Publications by authors named "Feng Zhang"

3,727 Publications

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Yi-Qi-Jian-Pi Formula Suppresses RIPK1/RIPK3-Complex-Dependent Necroptosis of Hepatocytes Through ROS Signaling and Attenuates Liver Injury and .

Front Pharmacol 2021 23;12:658811. Epub 2021 Apr 23.

Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Acute-on-chronic liver failure (ACLF) is described as a characteristic of acute jaundice and coagulation dysfunction. Effective treatments for ACLF are unavailable and hence are urgently required. We aimed to define the effect of Yi-Qi-Jian-Pi Formula (YQJPF) on liver injury and further examine the molecular mechanisms. In this study, we established CCl-, LPS-, and d-galactosamine (D-Gal)-induced ACLF rat models and LPS- and D-Gal-induced hepatocyte injury models . We found that YQJPF significantly ameliorates liver injury and that is associated with the regulation of hepatocyte necroptosis. Specifically, YQJPF decreased expression of receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3) and pseudokinase mixed lineage kinase domain-like (MLKL) to inhibit the migration of RIPK1 and RIPK3 into necrosome. YQJPF also reduces the expression of inflammatory cytokines IL-6, IL-8, IL-1β, and TNF-α, which were regulated by RIPK3 mediates cell death. RIPK1 depletion was found to enhance the protective effect of YQJPF. Furthermore, we showed that YQJPF significantly downregulates the mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarization, with ROS scavenger, 4-hydroxy-TEMPO treatment recovering impaired RIPK1-mediated necroptosis and reducing the expression of IL-6, IL-8, IL-1β, and TNF-α. In summary, our study revealed the molecular mechanism of protective effect of YQJPF on hepatocyte necroptosis, targeting RIPK1/RIPK3-complex-dependent necroptosis ROS signaling. Overall, our results provided a novel perspective to indicate the positive role of YQJPF in ACLF.
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http://dx.doi.org/10.3389/fphar.2021.658811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102982PMC
April 2021

Genetic association scan of 32 osteoarthritis susceptibility genes identified TP63 associated with endemic osteoarthritis Kashin-Beck disease.

Bone 2021 May 5:115997. Epub 2021 May 5.

Key Laboratory of Trace Elements and Endemic Diseases, Collaborative Innovation Center of Endemic Disease and Health Promotion for Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, 710061, PR China. Electronic address:

Background: Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The clinical manifestations and radiographic features of KBD were similar to that of osteoarthritis (OA).

Methods: We first performed a genetic association scan of 32 OA susceptibility genes with KBD in 898 Han Chinese subjects. The MassARRAY genotyping system (Agena) was used for SNP genotyping. PLINK 1.9 was used for quality control and association testing. Using articular cartilage specimens from 7 adult KBD patients and 4 healthy control subjects, lentivirus-mediated RNA interference (RNAi), qRT-PCR, Western blot and immunohistochemistry were employed to validate the functional relevance of TP63 in KBD chondrocyte.

Results: SNP genotyping and association analysis identified TP63 (rs12107036, OR = 0.7133, P = 0.005) and OARD1 (rs11280, OR = 1.512, P = 0.004) were significantly associated with KBD. We found that TP63 was significantly up-regulated in KBD articular cartilage in both mRNA and protein level compared to healthy controls (P < 0.05). Lentivirus-mediated RNAi of TP63 suppression notably decreased the abundance of Caspase3 and SOX9 in chondrocytes. Most importantly, compared to the untransfected chondrocytes, the TP63 inhibition increased the production of ACAN. The mRNA expression of chondrocyte marker genes (COL2A1 and ACAN) was partly stable by TP63 knockdown relative to control group.

Conclusion: Our study identifies TP63 as a novel susceptibility gene for KBD, and demonstrates that inhibition of TP63 suppress chondrocyte apoptosis and partly facilitates chondrogenesis. The combination of SNP genotyping and genetic manipulation techniques provides a useful tool for understanding the biological mechanism and differential diagnosis studies of KBD and OA.
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http://dx.doi.org/10.1016/j.bone.2021.115997DOI Listing
May 2021

Carbonyl Reductase 1 Attenuates Ischemic Brain Injury by Reducing Oxidative Stress and Neuroinflammation.

Transl Stroke Res 2021 May 8. Epub 2021 May 8.

Department of Neurology, The Second Affiliated Hospital; Key Laboratory of Cerebral Microcirculation in Universities of Shandong; Brain Science Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, Shandong, China.

Oxidative stress and neuroinflammatory response after the ischemic injury are important pathophysiologic mechanisms that cause brain tissue loss and neurological deficit. This study aims to observe the expression and role of carbonyl reductase 1 (CBR1), an NADPH-dependent oxidoreductase with specificity for carbonyl compounds such as 4-hydroxynonenal (4-HNE), in the brain after ischemic injury and to investigate the influence of CBR1 on ischemia-induced neuroinflammation. CBR1 expresses in the neurons, astrocyte, and microglia in the normal brain. The expression of CBR1 decreased in the ischemic regions following cerebral ischemia, and also reduced in primary neurons after OGD (oxygen-glucose deprivation); however, the expression of CBR1 significantly increased in microglia in the ischemic penumbra. Furthermore, TAT-CBR1 fusion protein played neuroprotective effects in reducing the infarct volume and improving neurological outcomes after ischemic injury. Mechanistically, CBR1 decreased the levels of 4-HNE in the brain after stroke; it also modulated microglial polarization toward the M2 phenotype, which was well-known to confer neuroprotection after ischemic injury. Our results demonstrate that CBR1 provides neuroprotection against ischemic injury by reducing oxidative stress and neuroinflammation, making a promising agent for cerebral ischemia treatment.
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http://dx.doi.org/10.1007/s12975-021-00912-6DOI Listing
May 2021

Double kissing inflation outside the stent secures the patency of small side branch without rewiring.

BMC Cardiovasc Disord 2021 May 7;21(1):232. Epub 2021 May 7.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Xietu Road No. 1609, Shanghai, 200032, People's Republic of China.

Background: The jailed balloon technique is widely used for coronary bifurcation lesions, but a residual risk of SB occlusion remains, necessitating SB rewiring and further interventions, including balloon inflation or stenting, which may result in failure and SB loss. This study introduced a novel modified technique of small side branch (SB) protection, namely, double kissing inflation outside the stent (DKo) technique, for coronary bifurcations without the need for SB rewiring.

Methods: We performed the DKo technique in consecutive patients in our center from 1/2019 to 12/2019. The procedure was as follows. We inserted a guide wire into both branches followed by proper preparation. The SB balloon was simultaneously inflated with main vessel (MV) stenting. The SB balloon remained in situ until it was kissing inflated with postdilation of the bifurcation core, which is different from traditional strategies. The proximal optimization technique was performed with a short noncompliant balloon strictly not exceeding the bifurcation. Rates of SB loss and in-hospital outcomes were evaluated.

Results: The technique was successfully performed in all 117 enrolled patients without any rewiring or SB loss. The mean lesion lengths of the MV and SB were 38.3 ± 19.9 mm and 11.7 ± 7.1 mm, respectively. On average, 1.5 ± 0.6 stents were used per patient, while the mean pressure of the SB balloon was 7.4 ± 3.1 atm. DKo achieved excellent procedural success in the proximal and distal MVs: increased minimal lumen diameter (0.64 ± 0.58 mm to 3.05 ± 0.38 mm, p < 0.001; 0.57 ± 0.63 mm to 2.67 ± 0.35 mm, p < 0.001) and low residual stenosis (11.4 ± 3.4%; 7.2 ± 4.6%). DKo secured the patency of the SB without any rewiring and improved the SB stenosis with minimal lumen diameter (0.59 ± 0.48 mm to 1.20 ± 0.42 mm, p < 0.001) and stenosis (71.9 ± 19.4% to 42.2 ± 14.0%, p < 0.001). No MACE was noted in the hospital.

Conclusions: DKo for bifurcation lesions was shown to be acceptable with high procedural success and excellent SB protection.
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http://dx.doi.org/10.1186/s12872-021-02028-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106182PMC
May 2021

Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.

Cell Stem Cell 2021 Apr 28. Epub 2021 Apr 28.

Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Human brain organoids represent remarkable platforms for recapitulating features of human brain development and diseases. Existing organoid models do not resolve fine brain subregions, such as different nuclei in the hypothalamus. We report the generation of arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) to model the development of the human hypothalamic arcuate nucleus. Single-cell RNA sequencing of ARCOs revealed significant molecular heterogeneity underlying different arcuate cell types, and machine learning-aided analysis based on the neonatal human hypothalamus single-nucleus transcriptome further showed a human arcuate nucleus molecular signature. We also explored ARCOs generated from Prader-Willi syndrome (PWS) patient iPSCs. These organoids exhibit aberrant differentiation and transcriptomic dysregulation similar to postnatal hypothalamus of PWS patients, indicative of cellular differentiation deficits and exacerbated inflammatory responses. Thus, patient iPSC-derived ARCOs represent a promising experimental model for investigating nucleus-specific features and disease-relevant mechanisms during early human arcuate development.
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http://dx.doi.org/10.1016/j.stem.2021.04.006DOI Listing
April 2021

Multicomponent crystalline solid forms of aripiprazole produced via hot melt extrusion techniques: An exploratory study.

J Drug Deliv Sci Technol 2021 Jun 20;63. Epub 2021 Apr 20.

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

Multicomponent crystalline solid forms (salts, cocrystals and eutectics) are a promising means of enhancing the dissolution behavior of poorly soluble drugs. The present study demonstrates the development of multicomponent solid forms of aripiprazole (ARP) prepared with succinic acid (SA) and nicotinamide (NA) as coformers using the hot melt extrusion (HME) technique. The HME-processed samples were characterized and analyzed using differential scanning calorimetry (DSC), hot stage microscopy (HSM), Fourier transform infrared (FTIR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and HSM analyses revealed a characteristic single melting temperature in the solid forms, which differed from the melting points of the individual components. The discernible changes in the FTIR (amide C=O stretching) and PXRD results for ARP-SA confirm the formation of new crystalline solid forms. In the case of ARP-NA, these changes were less prominent, without the appearance or disappearance of peaks, suggesting no change in the crystal lattice. The SEM images demonstrated morphological differences between the HME-processed samples and the individual parent components. The in vitro dissolution and microenvironment pH measurement studies revealed that ARP-SA showed a higher dissolution rate, which could be due to the acidic microenvironment pH imparted by the coformer. The observations of the present study demonstrate the applicability of the HME technique for the development of ARP multicomponent solid forms.
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http://dx.doi.org/10.1016/j.jddst.2021.102529DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095679PMC
June 2021

Differentiation between Fresh and Frozen-Thawed Meat using Rapid Evaporative Ionization Mass Spectrometry: The Case of Beef Muscle.

J Agric Food Chem 2021 May 6. Epub 2021 May 6.

Institute of Food Safety, Chinese Academy of Inspection and Quarantine, Beijing 100176, China.

An intelligent surgical knife (iKnife) coupled with rapid evaporative ionization mass spectrometry (REIMS) was employed for the lipidomic profiling of fresh and frozen-thawed beef muscle. The data were obtained by REIMS and then processed using multivariate statistical analysis methods including principal component analysis-linear discriminant analysis (PCA-LDA) and orthogonal partial least-squares discriminant analysis (OPLS-DA). The discrimination of fresh and frozen-thawed meat has been achieved, and the real-time identification accuracy was 92-100%. Changes in the composition and content of fatty acids and phospholipids were statistically analyzed by OPLS-DA, and the ions of / 279.2317, / 681.4830, and / 697.4882 were selected as differential compounds/metabolites. The developed method was also successfully applied in the discrimination of fresh and frozen-thawed meat samples. These results showed that REIMS as a high-throughput, rapid, and real-time mass spectrometry detection technology can be used for the identification of fresh and frozen-thawed meat samples.
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http://dx.doi.org/10.1021/acs.jafc.0c07942DOI Listing
May 2021

Multicenter clinical evaluation of a piezoresistive-MEMS-sensor rapid-exchange pressure microcatheter system for fractional flow reserve measurement.

Catheter Cardiovasc Interv 2021 May 5. Epub 2021 May 5.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China.

Objectives: This multicenter, prospective clinical study investigates whether the microelectromechanical-systems-(MEMS)-sensor pressure microcatheter (MEMS-PMC) is comparable to a conventional pressure wire in fractional flow reserve (FFR) measurement.

Background: As a conventional tool for FFR measurement, pressure wires (PWs) still have some limitations such as suboptimal handling characteristics and unable to maintain the wire position during pullback assessment. Recently, a MEMS-PMC compatible with any 0.014″ guidewire is developed. Compared with the existing optical-sensor PMC, this MEMS-PMC has smaller profiles at both the lesion crossing and sensor packaging areas.

Methods: Two hundred and forty-two patients with visually 30-70% coronary stenosis were enrolled at four centers. FFR was measured first with the MEMS-PMC, and then with the PW. The primary endpoint was the Bland-Altman mean bias between the MEMS-PMC and PW FFR.

Results: From the 224-patient per-protocol data, quantitative coronary angiography showed 17.9% and 55.9% vessels had diameter < 2.5 mm and stenosis >50%, respectively. The two systems' mean bias was -0.01 with [-0.08, 0.06] 95% limits-of-agreement. Using PW FFR≤0.80 as cutoff, the MEMS-PMC per-vessel diagnostic accuracy was 93.4% [95% confidence interval: 89.4-96.3%]. The MEMS-PMC's success rate was similar to that of PW (97.5 vs. 96.3%, p = .43) with no serious adverse event, and its clinically-significant (>0.03) drift rate was 43% less (9.5 vs. 16.7%, p = .014).

Conclusions: Our study showed the MEMS-PMC is safe to use and has a minimal bias equal to the resolution of current FFR systems. Given the MEMS-PMC's high measurement accuracy and rapid-exchange nature, it may become an attractive new tool facilitating routine coronary physiology assessment.
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http://dx.doi.org/10.1002/ccd.29678DOI Listing
May 2021

G3BP1 Inhibition Alleviates Intracellular Nucleic Acid-Induced Autoimmune Responses.

J Immunol 2021 May 3;206(10):2453-2467. Epub 2021 May 3.

State Key Laboratory of Proteomics, National Center of Biomedical Analysis, Beijing, China

The detection of intracellular nucleic acids is a fundamental mechanism of host defense against infections. The dysregulated nucleic acid sensing, however, is a major cause for a number of autoimmune diseases. In this study, we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for both intracellular DNA- and RNA-induced immune responses. We found that in both human and mouse cells, the deletion of G3BP1 led to the dampened cGAS activation by DNA and the insufficient binding of RNA by RIG-I. We further found that resveratrol (RSVL), a natural compound found in grape skin, suppressed both intracellular DNA- and RNA-induced type I IFN production through inhibiting G3BP1. Importantly, using experimental mouse models for Aicardi-Goutières syndrome, an autoimmune disorder found in humans, we demonstrated that RSVL effectively alleviated intracellular nucleic acid-stimulated autoimmune responses. Thus, our study demonstrated a broader role of G3BP1 in sensing different kinds of intracellular nucleic acids and presented RSVL as a potential treatment for autoimmune conditions caused by dysregulated nucleic acid sensing.
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http://dx.doi.org/10.4049/jimmunol.2001111DOI Listing
May 2021

Curcumin Derivative Cur20 Attenuated Cerebral Ischemic Injury by Antioxidant Effect and HIF-1α/VEGF/TFEB-Activated Angiogenesis.

Front Pharmacol 2021 15;12:648107. Epub 2021 Apr 15.

Key Laboratory of Natural Medicine and Immune Engineering, School of Pharmacy, Henan University, Kaifeng, China.

In this paper, a curcumin derivative Cur20 was synthesized for better hydrolytic stability, which showed a higher angiogenic effect on zebrafish model than curcumin. In order to reveal the potential effects on neuroprotection, a mouse model of vascular dementia (VaD) induced by permanent right common carotid artery occlusion (rUCCAO) was established. After two weeks of curcumin administration, the cognitive function of mice was detected by Morris water maze and Y maze. The alteration on oxidative injuries and morphological damage were also analyzed by reactive oxygen species, superoxide dismutase, GSH, malondialdehyde tests, and Nissl stain on cortex/hippocampus. The angiogenesis and related signal factors were evaluated as well. The results showed that Cur20 significantly attenuated the cognitive dysfunction and histopathological changes of the VaD mice with enhanced antioxidant system and angiogenesis. In addition, primary rat brain microvessel endothelial cells (rBMECs) with oxygen glucose deprivation (OGD) were applied to further verify the possible mechanisms of Cur20-induced angiogenesis. The results demonstrated that the proliferation effect and the activation of pro-angiogenesis factors such as HIF-1α, VEGF, and TFEB might contribute to the protection of ischemic injury. Based on the above, our conclusion is that Cur20 can be considered as a promising therapeutic strategy for VaD.
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http://dx.doi.org/10.3389/fphar.2021.648107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082391PMC
April 2021

Reattempt Percutaneous Coronary Intervention of Chronic Total Occlusions after Prior Failures: A Single-Center Analysis of Strategies and Outcomes.

J Interv Cardiol 2021 20;2021:8835104. Epub 2021 Apr 20.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai, China.

Objective: The initial recanalization rate of coronary chronic total occlusions (CTOs) is >85% when performed by experienced operators, but only 10% of prior failed CTO patients receive reattempted recanalization. This retrospective study analyzed the success rate and strategies used in reattempt percutaneous coronary intervention (PCI) of CTOs after prior failures.

Methods: Overall, 206 patients with 212 CTOs were enrolled. All patients with prior recanalization failures received reattempt PCIs from January 2015 to March 2019 at Zhongshan Hospital, Fudan University. Data on clinical factors (age, sex, comorbidities, left ventricular ejection fraction, history of cigarette usage, and revascularization), angiographic characteristics of CTOs (target lesion, Japanese Chronic Total Occlusion (J-CTO) score, the morphology of CTO lesions, and collateral channel scale), strategies (procedural approach and use of devices), and major adverse events were obtained and analyzed.

Results: The mean age of enrolled patients was 60.96 ± 12.36 years, with a male predominance of 90.3%. Of the patients, 47.1% had a prior myocardial infarction and 70.4% underwent stent implantation previously, while the in-stent occlusion rate was 6.6%. CTOs were primarily localized in the left anterior descending artery (43.9%) and the right coronary artery (43.9%). 80.7% of lesions were classified as very difficult (J-CTO score ≥3), and the overall success rate was 81.1%. In multivariable regression analysis, J-CTO score, collateral channel scale, application of coronary multispiral computed tomography angiography, dual injection, intravascular ultrasound, active greeting technique, parallel wiring, and CTO morphology were predictors of recanalization success. There were no significant differences in rates of procedural complications between the final recanalization success and failure groups.

Conclusions: Recanalization of complex CTOs is associated with high success rate and low complication rates when performed by high-volume CTO operators and after multiple reattempts.
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http://dx.doi.org/10.1155/2021/8835104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079192PMC
April 2021

Polymer-Assisted Aripiprazole-Adipic Acid Cocrystals Produced by Hot Melt Extrusion Techniques.

Cryst Growth Des 2020 Jul 2;20(7):4335-4345. Epub 2020 Jun 2.

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.

Pharmaceutical cocrystals are a promising strategy to increase the solubility and dissolution rate of poorly soluble drugs. However, their manufacturing process requires a large quantity of solvents. The present study aimed to produce cocrystals by a solvent-free hot melt extrusion (HME) method to improve their solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a weakly basic drug and acidic coformer, respectively. The processability of a plain ARP-ADP physical mixture (PM) compared with a PM with 5% Soluplus® (SOL) was investigated. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. The effects of temperature and screw speed on the formation of cocrystals were studied, and cocrystals were characterized by differential scanning calorimetry (DSC), fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction (PXRD), scanning electron microscopy, and hot-stage microscopy. FTIR spectra revealed noncovalent interaction between ARP and ADP, which was confirmed by NMR spectra. Similarly, PXRD data exhibited characteristic peaks confirming the formation of new crystalline material. Further, the results indicated that cocrystals demonstrated higher dissolution rates and improved compressibility, as well as enhanced flow characteristics compared with pure ARP, suggesting its suitability in the development of solid dosage forms.
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http://dx.doi.org/10.1021/acs.cgd.0c00020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081332PMC
July 2020

A cellular and spatial map of the choroid plexus across brain ventricles and ages.

Cell 2021 Apr 27. Epub 2021 Apr 27.

Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA; Graduate Program in Biophysics, Harvard University, Cambridge, MA 02115, USA. Electronic address:

The choroid plexus (ChP) in each brain ventricle produces cerebrospinal fluid (CSF) and forms the blood-CSF barrier. Here, we construct a single-cell and spatial atlas of each ChP in the developing, adult, and aged mouse brain. We delineate diverse cell types, subtypes, cell states, and expression programs in epithelial and mesenchymal cells across ages and ventricles. In the developing ChP, we predict a common progenitor pool for epithelial and neuronal cells, validated by lineage tracing. Epithelial and fibroblast cells show regionalized expression by ventricle, starting at embryonic stages and persisting with age, with a dramatic transcriptional shift with maturation, and a smaller shift in each aged cell type. With aging, epithelial cells upregulate host-defense programs, and resident macrophages upregulate interleukin-1β (IL-1β) signaling genes. Our atlas reveals cellular diversity, architecture and signaling across ventricles during development, maturation, and aging of the ChP-brain barrier.
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http://dx.doi.org/10.1016/j.cell.2021.04.003DOI Listing
April 2021

Dietary Selenium Deficiency and Excess Accelerate Ubiquitin-Mediated Protein Degradation in the Muscle of Rainbow Trout (Oncorhynchus mykiss) via Akt/FoxO3a and NF-κB Signaling Pathways.

Biol Trace Elem Res 2021 Apr 29. Epub 2021 Apr 29.

Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, College of Fisheries, Huazhong Agricultural University, Shizishan street 1, Wuhan, 430070, People's Republic of China.

Selenium (Se) deficiency and excess can lead to protein degradation in fish. However, the underlying mechanisms remain unclear. Ubiquitin proteasome system (UPS) is the main pathway of muscle proteolysis. This study aimed to investigate the effect and molecular mechanism of dietary Se on ubiquitin-mediated muscle protein degradation in rainbow trout (Oncorhynchus mykiss). The fish were fed with the Se-deficient diet (0 mg/kg, DSe), Se-adequate diet (4 mg/kg, ASe), and Se-excessive diet (16 mg/kg, ESe), respectively. After a 10-week feeding trial, the growth performance, body composition, antioxidant enzyme activities, and UPS-related gene and protein expressions were detected. Results indicated that DSe and ESe diets significantly decreased the weight gain rate, specific growth rate, feed efficiency, and muscle crude protein content compared with ASe diet. The histological analysis showed that the mean diameter of muscle fibers was significantly decreased in DSe and ESe groups. And DSe and ESe diets significantly increased the contents of malondialdehyde and nitric oxide, but reduced the glutathione peroxidase activity. Additionally, the abundance of muscle ubiquitinated proteins and the expression levels of MuRF1 and Atrogin-1 were significantly increased in DSe and ESe groups. Compared to ASe diet, DSe and ESe diets significantly decreased the phosphorylation level of Akt Ser and the ratio of p-FoxO3a/FoxO3a, but significantly increased the phosphorylation level of IκBα and upregulated the expressions of TNF-α, IL-8, and NF-κB. Overall, this study indicated that dietary Se deficiency and excess accelerated the ubiquitin-mediated muscle protein degradation through regulating Akt/FoxO3a and NF-κB signaling pathways in rainbow trout.
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http://dx.doi.org/10.1007/s12011-021-02726-xDOI Listing
April 2021

An Improved Localization Method for the Transition between Autonomous Underwater Vehicle Homing and Docking.

Sensors (Basel) 2021 Apr 2;21(7). Epub 2021 Apr 2.

State Key Laboratory of Fluid Power and Mechatronic Systems, Zhejiang University, Hangzhou 310027, China.

Docking technology for autonomous underwater vehicles (AUVs) involves energy supply, data exchange and navigation, and plays an important role to extend the endurance of the AUVs. The navigation method used in the transition between AUV homing and docking influences subsequent tasks. How to improve the accuracy of the navigation in this stage is important. However, when using ultra-short baseline (USBL), outliers and slow localization updating rates could possibly cause localization errors. Optical navigation methods using underwater lights and cameras are easily affected by the ambient light. All these may reduce the rate of successful docking. In this paper, research on an improved localization method based on multi-sensor information fusion is carried out. To improve the localization performance of AUVs under motion mutation and light variation conditions, an improved underwater simultaneous localization and mapping algorithm based on ORB features (IU-ORBSALM) is proposed. A nonlinear optimization method is proposed to optimize the scale of monocular visual odometry in IU-ORBSLAM and the AUV pose. Localization tests and five docking missions are executed in a swimming pool. The localization results indicate that the localization accuracy and update rate are both improved. The 100% successful docking rate achieved verifies the feasibility of the proposed localization method.
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http://dx.doi.org/10.3390/s21072468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038153PMC
April 2021

SLCO4A1-AS1 regulates laryngeal squamous cell carcinoma cell phenotypes via the Wnt pathway.

Oral Dis 2021 Apr 29. Epub 2021 Apr 29.

Department of Otolaryngology, Yongchuan Hospital (T.C.M) of Chongqing Medical University, Chongqing, China.

Aim: Long non-coding RNAs were widely reported to regulate laryngeal squamous cell carcinoma (LSCC), a prevalent tumor in the head and neck. We aimed to investigate the role of solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1-AS1) in LSCC.

Materials & Methods: CCK-8 and colony formation assays were conducted to examine the viability and proliferation of LSCC cells. The apoptosis of LSCC cells was evaluated using flow cytometry and TUNEL assays. The distribution of SLCO4A1-AS1 in LSCC cells was detected by subcellular fractionation assay. The interaction between molecules was confirmed using luciferase reporter assay.

Results: SLCO4A1-AS1 was overexpressed in LSCC tissues and cells. Furthermore, silenced SLCO4A1-AS1 repressed the proliferation and facilitated apoptosis of LSCC cells. Mechanistical investigation revealed that SLCO4A1-AS1 was a competing endogenous RNA (ceRNA) to upregulate SETD7 by binding with miR-7855-p. Additionally, SLCO4A1-AS1 positively regulated the Wnt/β-catenin signaling pathway by upregulating SETD7. Rescue experiments demonstrated that SLCO4A1-AS1 promoted LSCC proliferation and inhibited LSCC apoptosis by upregulation of SETD7 and activation of the Wnt/β-catenin pathway.

Conclusion: SLCO4A1-AS1 promotes proliferation and inhibits apoptosis of LSCC cells by upregulation of SETD7 in a miR-7855-5p dependent way to activate the Wnt/β-catenin pathway.
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http://dx.doi.org/10.1111/odi.13893DOI Listing
April 2021

Members of highly entitative groups are implicitly expected to behave consistently based on their deep-level goals instead of their shallow-level movements.

J Exp Psychol Learn Mem Cogn 2021 Apr 29. Epub 2021 Apr 29.

Department of Psychology.

The current study investigated whether the deep properties or shallow features of behaviors are implicitly expected to be consistent across members of highly entitative groups, by exploiting the notion that goals-as deep properties-and movements-as shallow features-can be dissociated in object-directed behaviors. Participants were asked to view group members' goal-directed behaviors toward an object. Whether perceivers implicitly expected that a new member would perform the same movement to the previously visited location (i.e., exhibit shallow feature-based behavior) or a new movement to the previously visited object (i.e., exhibit deep property-based behavior) was recorded. Study 1 revealed that perceivers implicitly expected members of a highly entitative group to approach the previously visited object with a new movement (i.e., to have a consistent goal) rather than perform the same movement to the previously visited location (i.e., to express a consistent movement). Study 2 confirmed that the responses in Study 1 were explained by group members conforming to, rather than violating, internal expectations (i.e., of consistent movement). Importantly, the implicit expectation of shared behaviors across group members relies on the goal interpretation of actions instead of the associations between actions and outcomes (Study 3). Study 4 replicated the facilitation effect of Study 1 and revealed that the goal-based expectation of common behaviors among group members is based on the majority behavior instead of a single demonstration. Hence, individuals in highly entitative groups are implicitly expected to behave consistently based on the deep properties of behaviors instead of their shallow features. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/xlm0001009DOI Listing
April 2021

Identification and mapping of CpPM10.1, a major gene involved in powdery mildew (race 2 France of Podosphaera xanthii) resistance in zucchini (Cucurbita pepo L.).

Theor Appl Genet 2021 Apr 29. Epub 2021 Apr 29.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs, Northeast Agricultural University, Harbin, 150030, China.

Key Message: Powdery mildew resistance in zucchini is controlled by one major dominant locus, CpPM10.1. CpPM10.1 was fine mapped. The expression of candidate gene Cp4.1LG10g02780 in resistant individuals was significantly upregulated after inoculation with the powdery mildew. Powdery mildew (PM) is one of the most destructive fungal diseases, reducing the productivity of Cucurbita crops globally. PM influences the photosynthesis, growth and development of infected zucchini and seriously reduces fruit yield and quality. In the present study, the zucchini inbred line 'X10' had highly stable PM resistance, and the inbred line 'Jin234' was highly susceptible to PM in the seedling stage and adult stages. Genetic analysis revealed that PM resistance in 'X10' is controlled by one major dominant locus. Based on the strategy of QTL-seq combined with linkage analysis and developed molecular markers, the major locus was found to be located in a 382.9-kb candidate region on chromosome 10; therefore, the major locus was named CpPM10.1. Using 1,400 F individuals derived from a cross between 'X10' and 'JIN234' and F offspring of the recombinants, the CpPM10.1 locus was defined in a region of approximately 20.9 kb that contained 5 coding genes. Among them, Cp4.1LG10g02780 contained a conserved domain (RPW8), which controls resistance to a broad range of PM pathogens. Cp4.1LG10g02780 also had nonsynonymous SNPs between the resistant 'X10' and susceptible 'Jin234.' Furthermore, the expression of Cp4.1LG10g02780 was strongly positively involved in PM resistance in the key period of inoculation. Further allelic diversity analysis in zucchini germplasm resources indicated that PM resistance was associated with two SNPs in the Cp4.1LG10g02780 RPW8 domain. This study not only provides highly stable PM resistance gene resources for cucurbit crops but also lays the foundation for the functional analysis of PM resistance and resistance breeding in zucchini.
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http://dx.doi.org/10.1007/s00122-021-03840-zDOI Listing
April 2021

Genome-wide CRISPR screens reveal synthetic lethal interaction between CREBBP and EP300 in diffuse large B-cell lymphoma.

Cell Death Dis 2021 Apr 28;12(5):419. Epub 2021 Apr 28.

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoid malignancy and a highly heterogeneous disease. In this study, we performed whole-genome and transcriptome sequencing, and a genome-wide CRISPR-Cas9-knockout screen to study an activated B-cell-like DLBCL cell line (RC-K8). We identified a distinct pattern of genetic essentialities in RC-K8, including a dependency on CREBBP and MDM2. The dependency on CREBBP is associated with a balanced translocation involving EP300, which results in a truncated form of the protein that lacks the critical histone acetyltransferase (HAT) domain. The synthetic lethal interaction between CREBBP and EP300 genes, two frequently mutated epigenetic modulators in B-cell lymphoma, was further validated in the previously published CRISPR-Cas9 screens and inhibitor assays. Our study suggests that integration of the unbiased functional screen results with genomic and transcriptomic data can identify both common and unique druggable vulnerabilities in DLBCL and histone acetyltransferases inhibition could be a therapeutic option for CREBBP or EP300 mutated cases.
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http://dx.doi.org/10.1038/s41419-021-03695-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080727PMC
April 2021

Prognostic significance of preoperative systemic immune-inflammation index in combined hepatocellular-cholangiocarcinoma.

Cancer Biomark 2021 Apr 23. Epub 2021 Apr 23.

Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Inflammation-based prognostic scores have been increasingly used for prognosis prediction in malignant tumors. However, no existing study has comprehensively evaluated these scores in combined hepatocellular-cholangiocarcinoma (cHCC-CCA).

Objective: This study aimed to identify a robust inflammation-based prognostic predictor for cHCC-CCA.

Methods: We retrospectively analyzed 220 patients pathologically confirmed as Allen type C cHCC-CCA. The univariate and multivariate analyses were used to explore the associations between clinical variables and prognosis of cHCC-CCA. The propensity score-matching (PSM) was performed to reduce the effects of potential cofounders and selection bias. Finally, the predictive values of different inflammation-based indices were compared by using time-dependent receiver operating characteristic (ROC) curves.

Results: The systemic immune-inflammation index (SII) and aspartate aminotransferase to platelet ratio index (APRI) were identified as independent prognostic predictors in multivariate analysis. After PSM, the survival differences were still significant between SII-high group and SII-low group (P= 0.016 for RFS and P= 0.001 for OS). Further ROC analysis showed that the SII harbored the largest 1-, 3- and 5-year area under the curves (AUC) values as compared with other scores.

Conclusions: The SII may serve as a preferable predictor of both recurrence-free survival (RFS) and overall survival (OS) in patients with cHCC-CCA.
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http://dx.doi.org/10.3233/CBM-200643DOI Listing
April 2021

Enhanced light-driven hydrogen generation on carbon quantum dots with TiO nanoparticles.

Phys Chem Chem Phys 2021 May;23(17):10448-10455

School of Science, Dalian Maritime University, Dalian, Liaoning 116026, China.

Solar to hydrogen (H2) conversion systems based on carbon nanomaterials have shown great potentials in the clean energy field recently. However, for most systems, energy level alignments and light-induced redox processes are still unclear, which hinder artificial designing for higher efficiency of solar energy conversion and further applications. Here we report 77% enhancement in the light-driven H2 generation efficiency of N,S co-doped carbon quantum dot (N,S-CQD) aqueous system by adding TiO2 nanoparticles. Using steady-state and transient spectroscopy, four specific energy levels of CQDs are confirmed with the band gaps of 3.55 eV (X4), 2.99 eV (X3), 2.76 eV (X2) and 1.75 eV (X1), respectively. The X2 energy band is highly active for H+ reduction with a longer lifetime of 13.38 ns. Moreover, the observed low efficiency of intrinsic transition from X3 to X2 band of N,S-CQDs accounts for the poor performance of solar to H2 conversion for pure N,S-CQDs based on H2 generation and detailed time-resolved spectroscopic results. The mechanism of H2 generation enhancement can be explained by multiple electron transfer processes between N,S-CQDs and TiO2 NPs where TiO2 NPs act as electron intermediates that efficiently transfer electrons from the inert band (X3) to the active band (X2) for H2 generation. This study enriches the fundamental understanding of N,S-CQDs and provides a new pathway toward high-performance N,S-CQD-based solar to H2 conversion systems.
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http://dx.doi.org/10.1039/d1cp00417dDOI Listing
May 2021

Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice.

J Med Genet 2021 Apr 22. Epub 2021 Apr 22.

Obstetrics and Gynecology Hospital, NHC Key Laboratory of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), State Key Laboratory of Genetic Engineering at School of Life Sciences, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China

Background: Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. The aetiology of POI is genetically heterogeneous, with certain double-strand break (DSB) repair genes being implicated in POI. Although non-homologous end joining (NHEJ) is an efficient DSB repair pathway, the functional relationship between this pathway and POI remains unknown.

Methods And Results: We conducted whole-exome sequencing in a Chinese family and identified a rare heterozygous loss-of-function variant in non-homologous end joining factor 1 (): c.532C>T (p.R178*), which co-segregated with POI and irregular menstruation. The amount of NHEJ1 protein in the proband was half of the normal level, indicating a link between haploinsufficiency and POI. Furthermore, another rare heterozygous variant c.500A>G (p.Y167C) was identified in one of 100 sporadic POI cases. Both variants were predicted to be deleterious by multiple in silico tools. In vitro assays showed that knock-down of in human KGN ovarian cells impaired DNA repair capacity. We also generated a knock-in mouse model with a heterozygous variant equivalent to p.R178* in familial patients. Compared with wild-type mice, heterozygous -mutated female mice required a longer time to first birth, and displayed reduced numbers of primordial and growing follicles. Moreover, these mice exhibited higher sensitivity to DSB-inducing drugs. All these phenotypes are analogous to the progressive loss of ovarian function observed in POI.

Conclusions: Our observations in both humans and mice suggest that haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI.
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http://dx.doi.org/10.1136/jmedgenet-2020-107398DOI Listing
April 2021

Intracellular Hybrid Biosystem in a Protozoan to Trigger Visible-Light-Driven Photocatalysis.

ACS Appl Mater Interfaces 2021 May 22;13(17):19846-19854. Epub 2021 Apr 22.

CAS Key Laboratory of Urban Pollutant Conversion, Department of Environmental Science and Engineering, University of Science and Technology of China, Hefei 230026, China.

Incorporating artificial photosensitizers with microorganisms has recently been recognized as an effective way to convert light energy into chemical energy. However, the incorporated biosystem is usually constructed in an extracellular manner and is vulnerable to the external environment. Here, we develop an intracellular hybrid biosystem in a higher organism protozoa , in which the synthesized CdS nanoparticles trigger photoreduction of nitrobenzene into aniline under visible-light irradiation. Integrating a photosensitizer CdS into enables the photosensitizer CdS, inherent nitroreductase, and the cytoplasmic reductive substance in to synergistically engage in the photocatalysis process, generating a greatly enhanced aniline yield with a 40-fold increment. Moreover, building an intracellular hybrid biosystem in mutant could even grant it new capability of reducing nitrobenzene into aniline under visible-light irradiation. Such an intracellular hybrid biosystem paves a new way to functionalize higher organisms and diversify light energy conversion.
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http://dx.doi.org/10.1021/acsami.0c21902DOI Listing
May 2021

Next-Generation Sequencing Reveals That Oxidative Phosphorylation Might Be a Key Pathway Differently Expressed in the Third and Fourth Stages Larvae of .

Iran J Parasitol 2020 Oct-Dec;15(4):587-595

School of Medicine, Huzhou University, Huzhou Cent Hosp, 759 Er Huan Rd, Huzhou, Zhejiang, China.

Background: When develops from the third and fourth stage, it needs to change its host from the middle host, snail to the final host, rat. However, the mechanism involved in this change remains unclear.

Methods: The transcriptome differences of the third and fourth stages of were explored by next-generation Illumina Hiseq/Miseq sequencing in China, in 2018.

Results: Overall, 137 956 488 clean reads and 20 406 213 373 clean bases of the two stages larvae were produced. Based on the queries against the Gene Ontology (GO), NCBI non-redundant protein sequences (Nr), Swissprot, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, 14 204 differentially expressed genes (DEGs) were predicted. GO enrichment analysis revealed 5660 DEGs with the top s categories as followings: biological process (GO:0008150, related to 5345 DEGs), cellular component (GO:0005575, related to 5297 DEGs), molecular function (GO:0003674, related to 5290 DEGs). In KEGG enrichment analysis, 116 genes were related to oxidative phosphorylation and 49 genes involved in the glycolytic process.

Conclusion: Metabolism changes, especially oxidative phosphorylation and glycolysis, might play a key role in infection of its final rat host. Many other pathways might also contribute to the transcriptome changes between these two life stages. Overall, additional studies are needed for further details.
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http://dx.doi.org/10.18502/ijpa.v15i4.4869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039486PMC
April 2021

Application of metagenomic next-generation sequencing in the diagnosis and treatment guidance of Pneumocystis jirovecii pneumonia in renal transplant recipients.

Eur J Clin Microbiol Infect Dis 2021 Apr 21. Epub 2021 Apr 21.

Transplantation Center, The Third Xiangya Hospital, Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China.

Pneumocystis jirovecii pneumonia (PJP) is difficult to be diagnosed, so this study explored if PJP could be diagnosed by metagenomic next-generation sequencing (mNGS) and if mNGS could guide the therapy of PJP. mNGS was successfully diagnosed 13 out of 14 PJP recipients with 11 through peripheral blood samples, verified by PCR. Ten non-PJP recipients were enrolled as the control group. Blood tests revealed a high β-D-glucan (BDG) level in all recipients with PJP during the hospitalization. Four (28.6%) of 14 PJP patients were infected with cytomegalovirus simultaneously, while 8 (57.1%) suffered from a combined infection caused by Torque teno virus. Five (35.7%) of 14 cases died of PJP or the subsequent bacteremias/bacterial pneumonia with a longer interval between the onset and diagnosis of/the available therapy against PJP than survival cases. Univariate analysis of characteristics between PJP and non-PJP recipients revealed that BDG assays was higher at the admission in PJP group (P =0.011). This present study supports the value of mNGS detection of blood sample in diagnosing PJP, which could assist clinical decision for therapy against PJ and improve outcome of PJP. The study also highlights the sensitivity of BDG assays. Cytomegalovirus and Torque teno virus infections often occur at the same time of PJP, thus can be alerts of PJP.
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http://dx.doi.org/10.1007/s10096-021-04254-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057919PMC
April 2021

Comprehensive profiling and characterization of the absorbed components and metabolites in mice serum and tissues following oral administration of Qing-Fei-Pai-Du decoction by UHPLC-Q-Exactive-Orbitrap HRMS.

Chin J Nat Med 2021 Apr;19(4):305-320

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address:

Qing-Fei-Pai-Du decoction (QFPDD) is a Chinese medicine compound formula recommended for combating corona virus disease 2019 (COVID-19) by National Health Commission of the People's Republic of China. The latest clinical study showed that early treatment with QFPDD was associated with favorable outcomes for patient recovery, viral shedding, hospital stay, and course of the disease. However, the effective constituents of QFPDD remain unclear. In this study, an UHPLC-Q-Orbitrap HRMS based method was developed to identify the chemical constituents in QFPDD and the absorbed prototypes as well as the metabolites in mice serum and tissues following oral administration of QFPDD. A total of 405 chemicals, including 40 kinds of alkaloids, 162 kinds of flavonoids, 44 kinds of organic acids, 71 kinds of triterpene saponins and 88 kinds of other compounds in the water extract of QFPDD were tentatively identified via comparison with the retention times and MS/MS spectra of the standards or refereed by literature. With the help of the standards and in vitro metabolites, 195 chemical components (including 104 prototypes and 91 metabolites) were identified in mice serum after oral administration of QFPDD. In addition, 165, 177, 112, 120, 44, 53 constituents were identified in the lung, liver, heart, kidney, brain, and spleen of QFPDD-treated mice, respectively. These findings provided key information and guidance for further investigation on the pharmacologically active substances and clinical applications of QFPDD.
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http://dx.doi.org/10.1016/S1875-5364(21)60031-6DOI Listing
April 2021

Action Generalization Across Group Members: Action Efficiency Matters.

Cogn Sci 2021 Apr;45(4):e12957

Department of Psychology, Ningbo University.

Actions are usually generalized among social group members. Importantly, the efficiency of an action with respect to achieving an external target determines action understanding, and it may have different degrees of social relevance to social groups. Thus, this study explored the role of action efficiency in action generalization. We used computer animations to simulate actions in social groups initiated by visual action cues or category labels, and we measured differences in response times between identifying actions that were and were not consistent with group members, without explicit requirements regarding generalization. It was found that in both visually introduced and explicitly labeled social groups, when the group members acted inefficiently toward the external object, perceivers identified group-consistent actions faster than group-inconsistent actions, indicating that the exemplars' common inefficient actions are generalized to the unknown ingroup member, accordingly facilitating the identification of expected consistent inefficient action (Experiment 1). As this effect was not present when removing social group cues, it was determined to be specific to social groups (Experiment 2). Importantly, such generalization was not observed when the identical action was deemed efficient toward the external object (Experiment 3) and was specific to the demonstration of the action being completed by multiple group members rather than being repeated twice by one group member, supporting the group-based inference and ruling out the possibility of the increased memorability of inefficient actions leading to more generalization relative to efficient actions (Experiment 4). Therefore, the efficiency of an action bounds the generalization of the action across social group members through a process that is spontaneous and implicit. This constrained action generalization may be due to inefficient actions being represented as culture-specific conventional forms.
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http://dx.doi.org/10.1111/cogs.12957DOI Listing
April 2021

Ring finger 20/ring finger 40/WW domain-containing adaptor with coiled-coil complex interacts with p53 to regulate gene transcription in DNA damage response.

Oncol Lett 2021 Jun 1;21(6):436. Epub 2021 Apr 1.

College of Life Sciences, Shanghai Normal University, Shanghai 200234, P.R. China.

p53 is one of the most important tumor suppressor genes, and its primary function is to act as a transcriptional activator to control cell cycle arrest, DNA repair and cellular metabolism by recognizing and binding to specific DNA sequences. Defects in the ring finger (RNF)20/RNF40/WW domain-containing adaptor with coiled-coil (WAC) complex, one of the histone H2B ubiquitination E3 ligases, have been reported to be a key factor in oncogenesis, cancer cell migration and invasion. Histone H2B mono-ubiquitination has been demonstrated to be essential for maintaining the functionality of the p53 tumor suppressor protein. The aim of the present study was to identify any sites in the p53 DNA-binding domain (DBD) specific to the RNF20/RNF40/WAC complex that may be involved in the gene regulation in DNA damage response. The results demonstrated that p53 and the RNF20/RNF40/WAC complex interacted with each other, and the coiled-coil regions in RNF20, RNF40 and WAC were identified to directly interact with p53. The R282 site in the p53 DBD, one of the frequent missense mutations associated with p53 mutation-dependent cancer, was demonstrated to be the key binding site for the RNF20/RNF40/WAC complex. Furthermore, knockout of RNF20/RNF40 suppressed the expression levels of p53 and its target genes in HCT116 cells compared with those in wild-type HCT116 cells. Consistent with these results, the R282W mutation in p53 inhibited the expression levels of p53 and its downstream genes by inactivating the interaction between p53 and RNF20/RNF40 compared with those in wild-type HCT116 cells. In conclusion, the results of the present study revealed the molecular mechanism of the interaction between the RNF20/RNF40/WAC complex and p53, and demonstrated that these proteins regulated gene transcription in the DNA damage response.
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http://dx.doi.org/10.3892/ol.2021.12697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045150PMC
June 2021

A small collection of juveniles (Arthropoda: Pycnogonida: Endeidae) sorted from the fouling organisms on the R/V Dayangyihao.

Biodivers Data J 2021 8;9:e62343. Epub 2021 Apr 8.

The Key Laboratory of Invertebrate Systematics and Application, College of Life Sciences, Hebei University, Baoding, China The Key Laboratory of Invertebrate Systematics and Application, College of Life Sciences, Hebei University Baoding China.

Background: Clark, 1970 was originally described from Queensland, Australia. Its range was extended to Ghana, West Africa when Bamber, 1979 was synonymised with by Staples (1982). The current paper extends this range further, to include Port Louis, Mauritius.

New Information: Five immature individuals gathered amongst hydroids during the 5 leg of the DY125-34 expedition were tentatively identified as juveniles. Since these were collected from the fouling community on the ship's hull, they probably originated in Port Louis (Mauritius) when the ship was docked there.
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http://dx.doi.org/10.3897/BDJ.9.e62343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050013PMC
April 2021