Publications by authors named "Pan Zhang"

453 Publications

Identification of Flap Endonuclease 1 With Diagnostic and Prognostic Value in Breast Cancer.

Front Oncol 2021 30;11:603114. Epub 2021 Jun 30.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.

Objective: This study aims to identify the potential value of flap endonuclease 1 (FEN1) as a diagnostic and prognostic marker for breast cancer (BC).

Methods: ELISA was used to measure serum FEN1 levels and ECLIA for CA153 and CEA levels. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value. Oncomine and UALCAN databases were used to analyze the differences in FEN1 mRNA and protein expressions. Kaplan-Meier Plotter database was then used to assess the prognostic value.

Results: Bioinformatics analysis showed that the FEN1 mRNA and protein levels were significantly higher in BC tissues than in normal tissues. FEN1 was detected in culture medium of BC cell lines and serum FEN1 concentrations were significantly increased in BC patients than in cancer-free individuals. Besides, FEN1 exhibited higher diagnostic accuracy (AUC values>0.800) than CA153 and CEA for distinguishing BC patients, especially early BC, from the healthy and benign groups, or individually. Additionally, serum FEN1 levels were significantly associated with the stage (P=0.001) and lymph invasion (P=0.016), and serum FEN1 levels were increased with the development of BC. Furthermore, serum FEN1 levels were significantly decreased in post-operative patients than in pre-operative patients (P=0.016). Based on the Kaplan-Meier Plotter database, the survival analysis indicated that FEN1 overexpression was associated with poor prognoses for overall survival (OS), relapse-free survival (RFS), and distant metastasis-free survival (DMFS) in BC patients.

Conclusion: FEN1 might be a novel diagnostic and prognostic marker for BC.
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http://dx.doi.org/10.3389/fonc.2021.603114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278286PMC
June 2021

Transcriptome analysis of resistant and susceptible mulberry responses to Meloidogyne enterolobii infection.

BMC Plant Biol 2021 Jul 16;21(1):338. Epub 2021 Jul 16.

StateKey Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, P. R. China.

Background: Mulberry (Morus alba L.) is an important sericulture crop; however, root-knot nematode infection seriously limits its production. Understanding the mechanism of interaction between mulberry and nematode is important for control of infection.

Results: Using sequencing and de novo transcriptome assembly, we identified 55,894 unigenes from root samples of resistant and susceptible mulberry cultivars at different stages after infection with the nematode Meloidogyne enterolobii; 33,987 of these were annotated in the Nr, SWISS-PROT, KEGG, and KOG databases. Gene ontology and pathway enrichment analyses of differentially expressed genes (DEGs) revealed key genes involved in hormone metabolic processes, plant hormone signal transduction, flavonoid biosynthesis, phenylpropanoid biosynthesis, and peroxisomal and photosynthetic pathways. Analysis of key trends in co-expression networks indicated that expression of unigenes 0,015,083, 0,073,272, 0,004,006, and 0,000,628 was positively correlated with resistance to M. enterolobii. Unigene 0015083 encodes tabersonine 16-O-methyltransferase (16OMT), which is involved in alkaloid biosynthesis. Unigene 0073272 encodes a transcription factor contributing to nitric oxide accumulation during plant immune responses. Unigenes 0,004,006 and 0,000,628 encode ERF and MYB transcription factors, respectively, involved in plant hormone signaling. We verified the accuracy of transcriptome sequencing results by RT-qPCR of 21 DEGs.

Conclusions: The results of this study increase our understanding of the resistance mechanisms and candidate genes involved in mulberry-M. enterolobii interaction. Thus, our data will contribute to the development of effective control measures against this pathogen.
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http://dx.doi.org/10.1186/s12870-021-03128-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285880PMC
July 2021

Long-loop feedback vertex set and dismantling on bipartite factor graphs.

Phys Rev E 2021 Jun;103(6):L061302

CAS Key Laboratory for Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China.

Network dismantling aims at breaking a network into disconnected components and attacking vertices that intersect with many loops has proven to be a most efficient strategy. Yet existing loop-focusing methods do not distinguish the short loops within densely connected local clusters (e.g., cliques) from the long loops connecting different clusters, leading to lowered performance of these algorithms. Here we propose a new solution framework for network dismantling based on a two-scale bipartite factor-graph representation, in which long loops are maintained while local dense clusters are simplistically represented as individual factor nodes. A mean-field spin-glass theory is developed for the corresponding long-loop feedback vertex set problem. The framework allows for the advancement of various existing dismantling algorithms; we developed the new version of two benchmark algorithms BPD (which uses the message-passing equations of the spin-glass theory as the solver) and CoreHD (which is fastest among well-performing algorithms). New solvers outperform current state-of-the-art algorithms by a considerable margin on networks of various sorts. Further improvement in dismantling performance is achievable by opting flexibly the choice of local clusters.
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http://dx.doi.org/10.1103/PhysRevE.103.L061302DOI Listing
June 2021

PD-L1/LAG-3 bispecific antibody enhances tumor-specific immunity.

Oncoimmunology 2021 24;10(1):1943180. Epub 2021 Jun 24.

Department of Drug Discovery, Innovent Biologics (Suzhou) Co, Suzhou, China.

Anti-programmed cell death-1 (PD-1)/PD-ligand-1 (PD-L1) treatments are effective in a fraction of patients with advanced malignancies. However, the majority of patients do not respond to it. Resistance to cancer immunotherapy can be mediated by additional immune checkpoints. We hypothesized that co-targeting of PD-L1 and lymphocyte-activation gene 3 (LAG-3) could provide an alternative therapeutic approach. Here, we developed IBI323, a dual blockade bispecific antibody targeting PD-L1 and LAG-3. We assessed the binding affinity, blocking activity, cell bridging effect, and immunomodulation function of IBI323 using in vitro assays. We also evaluated, in two humanized mouse models, anti-tumor effects and antitumor T cell immunity induced by IBI323. IBI323 bound to PD-L1 and LAG-3 with similar potency as its parental antibodies and blocked the interaction of PD-1/PD-L1, CD80/PD-L1, and LAG-3/MHC-II. Moreover, IBI323 mediated the bridging of PD-L1+ cells and LAG-3+ cells and demonstrated superior immune stimulatory activity compared to each parent antibody in mixed leukocyte reaction. In PD-L1/LAG-3 double knock-in mice bearing human PD-L1 knock-in MC38 tumors, IBI323 showed stronger anti-tumor activity compared to each parental antibody. The better antitumor response correlated with increased tumor-specific CD8+ and CD4+ T cells. IBI323 also induced stronger anti-tumor effect against established A375 tumors compared with combination in mice reconstituted with human immune cells. Collectively, these data demonstrated that IBI323 preserved the blockade activities of parental antibodies while processing a novel cell bridging function. Based on the encouraging preclinical results, IBI323 has significant value in further clinical development.
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http://dx.doi.org/10.1080/2162402X.2021.1943180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237984PMC
June 2021

The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations.

Nat Commun 2021 07 5;12(1):4130. Epub 2021 Jul 5.

Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, USA.

Chromosomal translocations of the AF10 (or MLLT10) gene are frequently found in acute leukemias. Here, we show that the PZP domain of AF10 (AF10), which is consistently impaired or deleted in leukemogenic AF10 translocations, plays a critical role in blocking malignant transformation. Incorporation of functional AF10 into the leukemogenic CALM-AF10 fusion prevents the transforming activity of the fusion in bone marrow-derived hematopoietic stem and progenitor cells in vitro and in vivo and abrogates CALM-AF10-mediated leukemogenesis in vivo. Crystallographic, biochemical and mutagenesis studies reveal that AF10 binds to the nucleosome core particle through multivalent contacts with the histone H3 tail and DNA and associates with chromatin in cells, colocalizing with active methylation marks and discriminating against the repressive H3K27me3 mark. AF10 promotes nuclear localization of CALM-AF10 and is required for association with chromatin. Our data indicate that the disruption of AF10 function in the CALM-AF10 fusion directly leads to transformation, whereas the inclusion of AF10 downregulates Hoxa genes and reverses cellular transformation. Our findings highlight the molecular mechanism by which AF10 targets chromatin and suggest a model for the AF10-dependent CALM-AF10-mediated leukemogenesis.
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http://dx.doi.org/10.1038/s41467-021-24418-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257627PMC
July 2021

Initial performance predicts improvements in computerized cognitive training: Evidence from a selective attention task.

Psych J 2021 Jul 4. Epub 2021 Jul 4.

School of Nursing, Yueyang Vocational and Technical College, Yueyang, China.

Computerized cognitive training (CCT) has been found to improve a range of skills such as attention, working memory, inhibition control, and decision making. However, the relationship between the initial performance, amount of improvement, time constant, and asymptotic performance level in CCT is still unclear. In the current study, we performed selective attention training on college students and addressed this issue by mathematically modeling the learning curve with an exponential function. Twenty-nine students completed approximately 10 days of CCT. Presentation time served as the dependent variable and was measured by three-down/one-up adaptive algorithms. We fitted an exponential function to the estimated block thresholds during CCT and obtained three learning parameters (amount of improvement, time constant, and asymptotic performance level) for all subjects. The initial performance was defined by the sum of the amount of improvement and the asymptotic performance level. Pearson correlation analyses were conducted between the initial performance and the three leaning parameters. The initial performance was positively correlated with the amount of improvement and asymptotic performance level, but was negatively correlated with the time constant. The time constant was negatively correlated with the amount of improvement and asymptotic performance level. Poorer initial performance was linked to a larger amount of improvement, shorter time constant, and higher asymptotic threshold, which supported the compensation account. Our results may help improve the present understanding of the nature of the CCT process and demonstrate the advantages of using a customized training protocol to enhance the efficiency of cognitive training in practical applications.
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http://dx.doi.org/10.1002/pchj.465DOI Listing
July 2021

Separation of normal and impaired dynamic cerebral autoregulation using deep embedded clustering: a proof-of-concept study.

Physiol Meas 2021 Jun 24. Epub 2021 Jun 24.

Institute of Advanced Computing and Digital Engineering, Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences, Shenzhen, Guangdong, CHINA.

A previous study has shown that a data-driven approach can significantly improve the discriminative power of transfer function analysis (TFA) used to differentiate between normal and impaired cerebral autoregulation (CA) in two groups of data. The data was collected from both healthy subjects (assumed to have normal CA) and symptomatic patients with severe stenosis (assumed to have impaired CA). However, the sample size of the labeled data was relatively small, owing to the difficulty in data collection. Therefore, in this proof-of-concept study, we investigate the feasibility of using an unsupervised learning model to differentiate between normal and impaired CA on TFA variables without requiring labeled data for learning. Continuous arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV), which were recorded simultaneously for approximately 10 min, were included from 148 subjects (41 healthy subjects, 31 with mild stenosis, 13 with moderate stenosis, 22 asymptomatic patients with severe stenosis, and 41 symptomatic patients with severe stenosis). Tiecks' model was used to generate surrogate data with normal and impaired CA. A recently proposed unsupervised learning model was optimized and applied to separate the normal and impaired CA for both the surrogate data and real data, and it achieved 98.9% and 74.1% accuracy for the surrogate and real data, respectively. To our knowledge, this is the first attempt to employ an unsupervised data-driven approach to assess CA using TFA. This method enables the development of a classifier to determine the status of CA, which is currently lacking.
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http://dx.doi.org/10.1088/1361-6579/ac0e81DOI Listing
June 2021

Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody.

Cancer Immunol Immunother 2021 Jun 24. Epub 2021 Jun 24.

Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, 215123, Jiangsu, China.

CD47 is a widely expressed cell-surface protein that regulates phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate immune cells, signal regulatory protein (SIRP)-α, which in turn inhibits phagocytosis. Several targeted CD47 therapeutic antibodies have been investigated clinically; however, how to improve its therapeutic efficacy remains unclear. Herein, we developed a CD47 blocking antibody, named IBI188, that could specifically block the CD47-SIRP-α axis, which transduces the "don't eat me" signal to macrophages. In vitro phagocytosis assays demonstrated the pro-phagocytosis ability of IBI188. Furthermore, several in vivo models were chosen to evaluate the anti-tumor efficacy of IBI188. IBI188 treatment upregulated cell movement- and inflammation-related genes in macrophages. Synergism was observed when combined with an anti-CD20 therapeutic antibody, whose function depends on antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment.
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http://dx.doi.org/10.1007/s00262-021-02989-2DOI Listing
June 2021

A Targeted Erythrocyte Membrane-Encapsulated Drug-Delivery System with Anti-osteosarcoma and Anti-osteolytic Effects.

ACS Appl Mater Interfaces 2021 Jun 14;13(24):27920-27933. Epub 2021 Jun 14.

Department of Orthopedics, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.

Chemotherapy is one of the main treatment methods for osteosarcoma. However, conventional chemotherapy lacks targeting properties, and its long-term and extensive use will have serious side effects on patients. For this reason, a multifunctional nanodrug system (V-RZCD) targeting osteosarcoma was developed in this study. V-RZCD consists of two parts: (1) the core (ZCD), wherein calcium ions (Ca) and zoledronic acid (ZA) form a metal-organic framework for loading doxorubicin (DOX), and (2) the shell (V-R), a vascular endothelial growth factor (VEGF) ligand-modified red blood cell membrane nanovesicle. By targeting the VEGF, V-RZCD can specifically bind to the VEGF receptors that are highly expressed on the surface of osteosarcoma cells. Importantly, compared with free ZA and DOX, V-RZCD not only clearly inhibits the proliferation of osteosarcoma but also significantly inhibits osteolysis induced by osteosarcoma. In summary, V-RZCD represents a new way to treat osteosarcoma.
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http://dx.doi.org/10.1021/acsami.1c06059DOI Listing
June 2021

Highly sensitive gas sensing platforms based on field effect Transistor-A review.

Anal Chim Acta 2021 Aug 29;1172:338575. Epub 2021 Apr 29.

School of Science, Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University, Tianjin, 300072, PR China. Electronic address:

Highly selective, sensitive and fast gas sensing has attracted increasing attention in the fields of environmental protection, industrial production, personal safety as well as medical diagnostics. Field effect transistor (FET) sensors have been extensively investigated in gas sensing fields due to their small size, high sensitivity, high reliability and low energy consumption. This comprehensive review aims to discuss the recent advances in FET gas sensors based on materials such as carbon nanotubes, silicon carbide, silicon, metal oxides-, graphene-, transition metal dichalcogenides- and 2-dimensional black phosphorus. We first introduce different types of sensor structures and elaborate the gas-sensing mechanisms. Then, we describe the optimizing strategies for sensing performances, response parameters, FET based dual-mode sensors and FET based logic circuit sensors. Moreover, we present the key advances of the above materials in gas sensing performances. Meanwhile, shortcomings of such materials are also discussed and the future development of this field is proposed in this review.
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http://dx.doi.org/10.1016/j.aca.2021.338575DOI Listing
August 2021

Adipose matrix complex: a high-rigidity collagen-rich adipose-derived material for fat grafting.

Aging (Albany NY) 2021 06 9;13(11):14910-14923. Epub 2021 Jun 9.

Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.

Due to the low percentage of collagen, the rigid support capacity of fat grafts remains unsatisfactory for some clinical applications. In this study, we evaluated a strategy in which adipose matrix complex (AMC) was collected via a mechanical process and transplanted for supportive filling of the face. Our AMC samples were collected from adipose tissue by a filter device consisting of a sleeve, three internal sieves, and a filter bag (100 mesh). AMC derived from adipose tissue had fewer cells than Coleman fat, but much higher levels of collagen and stiffness. Retention rates 90 days after transplantation in nude mice were higher for AMC than for Coleman fat (75±7.5% 42±13.5%; P < 0.05). In addition, AMC maintained a higher stiffness (~6 kPa ~2 kPa; P < 0.01) and stably retained a higher level of collagen. Our findings demonstrate that mechanical collection of AMC from adipose tissue is a practical method for improving fat graft retention and rigid support. This strategy has the potential to improve the quality of lipoaspirates for patients requiring rigid supportive filling.
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http://dx.doi.org/10.18632/aging.203120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221321PMC
June 2021

LncRNA Bmp1 promotes the healing of intestinal mucosal lesions via the miR-128-3p/PHF6/PI3K/AKT pathway.

Cell Death Dis 2021 Jun 9;12(6):595. Epub 2021 Jun 9.

Department of Burn Surgery, the Affiliated Huaihai Hospital of Xuzhou Medical University, Xuzhou, 221004, Jiangsu Province, China.

Intestinal mucosal injuries are directly or indirectly related to many common acute and chronic diseases. Long non-coding RNAs (lncRNAs) are expressed in many diseases, including intestinal mucosal injury. However, the relationship between lncRNAs and intestinal mucosal injury has not been determined. Here, we investigated the functions and mechanisms of action of lncRNA Bmp1 on damaged intestinal mucosa. We found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury. Bmp1 overexpression was found to influence cell proliferation, colony formation, and migration in IEC-6 or HIEC-6 cells. Moreover, miR-128-3p was downregulated after Bmp1 overexpression, and upregulation of miR-128-3p reversed the effects of Bmp1 overexpression in IEC-6 cells. Phf6 was observed to be a target of miR-128-3p. Furthermore, PHF6 overexpression affected IEC-6 cells by activating PI3K/AKT signaling which was mediated by the miR-128-3p/PHF6 axis. In conclusion, Bmp1 was found to promote the expression of PHF6 through the sponge miR-128-3p, activating the PI3K/AKT signaling pathway to promote cell migration and proliferation.
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http://dx.doi.org/10.1038/s41419-021-03879-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190101PMC
June 2021

Association of KCTD15 gene with fat deposition in pigs.

J Anim Physiol Anim Nutr (Berl) 2021 Jun 9. Epub 2021 Jun 9.

National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.

KCTD15 is associated with body mass index and fat deposition in humans, mice and chickens. However, the function of KCTD15 in pig fat deposition remains unclear. In this study, we cloned and analysed the cDNA sequence of porcine KCTD15. The full length of the mRNA sequence of KCTD15 is 4,091 bp, encoding 283 amino acids. The protein is hydrophilic, it has a relative molecular mass of about 31.9 kDa and an isoelectric point of 7.09 with no signal peptide sequence or transmembrane structure. Expression analysis showed that KCTD15 expression level was significantly higher in the tissues of Large White pigs (LW) than in those of Tibetan pigs (TP) and Diannan Small-ear pigs (DN) at 6 months of age, whereas its expression level in embryonic tissues of LW at 60 days was lower than that in tissues of TP and Wujin pigs (WJ). In pig primary adipocytes, the expression level of KCTD15 is high in the early stage of differentiation and gradually decreases in later stages. Additionally, the single-nucleotide polymorphism (SNP) site T-2030C (T/C mutation, located 2,030 bp upstream of the start codon) showed a dominant allele T with high promoter activity in the LW population and a dominant allele C in the TP and WJ populations. Our results indicate that KCTD15 is involved in pig fat deposition and that T-2030C is an important regulatory site for transcriptional activity, affecting fat deposition.
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http://dx.doi.org/10.1111/jpn.13587DOI Listing
June 2021

pH-Responsive Nanoemulsions Based on a Dynamic Covalent Surfactant.

Nanomaterials (Basel) 2021 May 25;11(6). Epub 2021 May 25.

Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan 250100, China.

Developing solid-free nanoemulsions with pH responsiveness is desirable in enhanced oil recovery (EOR) applications. Here, we report the synthesis of an interfacial activity controllable surfactant (T-DBA) through dynamic imine bonding between taurine (T) and p-decyloxybenzaldehyde (DBA). Instead of macroemulsions, nanoemulsions can be prepared by using T-DBA as an emulsifier. The dynamic imine bond of T-DBA enables switching between the active and inactive states in response to pH. This switching of interfacial activity was used to gate the stability of nanoemulsions, thus enabling us to turn the nanoemulsions off and on. Using such dynamic imine bonds to govern nanoemulsion stability could enable intelligent control of many processes such as heavy oil recovery and interfacial reactions.
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http://dx.doi.org/10.3390/nano11061390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227844PMC
May 2021

Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis.

Cell Death Dis 2021 May 27;12(6):551. Epub 2021 May 27.

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, 710061, Xi'an, Shaanxi, P. R. China.

Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.
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http://dx.doi.org/10.1038/s41419-021-03832-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160352PMC
May 2021

Dynamic Covalent Nanoparticles for Acid-Responsive Nonaqueous Pickering Emulsions.

Langmuir 2021 Jun 27;37(22):6632-6640. Epub 2021 May 27.

Key Laboratory of Colloid and Interface Chemistry, Ministry of Education, Shandong University, Jinan, Shandong 250100, P. R. China.

Acid-responsive nonaqueous (glycerol in -decane) Pickering emulsions were prepared using preferentially oil-wetted dynamic covalent silica (SiO-pDB) nanoparticles as the Pickering emulsifiers. The acid-responsive Pickering emulsifier SiO-pDB was prepared based on a Schiff base reaction between amino silica (SiO-NH) and -decanoxybenzaldehyde (pDBA). The formation of SiO-pDB was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and elemental analysis. The preferentially oil-wetted character of SiO-pDB was indicated by contact angle measurement. Stable nonaqueous Pickering emulsions were prepared using preferentially oil-wetted SiO-pDB as the Pickering emulsifier. However, after adjusting the nonaqueous Pickering emulsions to an acidic environment, complete phase separation occurred. In the acidic environment, preferentially oil-wetted SiO-pDB decomposed into hydrophilic SiO-NH and hydrophobic pDBA due to the decomposition of the dynamic imine bond in the SiO-pDB. Then, the hydrophilic SiO-NH and hydrophobic pDBA desorbed from the two-phase interface, resulting in complete phase separation of the initially stable nonaqueous Pickering emulsions. The acid-responsive nonaqueous Pickering emulsions show great potential in application in water sensitive systems, such as oil-based drilling fluids.
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http://dx.doi.org/10.1021/acs.langmuir.1c00097DOI Listing
June 2021

Comparative Analysis of Core and Accessory Genes in Coexpression Network.

Methods Mol Biol 2021 ;2242:45-58

State Key Laboratory of Agrobiotechnology, and College of Biological Sciences, China Agricultural University, Beijing, China.

Prokaryotes harbor a various proportion of accessory genes in their genomes. The integration of accessory functions with the core regulation network is critical for environmental adaptation, particularly considering a theoretically unlimited number of niches on the earth for microorganisms. Comparative genomics can reveal a co-occurrence pattern between a subset of accessory genes (or variations in core genes) and an adaptation trait, while comparative transcriptomics can further uncover whether a coordinated regulation of gene expression is involved. In this chapter, we introduce a protocol for weighted gene coexpression network construction by using well-developed open source tools, and a further application of such a network in comparative analysis of bacterial core and accessory genes.
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http://dx.doi.org/10.1007/978-1-0716-1099-2_3DOI Listing
June 2021

Characterization of the gut DNA and RNA Viromes in a Cohort of Chinese Residents and Visiting Pakistanis.

Virus Evol 2021 Jan 24;7(1):veab022. Epub 2021 Mar 24.

School of Medicine, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing 210029, China.

Trillions of viruses inhabit the gastrointestinal tract. Some of them have been well-studied on their roles in infection and human health, but the majority remains unsurveyed. It has been established that the composition of the gut virome is highly variable based on the changes of diet, physical state, and environmental factors. However, the effect of host genetic factors, for example ethnic origin, on the gut virome is rarely investigated. Here, we characterized and compared the gut virome in a cohort of local Chinese residents and visiting Pakistani individuals, each group containing twenty-four healthy adults and six children. Using metagenomic shotgun sequencing and assembly of fecal samples, a huge number of viral operational taxonomic units (vOTUs) were identified for profiling the DNA and RNA viromes. National background contributed a primary variation to individuals' gut virome. Compared with the Chinese adults, the Pakistan adults showed higher macrodiversity and different compositional and functional structures in their DNA virome and lower diversity and altered composition in their RNA virome. The virome variations of Pakistan children were not only inherited from that of the adults but also tended to share similar characteristics with the Chinese cohort. We also analyzed and compared the bacterial microbiome between two cohorts and further revealed numerous connections between viruses and bacterial host. Statistically, the gut DNA and RNA viromes were covariant to some extent (<0.001), and they both correlated the holistic bacterial composition and vice versa. This study provides an overview of the gut viral community in Chinese and visiting Pakistanis and proposes a considerable role of ethnic origin in shaping the virome.
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http://dx.doi.org/10.1093/ve/veab022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087960PMC
January 2021

Brain gene co-expression networks link complement signaling with convergent synaptic pathology in schizophrenia.

Nat Neurosci 2021 Jun 6;24(6):799-809. Epub 2021 May 6.

Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

The most significant common variant association for schizophrenia (SCZ) reflects increased expression of the complement component 4A (C4A). Yet, it remains unclear how C4A interacts with other SCZ risk genes or whether the complement system more broadly is implicated in SCZ pathogenesis. Here, we integrate several existing, large-scale genetic and transcriptomic datasets to interrogate the functional role of the complement system and C4A in the human brain. Unexpectedly, we find no significant genetic enrichment among known complement system genes for SCZ. Conversely, brain co-expression network analyses using C4A as a seed gene reveal that genes downregulated when C4A expression increases exhibit strong and specific genetic enrichment for SCZ risk. This convergent genomic signal reflects synaptic processes, is sexually dimorphic and most prominent in frontal cortical brain regions, and is accentuated by smoking. Overall, these results indicate that synaptic pathways-rather than the complement system-are the driving force conferring SCZ risk.
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http://dx.doi.org/10.1038/s41593-021-00847-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178202PMC
June 2021

A novel antibody targeting TIM-3 resulting in receptor internalization for cancer immunotherapy.

Antib Ther 2020 Dec 9;3(4):227-236. Epub 2020 Nov 9.

Innovent Biologics (Suzhou) Co., Ltd., 168 Dongping Street, Suzhou Industrial Park, Suzhou 215123, Jiangsu, China.

Background: Strategies to reinvigorate exhausted T cells have achieved great efficacy in certain subpopulations of tumor patients. Blocking the antibodies that target programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 induces durable responses in Hodgkin's lymphoma, melanoma, renal and lung cancers. T cell immunoglobulin mucin-3 (TIM-3) is another well-defined inhibitory receptor that is expressed in terminally differentiated Th1/Tc1 cells, which produces interferon gamma and cytotoxic molecules. It is also significantly expressed on forkhead box P3+ regulatory T cells and innate immune cells such as dendritic cells and macrophages.

Methods: By immunizing BALB/c mice with recombinant TIM-3 and screening of 20 000 hybridoma clones, we selected a monoclonal TIM-3-blocking antibody (IBI104), which shows great efficacy and .

Results: IBI104 blocks phosphatidylserine interaction with TIM-3 but does not interfere with the interaction of TIM-3 with galectin-9 in ELISA assays. However, administration of IBI104 induces the potent internalization of TIM-3 in activated T cells to the extent that it will shut down the entire TIM-3 mediated signaling regardless of the ligands. IBI104 shows potent anti-tumor efficacy when combined with anti-PD1 .

Conclusions: Our results suggest that IBI104 is a promising blocking antibody for TIM-3-mediated suppressive signaling and can serve as effective cancer immunotherapy, especially in combination with anti-PD1.
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http://dx.doi.org/10.1093/abt/tbaa022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990255PMC
December 2020

Distinct mRNAs in Cancer Extracellular Vesicles Activate Angiogenesis and Alter Transcriptome of Vascular Endothelial Cells.

Cancers (Basel) 2021 Apr 22;13(9). Epub 2021 Apr 22.

NUS Graduate School-Integrative Sciences and Engineering Programme (ISEP), National University of Singapore, Singapore 119077, Singapore.

Cancer-derived extracellular vesicles (EVs) have been demonstrated to be implicated in various processes of cancer development, with most of the EV-induced changes attributed to EV-proteins and EV-microRNAs. However, the knowledge about the abundance of cancer EV-mRNAs and their contribution to cancer development remain elusive. Here, we show that mRNAs prevail in cancer EVs as compared with normal EVs, and cancer EVs that carry abundant angiogenic mRNAs activate angiogenesis in human umbilical vein endothelial cells (HUVECs). Specifically, of a gene panel comprising 61 hypoxia-targeted oncogenes, a larger proportion is harbored by cancer EVs (>40%) than normal EVs (14.8%). Fluorescent trafficking indicates cancer EVs deliver translatable mRNAs such as to HUVECs, contributing to the activation of VEGFR-dependent angiogenesis and the upregulation of epithelial-mesenchymal transition-related and metabolism-related genes. Overall, our findings provide novel insights into EV-mRNAs and their role in angiogenesis, and has potential for diagnostic and therapeutic applications.
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http://dx.doi.org/10.3390/cancers13092009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122258PMC
April 2021

Integrated Analysis of the Transcriptome and Metabolome Revealed Candidate Genes Involved in GA-Induced Dormancy Release in Seeds.

Int J Mol Sci 2021 Apr 17;22(8). Epub 2021 Apr 17.

College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, China.

is a perennial forage grass that has good palatability, high yield and high feed value, but seed dormancy is a major problem limiting the widespread cultivation of . Here, we performed transcriptomic and metabolomic analysis of hulled and de-hulled seeds of treated with or without GA to investigate the changes in gene and metabolites associated with dormancy release induced by GA. The germination test revealed that the optimum concentration of GA for disruption of seed dormancy was 577 μM. A total of 4327 and 11,919 differentially expressed genes (DEGs) and 871 and 650 differentially abundant metabolites were identified in de-hulled and hulled seeds treated with GA, respectively, compared with seeds soaked in sterile water. Most of the DEGs were associated with starch and sucrose metabolism, protein processing in the endoplasmic reticulum, endocytosis and ribosomes. Furthermore, isoquinoline alkaloid biosynthesis, tyrosine metabolism, starch and sucrose metabolism, arginine and proline metabolism, and amino sugar and nucleotide sugar metabolism were significantly enriched pathways. Integrative analysis of the transcriptomic and metabolomic data revealed that starch and sucrose metabolism is one of the most important pathways that may play a key role in providing carbon skeletons and energy supply for the transition of seeds from a dormant state to germination by suppressing the expression of , , , , and , enhancing the expression of , , and , and inhibiting the synthesis of cellobiose, cellodextrin, and trehalose while promoting the hydrolysis of sucrose, starch, cellobiose, cellodextrin, and trehalose to glucose. This study identified several key genes and provided new insights into the molecular mechanism of seed dormancy release induced by GA in . These putative genes will be valuable resources for improving the seed germination rate in future breeding studies.
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http://dx.doi.org/10.3390/ijms22084161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074249PMC
April 2021

Real-Time HD Map Change Detection for Crowdsourcing Update Based on Mid-to-High-End Sensors.

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

School of Geodesy and Geomatics, Wuhan University, Wuhan 430072, China.

Continuous maintenance and real-time update of high-definition (HD) maps is a big challenge. With the development of autonomous driving, more and more vehicles are equipped with a variety of advanced sensors and a powerful computing platform. Based on mid-to-high-end sensors including an industry camera, a high-end Global Navigation Satellite System (GNSS)/Inertial Measurement Unit (IMU), and an onboard computing platform, a real-time HD map change detection method for crowdsourcing update is proposed in this paper. First, a mature commercial integrated navigation product is directly used to achieve a self-positioning accuracy of 20 cm on average. Second, an improved network based on BiSeNet is utilized for real-time semantic segmentation. It achieves the result of 83.9% IOU (Intersection over Union) on Nvidia Pegasus at 31 FPS. Third, a visual Simultaneous Localization and Mapping (SLAM) associated with pixel type information is performed to obtain the semantic point cloud data of features such as lane dividers, road markings, and other static objects. Finally, the semantic point cloud data is vectorized after denoising and clustering, and the results are matched with a pre-constructed HD map to confirm map elements that have not changed and generate new elements when appearing. The experiment conducted in Beijing shows that the method proposed is effective for crowdsourcing update of HD maps.
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http://dx.doi.org/10.3390/s21072477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038307PMC
April 2021

Gut microbiota characterization in Chinese patients with alopecia areata.

J Dermatol Sci 2021 May 15;102(2):109-115. Epub 2021 Apr 15.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Background: The gut microbiota is known to play a key role in autoimmune diseases.

Objectives: To identify and compare the characteristics in the gut microbial composition of patients with alopecia areata (AA) and healthy controls (HCs).

Methods: In a cross-sectional discovery cohort, we enrolled 33 patients with AA and 35 HCs from the same geographic location in Shanghai, China. The 16S rRNA gene sequencing and bioinformatic analyses were conducted to analyze DNA extracted from the subjects.

Results: The α-diversity of the AA group demonstrated no statistically significant differences compared with the HC group (P > 0.05). However, the overall gut microbial communities in the AA group were distinct from the HCs (P = 0.0096). We also adopted a random forest model to select three AA-associated OTU biomarkers: OTU1237(Achromobacter), OTU257(Megasphaera), and OTU1784(Lachnospiraceae Incertae Sedis).

Conclusion: The overall gut microbial composition for AA was distinct from that of HCs. The gut microbial markers we identified may potentially be used for earlier diagnosis and as therapeutic targets.
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http://dx.doi.org/10.1016/j.jdermsci.2021.04.003DOI Listing
May 2021

Advances in epitope molecularly imprinted polymers for protein detection: a review.

Anal Methods 2021 04 6;13(14):1660-1671. Epub 2021 Apr 6.

College of Chemistry, Jilin University, Changchun, 130012, P. R. China.

Epitope molecularly imprinted polymers (EMIPs) are novel imprinted materials using short characteristic peptides as templates rather than entire proteins. To be specific, the amino acid sequence of the template peptide is the same as an exposed N- or C-terminus of a target protein, or its amino acid composition and sequence replicate a similar conformational arrangement as the same amino acid residues on the surface of the target protein. EMIPs have a good application prospect in protein research. Herein, we focus on classification of epitope imprinting techniques, methods of epitope immobilization on matrix materials including boronate affinity immobilization, covalent bonding immobilization, physical adsorption immobilization and metal ion chelation immobilization, and application of EMIPs in peptides, proteins, target imaging and target therapy fields. Finally, the main problems and future development are summarized.
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http://dx.doi.org/10.1039/d1ay00067eDOI Listing
April 2021

Epigenetic alteration contributes to the transcriptional reprogramming in T-cell prolymphocytic leukemia.

Sci Rep 2021 Apr 15;11(1):8318. Epub 2021 Apr 15.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

T cell prolymphocytic leukemia (T-PLL) is a rare disease with aggressive clinical course. Cytogenetic analysis, whole-exome and whole-genome sequencing have identified primary structural alterations in T-PLL, including inversion, translocation and copy number variation. Recurrent somatic mutations were also identified in genes encoding chromatin regulators and those in the JAK-STAT signaling pathway. Epigenetic alterations are the hallmark of many cancers. However, genome-wide epigenomic profiles have not been reported in T-PLL, limiting the mechanistic study of its carcinogenesis. We hypothesize epigenetic mechanisms also play a key role in T-PLL pathogenesis. To systematically test this hypothesis, we generated genome-wide maps of regulatory regions using H3K4me3 and H3K27ac ChIP-seq, as well as RNA-seq data in both T-PLL patients and healthy individuals. We found that genes down-regulated in T-PLL are mainly associated with defense response, immune system or adaptive immune response, while up-regulated genes are enriched in developmental process, as well as WNT signaling pathway with crucial roles in cell fate decision. In particular, our analysis revealed a global alteration of regulatory landscape in T-PLL, with differential peaks highly enriched for binding motifs of immune related transcription factors, supporting the epigenetic regulation of oncogenes and genes involved in DNA damage response and T-cell activation. Together, our work reveals a causal role of epigenetic dysregulation in T-PLL.
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http://dx.doi.org/10.1038/s41598-021-87890-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050249PMC
April 2021

Interacting impact of maternal inflammatory response and stress on the amygdala transcriptome of pigs.

G3 (Bethesda) 2021 Apr 15. Epub 2021 Apr 15.

Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61820, USA.

Changes at the molecular level capacitate the plasticity displayed by the brain in response to stress stimuli. Weaning stress can trigger molecular changes that influence the physiology of the offspring. Likewise, maternal immune activation (MIA) during gestation has been associated with behavior disorders and molecular changes in the amygdala of the offspring. This study advances the understanding of the effects of pre-and postnatal stressors in amygdala gene networks. The amygdala transcriptome was profiled on female and male pigs that were either exposed to viral-elicited MIA or not and were weaned or nursed. Overall, 111 genes presented interacting or independent effects of weaning, MIA or sex (FDR-adjusted P-value < 0.05). PIGY upstream reading frame (PYURF) and orthodenticle homeobox 2 (OTX2) are genes associated with MIA-related neurological disorders, and presented significant under-expression in weaned relative to nursed pigs exposed to MIA, with an opposite pattern was observed in non-MIA pigs. Enriched among the genes presenting highly over- or under-expression profiles were 24 KEGG pathways including inflammation, and neurological disorders. Our results indicate that MIA and sex can modulate the effect of weaning stress on the molecular mechanisms in the developing brain. Our findings can help identify molecular targets to ameliorate the effects of pre-and postnatal stressors on behaviors regulated by the amygdala such as aggression and feeding.
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http://dx.doi.org/10.1093/g3journal/jkab113DOI Listing
April 2021

Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes.

J Integr Neurosci 2021 Mar;20(1):21-31

Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, 61801 IL, USA.

The prolonged effects of maternal immune activation in response stressors during gestation on the offspring's molecular pathways after birth are beginning to be understood. An association between maternal immune activation and neurodevelopmental and behavior disorders such as autism and schizophrenia spectrum disorders has been detected in long-term gene dysregulation. The incidence of alternative splicing among neuropeptides and neuropeptide receptor genes, critical cell-cell signaling molecules, associated with behavior may compromise the replicability of reported maternal immune activation effects at the gene level. This study aims to advance the understanding of the effect of maternal immune activation on transcript isoforms of the neuropeptide system (including neuropeptide, receptor and connecting pathway genes) underlying behavior disorders later in life. Recognizing the wide range of bioactive peptides and functional receptors stemming from alternative splicing, we studied the effects of maternal immune activation at the transcript isoform level on the hippocampus and amygdala of three-week-old pigs exposed to maternal immune activation due to viral infection during gestation. In the hippocampus and amygdala, 29 and 9 transcript isoforms, respectively, had maternal immune activation effects (-value < 0.01). We demonstrated that the study of the effect of maternal immune activation on neuropeptide systems at the isoform level is necessary to expose opposite effects among transcript isoforms from the same gene. Genes were maternal immune activation effects have also been associated with neurodevelopmental and behavior disorders. The characterization of maternal immune activation effects at the transcript isoform level advances the understanding of neurodevelopmental disorders and identifies precise therapeutic targets.
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http://dx.doi.org/10.31083/j.jin.2021.01.332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103820PMC
March 2021

The initial visual performance modulates the effects of anodal transcranial direct current stimulation over the primary visual cortex on the contrast sensitivity function.

Neuropsychologia 2021 06 3;156:107854. Epub 2021 Apr 3.

Department of Psychology, Hebei Normal University, Shijiazhuang, China. Electronic address:

Transcranial direct current stimulation (tDCS) has great potential to modulate cortical excitability and further facilitate visual function or rehabilitation. However, tDCS modulation effects are largely variable, possibly because of the individual differences in initial performance. The present study investigated the influence of the initial performance on contrast sensitivity function (CSF) following tDCS. Fifty healthy participants were randomly assigned to three groups: anodal, cathodal and sham stimulation. The CSF was measured through a grating detection task before and immediately after tDCS. Active and reference electrodes were applied to the primary occipital cortex (Oz) and the middle of the head (Cz) for 20 min with an intensity of 1.5 mA, respectively. Compared with sham stimulation, anodal or cathodal stimulation had no effect on the area under the log CSF (AULCSF) or contrast sensitivity (CS) of various spatial frequencies at the group level. However, a negative relationship was found between initial performance and the AULCSF change (or CS change at a spatial of frequency 8 c/°) after the application of anodal tDCS, indicating that the degree of change was dependent on initial performance, with greater gains observed for those with poorer initial performance. Initial performance modulated the effect of anodal tDCS over the Oz on the CSF, indicating that the Oz plays a crucial role in visual function. These results contribute to a deep understanding of the mechanisms of tDCS and to the design of more precise and efficient personalized simulation approaches based on individual differences.
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http://dx.doi.org/10.1016/j.neuropsychologia.2021.107854DOI Listing
June 2021

Sob gene is critical to wing development in Bombyx mori and Tribolium castaneum.

Insect Sci 2021 Apr 6. Epub 2021 Apr 6.

State Key Laboratory of Silkworm Genome Biology, Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University, Chongqing, China.

The development of insect appendages requires the expression of multiple genes in a strict spatial and temporal order. The odd-skipped family genes are vital transcriptional factors involved in embryonic development. The development and morphogenesis of the insect wing requires multiple transcription factors to regulate the expression of wing patterning genes at the transcriptional level. However, the function of odd-related genes in insect wing morphogenesis and development during postembryonic stages is unclear. We focused on the roles of the sister of odd and bowl (sob) gene, a member of odd-skipped family genes, during the wing morphopoiesis in Bombyx mori using the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 system and in Tribolium castaneum by RNA interference. The results showed that the wings were significantly smaller and degenerated, and wing veins were indistinct in the sob gene loss-of-function group in both B. mori and T. castaneum. Quantitative real-time polymerase chain reaction revealed that the Tcsob gene regulated the expression of wing development genes, such as the cht 7 and the vg gene. The findings suggest the importance of sob gene in insect wing morphology formation during postembryonic stages.
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http://dx.doi.org/10.1111/1744-7917.12911DOI Listing
April 2021
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