45-54

f College of Life Science , Hunan Normal University , Changsha , People's Republic of China.

Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.
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http://dx.doi.org/10.1080/22221751.2018.1558962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455129PMC
July 2019

Systematic analysis of genes involved in oral cancer metastasis to lymph nodes.

Cell Mol Biol Lett 2018 15;23:53. Epub 2018 Nov 15.

2Institute of Tissue Engineering and Stem Cells, Nanchong Central Hospital, The Second Clinical Medical College of North Sichuan Medical College, No. 95, People's south Road, Shunqing District, Nanchong, Sichuan 637000 People's Republic of China.

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature - CCND1, JUN and SPP1 - which may be involved in oral cancer lymph node metastasis.
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http://dx.doi.org/10.1186/s11658-018-0120-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237046PMC
December 2018

Mesenchymal stem cells attenuate sepsis-induced liver injury via inhibiting M1 polarization of Kupffer cells.

Mol Cell Biochem 2019 Feb 3;452(1-2):187-197. Epub 2018 Sep 3.

Department of Infectious Disease, The First Affiliated Hospital, Jinan University, Guangzhou, 510630, Guangdong, People's Republic of China.

Sepsis is a leading cause of death in intensive care units that can result in acute hepatic damage. Animal experiments and clinical trials have shown that mesenchymal stem cell (MSC) therapy has some beneficial in several liver diseases. However, the protective effects of MSC therapy on sepsis-induced hepatic damage and associated mechanisms are not completely understood. The aim of the present study was to investigate the effects of MSCs on sepsis-induced liver injury and underlying mechanisms. A rat model of sepsis-induced liver injury was established by cecal ligation and puncture, and serum alanine aminotransferase and aspartate transaminase activities as well as liver histological changes were measured. Inflammatory cytokines, Kupffer cell M1 phenotype markers, and associated signal molecules were also determined in septic rats and in lipopolysaccharide (LPS)-treated Kupffer cells. Our results showed that injection of MSCs attenuated sepsis-induced liver injury. Treatment with MSCs inhibited activation of Kupffer cells towards M1 phenotype, attenuated TNF-α and IL-6 expression, and promoted IL-4 and IL-10 expression in septic rats and LPS-treated Kupffer cells. Furthermore, MSCs also inhibited the nuclear translocation of nuclear factor-kappa B in LPS-challenged Kupffer cells and the liver of septic rats. These results indicated that MSCs attenuated sepsis-induced liver injury through suppressing M1 polarization of Kupffer cells.
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http://dx.doi.org/10.1007/s11010-018-3424-7DOI Listing
February 2019

Evaluating Doctor Performance: Ordinal Regression-Based Approach.

J Med Internet Res 2018 07 18;20(7):e240. Epub 2018 Jul 18.

School of Economics and Management, University of Chinese Academy of Sciences, Beijing, China.

Background: Doctor's performance evaluation is an important task in mobile health (mHealth), which aims to evaluate the overall quality of online diagnosis and patient outcomes so that customer satisfaction and loyalty can be attained. However, most patients tend not to rate doctors' performance, therefore, it is imperative to develop a model to make doctor's performance evaluation automatic. When evaluating doctors' performance, we rate it into a score label that is as close as possible to the true one.

Objective: This study aims to perform automatic doctor's performance evaluation from online textual consultations between doctors and patients by way of a novel machine learning method.

Methods: We propose a solution that models doctor's performance evaluation as an ordinal regression problem. In doing so, a support vector machine combined with an ordinal partitioning model (SVMOP), along with an innovative predictive function will be developed to capture the hidden preferences of the ordering labels over doctor's performance evaluation. When engineering the basic text features, eight customized features (extracted from over 70,000 medical entries) were added and further boosted by the Gradient Boosting Decision Tree algorithm.

Results: Real data sets from one of the largest mobile doctor/patient communication platforms in China are used in our study. Statistically, 64% of data on mHealth platforms lack the evaluation labels from patients. Experimental results reveal that our approach can support an automatic doctor performance evaluation. Compared with other auto-evaluation models, SVMOP improves mean absolute error (MAE) by 0.1, mean square error (MSE) by 0.5, pairwise accuracy (PAcc) by 5%; the suggested customized features improve MAE by 0.1, MSE by 0.2, PAcc by 3%. After boosting, performance is further improved. Based on SVMOP, predictive features like politeness and sentiment words can be mined, which can be further applied to guide the development of mHealth platforms.

Conclusions: The initial modelling of doctor performance evaluation is an ordinal regression problem. Experiments show that the performance of our proposed model with revised prediction function is better than many other machine learning methods on MAE, MSE, as well as PAcc. With this model, the mHealth platform could not only make an online auto-evaluation of physician performance, but also obtain the most effective features, thereby guiding physician performance and the development of mHealth platforms.
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http://dx.doi.org/10.2196/jmir.9300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070724PMC
July 2018

A new method for neonatal rat ventricular myocyte purification using superparamagnetic iron oxide particles.

Int J Cardiol 2018 Nov 3;270:293-301. Epub 2018 Jun 3.

Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address:

Background: Neonatal rat ventricular myocytes (NRVMs) have proven to be an ideal research model for cardiac disease. However, the current methods to purify NRVMs have a limitation to obtain high purity. The purpose of this study was to develop a NRVM purification method by using superparamagnetic iron oxide particles (SIOP).

Methods: NRVMs were purified by using SIOP (SIOP group). The differential attachment with or without bromodeoxyuridine (BrdU) treatment served as control and BrdU groups, respectively. The Percoll gradient (Percoll) and magnetic-activated cell sorting (MACS) methods were performed to compare the purity and viability of NRVMs with SIOP method.

Results: The SIOP group enriched NRVMs up to 93.9 ± 2.0% purity determined by flow cytometry (FCM) and 95.6 ± 1.3% by immunofluorescence count (IF). In contrast, the control group gave purities of 71.9 ± 2.9% (by FCM) and 66.8 ± 8.9% (by IF), and the BrdU group obtained 82.0 ± 1.3% (by FCM) and 83.1 ± 2.4% (by IF). The purity of SIOP-isolated NRVMs was not different from that of Percoll and MACS groups. However, the cardiomyocytes separated by these methods, except SIOP protocol, were mixed with intrinsic cardiac adrenergic cells. NRVMs purified by SIOP shaped the similar three-dimensional morphology, with no difference in cell yield, viability and cytosolic Ca homeostasis at 24 h after isolation compared with NRVMs in other groups. Furthermore, SIOP-purified NRVMs retained the responses to phenylephrine and lipopolysaccharide challenge.

Conclusion: We first reported an efficient and novel method to purify NRVMs using SIOP, which may help accelerate innovative research in the field of cardiomyocyte biology.
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http://dx.doi.org/10.1016/j.ijcard.2018.05.133DOI Listing
November 2018
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