Publications by authors named "Jun Yao"

946 Publications

Event-related Beta EEG changes Induced by Various Neuromuscular Electrical Stimulation: A Pilot Study.

IEEE Trans Neural Syst Rehabil Eng 2021 Jun 15;PP. Epub 2021 Jun 15.

Previous results demonstrated that neuromuscular electrical stimulation (NMES) with various configurations could induce different activity at both the central and peripheral levels. Although NMES generating different peripheral movements have been studied, it is still unclear whether the difference in NMES-induced cortical activity is due to movement-or stimulation-related differences. Because NMES-induced cortical activity impacts motor function recovery, it is essential to know when NMES with various configurations evoke the same movement, whether the induced cortical activity is still different. Four NMES configurations: 1) Eight-let Frequency Trains, 2) Doublet frequency trains (DFT), 3) Constant-frequency trains with narrow-pulse, and 4) wide-pulse, were delivered to the right biceps brachii muscle in nine healthy young adults. We adjusted the intensities of these NMES to evoke the same elbow flexion and compared the cortical activities over sensorimotor regions. Our results showed that the four NMES patterns induced different beta-band Event-Related Desynchronization (ERD), with the DFT providing the strongest ERD value given the same NMES-induced elbow flexion (p<0.05). This difference is possibly due to NMES with different configuration activated in the amount of afferent proprioceptive fibers. Our pilot study suggests that the NMES-induced beta-band ERD may be an additional factor to consider when selecting the NMES configuration for a better motor function recovery.
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http://dx.doi.org/10.1109/TNSRE.2021.3089478DOI Listing
June 2021

Dairy Consumption and Risk of Conventional and Serrated Precursors of Colorectal Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

J Oncol 2021 25;2021:9948814. Epub 2021 May 25.

Department of Gastroenterology, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510632, China.

Objective: The consumption of dairy is associated with decreased risk of colorectal cancer (CRC), but few studies have assessed the relationship between dairy consumption and precursors of CRC. Therefore, we performed the first meta-analysis to further evaluate this association.

Methods: PubMed, Embase, Scopus, and Web of Science databases were searched through July 2020 for observational studies. Study-specific risk estimates for the highest versus lowest category were pooled using the random-effects and fixed-effects model. The methodological quality of included studies was assessed using the ROBINS-I Scale.

Results: A total of 12 studies were included (3 cohort studies and 9 case-control studies). Compared with the lowest level consumption, fermented dairy products had a decreased risk of precursors of CRC in both cohort (RR = 0.92 95% CI: 0.87-0.97) and case-control studies (RR = 0.98 95% CI: 0.96-0.99). Total dairy (RR = 0.80 95% CI: 0.68-0.96) and cheese (RR = 0.96 95% CI: 0.93-0.99) consumption was inversely associated with the risk in case-control studies whereas yogurt consumption was inversely associated with the risk in cohort studies (RR = 0.91 95%CI: 0.86-0.96). No significant associations were found for consumption of total milk and non/low-fat milk. For dose-response analyses, evidence of linear association was found in total dairy and yogurt consumption. The risk decreased by 12% for an increment of 200 g/d total dairy consumption (RR = 0.88 95% CI: 0.81-0.95) and decreased by 8% for an increment of 50 g/d yogurt consumption (RR = 0.92 95% CI: 0.85-0.99).

Conclusions: Fermented dairy products, specifically yogurt and cheese, were significantly associated with decreased risk of conventional and serrated precursors of colorectal cancer.
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http://dx.doi.org/10.1155/2021/9948814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172303PMC
May 2021

Targeting glucose metabolism sensitizes pancreatic cancer to MEK inhibition.

Cancer Res 2021 Jun 11. Epub 2021 Jun 11.

Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center

Pancreatic ductal adenocarcinoma (PDAC) is almost universally lethal. A critical unmet need exists to explore essential susceptibilities in PDAC and identify druggable targets to improve PDAC treatment. KRAS mutations dominate the genetic landscape of PDAC and lead to activation of multiple downstream pathways and cellular processes. Here, we investigated the requirement of these pathways for tumor maintenance using an inducible KrasG12D-driven PDAC mouse model (iKras model), identifying that RAF-MEK-MAPK signaling is the major effector for oncogenic KRAS-mediated tumor maintenance. However, consistent with previous studies, MEK inhibition had minimal therapeutic effect as a single agent for PDAC in vitro and in vivo. Although MEK inhibition partially downregulated transcription of glycolysis genes, it failed to suppress glycolytic flux in PDAC cells, which is a major metabolic effector of oncogenic KRAS. Accordingly, an in vivo genetic screen identified multiple glycolysis genes as potential targets that may sensitize tumor cells to MEK inhibition. Inhibition of glucose metabolism with low dose 2-deoxyglucose in combination with a MEK inhibitor induced apoptosis in KrasG12D-driven PDAC cells in vitro. The combination also inhibited xenograft PDAC tumor growth and prolonged overall survival in a genetically engineered PDAC mouse model. Molecular and metabolic analyses indicated that co-targeting glycolysis and MAPK signaling results in apoptosis via induction of lethal ER stress. Together, our work suggests that combined inhibition of glycolysis and the MAPK pathway may serve as an effective approach to target KRAS-driven PDAC.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3792DOI Listing
June 2021

Self-sustained green neuromorphic interfaces.

Nat Commun 2021 06 7;12(1):3351. Epub 2021 Jun 7.

Department of Electrical and Computer Engineering, University of Massachusetts, Amherst, MA, USA.

Incorporating neuromorphic electronics in bioelectronic interfaces can provide intelligent responsiveness to environments. However, the signal mismatch between the environmental stimuli and driving amplitude in neuromorphic devices has limited the functional versatility and energy sustainability. Here we demonstrate multifunctional, self-sustained neuromorphic interfaces by achieving signal matching at the biological level. The advances rely on the unique properties of microbially produced protein nanowires, which enable both bio-amplitude (e.g., <100 mV) signal processing and energy harvesting from ambient humidity. Integrating protein nanowire-based sensors, energy devices and memristors of bio-amplitude functions yields flexible, self-powered neuromorphic interfaces that can intelligently interpret biologically relevant stimuli for smart responses. These features, coupled with the fact that protein nanowires are a green biomaterial of potential diverse functionalities, take the interfaces a step closer to biological integration.
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http://dx.doi.org/10.1038/s41467-021-23744-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184933PMC
June 2021

Microbial community profiles in soils adjacent to mining and smelting areas: Contrasting potentially toxic metals and co-occurrence patterns.

Chemosphere 2021 May 28;282:130992. Epub 2021 May 28.

School of Water Resource and Environment, Research Center of Environmental Science and Engineering, MOE Key Laboratory of Groundwater Circulation and Environmental Evolution, China University of Geosciences (Beijing), 29 Xueyuan Road, Haidian District, Beijing, 100083, China; Equipe Environnement et Microbiologie, MELODY Group, Université de Pau et des Pays de L'Adour, E2S-UPPA, IPREM UMR CNRS 5254, BP 1155, 64013 Pau Cedex, France.

Mining and smelting activities have introduced severe potentially toxic metals (PTMs) contamination into surrounding soil settings. Influences of PTMs on microbial diversity have been widely studied. However, variations of microbial communities, network structures and community functions in different levels of PTMs contaminated soils adjacent to mining and smelting aera are still poorly investigated. In this study, microbial communities of soils around different levels of PTMs contamination were comprehensively studied by 16S rRNA gene amplicons high-throughput sequencing. Microbial interactions and module functions were also exploited to ascertain the discrepancies of PTMs concentration levels on microbial ecological functions. Results indicated that the microbial community composition was significantly distinct attributed to the phylum Protebacteria (p = 0.002) dominating in soil with high level PTMs contents but Actinobacteria (p = 0.002) in low level of PTMs-contaminated soil. Microbial α diversity was not significantly influenced by different levels of PTMs contaminations. Microorganisms proactively responded to PTMs content levels by means of strengthening network complexities and modularities among microbe-microbe interactions. The functions of main network modules were predicted associating membrane transport, amino acid metabolism, energy metabolism and carbohydrate metabolism. The PTMs detoxification and anti-oxidation were significantly strengthened at the high level of PTMs contamination. The present study demonstrated that modification of microbial community by the adaptive adjustment of microbial compositions and strengthening their network complexity and modularity.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130992DOI Listing
May 2021

In situ determination of secretory kinase Fam20C from living cells using fluorescence correlation spectroscopy.

Talanta 2021 Sep 29;232:122473. Epub 2021 Apr 29.

School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai, 200240, People's Republic of China. Electronic address:

Secretory proteins constitute a biologically crucial subset of proteins for regulation of some pathological and physiological processes, and they have become very important biomarkers in clinical diagnosis and therapeutic targets. So far, secretory protein functions and mechanisms have not been fully understood due to methodological limitations in detection of low-abundance proteins against medium background. Here, we propose a strategy to determine secretory protein from living cells in situ using fluorescence correlation spectroscopy (FCS). In this study, the recombinant protein Fam20C with SNAP-tag was used as a model protein, and O-benzylguanine (BG) derivatives bearing fluorescent dye as probes. We synthesized three fluorescent probes and investigated their fluorescent properties and diffusion behaviors in solution, and found the probe BG-Bodipy-561 more suitable for in situ labeling of Fam20C. We confirmed the specific binding of the probe to the target protein by combining FCS and in-gel fluorescence scanning methods. We studied the effects of some factors of the secretory Fam20C, and found that RNA interference significantly inhibited the synthesis of secretory fused Fam20C, and myriocin had no significant effect on the expression of secretory Fam20C, which indirectly illustrated that sphingolipid signaling can regulate the Fam20C activity. We believe that FCS is a very promising method to analyze secretory proteins from living cells in situ.
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http://dx.doi.org/10.1016/j.talanta.2021.122473DOI Listing
September 2021

Oxysterol-binding protein-like 2 contributes to the developmental progression of preadipocytes by binding to β-catenin.

Cell Death Discov 2021 May 17;7(1):109. Epub 2021 May 17.

Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing, China.

Oxysterol-binding protein-like 2 (OSBPL2), also known as oxysterol-binding protein-related protein (ORP) 2, is a member of lipid transfer protein well-known for its role in regulating cholesterol homeostasis. A recent study reported that OSBPL2/ORP2 localizes to lipid droplets (LDs) and is associated with energy metabolism and obesity. However, the function of OSBPL2/ORP2 in adipocyte differentiation is poorly understood. Here, we report that OSBPL2/ORP2 contributes to the developmental progression of preadipocytes. We found that OSBPL2/ORP2 binds to β-catenin, a key effector in the Wnt signaling pathway that inhibits adipogenesis. This complex plays a role in regulating the protein level of β-catenin only in preadipocytes, not in mature adipocytes. Our data further indicated that OSBPL2/ORP2 mediates the transport of β-catenin into the nucleus and thus regulates target genes related to adipocyte differentiation. Deletion of OSBPL2/ORP2 markedly reduces β-catenin both in the cytoplasm and in the nucleus, promotes preadipocytes maturation, and ultimately leads to obesity-related characteristics. Altogether, we provide novel insight into the function of OSBPL2/ORP2 in the developmental progression of preadipocytes and suggest OSBPL2/ORP2 may be a potential therapeutic target for the treatment of obesity-related diseases.
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http://dx.doi.org/10.1038/s41420-021-00503-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129138PMC
May 2021

Human ribonuclease 1 serves as a secretory ligand of ephrin A4 receptor and induces breast tumor initiation.

Nat Commun 2021 05 13;12(1):2788. Epub 2021 May 13.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Human ribonuclease 1 (hRNase 1) is critical to extracellular RNA clearance and innate immunity to achieve homeostasis and host defense; however, whether it plays a role in cancer remains elusive. Here, we demonstrate that hRNase 1, independently of its ribonucleolytic activity, enriches the stem-like cell population and enhances the tumor-initiating ability of breast cancer cells. Specifically, secretory hRNase 1 binds to and activates the tyrosine kinase receptor ephrin A4 (EphA4) signaling to promote breast tumor initiation in an autocrine/paracrine manner, which is distinct from the classical EphA4-ephrin juxtacrine signaling through contact-dependent cell-cell communication. In addition, analysis of human breast tumor tissue microarrays reveals a positive correlation between hRNase 1, EphA4 activation, and stem cell marker CD133. Notably, high hRNase 1 level in plasma samples is positively associated with EphA4 activation in tumor tissues from breast cancer patients, highlighting the pathological relevance of the hRNase 1-EphA4 axis in breast cancer. The discovery of hRNase 1 as a secretory ligand of EphA4 that enhances breast cancer stemness suggests a potential treatment strategy by inactivating the hRNase 1-EphA4 axis.
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http://dx.doi.org/10.1038/s41467-021-23075-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119676PMC
May 2021

Toxic response of the freshwater green algae Chlorella pyrenoidosa to combined effect of flotation reagent butyl xanthate and nickel.

Environ Pollut 2021 May 3;286:117285. Epub 2021 May 3.

School of Water Resources and Environment, Research Center of Environmental Science and Engineering, China University of Geosciences (Beijing), 29 Xueyuan Road, Haidian District, 100083, Beijing, China.

Butyl Xanthate (BX) is a typical flotation reagent used to extract non-ferrous nickel ores, discharged into the surrounding environment of mining areas in large quantities. However, few studies have focused on the toxicity of combined pollution of BX and nickel (Ni) on aquatic plants, especially phytoplankton, the main producer of aquatic ecosystems. The toxicity and potential mechanism of single and combined pollution of BX and Ni at different concentrations (0-20 mg L) on typical freshwater algae (Chlorella pyrenoidosa) were studied. BX slightly stimulated the growth of C. pyrenoidosa on the first day, but Ni and Ni/BX mixture significantly inhibited it during incubation. Results showed that the inhibition rate (I) of the pollutants on the growth of C. pyrenoidosa followed the order: Ni/BX mixture > Ni > BX. The 96-h 20% effective inhibitory concentrations (96h-EC) of Ni and BX on C. pyrenoidosa growth were 3.86 mg L and 19.25 mg L, respectively, indicating C. pyrenoidosa was sensitive to pollutants. The content of total soluble protein (TSP) and chlorophyll a (Chl-a) changed significantly, which may be caused by the damage of pollutants to cell structures (cell membranes and chloroplasts). In addition, the I of pollutants on C. pyrenoidosa growth was related to dose, superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA). The increasement of reactive oxygen species (ROS), antioxidant enzymes (SOD and CAT), and MDA content, suggested C. pyrenoidosa suffered from oxidative stress, leading to lipid oxidation. These results will help to understand the toxicity mechanism of pollutants in typical mining areas and assess the environmental risks of pollutants to primary producers in aquatic ecosystems.
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http://dx.doi.org/10.1016/j.envpol.2021.117285DOI Listing
May 2021

Signature of gene aberrant alternative splicing events in pancreatic adenocarcinoma prognosis.

J Cancer 2021 31;12(11):3164-3179. Epub 2021 Mar 31.

Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, China.

Alternative splicing (AS), as an effective and universal mechanism of transcriptional regulation, is involved in the development and progression of cancer. Therefore, systematic analysis of alternative splicing in pancreatic adenocarcinoma (PAAD) is warranted. The corresponding clinical information of the RNA-Seq data and PAAD cohort was downloaded from the TCGA data portal. Then, a java application, SpliceSeq, was used to evaluate the RNA splicing pattern and calculate the splicing percentage index (PSI). Differentially expressed AS events (DEAS) were identified based on PSI values between PAAD cancer samples and normal samples of adjacent tissues. Kaplan-Meier and Cox regression analyses were used to assess the association between DEAS and patient clinical characteristics. Unsupervised cluster analysis used to reveal four clusters with different survival patterns. At the same time, GEO and TCGA combined with GTEx to verify the differential expression of AS gene and splicing factor. After rigorous filtering, a total of 45,313 AS events were identified, 1,546 of which were differentially expressed AS events. Nineteen DEAS were found to be associated with OS with a five-year overall survival rate of 0.946. And the subtype clusters results indicate that there are differences in the nature of individual AS that affect clinical outcomes. Results also identified 15 splicing factors associated with the prognosis of PAAD. And the splicing factors ESRP1 and RBM5 played an important role in the PAAD-associated AS events. The PAAD-associated AS events, splicing networks, and clusters identified in this study are valuable for deciphering the underlying mechanisms of AS in PAAD and may facilitate the establishment of therapeutic goals for further validation.
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http://dx.doi.org/10.7150/jca.48661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100795PMC
March 2021

The efficacy and risk factors of mechanical thrombectomy for the treatment of vertebrobasilar artery occlusion: a single center study.

Ann Palliat Med 2021 Apr;10(4):4697-4704

Department of Neurology, Taixing People's Hospital, Taixing, China.

Background: The mortality of acute ischemic stroke patients caused by vertebrobasilar artery occlusion (VBAO) is high and mechanical thrombectomy has gradually become a promising treatment for acute ischemic stroke. This study analyzed the efficacy of mechanical thrombectomy and the risk factors associated with poor outcomes in VBAO patients caused by severe local atherosclerotic stenosis.

Methods: This retrospective study enrolled patients with acute ischemic stroke caused by VBAO between March 1, 2016 and August 31, 2019. Patient demographic and clinical data were collected retrospectively. All enrolled patients were retrospectively interviewed for at least 3 months. Patients with a modified Rankin scale (mRS) score between 0 and 3 points were defined as having satisfactory outcomes while those with more than 3 points were defined as having unsatisfactory outcomes. In-hospital mortality, the rates of recanalization, and the rates of intracerebral hemorrhage were also recorded. Multivariable logistic regression was used to determine the risk factors of unsatisfactory outcomes in enrolled patients.

Results: A total of 65 patients were enrolled in this study with a median age 69.0 (63.0-78.0) years and 48 patients (73.8%) were male. Approximately 50% of patients had a mRS score of 0 or 1 point within 90 days after treatment with mechanical thrombectomy and 14 patients had a mRS score of 6 points. A total of 11 patients died in hospital. Out of the 65 patients, 7 required recanalization and 9 patients suffered from intracerebral hemorrhage. Multivariate logistic regression analysis showed that older age, lower baseline posterior circulation acute stroke prognosis early CT score (pcASPECTS), higher baseline National Institutes of Health stroke scale (NIHSS) score, and residual stenosis were independent risk factors of both unsatisfactory outcomes and mortality of VBAO patients.

Conclusions: This study confirmed the important role of mechanical thrombectomy in the treatment of acute ischemic stroke caused by VBAO and may provide some guidance for improving the prognosis of patients.
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http://dx.doi.org/10.21037/apm-21-614DOI Listing
April 2021

Using MEST-C Scores and the International Study of Kidney Disease in Children Classification to Predict Outcomes of Henoch-Schönlein Purpura Nephritis in Children.

Front Pediatr 2021 14;9:658845. Epub 2021 Apr 14.

Department of Pediatrics, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.

Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) bear similarities in some aspects. The histological classification of HSPN was built on the International Study of Kidney Disease in Children (ISKDC) criteria, while IgAN was established on the 2016 Oxford classification (MEST-C scores). The purpose of this paper was to discuss the predictive value of the ISKDC classification and MEST-C scores in children with HSPN. We performed a retrospective study of 877 children with HSPN in a single center between 2001 and 2019. The primary outcome was defined as chronic kidney disease-estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m. During the follow-up period of 23.3 (10.9-47.9) months, 51 (5.8%) patients reached the primary outcome. As revealed in a Kaplan-Meier plot, segmental glomerulosclerosis (S) ( < 0.001) and tubular atrophy/interstitial fibrosis (T) ( < 0.001) significantly predict poor renal outcome. Other Oxford lesions and the ISKDC classification, however, did not show a significant difference in a worse outcome. In a multivariate Cox model adjusted for pathological and clinical factors, eGFR [hazard ratio (HR) = 2.831, 95% confidence interval (95% CI) = 1.359-5.896], S lesion (HR = 3.936, 95% CI = 2.078-7.457), and T lesion (HR = 4.002, 95% CI = 1.733-9.242) were independent risk factors for the renal outcome. This series constitutes the largest series reported so far in the literature of such patients. According to our findings, S and T of the Oxford classification, which are ignored by the ISKDC classification, could be applied to predict the renal prognosis of children with HSPN.
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http://dx.doi.org/10.3389/fped.2021.658845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079736PMC
April 2021

Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma.

BMC Cancer 2021 Apr 26;21(1):462. Epub 2021 Apr 26.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6#, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Backgroud: In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC).

Methods: The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database.

Results: Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44-2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05).

Conclusions: Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.
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http://dx.doi.org/10.1186/s12885-021-08104-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073913PMC
April 2021

Puromycin-Modified Silica Microsphere-Based Nascent Proteomics Method for Rapid and Deep Nascent Proteome Profile.

Anal Chem 2021 04 15;93(16):6403-6413. Epub 2021 Apr 15.

Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, P.R. China.

Nascent proteome is crucial in directly revealing how the expression of a gene is regulated on a translation level. In the nascent protein identification, puromycin capture is one of the pivotal methods, but it is still facing the challenge in the deep profiling of nascent proteomes due to the low abundance of most nascent proteins. Here, we describe the synthesis of puromycin-modified silica microspheres (PMSs) as the sorbent of dispersive solid-phase microextraction and the establishment of the PMS-based nascent proteomics (PMSNP) method for efficient capture and analysis of nascent proteins. The modification efficiency of puromycin groups on silica microspheres reached 91.8% through the click reaction. After the optimization and simplification of PMSNP, more than 3500 and 3900 nascent proteins were rapidly identified in HeLa cells and mouse brains within 13.5 h, respectively. The PMSNP method was successfully applied to explore changes in the translation process in a biological stress model, namely, the lipopolysaccharide-stimulated HeLa cells. Biological functional analyses revealed the unique characters of the nascent proteomes and exhibited the superiority of the PMSNP in the identification of low abundance and secreted nascent proteins, thus demonstrating the sensitivity and immediacy of the PMSNP method.
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http://dx.doi.org/10.1021/acs.analchem.0c05393DOI Listing
April 2021

TYRO3 induces anti-PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis.

J Clin Invest 2021 Apr;131(8)

Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.

Immune checkpoint blockade therapy has demonstrated promising clinical outcomes for multiple cancer types. However, the emergence of resistance as well as inadequate biomarkers for patient stratification have largely limited the clinical benefits. Here, we showed that tumors with high TYRO3 expression exhibited anti-programmed cell death protein 1/programmed death ligand 1 (anti-PD-1/PD-L1) resistance in a syngeneic mouse model and in patients who received anti-PD-1/PD-L1 therapy. Mechanistically, TYRO3 inhibited tumor cell ferroptosis triggered by anti-PD-1/PD-L1 and facilitated the development of a protumor microenvironment by reducing the M1/M2 macrophage ratio, resulting in resistance to anti-PD-1/PD-L1 therapy. Inhibition of TYRO3 promoted tumor ferroptosis and sensitized resistant tumors to anti-PD-1 therapy. Collectively, our findings suggest that TYRO3 could serve as a predictive biomarker for patient selection and a promising therapeutic target to overcome anti-PD-1/PD-L1 resistance.
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http://dx.doi.org/10.1172/JCI139434DOI Listing
April 2021

Transfer- or 'transmission'-RNA fragments? The roles of tsRNAs in the reproductive system.

Mol Hum Reprod 2021 May;27(5)

Institute of Reproductive Health/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Transfer-RNAs (tRNAs) help ribosomes decode mRNAs and synthesize proteins; however, tRNA fragments produced under certain conditions, known as tRNA-derived small RNAs (tsRNAs), have been found to play important roles in pathophysiological processes. In the reproductive system, tsRNAs are abundant in gametes and embryos and at the maternal-fetal interface, as well as in microvesicles like epididymosomes, seminal plasma exosomes, and syncytiotrophoblast-derived extracellular vesicles. tsRNAs can affect gamete cell maturation, zygote activation, and early embryonic development. tsRNAs can transmit epigenetic information to later generations. In particular, exposure to environmental factors such as nutrition, isoproterenol, and poly(I:C) may allow tsRNAs to transfer information to the gametes or placenta to alter offspring phenotype. The underlying mechanisms of tsRNAs action include transposon silencing, translation regulation, and target mRNA degradation. Herein, we review the currently reported tsRNAs in the reproductive system, their validated functions, and potential roles. A better understanding of this field may help to provide useful recommendations or develop strategies to increase fertility and conception of healthy babies.
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http://dx.doi.org/10.1093/molehr/gaab026DOI Listing
May 2021

Effects of on growth performance, serum biochemical parameters, antioxidant capacity, and immune function in suckling calves.

Open Life Sci 2020 31;15(1):1033-1041. Epub 2020 Dec 31.

College of Animal Science & Technology, Shihezi University, Shihezi 832003, China.

Background: This study was conducted to investigate the effects of on growth performance, serum biochemical parameters, antioxidant capacity, and immune function in suckling calves.

Methods: In total, 20 1-day-old Holstein calves with similar body weight (BW) and good health condition were randomly assigned into two groups with ten replicates per group and one calf per replicate. The control group (CON group) was fed a basal diet, whereas the group (BM group) was fed the basal diet supplemented with 500 mg/day/head of (10 CFU/g) for 28 days.

Results: The results revealed that the BM group showed an increase in final BW, daily weight gain, and feed-to-gain ratio ( < 0.05) and a decrease in diarrhea rate. Moreover, the concentrations of serum cholesterol and high-density lipoprotein decreased ( < 0.05) in the BM group compared with the CON group at 28 days. The level of serum glutathione was higher ( < 0.05) in the BM group than that of the CON group at 14 days, whereas the level of serum malondialdehyde decreased ( < 0.01) in the BM group compared with the CON group at 28 days. In addition, compared with the CON group ( < 0.05), the concentrations of serum IgA, IgM, IgG, and IL-4 were higher, whereas the concentration of serum TNF-α decreased in the BM group at 28 days.

Conclusion: had beneficial effects on the improvement of growth performance, immune function, and intestinal oxidative status of suckling calves.
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http://dx.doi.org/10.1515/biol-2020-0106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874550PMC
December 2020

-- regulates cognitive functions in the hippocampus through complement component 3-dependent modulation of synaptic vesicle release.

Proc Natl Acad Sci U S A 2021 Apr;118(14)

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, 100084 Beijing, China;

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that -- but not -- could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, -- deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the -- KO mice could rescue the synaptic and learning deficits. Therefore, -- played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders.
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http://dx.doi.org/10.1073/pnas.2021770118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040660PMC
April 2021

Specific Analysis of α-2,3-Sialylated N-Glycan Linkage Isomers by Microchip Capillary Electrophoresis-Mass Spectrometry.

Anal Chem 2021 04 22;93(13):5537-5546. Epub 2021 Mar 22.

Department of Chemistry and Shanghai Cancer Center, Fudan University, Shanghai 200032, People's Republic of China.

Sialylated N-glycan isomers with α-2,3 and α-2,6 linkages play crucial and distinctive roles in diverse physiological and pathological processes. Changes of α-2,3-linked sialic acids in sialylated N-glycans are especially important in monitoring the initiation and progression of diseases. However, the specific analysis of α-2,3-sialylated N-glycan linkage isomers remains challenging due to their extremely low abundance and technical limitations in separation and detection. Herein, we designed an integrated strategy that combines linkage-specific derivatization and a charge-sensitive separation method based on microfluidic chip capillary electrophoresis-mass spectrometry (microchip CE-MS) for specific analysis of α-2,3-sialylated N-glycan linkage isomers for the first time. The α-2,6- and α-2,3-sialic acids were selectively labeled with methylamine (MA) and ,-dimethylethylenediamine (DMEN), respectively, which selectively makes α-2,3-sialylated N-glycans positively charged and realizes online purification, concentration, and discrimination of α-2,3-sialylated N-glycans from other N-glycans in microchip CE-MS. This new approach was demonstrated with standard multisialylated N-glycans, and it was found that only the α-2,3-sialylated N-glycans migrated and were detected in order according to the number of α-2,3-sialic acids. Finally, this strategy was successfully applied in highly sensitive profiling and reproducible quantitation of the serum α-2,3-sialylated N-glycome from ovarian cancer (OC) patients, where 7 of 33 detected α-2,3-sialylated N-glycans significantly changed in the OC group compared with healthy controls.
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http://dx.doi.org/10.1021/acs.analchem.1c00064DOI Listing
April 2021

Synaptotagmin-1 interacts with PI(4,5)P2 to initiate synaptic vesicle docking in hippocampal neurons.

Cell Rep 2021 Mar;34(11):108842

State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

Synaptic vesicle (SV) docking is a dynamic multi-stage process that is required for efficient neurotransmitter release in response to nerve impulses. Although the steady-state SV docking likely involves the cooperation of Synaptotagmin-1 (Syt1) and soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), where and how the docking process initiates remains unknown. Phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) can interact with Syt1 and SNAREs to contribute to vesicle exocytosis. In the present study, using the CRISPRi-mediated multiplex gene knockdown and 3D electron tomography approaches, we show that in mouse hippocampal synapses, SV docking initiates at ∼12 nm to the active zone (AZ) by Syt1. Furthermore, we demonstrate that PI(4,5)P2 is the membrane partner of Syt1 to initiate SV docking, and disrupting their interaction could abolish the docking initiation. In contrast, the SNARE complex contributes only to the tight SV docking within 0-2 nm. Therefore, Syt1 interacts with PI(4,5)P2 to loosely dock SVs within 2-12 nm to the AZ in hippocampal neurons.
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http://dx.doi.org/10.1016/j.celrep.2021.108842DOI Listing
March 2021

Analysis of dental caries and the impact factors of caries in children aged 3-5 years old in Changdu, Xizang.

Hua Xi Kou Qiang Yi Xue Za Zhi 2021 Feb;39(1):53-57

Dept. of Stomatology, Changdu Women and Children Health Care Hospital, Changdu 854000, China.

Objectives: To investigate caries status and its impact factors in preschool children in plateau and to provide reference for caries prevention in highlands.

Methods: Examination of caries was performed on 1 597 children aged 3-5 years old in 11 kindergartens in Changdu, Xizang, in accordance with the 4th National Oral Health Survey standards and methods. Their parents were surveyed with the questionnaire regarding oral hygiene habit and consciousness about oral health and related factors. All the data were collected and analyzed.

Results: The prevalence of caries among children aged 3-5 years old in Changdu was 52.85%, with dmft index of 2.44. The caries rate and dmft of children aged 3 years old were lower than those of children aged 4 and 5 years old (<0.05). No significant difference was observed in the caries rate between males and females (>0.05). Single-factor analysis showed that the frequency of brushing teeth more than twice a day, low frequency of eating sweets, high frequency of drinking butter tea, and regular oral examination can reduce the rate of caries (<0.05). Multivariate logistic analysis showed that the frequency of eating sweets, drinking butter tea, and oral examination are related impact factors of caries.

Conclusions: The prevalence of ca-ries in children aged 3-5 years old in Changdu increases with aging. Good oral hygiene and eating habits and regular oral examination can reduce the rate of caries.
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http://dx.doi.org/10.7518/hxkq.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905412PMC
February 2021

Circ_0000003 regulates glutamine metabolism and tumor progression of tongue squamous cell carcinoma via the miR‑330‑3p/GLS axis.

Oncol Rep 2021 04 2;45(4). Epub 2021 Mar 2.

School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, P.R. China.

Various circular RNAs (circRNAs) have been shown to exert vital functions in tongue squamous cell carcinoma (TSCC). However, their roles in TSCC progression remain to be elucidated. This research aimed to investigate the role and mechanism of hsa_circ_0000003 (circ_0000003) in TSCC progression. Here, we found that circ_0000003 expression was upregulated in TSCC tissues and cell lines, and high circ_0000003 expression was correlated with advanced TNM stage, increased tumor size and poor patient survival. Circ_0000003 was revealed to facilitate cell proliferation, migration and invasion of TSCC cells. Mechanistically, we found that circ_0000003 acted as a competing endogenous RNA (ceRNA) that sponged miR‑330‑3p, thereby elevating glutaminase (GLS) expression. Accordingly, cell invasion, migration, glutamine consumption, α‑ketoglutarate (α‑KG) production and ATP production were significantly decreased by circ_0000003 knockdown in TSCC cells, and these effects were reversed by miR‑330‑3p inhibition. In conclusion, circ_0000003 facilitates TSCC cell proliferation, migration, invasion and glutamine catabolism by regulating the miR‑330‑3p/GLS pathway.
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http://dx.doi.org/10.3892/or.2021.7996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934215PMC
April 2021

Current Status and Challenge of Pseudorabies Virus Infection in China.

Virol Sin 2021 Feb 22. Epub 2021 Feb 22.

Laboratory of Animal Disease Prevention and Control and Animal Model, Hunan Provincial Key Laboratory of Protein Engineering in Animal Vaccines, College of Veterinary Medicine, Hunan Agricultural University (HUNAU), Changsha, 410128, China.

Pseudorabies (PR), also called Aujeszky's disease, is a highly infectious disease caused by pseudorabies virus (PRV). Without specific host tropism, PRV can infect a wide variety of mammals, including pig, sheep, cattle, etc., thereby causing severe clinical symptoms and acute death. PRV was firstly reported in China in 1950s, while outbreaks of emerging PRV variants have been documented in partial regions since 2011, leading to significant economic losses in swine industry. Although scientists have been devoting to the design of diagnostic approaches and the development of vaccines during the past years, PR remains a vital infectious disease widely prevalent in Chinese pig industry. Especially, its potential threat to human health has also attracted the worldwide attention. In this review, we will provide a summary of current understanding of PRV in China, mainly focusing on PRV history, the existing diagnosis methods, PRV prevalence in pig population and other susceptible mammals, molecular characteristics, and the available vaccines against its infection. Additionally, promising agents including traditional Chinese herbal medicines and novel inhibitors that may be employed to treat this viral infection, are also discussed.
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http://dx.doi.org/10.1007/s12250-020-00340-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897889PMC
February 2021

DNA methylation patterns-based subtype distinction and identification of soft tissue sarcoma prognosis.

Medicine (Baltimore) 2021 Feb;100(5):e23787

Department of Orthopedics Trauma and Hand Surgery.

Abstract: Soft tissue sarcomas (STSs) are heterogeneous at the clinical with a variable tendency of aggressive behavior. In this study, we constructed a specific DNA methylation-based classification to identify the distinct prognosis-subtypes of STSs based on the DNA methylation spectrum from the TCGA database. Eventually, samples were clustered into 4 subgroups, and their survival curves were distinct from each other. Meanwhile, the samples in each subgroup reflected differentially in several clinical features. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was also conducted on the genes of the corresponding promoter regions of the above-described specific methylation sites, revealing that these genes were mainly concentrated in certain cancer-associated biological functions and pathways. In addition, we calculated the differences among clustered methylation sites and performed the specific methylation sites with LASSO algorithm. The selection operator algorithm was employed to derive a risk signature model, and a prognostic signature based on these methylation sites performed well for risk stratification in STSs patients. At last, a nomogram consisted of clinical features and risk score was developed for the survival prediction. This study declares that DNA methylation-based STSs subtype classification is highly relevant for future development of personalized therapy as it identifies the prediction value of patient prognosis.
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http://dx.doi.org/10.1097/MD.0000000000023787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870194PMC
February 2021

Integrated analysis identifies oxidative stress genes associated with progression and prognosis in gastric cancer.

Sci Rep 2021 Feb 8;11(1):3292. Epub 2021 Feb 8.

Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.

Oxidative stress (OS) reactions are reported to be associated with oncogenesis and tumor progression. However, little is known about the potential diagnostic value of OS in gastric cancer (GC). This study identified hub OS genes associated with the prognosis and progression of GC and illustrated the underlying mechanisms. The transcriptome data and corresponding GC clinical information were collected from The Cancer Genome Atlas (TCGA) database. Aberrantly expressed OS genes between tumors and adjacent normal tissues were screened, and 11 prognosis-associated genes were identified with a series of bioinformatic analyses and used to construct a prognostic model. These genes were validated in the Gene Expression Omnibus (GEO) database. Furthermore, weighted gene co-expression network analysis (WGCNA) was subsequently conducted to identify the most significant hub genes for the prediction of GC progression. Analysis revealed that a good prognostic model was constructed with a better diagnostic accuracy than other clinicopathological characteristics in both TCGA and GEO cohorts. The model was also significantly associated with the overall survival of patients with GC. Meanwhile, a nomogram based on the risk score was established, which displayed a favorable discriminating ability for GC. In the WGCNA analysis, 13 progression-associated hub OS genes were identified that were also significantly associated with the progression of GC. Furthermore, functional and gene ontology (GO) analyses were performed to reveal potential pathways enriched with these genes. These results provide novel insights into the potential applications of OS-associated genes in patients with GC.
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http://dx.doi.org/10.1038/s41598-021-82976-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870842PMC
February 2021

Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy.

Nat Commun 2021 02 5;12(1):832. Epub 2021 Feb 5.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1TIM-3 T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3 cytotoxic CD8 T cells and immunosuppressive regulatory T cells (T cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes T cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-21099-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864927PMC
February 2021

MicroRNA-505, Suppressed by Oncogenic Long Non-coding RNA LINC01448, Acts as a Novel Suppressor of Glycolysis and Tumor Progression Through Inhibiting HK2 Expression in Pancreatic Cancer.

Front Cell Dev Biol 2020 15;8:625056. Epub 2021 Jan 15.

Department of Cardiology, Shenzhen People's Hospital, The Second Affiliated Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play vital regulatory roles in pancreatic cancer (PC) initiation and progression. We aimed to explore the biological functions and underlying mechanisms of miR-505-3p (miR-505) in PC. We first screened miRNA expression profiles using microarray in PC tissues and normal tissues, and then studied the function and underlying mechanism of miR-505. Moreover, we evaluated the regulatory effect of lncRNA LINC01448 on miR-505. We demonstrated miR-505 that was significantly downregulated in PC tissues. We further revealed that miR-505 significantly inhibited cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by targeting HK2. In addition, overexpression of miR-505 led to tumor growth inhibition , demonstrating that it acts as a tumor suppressor in PC. LINC01448 was identified as an oncogenic lncRNA that could reduce miR-505 expression. Subsequent studies confirmed that LINC01448 enhanced cell proliferation, invasion, sphere formation, glucose consumption, and lactate production by regulating the miR-505/HK2 pathway. These findings demonstrated that miR-505, suppressed by LINC01448, could function as a key tumor suppressor by targeting HK2 in PC, elucidating an important role of the LINC01448/miR-505/HK2 pathway in regulating PC glycolysis and progression.
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http://dx.doi.org/10.3389/fcell.2020.625056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843961PMC
January 2021

Production, purification, characterization, and biological properties of Rhodosporidium paludigenum polysaccharide.

PLoS One 2021 29;16(1):e0246148. Epub 2021 Jan 29.

College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang, China.

The yield of marine red yeast polysaccharide (MRYP) obtained from Rhodosporidium paludigenum was increased by optimizing fermentation conditions, and the pure polysaccharide was extracted by column chromatography. The molecular weight of pure MRYP and the ratio of mannose to glucose in components of MRYP were determined. Antioxidant and antibacterial abilities of MRYP were investigated in vitro and in vivo. The optimal fermentation parameters were as follows: Medium 4, pH = 6.72, temperature = 30.18°C, blades speed = 461.36 r/min; the optimized yield reached 4323.90 mg/L, which was 1.31 times the original yield. The sequence of factors that affected the MRYP yield was the blades speed>pH>temperature. The main components of MRYP were MYH-1 and MYH-2. The molecular weights of MYH-1 and MYH-2 were 246.92 kDa and 21.88 kDa, respectively; they accounted for 53.60% and 28.75% of total polysaccharide. In MYH-1 and MYH-2, the proportion of glucose and mannose accounted for 46.94%, 38.46%, and 67.10%, 7.17%, respectively. In vitro, the ability of scavenging DPPH•, •OH, and [Formula: see text] radical was 32.26%, 24.34%, and 22.09%; the minimum inhibitory concentration (MIC) of MRYP was 480 μg/mg. In vivo, MRYP improved the lambs' body weight, antioxidant enzyme activity, and the number of probiotics, but it reduced the feed/gain (F/G) ratio and the number of pathogenic bacteria in 60-days-old lambs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246148PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845956PMC
January 2021

Therapy-Induced Transdifferentiation Promotes Glioma Growth Independent of EGFR Signaling.

Cancer Res 2021 03 28;81(6):1528-1539. Epub 2021 Jan 28.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.

EGFR is frequently amplified, mutated, and overexpressed in malignant gliomas. Yet the EGFR-targeted therapies have thus far produced only marginal clinical responses, and the underlying mechanism remains poorly understood. Using an inducible oncogenic EGFR-driven glioma mouse model system, our current study reveals that a small population of glioma cells can evade therapy-initiated apoptosis and potentiate relapse development by adopting a mesenchymal-like phenotypic state that no longer depends on oncogenic EGFR signaling. Transcriptome analyses of proximal and distal treatment responses identified TGFβ/YAP/Slug signaling cascade activation as a major regulatory mechanism that promotes therapy-induced glioma mesenchymal lineage transdifferentiation. Following anti-EGFR treatment, TGFβ secreted from stressed glioma cells acted to promote YAP nuclear translocation that stimulated upregulation of the pro-mesenchymal transcriptional factor SLUG and subsequent glioma lineage transdifferentiation toward a stable therapy-refractory state. Blockade of this adaptive response through suppression of TGFβ-mediated YAP activation significantly delayed anti-EGFR relapse and prolonged animal survival. Together, our findings shed new insight into EGFR-targeted therapy resistance and suggest that combinatorial therapies of targeting both EGFR and mechanisms underlying glioma lineage transdifferentiation could ultimately lead to deeper and more durable responses. SIGNIFICANCE: This study demonstrates that molecular reprogramming and lineage transdifferentiation underlie anti-EGFR therapy resistance and are clinically relevant to the development of new combinatorial targeting strategies against malignant gliomas with aberrant EGFR signaling.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1810DOI Listing
March 2021

Successful treatment of a patient with multi-site infection of cerebrospinal fluid and testis due to Klebsiella pneumoniae.

Acta Biochim Biophys Sin (Shanghai) 2021 Mar;53(4):511-513

Department of Intensive Care Unit, China Coast Guard Hospital of the People's Armed Police Force, Jiaxing 314001, China.

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http://dx.doi.org/10.1093/abbs/gmab004DOI Listing
March 2021