Publications by authors named "Yili Wang"

153 Publications

An electro-peroxone oxidation-Fe(III) coagulation sequential conditioning process for the enhanced waste activated sludge dewatering: Bound water release and organics multivariate change.

Sci Total Environ 2022 Apr 12;833:155272. Epub 2022 Apr 12.

Beijing Key Lab for Source Control Technology of Water Pollution, College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China; Engineering Research Center for Water Pollution Source Control & Eco-remediation, College of Environmental Science and Engineering, Beijing Forestry University, Beijing 100083, China.

As a by-product of wastewater treatment, waste activated sludge (WAS) has complex composition, strong hydrophilic extracellular polymeric substance (EPS), which make it difficult to dewater. In this study, an electro-peroxone oxidation-Fe(III) coagulation (E-peroxone-Fe(III)) sequential conditioning approach was developed to improve WAS dewaterability. At E-peroxone oxidation stage, hydrogen peroxide was generated through 2-electron path on a carbon polytetrafluoroethylene cathode, and reacted with the sparged O to produce hydroxyl radicals. At the subsequent coagulation stage, Fe(III) was dosed to coagulate the small WAS fragments and release water from WAS. Along E-peroxone-Fe(III) subsequent conditioning process, the physicochemical properties of WAS, main components, functional groups and evolution of protein secondary structure, and typical amino acids in EPS, as well as the type and semi-quantitative of elements in WAS, were investigated. The results indicated that under the optimal conditions, the reductions of specific resistance to filterability (SRF) and capillary suction time (CST) for WAS equalled 78.18% and 71.06%, respectively, and its bound water content decreased from 8.87 g/g TSS to 7.67 g/g TSS. After E-peroxone oxidation, part of protein and polysaccharide migrated outside from TB-EPS to slime, the ratio of α-helix/(β-sheet + random coil) declined, even some of organic-N disintegrated to inorganic-N. At Fe(III) coagulation stage, re-coagulation of the dispersed WAS fragments and easy extraction from inner EPS for protein and polysaccharide occurred. Furthermore, the protein secondary structure of β-sheet increased by 13.48%, the contents of hydrophobic and hydrophilic amino acids also increased. In addition, a strong negative correlation between the hydrophobic amino acid content of Met in slime and CST or SRF (R = -0.999, p < 0.05 or R = -0.948, p < 0.05) occurred, while a strong positive correlation between the hydrophilic amino acid content of Cys in TB-EPS and CST or SRF (R = 0.992, p < 0.05 or R = 0.921, p < 0.05) occurred, which could be related to the WAS dewaterability.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155272DOI Listing
April 2022

Hybrid Hydrogel Composed of Hyaluronic Acid, Gelatin, and Extracellular Cartilage Matrix for Perforated TM Repair.

Front Bioeng Biotechnol 2021 24;9:811652. Epub 2021 Dec 24.

ENT Department, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

A novel series of composite hydrogels, built from the three components 1), hyaluronic acid methacryloyl (HAMA); 2), gelatin methacryloyl (GelMA), and 3), extracellular cartilage matrix (ECM), was prepared and studied regarding the possible utility in the surgical repair of damaged (perforated) tympanic membrane (TM). Noteworthy is component 3), which was harvested from the ribs of α-1,3-galactosidyltransferase-knockout (α-1,3 GalT-KO) pigs. The absence of α-1,3-galactosyl glycoprotein is hypothesized to prevent rejection due to foreign-body immunogenicity. The composite hydrogels were characterized by various aspects, using a variety of physicochemical techniques: aqueous swelling, structural degradation, behavior under compression, and morphology, e.g., biocompatibility was assessed by the CCK-8 and live-dead assays and through cytoskeleton staining/microscopy. Alcian blue staining and real-time PCR (RT-PCR) were performed to examine the chondrogenic induction potential of the hydrogels. Moreover, a rat TM defect model was used to evaluate the performance of the hydrogels in this particular application. Taken together, the results from this study are surprising and promising. Much further development work will be required to make the material ready for surgical use.
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http://dx.doi.org/10.3389/fbioe.2021.811652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741272PMC
December 2021

PTHG2 Reduces Bone Loss in Ovariectomized Mice by Directing Bone Marrow Mesenchymal Stem Cell Fate.

Stem Cells Int 2021 19;2021:8546739. Epub 2021 Nov 19.

Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.

Teriparatide, also known as 1-34 parathyroid hormone (PTH (1-34)), is commonly used for the treatment of osteoporosis in postmenopausal women. But its therapeutic application is restricted by poor metabolic stability, low bioavailability, and rapid clearance. Herein, PTHG2, a glycosylated teriparatide derivative, is designed and synthesized to improve PTH stability and exert more potent antiosteoporosis effect. Surface plasmon resonance (SPR) analysis shows that PTHG2 combines to PTH 1 receptor. Additional acetylglucosamine covalent bonding in the first serine at the N terminal of PTH (1-34) improves stability and increases protein hydrolysis resistance. Intermittent administration of PTHG2 preserves bone quality in ovariectomy- (OVX-) induced osteoporosis mice model, along with increased osteoblastic differentiation and bone formation, and reduced marrow adipogenesis. In vitro, PTHG2 inhibits adipogenic differentiation and promotes osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs). For molecular mechanism, PTHG2 directs BMSCs fate through stimulating the cAMP-PKA signaling pathway. Blocking PKA abrogates the pro-osteogenic effect of PTHG2. In conclusion, our study reveals that PTHG2 can accelerate osteogenic differentiation of BMSCs and inhibit adipogenic differentiation of BMSCs and show a better protective effect than PTH (1-34) in the treatment of osteoporosis.
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http://dx.doi.org/10.1155/2021/8546739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8720025PMC
November 2021

Strategies for Engineering Exosomes and Their Applications in Drug Delivery.

J Biomed Nanotechnol 2021 Dec;17(12):2271-2297

School of Basic Medicine, Henan University of Science & Technology, Luoyang, 471023, China.

Exosomes are representative of a promising vehicle for delivery of biomolecules. Despite their discovery nearly 40 years, knowledge of exosomes and extracellular vesicles (EVs) and the role they play in etiology of disease and normal cellular physiology remains in its infancy. EVs are produced in almost all cells, containing nucleic acids, lipids, and proteins delivered from donor cells to recipient cells. Consequently, they act as mediators of intercellular communication and molecular transfer. Recent studies have shown that, exosomes are associated with numerous physiological and pathological processes as a small subset of EVs, and they play a significant role in disease progression and treatment. In this review, we discuss several key questions: what are exosomes, why do they matter, and how do we repurpose them in their strategies and applications in drug delivery systems. In addition, opportunities and challenges of exosome-based theranostics are also described and directions for future research are presented.
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http://dx.doi.org/10.1166/jbn.2021.3196DOI Listing
December 2021

Phosphate removal by a La(OH) loaded magnetic MAPTAC-based cationic hydrogel: Enhanced surface charge density and Donnan membrane effect.

J Environ Sci (China) 2022 Mar 14;113:26-39. Epub 2021 Jun 14.

College of Environmental Science and Engineering, Beijing Key Lab for Source Control Technology of Water Pollution, Beijing Forestry University, Beijing 100083, China.

Cationic hydrogels have received great attention to control eutrophication and recycle phosphate. In this study, a type of La(OH) loaded magnetic MAPTAC-based cationic hydrogel (La(OH)@MMCH) was developed as a potential adsorbent for enhanced phosphate removal from aqueous environment. La(OH)@MMCH exhibited high adsorption capacity of 105.72±5.99 mg P/g, and reached equilibrium within 2 hr. La(OH)@MMCH could perform effectively in a wide pH range from 3.0 to 9.0 and in the presence of coexisting ions (including SO, Cl, NO, HCO, SiO and HA). The adsorption-desorption experiment indicated that La(OH)@MMCH could be easily regenerated by using NaOH-NaCl as the desorption agent, and 73.3% adsorption capacity remained after five cycles. Moreover, La(OH)@MMCH was employed to treat surface water with phosphate concentration of 1.90  mg/L and showed great removal efficiency of 95.21%. Actually, MMCH showed high surface charge density of 34.38-59.38 meq/kg in the pH range from 3.0 to 11.0 and great swelling ratio of 3014.57% within 24 h, indicating that MMCH could produce the enhanced Donnan membrane effect to pre-permeate phosphate. Furthermore, the bifunctional structure of La(OH)@MMCH enabled it to capture phosphate through electrostatic attraction and ligand exchange. All the results prove that La(OH)@MMCH is a promising adsorbent for eutrophication control and phosphate recovery.
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http://dx.doi.org/10.1016/j.jes.2021.05.041DOI Listing
March 2022

Identification and Validation of CYBB, CD86, and C3AR1 as the Key Genes Related to Macrophage Infiltration of Gastric Cancer.

Front Mol Biosci 2021 7;8:756085. Epub 2021 Dec 7.

Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Gastric cancer (GC) is rampant around the world. Most of the GC cases are detected in advanced stages with poor prognosis. The identification of marker genes for early diagnosis is of great significance. Studying the tumor environment is helpful to acknowledge the process of tumorigenesis, development, and metastasis. Twenty-two kinds of immune cells were calculated by CIBERSORT from Gene Expression Omnibus (GEO) database. Subsequently, higher infiltration of macrophages M0 was discovered in GC compared with normal tissues. WGCNA was utilized to construct the network and then identify key modules and genes related to macrophages in TCGA. Finally, 18 hub genes were verified. In the PPI bar chart, the top 3 genes were chosen as hub genes involved in most pathways. On the TIMER and THPA websites, it is verified that the expression levels of CYBB, CD86, and C3AR1 genes in tumor tissues were higher than those in normal tissues. These genes may work as biomarkers or targets for accurate diagnosis and treatment of GC in the future. Our findings may be a new strategy for the treatment of GC.
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http://dx.doi.org/10.3389/fmolb.2021.756085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688826PMC
December 2021

Deciphering a TB-related DNA methylation biomarker and constructing a TB diagnostic classifier.

Mol Ther Nucleic Acids 2022 Mar 19;27:37-49. Epub 2021 Nov 19.

Department of Laboratory Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, China.

We systemically identified tuberculosis (TB)-related DNA methylation biomarkers and further constructed classifiers for TB diagnosis. TB-related DNA methylation datasets were searched through October 3, 2020. Limma and DMRcate were employed to identify differentially methylated probes (DMPs) and regions (DMRs). Machine learning methods were used to construct classifiers. The performance of the classifiers was evaluated in discovery datasets and a prospective independent cohort. Eighty-nine DMPs and 24 DMRs were identified based on 67 TB patients and 45 healthy controls from 4 datasets. Nine and three DMRs were selected by elastic net regression and logistic regression, respectively. Among the selected DMRs, two regions (chr3: 195635643-195636243 and chr6: 29691631-29692475) were differentially methylated in the independent cohort (p = 4.19 × 10 and 0.024, respectively). Among the ten classifiers, the 3-DMR logistic regression classifier exhibited the strongest performance. The sensitivity, specificity, and area under the curve were, respectively, 79.1%, 84.4%, and 0.888 in the discovery datasets and 64.5%, 90.3%, and 0.838 in the independent cohort. The differential diagnostic ability of this classifier was also assessed. Collectively, these data showed that DNA methylation might be a promising TB diagnostic biomarker. The 3-DMR logistic regression classifier is a potential clinical tool for TB diagnosis, and further validation is needed.
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http://dx.doi.org/10.1016/j.omtn.2021.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645423PMC
March 2022

Comparative Study on Different Modified Preparation Methods of Cellulose Nanocrystalline.

Polymers (Basel) 2021 Oct 5;13(19). Epub 2021 Oct 5.

College of Marine Science and Biological Engineering, Qingdao University of Science & Technology, Qingdao 266042, China.

Different modification process routes are used to improve the modified cellulose nanocrystalline (MCNC) with higher fatty acid by esterification reaction and graft polymerization to obtain certain hydrophobic properties. Two preparation methods, product structure and surface activity, are compared and explored. Experimental results show that the modified product is still at the nanometer level and basically retains the crystal structure of the raw cellulose nanocrystalline (CNC). The energy consumption of the two preparation methods is low; however, the esterification method with co-reactant requires short reaction time, and the degree of substitution of the product is high. The modified product prepared by grafting polymerization method has a high HLB value and amphiphilicity, which can effectively reduce the surface tension of water. Therefore, it can be used as a green and environmentally friendly surface-active substance.
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http://dx.doi.org/10.3390/polym13193417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512115PMC
October 2021

Analysis of the Effect of Intensive Care Based on Lean Nursing Intervention.

J Healthc Eng 2021 29;2021:7805124. Epub 2021 Sep 29.

First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

In order to improve the effect of intensive care, this paper proposes a lean nursing intervention method and evaluates the lean nursing intervention through a controlled experiment. According to the actual situation of intensive care, this paper starts with the research from several aspects of patients' ICU nursing time, patients' satisfaction, patients' pathological knowledge familiarity, patients' autonomous nursing, and enthusiasm of patients and their families. Moreover, this paper collects and displays experimental results through mathematical statistics, gives patients lean management concepts and methods based on routine care, and finds that it has good management effects. Thus, lean management concepts and methods can effectively improve the anxiety state of critically ill patients, improve the patient's knowledge of disease, and reduce adverse nursing events to improve patient nursing satisfaction, which is worthy of further promotion in the clinic.
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http://dx.doi.org/10.1155/2021/7805124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494574PMC
March 2022

The potential utility of hybrid photo-crosslinked hydrogels with non-immunogenic component for cartilage repair.

NPJ Regen Med 2021 Sep 10;6(1):54. Epub 2021 Sep 10.

Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People's Republic of China.

Finding a suitable biomaterial for scaffolding in cartilage tissue engineering has proved to be far from trivial. Nonetheless, it is clear that biomimetic approaches based on gelatin (Gel) and hyaluronic acid (HA) have particular promise. Herein, a set of formulations consisting of photo-polymerizable Gel; photo-polymerizable HA, and allogenic decellularized cartilage matrix (DCM), is synthesized and characterized. The novelty of this study lies particularly in the choice of DCM, which was harvested from an abnormal porcine with α-1,3-galactose gene knockout. The hybrid hydrogels were prepared and studied extensively, by spectroscopic methods, for their capacity to imbibe water, for their behavior under compression, and to characterize microstructure. Subsequently, the effects of the hydrogels on contacting cells (in vitro) were studied, i.e., cytotoxicity, morphology, and differentiation through monitoring the specific markers ACAN, Sox9, Coll2, and Col2α1, hypertrophy through monitoring the specific markers alkaline phosphatase (ALP) and Col 10A1. In vivo performance of the hydrogels was assessed in a rat knee cartilage defect model. The new data expand our understanding of hydrogels built of Gel and HA, since they reveal that a significant augmenting role can be played by DCM. The data strongly suggest that further experimentation in larger cartilage-defect animal models is worthwhile and has potential utility for tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1038/s41536-021-00166-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433347PMC
September 2021

Contactless Simultaneous Breathing and Heart Rate Detections in Physical Activity Using IR-UWB Radars.

Sensors (Basel) 2021 Aug 16;21(16). Epub 2021 Aug 16.

School of Artificial Intelligence, Beijing University of Posts and Telecommunications, Beijing 100876, China.

Vital signs monitoring in physical activity (PA) is of great significance in daily healthcare. Impulse Radio Ultra-WideBand (IR-UWB) radar provides a contactless vital signs detection approach with advantages in range resolution and penetration. Several researches have verified the feasibility of IR-UWB radar monitoring when the target keeps still. However, various body movements are induced by PA, which lead to severe signal distortion and interfere vital signs extraction. To address this challenge, a novel joint chest-abdomen cardiopulmonary signal estimation approach is proposed to detect breath and heartbeat simultaneously using IR-UWB radars. The movements of target chest and abdomen are detected by two IR-UWB radars, respectively. Considering the signal overlapping of vital signs and body motion artifacts, Empirical Wavelet Transform (EWT) is applied on received radar signals to remove clutter and mitigate movement interference. Moreover, improved EWT with frequency segmentation refinement is applied on each radar to decompose vital signals of target chest and abdomen to vital sign-related sub-signals, respectively. After that, based on the thoracoabdominal movement correlation, cross-correlation functions are calculated among chest and abdomen sub-signals to estimate breath and heartbeat. The experiments are conducted under three kinds of PA situations and two general body movements, the results of which indicate the effectiveness and superiority of the proposed approach.
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http://dx.doi.org/10.3390/s21165503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402280PMC
August 2021

Rapid and selective harvest of low-concentration phosphate by La(OH) loaded magnetic cationic hydrogel from aqueous solution: Surface migration of phosphate from -N(CH) to La(OH).

Sci Total Environ 2021 Dec 3;800:149418. Epub 2021 Aug 3.

College of Environmental Science and Engineering, Beijing Key Lab for Source Control Technology of Water Pollution, Beijing Forestry University, Beijing 100083, China.

Phosphate is an important factor for the occurrence of surface water eutrophication, and is also a non-renewable resource which faces a potential depletion crisis. In this study, La(OH) loaded magnetic cationic hydrogel composite MCH-La(OH)-EW was used to absorb low strength phosphate in simulated water and real water. The adsorption amount of MCH-La(OH)-EW was 39.14 ± 0.31 mg P/g and the equilibrium time was 120 min at the initial phosphate concentration of 2.0 mg P/L. The adsorption process was a spontaneous endothermic reaction. MCH-La(OH)-EW exhibited a high selectivity towards phosphate within pH of 4.0-10.0 or in the presence of co-existing ions (including Cl, SO, NO, HCO, SiO) and humic acid. After 10 cycles of adsorption-desorption, the adsorption amount of regenerated MCH-La(OH)-EW still remained at 63.4% of its maximum value. For the real water sample with phosphate concentration of 2.0 mg P/L, the phosphate removal efficiency could achieve 97.65-98.90% and the effluent turbidity was 2.10-4.27 NTU at the MCH-La(OH)-EW dosage of 0.04 g/L. The adsorption mechanism analysis showed that both quaternary amine groups (-N(CH)) and La(OH) of MCH-La(OH)-EW were involved in the process of phosphate adsorption. The electrostatic interaction between phosphate and -N(CH) rapidly occurred at the initial stage of adsorption process, then the electrostatic absorbed phosphate migrated to La(OH) on the surface of MCH-La(OH)-EW via ligand exchange to form inner-sphere complex. This phenomenon was conducive to phosphate adsorption kinetics by MCH-La(OH)-EW.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149418DOI Listing
December 2021

Electrical impedance spectroscopy as a potential tool to investigate the structure and size of aggregates during water and wastewater treatment.

J Colloid Interface Sci 2022 Jan 10;606(Pt 1):500-509. Epub 2021 Aug 10.

State Key Laboratory of Environmental Aquatic Chemistry, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.

Microscopic structure and size are important metrics for estimating aggregates environmental behaviors during water and wastewater treatment. However, in-situ determination of these characteristics is still a challenge. Here, we drew inspiration from a block disassembly process to propose an electrical impedance spectroscopy (EIS) method and constructed a generalized framework to associate macroscale electrical properties with microscopic structure and size-related characteristics of aggregates of different hierarchies. Extracted via EIS, the proposed models were verified to be capable of describing the self-similarity of aggregates and capturing the fractal and size information. Further, the proposed models exhibited a wide range of applications, which agrees well with the data gathered from various activated sludges, other colloids, and microgels in water and wastewater treatment. Finally, the EIS method was achieved online monitoring of fractal dimension and floc size during a sludge pre-oxidation conditioning process, which was elected as an example to illustrate the potential online applications of this EIS method in real water and wastewater environment. The obtained on-line data were used to indicate the potential suitable oxidation time during sludge pre-oxidation conditioning. These observations may inspire new methods of quantifying the aggregate structure and promote intelligent and dynamic decision-making during water and wastewater treatment.
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http://dx.doi.org/10.1016/j.jcis.2021.08.038DOI Listing
January 2022

Decreased neuregulin1β1 in first episode and drug-naïve patients with schizophrenia: Negative correlation with cognitive impairment.

Psychiatry Res 2021 10 5;304:114164. Epub 2021 Aug 5.

Medical College of Yangzhou University, Yangzhou 225003, PR China; Institute of Mental Health, Suzhou Psychiatric Hospital, The Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, 215137, PR China. Electronic address:

Background: Neuregulin1β1 (NRG1β1) is essential for neuronal migration during development and for the ongoing neural plasticity underlying cognitive function. This study investigated the relationship between cognitive impairment and serum NRG1β1 concentration in first-episode drug-naïve (FEDN) patients with schizophrenia.

Method: We measured serum NRG1β1 from 65 FEDN schizophrenia patients and 67 healthy matched controls. Cognitive function was evaluated using the Hopkins Vocabulary Learning Test-Revised (HVLT-R), Verbal Fluency Test (VFT), Trail Making Test (TMT), Digit Span Test (DST), and Stroop Test.

Results: Serum NRG1β1 concentration was significantly lower in the FEDN patient group than the control group (7.25±0.49 vs. 12.52±0.77 ng/mL; F=23.716, P<0.0001, Cohen's d=1.00). Further, serum NRG1β1 concentration in FEDN schizophrenia patients was negatively correlated with TMT-part A score (r=-0.408, P=0.001) and positively correlated with Stroop color subtest score (r=0.246, P=0.048). Multiple regression analysis also revealed weak correlations among FEDN patients between TMT-part A score and both serum NRG1β1 concentration (R=0.116, F=8.235, P=0.011) and duration of untreated psychosis (R=0.193, F=5.969, P=0.017).

Conclusion: This preliminary study suggests that serum NRG1β1 levels are reduced in FEDN patients with schizophrenia and that NRG1β1 may be involved in the cognitive function.
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http://dx.doi.org/10.1016/j.psychres.2021.114164DOI Listing
October 2021

Quantitative control of noise in mammalian gene expression by dynamic histone regulation.

Elife 2021 08 11;10. Epub 2021 Aug 11.

School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.

Fluctuation ('noise') in gene expression is critical for mammalian cellular processes. Numerous mechanisms contribute to its origins, yet the mechanisms behind large fluctuations that are induced by single transcriptional activators remain elusive. Here, we probed putative mechanisms by studying the dynamic regulation of transcriptional activator binding, histone regulator inhibitors, chromatin accessibility, and levels of mRNAs and proteins in single cells. Using a light-induced expression system, we showed that the transcriptional activator could form an interplay with dual functional co-activator/histone acetyltransferases CBP/p300. This interplay resulted in substantial heterogeneity in H3K27ac, chromatin accessibility, and transcription. Simultaneous attenuation of CBP/p300 and HDAC4/5 reduced heterogeneity in the expression of endogenous genes, suggesting that this mechanism is universal. We further found that the noise was reduced by pulse-wide modulation of transcriptional activator binding possibly as a result of alternating the epigenetic states. Our findings suggest a mechanism for the modulation of noise in synthetic and endogenous gene expression systems.
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http://dx.doi.org/10.7554/eLife.65654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357418PMC
August 2021

Gut commensal-derived butyrate reverses obesity-induced social deficits and anxiety-like behaviors via regulation of microglial homeostasis.

Eur J Pharmacol 2021 Oct 13;908:174338. Epub 2021 Jul 13.

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. Electronic address:

Neuropsychiatric dysfunction and reactive microglia are hallmarks of high-fat diet (HFD)-induced obesity, yet whether these reactive microglia contribute to HFD-induced obesity-related behavioral abnormalities and the underlying mechanisms remain unclear. Here, we show that HFD feeding causes social deficits and anxiety-like behaviors with impaired neuronal activity and alters the gut microbiota, particularly by depleting Lactobacillus reuteri (L. reuteri), in mice. The profiles of microbiome and metabolome in HFD-fed mice predict that specific microbial taxa and their metabolites regulate HFD-induced obesity-related behavioral abnormalities. Oral treatment with the L. reuteri reduces microglial activation and increases dendritic spine density, thus ameliorates social deficits and anxiety in HFD-fed mice. HFD-fed mice that are administered L. reuteri are also found to accumulate butyrate in their gut, sera and brain. Moreover, supplementation of butyrate improves behavioral abnormalities and modulates microglial homeostasis in HFD-fed mice. In addition, selectively removal of microglia through a pharmacologic approach can rescue dendritic spine loss and increase neuronal activity that profoundly alleviates social deficits and anxiety arising from HFD-induced obesity. Overall, this study reveals an unexpected pivotal role of gut commensal-derived butyrate in HFD-induced social deficits and anxiety-like behaviors through regulation of microglial homeostasis and identifies a potential probiotic treatment for HFD-induced obesity-related behavioral abnormalities.
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http://dx.doi.org/10.1016/j.ejphar.2021.174338DOI Listing
October 2021

Siderite/PMS conditioning-pressurized vertical electro-osmotic dewatering process for activated sludge volume reduction: Evolution of protein secondary structure and typical amino acid in EPS.

Water Res 2021 Aug 10;201:117352. Epub 2021 Jun 10.

College of Science, Beijing Forestry University, Beijing 100083, China.

In this study, the siderite/PMS conditioning-pressurized vertical electro-osmotic dewatering (PEOD) process was used to reduce the volume of activated sludge (AS). The changes in water content, cell, extracellular polymeric substances (EPS) distribution, protein secondary structures and typical amino acids in EPS fractions of AS along siderite/PMS conditioning-PEOD process were investigated. Results showed that the final water content (WC) of dewatered AS was 58.02% under the RSM optimized conditioning conditions of 0.05 g/g TSS siderite dosage, 0.23 g/g TSS PMS dosage, 600 kPa mechanical pressure and 20 V voltage. At conditioning and PEOD stages, the bound water content(BWC) of AS decreased by 25.23% and 91.76%, respectively. The HO• and SO· generated from siderite activating PMS could lead to the disruption of cells. The ratio of Ala-to Lys (Ala/Lys) showed strong negative correlations with BWC or WC in slime (R=-0.803, p<0.01; R=-0.771, p<0.01) and TB-EPS (R=-0.693, p<0.01; R=-0.705, p<0.01), and could be considered as an indicator of AS dewaterability. Compared with raw AS, conditioning led to the occurrence of the denser protein structure in TB-EPS and the looser one in slime. The contact number between Ala-and water decreased in TB-EPS and increased in slime, which indicated that the migration of water adhered in TB-EPS to outer layer. At the DG, MC and EC process, while the looser protein structure in TB-EPS and the denser one in slime occurred, as well as higher contact number between Ala-and water in TB-EPS than that in slime, which indicated that more water flowed outsider of slime than TB-EPS. This implied that the variations of the compactness of protein secondary structures and the contact number between Ala-and water in EPS layers correlated with AS dewaterability.
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http://dx.doi.org/10.1016/j.watres.2021.117352DOI Listing
August 2021

Oncolytic Adenovirus H101 Synergizes with Radiation in Cervical Cancer Cells.

Curr Cancer Drug Targets 2021 ;21(7):619-630

Department of Radiation Oncology, Institute of Molecular Radiobiology of Cancer, The First Affiliated Hospital of Xi'an Jiaotong University, Xian, China.

Background: A major challenge in cervical cancer radiotherapy is tailoring the radiation doses efficiently to eliminate malignant cells and reduce the side effects in normal tissues. Oncolytic adenovirus drug H101 was recently tested and approved as a topical adjuvant treatment for several malignancies.

Objective: This study aimed to evaluate the potential neoadjuvant radiotherapy benefits of H101 by testing the inhibitory function of H101 in combination with radiation in different cervical cancer cells.

Methods: Human cervical cancer cell lines C33a, SiHa, CaSki, and HeLa were treated with varying concentrations of H101 alone or in combination with radiation (2 Gy or 4 Gy). Cell viability and apoptosis were measured at the indicated time intervals. HPV16 E6 and cellular p53 mRNA expression alteration was measured by qRT-PCR. In situ RNA scope was used to determine HPV E6 status. P53 protein alterations were detected by Western blot.

Results: Cell viability and apoptosis assays revealed that the combination of a high dose of H101 (MOI=1000, 10000) with radiation yielded a synergistic anticancer effect in all tested cervical cancer cell lines (P<0.05), with the greatest effect achieved in HPV-negative C33a cells (P<0.05). Low-HPV16-viral-load SiHa cells were more sensitive to the combination therapy than high-HPV16- viral-load CaSki cells (P<0.05). The combined treatment reduced HPV16 E6 expression and increased cellular P53 levels compared to those observed with radiation alone in SiHa and CaSki cells (P<0.05).

Conclusion: Oncolytic adenovirus H101 effectively enhances the antitumor efficacy of radiation in cervical cancer cells and may serve as a novel combination therapy for cervical cancer.
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http://dx.doi.org/10.2174/1568009621666210308103541DOI Listing
November 2021

Hydrogel composite scaffolds with an attenuated immunogenicity component for bone tissue engineering applications.

J Mater Chem B 2021 03;9(8):2033-2041

Department of Orthopaedics, Joint Centre of Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, P. R. China.

Xenogeneic bones are potential templates for bone regeneration. In this study, decellularized porcine bone powder with attenuated immunogenicity was incorporated into a photocurable hydrogel, gelatin methacryloyl (GelMA), to obtain scaffolds with good mechanical properties for bone tissue engineering. The decellularized bone powder (DCB)-GelMA hybrid scaffolds had higher compressive strength and stiffness values when the DCB content was increased. In vitro evaluations revealed the biocompatibility of these scaffolds. The scaffolds could induce human bone marrow mesenchymal stem cells (hMSCs) to undergo osteogenic differentiation even in the absence of an induction medium. The efficiency of the scaffolds for bone regeneration applications was further evaluated using an in vivo cranial bone defect model in rats. Micro-CT images showed that the hybrid scaffolds with 20% DCB content had the best effect in promoting new bone regeneration. Thus, it was concluded that the DCB-GelMA hybrid scaffolds have high potential in bone tissue engineering applications.
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http://dx.doi.org/10.1039/d0tb02588gDOI Listing
March 2021

Artesunate Provides Neuroprotection against Cerebral Ischemia-Reperfusion Injury via the TLR-4/NF-κB Pathway in Rats.

Biol Pharm Bull 2021 Mar 25;44(3):350-356. Epub 2020 Dec 25.

Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi'an Jiaotong University.

Inflammation has an important role in ischemia-reperfusion (I/R) injury. Artesunate (ART) has anti-microbial and anti-inflammatory pharmacological activities, and it is used for various types of serious malaria, including cerebral malaria. ART maintains a high concentration in the brain but little is known about the neuroprotective effect of ART against brain I/R injury. We studied the neuroprotection of ART against brain I/R injury and its underlying mechanism. In this study, rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. After 24 h of reperfusion, neurological deficits, cerebrum water content, infarct volume, hematoxylin-eosin (H&E)-staining, myeloperoxidase (MPO) activity, and proinflammatory cytokine levels were measured. Administration of 20, 40, 80, and 160 mg/kg ART intraperitoneally (i.p.) 10 min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. An 80 mg/kg dosage was optimal. ART significantly reduced infarct volume, suppressed MPO activity and diminished the expressions of toll-like receptor (TLR)-4, MyD88, nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the area of the ischemic cortex. The neuroprotective action of ART against focal cerebral I/R injury might be due to the attenuation of inflammation through the TLR-4/NF-κB pathway.
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http://dx.doi.org/10.1248/bpb.b20-00604DOI Listing
March 2021

ATTfold: RNA Secondary Structure Prediction With Pseudoknots Based on Attention Mechanism.

Front Genet 2020 15;11:612086. Epub 2020 Dec 15.

Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun, China.

Accurate RNA secondary structure information is the cornerstone of gene function research and RNA tertiary structure prediction. However, most traditional RNA secondary structure prediction algorithms are based on the dynamic programming (DP) algorithm, according to the minimum free energy theory, with both hard and soft constraints. The accuracy is particularly dependent on the accuracy of soft constraints (from experimental data like chemical and enzyme detection). With the elongation of the RNA sequence, the time complexity of DP-based algorithms will increase geometrically, as a result, they are not good at coping with relatively long sequences. Furthermore, due to the complexity of the pseudoknots structure, the secondary structure prediction method, based on traditional algorithms, has great defects which cannot predict the secondary structure with pseudoknots well. Therefore, few algorithms have been available for pseudoknots prediction in the past. The ATTfold algorithm proposed in this article is a deep learning algorithm based on an attention mechanism. It analyzes the global information of the RNA sequence via the characteristics of the attention mechanism, focuses on the correlation between paired bases, and solves the problem of long sequence prediction. Moreover, this algorithm also extracts the effective multi-dimensional features from a great number of RNA sequences and structure information, by combining the exclusive hard constraints of RNA secondary structure. Hence, it accurately determines the pairing position of each base, and obtains the real and effective RNA secondary structure, including pseudoknots. Finally, after training the ATTfold algorithm model through tens of thousands of RNA sequences and their real secondary structures, this algorithm was compared with four classic RNA secondary structure prediction algorithms. The results show that our algorithm significantly outperforms others and more accurately showed the secondary structure of RNA. As the data in RNA sequence databases increase, our deep learning-based algorithm will have superior performance. In the future, this kind of algorithm will be more indispensable.
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http://dx.doi.org/10.3389/fgene.2020.612086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770172PMC
December 2020

Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses.

Sci Rep 2020 12 14;10(1):21920. Epub 2020 Dec 14.

MRC Centre for Reproductive Health, The University of Edinburgh, Edinburgh, EH16 4TJ, UK.

Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.
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http://dx.doi.org/10.1038/s41598-020-78976-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736841PMC
December 2020

Systematic evaluation, verification and comparison of tuberculosis-related non-coding RNA diagnostic panels.

J Cell Mol Med 2021 01 13;25(1):184-202. Epub 2020 Dec 13.

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

We systematically summarized tuberculosis (TB)-related non-coding RNA (ncRNA) diagnostic panels, validated and compared panel performance. We searched TB-related ncRNA panels in PubMed, OVID and Web of Science up to 28 February 2020, and available datasets in GEO, SRA and EBI ArrayExpress up to 1 March 2020. We rebuilt models and synthesized the results of each model in validation sets by bivariate mixed models. Specificity at 90% sensitivity, area under curve (AUC) and inconsistence index (I ) were calculated. NcRNA biofunctions were analysed. Nineteen models based on 18 ncRNA panels (miRNA, lncRNA, circRNA and snoRNA panels) and 18 datasets were included. Limited available datasets only allowed to evaluate miRNA panels further. Cui 2017 and Latorre 2015 exhibited specificity >70% at 90% sensitivity and AUC >80% in all validation sets. Cui 2017 showed higher specificity at 90% sensitivity (92%) and AUC (95%) and lower heterogeneity (I  = 0%) in ethological-confirmation validation sets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that most ncRNAs in panels involved in immune cell activation, oxidative stress, and Wnt and MAPK signalling pathway. Cui 2017 outperformed other models in both all available and aetiological-confirmed validation sets, meeting the criteria of target product profile of WHO. This work provided a basis for clinical choice of TB-related ncRNA diagnostic panels to a certain extent.
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http://dx.doi.org/10.1111/jcmm.15903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810967PMC
January 2021

Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors.

Brain Res Bull 2021 01 3;166:161-171. Epub 2020 Dec 3.

School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China. Electronic address:

Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.
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http://dx.doi.org/10.1016/j.brainresbull.2020.12.001DOI Listing
January 2021

Corrigendum to 'Effects of acid, acid-ZVI/PMS, Fe(II)/PMS and ZVI/PMS conditioning on the wastewater activated sludge (WAS) dewaterability and extracellular polymeric substances (EPS)' [J. Environ. Sci. 91 (2020) 73-84].

J Environ Sci (China) 2021 Jan 18;99:274. Epub 2020 Jul 18.

Key Laboratory of the Three Gorges Reservoir Regions Eco-Environment, State Ministry of Education, Chongqing University, Chongqing 400045, China.

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http://dx.doi.org/10.1016/j.jes.2020.07.010DOI Listing
January 2021

Frontline Science: COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes.

J Leukoc Biol 2021 01 11;109(1):13-22. Epub 2020 Oct 11.

Department of Cell Biology and Genetics, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS), is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility. In this study, we performed flow cytometric analysis of peripheral blood samples from 34 COVID-19 patients in early 2020 in an attempt to identify factors that could help predict the severity of disease and patient outcome. Although we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals, we did identify significant morphologic and functional differences, which are more pronounced in patients requiring prolonged hospitalization and intensive care unit (ICU) admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter (FSC), side scatter analysis by routine flow cytometry, with the presence of a distinct population of monocytes with high FSC (FSC-high). On more detailed analysis, these CD14 CD16 , FSC-high monocytes show features of mixed M1/M2 macrophage polarization with higher expression of CD80 and CD206 compared with the residual FSC-low monocytes and secretion of higher levels of IL-6, IL-10, and TNF-α, when compared with the normal controls. In conclusion, the detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation.
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http://dx.doi.org/10.1002/JLB.4HI0720-470RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675546PMC
January 2021

Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer.

J Clin Oncol 2020 11 8;38(31):3638-3651. Epub 2020 Sep 8.

Princess Margaret Cancer Centre, UHN, Toronto, Ontario, Canada.

Purpose: The purpose of this study was to evaluate the prognostic value of Immunoscore in patients with stage III colon cancer (CC) and to analyze its association with the effect of chemotherapy on time to recurrence (TTR).

Methods: An international study led by the Society for Immunotherapy of Cancer evaluated the predefined consensus Immunoscore in 763 patients with American Joint Committee on Cancer/Union for International Cancer Control TNM stage III CC from cohort 1 (Canada/United States) and cohort 2 (Europe/Asia). CD3+ and cytotoxic CD8+ T lymphocyte densities were quantified in the tumor and invasive margin by digital pathology. The primary end point was TTR. Secondary end points were overall survival (OS), disease-free survival (DFS), prognosis in microsatellite stable (MSS) status, and predictive value of efficacy of chemotherapy.

Results: Patients with a high Immunoscore presented with the lowest risk of recurrence, in both cohorts. Recurrence-free rates at 3 years were 56.9% (95% CI, 50.3% to 64.4%), 65.9% (95% CI, 60.8% to 71.4%), and 76.4% (95% CI, 69.3% to 84.3%) in patients with low, intermediate, and high immunoscores, respectively (hazard ratio [HR; high low], 0.48; 95% CI, 0.32 to 0.71; = .0003). Patients with high Immunoscore showed significant association with prolonged TTR, OS, and DFS (all < .001). In Cox multivariable analysis stratified by participating center, Immunoscore association with TTR was independent (HR [high low], 0.41; 95% CI, 0.25 to 0.67; .0003) of patient's sex, T stage, N stage, sidedness, and microsatellite instability status. Significant association of a high Immunoscore with prolonged TTR was also found among MSS patients (HR [high low], 0.36; 95% CI, 0.21 to 0.62; .0003). Immunoscore had the strongest contribution χ2 proportion for influencing survival (TTR and OS). Chemotherapy was significantly associated with survival in the high-Immunoscore group for both low-risk (HR [chemotherapy no chemotherapy], 0.42; 95% CI, 0.25 to 0.71; = .0011) and high-risk (HR [chemotherapy no chemotherapy], 0.5; 95% CI, 0.33 to 0.77; = .0015) patients, in contrast to the low-Immunoscore group ( > .12).

Conclusion: This study shows that a high Immunoscore significantly associated with prolonged survival in stage III CC. Our findings suggest that patients with a high Immunoscore will benefit the most from chemotherapy in terms of recurrence risk.
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http://dx.doi.org/10.1200/JCO.19.03205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605397PMC
November 2020

Lupeol inhibits osteosarcoma progression by up-regulation of HMGA2 via regulating miR-212-3p.

J Orthop Surg Res 2020 Sep 3;15(1):374. Epub 2020 Sep 3.

Department of Oncology, The First Hospital of Tianmen City of Hubei Province, No. 1, East Renmin Avenue, Tianmen, 431700, Hubei, China.

Background: Osteosarcoma (OS) is a common severe illness globally. Lupeol has been reported to participate in the pathophysiologic properties of various cancers, including OS. This study aimed to explore the effects of lupeol on proliferation, invasion, and apoptosis on OS cells and the underlying mechanism.

Methods: The cell viability of OS cells was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The expression levels of miR-212-3p and high-mobility group AT-hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS cells. The cell apoptosis and invasion were detected by flow cytometry and transwell invasion assays, respectively. The functional target of miR-212-3p was predicted by online software and confirmed by luciferase reporter assay. The protein level of HMGA2 was measured by western blot analysis.

Results: Lupeol suppressed cell viability and invasion, and promoted apoptosis by upregulating the expression of miR-212-3p in OS cells. Knockdown of miR-212-3p restored the anti-tumor effect of lupeol. Interestingly, miR-212-3p directly targeted HMGA2 and suppressed its expression. Moreover, HMGA2 reversed the inhibited impact on viability and invasion, and the promoted effect on apoptosis induced by upregulation of miR-212-3p. Also, lupeol administration exerts its anti-tumor effect by overexpression of miR-212-3p to suppress the expression of HMGA2 in OS cells.

Conclusion: Lupeol inhibited OS progression by modulating the miR-212-3p/HMGA2 axis in vitro.
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http://dx.doi.org/10.1186/s13018-020-01879-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469105PMC
September 2020

High-dose dexamethasone plus recombinant human thrombopoietin vs high-dose dexamethasone alone as frontline treatment for newly diagnosed adult primary immune thrombocytopenia: A prospective, multicenter, randomized trial.

Am J Hematol 2020 12 19;95(12):1542-1552. Epub 2020 Oct 19.

Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.
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http://dx.doi.org/10.1002/ajh.25989DOI Listing
December 2020

Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: a meta-analysis and experimental validation.

Arch Med Sci 2020 9;16(5):1092-1103. Epub 2019 Sep 9.

Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University Xi'an, China.

Introduction: We performed a meta-analysis and an experimental validation to investigate the association between tumor infiltrating lymphocytes (TILs) and the outcome of gastric cancer (GC) patients to provide prognostic indicators for clinical practice.

Material And Methods: The relative literature of TILs in tumor tissue from patients with gastric cancer was searched from PubMed, Embase, NIH databases, from April 2000 to 31 December 2016. Studies on the prognostic value of TILs as CD3+, CD4+, CD8+, GrB+, and FOXP3+ lymphocytes for GC were retrieved, and also the related references were traced as supplements. Independent screening documents, extracting information and evaluating quality were implemented independently by 2 evaluators according to the inclusion and exclusion criteria, which were then analyzed by meta-analysis using STATA version 12.0 software.

Results: The results indicated that high levels of intratumoral CD8+, CD3+ and CD4+ T cell infiltration were associated with better overall survival(OS) in gastric cancer patients, while high density of intratumoral FOXP3+ T cells was not closely associated with a worse outcome. Additionally, in our study, higher density of granzyme B+ (GrB+) T cell infiltration indicated an optimistic prognosis, and infiltration of a larger number of general TILs also suggested a favorable prognosis by log-rank test analysis.

Conclusions: This meta-analysis clarified that high levels of CD8+, CD3+, and CD4+ T cell infiltration in tumor tissue showed better OS in GC patients, whereas high density of FOXP3+ T cell infiltration may not be recognized as a negative prognostic factor. These results may provide some useful prognostic indicators for clinical application in gastric cancer.
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http://dx.doi.org/10.5114/aoms.2019.86101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444703PMC
September 2019
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