Publications by authors named "Yong Xu"

2,032 Publications

  • Page 1 of 1

Simvastatin increases circulating endothelial progenitor cells and inhibits the formation of intracranial aneurysms in rats with diet-induced hyperhomocysteinemia.

Neurosci Lett 2021 Jun 17:136072. Epub 2021 Jun 17.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Background And Purpose: Endothelial dysfunction triggers early pathological changes in artery, leading to the formation of intracranial aneurysm (ICA). Increase in plasma homocysteine (Hcy) impairs endothelium and endothelial progenitor cells (EPCs) are critical in repairing damaged endothelium. The aim of this study was to assess the impact of simvastatin on ICA formation in rats with hyperhomocysteinemia (HHcy).

Methods: ICAs were induced in Male Sprague-Dawley rats after surgical induction in the presence of HHcy induced by a high L-methionine diet with or without oral simvastatin treatment. The size and media thickness of ICAs were evaluated 2 months after aneurysm induction. EPCs and serum vascular endothelial grow factor (VEGF) were measured be flow cytometry and ELISA respectively. Plasma Hcy levels and expression of VEGF, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and MMP-9 in aneurysmal walls were examined and correlated with ICA formation.

Results: HHcy accelerates ICA formation and rats treated with simvastatin exhibited a significant increase in media thickness and a reduction in aneurysmal size. Simvastatin increased levels of circulating EPCs and decreased iNOS, MMP-2, MMP-9 and VEGF mRNA levels, while increased eNOS mRNA in aneurysmal tissue.

Conclusion: In a rat model, HHcy reduces circulating EPCs and accelerates ICA formation. Simvastatin treatment increases circulating EPCs and inhabits the formation of ICA. We have shown a close association among circulating EPCs, biochemical markers related to vascular remodeling and the formation of ICA.
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http://dx.doi.org/10.1016/j.neulet.2021.136072DOI Listing
June 2021

Abnormality of subcortical volume and resting functional connectivity in adolescents with early-onset and prodromal schizophrenia.

J Psychiatr Res 2021 Jun 4;140:282-288. Epub 2021 Jun 4.

Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Department of Mental Health, Shanxi Medical University, Taiyuan, China. Electronic address:

Objective: Studies have found that there may be qualitative changes in brain structure and function in adolescents with early-onset schizophrenia (EOS) and prodromal schizophrenia (PDS). However, the abnormal brain structure and function of adolescents with EOS and PDS have received little attention, and their underlying neural mechanisms are still unknown.

Methods: In this study, structural and resting-state functional magnetic resonance imaging (fMRI) were used to compare the subcortical volume and functional connectivity (FC) among EOS, PDS, and a control group. The Positive and Negative Symptom Scale (PNASS) questionnaire was used for clinical evaluation. Structural MRI was used to calculate cortical-based morphological volume and subcortical volume, and resting-state fMRI was used to analyze seed-based FC.

Results: Structural MRI analyses showed that the gray matter volume of the hippocampus in EOS was significantly smaller than that in the control group, and the gray matter volume of the hippocampus, amygdala, and caudate nucleus in PDS was significantly smaller than that in the control group. Additionally, correlation analysis showed that the gray matter volume of the hippocampus was significantly negatively correlated with the negative symptom score of PANSS in EOS. When the hippocampus was used as the seed, fMRI analysis found that the FC between the hippocampus and the posterior cingulate gyrus and precuneus in EOS was significantly weaker than that in the control group.

Conclusion: Our results indicate that the brain structure and function are abnormal in EOS and PDS, with abnormalities mainly concentrated in the limbic system, including the hippocampus, amygdala, caudate nucleus, cingulate gyrus, and precuneus. These findings provide a new direction for early intervention and improvement of the prognosis of schizophrenic patients.
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http://dx.doi.org/10.1016/j.jpsychires.2021.05.052DOI Listing
June 2021

Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist.

J Med Chem 2021 Jun 14. Epub 2021 Jun 14.

Guangdong Provincial Key Laboratory of Biocomputing, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.

Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound (designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC) value of 64 nM and showed excellent selectivity against other nuclear receptors. also potently suppressed cell proliferation, colony formation, and the expression of androgen receptor (AR)-regulated genes in AR-positive prostate cancer cell lines. In addition, demonstrated good metabolic stability and a pharmacokinetic property with reasonable oral bioavailability (32.41%) and moderate half-life ( = 4.98 h). Significantly, oral administration of compound achieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound may serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00763DOI Listing
June 2021

Deciphering an AgRP-serotoninergic neural circuit in distinct control of energy metabolism from feeding.

Nat Commun 2021 06 10;12(1):3525. Epub 2021 Jun 10.

USDA/ARS Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA.

Contrasting to the established role of the hypothalamic agouti-related protein (AgRP) neurons in feeding regulation, the neural circuit and signaling mechanisms by which they control energy expenditure remains unclear. Here, we report that energy expenditure is regulated by a subgroup of AgRP neurons that send non-collateral projections to neurons within the dorsal lateral part of dorsal raphe nucleus (dlDRN) expressing the melanocortin 4 receptor (MC4R), which in turn innervate nearby serotonergic (5-HT) neurons. Genetic manipulations reveal a bi-directional control of energy expenditure by this circuit without affecting food intake. Fiber photometry and electrophysiological results indicate that the thermo-sensing MC4R neurons integrate pre-synaptic AgRP signaling, thereby modulating the post-synaptic serotonergic pathway. Specifically, the MC4R signaling elicits profound, bi-directional, regulation of body weight mainly through sympathetic outflow that reprograms mitochondrial bioenergetics within brown and beige fat while feeding remains intact. Together, we suggest that this AgRP neural circuit plays a unique role in persistent control of energy expenditure and body weight, hinting next-generation therapeutic approaches for obesity and metabolic disorders.
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http://dx.doi.org/10.1038/s41467-021-23846-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192783PMC
June 2021

Structural-Disorder-Induced Second-Order Topological Insulators in Three Dimensions.

Phys Rev Lett 2021 May;126(20):206404

Center for Quantum Information, IIIS, Tsinghua University, Beijing 100084, People's Republic of China.

Higher-order topological insulators are established as topological crystalline insulators protected by crystalline symmetries. One celebrated example is the second-order topological insulator in three dimensions that hosts chiral hinge modes protected by crystalline symmetries. Since amorphous solids are ubiquitous, it is important to ask whether such a second-order topological insulator can exist in an amorphous system without any spatial order. Here, we predict the existence of a second-order topological insulating phase in an amorphous system without any crystalline symmetry. Such a topological phase manifests in the winding number of the quadrupole moment, the quantized longitudinal conductance, and the hinge states. Furthermore, in stark contrast to the viewpoint that structural disorder should be detrimental to the higher-order topological phase, we remarkably find that structural disorder can induce a second-order topological insulator from a topologically trivial phase in a regular geometry. We finally demonstrate the existence of a second-order topological phase in amorphous systems with time-reversal symmetry.
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http://dx.doi.org/10.1103/PhysRevLett.126.206404DOI Listing
May 2021

Learning Curve for Lymph Node Dissection Around the Recurrent Laryngeal Nerve in McKeown Minimally Invasive Esophagectomy.

Front Oncol 2021 20;11:654674. Epub 2021 May 20.

Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: Compared to open esophagectomy (OE), minimally invasive esophagectomy (MIE) is associated with lower morbidity and mortality. However, lymph node (LN) dissection around the recurrent laryngeal nerve (RLN) is still an important factor that affects the length of the learning curve of MIE. This study aims to evaluate the surgical outcomes of the first nearly 5-year period and explore the learning curve for LN dissection around the RLN in McKeown MIE by a new single surgical team.

Methods: A total of 285 consecutive patients who underwent McKeown MIE between March 2016 and September 2020 were included at our institution. According to the cumulative sum (CUSUM) analysis of LN dissection around the RLN, the patients were divided into three groups: exploration period, adjustment period, and stable period. We assessed the impact of surgical proficiency on postoperative outcomes and explored the learning curve for LN dissection around the RLN in McKeown MIE.

Results: The CUSUM graph showed that a point of upward inflection for LN dissection around the RLN was observed in 151 cases. After 151 cases, LNs around the right and left RLNs were dissected thoroughly compared to the exploration and adjustment period (P = 0.010 and P = 0.012, respectively), and the postoperative incidence of hoarseness significantly decreased from 11.1 to 1.5% (P<0.001).

Conclusions: Our study results revealed that not only are the LN, around the RLN, sufficiently dissected but also the incidence of hoarseness significantly decreased in the stable phase. Consequently, the learning curve length was approximately 151 cases for LN dissection around the RLN in McKeown MIE.
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http://dx.doi.org/10.3389/fonc.2021.654674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174657PMC
May 2021

Suppressing Dehydroisomerization Boosts n-Butane Dehydrogenation with High Butadiene Selectivity.

Chemistry 2021 Jun 5. Epub 2021 Jun 5.

Guangdong University of Technology, Materials and Energy, Guangzhou, 510006, Guangzhou, CHINA.

Butadiene (BD) is a critical raw material in chemical industry, which is conventionally produced from naphtha cracking. The fast-growing demand of BD and the limited oil reserve motivate chemists to develop alternative methods for BD production. Shale gas, which mainly consists of light alkanes, has been considered as cheap raw materials to replace oil for BD production via n -butane direct dehydrogenation ( n -BDH). However, the quest for highly-efficient catalysts for n -BDH is driven by the current drawback of low BD selectivity. Here, we demonstrate a strategy for boosting the selectivity of BD by suppressing dehydroisomerization, an inevitable step in the conventional n -BDH process which largely reduces the selectivity of BD. Detailed investigations show that the addition of alkali-earth metals (e.g., Mg and Ca) into Pt-Ga 2 O 3 /S10 catalysts increases Pt dispersity, suppresses coke deposition and dehydroisomerization, and thus leads to the significant increase of BD selectivity. The optimized catalyst displays an initial BD selectivity of 34.7% at a n -butane conversion of 82.1% at 625 o C, which outperforms the reported catalysts in literatures. This work not only provides efficient catalysts for BD production via n -BDH, but also promotes the researches on catalyst design in heterogeneous catalysis.
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http://dx.doi.org/10.1002/chem.202101087DOI Listing
June 2021

Expression level of PLAC1 in osteosarcoma patients and its regulatory effect on the development of osteosarcoma.

J BUON 2021 Mar-Apr;26(2):592-598

Department of Orthopaedics, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, China.

Purpose: To detect the plasma levels of PLAC1 in osteosarcoma patients, and its regulatory effect on cell proliferation and apoptosis of osteosarcoma.

Methods: Plasma levels of PLAC1 in osteosarcoma patients were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Receiver operating characteristics (ROC) and Kaplan-Meier curves were performed for assessing the diagnostic and prognostic potentials of PLAC1 in osteosarcoma, respectively. Moreover, the regulatory effects of PLAC1 on proliferative and apoptotic rates of osteosarcoma cells were determined through cell counting kit-8 (CCK-8) and flow cytometry, respectively.

Results: PLAC1 was highly expressed in plasma of osteosarcoma patients showing diagnostic and prognostic potentials. Overexpression of PLAC1 in U2-OS cells increased the proliferative rate but decreased the apoptotic rate, while knockdown of PLAC1 yielded the opposite results.

Conclusions: PLAC1 is upregulated in the plasma of osteosarcoma patients, serving as a diagnostic biomarker, and is unfavorable to the prognosis if this disease. PLAC1 promotes the development of osteosarcoma by stimulating cell proliferation and inhibiting apoptosis.
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June 2021

Applications of deep-learning approaches in horticultural research: a review.

Authors:
Biyun Yang Yong Xu

Hortic Res 2021 Jun 1;8(1):123. Epub 2021 Jun 1.

College of Mechanical and Electronic Engineering, Fujian Agriculture and Forestry University, 350002, Fuzhou, China.

Deep learning is known as a promising multifunctional tool for processing images and other big data. By assimilating large amounts of heterogeneous data, deep-learning technology provides reliable prediction results for complex and uncertain phenomena. Recently, it has been increasingly used by horticultural researchers to make sense of the large datasets produced during planting and postharvest processes. In this paper, we provided a brief introduction to deep-learning approaches and reviewed 71 recent research works in which deep-learning technologies were applied in the horticultural domain for variety recognition, yield estimation, quality detection, stress phenotyping detection, growth monitoring, and other tasks. We described in detail the application scenarios reported in the relevant literature, along with the applied models and frameworks, the used data, and the overall performance results. Finally, we discussed the current challenges and future trends of deep learning in horticultural research. The aim of this review is to assist researchers and provide guidance for them to fully understand the strengths and possible weaknesses when applying deep learning in horticultural sectors. We also hope that this review will encourage researchers to explore some significant examples of deep learning in horticultural science and will promote the advancement of intelligent horticulture.
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http://dx.doi.org/10.1038/s41438-021-00560-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167084PMC
June 2021

PCB118 Induces Inflammation of Islet Beta Cells via Activating ROS-NLRP3 Inflammasome Signaling.

Biomed Res Int 2021 17;2021:5522578. Epub 2021 May 17.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Sichuan Luzhou 646000, China.

Background: Diabetes mellitus is a clinical syndrome caused by genetic and environmental factors. Growing evidence suggests that exposure to environmental endocrine disruptors and activation of NLRP3 inflammasome signaling play a vital role in diabetes. However, it is unclear how PCB118, a common environmental endocrine disruptor, contributes to the incidence of diabetes, and its specific mechanism of action is unknown. In this study, we explored whether ROS-induced NLRP3 inflammasome priming and activation were related to PCB118 exposure in mouse islet -TC-6 cells and the mechanisms of diabetes.

Methods: Mouse islet -TC-6 cells were cultured with PCB118 as a stimulating factor and ROS inhibitor N-acetyl cysteine (NAC) as an intervention. Cellular toxicity due to PCB118 was detected using the Cell Counting Kit-8; ROS was measured using DCFH-DA; the expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1, and IL-1 protein were detected by western blot; and IL-6, IL-18, and C-C chemokine ligand 2 (CCL-2) were measured by ELISA.

Results: PCB118 caused significant toxicity to the cells when the stimulation concentration was equal to or greater than 80 nmol/L at 72 hours ( < 0.05) and increased the levels of ROS, NLRP3, caspase-1, IL-1, IL-6, IL-18, and CCL-2 ( < 0.05); the expressions of procaspase-1 and pro-IL-1 were downregulated in a dose-dependent manner after PCB118 exposure ( < 0.05), which was prevented by pretreatment with NAC ( < 0.05).

Conclusions: PCB118 can activate NLRP3 inflammasome signaling in islet beta cells via the oxidative stress pathway and cause inflammation in islet beta cells. It suggests that environmental endocrine disruptors play an important role in the inflammation of islet beta cells and may contribute to the development of diabetes through NLRP3 inflammatory signaling.
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http://dx.doi.org/10.1155/2021/5522578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147541PMC
May 2021

LncRNA OIP5-AS1 inhibits ferroptosis in prostate cancer with long-term cadmium exposure through miR-128-3p/SLC7A11 signaling.

Ecotoxicol Environ Saf 2021 Sep 26;220:112376. Epub 2021 May 26.

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, PR China; The School of Medicine, Nankai University, Tianjin 300071, PR China. Electronic address:

Previous studies suggest that cadmium (Cd) is one of the causative factors of prostate cancer (PCa), but the effect of chronic Cd exposure on PCa progression remains unclear. Besides, whether long noncoding RNAs (lncRNAs) are involved in the regulation of prolonged exposure to Cd in PCa needs to be elucidated. In the present study, we found that the serum concentration of Cd in PCa patients was positively correlated with the Gleason score and tumor-node-metastasis (TNM) classification. To simulate chronic Cd exposure in PCa, we subjected PC3 and DU145 cells to long-term, low-dose Cd exposure and further examined tumor behavior. Functional studies identified that chronic Cd exposure promoted cell growth and ferroptosis resistance in vitro and in vivo. Furthermore, we found that lncRNA OIP5-AS1 expression was greatly elevated in PC3 and DU145 cells upon chronic Cd exposure. Dysregulation of OIP5-AS1 expression mediated cell growth and Cd-induced ferroptosis. Mechanistically, we demonstrated that OIP5-AS1 served as an endogenous sponge of miR-128-3p to regulate the expression of SLC7A11, a surrogate marker of ferroptosis. Moreover, miR-128-3p decreased cell viability by enhancing ferroptosis. Taken together, our data indicate that lncRNA OIP5-AS1 promotes PCa progression and ferroptosis resistance through miR-128-3p/SLC7A11 signaling.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112376DOI Listing
September 2021

Selective dispersion of neutral nanoplates and the interfacial structure of copolymers based on coarse-grained molecular dynamics simulations.

Soft Matter 2021 Jun 28;17(24):5950-5959. Epub 2021 May 28.

College of Materials and Metallurgy, Guizhou University, Guiyang 550025, China. and National Engineering Research Center for Compounding and Modification of Polymer Materials, Guiyang 550058, China.

The selective dispersion of neutral nanoplates (NNP) and the control of the interfacial structure of copolymers are challenging. In this work, we employ coarse-grained molecular dynamics (CGMD) to investigate the dispersion of NNP and the interfacial structure. The introduction of NNP significantly changes the interfacial structure and formation mechanism of diblock copolymers (DBCP), which is related to the matrix phase, distribution, composition, and length of two different chain segments (A and B) in AB-DBCP. The phase-weak groups that have a poor interaction with NNP will stack easily, whereas the stacking degree for the phase-rich groups that have a strong interaction with NNP decreases due to the addition of NNP. The interaction between two phases will be enhanced, which is favorable for the formation of a random network structure. Due to the strong interaction of the phase-rich groups with NNP, the NNP change the accumulation types of phase-weak groups and enhances the combination of two chain segments in favor of the formation of a cylindrical micelle-like structure. The transmission electron microscopy (TEM) images show that layered double hydroxide (LDH) orientationally distributes in the acrylic acid chain segments in ethylene acrylic acid (EAA) random copolymers, which is in agreement with the theoretical simulation results. This proves that the selective dispersion of LDH in copolymers affects their interfacial structure.
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http://dx.doi.org/10.1039/d1sm00352fDOI Listing
June 2021

A hindbrain dopaminergic neural circuit prevents weight gain by reinforcing food satiation.

Sci Adv 2021 May 26;7(22). Epub 2021 May 26.

USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

The neural circuitry mechanism that underlies dopaminergic (DA) control of innate feeding behavior is largely uncharacterized. Here, we identified a subpopulation of DA neurons situated in the caudal ventral tegmental area (cVTA) directly innervating DRD1-expressing neurons within the lateral parabrachial nucleus (LPBN). This neural circuit potently suppresses food intake via enhanced satiation response. Notably, this cohort of DA neurons is activated immediately before the cessation of each feeding bout. Acute inhibition of these DA neurons before bout termination substantially suppresses satiety and prolongs the consummatory feeding. Activation of postsynaptic DRD1 neurons inhibits feeding, whereas genetic deletion of within the LPBN causes robust increase in food intake and subsequent weight gain. Furthermore, the DRD1 signaling manifests the central mechanism in methylphenidate-induced hypophagia. In conclusion, our study illuminates a hindbrain DAergic circuit that controls feeding through dynamic regulation in satiety response and meal structure.
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http://dx.doi.org/10.1126/sciadv.abf8719DOI Listing
May 2021

Mechanisms of the Effects of Parental Emotional Warmth on Extraversion in Children and Adolescents.

Neuroscience 2021 May 24;467:134-141. Epub 2021 May 24.

Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China; Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorder, First Hospital of Shanxi Medical University, Taiyuan, China; MDT Center for Cognitive Impairment and Sleep Disorders, First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address:

The purpose of this study is to probe into the influence mechanism of parental emotional warmth (PEW) on extraversion for children and adolescents, as well as the moderating and mediating role of brain functional activity. Thirty-two children and adolescents underwent functional magnetic resonance imaging (fMRI) scans and completed Egna Minnen av Barndoms Uppfostran (EMBU) and Eysenck Personality Questionnaire (EPQ). Small-worldness (SW) of brain networks, fractional amplitude of low-frequency fluctuations (fALFF), and region-of-interest to region-of-interest (ROI-ROI) functional connectivity were calculated to study intrinsic neuronal activity. We found that PEW had a positive direct effect on extraversion, and all participants in the current study showed an efficient small-world structure. The positive association between PEW and extraversion was mediated by SW. Furthermore, the fALFF and extraversion were significantly and negatively correlated in the right precuneus and dorsolateral superior frontal gyrus. The mediating effect of SW was moderated by the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. The indirect effect was significant with lower level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus. These findings indicate that SW of brain networks may be a key factor that accounts for the positive association between PEW and extraversion in children and adolescents and the level of the functional connectivity between the right precuneus and the right dorsolateral superior frontal gyrus could moderate the relationship.
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http://dx.doi.org/10.1016/j.neuroscience.2021.05.021DOI Listing
May 2021

Multi-View 3D Shape Recognition via Correspondence-Aware Deep Learning.

IEEE Trans Image Process 2021 2;30:5299-5312. Epub 2021 Jun 2.

In recent years, multi-view learning has emerged as a promising approach for 3D shape recognition, which identifies a 3D shape based on its 2D views taken from different viewpoints. Usually, the correspondences inside a view or across different views encode the spatial arrangement of object parts and the symmetry of the object, which provide useful geometric cues for recognition. However, such view correspondences have not been explicitly and fully exploited in existing work. In this paper, we propose a correspondence-aware representation (CAR) module, which explicitly finds potential intra-view correspondences and cross-view correspondences via k NN search in semantic space and then aggregates the shape features from the correspondences via learned transforms. Particularly, the spatial relations of correspondences in terms of their viewpoint positions and intra-view locations are taken into account for learning correspondence-aware features. Incorporating the CAR module into a ResNet-18 backbone, we propose an effective deep model called CAR-Net for 3D shape classification and retrieval. Extensive experiments have demonstrated the effectiveness of the CAR module as well as the excellent performance of the CAR-Net.
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http://dx.doi.org/10.1109/TIP.2021.3082310DOI Listing
June 2021

Barbadin potentiates long-term effects of lorcaserin on POMC neurons and weight loss.

J Neurosci 2021 May 24. Epub 2021 May 24.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030

Obesity is a serious global health problem due to its increasing prevalence and comorbidities, but its treatments are limited. The serotonin 2C receptor (5-HTR), a G protein-coupled receptor, activates pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus (ARH) to reduce appetite and weight gain. However, several 5-HT analogs targeting this receptor, e.g. lorcaserin, suffer from diminished efficacy to reduce weight after prolonged administration. Here we show that barbadin, a novel β-arrestin/β2-adaptin inhibitor, can prevent 5-HTR internalization in cells and potentiate long-term effects of lorcaserin to reduce appetite and body weight in male mice. Mechanistically, we demonstrate that barbadin co-treatment can effectively maintain the sensitivity of the 5-HTR in POMC neurons, despite prolonged lorcaserin exposure, thereby allowing these neurons to be activated through opening the transient receptor potential cation channels. Thus, our results prove the concept that inhibition of 5-HTR desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin or other 5-HTR agonists, and also provide an intellectual framework to develop effective long-term management of weight by targeting 5-HTR desensitization.By demonstrating that the combination of barbadin with a GPCR agonist can provide prolonged weight-lowering benefits in a preclinical setting, our work should call for additional efforts to validate barbadin as a safe and effective medicine or to use barbadin as a lead compound to develop more suitable compounds for obesity treatment. These results prove the concept that inhibition of 5-HTR desensitization can be a valid strategy to improve the long-term weight loss effects of lorcaserin or other 5-HTR agonists. Since GPCRs represent a major category as therapeutic targets for various human diseases and desensitization of GPCRs is a common issue, our work may provide a conceptual framework to enhance effects of a broad range of GPCR medicines.
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http://dx.doi.org/10.1523/JNEUROSCI.3210-20.2021DOI Listing
May 2021

Could the EQ-5D-3L predict all-cause mortality in older Chinese? Evidence from a 5-year longitudinal study in eastern China.

Qual Life Res 2021 May 24. Epub 2021 May 24.

School of Public Health, Fudan University, 130 Dong An Road, Shanghai, 200032, China.

Purpose: To assess the ability of the 3-level EQ-5D (i.e., EQ-5D-3L) in predicting all-cause mortality in older Chinese adults.

Methods: The data were from a 5-year longitudinal study, Weitang Geriatric Diseases Study, including 4579 community-dwelling older people in eastern China, with the mean age of 72.5 years at baseline and female being 52.0%. Three multivariable logistic regression models were adopted to assess the associations of the baseline EQ-5D data [i.e., the EQ-5D problems, EQ-5D-3L index score, and EQ-5D visual analog scale (VAS) score] with the 5-year all-cause mortality, adjusting for socio-demographic characteristics, and subsequently, health conditions and lifestyle habits.

Results: A total of 183 participants died over the 5-year study period. A larger proportion of the dead reported problems in physical dimensions (i.e., including three dimensions: mobility, self-care, and usual activities, p < 0.05 for all). The mean EQ-5D index score (0.928) and EQ-VAS score (79.7) of the living were higher than those of the dead (0.915 and 73.2, p < 0.05 for both). In multivariable logistic analyses, the EQ-5D health problems in the physical-related dimensions [odds ratio (OR) 2.16, p < 0.05] and the EQ-VAS score (OR: 0.97, p < 0.001) were associated with the 5-year all-cause mortality when adjusting for socio-demographic characteristics, health conditions, and lifestyle habits.

Conclusions: It appears that the EQ-5D-3L could predict mortality in general older Chinese, which could be used to detect high-risk older individuals in China.
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http://dx.doi.org/10.1007/s11136-021-02883-5DOI Listing
May 2021

e-Graphene: A Computational Platform for the Prediction of Graphene-Based Drug Delivery System by Quantum Genetic Algorithm and Cascade Protocol.

Front Chem 2021 7;9:664355. Epub 2021 May 7.

School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

Graphene, as a novel category of carbon nanomaterials, has attracted a great attention in the field of drug delivery. Due to its large dual surface area, graphene can efficiently load drug molecules with high capacity non-covalent interaction without chemical modification of the drugs. Hence, it ignites prevalent interests in developing a new graphene/graphene oxide (GO)-based drug delivery system (GDDS). However, current design of GDDS primarily depends on the prior experimental experience with the trial-and-error method. Thus, it is more appealing to theoretically predict possible GDDS candidates before experiments. Toward this end, we propose to fuse quantum genetic algorithm (QGA) and quantum mechanics (QM)/semi-empirical quantum mechanics (SQM)/force field (FF) to globally search the optimal binding interaction between the graphene/GO and drug in a given GDDS and develop a free computational platform "e-Graphene" to automatically predict/screen potential GDDS candidates. To make this platform more pragmatic for the rapid yet relatively accurate prediction, we further propose a cascade protocol firstly conducting a fast QGA/FF calculation with fine QGA parameters and automatically passing the best chromosomes from QGA/FF to initialize a higher level QGA/SQM or QGA/QM calculation with coarse QGA parameters (e.g., small populations and short evolution generations). By harnessing this platform and protocol, systematic tests on a typical GDDS containing an anticancer drug SN38 illustrate that high fabrication rates of hydroxyl, epoxy, and carboxyl groups on a pristine graphene model will compromise the stability of GDDS, implying that an appropriate functionalization rate is crucial for the delicate balance between the stability and solubility/biocompatibility of GDDS. Moreover, automatic GDDS screen in the DrugBank database is performed and elicits four potential GDDS candidates with enhanced stability than the commonly tested GDDS containing SN38 from the computational point of view. We hope that this work can provide a useful program and protocol for experimental scientists to rationally design/screen promising GDDS candidates prior to experimental tests.
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http://dx.doi.org/10.3389/fchem.2021.664355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138207PMC
May 2021

Facial Emotion Recognition in Schizophrenia.

Front Psychiatry 2021 4;12:633717. Epub 2021 May 4.

Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, China.

Deficits in facial emotion recognition are one of the most common cognitive impairments, and they have been extensively studied in various psychiatric disorders, especially in schizophrenia. However, there is still a lack of conclusive evidence about the factors associated with schizophrenia and impairment at each stage of the disease, which poses a challenge to the clinical management of patients. Based on this, we summarize facial emotion cognition among patients with schizophrenia, introduce the internationally recognized Bruce-Young face recognition model, and review the behavioral and event-related potential studies on the recognition of emotions at each stage of the face recognition process, including suggestions for the future direction of clinical research to explore the underlying mechanisms of schizophrenia.
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http://dx.doi.org/10.3389/fpsyt.2021.633717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129182PMC
May 2021

Metformin and Fibrosis: A Review of Existing Evidence and Mechanisms.

J Diabetes Res 2021 29;2021:6673525. Epub 2021 Apr 29.

Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 646000.

Fibrosis is a physiological response to organ injury and is characterized by the excessive deposition of connective tissue components in an organ, which results in the disruption of physiological architecture and organ remodeling, ultimately leading to organ failure and death. Fibrosis in the lung, kidney, and liver accounts for a substantial proportion of the global burden of disability and mortality. To date, there are no effective therapeutic strategies for controlling fibrosis. A class of metabolically targeted chemicals, such as adenosine monophosphate-activated protein kinase (AMPK) activators and peroxisome proliferator-activated receptor (PPAR) agonists, shows strong potential in fighting fibrosis. Metformin, which is a potent AMPK activator and is the only recommended first-line drug for the treatment of type 2 diabetes, has emerged as a promising method of fibrosis reduction or reversion. In this review, we first summarize the key experimental and clinical studies that have specifically investigated the effects of metformin on organ fibrosis. Then, we discuss the mechanisms involved in mediating the antifibrotic effects of metformin in depth.
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http://dx.doi.org/10.1155/2021/6673525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102119PMC
April 2021

Cell lineage tracing links ERα loss in Erbb2-positive breast cancers to the arising of a highly aggressive breast cancer subtype.

Proc Natl Acad Sci U S A 2021 May;118(21)

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030;

HER2-positive (HER2) breast cancers (BrCs) contain approximately equal numbers of ERαHER2 and ERαHER2 cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERαHER2 BrCs could lose ERα to become ERαHER2 BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαRFP-T mice that produce an RFP-marked ERα mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERαRFPErbb2 and ERαRFPErbb2 MGECs. Early hyperplasia developed mostly from ERαRFPErbb2 cells and ERαRFPErbb2 cells in these lesions were rare. The subsequently developed ductal carcinomas in situ had 64% slow-proliferating ERαRFPErbb2 cells, 15% fast-proliferating ERαRFPErbb2 cells derived from ERαRFPErbb2 cells, and 20% fast-proliferating ERαRFPErbb2 cells. The advanced tumors had mostly ERαRFPErbb2 and ERαRFPErbb2 cells and only a very small population of ERαRFPErbb2 cells. In ERαRFPErbb2 cells, GATA3 and FoxA1 decreased expression and ERα promoter regions became methylated, consistent with the loss of ERα expression. Lung metastases consisted of mostly ERαRFPErbb2 cells, a few ERαRFPErbb2 cells, and no ERαRFPErbb2 cells. The high metastatic capacity of ERαRFPErbb2 cells was associated with ERK1/2 activation. These results show that the slow-proliferating, nonmetastatic ERαRFPErbb2 cells progressively lose ERα during tumorigenesis to become fast-proliferating, highly metastatic ERαRFPErbb2 cells. The ERαErbb2 BrCs with an ERα origin are more aggressive than those ERαErbb2 BrCs with an ERα origin, and thus, they should be distinguished and treated differently in the future.
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http://dx.doi.org/10.1073/pnas.2100673118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166171PMC
May 2021

Chromium (VI) promotes EMT by regulating FLNA in BLCA.

Environ Toxicol 2021 May 12. Epub 2021 May 12.

Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Hexavalent chromium (Cr (VI)), which is a recognized human carcinogen, is widely used in industrial production of raw materials. Evidence verifies that environmental contaminants in the urine can induce malignant transformation in the urinary bladder tract, and our data indicate that Cr (VI) could promote the proliferation and migration and inhibit the apoptosis of bladder cancer (BLCA) cells. However, the molecular mechanism remains ambiguous. We find that Filamin A (FLNA) is overexpressed in BLCA, and Cr (VI) promotes epithelial-to-mesenchymal transition by regulating FLNA in BLCA. Thus, inhibiting the expression of FLNA may be a prospective method for limiting the BLCA progression caused by Cr (VI) exposure.
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http://dx.doi.org/10.1002/tox.23165DOI Listing
May 2021

A neural basis for brain leptin action on reducing type 1 diabetic hyperglycemia.

Nat Commun 2021 05 11;12(1):2662. Epub 2021 May 11.

Brown Foundation of Molecular Medicine for the Prevention of Human Diseases of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Central leptin action rescues type 1 diabetic (T1D) hyperglycemia; however, the underlying mechanism and the identity of mediating neurons remain elusive. Here, we show that leptin receptor (LepR)-expressing neurons in arcuate (LepR) are selectively activated in T1D. Activation of LepR neurons, Arc GABAergic (GABA) neurons, or arcuate AgRP neurons, is able to reverse the leptin's rescuing effect. Conversely, inhibition of GABA neurons, but not AgRP neurons, produces leptin-mimicking rescuing effects. Further, AgRP neuron function is not required for T1D hyperglycemia or leptin's rescuing effects. Finally, T1D LepR neurons show defective nutrient sensing and signs of cellular energy deprivation, which are both restored by leptin, whereas nutrient deprivation reverses the leptin action. Our results identify aberrant activation of LepR neurons owing to energy deprivation as the neural basis for T1D hyperglycemia and that leptin action is mediated by inhibiting LepR neurons through reversing energy deprivation.
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http://dx.doi.org/10.1038/s41467-021-22940-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113586PMC
May 2021

Rap1 in the VMH regulates glucose homeostasis.

JCI Insight 2021 Jun 8;6(11). Epub 2021 Jun 8.

Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

The hypothalamus is a critical regulator of glucose metabolism and is capable of correcting diabetes conditions independently of an effect on energy balance. The small GTPase Rap1 in the forebrain is implicated in high-fat diet-induced (HFD-induced) obesity and glucose imbalance. Here, we report that increasing Rap1 activity selectively in the medial hypothalamus elevated blood glucose without increasing the body weight of HFD-fed mice. In contrast, decreasing hypothalamic Rap1 activity protected mice from diet-induced hyperglycemia but did not prevent weight gain. The remarkable glycemic effect of Rap1 was reproduced when Rap1 was specifically deleted in steroidogenic factor-1-positive (SF-1-positive) neurons in the ventromedial hypothalamic nucleus (VMH) known to regulate glucose metabolism. While having no effect on body weight regardless of sex, diet, and age, Rap1 deficiency in the VMH SF1 neurons markedly lowered blood glucose and insulin levels, improved glucose and insulin tolerance, and protected mice against HFD-induced neural leptin resistance and peripheral insulin resistance at the cellular and whole-body levels. Last, acute pharmacological inhibition of brain exchange protein directly activated by cAMP 2, a direct activator of Rap1, corrected glucose imbalance in obese mouse models. Our findings uncover the primary role of VMH Rap1 in glycemic control and implicate Rap1 signaling as a potential target for therapeutic intervention in diabetes.
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http://dx.doi.org/10.1172/jci.insight.142545DOI Listing
June 2021

Light quality and quantity affect graft union formation of tomato plants.

Sci Rep 2021 May 10;11(1):9870. Epub 2021 May 10.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.

It is already known that there are many factors responsible for the successful formation of a graft union. However, the role of light has been little studied. In an anatomical study, Scanning Electronic Microscope (SEM) was used to explore the effects of different light-emitting diodes (LEDs) on graft union formation in grafted tomato. In addition, the expression genes related to Auxin hormone signaling pathway (SAUR67, AUX1, ARF30, and LAX3) was investigated. The obtained results showed that the concrescence process occurred faster under R7:B3 light conditions, as compared to blue (B) and white fluorescent (WFL) lights. Red light application caused a delay in the vascular tissue differentiation, which may lead to callus development on both sides, causing junctional failure and resulting in ineffective graft junctional arrangement. The expression of genes related to Auxin hormone significantly increased by R7:B3 application. We suggest that LED spectra affects the graft development of tomato plants and can improve the performance of grafted tomato seedlings.
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http://dx.doi.org/10.1038/s41598-021-88971-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110817PMC
May 2021

Innate Immunity in Diabetic Wound Healing: Focus on the Mastermind Hidden in Chronic Inflammatory.

Front Pharmacol 2021 21;12:653940. Epub 2021 Apr 21.

Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, China.

A growing body of evidence suggests that the interaction between immune and metabolic responses is essential for maintaining tissue and organ homeostasis. These interacting disorders contribute to the development of chronic diseases associated with immune-aging such as diabetes, obesity, atherosclerosis, and nonalcoholic fatty liver disease. In Diabetic wound (DW), innate immune cells respond to the Pathogen-associated molecular patterns (PAMAs) and/or Damage-associated molecular patterns (DAMPs), changes from resting to an active phenotype, and play an important role in the triggering and maintenance of inflammation. Furthermore, the abnormal activation of innate immune pathways secondary to immune-aging also plays a key role in DW healing. Here, we review studies of innate immune cellular molecular events that identify metabolic disorders in the local microenvironment of DW and provide a historical perspective. At the same time, we describe some of the recent progress, such as TLR receptor-mediated intracellular signaling pathways that lead to the activation of NF-κB and the production of various pro-inflammatory mediators, NLRP3 inflammatory via pyroptosis, induction of IL-1β and IL-18, cGAS-STING responds to mitochondrial injury and endoplasmic reticulum stress, links sensing of metabolic stress to activation of pro-inflammatory cascades. Besides, JAK-STAT is also involved in DW healing by mediating the action of various innate immune effectors. Finally, we discuss the great potential of targeting these innate immune pathways and reprogramming innate immune cell phenotypes in DW therapy.
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http://dx.doi.org/10.3389/fphar.2021.653940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097165PMC
April 2021

iCircDA-LTR: identification of circRNA-disease associations based on Learning to Rank.

Bioinformatics 2021 May 8. Epub 2021 May 8.

School of Computer Science and Technology, Harbin Institute of Technology, Shenzhen, Guangdong 518055, China.

Motivation: Due to the inherent stability and close relationship with the progression of diseases, circRNAs are serving as important biomarkers and drug targets. Efficient predictors for identifying circRNA-disease associations are highly required. The existing predictors consider circRNA-disease association prediction as a classification task or a recommendation problem, failing to capture the ranking information among the associations and detect the diseases associated with new circRNAs. However, more and more circRNAs are discovered. Identification of the diseases associated with these new circRNAs remains a challenging task.

Results: In this study, we proposed a new predictor called iCricDA-LTR for circRNA-disease association prediction. Different from any existing predictor, iCricDA-LTR employed a ranking framework to model the global ranking associations among the query circRNAs and the diseases. The Learning to Rank (LTR) algorithm was employed to rank the associations based on various predictors and features in a supervised manner. The experimental results on two independent test datasets showed that iCircDA-LTR outperformed the other competing methods, especially for predicting the diseases associated with new circRNAs. As a result, iCircDA-LTR is more suitable for the real world applications.

Availability: For the convenience of researchers to detect new circRNA-disease associations. The web server of iCircDA-LTR was established and freely available at http://bliulab.net/iCircDA-LTR/.
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http://dx.doi.org/10.1093/bioinformatics/btab334DOI Listing
May 2021

Effects of light spectrum on morpho-physiological traits of grafted tomato seedlings.

PLoS One 2021 7;16(5):e0250210. Epub 2021 May 7.

College of Horticulture, Fujian Agriculture and Forestry University, Fuzhou, China.

It is already known that there are many factors responsible for the successful grafting process in plants, including light intensity. However, the influence of the spectrum of light-emitting diodes (LEDs) on this process has almost never been tested. During the pre-grafting process tomato seedlings grew for 30 days under 100 μmol m-2 s-1 of mixed LEDs (red 70%+ blue 30%). During the post-grafting period, seedlings grew for 20 days under the same light intensity but the lightening source was either red LED, mixed LEDs (red 70% + blue 30%), blue LED or white fluorescent lamps. This was done to determine which light source(s) could better improve seedling quality and increase grafting success. Our results showed that application of red and blue light mixture (R7:B3) caused significant increase in total leaf area, dry weight (total, shoot and root), total chlorophyll/carotenoid ratio, soluble protein and sugar content. Moreover, this light treatment maintained better photosynthetic performance i.e. more effective quantum yield of PSII photochemistry Y(II), better photochemical quenching (qP), and higher electron transport rate (ETR). This can be partially explained by the observed upregulation of gene expression levels of PsaA and PsbA and the parallel protein expression levels. This in turn could lead to better functioning of the photosynthetic apparatus of tomato seedlings and then to faster production of photoassimilate ready to be translocated to various tissues and organs, including those most in need, i.e., involved in the formation of the graft union.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250210PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104444PMC
May 2021

Genome sequencing sheds light on the contribution of structural variants to Brassica oleracea diversification.

BMC Biol 2021 May 5;19(1):93. Epub 2021 May 5.

National Engineering Research Center for Vegetables, Beijing Academy of Agriculture and Forestry Sciences, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (North China), Beijing Key Laboratory of Vegetable Germplasm Improvement, Beijing, 100097, China.

Background: Brassica oleracea includes several morphologically diverse, economically important vegetable crops, such as the cauliflower and cabbage. However, genetic variants, especially large structural variants (SVs), that underlie the extreme morphological diversity of B. oleracea remain largely unexplored.

Results: Here we present high-quality chromosome-scale genome assemblies for two B. oleracea morphotypes, cauliflower and cabbage. Direct comparison of these two assemblies identifies ~ 120 K high-confidence SVs. Population analysis of 271 B. oleracea accessions using these SVs clearly separates different morphotypes, suggesting the association of SVs with B. oleracea intraspecific divergence. Genes affected by SVs selected between cauliflower and cabbage are enriched with functions related to response to stress and stimulus and meristem and flower development. Furthermore, genes affected by selected SVs and involved in the switch from vegetative to generative growth that defines curd initiation, inflorescence meristem proliferation for curd formation, maintenance and enlargement, are identified, providing insights into the regulatory network of curd development.

Conclusions: This study reveals the important roles of SVs in diversification of different morphotypes of B. oleracea, and the newly assembled genomes and the SVs provide rich resources for future research and breeding.
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http://dx.doi.org/10.1186/s12915-021-01031-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097969PMC
May 2021

Three coordination polymers built by quaternary-ammonium-modified isophthalic acid.

Acta Crystallogr C Struct Chem 2021 May 9;77(Pt 5):221-226. Epub 2021 Apr 9.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing, Jiangsu Province 211800, People's Republic of China.

Three coordination polymers based on quaternary-ammonium-modified isophthalic acid, namely, catena-poly[[[aqua-μ-bromido-di-μ-hydroxido-methanoldinitratotetracopper(II)]-bis{μ-5-[2-(tripropylazaniumyl)ethoxy]benzene-1,3-dicarboxylato}] nitrate], {[CuBr(CHNO)(NO)(OH)(CHO)(HO)]NO}, 1, poly[μ-bromido-μ-bromido-bromido-μ-hydroxido-{μ-5-[2-(tripropylazaniumyl)ethoxy]benzene-1,3-dicarboxylato}tricopper(II)], [CuBr(CHNO)(OH)], 2, and poly[bromido{μ-5-[2-(tripropylazaniumyl)ethoxy]benzene-1,3-dicarboxylato}zinc(II)], [ZnBr(CHNO)], 3, were obtained by solvothermal reactions. Coordination polymer (CP) 1 contains tetranuclear Cu units, in which the four Cu atoms are linked by two μ-OH groups into a Cu(OH) cluster, which are in turn linked by 5-[2-(tripropylazaniumyl)ethoxy]benzene-1,3-dicarboxylate (cpa) ligands into a chain structure. CP 2 also contains a tetranuclear Cu(OH) cluster and these are linked with CuBr units into chains. The chains are then connected by cpa ligands into a two-dimensional layered structure. CP 3 contains a two-dimensional layer structure built by binuclear Zn units and cpa ligands. The Br counter-anions of the quaternary ammonium groups all take part in the construction of the polymeric networks.
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http://dx.doi.org/10.1107/S2053229621003296DOI Listing
May 2021