Publications by authors named "Tian Wang"

837 Publications

METTL3-mediated mA RNA methylation promotes the anti-tumour immunity of natural killer cells.

Nat Commun 2021 Sep 17;12(1):5522. Epub 2021 Sep 17.

Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China.

Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N-methyladenosine (mA) methylation) is unclear. Here we report decreased expression of the mA "writer" METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is mA modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity renders NK cells hyporesponsive to IL-15, which is associated with suppressed activation of the AKT and MAPK signaling pathway in METTL3-deficient NK cells. These findings show that mA methylation safeguards the homeostasis and tumor immunosurveillance function of NK cells.
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http://dx.doi.org/10.1038/s41467-021-25803-0DOI Listing
September 2021

Dual-functional Z-scheme CdSe/Se/BiOBr photocatalyst: Generation of hydrogen peroxide and efficient degradation of ciprofloxacin.

J Colloid Interface Sci 2021 Aug 27;606(Pt 2):1715-1728. Epub 2021 Aug 27.

School of Environment, Henan Normal University, Key Laboratory for Yellow River and Huai River Water Environmental and Pollution Control, Ministry of Education, Henan Key Laboratory for Environmental Pollution Control, Xinxiang, Henan 453007, PR China. Electronic address:

The major challenges of clean energy and environmental pollution have resulted in the development of photocatalysis technologies for energy conversion and the degradation of refractory pollutants. Herein, a novel CdSe/Se/BiOBr hydrangea-like photocatalyst was used to produce hydrogen peroxide (HO) and degrade ciprofloxacin (CIP). The Z-scheme heterojunction structure of the photocatalyst and the doping of selenium (Se) led to the efficient separation of electron-hole pairs and charge transfer. The optimized sample of 2 wt% CdSe/Se/BiOBr produced 142.15 mg·L rate of HO, which was much higher than that produced by pure BiOBr (89.4 mg·L) or CdSe/Se (10.9 mg·L). Additionally, almost 100 % of CIP was degraded within 30 min, with a first order rate constant of nearly 5.35 times that of pure BiOBr and 81.44 times that of pure CdSe/Se. The excellent removal efficiency of CIP from natural water matrices confirmed that the composites are promising for the removal of contaminants from natural waterways. Based on trapping experiments, electron spin resonance spectra (ESR) spectroscopy, and density functional theory (DFT) calculations, the photocatalytic mechanisms of HO and CIP degradation by the Z-scheme CdSe/Se/BiOBr composites were proposed. Overall, the dual-functional CdSe/Se/BiOBr composite could potentially be applied for photocatalytic production of HO and treatment of organic pollutants in water.
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http://dx.doi.org/10.1016/j.jcis.2021.08.152DOI Listing
August 2021

Influence of Screw-Hole Defect Size on the Biomechanical Properties of Feline Femora in an Ex Vivo Model.

Vet Comp Orthop Traumatol 2021 Sep 6. Epub 2021 Sep 6.

Sydney School of Veterinary Science, Faculty of Science, University of Sydney, Sydney, NSW, Australia.

Objective:  The study aims to evaluate the biomechanical properties of feline femora with craniocaudal screw-hole defects of increasing diameter, subjected to three-point bending and torsion to failure at two different loading rates.

Study Design:  Eighty femoral pairs were harvested from adult cat cadavers. For each bending and torsional experiment, there were five groups ( = 8 pairs) of increasing craniocaudal screw-hole defects (intact, 1.5 mm, 2.0 mm, 2.4 mm, 2.7mm). Mid-diaphyseal bicortical defects were created with an appropriate pilot drill-hole and tapped accordingly. Left and right femora of each pair were randomly assigned to a destructive loading protocol at low (10 mm/min; 0.5 degrees/s) or high rates (3,000 mm/min; 90 degrees/s) respectively. Stiffness, load/torque-to-failure, energy-to-failure and fracture morphology were recorded.

Results:  Defect size to bone diameter ratio was significantly different between defect groups within bending and torsional experiments respectively (intact [0%; 0%], 1.5 mm [17.8%; 17.1%], 2.0 mm [22.8%; 23.5%], 2.4 mm [27.8%; 27.6%], 2.7 mm [31.1%; 32.4%]) ( < 0.001). No significant differences in stiffness and load/torque-to-failure were noted with increasing deficit sizes in all loading conditions. Screw-hole (2.7 mm) defects up to 33% bone diameter had a maximum of 20% reduction in bending and torsional strength compared with intact bone at both loading rates. Stiffness and load/torque-to-failure in both bending and torsion were increased in bones subjected to higher loading rates ( < 0.001).

Conclusion:  Screw-hole defects up to 2.7 mm did not significantly reduce feline bone failure properties in this femoral study. These findings support current screw-size selection guidelines of up to 33% bone diameter as appropriate for use in feline fracture osteosynthesis.
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http://dx.doi.org/10.1055/s-0041-1735551DOI Listing
September 2021

Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice.

Cell Death Discov 2021 Sep 4;7(1):230. Epub 2021 Sep 4.

Mini-invasive Neurosurgery and Translational Medical Center, Xi'an Central Hospital, Xi'an Jiaotong University, No. 161, West 5th Road, Xincheng District, 710003, Xi'an, P.R. China.

Mesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer's disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aβ aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.
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http://dx.doi.org/10.1038/s41420-021-00620-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418600PMC
September 2021

Effects of Bacillus subtilis on jejunal integrity, redox status and microbial composition of intrauterine growth restriction suckling piglets.

J Anim Sci 2021 Sep 2. Epub 2021 Sep 2.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, China.

The present study used intrauterine growth restriction (IUGR) piglets as an animal model to determine the effect of Bacillus subtilis on intestinal integrity, antioxidant capacity, and microbiota in the jejunum of suckling piglets. In total, 8 normal birth weight (NBW) newborn piglets (1.62 ± 0.10 kg) and 16 newborn IUGR piglets (0.90 ± 0.08 kg) were selected and assigned to 3 groups. Piglets were orally gavaged with 10 mL sterile saline (NBW and IUGR groups), IUGR piglets were orally gavaged with 10 mL/d bacterial fluid (Bacillus subtilis diluted in sterile saline, gavage in the dose of 2 × 109 colony-forming units per kg of body weight) (IBS group) (n = 8). IUGR induced jejunal barrier dysfunction and redox status imbalance of piglets, and changed the abundances of bacteria in the jejunum. Treatment with Bacillus subtilis increased (P < 0.05) the ratio of villus height to crypt depth (VH/CD) in the jejunum, decreased (P < 0.05) the plasma diamine oxidase (DAO) activity, and enhanced (P < 0.05) the gene expressions of zonula occludens-1 (ZO-1), Occludin and Claudin-1 in the jejunum of IUGR piglets. Treatment with Bacillus subtilis decreased (P < 0.05) the concentration of protein carbonyl (PC), and increased (P < 0.05) the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in the jejunum of IUGR piglets. Treatment with Bacillus subtilis also increased (P < 0.05) gene expressions of superoxide dismutase 1 (SOD1), CAT, and nuclear factor erythroid 2-related factor (Nrf2), as well as the protein expressions of heme oxygenase-1 (HO-1), SOD1, and Nrf2 in the jejunum of IUGR piglets. Treatment with Bacillus subtilis also improved the abundances and the community structure of bacteria in the jejunum of IUGR piglets. These results suggested that IUGR damaged the jejunal barrier function and antioxidant capacity of suckling piglets, altered the abundances of bacteria in the jejunum. Treatment with Bacillus subtilis improved the intestinal integrity and antioxidant capacity, while also improved the abundances and structure of bacteria in the jejunum of suckling piglets.
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http://dx.doi.org/10.1093/jas/skab255DOI Listing
September 2021

Polycystic ovary syndrome in adolescents with obesity.

Rev Assoc Med Bras (1992) 2021 Mar;67(3):468-473

Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age with the prevalence from 5% to 15%, and the prevalence of PCOS in adolescents with obesity seems even higher. The weight status is significantly associated with the quality of life in adolescents with PCOS.

Objective: This review aims to summarize the latest findings of pathogenesis, diagnosis, comorbidity, and management in PCOS adolescents with obesity.

Methods: This is a narrative review of articles published in PubMed from June 2013 to June 2020 Data were searched using the key words of "polycystic ovary syndrome" AND "adolescent" AND "obesity."

Results: Pubertal obesity, particularly central obesity, could have a negative impact on the pathophysiology of PCOS. In adolescents with obesity, a review of medical history and a long-term follow-up for PCOS symptoms are essential to avoid misdiagnosis. There is a link between obesity and comorbidities of PCOS in adolescents. Holistic treatment and concern for related comorbidities should ideally begin as early as possible in obese adolescents once the diagnosis of PCOS is confirmed.

Conclusion: Adolescents with PCOS and obesity need more attention from physicians and researchers, and the effective interventions in the early stage are critical to improve their life quality.
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http://dx.doi.org/10.1590/1806-9282.20200890DOI Listing
March 2021

Rotigotine-loaded microspheres exerts the antinociceptive effect via central dopaminergic system.

Eur J Pharmacol 2021 Aug 28;910:174443. Epub 2021 Aug 28.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, PR China; State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Luye Pharma Group Ltd., Yantai, Shandong, 264003, PR China. Electronic address:

Rotigotine-loaded microspheres (RoMS), a sustained-release formulation with a continuous release of rotigotine for more than 7 days in vivo, have been conducted a clinical trial for the treatment of Parkinson's disease (PD). Previous work from our laboratory showed that RoMS exerted an antinociceptive effect in rat models of inflammatory pain. The purpose of this study was to investigate the mechanisms of action underlying the antinociceptive effect of RoMS. A rat model of inflammatory pain was prepared by an intraplantar injection of carrageenan. The hot plate test and the Randall-Selitto test were used to evaluate the effect of domperidone (selective D receptor antagonist), DD shRNA, and naloxone (nonselective opioid receptor antagonist) on RoMS-mediated antinociceptive efficacy. The expressions of D and D receptors in the striatum and periaqueductal gray were measured by Western blotting. Intracerebroventricular injection of domperidone abated the antinociceptive effect of RoMS. However, intraperitoneal injection of domperidone had no significant effect on the antinociceptive action of RoMS. Intracerebroventricular injection with DD shRNA significantly attenuated the expressions of D and D receptors in the striatum and the periaqueductal gray. D and D receptors silence significantly weakened RoMS-mediated antinociceptive effect. Intracerebroventricular injection of naloxone also alleviated the antinociceptive effect of RoMS. The results suggest that RoMS-mediated antinociceptive efficacy is associated with activating central dopamine D and D receptors. Opioid receptors play a role in the antinociceptive effect of RoMS.
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http://dx.doi.org/10.1016/j.ejphar.2021.174443DOI Listing
August 2021

End-to-End Deep One-Class Learning for Anomaly Detection in UAV Video Stream.

J Imaging 2021 May 19;7(5). Epub 2021 May 19.

CES Laboratory, ENIS National Engineering School, University of Sfax, Sfax 3038, Tunisia.

In recent years, the use of drones for surveillance tasks has been on the rise worldwide. However, in the context of anomaly detection, only normal events are available for the learning process. Therefore, the implementation of a generative learning method in an unsupervised mode to solve this problem becomes fundamental. In this context, we propose a new end-to-end architecture capable of generating optical flow images from original UAV images and extracting compact spatio-temporal characteristics for anomaly detection purposes. It is designed with a custom loss function as a sum of three terms, the reconstruction loss (Rl), the generation loss (Gl) and the compactness loss (Cl) to ensure an efficient classification of the "deep-one" class. In addition, we propose to minimize the effect of UAV motion in video processing by applying background subtraction on optical flow images. We tested our method on very complex datasets called the mini-drone video dataset, and obtained results surpassing existing techniques' performances with an AUC of 85.3.
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http://dx.doi.org/10.3390/jimaging7050090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321331PMC
May 2021

The Detrimental and Beneficial Functions of Macrophages After Cochlear Injury.

Front Cell Dev Biol 2021 11;9:631904. Epub 2021 Aug 11.

MOE Key Laboratory for Developmental Genes and Human Disease, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, School of Life Sciences and Technology, Southeast University, Nanjing, China.

Macrophages are the main intrinsic immune cells in the cochlea; they can be activated and play a complicated role after cochlear injury. Many studies have shown that the number of macrophages and their morphological characteristics within the major cochlear partitions undergo significant changes under various pathological conditions including acoustic trauma, ototoxic drug treatment, age-related cochlear degeneration, selective hair cell (HC) and spiral ganglion neuron (SGN) elimination, and surgery. However, the exact role of these macrophages after cochlear injury is still unclear. Regulating the migration and activity of macrophages may be a therapeutic approach to reduce the risk or magnitude of trauma-induced hearing loss, and this review highlights the role of macrophages on the peripheral auditory structures of the cochlea and elucidate the mechanisms of macrophage injury and the strategies to reduce the injury by regulating macrophage.
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http://dx.doi.org/10.3389/fcell.2021.631904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8385413PMC
August 2021

Chemical constituents from the rhizome of Ligusticum chuanxiong Hort. and their Nrf2 inducing activity.

Chem Biodivers 2021 Aug 26. Epub 2021 Aug 26.

Shandong University Cheeloo College of Medicine, pharmacy, West Wenhua Road 44, 250012, jinan, CHINA.

The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1-2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6, 10-13, 14) and four other compounds (17, 18, 20, 28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.
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http://dx.doi.org/10.1002/cbdv.202100302DOI Listing
August 2021

2-Hydroxypropyl-β-cyclodextrin Regulates the Epithelial to Mesenchymal Transition in Breast Cancer Cells by Modulating Cholesterol Homeostasis and Endoplasmic Reticulum Stress.

Metabolites 2021 Aug 23;11(8). Epub 2021 Aug 23.

Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Nanchang University, Nanchang 330006, China.

Cholesterol metabolism affects endoplasmic reticulum (ER) stress and modulates epithelial-mesenchymal transition (EMT). Our previous study demonstrated that 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) attenuated EMT by blocking the transforming growth factor (TGF)-β/Smad signaling pathway and activating ER stress in MDA-MB-231 cells. To further assess the detailed mechanisms between cholesterol metabolism, ER stress, and EMT, LXR-623 (an agonist of LXRα) and simvastatin were used to increase and decrease cholesterol efflux and synthesis, respectively. Here, we found that high HP-β-CD concentrations could locally increase cholesterol levels in the ER by decreasing LXRα expression and increasing Hydroxymethylglutaryl-Coenzyme A reductase (HMGCR) expression in MDA-MB-231 and BT-549 cells, which triggered ER stress and inhibited EMT. Meanwhile, tunicamycin-induced ER stress blocked the TGF-β/Smad signaling pathway. However, low HP-β-CD concentrations can decrease the level of membrane cholesterol, enhance the TGF-β receptor I levels in lipid rafts, which helped to activate TGF-β/Smad signaling pathway, inhibit ER stress and elevate EMT. Based on our findings, the use of high HP-β-CD concentration can lead to cholesterol accumulation in the ER, thereby inducing ER stress, which directly suppresses TGF-β pathway-induced EMT. However, HP-β-CD is proposed to deplete membrane cholesterol at low concentrations and concurrently inhibit ER stress and induce EMT by promoting the TGF-β signaling pathways.
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http://dx.doi.org/10.3390/metabo11080562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399758PMC
August 2021

Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4/NOD/NF-κB signaling pathway in weaned piglets with intrauterine growth retardation.

Anim Nutr 2021 Sep 3;7(3):667-678. Epub 2021 May 3.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin (DHA) could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation (IUGR). Twelve normal birth weight (NBW) piglets and 12 piglets with IUGR were fed a basal diet (NBW-CON and IUCR-CON groups), and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg (IUGR-DHA group) from 21 to 49 d of age. At 49 d of age, 8 piglets with similar body weight in each group were sacrificed. The jejunal and ileal samples were collected for further analysis. The results showed that IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated transmembrane toll-like receptor 4 (TLR4)/nucleotide-binding and oligomerization domain (NOD)/nuclear factor-κB (NF-κB) signaling pathway. Dihydroartemisinin inclusion ameliorated intestinal morphology, indicated by increased villus height, villus height-to-crypt depth ratio, villus surface area and decreased villus width of piglets with IUGR ( < 0.05). Compared with NBW piglets, IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression, and lower proliferation index and proliferating cell nuclear antigen expression in the intestine ( < 0.05). Dihydroartemisinin supplementation attenuated the intestinal inflammation of piglets with IUGR, indicated by increased concentrations of intestinal inflammatory cytokines and lipopolysaccharides ( < 0.05). In addition, DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-κB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR ( < 0.05). Piglets in the IUGR-DHA group showed lower protein expressions of TLR4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and higher protein expression of cytoplasmic pNF-κB in the intestine than those in the IUGR-CON group ( < 0.05). In conclusion, DHA supplementation could improve intestinal morphology, regulate enterocyte proliferation and apoptosis, and alleviate intestinal inflammation through TLR4/NOD/NF-κB signaling pathway in weaned piglets with IUGR.
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http://dx.doi.org/10.1016/j.aninu.2020.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361298PMC
September 2021

Betaine improves growth performance, liver health, antioxidant status, breast meat yield, and quality in broilers fed a mold-contaminated corn-based diet.

Anim Nutr 2021 Sep 29;7(3):661-666. Epub 2021 Apr 29.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, China.

Betaine has been demonstrated to improve growth performance and antioxidant status of animals under various stress conditions. However, there is no literature on the effects of betaine in animals exposed to mycotoxins, which are among the most prevalent contaminants in feed. Therefore, this study was conducted to evaluate the influence of dietary betaine on broilers fed a diet based on mold-contaminated corn (MCC). A total of 192 Ross 308 male broiler chicks at 1 d of age were randomly divided into 4 groups with 6 replicates and fed an MCC-based diet supplemented with 0, 250, 500, and 1,000 mg/kg betaine, respectively. Betaine increased average daily gain (linear,  = 0.030) and decreased feed conversion ratio (linear,  = 0.027) of broilers during d 1 - 21, and decreased feed conversion ratio during d 22 - 42 (linear,  = 0.012; quadratic,  < 0.001) and d 1 - 42 (linear,  = 0.003; quadratic,  = 0.004), whereas feed intake was not affected. Total cholesterol (linear,  = 0.024), alanine aminotransferase (quadratic,  < 0.001) and alkaline phosphatase (linear,  = 0.007; quadratic,  = 0.025) activities in serum were decreased by betaine. Betaine linearly increased breast muscle yield ( = 0.003) and pH ( = 0.008), and decreased drip loss ( = 0.022). Betaine increased (linear,  = 0.025; quadratic,  = 0.016) total superoxide dismutase activity in breast muscle and reduced malondialdehyde content in serum (linear,  = 0.006), liver (quadratic,  = 0.006) and breast muscle (linear,  = 0.003). Moreover, the zearalenone concentrations in breast muscle were linearly decreased by betaine ( = 0.006). It was concluded that betaine could improve growth performance, liver health, antioxidant status, and breast meat yield and quality, and reduce zearalenone residue in broilers fed the MCC-based diet, especially at 500 or 1,000 mg/kg.
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http://dx.doi.org/10.1016/j.aninu.2020.11.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358445PMC
September 2021

The High Expression of RRM2 Can Predict the Malignant Transformation of Endometriosis.

Adv Ther 2021 Aug 21. Epub 2021 Aug 21.

Department of Gynecological Oncology, Tianjin Central Hospital of Gynecology Obstetrics, No. 156 Nankai San Ma Road, Nankai District, Tianjin, China.

Introduction: A large number of epidemiological studies have revealed that women with endometriosis (EMS) have a higher risk of developing endometriosis-associated ovarian cancer (EAOC). At present, there are few studies on predicting the malignant transformation of ovarian endometriosis (OE). The purpose of this study is to identify and verify the molecules that may be able to predict the malignant transformation of OE.

Methods: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene ribonucleotide reductase M2 (RRM2) was identified. A total of 44 patients with EAOC and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization.

Results: Bioinformatics analysis showed that the expression of RRM2 was low in EMS and high in ovarian cancer. RRM2 was obviously positively expressed in eutopic endometrium (EU), ectopic endometrium (EC), and cancer tissues of EAOC patients. The IHC signal and mRNA levels of RRM2 were higher in the EC of EAOC patients compared with OE patients (P < 0.01). In addition, there was a correlation between the expression of RRM2 and Ki-67 in EC of EAOC patients (P < 0.01).

Conclusion: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. High expression of RRM2 promotes abnormal proliferation of histiocytes. RRM2 can be used as a potential marker of malignant transformation of OE.
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http://dx.doi.org/10.1007/s12325-021-01888-3DOI Listing
August 2021

The effect of a novel pillar surface morphology and material composition demonstrates uniform osseointegration.

J Mech Behav Biomed Mater 2021 Nov 14;123:104775. Epub 2021 Aug 14.

The University of New South Wales, Australia.

Long-term survival of orthopedic implants requires a strong and compliant interface between the implant and surrounding bone. This paper further explores the in-vivo response to a novel, macro-scale osseointegration surface morphology. In this study, we examine the effects of material composition on osseointegration in relation to the controlled surface geometry. The pillared surface is constructed of discontinuous surface geometry which creates an open space for unencumbered bone migration. In creating an open, macro-scale morphology we have demonstrated a bone migration and integration that is less dependent on the underlying implant material and is substantially driven thru surface geometry. In this in-vivo study an established ovine model was used to examine the effects of implant material composition on bone ingrowth and mechanical performance. Cortical and cancellous sites in the tibia and distal femur were examined at 6 and 12 weeks with μCT, histology, histomorphometry, and mechanical performance. Implant materials tested included PEEK (Evonik, VISTAKEEP®), PEEK HA (Invibio, PEEK-OPTIMA HA Enhanced), Titanium coated PEEK, Titanium (Ti-6Al-4V, Grade 5), and Ultra-High Molecular Weight Polyethylene (UHMWPE). Extensive bone ingrowth was noted in all implant materials at 12 weeks with maturation of the bone within the pillar structure from 6 weeks to 12 weeks. Histology demonstrated little fibrous deposition at the implant interface with no adverse cellular reactions. Histomorphometric review of cortical sites revealed greater than 60% bone ingrowth at 6 weeks increasing to nearly 80% by the 12 week timepoint. Cancellous sites yielded a mean of 30% ingrowth at 6 weeks increasing to 35% by 12 weeks. Pushout testing of cortical site samples demonstrated increase in pushout force between the 6 and 12 week timepoints. Increases were significant in all but the UHMWPE samples. Stiffness likewise increased in all samples between the two times. These results demonstrated the effectiveness of the pillar morphology with full integrating from the surrounding bony tissue regardless of the material.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104775DOI Listing
November 2021

Gpr125 Marks Distinct Cochlear Cell Types and Is Dispensable for Cochlear Development and Hearing.

Front Cell Dev Biol 2021 28;9:690955. Epub 2021 Jul 28.

Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, United States.

The G protein-coupled receptor (GPR) family critically regulates development and homeostasis of multiple organs. As a member of the GPR adhesion family, Gpr125 (Adgra3) modulates Wnt/PCP signaling and convergent extension in developing zebrafish, but whether it is essential for cochlear development in mammals is unknown. Here, we examined the knock-in mice and show that Gpr125 is dynamically expressed in the developing and mature cochleae. From embryonic day (E) 15.5 to postnatal day (P) 30, Gpr125-β-Gal is consistently expressed in the lesser epithelial ridge and its presumed progenies, the supporting cell subtypes Claudius cells and Hensen's cells. In contrast, Gpr125-β-Gal is expressed transiently in outer hair cells, epithelial cells in the lateral cochlear wall, interdental cells, and spiral ganglion neurons in the late embryonic and early postnatal cochlea. hybridization for mRNA confirmed expression and validated loss of expression in cochleae. Lastly, and cochleae displayed no detectable loss or disorganization of either sensory or non-sensory cells in the embryonic and postnatal ages and exhibited normal auditory physiology. Together, our study reveals that Gpr125 is dynamically expressed in multiple cell types in the developing and mature cochlea and is dispensable for cochlear development and hearing.
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http://dx.doi.org/10.3389/fcell.2021.690955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355630PMC
July 2021

Ginsenoside Rg3 exerts a neuroprotective effect in rotenone-induced Parkinson's disease mice via its anti-oxidative properties.

Eur J Pharmacol 2021 Oct 12;909:174413. Epub 2021 Aug 12.

Center for Mitochondria and Healthy Aging, College of Life Science, Yantai University, Yantai, 264005, PR China. Electronic address:

Ginsenoside Rg3, extracted from Panax ginseng C.A. Meyer, has been shown to possess neuroprotective properties. The present study aims to investigate the neuroprotective effects of ginsenoside Rg3 on rotenone-induced Parkinson's disease mice. Rotenone, a mitochondrial complex I inhibitor, leads to the augmentation of reactive oxygen species production in cells. Male C57/BL6 mice were intragastrically administered rotenone (30 mg/kg) and then treated with ginsenoside Rg3 (5, 10, or 20 mg/kg). Pole, rotarod, and open field tests were performed to evaluate motor function. Ginsenoside Rg3 decreased the climbing time in the pole test (p < 0.01), whereas it increased the latency in the rotarod test (p < 0.01) and the total distance (p < 0.01) and mean speed in the open field test (p < 0.01). Ginsenoside Rg3 treatment augmented the number of tyrosine hydroxylase-positive neurons in the substantia nigra (p < 0.01), mean density of tyrosine hydroxylase-positive nerve fibers (p < 0.01), and dopamine content (p < 0.01) in the striatum and reduced the reactive oxygen species level in the substantia nigra (p < 0.01). Glutathione cysteine ligase regulatory subunit and glutathione cysteine ligase modulatory subunit expression levels were elevated in the ginsenoside Rg3 groups. Ginsenoside Rg3 also improved motor function in rotenone-induced Parkinson's disease mice. The neuroprotective effects of ginsenoside Rg3 are at least partly associated with its anti-oxidative properties via regulation of glutathione cysteine ligase modulatory subunit and glutathione cysteine ligase regulatory subunit expression.
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http://dx.doi.org/10.1016/j.ejphar.2021.174413DOI Listing
October 2021

Temporal response of an injectable calcium phosphate material in a critical size defect.

J Orthop Surg Res 2021 Aug 13;16(1):496. Epub 2021 Aug 13.

Vertex Pharmaceuticals, 50 Northern Ave, Boston, MA, 02210, USA.

Background: Calcium phosphate-based bone graft substitutes are used to facilitate healing in bony defects caused by trauma or created during surgery. Here, we present an injectable calcium phosphate-based bone void filler that has been purposefully formulated with hyaluronic acid to offer a longer working time for ease of injection into bony defects that are difficult to access during minimally invasive surgery.

Methods: The bone substitute material deliverability and physical properties were characterized, and in vivo response was evaluated in a critical size distal femur defect in skeletally mature rabbits to 26 weeks. The interface with the host bone, implant degradation, and resorption were assessed with time.

Results: The calcium phosphate bone substitute material could be injected as a paste within the working time window of 7-18 min, and then self-cured at body temperature within 10 min. The material reached a maximum ultimate compressive strength of 8.20 ± 0.95 MPa, similar to trabecular bone. The material was found to be biocompatible and osteoconductive in vivo out to 26 weeks, with new bone formation and normal bone architecture observed at 6 weeks, as demonstrated by histological evaluation, microcomputed tomography, and radiographic evaluation.

Conclusions: These findings show that the material properties and performance are well suited for minimally invasive percutaneous delivery applications.
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http://dx.doi.org/10.1186/s13018-021-02651-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362253PMC
August 2021

[Effects of miR-125b-5p on the proliferation and apoptosis of human hemangioma endothelial cells HemES and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 May;37(3):247-253

Department of Tumor Hematology, Yan'an People's Hospital, Yanan 716000, China.

This article mainly studies the effects of miR-125b-5p on the proliferation and apoptosis of human hemangioma endothelial cells HemECs. RT-qPCR was used to detect the expressions of miR-125b-5p and MCL-1 mRNA in HemECs and collateral cells of human hemangioma endothelial cells. HemECs were selected and divided into control group, miR-NC group, miR-125b-5p mimic group, miR-125b-5p inhibitor group, pc-MCL-1 group, miR-125b-5p+ pc-MCL-1 group, 9 multiple holes in each group. . HemECs were transfected with 100 nmol · L of miR-NC, miR-125b-5p mimic, miR-125b-5p inhibitor, pc-MCL-1 plasmids separately or in combination. MTT method was used to detect the proliferation of HemECs. The apoptosis of HemECs was detected by flow cytometry. Dual luciferase report was used to to detect targeting relationship. The relative expression levels of Ki67, PCNA, cleaved caspase-3, Bax, Bcl-2, p-p70s6k/ p70s6k, p-AKT/AKT, and p-mTOR/mTOR proteins were detected by Western blot. By comparing the expression levels of miR-125b-5p in hemangioma tissues and cells, HemECs cell lines with obvious down-regulation effects were selected for follow-up experiments. Compared with the control group, the proliferation of HemECs and the expressions of Ki67 and PCNA in the miR-125b-5p mimic group were decreased significantly (<0.01). The apoptotic rate of HemECs and the expression levels of cleaved Caspase-3 and Bax were increased significantly, while the expression of Bcl-2 was decreased significantly (<0.01). The expression levels of p-AKT/AKT, p-mTOR/mTOR and p-p70S6K/p70S6K were down-regulated significantly <0.01); the proliferation of HemECs and the expressions of Ki67 and PCNA in the miR-125b-5p inhibitor group were increased significantly <0.01); the apoptosis rate and the expressions of cleaved Caspase-3 and Bax were decreased significantly, and the expression of Bcl-2 was increased (<0.05, <0.01). miR-125b-5p targeted down-regulation of MCL-1. Compared with miR-125b-5p mimic group, the proliferation of HemECs and the expressions of Ki67 and PCNA in miR-125b-5p+ pc-MCL-1 group were increased significantly (<0.01), the apoptosis rate of HemECs and the expressions of cleaved Caspase-3 and Bax were decreased significantly, while the expression of Bcl-2 was increased (<0.01). The expressions of p-AKT/AKT, p-mTOR/mTOR, and p-p70S6K/p70S6K was also increased significantly (<0.01). miR-125b-5p inhibits the proliferation of human hemangioma endothelial cells and induces apoptosis. The mechanism may be related to the targeted down-regulation of MCL-1 expression and inhibition of AKT/mTOR pathway activation.
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http://dx.doi.org/10.12047/j.cjap.6068.2021.021DOI Listing
May 2021

ORY-1001, a KDM1A inhibitor, inhibits proliferation, and promotes apoptosis of triple negative breast cancer cells by inactivating androgen receptor.

Drug Dev Res 2021 Aug 4. Epub 2021 Aug 4.

Department of Thyroid and Breast Surgery, The Second People's Hospital of Nantong, Nantong City, Jiangsu Province, China.

Breast cancer (BC), which is widely considered as the most common cancer in women around the world, evokes ~1.7 million new BC cases and 522,000 BC-related deaths each year. Triple negative breast cancer (TNBC) is clinically confirmed as one of the most aggressive subtypes of BC. ORY-1001, a clinically used lysine specific demethylase 1 (LSD1/KDM1A) inhibitor, was investigated herein to confirm its role in the progression of TNBC and reveal the potential mechanism. After treatment with ORY-1001 in MDA-MB-231 and BT549 cells, the cell proliferation and apoptosis were respectively measured by CCK-8 and TUNEL assays. The expression of proliferation- and apoptosis-associated proteins was tested by means of western blot analysis. Then, R1881, an androgen receptor (AR) agonist, was used to evaluate whether the effects of ORY-1001 on proliferation and apoptosis of TNBC cells was mediated by regulating AR. Results indicated that ORY-1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation- and apoptosis-related proteins expression. Furthermore, ORY-1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY-1001 intervention were partially abolished. In conclusion, this paper has presented the first evidence to suggest that ORY-1001 inhibits proliferation and promotes apoptosis of TNBC cells by suppressing AR expression, which may constitute the theoretical basis for the clinical use of ORY-1001 in the treatment of this disease.
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http://dx.doi.org/10.1002/ddr.21860DOI Listing
August 2021

Effects of a yeast-derived product on growth performance, antioxidant capacity, and immune function of broilers.

Poult Sci 2021 Sep 24;100(9):101343. Epub 2021 Jun 24.

College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu 210095, China. Electronic address:

Yeast culture plus enzymatically hydrolyzed yeast cell wall (YC-EHY) contains crude protein, mannan-oligosaccharide, β-glucan and yeast culture. This study was carried out to explore the effects of dietary YC-EHY at different levels on growth performance, antioxidant capacity, and immune function of broiler chickens. A total of 320 one-day-age male broiler chicks were allocated into 4 groups and were fed with a basal diet supplemented with 0 mg/kg (the control group), 50 mg/kg, 100 mg/kg, 150 mg/kg YC-EHY for 42 d. Dietary YC-EHY improved average daily gain and feed efficiency during the starter, grower, and overall periods as well as average body weight of broiler chickens on 42 d (linear and quadratic, P < 0.05). Broiler chickens fed with YC-EHY quadratically increased jejunal sucrase activity on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced maltase activity on 21 and 42 d (linear and quadratic, P < 0.05). Supplementing YC-EHY linearly and quadratically enhanced jejunal superoxide dismutase (SOD) activity on 21 and 42 d and glutathione peroxidase (GPX) activity on 42 d whereas decreased malonaldehyde (MDA) concentration on 42 d (linear and quadratic, P < 0.05). Consistently, the jejunal genes expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and SOD1 on 21 and 42 d, heme oxygenase-1 (HO-1) and GPX1 on 42 d were enhanced by YC-EHY supplementation (linear and quadratic, P < 0.05). The concentrations of jejunal immunoglobulin G (IgG) on 21 and 42 d and secreted immunoglobulin A (SIgA) on 42 d were linearly and quadratically elevated by supplementing YC-EHY (linear and quadratic, P < 0.05). Dietary YC-EHY quadratically increased jejunal IgG and IgM genes expression on 21 d (quadratic, P < 0.05), and linearly and quadratically enhanced the genes expression of IgG and IgM on 42 d (linear and quadratic, P < 0.05). Overall, this study indicated that supplementing YC-EHY could exert beneficial effects on growth performance, intestinal antioxidant capacity and immune function in broiler chickens.
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http://dx.doi.org/10.1016/j.psj.2021.101343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334739PMC
September 2021

GdClean: removal of Gadolinium contamination in mass cytometry data.

Bioinformatics 2021 Jul 28. Epub 2021 Jul 28.

Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory for Biomedical Engineering of the Ministry of Education, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, 310058, China.

Motivation: Mass cytometry (Cytometry by time-of-flight, CyTOF) is a single-cell technology that is able to quantify multiplex biomarker expressions and is commonly used in basic life science and translational research. However, the widely used Gadolinium (Gd) based contrast agents (GBCAs) in Magnetic Resonance Imaging (MRI) scanning in clinical practice can lead to signal contamination on the Gd channels in the CyTOF analysis. This Gd contamination greatly affects the characterization of the real signal from Gd-isotope-conjugated antibodies, severely impairing the CyTOF data quality and ruining downstream single-cell data interpretation.

Results: We first in-depth characterized the signals of Gd isotopes from a control sample that was not stained with Gd-labeled antibodies but was contaminated by Gd isotopes from GBCAs, and revealed the collinear intensity relationship across Gd contamination signals. We also found that the intensity ratios of detected Gd contamination signals to the reference Gd signal were highly correlated with the natural abundance ratios of corresponding Gd isotopes. We then developed a computational method named by GdClean to remove the Gd contamination signal at the single-cell level in the CyTOF data. We further demonstrated that the GdClean effectively cleaned up the Gd contamination signal while preserving the real Gd-labeled antibodies signal in Gd channels. All of these shed lights on the promising applications of the GdClean method in pre-processing CyTOF datasets for revealing the true single-cell information.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btab537DOI Listing
July 2021

A dynamic, convenient and accurate method for assessing the flood risk of people and vehicle.

Sci Total Environ 2021 Jul 18;797:149036. Epub 2021 Jul 18.

Beijing Capital Co Ltd, Beijing 100028, China.

With the increase of extreme rainstorm caused by climate change, and the development of urbanization and the improvement of people's living standard, there is an urgent need to draw a dynamic, convenient and accurate flood risk map for different disaster bearing bodies, so as to protect people's lives and properties, as well as improve people's risk awareness and facilitate people's lives. This study mainly researched a method of drawing a dynamic, convenient and accurate flood risk map for people and vehicle. In this study, the surface runoff is simulated by GPU (Graphics Processing Unit) Accelerated Surface Water Flow and Transport model (GAST model), meanwhile, the flood risk of people and vehicle is graded base on the incipient velocity formulas, the most unfavorable principle and grading method, finally, the method is applied in two application cases. The following results are obtained: (1) this method could assess the flood risk of people and vehicle dynamically, conveniently and accurately; (2) the flood risk of people is less than that of vehicle, for the same flood hazard, time and place; (3) the adverse effect of water depth on flood risk for vehicle is greater than that for people. This method of assessing the flood risk map of people and vehicle is of great significance, for flood risk management, land use plan and emergency management department to reduce flood disaster risk.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149036DOI Listing
July 2021

GTPase ROP6 negatively modulates phosphate deficiency through inhibition of PHT1;1 and PHT1;4 in Arabidopsis thaliana.

J Integr Plant Biol 2021 Jul 20. Epub 2021 Jul 20.

State Key Laboratory of Crop Stress Biology for Arid Areas and College of Life Sciences, Northwest A&F University, Yangling, 712100, China.

Phosphorus, an essential macroelement for plant growth and development, is a major limiting factor for sustainable crop yield. The Rho of plant (ROP) GTPase is involved in regulating multiple signal transduction processes in plants, but potentially including the phosphate deficiency signaling pathway remains unknown. Here, we identified that the rop6 mutant exhibited a dramatic tolerant phenotype under Pi-deficient conditions, with higher phosphate accumulation and lower anthocyanin content. In contrast, the rop6 mutant was more sensitive to arsenate (As(V)) toxicity, the analog of Pi. Immunoblot analysis displayed that the ROP6 protein was rapidly degraded through ubiquitin/26S proteasome pathway under Pi-deficient conditions. In addition, pull-down assay using GST-RIC1 demonstrated that the ROP6 activity was decreased obviously under Pi-deficient conditions. Strikingly, protein-protein interaction and two-voltage clamping assays demonstrated that ROP6 physically interacted with and inhibited the key phosphate uptake transporters PHT1;1 and PHT1;4 in vitro and in vivo. Moreover, genetic analysis showed that ROP6 functioned upstream of PHT1;1 and PHT1;4. Thus, we conclude that GTPase ROP6 modulates the uptake of phosphate by inhibiting the activities of PHT1;1 and PHT1;4 in Arabidopsis.
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http://dx.doi.org/10.1111/jipb.13153DOI Listing
July 2021

Mitochondrial DNA haplogroup M7 confers a reduced risk of colorectal cancer in a Han population from northern China.

J Cell Mol Med 2021 Aug 19;25(15):7538-7544. Epub 2021 Jul 19.

State Key Laboratory of Cancer Biology and Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an, China.

Mitochondria are central eukaryotic organelles in cellular metabolism and ATP production. Mitochondrial DNA (mtDNA) alterations have been implicated in the development of colorectal cancer (CRC). However, there are few reports on the association between mtDNA haplogroups or single nucleotide polymorphisms (SNPs) and the risk of CRC. The mtDNA of 286 Northern Han Chinese CRC patients were sequenced by next-generation sequencing technology. MtDNA data from 811 Han Chinese population controls were collected from two public data sets. Then, logistic regression analysis was used to determine the effect of mtDNA haplogroup or SNP on the risk of CRC. We found that patients with haplogroup M7 exhibited a reduced risk of CRC when compared to patients with other haplogroups (odds ratio [OR] = 0.532, 95% confidence interval [CI] = 0.285-0.937, p = 0.036) or haplogroup B (OR = 0.477, 95% CI = 0.238-0.916, p = 0.030). Furthermore, haplogroup M7 was still associated with the risk of CRC when the validation and combined control cohort were used. In addition, several haplogroup M7 specific SNPs, including 199T>C, 4071C>T and 6455C>T, were significantly associated with the risk of CRC. Our results indicate the risk potential of mtDNA haplogroup M7 and SNPs in CRC in Northern China.
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http://dx.doi.org/10.1111/jcmm.16789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335663PMC
August 2021

Ginsenoside Rg2 Ameliorates Brain Injury After Intracerebral Hemorrhage in a Rat Model of Preeclampsia.

Reprod Sci 2021 Jul 16. Epub 2021 Jul 16.

Department of Pharmacology, School of Pharmacy, Jilin University, Changchun, 130021, People's Republic of China.

The incidence of maternal hemorrhagic stroke is elevated in women with preeclampsia during pregnancy. Panax ginseng is a traditional medicinal herb with numerous applications, and ginsenosides are the key bioactive compounds in Panax ginseng. This study aims to evaluate the effects of ginsenoside Rg2 on pregnancy outcomes and brain injury after intracerebral hemorrhage (ICH) in a rat model of preeclampsia. Preeclampsia was induced in rats by N(ω)-nitro-L-arginine methyl ester. Then, an ICH model was prepared by intrastriatal injection of bacterial collagenase. Ginsenoside Rg2 markedly elevated the survival ratio of fetuses. The placental and body weights were increased in the ginsenoside Rg2 group. Compared with the preeclampsia group, the Garcia test score of ginsenoside Rg2-treated rats was significantly increased. Ginsenoside Rg2 treatment ameliorated the ICH-induced augmentation of Evans blue extravasation, inhibited the ICH-induced elevation of brain water content, and reduced the interleukin-1β and tumor necrosis factor-α levels in the hemorrhagic hemisphere after ICH in preeclampsia model rats. Furthermore, ginsenoside Rg2 treatment not only inhibited augmentation of TLR-4, MyD88, p-IκBα, and p-NF-κB expression but also abated the reduction of occludin and claudin-5 expression in the hemorrhagic hemisphere. The findings indicated that ginsenoside Rg2 improved pregnancy outcomes in a rat model of preeclampsia without decreasing the blood pressure and urine protein level. The findings also demonstrated that ginsenoside Rg2 ameliorated ICH-induced neurological disorder and blood-brain barrier dysfunction in an animal model of preeclampsia by regulating the TLR4/NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s43032-021-00692-2DOI Listing
July 2021

Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine.

BMC Genomics 2021 Jul 13;22(1):534. Epub 2021 Jul 13.

NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, 200025, Shanghai, China.

Background: Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND.

Results: A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70.

Conclusions: PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs.
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http://dx.doi.org/10.1186/s12864-021-07875-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276484PMC
July 2021

Isolation of a novel insect-specific flavivirus with immunomodulatory effects in vertebrate systems.

Virology 2021 Oct 8;562:50-62. Epub 2021 Jul 8.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.

We describe the isolation and characterization of a novel insect-specific flavivirus (ISFV), tentatively named Aripo virus (ARPV), that was isolated from Psorophora albipes mosquitoes collected in Trinidad. The ARPV genome was determined and phylogenetic analyses showed that it is a dual host associated ISFV, and clusters with the main mosquito-borne flaviviruses. ARPV antigen was significantly cross-reactive with Japanese encephalitis virus serogroup antisera, with significant cross-reactivity to Ilheus and West Nile virus (WNV). Results suggest that ARPV replication is limited to mosquitoes, as it did not replicate in the sandfly, culicoides or vertebrate cell lines tested. We also demonstrated that ARPV is endocytosed into vertebrate cells and is highly immunomodulatory, producing a robust innate immune response despite its inability to replicate in vertebrate systems. We show that prior infection or coinfection with ARPV limits WNV-induced disease in mouse models, likely the result of a robust ARPV-induced type I interferon response.
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http://dx.doi.org/10.1016/j.virol.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419152PMC
October 2021

Novel strategy for wide-range wind vector measurement using the hybrid CP/CTD heating mode and sequential measuring and correcting.

PLoS One 2021 8;16(7):e0254256. Epub 2021 Jul 8.

The Higher Educational Key Laboratory for Measuring & Control Technology and Instrumentations of Heilongjiang Province, School of Measurement-Control Technology & Communications Engineering, Harbin University of Science and Technology, Harbin, Heilongjiang, China.

To improve the performance of wind sensors in the high velocity range, this paper proposes a wind measurement strategy for thermal wind velocity sensors that combines the constant power and constant temperature difference driving modes of the heating element. Based on the airflow distribution characteristics from fluid dynamics, sequential measurement and correction is proposed as a method of measuring wind direction. In addition, a wind velocity and direction measurement instrument was developed using the above-mentioned approaches. The test results showed that the proposed instrument can obtain large dynamic wind velocity measurements from 0 to 60 m/s. The wind velocity measurement accuracy was ±0.5 m/s in the common velocity range of 0-20 m/s and ±1 m/s in the high velocity range of 20-60 m/s. The wind direction accuracy was ±3° throughout the 360° range. The proposed approaches and instrument are not only practical but also capable of meeting the requirements of wide-range and large dynamic wind vector measurement applications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254256PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266126PMC
July 2021

Association of gut microbiomes with lung and esophageal cancer: a pilot study.

World J Microbiol Biotechnol 2021 Jul 2;37(8):128. Epub 2021 Jul 2.

Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.

Gut microbiota, especially human pathogens, has been shown to be involved in the occurrence and development of cancer. Esophageal squamous cell carcinoma and lung cancer are two malignant cancers, and their relationship with gut microbiota is still unclear. Virulence factor database (VFDB) is an integrated and comprehensive online resource for curating information about human pathogens. Here, based on VFDB database, we analyzed the differences of bacteria at genus level in the gut of patients with esophageal squamous cell carcinoma, lung cancer, and healthy controls. We proposed the possible cancer-associated bacteria in gut and put forward their possible effects. Apart from this, principal coordinate analysis (PCoA) and analysis of similarities (ANSOIM) suggested that some bacteria in the gut can be used as potential biomarkers to screen esophageal squamous cell carcinoma and lung cancer, and their effectiveness was preliminary verified. The relative abundance of Klebsiella and Streptococcus can be used to distinguish patients with esophageal squamous cell carcinoma and lung cancer from healthy controls. The absolute abundance of Klebsiella can further distinguish patients with esophageal squamous cell carcinoma from patients with lung cancer. In particular, the relative abundance of Fusobacterium can directly distinguish between patients with esophageal squamous cell carcinoma and healthy controls. Additionally, the absolute abundance of Haemophilus can distinguish lung cancer from healthy controls. Our study provided a new way based on VFDB database to explore the relationship between gut microbiota and cancer, and initially proposed a feasible cancer screening method.
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http://dx.doi.org/10.1007/s11274-021-03086-3DOI Listing
July 2021
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