Publications by authors named "Hua Yang"

2,313 Publications

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Large-Scale Studies on Antimicrobial Resistance and Molecular Characterization of Escherichia coli from Food Animals in Developed Areas of Eastern China.

Microbiol Spectr 2022 Aug 11:e0201522. Epub 2022 Aug 11.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, China.

Widely distributed multidrug-resistant (MDR) bacteria threaten animals and human health. Nevertheless, few antimicrobial resistance (AMR) surveys of large-scale animal-derived bacteria have been explored. Here, 1,468 (97.54%) Escherichia coli strains were isolated from 1,505 pig (1,060) and chicken (445) anal swab samples from 11 cities in Zhejiang Province, China, in 2020. These isolates had a high resistance to tetracycline (92.92%), sulfisoxazole (93.05%), florfenicol (83.11%), and ampicillin (78.27%). More than 88.68% of the strains were MDR bacteria. A low AMR ratio to the "last-resort" antimicrobials tigecycline (0.75%), colistin (1.36%), and meropenem (0.75%) were found. The AMR of E. coli from pigs was higher than that of chickens. Eighteen strains among 31 MDR strains that were resistant to "last-resort" antimicrobials could transfer the AMR genes (, (X), and ) to the recipient strain J53, which confer colistin, tigecycline, and carbapenem resistance, respectively. The homology among -carrying isolates was relatively high, and the sequence types were mainly ST5529, ST101, and ST354, while the homology of isolates harboring (X4) and genes were different. The , , and (X4) genes in strains LS45, JH51, and TZ118 were identified on the Incl2, IncHI2, and IncX1 plasmids, respectively. Moreover, (A), , and were the most common ARGs in 31 strains. Additionally, the heavy metals copper and zinc had a significant correlation with amoxicillin/clavulanate and tetracycline resistance. Controlling the movement of animals between cities and reducing the use of antimicrobials are effective methods to reduce the threat of AMR bacteria. Pigs and chickens are the most common food animals that are the important vectors for spreading antimicrobial-resistant pathogens among animals and humans. Limited systematic AMR monitoring of these food animal origin bacteria had been reported, especially in developed areas of China. Our study provides a comprehensive and systematic study of AMR in Escherichia coli from eastern China. The AMR of E. coli strains among the animals or cities has statistically significant differences. Moreover, the , (X4), and genes, considered resistant to the last line of AMR, were identified in part of farms. The transferability and the prevalence of these AMR strains were intensively studied. Our monitoring is comparable to human clinical research and has an essential reference for public health safety. These findings will provide early warning for AMR strains and guide the clinical use of antibiotics to control the spread of antibiotic resistance.
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http://dx.doi.org/10.1128/spectrum.02015-22DOI Listing
August 2022

Phenylalanine suppresses cell death caused by loss of fumarylacetoacetate hydrolase in Arabidopsis.

Sci Rep 2022 Aug 8;12(1):13546. Epub 2022 Aug 8.

College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, 410128, China.

Fumarylacetoacetate hydrolase (FAH) catalyzes the final step of Tyrosine (Tyr) degradation pathway essential to animals and the deficiency of FAH causes an inborn lethal disease. In plants, a role of this pathway was unknown until we found that mutation of Short-day Sensitive Cell Death1 (SSCD1), encoding Arabidopsis FAH, results in cell death under short day. Phenylalanine (Phe) could be converted to Tyr and then degraded in both animals and plants. Phe ingestion in animals worsens the disease caused by FAH defect. However, in this study we found that Phe represses cell death caused by FAH defect in plants. Phe treatment promoted chlorophyll biosynthesis and suppressed the up-regulation of reactive oxygen species marker genes in the sscd1 mutant. Furthermore, the repression of sscd1 cell death by Phe could be reduced by α-aminooxi-β-phenylpropionic acid but increased by methyl jasmonate, which inhibits or activates Phe ammonia-lyase catalyzing the first step of phenylpropanoid pathway, respectively. In addition, we found that jasmonate signaling up-regulates Phe ammonia-lyase 1 and mediates the methyl jasmonate enhanced repression of sscd1 cell death by Phe. These results uncovered the relation between chlorophyll biosynthesis, phenylpropanoid pathway and jasmonate signaling in regulating the cell death resulting from loss of FAH in plants.
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http://dx.doi.org/10.1038/s41598-022-17819-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9360007PMC
August 2022

Antimicrobial resistance surveillance of from chickens in the Qinghai Plateau of China.

Front Microbiol 2022 22;13:885132. Epub 2022 Jul 22.

College of Agriculture and Animal Husbandry, Qinghai University, Xining, China.

Antimicrobial resistance (AMR) may lead to worldwide epidemics through human activities and natural transmission, posing a global public safety threat. Colistin resistance mediated by the 1 gene is the most prevalent among animal-derived , and 1-carrying have been frequently detected in central-eastern China. However, animal-derived with AMR and the prevalence of -1 in the Qinghai Plateau have been rarely investigated. Herein, 375 stool samples were collected from 13 poultry farms in Qinghai Province and 346 strains were isolated, of which eight carried 1. The AMR rates of the strains to ampicillin, amoxicillin/clavulanic acid, and tetracycline were all above 90%, and the resistance rates to ciprofloxacin, cefotaxime, ceftiofur, and florfenicol were above 70%. Multidrug-resistant strains accounted for 95.66% of the total isolates. Twelve strains showed colistin resistance, from which a total of 46 AMR genes and 36 virulence factors were identified through whole-genome sequencing. The -1 gene resided on the IncHI2, IncI2-type and IncY-type plasmids, and -1 was located in the 1- gene cassette (three strains) or the 1-IS structure (one strain). Completed IncI2-type plasmid pMCR4D31-3 sequence (62,259 bp) revealed that it may cause the horizontal transmission of 1 and may increase the risk of its spread through the food chain. Taken together, the AMR of chicken-derived in the plateau is of concern, suggesting that it is very necessary for us to strengthen the surveillance in various regions under the background of one health.
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http://dx.doi.org/10.3389/fmicb.2022.885132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354467PMC
July 2022

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA.

BMC Cancer 2022 Aug 5;22(1):858. Epub 2022 Aug 5.

Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Baiyun District, Jingxi Street, Guangzhou, 510515, People's Republic of China.

Background: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA.

Methods: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test.

Results: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters.

Conclusions: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.
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http://dx.doi.org/10.1186/s12885-022-09942-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356473PMC
August 2022

Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma.

Cell Death Discov 2022 Aug 4;8(1):349. Epub 2022 Aug 4.

Department of Neurosurgery, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.

Glioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy.
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http://dx.doi.org/10.1038/s41420-022-01136-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352789PMC
August 2022

Determination of the structures of lignin subunits and nanoparticles in solution by small-angle neutron scattering: towards improving lignin valorization.

ChemSusChem 2022 Aug 2. Epub 2022 Aug 2.

Beijing University of Chemical Technology, Life Science and Technology, North 3rd Ring East, 15, 100029, Beijing, CHINA.

Lignin nanoparticles (LNPs) are usually produced from lignin solutions through supersaturation. The structure of the lignin in solution is still poorly understood due to structural variability of isolated lignins. Lignins were extracted from different plants to establish a general pattern of their structure in several lignin solvents. Lignin molecules (lignin subunits) and larger aggregates were observed in dimethyl sulfoxide (DMSO), ethylene glycol(EG) and 0.1N NaOD solutions by small-angle neutron scattering (SANS). It was proposed that the aggregates are composed of lignin subunits with a higher molecular weight and a higher ratio of the aliphatic to phenolic hydroxyl groups. The size, shape, and compactness are important factors that affect the uses of the LNPs, which were obtained from the SANS data for the first time. A discrepancy in the radius between SANS and DLS was discovered, pointing to a large hydration shell around the LNPs in aqueous solutions. The cytotoxicity of the corncob lignin, kraft lignin, and their LNPs were measured and compared.
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http://dx.doi.org/10.1002/cssc.202201230DOI Listing
August 2022

Building a Self-Adaptive Protective Layer on Ni-Rich Layered Cathodes to Enhance the Cycle Stability of Lithium-Ion Batteries.

Adv Mater 2022 Aug 2:e2204835. Epub 2022 Aug 2.

College of Science, Huazhong Agricultural University, Wuhan, 430070, China.

Layered Ni-rich lithium transition metal oxides are promising battery cathodes due to their high specific capacity, but their poor cycling stability due to intergranular cracks in secondary particles restricts their practical applications. Surface engineering is an effective strategy for improving a cathode's cycling stability, but most reported surface coatings cannot adapt to the dynamic volume changes of cathodes. Herein, we build a self-adaptive polymer (polyrotaxane-co-polyacrylic acid) interfacial layer on LiNi Co Mn O . The polymer layer with a slide-ring structure exhibits high toughness and can withstand the stress caused by particle volume changes, which can prevent the cracking of particles. In addition, the slide-ring polymer acts as a physicochemical barrier that suppresses surface side reactions and alleviates the dissolution of transition metallic ions, which ensures stable cycling performance. Thus, the as-prepared cathode shows significantly improved long-term cycling stability in situations in which cracks may easily occur, especially under high-rate, high-voltage, and high-temperature conditions. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202204835DOI Listing
August 2022

Molecular characterisation, temporal expression and involvement of ANGPTL4 in fat deposition in Muscovy ducks.

Br Poult Sci 2022 Aug 1. Epub 2022 Aug 1.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

1. Angiopoietin-like protein 4 (ANGPTL4) plays a key role in promoting fat metabolism and reducing blood lipid. This study characterised the gene in Muscovy ducks () and investigated its potential functions in fat metabolism in Muscovy ducks.2. The Muscovy duck cDNA was successfully cloned for the first time, showing a length of 2591 bp. After phylogenetic analysis by RT-qPCR analysis, it was found that the gene of shared the highest sequence similarity with that of Muscovy ducks.3. The gene was commonly expressed in 23 different tissues with the highest expression in the abdominal fat in Muscovy ducks. A significant association was observed between abdominal fat percentage (AFP) and the mRNA expression of the gene. Moreover, Muscovy ducks showed a peak of expression in the liver and abdominal fat at 1-2 weeks old.4. These findings suggested that the gene might be related to fat deposition in Muscovy ducks and provided a basis for the regulation of fat deposition by the gene in the duck industry.
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http://dx.doi.org/10.1080/00071668.2022.2102888DOI Listing
August 2022

To Estimate Performance of Artificial Neural Network Model Based on Terahertz Spectrum: Gelatin Identification as an Example.

Front Nutr 2022 14;9:925717. Epub 2022 Jul 14.

Shandong Fupai Ejiao, Co., Ltd., Jinan, China.

It is a necessity to determine significant food or traditional Chinese medicine (TCM) with low cost, which is more likely to achieve high accurate identification by THz-TDS. In this study, feedforward neural networks based on terahertz spectra are employed to predict the animal origin of gelatins, whose adaption to the mission is examined by parallel models built by random sample partition and initialization. It is found that the generalization performance of feedforward ANNs in original data is not satisfactory although prediction on trained samples can be accurate. A multivariate scattering correction is conducted to enhance prediction accuracy, and 20 additional models verify the effectiveness of such dispose. A special partition of total dataset is conducted based on statistics of parallel models, whose influence on ANN performance is investigated with another 20 models. The performance of the models is unsatisfactory because of notable differences in training and test sets according to principal component analysis. By comparing the distribution of the first two principal components before and after multivariate scattering correction, we found that the reciprocal of the minimum number of line segments required for error-free classification in 2-D feature space can be viewed as an index to describe linear separability of data. The rise of proposed linear separability would have a lower requirement for harsh parameter tuning of ANN models and tolerate random initialization. The difference in principal components of samples between a training set and a data set determines whether partition is acceptable or whether a model would have generality. A rapid way to estimate the performance of an ANN before sufficient tuning on a classification mission is to compare differences between groups and differences within groups. Given that a representative peak missing curve is discussed in this article, an analysis based on gelatin THz spectra may be helpful for studies on some other feature-less species.
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http://dx.doi.org/10.3389/fnut.2022.925717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330513PMC
July 2022

Probabilistic Risk Assessment of Combined Exposure to Deoxynivalenol and Emerging Toxins in Cereal-Based Food Products for Infants and Young Children in China.

Toxins (Basel) 2022 Jul 25;14(8). Epub 2022 Jul 25.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, Institute of Agro-Product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.

Deoxynivalenol (DON) and emerging toxins often co-occur in cereal-based products, but the current risk assessment is commonly conducted for only one type of mycotoxin at a time. Compared to adults, infants and young children are more susceptible to mycotoxins through food consumption, especially with cereal-based food products which are the main source of exposure. This study aimed to perform a probabilistic risk assessment of combined exposure to DON and three major toxins, namely including alternariol monomethyl ether (AME), alternariol (AOH), and tenuazonic acid (TeA) through consumption of cereal-based foods for Chinese infants and young children. A total of 872 cereal-based food products were randomly collected and tested for the occurrence of DON and three major toxins. The results on mycotoxin occurrence showed the DON, TeA, AOH, and AME was detected in 56.4%, 47.5%, 7.5%, and 5.7% of the samples, respectively. Co-contamination of various mycotoxins was observed in 39.9% of the analyzed samples. A preliminary cumulative risk assessment using the models of hazard index () and combined margin of exposure () was performed on DON and toxins that were present in cereal-based food products for infants and young children in China for the first time. The results showed that only 0.2% and 1.5%, respectively, of individuals exceeded the corresponding reference value for DON and TeA, indicating a low health risk. However, in the case of AME and AOH, the proportion of individuals exceeding the reference value was 24.1% and 33.5%, respectively, indicating the potential health risks. In the cumulative risk assessment of AME and AOH, both and values indicated a more serious risk than that related to individual exposure. Further research is necessary to reduce the uncertainties that are associated with the toxicities of the toxins and cumulative risk assessment methods.
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http://dx.doi.org/10.3390/toxins14080509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330788PMC
July 2022

Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1-Induced Endothelium Injury.

Antioxidants (Basel) 2022 Jul 26;11(8). Epub 2022 Jul 26.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China.

Claudin 5 is one of the major proteins of tight junctions and is responsible for cerebrovascular integrity and BBB function. Muscone and (+)-borneol is the major ingredient of moschus and borneolum, respectively, with antioxidative and anti-inflammatory activities. This study investigated whether muscone and (+)-borneol combination protected claudin 5 by targeting ROS-mediated IL-1 accumulation. Muscone and (+)-borneol reduced cerebral infarct volume and cerebrovascular leakage with claudin 5 protection in mice after stroke, largely due to inhibiting ROS accumulation and inflammatory infiltrate of microglia. Muscone reduced ROS and then blocked the CaN/Erk1/2 pathway to decrease IL-1 release, while (+)-borneol removed mitochondrial ROS and attenuated the SDH/Hif-1 pathway to inhibit IL-1 transcription, thereby jointly reducing IL-1 production. Accumulated IL-1 disrupted cAMP/CREB activation and attenuated transcriptional regulation of claudin 5. Muscone and (+)-borneol combination cooperatively protected BBB function by blocking IL-1-mediated cAMP/CREB/claudin 5 cascades. Mutation of Ser133 site of CREB or knockdown of claudin 5 weakened the effects of muscone and (+)-borneol on upregulation of TEER value and downregulation of FITC-dextran permeability, suggesting that targeting CREB/claudin 5 was an important strategy to protect vascular integrity. This study provided ideas for the studies of synergistic protection against ischemic brain injury about the active ingredients of traditional Chinese medicines (TCMs).
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http://dx.doi.org/10.3390/antiox11081455DOI Listing
July 2022

Trastuzumab-conjugated oxine-based ligand for [Zr]Zr immunoPET.

J Inorg Biochem 2022 Jul 18;235:111936. Epub 2022 Jul 18.

Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. Electronic address:

A new, bifunctional chelating ligand for immuno-Positron Emission Tomography (PET) was designed, synthesized, and conjugated to Trastuzumab for a proof-of-concept study with Zr. Hneunox was synthesized from the tris(2-aminoethyl)amine backbone, decorated with 8-hydroxyquinoline moieties, and utilizes a primary amine for functionalization. A maleimide moiety extends the chelator to create Hneunox-mal for antibody conjugation via maleimide-thiol click chemistry. Preliminary Zr radiolabeling of Hneunox indicated quantitative radiolabeling at 1 × 10 M, but improved inertness towards human serum (96% intact at 7 d) and Fe (92% intact at 24 h) compared to the previously synthesized Hdecaox. The chelator was successfully conjugated to the monoclonal antibody, Trastuzumab, and used in preliminary radiolabeling reactions (37 °C, 2 h) with Zr. Radiochemical assessments of the new Hneunox-Trastuzumab conjugate include Zr radiolabeling, spin filter purification, cell-binding immunoreactivity, and in vivo PET imaging and biodistribution in SKOV-3 tumour bearing nude mice, performed in comparison with the desferrioxamine B analog, DFO-Trastuzumab. The [Zr]Zr(neunox-Trastuzumab) showed lowered inertness towards serum (76% intact at 24 h) as well as demetallation in vivo through bone uptake (21% ID/g) in PET imaging and biodistribution studies when compared to [Zr]Zr(DFO-Trastuzumab). Although the combination of the chelator and antibody had detrimental effects on their intended purposes, nonetheless, the primary amine platform of Hneunox developed here provides an oxine-based bifunctional ligand for further derivatizations with other targeting vectors.
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http://dx.doi.org/10.1016/j.jinorgbio.2022.111936DOI Listing
July 2022

SUMOylation of microtubule-cleaving enzyme KATNA1 promotes microtubule severing and neurite outgrowth.

J Biol Chem 2022 Jul 19:102292. Epub 2022 Jul 19.

Department of Orthopaedics, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China. Electronic address:

Katanin p60 ATPase-containing subunit A1 (KATNA1) is a microtubule-cleaving enzyme that regulates the development of neural protrusions through cytoskeletal rearrangements. However, the mechanism underlying the linkage of the small ubiquitin-like modifier (SUMO) protein to KATNA1 and how this modification regulates the development of neural protrusions is unclear. Here we discovered, using mass spectrometry analysis, that SUMO-conjugating enzyme UBC9, an enzyme necessary for the SUMOylation process, was present in the KATNA1 interactome. Moreover, GST-pull down and co-IP assays confirmed that KATNA1 and SUMO interact. We further demonstrated using immunofluorescence experiments that KATNA1 and the SUMO2 isoform co-localized in hippocampal neurites. We also performed a bioinformatics analysis of KATNA1 protein sequences to identify three potentially conserved SUMOylation sites (K77, K157, and K330) among vertebrates. Mutation of K330, but not K77 or K157, abolished KATNA1-induced microtubule severing and decreased the level of binding observed for KATNA1 and SUMO2. Co-transfection of SUMO2 and wild-type KATNA1 in COS7 cells increased microtubule severing, whereas no effect was observed after co-transfection with the K330R KATNA1 mutant. Furthermore, in cultured hippocampal neurons, overexpression of wild-type KATNA1 significantly promoted neurite outgrowth, whereas the K330R mutant eliminated this effect. Taken together, our results demonstrate that the K330 site in KATNA1 is modified by SUMOylation, and SUMOylation of KATNA1 promotes microtubule dynamics and hippocampal neurite outgrowth.
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http://dx.doi.org/10.1016/j.jbc.2022.102292DOI Listing
July 2022

Identification of Key Biomarkers in Systemic Lupus Erythematosus by a Multi-Cohort Analysis.

Front Immunol 2022 4;13:928623. Epub 2022 Jul 4.

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Jiangxi, China.

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple body systems with heterogeneous clinical manifestations. Since gene expression analyses have been accomplished on diverse types of samples to specify SLE-related genes, single-cohort transcriptomics have not produced reliable results. Using an integrated multi-cohort analysis framework, we analyzed whole blood cells from SLE patients from three transcriptomics cohorts (n=1222) and identified a five-gene signature that distinguished SLE patients from controls. We validated the diagnostic performance of this five-gene signature in six independent validation cohorts (n= 469), with an area under the receiver operating characteristic curve of 0.88 [95% CI 0.7 - 0.96]. This five-gene signature may be associated with the proportion of SLE immune cells, and generalizable across ages and sample types with real diagnostic value for clinical application.
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http://dx.doi.org/10.3389/fimmu.2022.928623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289109PMC
July 2022

Visible-Light-Induced, Palladium-Catalyzed Annulation of 1,3-Dienes to Construct Vinyl -Heterocycles.

Org Lett 2022 07 17;24(29):5407-5411. Epub 2022 Jul 17.

College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, P. R. China.

Herein, a photoinduced palladium-catalyzed annulation of 1,3-dienes with bifunctional halognated alkylamines has been developed, offering a facile route to access a broad range of vinylpyrrolidines. The reactivity profile of this protocol was able to be readily manipulated to assemble vinylpyrrolidine and vinlysilaazacycle. Remarkably, the utility of this strategy was further illustrated in the construction of complex and biologically important molecules as well as the diversity-oriented transformations of the resulting product.
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http://dx.doi.org/10.1021/acs.orglett.2c02101DOI Listing
July 2022

A case report of otoendoscopic radiofrequency resection of squamous cell carcinoma of the external auditory canal.

Ear Nose Throat J 2022 Jul 11:1455613221112357. Epub 2022 Jul 11.

Department of Otolaryngology, The Fifth People's Hospital of Ningxia Autonomous Region, Shizuishan, China.

Squamous cell carcinoma is the most common pathological type of external and middle ear malignancy. Squamous cell carcinoma of the external auditory canal and middle ear is closely associated with long-term chronic inflammatory irritation. The patient was admitted with a major complaint of a "stuffy feeling in the left ear for more than three months." The results of the otoendoscopic examination were as follows: The left external auditory canal was filled with a granuloma-shaped mass with an unsmooth surface that showed obvious oozing of blood. The tympanic membrane was not visible. After the completion of the relevant examinations, radiofrequency resection of the external auditory canal mass was performed under otoendoscopy and the wound healed well with postoperative dressing changes. Pathological results revealed a well-differentiated keratinizing cutaneous squamous cell carcinoma and there was no recurrence throughout the next 5 years after the operation. Proper preoperative evaluation and the correct selection of surgical approaches can be of great importance. The primary complication of ear squamous cell carcinoma was local recurrence with a low incidence of metastasis. Early and complete resection was determined to be the optimal course of treatment.
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http://dx.doi.org/10.1177/01455613221112357DOI Listing
July 2022

Median Effective Dose of Dexmedetomidine Inducing Bradycardia in Elderly Patients Determined by Up-and-Down Sequential Allocation Method.

Int J Med Sci 2022 13;19(6):1065-1071. Epub 2022 Jun 13.

Department of Anesthesiology, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China.

When dexmedetomidine is used in elderly patients, high incidence of bradycardia is reported. Given age-related physiological changes in this population, it is necessary to know the safety margin between the loading dose of dexmedetomidine and bradycardia. Therefore, we conducted this study to investigate the median effective dose (ED50) of dexmedetomidine causing bradycardia in elderly patients. Thirty patients with ages over 65 years undergoing elective general surgery were enrolled. The Dixon and Massay sequential method were applied to determine the loading dose of dexmedetomidine, starting from 1.0 µg/kg. The dose for the follow-up subjects increased or decreased according to the geometric sequence with the common ratio 1.2, based on the 'negative' or 'positive' response of the previous subject. Positive mean that the subject developed bradycardia during the test. Hemodynamic data including heart rate and systolic blood pressure were recorded. The level of sedation was assessed with the Observer Assessment of Alertness and Sedation Scale (OAA/S). Bradycardia occurred in 13 patients (43.3%). The ED50 of dexmedetomidine causing bradycardia was 1.97 µg/kg (95% CI, 1.53-2.53 µg/kg). OAA/S scores at 10 min after the beginning of the dexmedetomidine infusion and 10 min after the termination of dexmedetomidine administration showed no significant differences between the positive and negative groups ( > 0.05). The ED50 of dexmedetomidine causing bradycardia in our cohort was higher than clinical recommended dose. A higher loading dose appears acceptable for a faster onset of sedation under careful hemodynamic monitoring. ChiCTR 15006368.
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http://dx.doi.org/10.7150/ijms.71380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254370PMC
July 2022

Higher tolerance of predominant Salmonella serovars circulating in the antibiotic-free feed farms to environmental stresses.

J Hazard Mater 2022 Jun 27;438:129476. Epub 2022 Jun 27.

Department of Veterinary Medicine & Institute of Preventive Veterinary Sciences, Zhejiang University College of Animal Sciences, Hangzhou, Zhejiang, China; Hainan Institute of Zhejiang University, Sanya, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Hangzhou, China. Electronic address:

To counteract the dramatic increase in antibiotic-resistant bacterial pathogens, many countries, including China, have banned the use of antibiotic-supplemented feed for farming animals. However, the exact consequences of this policy have not been systematically evaluated. Therefore, Salmonella isolates from farms that ceased using antibiotics 1-5 years ago were compared with isolates from farms that continue to use antimicrobials as growth promotors. Here, we used whole-genome sequencing combined with in-depth phenotypic assays to investigate the ecology, epidemiology, and persistence of multi-drug resistant (MDR) Salmonella from animal farms during the withdrawal of antibiotic growth promotors. Our results showed that the prevalence of Salmonella was significantly lower in antibiotic-free feed (AFF) farms compared to conventional-feed (CF) farms, even though all isolates obtained from AFF farms were MDR (>5 classes) and belonged to well-recognized predominant serovars. The additional phylogenomic analysis combined with principal component analysis showed high similarity between the predominant serovars in AFF and CF farms. This result raised questions regarding the environmental persistence capabilities of MDR strain despite AFF policy. To address this question, a representative panel of 20 isolates was subjected to disadvantageous environmental stress assays. These results showed that the predominant serovars in AFF and CF farms were more tolerant to stress conditions than other serovars. Collectively, our findings suggest that AFF helps eliminate only specific MDR serovars, and future guiding policies would benefit by identifying predominant Salmonella clones in problematic farms to determine the use of AFF and additional targeted interventions.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129476DOI Listing
June 2022

An alternative radiochemical separation strategy for isolation of Ac and Ra isotopes from high energy proton irradiated thorium targets for further application in Targeted Alpha Therapy (TAT).

Nucl Med Biol 2022 Jun 17;112-113:35-43. Epub 2022 Jun 17.

Life Sciences Division, TRIUMF, 4004 Wesbrook Mall, V6T 2A3 Vancouver, Canada; Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada. Electronic address:

Targeted Alpha Therapy (TAT) has shown very high potential for the treatment of cancers that were not responsive to other therapy options (e.g., β therapy and chemotherapy). The main constraint to the widespread use of TAT in clinics is the limited availability of alpha-emitting radionuclides. One of the most promising candidates for TAT is Ac (t = 9.92 days), which can be used directly in combination with selective biomolecules (e.g., antibodies, peptides, etc.) or be a generator source of Bi (t = 45.6 min), another shorter-lived TAT radionuclide. Several strategies are currently under investigation to increase the supply of Ac. One of the most attractive options is the irradiation of natural thorium-232 targets with high-energy protons (≥100 MeV). However, there are several challenges associated with this production method including the development of an efficient radiochemical purification method. During irradiation of natural thorium with proton energy above 100 MeV, several Ra isotopes (Ra) are produced. Ra (t = 11.43 days) is used for the treatment of bone metastases and can also be used as a generator source for Pb. Additionally, Ra (t = 14.9 days) can be a valuable source of isotopically pure Ac. In the present work, we address the radiochemical separation aspects of isolating Ac and Ra isotopes from irradiated thorium targets.
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http://dx.doi.org/10.1016/j.nucmedbio.2022.06.003DOI Listing
June 2022

Emergence of plasmid-mediated tigecycline resistance gene, tet(X4), in Escherichia fergusonii from pigs.

J Glob Antimicrob Resist 2022 Jul 3;30:249-251. Epub 2022 Jul 3.

Department of Life Science and Engineering, Foshan University, Foshan, China. Electronic address:

Objectives: This study aimed to identify tigecycline-resistant tet(X4)-bearing Escherichia fergusonii isolated from pigs in China with a complete genome sequence.

Methods: E. fergusonii was isolated by selective medium and screened from tigecycline-supplemented agar plates. The microbroth dilution method was used for antimicrobial susceptibility testing, and the minimal inhibitory concentration (MIC) results refer to the interpretation standard in the Clinical and Laboratory Standards Institute of America (CLSI). Whole-genome sequencing was performed on the Illumina HiSeq and Nanopore GridION platforms. The antimicrobial resistance (AMR) genes virulence genes and replicon types of plasmids were predicted by the CGE server.

Results: E. fergusonii EF21QZZ116 was identified from 760 faecal and caecal content samples and was resistant to tigecycline, tetracycline, ampicillin, sulfisoxazole, trimethoprim-sulfamethoxazole, spectinomycin, and florfenicol. The AMR genes tet(X4), bla, and floR are located on the hybrid IncFIA-IncHI1A-IncHI1B plasmid pQZZ166-tetX-190K and are 190 391 bp in length. This hybrid plasmid has high homology with the plasmids of Escherichia coli, Enterobacter cloacae, Klebsiella, Citrobacter, and Salmonella based on comparison and analysis with the NCBI database. Notably, conjugative transfer and S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) assays show that the plasmid can transfer horizontally.

Conclusion: To the best of our knowledge, this is the first report of E. fergusonii carrying the tet(X4) gene isolated from a pig; this report provides insight into the AMR characteristics of E. fergusonii and offers insight into public health.
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http://dx.doi.org/10.1016/j.jgar.2022.06.029DOI Listing
July 2022

Development of a humanized HLA-A30 transgenic mouse model.

Animal Model Exp Med 2022 Jul 6. Epub 2022 Jul 6.

Department of Laboratory Animal Science, Shanghai Public Health Clinical Center, Shanghai, China.

Background: There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-A-restricted responses against infection in human.

Methods: A recombinant gene encoding the chimeric HLA-A30 monochain was constructed. This HHD molecule contains the following: α1-α2 domains of HLA-A30, α3 and cytoplasmic domains of H-2D , linked at its N-terminus to the C-terminus of human β2m by a 15-amino-acid peptide linker. The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination. Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed.

Results: We describe a novel human β2m-HLA-A30 (α1α2)-H-2D (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA-A01 gene locus including 49 kb 5'-UTR and 74 kb 3'-UTR of HLA-A01*01. Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30-18# and A30-19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice, and induced the rapid increase of cytokines, including IFN-γ, TNF-α, and IL-6, in both HLA-A30 humanized Tg mice and wild-type mice. The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9# line at 3 days post-infection (dpi).

Conclusions: We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse, which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development, and support the study of HLA-A-restricted responses against infection in humans.
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http://dx.doi.org/10.1002/ame2.12225DOI Listing
July 2022

Magnetic microswarm for MRI contrast enhancer.

Chem Asian J 2022 Jul 6:e202200561. Epub 2022 Jul 6.

State Key Laboratory of Robotics and System, Harbin Institute of Technology, Harbin, 150001, China.

Highly effective contrast enhancer that processes targeting ability and maneuverability is in great demand in clinics for accurate diagnosis. Here a new strategy using deformable and manipulatable magnetic microswarm as MRI contrast enhancer is developed. Magnetic microswarm aggregated from nanoparticles is inherently deformable and they can be controlled with multiple programmable deform abilities. It is demonstrated that spatiotemporal programming magnetic field enables the magnetic microswarm not only to exhibit both ribbon-like and round-like behaviours but also to adaptively navigate multiple terrains. Intestinal model is conducted to explore the effect of magnetic microswarm as MRI enhancer, indicating the obvious enhancement of T -weighted MRI sequences. This magnetic microswarm holds great promise for highly sensitive and accurate intestinal MRI in the clinic.
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http://dx.doi.org/10.1002/asia.202200561DOI Listing
July 2022

Efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels.

Pak J Pharm Sci 2022 May;35(3(Special)):878-883

Neurosurgery Department 1, Handan Central Hospital, Handan, China.

To determine the efficacy and safety assessment of urokinase plus tirofiban in acute cerebral infarction patients without clear criminal vessels. Totally 96 cases of acute cerebral infarction (ACI) patients without clear criminal vessels enrolled in our hospital from July 2017 to July 2020 were randomized to the control group (n=48) with urokinase (n=48) and the observation group (n=48) with urokinase and tirofiban. Clinical efficacy, National Institute of Health Stroke Scale (NIHSS) score, Barthel Index (BI), Clusterin (CLU), tumor necrosis factor-α (TNF-α), serum hypersensitive C-reactive protein (hs - CRP), interleukin-6 (IL-6) and safety were compared. The observation group outperformed the control group in terms of clinical efficacy. Before treatment, the NIHSS scores, BI scores and serum levels of CLU, TNF-α, hs - CRP, and IL-6 in the control group were similar to those in the observation group. After treatment, the above indicators were all decreased, and lower in the observation group. The observation group had a lower incidence of adverse reactions. Arterial thrombolysis of urokinase plus tirofiban in ACI patients without clear responsible vessels effectively reduces postoperative NIHSS score, improves self-care ability, relieves the level of inflammatory factors, with fewer adverse reactions and higher safety profile.
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May 2022

Perceptual Data Augmentation for Biomedical Coronary Vessel Segmentation.

IEEE/ACM Trans Comput Biol Bioinform 2022 Jul 4;PP. Epub 2022 Jul 4.

Sufficient annotated data is critical to the success of deep learning methods. Annotating for vessel segmentation in X-ray coronary angiograms is extremely difficult because of the small and complex structures to be processed. Although unsupervised domain adaptation methods can be utilized to alleviate the annotation burden by using data in other domains, e.g., eye fundus images, these methods cannot perform well due to the characteristic of medical images. Data augmentation can help improve the similarity of source domain and target domain in unsupervised domain adaptation tasks. Existing data augmentation methods play a limited role in improving domain adaptation performance, especially for special medical image segmentation tasks. In this paper, we propose an effective perceptual data augmentation method to improve the similarity between eye fundus images and coronary angiograms by synthesizing virtual samples. Auto Foreground Augment method is designed to search for geometric transformations that improve the similarity between foreground vessels of eye fundus images and coronary angiograms. The Haar Wavelet-Based Perceptual Similarity Index is utilized to guide the synthesis of virtual samples in foreground and background mixup. Extensive experiments show that our data augmentation method can synthesize high-quality virtual samples and thus improve the domain adaptation performance. To our best knowledge, this is the first work to apply perceptual data augmentation to vessel segmentation in coronary angiograms.
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http://dx.doi.org/10.1109/TCBB.2022.3188148DOI Listing
July 2022

Kinesin Family Member 2A Serves as a Potential Biomarker Reflecting More Frequent Lymph Node Metastasis and Tumor Recurrence Risk in Basal-Like Breast Cancer Patients.

Front Surg 2022 16;9:889294. Epub 2022 Jun 16.

Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Kinesin family member 2A (KIF2A) is reported as an oncogene and a potential biomarker for progression and prognosis in several cancers such as cervical, ovarian, and gastric. However, its clinical value in basal-like breast cancer (BLBC) is unclear. This study aims to evaluate KIF2A expression and its correlation with clinical features and survival rates in BLBC patients.

Methods: KIF2A mRNA and protein expressions in tumor and adjacent tissues from 89 BLBC patients are assessed by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry assays, respectively.

Results: Both KIF2A protein (< 0.001) and mRNA expressions (< 0.001) were higher in tumor than in adjacent tissue. Besides, tumor KIF2A protein expression was positively correlated with N (= 0.028) and TNM (= 0.014) stages; meanwhile, tumor KIF2A mRNA expression was positively correlated with N stage (= 0.046), TNM stage (= 0.006), and tumor size (= 0.043). Additionally, both tumor KIF2A protein (= 0.035) and mRNA (= 0.039) high expressions were correlated with worse disease-free survival (DFS) but not with overall survival (both > 0.05). Moreover, tumor KIF2A protein expression was higher in relapsed patients than in non-relapsed patients within 3 years (= 0.015) and 5 years (= 0.031), whereas no difference was found between the dead and survivors within 3 years (= 0.057) or 5 years (= 0.107). Lastly, after adjustment, tumor KIF2A mRNA high exhibited a trend that correlated with DFS but without statistical significance (= 0.051).

Conclusion: KIF2A correlates with more frequent lymph node metastasis and worse DFS in BLBC patients, shedding light on its potency as a biomarker for BLBC.
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http://dx.doi.org/10.3389/fsurg.2022.889294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243457PMC
June 2022

A Multifunctional Gradient Solid Electrolyte Remarkably Improving Interface Compatibility and Ion Transport in Solid-State Lithium Battery.

ACS Appl Mater Interfaces 2022 Jul 1;14(27):30786-30795. Epub 2022 Jul 1.

Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, Zhenjiang 212013, China.

Solid electrolytes with both interface compatibility and efficient ion transport have been an urgent technical requirement for the practical application of solid-state lithium batteries. Herein, a multifuctional poly(1,3-dioxolane) (PDOL) electrolyte combining the gradient structure from the solid state to the gel state with the LiLaZrTaO (LLZTO) interfacial modification layer was designed, in which the "solid-to-gel" gradient structure greatly improved the electrode/electrolyte interface compatibility and ion transport, while the solid PDOL and LLZTO layers effectively improved the interface stability of the electrolyte/lithium anode and the inhibition of the lithium dendrites via their high mechanical strength and forming a stable interfacial SEI composite film. This gradient PDOL/LLZTO composite electrolyte possesses a high ionic conductivity of 2.9 × 10 S/cm with a wide electrochemical window up to 4.9 V vs Li/Li. Compared with the pristine PDOL electrolyte and PDOL solid electrolyte membrane coated with a layer of LLZTO, the gradient PDOL/LLZTO composite electrolyte shows better electrode/electrolyte interfacial compatibility, lower interface impedance, and smaller polarization, resulting in enhanced rate and cycle performances. The NCM622/PDOL-LLZTO/Li battery can be stably cycled 200 times at 0.3C and 25 °C. This multifunctional gradient structure design will promote the development of high-performance solid electrolytes and is expected to be widely used in solid-state lithium batteries.
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http://dx.doi.org/10.1021/acsami.2c05578DOI Listing
July 2022

Intraoperative Transcranial Doppler Monitoring Predicts the Risk of Cerebral Hyperperfusion Syndrome After Carotid Endarterectomy.

World Neurosurg 2022 Jun 26. Epub 2022 Jun 26.

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

Objective: Cerebral hyperperfusion syndrome (CHS) is a rare but serious complication following carotid endarterectomy (CEA). The aim of this study was to identify intraoperative transcranial Doppler (TCD) hemodynamic predictors of CHS after CEA.

Methods: Between January 2013 and December 2018, intraoperative TCD monitoring was performed for 969 patients who underwent CEA. The percentage increase in the mean velocity of the middle cerebral artery (MCAV%) at 3 postdeclamping time points (immediately after declamping, 5 minutes after declamping, and after suturing the skin) over baseline was compared between CHS and non-CHS patients.

Results: CHS was diagnosed in 31 patients (3.2%), including 11 with intracranial hemorrhage. The MCAV% values at the 3 postdeclamping time points over baseline were 177% (81%-275%), 90% (41%-175%), and 107% (55%-191%) in the CHS group, significantly higher than those in the non-CHS group (40% [14%-75%], 15% [1%-36%], and 18% [3%-41%], respectively, all P < 0.001). Receiver operating characteristic curve analysis showed that the 3 intraoperative MCAV% parameters all had excellent accuracy in identifying CHS (areas under the curve: 0.854, 0.839, and 0.858, respectively, all P < 0.001). The predictive value of the model consisting only of preoperative parameters was significantly increased by adding the intraoperative TCD hemodynamic parameters (area under the curve: 0.747 vs. 0.858, P = 0.006). Multivariate analyses identified the intraoperative MCAV% immediately after declamping (odds ratio: 9.840, 95% confidence interval: 2.638-36.696, P < 0.001) as an independent predictor of CHS.

Conclusions: Our results indicate that intraoperative TCD monitoring helps predict CHS after CEA at an early stage.
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http://dx.doi.org/10.1016/j.wneu.2022.06.100DOI Listing
June 2022

Low expression of exosomal miR-150 predicts poor prognosis in colorectal cancer patients after surgical resections.

Carcinogenesis 2022 Jun 29. Epub 2022 Jun 29.

Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, Shanghai, China.

Liver metastasis is a leading indicator of poor prognosis in patients with colorectal cancer (CRC). Exosomal intercellular communication has been reported to play an important role in cancer invasion and metastasis. Here, we characterized exosomal miRNAs underlying liver metastasis in CRC patients (Cohort 1, n = 30) using miRNA arrays. Exosomal miR-150 was found to be down-regulated in CRC patients with liver metastases compared to those without (P = 0.025, Fold Change = 2.01). These results were then validated using another independent cohort of CRC patients (Cohort 2, n = 64). Patients with low expression of exosomal miR-150 had significantly shorter overall survival time (33.3 months vs. 43.3 months, P = 0.002). In addition, the low expression of exosomal miR-150 was significantly correlated with advanced TNM staging (P = 0.013), higher CA199 level (P = 0.018), and the presence of liver metastasis (P = 0.048). Multivariate analysis showed that low expression of exosomal miR-150 (P = 0.035) and liver metastasis (P < 0.001) were independent prognostic factors for overall survival. In vivo and in vitro studies showed that the viability and invasion of CRC cells were both significantly suppressed by Exo miR-150. Target-prediction assessment and dual luciferase reporter assay indicated that FTO (the fat mass and obesity-associated gene) was a direct target for miR-150. This study first demonstrated that exosomal miR-150 may be a potential prognostic factor and treatment target for CRC.
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http://dx.doi.org/10.1093/carcin/bgac059DOI Listing
June 2022

Clostridium butyricum and Its Derived Extracellular Vesicles Modulate Gut Homeostasis and Ameliorate Acute Experimental Colitis.

Microbiol Spectr 2022 Jun 28:e0136822. Epub 2022 Jun 28.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China.

Microbiological treatments are expected to have a role in the future management of inflammatory bowel disease (IBD). Clostridium butyricum () is a probiotic microorganism that exhibits beneficial effects on various disease conditions. Although many studies have revealed that C. butyricum provides protective effects in mice with colitis, the way C. butyricum establishes beneficial results in the host remains unclear. In this study, we investigated the mechanisms by which C. butyricum modifies the gut microbiota, produces bacterial metabolites that may be involved, and, specifically, how microbial extracellular vesicles (EVs) positively influence IBD, using a dextran sulfate sodium (DSS)-induced colitis murine model in mice. First, we showed that C. butyricum provides a protective effect against colitis, as evidenced by the prevention of body weight loss, a reduction in the disease activity index (DAI) score, a shortened colon length, decreased histology score, and an improved gut barrier function, accompanied by reduced levels of pathogenic bacteria, including Escherichia/Shigella, and an increased relative abundance of butyrate-producing Clostridium sensu stricto-1 and . Second, we also confirmed that the gut microbiota and metabolites produced by C. butyricum played key roles in the attenuation of DSS-induced experimental colitis, as supported by the profound alleviation of colitis effects following fecal transplantation or fecal filtrate insertion supplied from C. butyricum-treated mice. Finally, C. butyricum-derived EVs protected the gut barrier function, improved gut microbiota homeostasis in ulcerative colitis, and contributed to overall colitis alleviation. This study indicated that C. butyricum provided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced by C. butyricum also contributed to the attenuation of DSS-induced colitis. Importantly, C. butyricum-derived EVs showed an effective impact in alleviating colitis.
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http://dx.doi.org/10.1128/spectrum.01368-22DOI Listing
June 2022

Serum exosomal microRNA-370-3p and microRNA-196a-5p are potential biomarkers for the diagnosis and prognosis of hepatocellular carcinoma.

Folia Histochem Cytobiol 2022 Jun 28. Epub 2022 Jun 28.

Affifiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, NO 648 DongFeng East Road, 071000 Baoding, China.

Introduction: Evidence has shown that some microRNAs (miRNAs) play a role in tumorigenesis of hepatocellular carcinoma (HCC). Herein, we aimed to evaluate the diagnostic and prognostic values of serum exosomal miR-370-3p and miR-196a-5p in patients with HCC.

Material And Methods: Serum exosomes in 90 HCC patients were extracted and identified. Serum exosomal miR-370-3p and miR-196a-5p expression in HCC patients were detected. The diagnostic value of miR-370-3p and miR-196a-5p, relationship between miR-370-3p and miR-196a-5p expression and clinicopathological features and prognosis of patients with HCC were analyzed. Relationship between miR-370-3p and miR-196a-5p expression and liver function indices such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in HCC patients were analyzed. The effects of miR-370-3p and miR-196a-5p on Huh7 HCC cells' proliferation, invasion and migration were determined.

Results: Lower expression of miR-370-3p and higher expression of miR-196a-5p were found in serum exosomes of HCC patients. Serum exosomal miR-370-3p and miR-196a-5p were associated with tumor size, tumor grade and TNM stage as well as prognosis and liver function indices of HCC patients. Overexpressed miR-370-3p or silenced miR-196a-5p suppressed proliferation, invasion and migration of Huh7 HCC cells.

Conclusions: We suggest that miR-370-3p/miR-196a-5p in serum exosomes of HCC patients could be potential biomarkers for the diagnosis and prognosis of HCC.
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http://dx.doi.org/10.5603/FHC.a2022.0019DOI Listing
June 2022
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