Publications by authors named "Yang Ou"

147 Publications

Facet-Dependent Oxidative Strong Metal-Support Interactions of Palladium-TiO Determined by In Situ Transmission Electron Microscopy.

Angew Chem Int Ed Engl 2021 Aug 5. Epub 2021 Aug 5.

Center of Electron Microscopy and State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

The strong metal-support interaction (SMSI) is widely used in supported metal catalysts and extensive studies have been performed to understand it. Although considerable progress has been achieved, the surface structure of the support, as an important influencing factor, is usually ignored. We report a facet-dependent SMSI of Pd-TiO in oxygen by using in situ atmospheric pressure TEM. Pd NPs supported on TiO (101) and (100) surfaces showed encapsulation. In contrast, no such cover layer was observed in Pd-TiO (001) catalyst under the same conditions. This facet-dependent SMSI, which originates from the variable surface structure of the support, was demonstrated in a probe reaction of methane combustion catalyzed by Pd-TiO . Our discovery of the oxidative facet-dependent SMSI gives direct evidence of the important role of the support surface structure in SMSI and provides a new way to tune the interaction between metal NPs and the support as well as catalytic activity.
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http://dx.doi.org/10.1002/anie.202106805DOI Listing
August 2021

Correction to: CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism.

Signal Transduct Target Ther 2020 Jun 19;5(1):103. Epub 2020 Jun 19.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, Tianjin, 300071, China.

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http://dx.doi.org/10.1038/s41392-020-00212-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305231PMC
June 2020

Improvement of the efficiency and quality in developing a new CHO host cell line.

Biotechnol Prog 2021 Jun 18:e3185. Epub 2021 Jun 18.

Biologics Upstream Process Development, MRL, Merck & Co., Inc., Kenilworth, New Jersey, USA.

Chinese hamster ovary (CHO) cells are a ubiquitous tool for industrial therapeutic recombinant protein production. However, consistently generating high-producing clones remains a major challenge during the cell line development process. The glutamine synthetase (GS) and dihydrofolate reductase (DHFR) selection systems are commonly used CHO expression platforms based on controlling the balance of expression between the transgenic and endogenous GS or DHFR genes. Since the expression of the endogenous selection gene in CHO hosts can interfere with selection, generating a corresponding null CHO cell line is required to improve selection stringency, productivity, and stability. However, the efficiency of generating bi-allelic genetic knockouts using conventional protocols is very low (<5%). This significantly affects clone screening efficiency and reduces the chance of identifying robust knockout host cell lines. In this study, we use the GS expression system as an example to improve the genome editing process with zinc finger nucleases (ZFNs), resulting in improved GS-knockout efficiency of up to 46.8%. Furthermore, we demonstrate a process capable of enriching knockout CHO hosts with robust bioprocess traits. This integrated host development process yields a larger number of GS-knockout hosts with desired growth and recombinant protein expression characteristics.
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http://dx.doi.org/10.1002/btpr.3185DOI Listing
June 2021

Traumatic brain injury induced by exposure to blast overpressure via ear canal.

Neural Regen Res 2022 Jan;17(1):115-121

Departmant of Otolaryngology and Head Neck Surgery; Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, USA.

Exposure to explosive shockwave often leads to blast-induced traumatic brain injury in military and civilian populations. Unprotected ears are most often damaged following exposure to blasts. Although there is an association between tympanic membrane perforation and TBI in blast exposure victims, little is known about how and to what extent blast energy is transmitted to the central nervous system via the external ear canal. The present study investigated whether exposure to blasts directed through the ear canal causes brain injury in Long-Evans rats. Animals were exposed to a single blast (0-30 pounds per square inch (psi)) through the ear canal, and brain injury was evaluated by histological and behavioral outcomes at multiple time-points. Blast exposure not only caused tympanic membrane perforation but also produced substantial neuropathological changes in the brain, including increased expression of c-Fos, induction of a profound chronic neuroinflammatory response, and apoptosis of neurons. The blast-induced injury was not limited only to the brainstem most proximal to the source of the blast, but also affected the forebrain including the hippocampus, amygdala and the habenula, which are all involved in cognitive functions. Indeed, the animals exhibited long-term neurological deficits, including signs of anxiety in open field tests 2 months following blast exposure, and impaired learning and memory in an 8-arm maze 12 months following blast exposure. These results suggest that the unprotected ear canal provides a locus for blast waves to cause TBI. This study was approved by the Institutional Animal Care and Use Committee at the University of Mississippi Medical Center (Animal protocol# 0932E, approval date: September 30, 2016 and 0932F, approval date: September 27, 2019).
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http://dx.doi.org/10.4103/1673-5374.314311DOI Listing
January 2022

Additive grain-size: An innovative perspective to investigate the transformation among heavy metal and phosphorus fractions during aerobic composting.

J Environ Manage 2021 Aug 10;292:112768. Epub 2021 May 10.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China; Jilin Provincial Engineering Center of CWs Design in Cold Region & Beautiful Country Construction, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China; University of Chinese Academy of Sciences, Beijing, 100049, China.

Considerable researches have been devoted to ascertain the transformation among heavy metal (HM) or phosphorus (P) fractions during aerobic composting. However, available information that additives with different grain-sizes regulate the activation mechanism on P through influencing the passivation effect on HMs remains limited. Thus, this work aimed to investigate the dynamic changes in HM-fractions and P-fractions, and ascertain the interaction pathway between HMs and P during aerobic composting amended with medical stone (Coarse medical stone, 3-5 mm; Fine medical stone, < 0.1 mm). Medical stone, especially for coarse-grained medical stone, significantly enhanced the HM-passivation and P-activation during the composting (P < 0.05). The bioavailability factor of HMs decreased by 48.05% (Cu), 20.65% (Pb), 15.58% (Cd) and 6.10% (Zn), and the content of labile available P (LAP) increased by 6.45%. HMs, with the explanatory capacity of 65.9%-84.9%, was important parameter superior to temperature (0.8%-5.4%), moisture content (MC, 0.1%-1.7%), pH (0.1%-8.7%), electric conductivity (EC, 0.8%-9.8%), carbon-to-nitrogen (C:N, 0.3%-2.3%) ratio and dissolved organic carbon (DOC, 0.4%-3.1%), to evaluate the transformation among P-fractions. Our results cast a new light on P-activation with respect to HM-passivation during aerobic composting.
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http://dx.doi.org/10.1016/j.jenvman.2021.112768DOI Listing
August 2021

The basic route of nuclear-targeted transport of IGF-1/IGF-1R and potential biological functions in intestinal epithelial cells.

Cell Prolif 2021 Jun 1;54(6):e13030. Epub 2021 May 1.

Department of Intensive care unit, The first hospital of Jilin University, Changchun, China.

Objectives: Insulin-like growth factor (IGF-1) plays an important role in many biological processes in the intestinal tract. However, the cellular behaviour and characteristics of IGF-1/IGF-1R in intestinal cells remain unclear.

Materials And Methods: A series of techniques (such as indirect immunofluorescence, co-localization and Western blot) have been used to systematically study the cellular behaviour of IGF-1/IGF-1R on intestinal cells.

Results: We found that IGF-1 can not only internalize into the cytoplasm, but also transport into the cell nuclei. We systematically studied the detailed molecular pathways of IGF-1/IGF-1R's nuclear translocation. We found that IGF-1R underwent clathrin-mediated endocytosis into cells and then entered into Rab-5-positive endosomes. Dynein/dynactin were used as motors to drive Rab-5-positive endosomes carrying IGF-1R (cargo molecule) to Golgi apparatus (transit station) along the surface of the microtubule. IGF-1 and/or IGF-1R entered the cell nuclei through NPC (nuclear pore complex), a process mediated by NUP358. Further study indicated that nuclear localization of IGF-1 and/or IGF-1R promoted cell proliferation and increased the nuclear residence time of signalling molecules activated by IGF-1. Further experiments showed that IGF-1R may regulate the transcription of genes in the cell nuclei, indicating that nuclear-localized IGF-1R plays an important in cell proliferation.

Conclusions: In short, we revealed the molecular mechanism by which IGF-1/IGF-1R transports into the cell nuclei of intestinal cells. More importantly, the current work showed that the nuclear-localized IGF-1R has important biological functions.
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http://dx.doi.org/10.1111/cpr.13030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168413PMC
June 2021

Nursing Home Competition, Prices and Quality: A Scoping Review and Policy Lessons.

Gerontologist 2021 Apr 14. Epub 2021 Apr 14.

Melbourne Institute: Applied Economic & Social Research, The University of Melbourne, Parkville, Victoria, Australia.

Background And Objectives: In recent years, countries have increasingly relied on markets to improve efficiency, contain costs, and maintain quality in aged care. Under the right conditions, competition can spur providers to compete by offering better prices and higher quality of services. However, in aged care, market failures can be extensive. Information about prices and quality may not be readily available and search costs can be high. This study undertakes a scoping review on competition in the nursing home sector, with an emphasis on empirical evidence in relation to how competition affects prices and quality of care.

Research Design And Methods: Online databases were used to identify studies published in English language between 1988 and 2020. A total of 50 studies covering nine countries are reviewed.

Results: The review finds conflicting evidence on the relationship between competition and quality. Some studies find greater competition leading to higher quality, others find the opposite. Institutional features such as the presence of binding supply restrictions on nursing homes and public reporting of quality information are important considerations. Most studies find greater competition tends to result in lower prices, although the effect is small.

Discussion And Implications: The literature offers several key policy lessons, including the relationship between supply restrictions and quality which has implications on whether increasing subsidies can result in higher quality and the importance of price transparency and public reporting of quality.
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http://dx.doi.org/10.1093/geront/gnab050DOI Listing
April 2021

Transfer of Learning in the Convolutional Neural Networks on Classifying Geometric Shapes Based on Local or Global Invariants.

Front Comput Neurosci 2021 19;15:637144. Epub 2021 Feb 19.

Department of Otolaryngology-Head and Neck Surgery, University of Mississippi Medical Centre, Jackson, MS, United States.

The convolutional neural networks (CNNs) are a powerful tool of image classification that has been widely adopted in applications of automated scene segmentation and identification. However, the mechanisms underlying CNN image classification remain to be elucidated. In this study, we developed a new approach to address this issue by investigating transfer of learning in representative CNNs (AlexNet, VGG, ResNet-101, and Inception-ResNet-v2) on classifying geometric shapes based on local/global features or invariants. While the local features are based on simple components, such as orientation of line segment or whether two lines are parallel, the global features are based on the whole object such as whether an object has a hole or whether an object is inside of another object. Six experiments were conducted to test two hypotheses on CNN shape classification. The first hypothesis is that transfer of learning based on local features is higher than transfer of learning based on global features. The second hypothesis is that the CNNs with more layers and advanced architectures have higher transfer of learning based global features. The first two experiments examined how the CNNs transferred learning of discriminating local features (square, rectangle, trapezoid, and parallelogram). The other four experiments examined how the CNNs transferred learning of discriminating global features (presence of a hole, connectivity, and inside/outside relationship). While the CNNs exhibited robust learning on classifying shapes, transfer of learning varied from task to task, and model to model. The results rejected both hypotheses. First, some CNNs exhibited lower transfer of learning based on local features than that based on global features. Second the advanced CNNs exhibited lower transfer of learning on global features than that of the earlier models. Among the tested geometric features, we found that learning of discriminating inside/outside relationship was the most difficult to be transferred, indicating an effective benchmark to develop future CNNs. In contrast to the "ImageNet" approach that employs natural images to train and analyze the CNNs, the results show proof of concept for the "ShapeNet" approach that employs well-defined geometric shapes to elucidate the strengths and limitations of the computation in CNN image classification. This "ShapeNet" approach will also provide insights into understanding visual information processing the primate visual systems.
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http://dx.doi.org/10.3389/fncom.2021.637144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935523PMC
February 2021

JASMONATE-ZIM DOMAIN proteins engage Polycomb chromatin modifiers to modulate Jasmonate signaling in Arabidopsis.

Mol Plant 2021 05 3;14(5):732-747. Epub 2021 Mar 3.

Shanghai Center for Plant Stress Biology, Chinese Academy of Sciences Center for Excellence in Molecular Plant Sciences, Shanghai 201602, China; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; Peking University Institute of Advanced Agricultural Sciences, Weifang, Shandong 261000, China; State Key Laboratory of Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences, School of Advanced Agriculture Sciences, Peking University, Beijing 100871, China. Electronic address:

Jasmonate (JA) regulates various aspects of plant growth and development and stress responses, with prominent roles in male reproductive development and defenses against herbivores and necrotrophic pathogens. JASMONATE-ZIM DOMAIN (JAZ) proteins are key regulators in the JA signaling pathway and function to repress the expression of JA-responsive genes. Here, we show that JAZ proteins directly interact with several chromatin-associated Polycomb proteins to mediate repressive chromatin modifications at JA-responsive genes and, thus, their transcriptional repression in Arabidopsis. Genetic analyses revealed that the developmental defects, including anther and pollen abnormalities, resulting from loss or block of JA signaling were partially rescued by loss of Polycomb protein-mediated chromatin silencing (Polycomb repression). We further found that JAZ-mediated transcriptional repression during anther and pollen development requires Polycomb proteins at four key regulatory loci. Analysis of genome-wide occupancy of a Polycomb factor and transcriptome reprogramming in response to JA revealed that Polycomb repression is involved in the repression of various JA-responsive genes. Taken together, our study reveals an important chromatin-based mechanism for JAZ-mediated transcriptional repression and JA signaling in plants.
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http://dx.doi.org/10.1016/j.molp.2021.03.001DOI Listing
May 2021

The prognostic significance of single-nucleotide polymorphism array-based whole-genome analysis and uniparental disomy in myelodysplastic syndrome.

Int J Lab Hematol 2021 Mar 2. Epub 2021 Mar 2.

Department of Hematology and Hematology Research Laboratory, West China Hospital, Sichuan University, Chengdu, China.

Introduction: Myelodysplastic syndrome (MDS) is a group of heterogeneous hematological diseases characterized by ineffective hematopoiesis and dysplastic morphology. Single nucleotide polymorphism array (SNP-A)-based whole genome analysis has a much higher resolution for chromosomal alterations when compared with conventional cytogenetic tools. In the present study, we evaluated the diagnostic value and prognostic significance of SNP-A in MDS patients with normal karyotypes.

Methods: A total of 127 patients with MDS and myeloproliferative neoplasms or acute myeloid leukemia with myelodysplasia-related changes were included in our study. The advantages and disadvantages of SNP-A were compared with those of traditional metaphase cytogenetic analysis (MC). The Kaplan-Meier analysis and COX regression analysis were used to investigate the prognostic value of SNP-A and uniparental disomy (UPD) in MDS patients with normal karyotype. Furthermore, the chromosomal abnormalities detected by SNP-A in patients with specific gene mutations were explored.

Results: SNP-A was more sensitive toward meaningful chromosomal aberrations (58.2% vs 36.9%; P < .05) than MC. Among the patients with normal karyotype, those who were detected with new chromosomal abnormalities via SNP-A presented with inferior survival compared with those without the abnormalities (P = .003). Additionally, the presence of UPD was an independent prognostic factor in patients with normal karyotype (P = .01). TP53 and RUNX1 mutations often occurred with abnormalities in chromosomes 17p and 21q, respectively.

Conclusions: Compared with MC, SNP-A capable of detecting UPD can offer more diagnostic and prognostic information; TP53 and RUNX1 gene mutations are often accompanied by abnormalities in their chromosomes (17p, 22q).
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http://dx.doi.org/10.1111/ijlh.13502DOI Listing
March 2021

Effect of inorganic additives (rock phosphate, PR and boron waste, BW) on the passivation of Cu, Zn during pig manure composting.

J Environ Manage 2021 May 17;285:112101. Epub 2021 Feb 17.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun, 130102, China. Electronic address:

The bioavailability of heavy metals in compost is critical for their agronomic value. The effect of inorganic additives (rock phosphate, PR and boron waste, BW) on Copper (Cu) and Zinc (Zn) bioavailability during co-compost of swine manure and rice straw was assessed using sequential extraction procedure (European Community Bureau of Reference). The result showed that both additives, applied at rates of 2.5%-7.5% (w/w) could promote the change of exchangeable Cu and reducible Cu into oxidizable Cu, thereby reducing their bioavailability factor (BF) by 15.5%-47.2%. While additives provided no significant reduction in BF of Zn, the shift from exchangeable Zn into reducible Zn can still reduce the mobility of Zn. Based on redundancy analysis (RDA), organic matter (OM) and electrical conductivity (EC) were identified as the most important controlling factors for redistribution of Cu and Zn fractions during composting. The inorganic additives strengthened the passivation of Cu and Zn bioavailability by stimulating OM degradation. The 7.5% (w/w) rock phosphate showed best passivating effect on the bioavailability of Cu.
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http://dx.doi.org/10.1016/j.jenvman.2021.112101DOI Listing
May 2021

Magnetic resonance imaging and contrast-enhanced ultrasound findings of a recurrent primary breast angiosarcoma: A case report.

Medicine (Baltimore) 2021 Feb;100(5):e24625

Department of Breast Surgery.

Rationale: Primary breast angiosarcoma (PBA) is a rare and overly aggressive entity and account for less than 1% of all breast cancer cases. PBA had a high rate of delayed preoperative diagnosis due to absent distinctive radiographic characteristics.

Patient Concerns: We report a case of a 47-year-old female patient who had a previous history of luminal cancer in the right breast with mastectomy; the patient complained of asymmetrically diffuse enlarged, accompanying with a painless mass in the left breast 12 years after the mastectomy of her right breast.

Diagnoses: The tumor mimicked idiopathic granulomatous mastitis on magnetic resonance imaging (MRI) at the first presentation. Contrast-enhanced ultrasound (CEUS) was performed for further lesion characterization and showed heterogeneous rapid hyper enhanced. An ultrasound-guided core needle biopsy was performed, and the pathology report indicated a breast angiosarcoma.

Interventions: The patient underwent a nipple-sparing simple mastectomy with immediate reconstruction of the left breast.

Outcomes: After 8 months later, the tumor recurred, CEUS and MRI examination suggested PBA recurrence, then re-excision with implant removal was performed, the patient had a lung metastasis 4 months later eventually died 22 months after diagnosis.

Lessons: It is not easy to diagnose PBA with the radiographic examination. This case's importance is by combining CEUS and MRI to reflect enhanced morphology and hemodynamic characteristics of PBA and help diagnose breast angiosarcomas.
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http://dx.doi.org/10.1097/MD.0000000000024625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870214PMC
February 2021

In situ manipulation of the active Au-TiO interface with atomic precision during CO oxidation.

Science 2021 01;371(6528):517-521

State Key Laboratory of Silicon Materials and Center of Electron Microscopy, School of Materials Science and Engineering, Zhejiang University, Hangzhou, 310027 China.

The interface between metal catalyst and support plays a critical role in heterogeneous catalysis. An epitaxial interface is generally considered to be rigid, and tuning its intrinsic microstructure with atomic precision during catalytic reactions is challenging. Using aberration-corrected environmental transmission electron microscopy, we studied the interface between gold (Au) and a titanium dioxide (TiO) support. Direct atomic-scale observations showed an unexpected dependence of the atomic structure of the Au-TiO interface with the epitaxial rotation of gold nanoparticles on a TiO surface during carbon monoxide (CO) oxidation. Taking advantage of the reversible and controllable rotation, we achieved in situ manipulation of the active Au-TiO interface by changing gas and temperature. This result suggests that real-time design of the catalytic interface in operating conditions may be possible.
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http://dx.doi.org/10.1126/science.abe3558DOI Listing
January 2021

Hidden Vacancy Benefit in Monolayer 2D Semiconductors.

Adv Mater 2021 Feb 14;33(7):e2007051. Epub 2021 Jan 14.

Beijing Advanced Innovation Center for Materials Genome Engineering, Beijing Key Laboratory for Advanced Energy Materials and Technologies, University of Science and Technology Beijing, Beijing, 100083, P. R. China.

Monolayer 2D semiconductors (e.g., MoS ) are of considerable interest for atomically thin transistors but generally limited by insufficient carrier mobility or driving current. Minimizing the lattice defects in 2D semiconductors represents a common strategy to improve their electronic properties, but has met with limited success to date. Herein, a hidden benefit of the atomic vacancies in monolayer 2D semiconductors to push their performance limit is reported. By purposely tailoring the sulfur vacancies (SVs) to an optimum density of 4.7% in monolayer MoS , an unusual mobility enhancement is obtained and a record-high carrier mobility (>115 cm V s ) is achieved, realizing monolayer MoS transistors with an exceptional current density (>0.60 mA µm ) and a record-high on/off ratio >10 , and enabling a logic inverter with an ultrahigh voltage gain >100. The systematic transport studies reveal that the counterintuitive vacancy-enhanced transport originates from a nearest-neighbor hopping conduction model, in which an optimum SV density is essential for maximizing the charge hopping probability. Lastly, the vacancy benefit into other monolayer 2D semiconductors is further generalized; thus, a general strategy for tailoring the charge transport properties of monolayer materials is defined.
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http://dx.doi.org/10.1002/adma.202007051DOI Listing
February 2021

Comparison of CellSearch and Circulating Tumor Cells (CTC)-Biopsy Systems in Detecting Peripheral Blood Circulating Tumor Cells in Patients with Gastric Cancer.

Med Sci Monit 2021 Jan 7;27:e926565. Epub 2021 Jan 7.

Department of Cardiovascular Surgery, Guangzhou Red Cross Hospital, Medical college, Jinan University, Guangzhou, Guangdong, China (mainland).

BACKGROUND The purpose of this study was to compare circulating tumor cells (CTCs)/circulating tumor microemboli (CTM) detection rates of the CellSearch and CTC-Biopsy systems in patients with gastric cancer (GC). We also investigated potential correlations between clinicopathological characteristics and prognosis in patients with GC. MATERIAL AND METHODS This prospective study was conducted at the Shandong Institute of Cancer Prevention and Control in China. Fifty-nine patients with GC and 22 healthy volunteers were recruited and their peripheral blood samples were examined by the CTC-Biopsy system and CellSearch system for CTC. RESULTS The rate of detection of CTCs/CTM was significantly higher with the CTC-Biopsy system than with the CellSearch system (59.32% vs. 27.12%, P<0.001). The Kappa value was 0.179, indicating poor consistency. CTCs detected with the CellSearch system in patients with stage III/IV GC was significantly correlated with neutrophil count (P=0.020), neutrophil/lymphocyte ratio (N/L ratio) (P=0.009), CA19-9 (P=0.049), tumor size (P=0.026), and the extent of vascular invasion (P=0.007). CTCs detected with the CTC-Biopsy system correlated with tumor differentiation (P=0.010). CTM in patients with stage I/II GC and stage II/IV GC correlated with CEA (P=0.004) and tumor differentiation (P=0.030), respectively. A CTC count >3 detected with the CellSearch system, and not the CTC-Biopsy system, correlated with reduced progression-free survival and overall survival. CONCLUSIONS The CTC-Biopsy system was superior to the CellSearch system for detecting CTCs in GC patients. CTM were detected with the CTC-Biopsy system but not with the CellSearch system. CTCs detected with the CellSearch system correlated with various clinicopathological factors and long-term survival outcomes.
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http://dx.doi.org/10.12659/MSM.926565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802377PMC
January 2021

Does socioeconomic status affect hospital utilization and health outcomes of chronic disease patients?

Eur J Health Econ 2021 Mar 3;22(2):329-339. Epub 2021 Jan 3.

Melbourne Institute of Applied Economic and Social Research, The University of Melbourne, L5, 111 Barry Street, FBE Building, Parkville, VIC, 3010, Australia.

This study quantifies the extent socioeconomic status (SES) affects hospital utilization and adverse hospital events of chronic disease patients. After identifying the initial first-year spell of the disease, we examine six outcomes that include measures of utilization and incidence of adverse in-hospital events. Three years of hospital administrative data from the state of Victoria, Australia, are used to extract a sample of 237,743 patients with chronic disease spells. SES is measured using the utilization records of specific health and human services. The study finds that, compared to patients with no disadvantage, SES disadvantaged patients tend to incur higher hospital costs and longer utilization by about 20% and greater incidence of in-hospital adverse outcomes by up to 80% than non-disadvantaged patients. Further analysis shows that hospital adverse outcomes indirectly contribute to about a quarter of the observed difference in hospital costs between SES disadvantaged and non-disadvantaged patients.
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http://dx.doi.org/10.1007/s10198-020-01255-zDOI Listing
March 2021

Efficacy and Safety of CAR-Modified T Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Prospective Clinical Trials.

Front Pharmacol 2020 3;11:544754. Epub 2020 Dec 3.

Hematology Research Laboratory, West China Hospital, Department of Hematology, Sichuan University, Chengdu, China.

: In recent years, chimeric antigen receptor-modified T (CAR-T) cell therapy for B-cell leukemia and lymphoma has shown high clinical efficacy. Similar CAR-T clinical trials have also been carried out in patients with refractory/relapsed multiple myeloma (RRMM). However, no systematic review has evaluated the efficacy and safety of CAR-T cell therapy in RRMM. The purpose of this study was to fill this literature gap. : Eligible studies were searched in PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, and WanFang from data inception to December 2019. For efficacy assessment, the overall response rate (ORR), minimal residual disease (MRD) negativity rate, strict complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) were calculated. The incidence of any grade cytokine release syndrome (CRS) and grade ≥3 adverse events (AEs) were calculated for safety analysis. The effect estimates were then pooled using an inverse variance method. : Overall, 27 studies involving 497 patients were included in this meta-analysis. The pooled ORR and MRD negativity rate were 89% (95% Cl: 83-94%) and 81% (95% Cl: 67-91%), respectively. The pooled sCR, CR, VGPR, and PR were 14% (95% Cl: 5-27%), 13% (95% Cl: 4-26%), 23% (95% Cl: 14-33%), and 15% (95% Cl: 10-21%), respectively. Subgroup analyses of ORR by age, proportion of previous autologous stem cell transplantation (ASCT), and target selection of CAR-T cells revealed that age ≤ 55 years (≤55 years vs. > 55 years, = 0.0081), prior ASCT ≤70% (≤70% vs. > 70%, = 0.035), and bispecific CAR-T cells (dual B-cell maturation antigen (BCMA)/BCMA + CD19 vs specific BCMA, = 0.0329) associated with higher ORR in patients. Subgroup analyses of remission depth by target selection suggested that more patients achieved a better response than VGPR with dual BCMA/BCMA + CD19 CAR-T cells compared to specific BCMA targeting ( = 0.0061). In terms of safety, the pooled incidence of any grade and grade ≥ 3 CRS was 76% (95% CL: 63-87%) and 11% (95% CL: 6-17%). The most common grade ≥ 3 AEs were hematologic toxic effects. : In heavily treated patients, CAR-T therapy associates with promising responses and tolerable AEs, as well as CRS in RRMM. However, additional information regarding the durability of CAR-T cell therapy, as well as further randomized controlled trials, is needed.
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http://dx.doi.org/10.3389/fphar.2020.544754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744881PMC
December 2020

Receptor-like Kinases in Root Development: Current Progress and Future Directions.

Mol Plant 2021 01 11;14(1):166-185. Epub 2020 Dec 11.

Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address:

Cell-to-cell and cell-to-environment communications are critical to the growth and development of plants. Cell surface-localized receptor-like kinases (RLKs) are mainly involved in sensing various extracellular signals to initiate their corresponding cellular responses. As important vegetative organs for higher plants to adapt to a terrestrial living situation, roots play a critical role for the survival of plants. It has been demonstrated that RLKs control many biological processes during root growth and development. In this review, we summarize several key regulatory processes during Arabidopsis root development in which RLKs play critical roles. We also put forward a number of relevant questions that are required to be explored in future studies.
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http://dx.doi.org/10.1016/j.molp.2020.12.004DOI Listing
January 2021

mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppression.

Genes Dev 2021 01 10;35(1-2):59-64. Epub 2020 Dec 10.

Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.

Here, we showed that the acetylation-defective mice, lacking the ability of cell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop early-onset tumors. By identifying a novel p53 acetylation site at lysine K136, we found that simultaneous mutations at all five acetylation sites (p53-5KR) diminished its remaining tumor suppression function. Moreover, the embryonic lethality caused by the deficiency of was fully rescued in the background of , but not background. p53-4KR retained the ability to suppress mTOR function but this activity was abolished in cells. Notably, the early-onset tumor formation observed in and -null mice was suppressed upon the treatment of the mTOR inhibitor. These results suggest that p53-mediated mTOR regulation plays an important role in both embryonic development and tumor suppression, independent of cell cycle arrest, senescence, apoptosis, and ferroptosis.
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http://dx.doi.org/10.1101/gad.340919.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778266PMC
January 2021

The quest for improved air quality may push China to continue its CO reduction beyond the Paris Commitment.

Proc Natl Acad Sci U S A 2020 11 9;117(47):29535-29542. Epub 2020 Nov 9.

School of Environment, State Key Joint Laboratory of Environment Simulation and Pollution Control, Tsinghua University, 100084 Beijing, People's Republic of China.

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The "Beautiful China" strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 μg/m or below for annual mean concentration of PM (particulate matter with aerodynamic diameter less than 2.5 μm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO mitigation, attributed particularly to the cost-effective reduction in household PM exposure. The additional low-carbon energy polices required for China's air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.
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http://dx.doi.org/10.1073/pnas.2013297117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703636PMC
November 2020

Alzheimer amyloid-β- peptide disrupts membrane localization of glucose transporter 1 in astrocytes: implications for glucose levels in brain and blood.

Neurobiol Aging 2021 01 10;97:73-88. Epub 2020 Oct 10.

Department of Neurobiology & Developmental Sciences, Little Rock, AR, USA; Department of Geriatrics, Little Rock, AR, USA; Geriatric Research, Education & Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address:

Alzheimer's disease (AD) is associated with disturbances in blood glucose regulation, and type-2 diabetes elevates the risk for dementia. A role for amyloid-β peptide (Aβ) in linking these age-related conditions has been proposed, tested primarily in transgenic mouse lines that overexpress mutated amyloid precursor protein (APP). Because APP has its own impacts on glucose regulation, we examined the BRI-Aβ42 line ("Aβ-tg"), which produces extracellular Aβ in the CNS without elevation of APP. We also looked for interactions with diet-induced obesity (DIO) resulting from a high-fat, high-sucrose ("western") diet. Aβ-tg mice were impaired in both spatial memory and glucose tolerance. Although DIO induced insulin resistance, Aβ accumulation did not, and the impacts of DIO and Aβ on glucose tolerance were merely additive. Aβ-tg mice exhibited no significant differences from wild-type in insulin production, body weight, lipidemia, appetite, physical activity, respiratory quotient, an-/orexigenic factors, or inflammatory factors. These negative findings suggested that the phenotype in these mice arose from perturbation of glucose excursion in an insulin-independent tissue. To wit, cerebral cortex of Aβ-tg mice had reduced glucose utilization, similar to human patients with AD. This was associated with insufficient trafficking of glucose transporter 1 to the plasma membrane in parenchymal brain cells, a finding also documented in human AD tissue. Together, the lower cerebral metabolic rate of glucose and diminished function of parenchymal glucose transporter 1 indicate that aberrant regulation of blood glucose in AD likely reflects a central phenomenon, resulting from the effects of Aβ on cerebral parenchyma, rather than a generalized disruption of hypothalamic or peripheral endocrinology. The involvement of a specific glucose transporter in this deficit provides a new target for the design of AD therapies.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736209PMC
January 2021

Critical passivation mechanisms on heavy metals during aerobic composting with different grain-size zeolite.

J Hazard Mater 2021 03 19;406:124313. Epub 2020 Oct 19.

Key Laboratory of Wetland Ecology and Environment, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China; Jilin Provincial Engineering Center of CWs Design in Cold Region & Beautiful Country Construction, Northeast Institute of Geography and Agroecology, Chinese Academy of Sciences, Changchun 130102, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Available information about the passivation effect on heavy metals (HMs) through adsorption and humification during zeolite-amended composting remains limited. Thus, this study explored the dynamic changes in HM-fractions (Zn, Cu, Cd, Cr and Pb) during aerobic composting added with different grain-size zeolite (Fine zeolite, < 0.1 mm, ZF; Coarse zeolite: 3-5 mm, ZC). Compared to the control (without zeolite, CK) and ZF treatments, ZC treatment got the highest temperature in the thermophilic phase, and significantly reduced the bioavailability factor (BF) of HMs, especially for Cu (45.13%), Cd (16.11%) and Pb (25.49%). Redundancy analysis (RDA) and structural equation models (SEMs) indicated that zeolite accelerated the passivation effect on Cd and Pb through regulating the electrical conductivity (EC) as a result of surface adsorption, and on Cu by influencing total carbon (TC) under the function of humification. These results increase our understanding of the passivation mechanisms of HMs during aerobic composting.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124313DOI Listing
March 2021

Atomic-Thin ZnO Sheet for Visible-Blind Ultraviolet Photodetection.

Small 2020 Nov 2;16(47):e2005520. Epub 2020 Nov 2.

Beijing Advanced Innovation Center for Materials Genome Engineering, Beijing Key Laboratory for Advanced Energy Materials and Technologies, University of Science and Technology Beijing, Beijing, 100083, P. R. China.

The atomic-thin 2D semiconductors have emerged as plausible candidates for future optoelectronics with higher performance in terms of the scaling process. However, currently reported 2D photodetectors still have huge shortcomings in ultraviolet and especially visible-blind wavelengths. Here, a simple and nontoxic surfactant-assisted synthesis strategy is reported for the controllable growth of atomically thin (1.5 to 4 nm) ZnO nanosheets with size ranging from 3 to 30 µm. Benefit from the short carbon chains and the water-soluble ability of sodium dodecyl sulfate (SDS), the synthesized ZnO nanosheets possess high crystal quality and clean surface, leading to good compatibility with traditional micromanufacturing technology and high sensitivity to UV light. The photodetectors constructed with ZnO demonstrate the highest responsivity (up to 2.0 × 10 A W ) and detectivity (D* = 6.83 × 10 Jones) at a visible-blind wavelength of 254 nm, and the photoresponse speed is optimized by the 400 °C annealing treatment (τ  = 3.97 s, τ  = 5.32 s), thus the 2D ZnO can serve as a promising material to fill in the gap for deep-UV photodetection. The method developed here opens a new avenue to controllably synthesize 2D nonlayered materials and accelerates their applications in high-performance optoelectronic devices.
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http://dx.doi.org/10.1002/smll.202005520DOI Listing
November 2020

Changes of air quality and its associated health and economic burden in 31 provincial capital cities in China during COVID-19 pandemic.

Atmos Res 2021 Feb 20;249:105328. Epub 2020 Oct 20.

Jiangsu Key Laboratory of Atmospheric Environment Monitoring and Pollution Control, Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, School of Environmental Science and Engineering, Nanjing University of Information Science and Technology, Nanjing 210044, China.

With outbreak of the novel coronavirus disease (COVID-19), immediate prevention and control actions were imposed in China. Here, we conducted a timely investigation on the changes of air quality, associated health burden and economic loss during the COVID-19 pandemic (January 1 to May 2, 2020). We found an overall improvement of air quality by analyzing data from 31 provincial cities, due to varying degrees of NO, PM, PM and CO reductions outweighing the significant O increase. Such improvement corresponds to a total avoided premature mortality of 9410 (7273-11,144) in the 31 cities by comparing the health burdens between 2019 and 2020. NO reduction was the largest contributor (55%) to this health benefit, far exceeding PM (10.9%) and PM (23.9%). O instead was the only negative factor among six pollutants. The period with the largest daily avoided deaths was rather not the period with strict lockdown but that during February 25 to March 31, due to largest reduction of NO and smallest increase of O. Southwest, Central and East China were regions with relatively high daily avoided deaths, while for some cities in Northeast China, the air pollution was even worse, therefore could cause more deaths than 2019. Correspondingly, the avoided health economic loss attributable to air quality improvement was 19.4 (15.0-23.0) billion. Its distribution was generally similar to results of health burden, except that due to regional differences in willingness to pay to reduce risks of premature deaths, East China became the region with largest daily avoided economic loss. Our results here quantitatively assess the effects of short-term control measures on changes of air quality as well as its associated health and economic burden, and such information is beneficial to future air pollution control.
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http://dx.doi.org/10.1016/j.atmosres.2020.105328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574695PMC
February 2021

Shionone suppresses the growth, migration and invasion of human breast cancer cells via induction of apoptosis and inhibition of MEK/ERK and STAT3 signalling pathways.

J BUON 2020 Jul-Aug;25(4):1821-1826

Department of General Surgery, the 5th People's Hospital of Jinan, Jinan, China, 250022.

Purpose: Breast cancer is responsible for high morbidity and mortality across the globe. Studies are focusing to develop novel systemic therapies for the treatment of this disease. The present study was designed to examine the anticancer effects of Shionone against human breast cancer cells along with the underlying mechanism of its action.

Methods: The breast cancer SK-BR-3 and normal breast MB-157 cell lines were used in the study. CCK8 assay was used for cell viability assessment. DAPI was used for the assessment of nuclear morphology. Acridine orange (AO)/ ethidium bromide (EB) and annexin V/propidium iodide (PI) assays were used for detection of apoptosis. Cell cycle analysis was done by flow cytometry. Protein expression was examined by western blot analysis.

Results: The results showed that in vitro administration of Shionone led to decline of proliferation of breast cancer cells. The reduction of proliferative rates was attributed to the induction of apoptosis of breast cancer cells. Shionone caused cleavage of caspase-3 and 9. The expression of Bax was increased and that of Bcl-2 was decreased upon Shionone treatment. The transwell assays showed that Shionone suppressed the migration and invasion of breast cancer cells in a dose-dependent manner. Finally, western blot analysis showed that Shionone blocked the Ras/Raf/MEK/ERK and STAT3 signaling pathways in breast cancer cells.

Conclusion: Taken all together, the study established the anticancer role of triterpenoid Shionone in restricting the growth and proliferation of human breast cancer cells.
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July 2021

Frequency Domain Analysis and Precision Realization in Deterministic Figuring of Ultra-Precision Shaft Parts.

Materials (Basel) 2020 Oct 14;13(20). Epub 2020 Oct 14.

College of Intelligent Science and Technology, National University of Defense Technology, Changsha 410073, China.

An aerostatic spindle is a core component in ultra-precision machine tools. The rotor of the spindle has extremely high manufacturing accuracy, which cannot be directly achieved via traditional machining, but always via manual grinding. The deterministic figuring theory is introduced into the machining of shaft parts, which overcomes many shortcomings of manual grinding. The manufacturing error of the shaft's surface contains different frequency components, which have different effects on its working performance and the figuring process. Because the deterministic figuring method can only correct the error within a limited frequency range, in order to ensure high efficiency and high precision of the figuring process, we need to use reasonable filtering parameters to filter out the error with unnecessary frequencies. In this paper, the influence of contour error with different frequencies and amplitudes on the air film are analyzed using computational fluid dynamics (CFD) software, and the amplitude-frequency analysis as a function of the power spectral density (PSD) characteristic curve is used to study the filtering parameters of the measured data. After the figuring experiment using the filtering parameters obtained from the analysis, the average roundness of the shaft converged from 0.419 μm to 0.101 μm, and the cylindricity converged from 0.76 μm to 0.35 μm. The precision reached the level of manual grinding, which proves the rationality of the analysis using filtering parameters in a shaft's deterministic figuring.
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http://dx.doi.org/10.3390/ma13204561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602269PMC
October 2020

Jagged1-Notch1-deployed tumor perivascular niche promotes breast cancer stem cell phenotype through Zeb1.

Nat Commun 2020 10 12;11(1):5129. Epub 2020 Oct 12.

Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical College of Nankai University, 300071, Tianjin, China.

Zinc finger E-box binding homeobox 1 (Zeb1) has been demonstrated to participate in the acquisition of the properties of cancer stem cells (CSCs). However, it is largely unknown how signals from the tumor microenvironment (TME) contribute to aberrant Zeb1 expression. Here, we show that Zeb1 depletion suppresses stemness, colonization and the phenotypic plasticity of breast cancer. Moreover, we demonstrate that, with direct cell-cell contact, TME-derived endothelial cells provide the Notch ligand Jagged1 (Jag1) to neighboring breast CSCs, leading to Notch1-dependent upregulation of Zeb1. In turn, ectopic Zeb1 in tumor cells increases VEGFA production and reciprocally induces endothelial Jag1 in a paracrine manner. Depletion of Zeb1 disrupts this positive feedback loop in the tumor perivascular niche, which eventually lessens tumor initiation and progression in vivo and in vitro. In this work, we highlight that targeting the angiocrine Jag1-Notch1-Zeb1-VEGFA loop decreases breast cancer aggressiveness and thus enhances the efficacy of antiangiogenic therapy.
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http://dx.doi.org/10.1038/s41467-020-18860-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552407PMC
October 2020

Clinical value of circulating tumor cells for the diagnosis and prognosis of hepatocellular carcinoma (HCC): A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Oct;99(40):e22242

Department of Vascular Surgery, Affiliated Hospital of Jining Medical College, Ji'ning, Shandong, People's Republic of China.

Background: To evaluate the clinical value of circulating tumor cell (CTC) detection in peripheral blood for the diagnosis and prognosis of hepatocellular carcinoma (HCC).

Methods: Public databases were searched, and a meta-analysis was performed to determine the specificity, sensitivity, negative- likelihood ratio (NLR) and positive-likelihood ratio (PLR), and diagnostic odds ratio (dOR) of CTC detection for the diagnosis of HCC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed for the association of CTC detection with overall survival (OS) and HCC recurrence. The Meta-DiSc 1.4 and Review Manager 5.2 software programs were used for statistical analysis.

Results: Meta-analysis of 20 studies including 1191 patients showed that the specificity, sensitivity, NLR, PLR, and dOR of CTC testing for HCC diagnosis were 0.60 (95% CI = 0.57-0.63), 0.95 (95%CI = 0.93-0.96), 0.36 (95%CI = 0.28-0.48), 11.64 (95%CI = 5.85-23.14), and 38.94 (95%CI = 18.33-82.75), respectively. Meta-analysis of 18 studies including 1466 patients indicated that the OS of CTC-positive HCC patients was less than that of CTC-negative patients (HR = 2.31; 95% CI = 1.55-3.42; P < .01). Meta-analysis of 5 studies including 339 patients revealed that the presence of CTCs in peripheral blood significantly increased the risk of HCC recurrence (HR = 3.03, 95% CI = 1.89-4.86; P < .01).

Conclusion: CTCs in peripheral blood may be a useful marker for HCC diagnosis. In addition, the prognosis of CTC-positive HCC patients was significantly worse than that of CTC-negative HCC patients. Therefore, further studies are warranted to confirm the clinical potential of CTC detection in peripheral blood in patients with primary HCC.
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http://dx.doi.org/10.1097/MD.0000000000022242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535562PMC
October 2020

Maternal transmission of the epigenetic 'memory of winter cold' in Arabidopsis.

Nat Plants 2020 10 21;6(10):1211-1218. Epub 2020 Sep 21.

Shanghai Center for Plant Stress Biology & National Key Laboratory of Plant Molecular Genetics, Chinese Academy of Sciences Center for Excellence in Molecular Plant Sciences, Shanghai, China.

Some plants can 'remember' past environmental experience to become adapted to a given environment. For instance, after experiencing prolonged low-temperature exposure in winter (winter cold), vernalization-responsive plants remember past cold experience when temperature rises in spring, to acquire competence to flower at a later season favourable for seed production. In Arabidopsis thaliana, prolonged cold induces silencing of the potent floral repressor FLOWERING LOCUS C (FLC) by Polycomb group (PcG) chromatin modifiers. This Polycomb-repressed chromatin state is epigenetically maintained and thus 'memorized' in subsequent growth and development upon return to warmth. 'Memory of winter cold' has been viewed as being mitotically stable but meiotically unstable, and thus not to be transmitted intergenerationally. In general, whether and how chromatin-mediated environmental memories are transmitted across generations are unknown in plants. Here, we show that the cold-induced Polycomb-repressed chromatin state at FLC or memory of winter cold is maintained in the egg cell, that is meiotically stable in the process of female gamete formation, and provide evidence that this Polycomb-mediated memory is not maintained in the sperm cell. Moreover, we show that this cold memory is inherited maternally but not paternally to the zygote and early embryos. Our study demonstrates and further provides mechanistic insights into intergenerational transmission of chromatin state-mediated environmental memories in plants.
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http://dx.doi.org/10.1038/s41477-020-00774-0DOI Listing
October 2020
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