Publications by authors named "Xiao Cheng"

457 Publications

A Novel Two-Stage Refine Filtering Method for EEG-Based Motor Imagery Classification.

Front Neurosci 2021 1;15:657540. Epub 2021 Sep 1.

College of Mechanical and Electrical Engineering, Soochow University, Suzhou, China.

Cerebral stroke is a common disease across the world, and it is a promising method to recognize the intention of stroke patients with the help of brain-computer interface (BCI). In the field of motor imagery (MI) classification, appropriate filtering is vital for feature extracting of electroencephalogram (EEG) signals and consequently influences the accuracy of MI classification. In this case, a novel two-stage refine filtering method was proposed, inspired by Gradient-weighted Class Activation Mapping (Grad-CAM), which uses the gradients of any target concept flowing into the final convolutional layer to highlight the important part of training data for predicting the concept. In the first stage, MI classification was carried out and then the frequency band to be filtered was calculated according to the Grad-CAM of the MI classification results. In the second stage, EEG was filtered and classified for a higher classification accuracy. To evaluate the filtering effect, this method was applied to the multi-branch neural network proposed in our previous work. Experiment results revealed that the proposed method reached state-of-the-art classification kappa value levels and acquired at least 3% higher kappa values than other methods This study also proposed some promising application scenarios with this filtering method.
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http://dx.doi.org/10.3389/fnins.2021.657540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440963PMC
September 2021

Nutritive value of faba bean ( L.) as a feedstuff resource in livestock nutrition: A review.

Food Sci Nutr 2021 Sep 22;9(9):5244-5262. Epub 2021 Jul 22.

Department of Animal Science and Technology Anhui Agricultural University Hefei China.

The review evaluates faba bean ( L.; FB) seeds relative to their nutritional composition, their content of antinutritional factors, and their impact on animal performance. The literature indicates that FB plant is a cool-season, annual grain legume that grows the best in cool and humid conditions. Its seeds are rich in protein, energy, and mineral compounds and have particularly high unsaturated fatty acid levels. However, FB seeds also contain various proportions of antinutritional factors (ANFs) that can interfere with nutrient utilization in nonruminants. The various processing methods are efficient in either reducing or inactivating the ANFs of FB seeds, with extrusion treatment offering the most effective method of improving apparent nutrient and energy digestibility of nonruminants. In vivo studies on ruminants, pigs, poultry, and fishes reveal that FB seeds have the potential to be used as a substitute for soybean meal and/or cereal seeds in livestock diets in order to support milk, meat, and/or egg production.
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http://dx.doi.org/10.1002/fsn3.2342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441412PMC
September 2021

Dysfunctions, Molecular Mechanisms, and Therapeutic Strategies of Regulatory T Cells in Rheumatoid Arthritis.

Front Pharmacol 2021 26;12:716081. Epub 2021 Aug 26.

Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.

Regulatory T cells (Tregs) represent a distinct subpopulation of CD4 T lymphocytes that promote immune tolerance and maintain immune system homeostasis. The dysfunction of Tregs is tightly associated with rheumatoid arthritis (RA). Although the complex pathogenic processes of RA remain unclear, studies on Tregs in RA have achieved substantial progress not only in fundamental research but also in clinical application. This review discusses the current knowledge of the characterizations, functions, and molecular mechanisms of Tregs in the pathogenesis of RA, and potential therapies for these disorders are also involved.
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http://dx.doi.org/10.3389/fphar.2021.716081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428974PMC
August 2021

Development and Validation of a Forensic Multiplex System With 38 X-InDel Loci.

Front Genet 2021 17;12:670482. Epub 2021 Aug 17.

School of Forensic Medicine, Southern Medical University, Guangzhou, China.

In the present study, a novel multiplex system, AGCU X-InDel 38 kit, was designed to amplify 38 X-InDel markers and amelogenin in a single Polymerase Chain Reaction (PCR). To demonstrate the suitability and efficiency for forensic applications, a series of validation experiments were conducted, including sensitivity, species specificity, reproducibility, stability, case samples, balance of peak height, size precision, as well as allele frequency and forensic parameter analysis. The results showed that AGCU X-InDel 38 kit was capable to get full profiles even with 62.5 pg of template DNA, and full profiles can be obtained when hematin concentration ≤25 μmol/L, or hemoglobin concentration ≤50 μmol/L, showing good tolerance to six common inhibitors. Moreover, the analyzed case samples indicated that AGCU X-InDel 38 kit had better performance for degraded and trace DNA samples. The 200 unrelated males from Guangdong Han population showed that the combined PD and PD were both more than 0.999999999, and the combined MEC, MEC, and MEC were 0.999369481, 0.999999917, and 0.999941556, respectively. Robust discrimination capability of this novel multiplex system could be demonstrated through the high values of forensic parameters. In conclusion, AGCU X-InDel 38 kit is sensitive, precise, reproducible, and highly informative and could be used as a complementary tool for complex and challenging kinship cases.
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http://dx.doi.org/10.3389/fgene.2021.670482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416044PMC
August 2021

Validation and forensic application of a new 19 X-STR loci multiplex system.

Leg Med (Tokyo) 2021 Aug 21;53:101957. Epub 2021 Aug 21.

Guangzhou Forensic Science Institute, Guangdong Province Key Laboratory of Forensic Genetics, Guangzhou 510030, China; School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address:

The Microreader™ 19X Direct ID System was a newly developed multiplex PCR kit, which could detect 19 X-chromosomal STR loci (DXS6795, DXS9907, DXS6803, GATA172D05, DXS6807, GATA31E08, DXS7423, DXS6810, DXS101, DXS9902, DXS7133, DXS6800, DXS981, DXS10162, DXS6809, DXS10135, HPRTB, GATA165B12, DXS10079) and the sex determination locus of AMEL simultaneously. Different from other X-STR multiplex PCR kits, no linkage groups are included in this system, so the likelihood ratios could be calculated without the consideration of linkage groups. In this study, PCR conditions, sensitivity, species specificity, stability, DNA mixtures, concordance, stutter, sizing precision and population studies were conducted according to the SWGDAM developmental validation guidelines. The results indicated that this new X-STRs multiplex system was an efficient and reliable detection system, which could facilitate human kinship analysis and identification testing, as a powerful supplementary to autosomal STR kits.
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http://dx.doi.org/10.1016/j.legalmed.2021.101957DOI Listing
August 2021

A Study Protocol for a Randomized, Double-Blind, Placebo-Controlled Clinical Study on the Effect of Qishen Yiqi Dripping Pills on Exercise Endurance and Quality of Life in Patients with Coronary Heart Disease after Percutaneous Coronary Intervention.

Evid Based Complement Alternat Med 2021 24;2021:7439852. Epub 2021 Aug 24.

China-Japan Friendship Hospital, Beijing, China.

Background: Percutaneous coronary intervention (PCI) is widely used in China, but it does not fundamentally improve exercise endurance or reduce mortality associated with cardiovascular disease. Standardized cardiac rehabilitation (CR) can reduce the mortality associated with coronary heart disease and reduce the need for repeated PCI procedures. Currently, research on CR after PCI is mainly based on traditional exercise prescription, while research on TCM is limited. Often, the combination of traditional Chinese medicine (TCM) and exercise rehabilitation is adopted, from which it is difficult to determine the unique advantages of TCM. Qishen Yiqi dripping pills (QSYQ) can improve myocardial energy metabolism and alleviate myocardial reperfusion injury after PCI. This paper describes the protocol for the clinical assessment of QSYQ on CR.

Methods: A randomized, double-blind, placebo-controlled trial will be used to evaluate the efficacy and safety of QSYQ on improving exercise endurance and quality of life. We plan to recruit 66 patients with stable angina pectoris with Qi deficiency and blood stasis syndrome differentiation after PCI from the China-Japan Friendship Hospital. On the basis of conventional drug treatment, QSYQ or placebo will be used for 12 weeks. PeakVO will be the main efficacy evaluation index, while Seattle scale and quality of life scale will be the secondary efficacy evaluation indexes. . CR therapy with integrated traditional Chinese and Western medicine has been developed as a treatment modality in China and has been included in the expert consensus of TCM diagnosis and treatment. A rigorous trial design will ensure objective and scientific evaluation of the efficacy and safety of QSYQ in improving exercise endurance and quality of life in patients with PCI. . This trial is registered with Clinical trial registration in China: ChiCTR2000040838 (registration date: December 11, 2020).
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http://dx.doi.org/10.1155/2021/7439852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8407996PMC
August 2021

The latest information on the RIPK1 post-translational modifications and functions.

Biomed Pharmacother 2021 Aug 24;142:112082. Epub 2021 Aug 24.

Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing 100029, China; Department of Emergency, China-Japan Friendship Hospital, Beijing 100029, China. Electronic address:

RIPK1 is a protein kinase that simultaneously regulates inflammation, apoptosis, and necroptosis. It is thought that RIPK1 has separate functions through its scaffold structure and kinase domains. Moreover, different post-translational modifications in RIPK1 play distinct or even opposing roles. Under different conditions, in different cells and species, and/or upon exposure to different stimuli, infections, and substrates, RIPK1 activation can lead to diverse results. Despite continuous research, many of the conclusions that have been drawn regarding the complex interactions of RIPK1 are controversial. This review is based on an examination and analysis of recent studies on the RIPK1 structure, post-translational modifications, and activation conditions, which can affect its functions. Finally, because of the diverse functions of RIPK1 and their relevance to the pathogenesis of many diseases, we briefly introduce the roles of RIPK1 in inflammatory and autoimmune diseases and the prospects of its use in future diagnostics and treatments.
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http://dx.doi.org/10.1016/j.biopha.2021.112082DOI Listing
August 2021

Liraglutide Improves Endothelial Function via the mTOR Signaling Pathway.

J Diabetes Res 2021 16;2021:2936667. Epub 2021 Aug 16.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Background: Mammalian target of rapamycin (mTOR) is crucial for endothelial function. This study is aimed at assessing whether the glucagon-like peptide-1 (GLP-1) analogue liraglutide has a protective effect on endothelial function via the mTOR signaling pathway.

Methods: Human umbilical vein endothelial cells (HUVECs) were administered liraglutide (100 nM) for 0, 10, 30, 60, 720, and 1440 minutes, respectively. Then, the expression and phosphorylation levels of mTOR, mTOR-Raptor complex (mTORC1), and mTOR-Rictor complex (mTORC2) were determined by Western blot and immunoprecipitation, while mTORC1 and mTORC2 expression was blocked by siRNA-Raptor and siRNA-Rictor, respectively. Akt phosphorylation was detected by Western blot. HUVECs were then incubated with liraglutide in the absence or presence of Akt inhibitor IV. Nitric oxide (NO) release was assessed by the nitrate reductase method. Phosphorylated endothelial nitric oxide synthase (eNOS), human telomerase reverse transcriptase (hTERT), and apoptosis-related effectors were assessed for protein levels by Western blot. Telomerase activity was evaluated by ELISA.

Results: Sustained mTOR phosphorylation, mTORC2 formation, and mTORC2-dependent Akt phosphorylation were induced by liraglutide. In addition, eNOS phosphorylation, NO production, nuclear hTERT accumulation, and nuclear telomerase activity were enhanced by mTORC2-mediated Akt activation. Liraglutide also showed an antiapoptotic effect by upregulating antiapoptotic proteins and downregulating proapoptotic proteins in an mTORC2-Akt activation-dependent manner.

Conclusion: Liraglutide significantly improves endothelial function, at least partially via the mTORC2/Akt signaling pathway.
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http://dx.doi.org/10.1155/2021/2936667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384515PMC
August 2021

Vegetation grows more luxuriantly in Arctic permafrost drained lake basins.

Glob Chang Biol 2021 Aug 19. Epub 2021 Aug 19.

School of Geospatial Engineering and Science, Sun Yat-Sen University, Zhuhai, China.

As Arctic warming, permafrost thawing, and thermokarst development intensify, increasing evidence suggests that the frequency and magnitude of thermokarst lake drainage events are increasing. Presently, we lack a quantitative understanding of vegetation dynamics in drained lake basins, which is necessary to assess the extent to which plant growth in thawing ecosystems will offset the carbon released from permafrost. In this study, continuous satellite observations were used to detect thermokarst lake drainage events in northern Alaska over the past 20 years, and an advanced temporal segmentation and change detection algorithm allowed us to determine the year of drainage for each lake. Quantitative analysis showed that the greenness (normalized difference vegetation index [NDVI]) of tundra vegetation growing on wet and nutrient-rich lake sediments increased approximately 10 times faster than that of the peripheral vegetation. It takes approximately 5 years (4-6 years for the 25%-75% range) for the drainage lake area to reach the greenness level of the peripheral vegetation. Eventually, the NDVI values of the drained lake basins were 0.15 (or 25%) higher than those of the surrounding areas. In addition, we found less lush vegetation in the floodplain drained lake basins, possibly due to water logging. We further explored the key environmental drivers affecting vegetation dynamics in and around the drained lake basins. The results showed that our multivariate regression model well simulated the growth dynamics of the drainage lake ecosystem ( , p < .001) and peripheral vegetation ( , p < .001). Among climate variables, moisture variables were more influential than temperature variables, indicating that vegetation growth in this area is susceptible to water stress. Our study provides valuable information for better modeling of vegetation dynamics in thermokarst lake areas and provides new insights into Arctic greening and carbon balance studies as thermokarst lake drainage intensifies.
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http://dx.doi.org/10.1111/gcb.15853DOI Listing
August 2021

Whole-Transcriptome Analysis of Preadipocyte and Adipocyte and Construction of Regulatory Networks to Investigate Lipid Metabolism in Sheep.

Front Genet 2021 29;12:662143. Epub 2021 Jul 29.

Jilin Academy of Agricultural Sciences, Gongzhuling, China.

Many local sheep breeds in China have poor meat quality. Increasing intramuscular fat (IMF) content can significantly improve the quality of mutton. However, the molecular mechanisms of intramuscular adipocyte formation and differentiation remain unclear. This study compared differences between preadipocytes and mature adipocytes by whole-transcriptome sequencing and constructed systematically regulatory networks according to the relationship predicted among the differentially expressed RNAs (DERs). Sequencing results showed that in this process, there were 1,196, 754, 100, and 17 differentially expressed messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), respectively. Gene Ontology analysis showed that most DERs enriched in Cell Part, Cellular Process, Biological Regulation, and Binding terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DERs primarily focused on Focal adhesion, phosphoinositide 3-kinase (PI3K)-Akt, mitogen-activated protein kinase (MAPK), peroxisome proliferator-activated receptor (PPAR) signaling pathways. Forty (40) DERs were randomly selected from the core regulatory network to verify the accuracy of the sequence data. The results of qPCR showed that the DER expression trend was consistent with sequence data. Four novel promising candidate miRNAs (miR-336, miR-422, miR-578, and miR-722) played crucial roles in adipocyte differentiation, and they also participated in multiple and important regulatory networks. We verified the expression pattern of the miRNAs and related pathways' members at five time points in the adipocyte differentiation process (0, 2, 4, 6, 8, 10 days) by qPCR, including miR-336/ACSL4/LncRNA-MSTRG71379/circRNA0002331, miR-422/FOXO4/LncRNA-MSTRG54995/circRNA0000520, miR-578/IGF1/LncRNA-MSTRG102235/circRNA0002971, and miR-722/PDK4/LncRNA-MSTRG107440/circ RNA0002909. In this study, our data provided plenty of valuable candidate DERs and regulatory networks for researching the molecular mechanisms of sheep adipocyte differentiation and will assist studies in improving the IMF.
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http://dx.doi.org/10.3389/fgene.2021.662143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358208PMC
July 2021

Stereotactic technology for 3D bioprinting: from the perspective of robot mechanism.

Biofabrication 2021 08 13;13(4). Epub 2021 Aug 13.

Key Laboratory for Biomechanics and Mechanobiology of Chinese Education Ministry, Beijing Advanced Innovation Centre for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, People's Republic of China.

Three-dimensional (3D) bioprinting has been widely applied in the field of biomedical engineering because of its rapidly individualized fabrication and precisely geometric designability. The emerging demand for bioprinted tissues/organs with bio-inspired anisotropic property is stimulating new bioprinting strategies. Stereotactic bioprinting is regarded as a preferable strategy for this purpose, which can perform bioprinting at the target position from any desired orientation in 3D space. In this work, based on the motion characteristics analysis of the stacked bioprinting technologies, mechanism configurations and path planning methods for robotic stereotactic bioprinting were investigated and a prototype system based on the double parallelogram mechanism was introduced in detail. Moreover, the influence of the time dimension on stereotactic bioprinting was discussed. Finally, technical challenges and future trends of stereotactic bioprinting within the field of biomedical engineering were summarized.
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http://dx.doi.org/10.1088/1758-5090/ac1846DOI Listing
August 2021

Platelet membrane and stem cell exosome hybrid enhances cellular uptake and targeting to heart injury.

Nano Today 2021 Aug 8;39. Epub 2021 Jun 8.

Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, and North Carolina State University, Raleigh, North Carolina 27606, United States.

Exosomes from mesenchymal stem cells have been largely studied as therapeutics to treat myocardial infarctions. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from exosomes already in circulation, and the internalization/clearance by the mononuclear phagocyte system. In this study, we hybrid exosomes with platelet membranes to enhance their ability to target the injured heart and avoid being captured by macrophages. Furthermore, we found that encapsulation by the platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes strikingly. studies showed that the cardiac targeting ability of hybrid exosomes in a mice model with myocardial infarction injury. Last, we tested cardiac functions and performed immunohistochemistry to confirm a better therapeutic effect of platelet membrane modified exosomes compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues.
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http://dx.doi.org/10.1016/j.nantod.2021.101210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294084PMC
August 2021

Age-dependent alterations in key components of the nigrostriatal dopaminergic system and distinct motor phenotypes.

Acta Pharmacol Sin 2021 Jul 9. Epub 2021 Jul 9.

Jiangsu Province Key Laboratory in Anesthesiology, School of Anesthesiology, Xuzhou Medical University, Xuzhou, 221004, China.

The nigrostriatal dopaminergic (DA) system, which includes DA neurons in the ventral and dorsal tiers of the substantia nigra pars compacta (vSNc, dSNc) and DA terminals in the dorsal striatum, is critically implicated in motor control. Accumulating studies demonstrate that both the nigrostriatal DA system and motor function are impaired in aged subjects. However, it is unknown whether dSNc and vSNc DA neurons and striatal DA terminals age in similar patterns, and whether these changes parallel motor deficits. To address this, we performed ex vivo patch-clamp recordings in dSNc and vSNc DA neurons, measured striatal dopamine release, and analyzed motor behaviors in rodents. Spontaneous firing in dSNc and vSNc DA neurons and depolarization-evoked firing in dSNc DA neurons showed inverse V-shaped changes with age. But depolarization-evoked firing in vSNc DA neurons increased with age. In the dorsal striatum, dopamine release declined with age. In locomotor tests, 12-month-old rodents showed hyperactive exploration, relative to 6- and 24-month-old rodents. Additionally, aged rodents showed significant deficits in coordination. Elevating dopamine levels with a dopamine transporter inhibitor improved both locomotion and coordination. Therefore, key components in the nigrostriatal DA system exhibit distinct aging patterns and may contribute to age-related alterations in locomotion and coordination.
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http://dx.doi.org/10.1038/s41401-021-00713-5DOI Listing
July 2021

Effect of the Gene on Preadipocyte Differentiation in Sheep.

Front Genet 2021 21;12:649140. Epub 2021 Jun 21.

Institute of Animal Biotechnology, Jilin Academy of Agricultural Science, Changchun, China.

Acetyl-CoA acyltransferase 1 () functions as a key regulator of fatty acid β-oxidation in peroxisomes by catalyzing the cleavage of 3-ketoacyl-CoA to acetyl-CoA and acyl-CoA, which participate in the extension and degradation of fatty acids. Thus, is an important regulator of lipid metabolism and plays an essential role in fatty acid oxidation and lipid metabolism. Our previous study findings revealed that is closely associated with the peroxisome proliferator-activated receptor () signaling and fatty acid metabolism pathways, which are involved in fat deposition in sheep, leading to our hypothesis that may be involved in fat deposition by regulating lipid metabolism. However, the associated molecular mechanism remains unclear. In the present study, to assess the potential function of in sheep preadipocyte differentiation, we knocked down and overexpressed in sheep preadipocytes and evaluated the pattern of gene expression during preadipocyte differentiation by qRT-PCR. was significantly expressed in the early stage of adipocyte differentiation, and then its expression decreased. deficiency increased lipid accumulation and the triglyceride content and promoted sheep preadipocyte differentiation, whereas overexpression inhibited adipogenesis and decreased lipid accumulation and the triglyceride content. Simultaneously, we demonstrated that deficiency upregulated the expressions of the adipogenic marker genes γ and α in sheep preadipocytes, but overexpression inhibited the expressions of these markers, indicating that affects lipid metabolism by regulating adipogenic marker genes. Our results may promote a better understanding of the regulation of adipogenesis by .
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http://dx.doi.org/10.3389/fgene.2021.649140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255805PMC
June 2021

Preoperative risk factors for postoperative blood transfusion after hip fracture surgery: establishment of a nomogram.

J Orthop Surg Res 2021 Jun 23;16(1):406. Epub 2021 Jun 23.

Department of Minimally Invasive Spine Surgery, Chengde Medical University Affiliated Hospital, Chengde, 067000, Hebei, China.

Background: This study aimed to explore the preoperative risk factors related to blood transfusion after hip fracture operations and to establish a nomogram prediction model. The application of this model will likely reduce unnecessary transfusions and avoid wasting blood products.

Methods: This was a retrospective analysis of all patients undergoing hip fracture surgery from January 2013 to January 2020. Univariate and multivariate logistic regression analyses were used to evaluate the association between preoperative risk factors and blood transfusion after hip fracture operations. Finally, the risk factors obtained from the multivariate regression analysis were used to establish the nomogram model. The validation of the nomogram was assessed by the concordance index (C-index), the receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and calibration curves.

Results: A total of 820 patients were included in the present study for evaluation. Multivariate logistic regression analysis demonstrated that low preoperative hemoglobin (Hb), general anesthesia (GA), non-use of tranexamic acid (TXA), and older age were independent risk factors for blood transfusion after hip fracture operation. The C-index of this model was 0.86 (95% CI, 0.83-0.89). Internal validation proved the nomogram model's adequacy and accuracy, and the results showed that the predicted value agreed well with the actual values.

Conclusions: A nomogram model was developed based on independent risk factors for blood transfusion after hip fracture surgery. Preoperative intervention can effectively reduce the incidence of blood transfusion after hip fracture operations.
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http://dx.doi.org/10.1186/s13018-021-02557-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220667PMC
June 2021

UHRF2 commissions the completion of DNA demethylation through allosteric activation by 5hmC and K33-linked ubiquitination of XRCC1.

Mol Cell 2021 07 9;81(14):2960-2974.e7. Epub 2021 Jun 9.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 311121, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address:

The transition of oxidized 5-methylcytosine (5mC) intermediates into the base excision repair (BER) pipeline to complete DNA demethylation remains enigmatic. We report here that UHRF2, the only paralog of UHRF1 in mammals that fails to rescue Uhrf1 phenotype, is physically and functionally associated with BER complex. We show that UHRF2 is allosterically activated by 5-hydroxymethylcytosine (5hmC) and acts as a ubiquitin E3 ligase to catalyze K33-linked polyubiquitination of XRCC1. This nonproteolytic action stimulates XRCC1's interaction with the ubiquitin binding domain-bearing RAD23B, leading to the incorporation of TDG into BER complex. Integrative epigenomic analysis in mouse embryonic stem cells reveals that Uhrf2-fostered TDG-RAD23B-BER complex is functionally linked to the completion of DNA demethylation at active promoters and that Uhrf2 ablation impedes DNA demethylation on latent enhancers that undergo poised-to-active transition during neuronal commitment. Together, these observations highlight an essentiality of 5hmC-switched UHRF2 E3 ligase activity in commissioning the accomplishment of active DNA demethylation.
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http://dx.doi.org/10.1016/j.molcel.2021.05.022DOI Listing
July 2021

Effects of short-chain fatty acids in inhibiting HDAC and activating p38 MAPK are critical for promoting B10 cell generation and function.

Cell Death Dis 2021 06 7;12(6):582. Epub 2021 Jun 7.

Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, 510055, China.

B10 cells are regulatory B cells capable of producing IL-10 for maintaining immune homeostasis. Dysregulation of B10 cells occurs in autoimmune and inflammatory diseases. Modulation or adoptive transfer of B10 cells is a promising therapeutic strategy. The short-chain fatty acids (SCFAs), the metabolites of microbiota, play a critical role in maintaining immune homeostasis and are the potential drugs for the modulation of B10 cells. It is not clear whether and how SCFAs upregulate the frequency of B10 cells. Here, we found that SCFAs could promote murine and human B10 cell generation in vitro. Upregulation of B10 cells by butyrate or pentanoate was also observed in either healthy mice, mice with dextran sodium sulfate (DSS)-induced colitis, or mice with collagen-induced arthritis. Moreover, SCFA treatment could ameliorate clinical scores of colitis and arthritis. Adoptive transfer of B cells pretreated with butyrate showed more alleviation of DSS-induced colitis than those without butyrate. A further study demonstrates that SCFAs upregulate B10 cells in a manner dependent on their histone deacetylase (HDAC) inhibitory activity and independent of the G-protein-coupled receptor pathway. Transcriptomic analysis indicated that the MAPK signaling pathway was enriched in B10 cells treated with butyrate. A study with inhibitors of ERK, JNK, and p38 MAPK demonstrated that activating p38 MAPK by butyrate is critical for the upregulation of B10 cells. Moreover, HDAC inhibitor has similar effects on B10 cells. Our study sheds light on the mechanism underlying B10 cell differentiation and function and provides a potential therapeutic strategy with SCFAs and HDAC inhibitors for inflammation and autoimmune diseases.
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http://dx.doi.org/10.1038/s41419-021-03880-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184914PMC
June 2021

Porphyromonas gingivalis induces periodontitis, causes immune imbalance, and promotes rheumatoid arthritis.

J Leukoc Biol 2021 09 31;110(3):461-473. Epub 2021 May 31.

Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University, Guangzhou, China.

Periodontitis induced by bacteria especially Porphyromonas gingivalis (P. gingivalis) is the most prevalent microbial disease worldwide and is a significant risk factor for systemic diseases such as rheumatoid arthritis (RA). RA and periodontitis share similar clinical and pathologic features. Moreover, the prevalence of RA is much higher in patients with periodontitis than in those without periodontitis. To explore the immunologic mechanism of periodontitis involved in RA, we established a mouse model of periodontitis and then induced RA. According to the results of paw thickness, arthritis clinical score, arthritis incidence, microscopic lesion using H&E staining, and micro-CT analysis, periodontitis induced by P. gingivalis promoted the occurrence and development of collagen-induced arthritis (CIA) in mice. Furthermore, periodontitis enhanced the frequency of CD19 B cells, Th17, Treg, gMDSCs, and mMDSCs, whereas down-regulated IL-10 producing regulatory B cells (B10) in CIA mice preinduced for periodontitis with P. gingivalis. In vitro stimulation with splenic cells revealed that P. gingivalis directly enhanced differentiation of Th17, Treg, and mMDSCs but inhibited the process of B cell differentiation into B10 cells. Considering that adoptive transfer of B10 cells prevent RA development, our study, although preliminary, suggests that down-regulation of B10 cells may be the key mechanism that periodontitis promotes RA as the other main immune suppressive cells such as Treg and MDSCs are up-regulated other than down-regulated in group of P. gingivalis plus CIA.
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http://dx.doi.org/10.1002/JLB.3MA0121-045RDOI Listing
September 2021

A Novel Small Molecular Antibody, HER2-Nanobody, Inhibits Tumor Proliferation in HER2-Positive Breast Cancer Cells and .

Front Oncol 2021 12;11:669393. Epub 2021 May 12.

Department of Pathology, School of Basic Medicine, Anhui Medical University, Hefei, China.

Breast cancer is the most common malignant cancer in women worldwide, especially in developing countries. Herceptin is a monoclonal antibody with an antitumor effect in HER2-positive breast cancer. However, the large molecular weight of Herceptin limited its employment. In this study, we constructed and screened HER2-nanobody and verified its tumor-suppressive effect in HER2-positive breast cancer cells. HER2-nanobody was established, filtrated, purified, and was demonstrated to inhibit cell total number, viability, colony formation and mitosis, and promote cell apoptosis in HER2-positive breast cancer cells . Treated with HER2-nanobody, tumor growth was significantly inhibited by both intratumor injection and tail intravenous injection . The phosphorylation of ERK and AKT was restrained by HER2-nanobody in HER2-positive breast cancer cells. RAS-RAF-MAPK and PI3K-AKT-mTOR are two important pathways involved in HER2. It was credible for HER2-nanobody to play the tumor suppressive role by inhibiting the phosphorylation of ERK and AKT. Therefore, HER2-nanobody could be employed as a small molecular antibody to suppress HER2-positive breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.669393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149955PMC
May 2021

Milky Layered Cerebrospinal Fluid in Intracranial Hemorrhage.

Eur Neurol 2021 27;84(5):389-390. Epub 2021 May 27.

Department of Neurocritical Care, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

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http://dx.doi.org/10.1159/000516259DOI Listing
May 2021

Autophagy-related genes serve as heat shock protein 90 co-chaperones in disease resistance against cassava bacterial blight.

Plant J 2021 Aug 21;107(3):925-937. Epub 2021 Jun 21.

Hainan Key Laboratory for Sustainable Utilization of Tropical Bioresources, College of Tropical Crops, Hainan University, Haikou, Hainan, 570228, China.

Heat shock protein 90 (HSP90) is involved in plant growth and various stress responses via regulating protein homeostasis. Autophagy keeps cellular homeostasis by recycling the components of cellular cytoplasmic constituents. Although they have similar effects on cellular protein homeostasis, the direct association between HSP90 and autophagy signaling remains unclear in plants, especially in tropical crops. In this study, the correlation between HSP90 and autophagy signaling was systematically analyzed by protein-protein interaction in cassava, one of the most important economy fruit in tropic. In addition, their effects on plant disease response and underlying mechanisms in cassava were investigated by functional genomics and genetic phenotype assay. The potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex interacts with MeATGs and subsequently triggers autophagy signaling, conferring improved disease resistance to cassava bacterial blight (CBB). On the contrary, HSP90 inhibitor and autophagy inhibitor decreased disease resistance against CBB in cassava, and autophagy may be involved in the potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex-mediated multiple immune responses. This study highlights the precise modulation of autophagy signaling by potential MeHSP90.9-MeSGT1-MeRAR1 chaperone complex in autophagy-mediated disease resistance to CBB.
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http://dx.doi.org/10.1111/tpj.15355DOI Listing
August 2021

Genetic diversity of Amomum xanthioides and its related species from Southeast Asia and China.

J Nat Med 2021 Sep 25;75(4):798-812. Epub 2021 May 25.

Section of Pharmacognosy, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

Amomum Semen, the seed mass of Amomum xanthioides, has been imported from Southeast Asia and China and used for the treatment of gastric and intestinal disorders. A. xanthioides has been treated as a synonym of A. villosum var. xanthioides. Furthermore, A. villosum var. villosum, A. villosum var. xanthioides, or A. longiligulare have been described as the botanical origin of Amomi Fructus, which is a similar crude drug in Chinese Pharmacopoeia. Under these circumstances, the botanical origin of Amomum Semen was changed to A. villosum var. xanthioides, A. villosum var. villosum, or A. longiligulare in Supplement II to the 17th edition of the Japanese Pharmacopoeia. To develop an objective identification method for Amomum Semen and to confirm the phylogenetic relationship among Amomum taxa, the nucleotide sequences of the nuclear ribosomal DNA internal transcribed spacer region and chloroplast DNA partial matK-trnK and trnH-psbA intergenic spacer regions were determined in specimens collected from Southeast Asia and China, including those from the type localities of each taxon. Six taxa were divided into four groups. A. xanthioides from Myanmar belonging to group 1 was discriminated from A. villosum var. xanthioides from China of group 2. A. villosum and its varieties were divided into two groups: group 2 included those from China, and group 3 consisted of A. villosum from Laos. A. longiligulare from China and Laos and A. uliginosum from Laos belonged to group 3 and group 4, respectively. These findings illustrate the phylogenetic basis for the need for taxonomical reorganization among the Amomum species.
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http://dx.doi.org/10.1007/s11418-021-01512-2DOI Listing
September 2021

Divergent Synthesis of Aziridine and Imidazolidine Frameworks under Blue LED Irradiation.

Org Lett 2021 Jun 14;23(11):4109-4114. Epub 2021 May 14.

Anhui Province Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials, College of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui 230601, People's Republic of China.

We develop a visible light-promoted divergent cycloaddition of α-diazo esters with hexahydro-1,3,5-triazines, leading to a series of aziridine and imidazolidine frameworks in average good yield, by simply changing the reaction media used. It is noteworthy that the reaction occurs under sole visible light irradiation without the need for exogenous photoredox catalysts. More significantly, a reasonable reaction mechanism was proposed on the basis of the control experiments and density functional theory calculation results.
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http://dx.doi.org/10.1021/acs.orglett.1c00979DOI Listing
June 2021

Arsenic compounds: The wide application and mechanisms applied in acute promyelocytic leukemia and carcinogenic toxicology.

Eur J Med Chem 2021 Oct 4;221:113519. Epub 2021 May 4.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China. Electronic address:

Arsenic (As), as well as its various compounds have been widely used for nearly 4000 years either as drugs or poisons. These compounds are valuable in the treatment of various diseases ranging from dermatosis to cancer, thereby emphasizing their important roles as therapeutic agents. The ability of As compounds, especially arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL), has fundamentally altered people's understanding of the poison, and has become a major factor in the re-emergence of Western medicine candidates to treat leukemia and other solid tumors. However, long-term exposure to As has been correlated with numerous disadvantageous influences on health, particularly carcinogenesis. Importantly, accumulating evidence suggests that biotransformation of As, as a step to eliminate As from the human body, can induce alterations at the genetic and epigenetic levels, resulting in therapeutic effects or carcinogenesis. In this article, we aimed to provide a systematic overview of the primary contributions associated with As and its compounds, as well as the detailed mechanisms applied in APL cells and carcinogenic toxicology. This review may help to understand the underlying mechanisms and safe wide clinical applications of medicinal As along with its compounds.
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http://dx.doi.org/10.1016/j.ejmech.2021.113519DOI Listing
October 2021

Molecular characterization of a novel single-stranded RNA virus, ChRV1, isolated from the plant-pathogenic fungus Colletotrichum higginsianum.

Arch Virol 2021 Jun 6;166(6):1805-1809. Epub 2021 May 6.

Hunan Provincial Key Laboratory for Biology and Control of Plant Diseases and Insect Pests, Hunan Agricultural University, Nongda Road 1, Furong District, Changsha, 410128, Hunan, People's Republic of China.

In this study, a novel single-stranded RNA virus was isolated from the plant-pathogenic fungus Colletotrichum higginsianum strain HTC-5, and the virus was named "Colletotrichum higginsianum ssRNA virus 1" (ChRV1). The complete genome of ChRV1 is 3850 nucleotides in length with a GC content of 52% and contains two in-frame open reading frames (ORFs): ORF1 (smaller) and ORF2 (larger). ORF1 encodes a protein with the highest sequence similarity to proteins encoded by Phoma matteucciicola RNA virus 1 (PmRV1, 47.99% identity) and Periconia macrospinosa ambiguivirus 1 (PmAV1, 50.73% identity). ORF2 encodes a protein with a conserved RNA-dependent RNA polymerase (RdRp) domain with similarity to the RdRps of PmRV1 (61.41% identity) and PmAV1 (60.61% identity), which are recently reported unclassified (+) ssRNA mycoviruses. Phylogenetic analysis of the RdRp domain showed that ChRV1 grouped together with PmRV1, PmAV1, and other unclassified (+) ssRNA mycoviruses and had a distant relationship to invertebrate viruses and plant viruses of the family Tombusviridae. This is the first report of a novel (+) ssRNA virus infecting the phytopathogenic fungus C. higginsianum.
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http://dx.doi.org/10.1007/s00705-021-05071-5DOI Listing
June 2021

A 4-gene-based hypoxia signature is associated with tumor immune microenvironment and predicts the prognosis of pancreatic cancer patients.

World J Surg Oncol 2021 Apr 17;19(1):123. Epub 2021 Apr 17.

Department of General Surgery, Chaohu Hospital of Anhui Medical University, Chaohu, 238000, Anhui, China.

Background: Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood.

Methods: The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score.

Results: We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor.

Conclusions: In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.
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http://dx.doi.org/10.1186/s12957-021-02204-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053300PMC
April 2021

Valtrate as a novel therapeutic agent exhibits potent anti-pancreatic cancer activity by inhibiting Stat3 signaling.

Phytomedicine 2021 May 3;85:153537. Epub 2021 Mar 3.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China. Electronic address:

Background: Valtrate is a novel epoxy iridoid ester isolated from Chinese herbal medicine Valeriana jatamansi Jones with anti-proliferative activity against various human cancer cell lines. However, its efficacy and molecular mechanisms against pancreatic cancer (PC) cells are largely unclear.

Purpose: To investigate the anti-cancer effects of valtrate on PC cell lines and its underlying mechanisms.

Methods: MTT assay was first performed to detect the effect of valtrate on cell viability in human PC cell lines and normal pancreatic epithelial cells HPDE. Cell apoptosis and cycle phase assay were detected by flow cytometry. The relative mRNA expressions of Bax, Bcl-2, c-Myc, and CyclinB1 were tested by quantitative PCR (qPCR) assay. The expression of relative proteins was detected by Western blotting (WB). A PANC-1 cells xenograft mouse model in nu/nu female mice was used to elucidate the effect of valtrate on tumor growth in vivo.

Results: Valtrate significantly inhibited the growth of PC cells without affecting the growth of normal pancreatic epithelial cells HPDE, induced significant apoptosis and cell cycle arrest in G2/M phase. Moreover, valtrate inhibited the tumor growth of PC cell PANC-1 in xenograft mice by 61%. Further mechanism study demonstrated that valtrate could increase the expression level of Bax, suppress Bcl-2 as well as c-Myc and Cyclin B1, inhibit the transcriptional activity of Stat3, while valtrate decreased the expression level of Stat3 and phosphated-Stat3 (Tyr705) and induced the high molecular aggregation of Stat3. Molecular docking analysis predicted that valtrate might interact with Cys712 of Stat3 protein. Valtrate could also induce a transient depleted intracellular glutathione (GSH) level and increased reactive oxygen species (ROS). NAC (N-acetylcysteine), a reducer reversed valtrate-induced the depletion of Stat3, p-Stat3, c-Myc, and Cyclin B1.

Conclusion: Valtrate exerts anti-cancer activity against PC cells by directly targeting Stat3 through a covalent linkage to inhibit Stat3 activity, which causes apoptosis and cell cycle arrest.
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http://dx.doi.org/10.1016/j.phymed.2021.153537DOI Listing
May 2021

Clinical characteristics of endocrinopathies in Chinese patients with hereditary haemochromatosis.

Diabetes Metab Res Rev 2021 May 4;37(4):e3448. Epub 2021 Apr 4.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Aims: Hereditary haemochromatosis (HH) is a genetic disorder characterised by systemic iron overload and can lead to end-organ failure. However, very few data on this disorder, especially those on endocrine gland involvement in Chinese populations, are currently available. This study aimed to analyse the clinical features of endocrinopathies in patients with HH to generate concern among endocrinologists and improve the management of this disorder.

Materials And Methods: Chinese patients with HH-related endocrine dysfunction were enrolled at Peking Union Medical College Hospital from January 2010 to December 2018. All clinical data were analysed and summarised.

Results: A total of six patients were enrolled in this study, comprising five men and one woman; the average age was 36.5 ± 13.3 years. Mean serum ferritin concentration was 4508.8 ± 1074.3 ng/ml, and median transferrin saturation was 97.9% (96.6%-110.0%). Endocrine gland involvement associated with HH included the pancreas (5/6 patients), the adenohypophysis (5/6 patients) and the bones (1/6 patients); secondary endocrinopathies consisted of diabetes mellitus, hypogonadism, adrenal insufficiency and osteoporosis. Based on phlebotomy and iron chelation therapy, five patients were treated with exogenous insulin preparations, and three patients were treated with exogenous sex hormone replacement therapy. The clinical symptoms of five patients improved, although one patient died of hepatic encephalopathy and multiple organ failure.

Conclusions: HH can cause multiple endocrinopathies. The possibility of HH should be carefully considered in patients with endocrine gland dysfunctions and concomitant elevated serum ferritin levels. Endocrine gland function should also be assessed and followed up in patients with a clear diagnosis of HH.
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http://dx.doi.org/10.1002/dmrr.3448DOI Listing
May 2021

DEAH-box polypeptide 32 promotes hepatocellular carcinoma progression via activating the β-catenin pathway.

Ann Med 2021 12;53(1):437-447

State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Purpose: Hepatocellular carcinoma (HCC) is refractory cancer with high morbidity and high mortality. DEAH-box polypeptide 32 (DHX32) was upregulated in several types of malignancies and predicted poor prognosis. Herein, we investigated the role of DHX32 in HCC progression.

Methods: The expression of DHX32, β-catenin, and epithelial-mesenchymal transition (EMT)-related makers were determined by Western blot and quantitative real-time PCR assays. Cell proliferation was tested by EdU cell proliferation assay. The effect of DHX32 and β-catenin on cell migration and invasion were detected by wound-healing and Traswell invasion assays. Tumour xenografts were performed to determine the effect of DHX32 on HCC tumour growth.

Results: High level of DHX32 expression was associated with reduced overall survival in HCC patients. DHX32 expression was upregulated in human HCC cells and ectopic expression of DHX32 induced EMT, promoted the mobility and proliferation of HCC cells, and enhanced tumour growth . Silencing DHX32 reversed EMT, inhibited the malignancy behaviors of HCC cells, and suppressed tumour growth. Mechanistically, silencing DHX32 decreased the expression of β-cateninin in nucleus and β-catenin siRNA abrogated DHX32-mediated HCC progression.

Conclusion: DHX32 was an attractive regulator of HCC progression and indicated DHX32 canserve as a potential biomarker and therapeutic target for HCC patients.
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http://dx.doi.org/10.1080/07853890.2021.1898674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971220PMC
December 2021

Development and application of a multiplex PCR system for drowning diagnosis.

Electrophoresis 2021 Jun 20;42(11):1270-1278. Epub 2021 Mar 20.

Guangdong Province Key Laboratory of Forensic Genetics, Guangzhou Forensic Science Institute, Guangzhou, P. R. China.

In recent years, the DNA detection of drowning-related diatoms, cyanobacteria, and aeromonas has gradually attracted interest from forensic scientists. In this study, we described the validation and application of a novel multiplex PCR system. This system integrated 12 fluorescently labelled primers designed to amplify specific genes of diatoms, cyanobacteria, and aeromonas. The specificity studies demonstrated that this multiplex PCR system could detect nine species of diatom, seven species of cyanobacteria, and five species of aeromonas, all of which were drowning-related and widely distributed in various water circumstance of southern China. The sensitivity studies indicated that the limit concentration of template DNA was 0.0125 ng. Besides, this multiplex PCR system had good performance in sizing precision and stability, but it is not suitable for degraded DNA samples. The application into forensic casework showed that all the tissue samples from ten nondrowning cases showed negative results, and the positive rates of lung, liver, kidney, and water samples from 30 drowning bodies were 100, 86.7, 90, and 100%, respectively. Combined with results of diatom tests of MD-VF-Auto SEM method, this multiplex PCR system could help rule out nondrowning bodies and provide extra evidences to support drowning diagnosis, especially for those cases with few diatoms observed. It is expected that this multiplex PCR system has great potential for forensic drowning diagnosis.
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http://dx.doi.org/10.1002/elps.202000265DOI Listing
June 2021
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