Publications by authors named "Wu Zhou"

405 Publications

Chain-Structure Echo State Network With Stochastic Optimization: Methodology and Application.

IEEE Trans Neural Netw Learn Syst 2021 Jul 29;PP. Epub 2021 Jul 29.

In this article, a chain-structure echo state network (CESN) with stacked subnetwork modules is newly proposed as a new kind of deep recurrent neural network for multivariate time series prediction. Motivated by the philosophy of ``divide and conquer,'' the related input vectors are first divided into clusters, and the final output results of CESN are then integrated by successively learning the predicted values of each clustered variable. Network structure, mathematical model, training mechanism, and stability analysis are, respectively, studied for the proposed CESN. In the training stage, least-squares regression is first used to pretrain the output weights in a module-by-module way, and stochastic local search (SLS) is developed to fine-tune network weights toward global optima. The loss function of CESN can be effectively reduced by SLS. To avoid overfitting, the optimization process is stopped when the validation error starts to increase. Finally, SLS-CESN is evaluated in chaos prediction benchmarks and real applications. Four different examples are given to verify the effectiveness and robustness of CESN and SLS-CESN.
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http://dx.doi.org/10.1109/TNNLS.2021.3098866DOI Listing
July 2021

Synergizing metal-support interactions and spatial confinement boosts dynamics of atomic nickel for hydrogenations.

Nat Nanotechnol 2021 Jul 26. Epub 2021 Jul 26.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemical Physics, Key Laboratory of Surface and Interface Chemistry and Energy Catalysis of Anhui Higher Education Institutes, CAS Center for Excellence in Nanoscience, University of Science and Technology of China, Hefei, China.

Atomically dispersed metal catalysts maximize atom efficiency and display unique catalytic properties compared with regular metal nanoparticles. However, achieving high reactivity while preserving high stability at appreciable loadings remains challenging. Here we solve the challenge by synergizing metal-support interactions and spatial confinement, which enables the fabrication of highly loaded atomic nickel (3.1 wt%) along with dense atomic copper grippers (8.1 wt%) on a graphitic carbon nitride support. For the semi-hydrogenation of acetylene in excess ethylene, the fabricated catalyst shows extraordinary catalytic performance in terms of activity, selectivity and stability-far superior to supported atomic nickel alone in the absence of a synergizing effect. Comprehensive characterization and theoretical calculations reveal that the active nickel site confined in two stable hydroxylated copper grippers dynamically changes by breaking the interfacial nickel-support bonds on reactant adsorption and making these bonds on product desorption. Such a dynamic effect confers high catalytic performance, providing an avenue to rationally design efficient, stable and highly loaded, yet atomically dispersed, catalysts.
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http://dx.doi.org/10.1038/s41565-021-00951-yDOI Listing
July 2021

A novel ESIPT fluorescent probe derived from 3-hydroxyphthalimide for hydrazine detection in aqueous solution and living cells.

Anal Bioanal Chem 2021 Jul 21. Epub 2021 Jul 21.

School of Life Science, Hubei Normal University, Huangshi, 435002, Hubei, China.

Hydrazine is a highly toxic and flammable liquid that can damage human liver, kidney, and central nervous system. Therefore, it is valuable to seek a quick and sensitive method for hydrazine detection in environmental and biological science. Herein, a new fluorescent probe derived from 3-hydroxyphthalimide was synthesized. This probe can rapidly and selectively detect hydrazine with a low detection limit of 4.3 × 10 M. The recognition principle is based on hydrazine-induced acetyl deprotection and excited-state intramolecular proton transfer (ESIPT) process. Moreover, test paper and fluorescence image experiments showed that this probe had potential to monitor hydrazine in the environment and living cells.
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http://dx.doi.org/10.1007/s00216-021-03530-1DOI Listing
July 2021

Potential correlation between depression-like behavior and the MAPK pathway in the rat hippocampus following spinal cord injury.

World Neurosurg 2021 Jul 13. Epub 2021 Jul 13.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi,People's Republic of China. Electronic address:

Depression induced by spinal cord injury (SCI) has been demonstrated in clinical and experimental studies; it significantly impacts patients' lives and may be associated with changes in the hippocampus. However, the biological mechanisms underlying depression after SCI are unknown. The mitogen-activated protein kinase (MAPK) signaling pathway participates in the potential mechanisms of depression; however, it is unknown whether the pathway plays a role in SCI-induced depression. We applied an animal model of depression induced by SCI, established using an aneurysm clip, to determine whether MAPK activation in the hippocampus is associated with depression-like behavior. The results showed that SCI led to depression-like behavior such as anhedonia in the sucrose preference test, decreased number of crossings in the open field test, decreased body weight, and decreased immobility time in the forced swim test. Western blot analysis further showed that SCI significantly increased the levels of phosphorylated p38MPAK (p-p38MPAK) and cleaved caspase-3 in the hippocampus and inhibited the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK1/2). In addition, there were significant negative correlations between depression-like behavior and p-ERK1/2, and positive correlations between depression-like behavior and p-p38MPAK and cleaved caspase-3. These findings suggest that the MAPK pathway in the rat hippocampus may be involved in the pathophysiology of depression induced by SCI.
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http://dx.doi.org/10.1016/j.wneu.2021.06.093DOI Listing
July 2021

Relationship Between Serum Fibrinogen Level and Depressive Symptoms in an Adult Population with Spinal Cord Injury: A Cross-Sectional Study.

Neuropsychiatr Dis Treat 2021 6;17:2191-2198. Epub 2021 Jul 6.

Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330006, People's Republic of China.

Purpose: Depression is associated with an inflammatory immune response. There are minimal data regarding the association of inflammatory markers with depression in patients with spinal cord injury (SCI). We aimed to investigate the association of inflammatory markers with depression in middle-aged and elderly SCI patients.

Methods: Data were obtained from the Midlife in the United States (MIDUS) study, a longitudinal study of a representative sample of the adult population. We analyzed the associations of serum levels of fibrinogen, interleukin-6, tumor necrosis factor-ɑ, and C-reactive protein with depressive symptoms.

Results: The median participant age was 52.5 years; 44.9% of participants were men. Multivariate linear regression analyses showed that an increased serum fibrinogen level (Sβ = 0.114, p = 0.005) was associated with higher Centre for Epidemiological Studies-Depression (CES-D) scores after adjustment for age, sex, body mass index (BMI), ethnicity, education, marital status, smoking, alcohol use, exercise, perceived stress score, and cardiovascular disease (CVD). Multivariate logistic regression analysis showed that an increased serum fibrinogen level was independently associated with a history of depression (odds ratio [OR] = 1.240, 95% confidence interval [CI] = 1.103-1.997, p = 0.012) and depressive symptoms (OR = 1.884, 95% CI = 1.165-2.499, p < 0.001; CES-D score ≥ 16) after adjustment for confounding factors. Stratified analysis revealed that the association between serum fibrinogen level and depressive symptoms was affected by antidepressant use.

Conclusion: Serum fibrinogen level had a significantly positive association with depressive symptoms in middle-aged and elderly patients with SCI. Future longitudinal cohort studies should evaluate the possible use of serum fibrinogen for diagnosis of depression in SCI patients.
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http://dx.doi.org/10.2147/NDT.S311473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275144PMC
July 2021

Nomogram for Predicting Deep Venous Thrombosis in Lower Extremity Fractures.

Biomed Res Int 2021 22;2021:9930524. Epub 2021 Jun 22.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road. 1277#, Wuhan, 430022 Hubei, China.

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability.
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http://dx.doi.org/10.1155/2021/9930524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245242PMC
June 2021

Antioxidant Therapy and Antioxidant-Related Bionanomaterials in Diabetic Wound Healing.

Front Bioeng Biotechnol 2021 24;9:707479. Epub 2021 Jun 24.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ulcers are a lower-extremity complication of diabetes with high recurrence rates. Oxidative stress has been identified as a key factor in impaired diabetic wound healing. Hyperglycemia induces an accumulation of intracellular reactive oxygen species (ROS) and advanced glycation end products, activation of intracellular metabolic pathways, such as the polyol pathway, and PKC signaling leading to suppression of antioxidant enzymes and compounds. Excessive and uncontrolled oxidative stress impairs the function of cells involved in the wound healing process, resulting in chronic non-healing wounds. Given the central role of oxidative stress in the pathology of diabetic ulcers, we performed a comprehensive review on the mechanism of oxidative stress in diabetic wound healing, focusing on the progress of antioxidant therapeutics. We summarize the antioxidant therapies proposed in the past 5 years for use in diabetic wound healing, including Nrf2- and NFκB-pathway-related antioxidant therapy, vitamins, enzymes, hormones, medicinal plants, and biological materials.
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http://dx.doi.org/10.3389/fbioe.2021.707479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264455PMC
June 2021

Deleterious Mutations in the TPO Gene Associated with Familial Thyroid Follicular Cell Carcinoma in Dutch German Longhaired Pointers.

Genes (Basel) 2021 Jun 29;12(7). Epub 2021 Jun 29.

Animal Breeding and Genomics, Wageningen University & Research, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.

Familial thyroid cancer originating from follicular cells accounts for 5-15% of all the thyroid carcinoma cases in humans. Previously, we described thyroid follicular cell carcinomas in a large number of the Dutch German longhaired pointers (GLPs) with a likely autosomal recessive inheritance pattern. Here, we investigated the genetic causes of the disease using a combined approach of genome-wide association study and runs of homozygosity (ROH) analysis based on 170k SNP array genotype data and whole-genome sequences. A region 0-5 Mb on chromosome 17 was identified to be associated with the disease. Whole-genome sequencing revealed many mutations fitting the recessive inheritance pattern in this region including two deleterious mutations in the TPO gene, chr17:800788G>A (686F>V) and chr17:805276C>T (845T>M). These two SNP were subsequently genotyped in 186 GLPs (59 affected and 127 unaffected) and confirmed to be highly associated with the disease. The recessive genotypes had higher relative risks of 16.94 and 16.64 compared to homozygous genotypes for the reference alleles, respectively. This study provides novel insight into the genetic causes leading to the familial thyroid follicular cell carcinoma, and we were able to develop a genetic test to screen susceptible dogs.
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http://dx.doi.org/10.3390/genes12070997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306087PMC
June 2021

Response: Astrocytes as alternative targets for more efficient antiepileptogenic drugs.

Epilepsia 2021 Jun 24. Epub 2021 Jun 24.

Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.

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http://dx.doi.org/10.1111/epi.16965DOI 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

Differential patterns of dynamic functional connectivity variability in major depressive disorder treated with cognitive behavioral therapy.

J Affect Disord 2021 08 23;291:322-328. Epub 2021 May 23.

Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Functional Brain Imaging Institute of Nanjing Medical University, Nanjing, 210029, Jiangsu, China; Cognitive Behavioral Therapy Institute of Nanjing Medical University, Nanjing, 210029, Jiangsu, China. Electronic address:

Background: Numerous studies have shown that major depressive disorder (MDD) is characterized by a range of impairments in emotional and cognitive functions that are closely related to abnormalities in brain structure and function. Cognitive behavioral therapy (CBT) can be used as treatment for mild to moderate MDD, which can assist with ameliorating the symptoms. Previous studies have assumed that the internal fluctuations throughout the entire scan are static. However, it has recently been suggested that the brain connectivity is dynamic and relative to continuous rhythmic activity. The effect of dynamic changes in CBT on MDD patients is unknown.

Methods: Nineteen first-episode, unmedicated MDD patients and twenty-two healthy controls (HC) participated in the study. The patients received early CBT treatment once a week for 6 weeks. Symptom examinations and magnetic resonance imaging (MRI) scans were performed pre and post treatment. Degree centrality (DC) was used to investigate the whole-brain connectivity differences between patients with MDD and healthy controls, and sliding window correlation analysis was applied to investigate the dynamic changes of functional connectivity among MDD patients treated with CBT. The variance of dynamic functional connectivity (dFC) was calculated to evaluate the temporal variability along the time.

Results: Patients with MDD showed abnormal DC in dorsolateral prefrontal cortex (dlPFC), insula and postcentral gyrus. Correlation analysis revealed that degree centrality of dlPFC was negatively correlated with the course of disease in patients with MDD. Results of dynamic functional connectivity showed that, compared to HC, MDD patients-remained excessively stable in dlPFC and precuneus connectivity, which is associated with emotional cognitive symptoms. After CBT, patients showed increased dFC variability in dlPFC and precuneus (p < 0.01, GRF corrected).

Conclusion: DLPFC plays an important role in pathophysiological mechanism of MDD. CBT helped patients suppress redundant thoughts and negative self-focus. As a connecting node, dlPFC participates in the mechanism of action of CBT.
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http://dx.doi.org/10.1016/j.jad.2021.05.017DOI Listing
August 2021

Driving effect of BDNF in the spinal dorsal horn on neuropathic pain.

Neurosci Lett 2021 06 19;756:135965. Epub 2021 May 19.

Jiangxi Academy of Medical Sciences, Nanchang, Jiangxi Province, 330006, China. Electronic address:

Neuropathic pain (NP) is caused by direct or indirect damage to the nervous system and is a common symptom of many diseases. The mechanisms underlying the onset and persistence of NP are unclear. Therefore, research concerning these mechanisms has become an important focus in the medical field. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. BDNF is an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity, which are essential for nerve maintenance and repair. However, BDNF is upregulated in the spinal dorsal horn and can promote NP by activating glial cells, reducing inhibitory functions and enhancing excitement after nociceptive stimulation. This review considers the relationship between NP and BDNF signaling in the spinal dorsal horn and discusses potentially related pathological mechanisms.
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http://dx.doi.org/10.1016/j.neulet.2021.135965DOI Listing
June 2021

Cell death of hippocampal CA1 astrocytes during early epileptogenesis.

Epilepsia 2021 Jul 6;62(7):1569-1583. Epub 2021 May 6.

Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.

Objective: Growing evidence suggests that dysfunctional astrocytes are crucial players in the development of mesial temporal lobe epilepsy (MTLE). Using a mouse model closely recapitulating key alterations of chronic human MTLE with hippocampal sclerosis, here we asked whether death of astrocytes contributes to the initiation of the disease and investigated potential underlying molecular mechanisms.

Methods: Antibody staining was combined with confocal imaging and semiquantitative real-time polymerase chain reaction analysis to identify markers of different cellular death mechanisms between 4 h and 3 days after epilepsy induction.

Results: Four hours after kainate-mediated induction of status epilepticus (SE), we found a significant reduction in the density of astrocytes in the CA1 stratum radiatum (SR) of the ipsilateral hippocampus. This reduction was transient, as within the next 3 days, astrocyte cell numbers recovered to the initial values, which was accompanied by enhanced proliferation. Four hours after SE induction, a small proportion of astrocytes in the ipsilateral CA1 SR expressed autophagy-related genes and proteins, whereas we did not find astrocytes positive for cleaved caspase 3 or terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling, ruling out apoptosis-related astrocytic death. Importantly, at the same early time point post-SE, many astrocytes in the ipsilateral CA1 SR showed strong expression of genes encoding pro-necroptosis factors, including receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL). Phosphorylation of MLKL (pMLKL), formation of necrosome complexes composed of RIPK3 and pMLKL, and translocation of pMLKL to the nucleus and to the plasma membrane were often observed in astrocytes of the ipsilateral hippocampus 4 h post-SE.

Significance: The present study revealed that astrocytes die shortly after induction of SE. Our expression data and immunohistochemistry suggest that necroptosis and autophagy contribute to astrocytic death. These findings help to better understand how dysfunctional and pathological remodeling of astrocytes contributes to the initiation of temporal lobe epilepsy.
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http://dx.doi.org/10.1111/epi.16910DOI Listing
July 2021

Atomically sharp interface enabled ultrahigh-speed non-volatile memory devices.

Nat Nanotechnol 2021 May 3. Epub 2021 May 3.

Institute of Physics, Chinese Academy of Sciences, Beijing, People's Republic of China.

The development of high-performance memory devices has played a key role in the innovation of modern electronics. Non-volatile memory devices have manifested high capacity and mechanical reliability as a mainstream technology; however, their performance has been hampered by low extinction ratio and slow operational speed. Despite substantial efforts to improve these characteristics, typical write times of hundreds of micro- or milliseconds remain a few orders of magnitude longer than that of their volatile counterparts. Here we demonstrate non-volatile, floating-gate memory devices based on van der Waals heterostructures with atomically sharp interfaces between different functional elements, achieving ultrahigh-speed programming/erasing operations in the range of nanoseconds with extinction ratio up to 10. This enhanced performance enables new device capabilities such as multi-bit storage, thus opening up applications in the realm of modern nanoelectronics and offering future fabrication guidelines for device scale up.
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http://dx.doi.org/10.1038/s41565-021-00904-5DOI Listing
May 2021

Heterogeneity of a dwarf phenotype in Dutch traditional chicken breeds revealed by genomic analyses.

Evol Appl 2021 Apr 19;14(4):1095-1108. Epub 2021 Jan 19.

Wageningen University & Research, Animal Breeding and Genomics Wageningen The Netherlands.

The growth of animals is a complex trait, in chicken resulting in a diverse variety of forms, caused by a heterogeneous genetic basis. Bantam chicken, known as an exquisite form of dwarfism, has been used for crossbreeding to create corresponding dwarf counterparts for native fowls in the Dutch populations. Here, we demonstrate the heterogeneity of the bantam trait in Dutch chickens and reveal the underlying genetic causes, using whole-genome sequence data from matching pairs of bantam and normal-sized breeds. During the bantam-oriented crossbreeding, various bantam origins were used to introduce the bantam phenotype, and three major bantam sources were identified and clustered. The genome-wide association studies revealed multiple genetic variants and genes associated with bantam phenotype, including and , genes involved in body growth and stature. The comparison of associated variants among studies illustrated differences related to divergent bantam origins, suggesting a clear heterogeneity among bantam breeds. We show that in neo-bantam breeds, the bantam-related regions underwent a strong haplotype introgression from the bantam source, outcompeting haplotypes from the normal-sized counterpart. The bantam heterogeneity is further confirmed by the presence of multiple haplotypes comprising associated alleles, which suggests the selection of the bantam phenotype is likely subject to a convergent direction across populations. Our study demonstrates that the diverse history of human-mediated crossbreeding has contributed to the complexity and heterogeneity of the bantam phenotype.
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http://dx.doi.org/10.1111/eva.13183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061282PMC
April 2021

SARS-CoV-2-induced Overexpression of miR-4485 Suppresses Osteogenic Differentiation and Impairs Fracture Healing.

Int J Biol Sci 2021 25;17(5):1277-1288. Epub 2021 Mar 25.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan, Hubei 430022, China.

The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both and . Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation . Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.
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http://dx.doi.org/10.7150/ijbs.56657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040480PMC
May 2021

Prediction of Microvascular Invasion of Hepatocellular Carcinoma Based on Contrast-Enhanced MR and 3D Convolutional Neural Networks.

Front Oncol 2021 4;11:588010. Epub 2021 Mar 4.

Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Background And Purpose: It is extremely important to predict the microvascular invasion (MVI) of hepatocellular carcinoma (HCC) before surgery, which is a key predictor of recurrence and helps determine the treatment strategy before liver resection or liver transplantation. In this study, we demonstrate that a deep learning approach based on contrast-enhanced MR and 3D convolutional neural networks (CNN) can be applied to better predict MVI in HCC patients.

Materials And Methods: This retrospective study included 114 consecutive patients who were surgically resected from October 2012 to October 2018 with 117 histologically confirmed HCC. MR sequences including 3.0T/LAVA (liver acquisition with volume acceleration) and 3.0T/e-THRIVE (enhanced T1 high resolution isotropic volume excitation) were used in image acquisition of each patient. First, numerous 3D patches were separately extracted from the region of each lesion for data augmentation. Then, 3D CNN was utilized to extract the discriminant deep features of HCC from contrast-enhanced MR separately. Furthermore, loss function for deep supervision was designed to integrate deep features from multiple phases of contrast-enhanced MR. The dataset was divided into two parts, in which 77 HCCs were used as the training set, while the remaining 40 HCCs were used for independent testing. Receiver operating characteristic curve (ROC) analysis was adopted to assess the performance of MVI prediction. The output probability of the model was assessed by the independent student's t-test or Mann-Whitney U test.

Results: The mean AUC values of MVI prediction of HCC were 0.793 (p=0.001) in the pre-contrast phase, 0.855 (p=0.000) in arterial phase, and 0.817 (p=0.000) in the portal vein phase. Simple concatenation of deep features using 3D CNN derived from all the three phases improved the performance with the AUC value of 0.906 (p=0.000). By comparison, the proposed deep learning model with deep supervision loss function produced the best results with the AUC value of 0.926 (p=0.000).

Conclusion: A deep learning framework based on 3D CNN and deeply supervised net with contrast-enhanced MR could be effective for MVI prediction.
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http://dx.doi.org/10.3389/fonc.2021.588010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040801PMC
March 2021

The Notch Signaling Pathway Regulates Differentiation of NG2 Cells into Oligodendrocytes in Demyelinating Diseases.

Cell Mol Neurobiol 2021 Apr 7. Epub 2021 Apr 7.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, No. 17 Yongwai Zheng Street, Nanchang, 330006, Jiangxi, People's Republic of China.

NG2 cells are highly proliferative glial cells that can self-renew or differentiate into oligodendrocytes, promoting remyelination. Following demyelination, the proliferative and differentiation potentials of NG2 cells increase rapidly, enhancing their differentiation into functional myelinating cells. Levels of the transcription factors Olig1 and Olig2 increase during the differentiation of NG2 cells and play important roles in the development and repair of oligodendrocytes. However, the ability to generate new oligodendrocytes is hampered by injury-related factors (e.g., myelin fragments, Wnt and Notch signaling components), leading to failed differentiation and maturation of NG2 cells into oligodendrocytes. Here, we review Notch signaling as a negative regulator of oligodendrocyte differentiation and discuss the extracellular ligands, intracellular pathways, and key transcription factors involved.
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http://dx.doi.org/10.1007/s10571-021-01089-0DOI Listing
April 2021

[Acupoint selection rules of acupuncture for cervical spondylotic radiculopathy based on data mining].

Zhongguo Zhen Jiu 2020 Nov;40(11):1259-62

College of Medical Information Engineering, Guangzhou University of CM, Guangzhou 510006, Guangdong Province, China.

Objective: To analyze the rules of acupoint selection in the acupuncture treatment of cervical spondylotic radiculopathy by data mining.

Methods: The randomized controlled trials (RCTs) regarding acupuncture for cervical spondylotic radiculopathy published from July 15 of 2009 to July 15 of 2019 were retrieved from databases of CNKI, VIP, Wanfang, SinoMed, PubMed and EMbase. A database was established with Microsoft Excel 2016. The frequency and total effective rate of high-frequency acupoints, meridians and acupoint combinations were analyzed, and the association rules of acupoints and meridians were analyzed by Apriori algorithm.

Results: A total of 87 RCTs were included, involving 104 acupoints with a total frequency of 921. Among them, the high-frequency acupoints were cervical Jiaji (EX-B 2, 87 times), Fengchi (GB 20, 70 times), Houxi (SI 3, 54 times), etc. The frequently-used acupoints were mainly distributed in the hand large intestine meridian, the foot gallbladder meridian and hand small intestine meridian. The frequently-used acupoint combination was Fengchi (GB 20)-cervical Jiaji (EX-B 2), and most of the combinations were acupoints at the proximal end and acupoints at the far and near end. With the analysis of association rules, 15 groups of acupoint association rules and meridian association rules were obtained.

Conclusion: It is feasible to explore the acupoint selection and compatibility rules of acupuncture for cervical spondylotic radiculopathy by data mining. This study could provide corresponding reference for clinical treatment.
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http://dx.doi.org/10.13703/j.0255-2930.20190905-0001DOI Listing
November 2020

Correction to: M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3.

J Nanobiotechnology 2021 Mar 27;19(1):88. Epub 2021 Mar 27.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

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http://dx.doi.org/10.1186/s12951-021-00828-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004442PMC
March 2021

Unveiling Atomic-Scale Moiré Features and Atomic Reconstructions in High-Angle Commensurately Twisted Transition Metal Dichalcogenide Homobilayers.

Nano Lett 2021 Apr 22;21(7):3262-3270. Epub 2021 Mar 22.

Department of Chemistry, National University of Singapore, 3 Science Drive 3 117543, Singapore.

Twisting the angle between van der Waals stacked 2D layers has recently sparked great interest as a new strategy to tune the physical properties of the materials. The twist angle and associated strain profiles govern the electrical and optical properties of the twisted 2D materials, but their detailed atomic structures remain elusive. Herein, using combined atomic-resolution electron microscopy and density functional theory (DFT) calculations, we identified five unique types of moiré features in commensurately twisted transition metal dichalcogenide (TMD) bilayers. These stacking variants are distinguishable only when the moiré wavelength is short. Periodic lattice strain is observed in various commensurately twisted TMD bilayers. Assisted by Zernike polynomial as a hierarchical active-learning framework, a hexagon-shaped strain soliton network has been atomically unveiled in nearly commensurate twisted TMD bilayers. Unlike stacking-polytype-dependent properties in untwisted structures, the stacking variants have the same electronic structures that suggest twisted bilayer systems are invariant against interlayer gliding.
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http://dx.doi.org/10.1021/acs.nanolett.1c00563DOI Listing
April 2021

miRNA-92a-3p regulates osteoblast differentiation in patients with concomitant limb fractures and TBI via IBSP/PI3K-AKT inhibition.

Mol Ther Nucleic Acids 2021 Mar 15;23:1345-1359. Epub 2021 Feb 15.

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China.

Patients who sustain concomitant fractures and traumatic brain injury (TBI) are known to have significantly quicker fracture-healing rates than patients with isolated fractures. The mechanisms underlying this phenomenon have yet to be identified. In the present study, we found that the upregulation of microRNA-92a-3p (miRNA-92a-3p) induced by TBI correlated with a decrease in integrin binding sialoprotein (IBSP) expression in callus formation. , overexpressing miRNA-92a-3p inhibited IBSP expression and accelerated osteoblast differentiation, whereas silencing of miRNA-92a-3p inhibited osteoblast activity. A decrease in IBSP facilitated osteoblast differentiation via the Phosphatidylinositol 3-kinase/threonine kinase 1 (PI3K/AKT) signaling pathway. Through luciferase assays, we found evidence that IBSP is a miRNA-92a-3p target gene that negatively regulates osteoblast differentiation. Moreover, the present study confirmed that pre-injection of agomiR-92a-3p leads to increased bone formation. Collectively, these results indicate that miRNA-92a-3p overexpression may be a key factor underlying the improved fracture healing observed in TBI patients. Upregulation of miRNA-92a-3p may therefore be a promising therapeutic strategy for promoting fracture healing and preventing nonunion.
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http://dx.doi.org/10.1016/j.omtn.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920808PMC
March 2021

Inflammation Spreading: Negative Spiral Linking Systemic Inflammatory Disorders and Alzheimer's Disease.

Authors:
Junjun Ni Zhou Wu

Front Cell Neurosci 2021 25;15:638686. Epub 2021 Feb 25.

Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

As a physiological response to injury in the internal body organs, inflammation is responsible for removing dangerous stimuli and initiating healing. However, persistent and exaggerative chronic inflammation causes undesirable negative effects in the organs. Inflammation occurring in the brain and spinal cord is known as neuroinflammation, with microglia acting as the central cellular player. There is increasing evidence suggesting that chronic neuroinflammation is the most relevant pathological feature of Alzheimer's disease (AD), regulating other pathological features, such as the accumulation of amyloid-β (Aβ) and hyperphosphorylation of Tau. Systemic inflammatory signals caused by systemic disorders are known to strongly influence neuroinflammation as a consequence of microglial activation, inflammatory mediator production, and the recruitment of peripheral immune cells to the brain, resulting in neuronal dysfunction. However, the neuroinflammation-accelerated neuronal dysfunction in AD also influences the functions of peripheral organs. In the present review, we highlight the link between systemic inflammatory disorders and AD, with inflammation serving as the common explosion. We discuss the molecular mechanisms that govern the crosstalk between systemic inflammation and neuroinflammation. In our view, inflammation spreading indicates a negative spiral between systemic diseases and AD. Therefore, "dampening inflammation" through the inhibition of cathepsin (Cat)B or CatS may be a novel therapeutic approach for delaying the onset of and enacting early intervention for AD.
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http://dx.doi.org/10.3389/fncel.2021.638686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947253PMC
February 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

Anomalous thickness dependence of Curie temperature in air-stable two-dimensional ferromagnetic 1T-CrTe grown by chemical vapor deposition.

Nat Commun 2021 Feb 5;12(1):809. Epub 2021 Feb 5.

School of Materials Science and Engineering, Beihang University, 100191, Beijing, P. R. China.

The discovery of ferromagnetic two-dimensional van der Waals materials has opened up opportunities to explore intriguing physics and to develop innovative spintronic devices. However, controllable synthesis of these 2D ferromagnets and enhancing their stability under ambient conditions remain challenging. Here, we report chemical vapor deposition growth of air-stable 2D metallic 1T-CrTe ultrathin crystals with controlled thickness. Their long-range ferromagnetic ordering is confirmed by a robust anomalous Hall effect, which has seldom been observed in other layered 2D materials grown by chemical vapor deposition. With reducing the thickness of 1T-CrTe from tens of nanometers to several nanometers, the easy axis changes from in-plane to out-of-plane. Monotonic increase of Curie temperature with the thickness decreasing from ~130.0 to ~7.6 nm is observed. Theoretical calculations indicate that the weakening of the Coulomb screening in the two-dimensional limit plays a crucial role in the change of magnetic properties.
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http://dx.doi.org/10.1038/s41467-021-21072-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864961PMC
February 2021

A novel cyclic peptide (Naturido) modulates glia-neuron interactions in vitro and reverses ageing-related deficits in senescence-accelerated mice.

PLoS One 2021 27;16(1):e0245235. Epub 2021 Jan 27.

Biococoon Laboratories, Inc., Ueda, Morioka, Japan.

The use of agents that target both glia and neurons may represent a new strategy for the treatment of ageing disorders. Here, we confirmed the presence of the novel cyclic peptide Naturido that originates from a medicinal fungus (Isaria japonica) grown on domestic silkworm (Bombyx mori). We found that Naturido significantly enhanced astrocyte proliferation and activated the single copy gene encoding the neuropeptide VGF and the neuron-derived NGF gene. The addition of the peptide to the culture medium of primary hippocampal neurons increased dendrite length, dendrite number and axon length. Furthermore, the addition of the peptide to primary microglial cultures shifted CGA-activated microglia towards anti-inflammatory and neuroprotective phenotypes. These findings of in vitro glia-neuron interactions led us to evaluate the effects of oral administration of the peptide on brain function and hair ageing in senescence-accelerated mice (SAMP8). In vivo analyses revealed that spatial learning ability and hair quality were improved in Naturido-treated mice compared with untreated mice, to the same level observed in the normal ageing control (SAMR1). These data suggest that Naturido may be a promising glia-neuron modulator for the treatment of not only senescence, but also Alzheimer's disease and other neurodegenerative diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245235PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840003PMC
May 2021

A stable low-temperature H-production catalyst by crowding Pt on α-MoC.

Nature 2021 01 20;589(7842):396-401. Epub 2021 Jan 20.

Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering and College of Engineering, and BIC-ESAT, Peking University, Beijing, China.

The water-gas shift (WGS) reaction is an industrially important source of pure hydrogen (H) at the expense of carbon monoxide and water. This reaction is of interest for fuel-cell applications, but requires WGS catalysts that are durable and highly active at low temperatures. Here we demonstrate that the structure (Pt-Pt)/α-MoC, where isolated platinum atoms (Pt) and subnanometre platinum clusters (Pt) are stabilized on α-molybdenum carbide (α-MoC), catalyses the WGS reaction even at 313 kelvin, with a hydrogen-production pathway involving direct carbon monoxide dissociation identified. We find that it is critical to crowd the α-MoC surface with Pt and Pt species, which prevents oxidation of the support that would cause catalyst deactivation, as seen with gold/α-MoC (ref. ), and gives our system high stability and a high metal-normalized turnover number of 4,300,000 moles of hydrogen per mole of platinum. We anticipate that the strategy demonstrated here will be pivotal for the design of highly active and stable catalysts for effective activation of important molecules such as water and carbon monoxide for energy production.
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http://dx.doi.org/10.1038/s41586-020-03130-6DOI Listing
January 2021

True Aneurysm of the Breast After Vacuum-assisted Removal of Benign Masses: A Case Report.

Int J Gen Med 2021 12;14:67-71. Epub 2021 Jan 12.

Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Rationale: The most common complications of vacuum-assisted removal (VAR) for benign breast masses are hematoma, infection, and occasionally pseudoaneurysms. To the best of our knowledge, this is the first report of a true aneurysm following VAR for breast fibroadenomas.

Case Presentation: A 50-year-old woman underwent VAR of bilateral benign breast masses under ultrasonic guidance. Routine breast ultrasound examination was performed 3 months later, and no discomfort was observed during follow-up.

Diagnoses And Interventions: Physical examination revealed a slightly palpable, arterial-like pulsation in the lateral part of the right breast. The two-dimensional ultrasound showed that there was a well-defined anechoic nodule in the right breast at the 9 o'clock position 3 cm from the nipple, measuring 6 mm × 4 mm. Color Doppler sonography demonstrated that it was a localized dilated intramammary arteriole within the colorful flow. Spectral Doppler illustrated a high-velocity turbulent arterial flow component inside. Based on these findings, the patient was diagnosed with an iatrogenic true aneurysm of the breast. Given her overall good condition, conservative treatment with regular imaging surveillance was adopted.

Outcomes: Up to now, the patient remains asymptomatic, and the size of the aneurysm has not changed.

Lessons: With the increasing use of interventional diagnosis and treatment techniques, iatrogenic vascular complications are likely to occur more frequently. Careful duplex ultrasound examination prior to or following the procedure is strongly recommended. In the absence of risk factors, we recommend a conservative approach to small, stable aneurysms.
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http://dx.doi.org/10.2147/IJGM.S288019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813131PMC
January 2021

Children with euthymic bipolar disorder during an emotional go/nogo task: Insights into the neural circuits of cognitive-emotional regulation.

J Affect Disord 2021 03 30;282:669-676. Epub 2020 Dec 30.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

Background: Pediatric bipolar disorder (PBD), manifested by alternating episodes of depression and mania, is more likely to relapse than adult BD and develop into chronic BD. Although it can be asymptomatic during the remission of PBD, subtle changes in the brain neural response can still exist. Abnormal activities in the neural circuits of cognitive-emotional regulation have been found in adult BD patients using fMRI. However, few fMRI studies focus on emotional regulation on cognitive function in euthymic PBD, especially during an emotional go/nogo task. Therefore, this study aims to compare differences in the activities of both emotional and cognitive circuits between euthymic BD children and healthy controls.

Methods: 18 euthymic PBD and 17 healthy subjects from 12 to 17 years of age were enrolled in our study. Simultaneous neural activity was recorded during the overall task and the effect of emotional factors on task performances was assessed.

Results: There were no significant differences in behavioral performances between the PBD group and the control group. During a task with emotional versus neutral distractors, euthymic PBD patients showed increased activities in the DLPFC, inferior parietal lobule, superior/middle frontal gyrus, superior/middle temporal gyrus, insula, posterior cingulate gyrus and posterior cerebellum lobe relative to healthy controls. The insula and DLPFC activities in response to emotional versus neutral distractors were positively associated with the differences in false response errors.

Conclusions: This study confirms the enhanced neural activities in euthymic PBD during a task with emotional versus control distractors. These brain regions supporting the cognitive and emotional dysregulation of PBD mainly coincide with the salience and executive control networks. As neural responses are more sensitive than behavioral manifestations in euthymic PBD, our findings will inspire more clinical studies to unveil the characteristic neuromechanism of PBD.
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http://dx.doi.org/10.1016/j.jad.2020.12.157DOI Listing
March 2021

Genome-Wide Association Study and Transcriptome Differential Expression Analysis of the Feather Rate in Shouguang Chickens.

Front Genet 2020 22;11:613078. Epub 2020 Dec 22.

National Engineering Laboratory for Animal Breeding, Beijing Key Laboratory of Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China.

The feather rate phenotype in chicks, including early-feathering and late-feathering phenotypes, are widely used as a sexing system in the poultry industry. The objective of this study was to obtain candidate genes associated with the feather rate in Shouguang chickens. In the present study, we collected 56 blood samples and 12 hair follicle samples of flight feathers from female Shouguang chickens. Then we identified the chromosome region associated with the feather rate by genome-wide association analysis (GWAS). We also performed RNA sequencing and analyzed differentially expressed genes between the early-feathering and late-feathering phenotypes using HISAT2, StringTie, and DESeq2. We identified a genomic region of 10.0-13.0 Mb of chromosome Z, which is statistically associated with the feather rate of Shouguang chickens at one-day old. After RNA sequencing analysis, 342 differentially expressed known genes between the early-feathering (EF) and late-feathering (LF) phenotypes were screened out, which were involved in epithelial cell differentiation, intermediate filament organization, protein serine kinase activity, peptidyl-serine phosphorylation, retinoic acid binding, and so on. The sperm flagellar 2 gene () and prolactin receptor () gene were the only two overlapping genes between the results of GWAS and differential expression analysis, which implies that and are possible candidate genes for the formation of the chicken feathering phenotype in the present study. Our findings help to elucidate the molecular mechanism of the feather rate in chicks.
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http://dx.doi.org/10.3389/fgene.2020.613078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783405PMC
December 2020
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