1.BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period.
Zhenmeiyu LI ; Guoping LIU ; Lin YANG ; Mengge SUN ; Zhuangzhi ZHANG ; Zhejun XU ; Yanjing GAO ; Xin JIANG ; Zihao SU ; Xiaosu LI ; Zhengang YANG
Protein & Cell 2024;15(1):21-35
The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals
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Mice
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Humans
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Ependymoglial Cells/metabolism*
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Hedgehog Proteins/metabolism*
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Ferrets/metabolism*
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Cerebral Cortex
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Neurogenesis
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Mammals/metabolism*
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Neuroglia/metabolism*
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Bone Morphogenetic Protein 7/metabolism*
2.Effects of canthaxanthin in increasing reproductive hormone secretion through re-ducing ovarian oxidative stress injury on egg production rate of Huaixiang chickens
Zhuo SUN ; Tingting XIE ; Zhuangzhi ZHAO ; Junwen ZHAO ; Anting ZHANG ; Jiang WU ; Mei XIAO ; Lilong AN
Chinese Journal of Veterinary Science 2024;44(10):2266-2276
A total of 360 healthy 26 week old Huaixiang hens were randomly divided into 10 groups,of which,five groups were reared at normal temperature(NC,NT1,NT2,NT3,NT4)and other five groups were reared at high temperature(HC,HT1,HT2,HT3,HT4),all chickens were feed with 0,4,6,8,10 mg/kg canthaxanthin(CX)respectively.The pre-test period was 2 weeks and the main test period was 9 weeks.The results showed that high temperature reduced the egg pro-duction rate(P<0.05),led to damage and hemorrhage in the ovaries,decreased the activity of su-peroxide dismutase(SOD),glutathione peroxidase(GSH-Px)in the serum and the ovaries(P<0.05),decreased the levels of FSH,LH,P4,and E2(P<0.05),decreased the expression of FSHR,LHR,ER,and PR(P<0.05),and increased the levels of malonaldehyde(MDA)(P<0.05)in the ovaries.Addition of CX increased the egg production rate(P<0.05),increased the activity of serum and ovarian SOD and GSH-Px enzymes(P<0.05),decreased the content of serum and ovarian MDA(P<0.05)),increased the ovarian levels of FSH,LH,P4,E2(P<0.05),and increased the o-varian expression of FSHR,LHR,ER,and PR(P<0.05)in Huaixiang chickens at normal and high temperature environmental conditions,respectively.Among them,the highest egg production rate,the strongest antioxidant capacity of serum and ovarian tissues,the best integrity of ovarian tis-sues,ovarian reproductive hormone secretion and expression of reproductive hormone receptors were observed in Huaixiang chickens when 6 mg/kg of CX was added to the diet under normal temperature and when 8 mg/kg CX was added to the diet under high temperature conditions.The results showed that under normal and high temperature conditions,adding CX to the diet signifi-cantly increased the antioxidant capacity of serum and ovaries,alleviated the damage of ovary,pro-moted the secretion of reproductive hormone and the expression of reproductive hormone recep-tors,and increased egg production rate.Dietary supplemented with CX could not restore the dam-age and repair of ovarian tissue,the secretion of reproductive hormone and receptor to normal tem-perature level.The effects of CX on egg production rate,ovarian tissue structure,reproductive hor-mone and receptor expression in chickens were affected by the environmental temperature.When the egg production rate,antioxidant capacity of ovarian tissues,reproductive hormone levels and receptor expression of Huaixiang chickens were optimal,the amount of CX in high temperature en-vironment was more than that of the dose in normal temperature environment.
3.Genetically-engineered "all-in-one" vaccine platform for cancer immunotherapy.
Aihua WU ; Yingzhi CHEN ; Hairui WANG ; Ya CHANG ; Meng ZHANG ; Pengfei ZHAO ; Yisi TANG ; Qin XU ; Zhuangzhi ZHU ; Yang CAO ; Yongzhuo HUANG
Acta Pharmaceutica Sinica B 2021;11(11):3622-3635
An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity. A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human use. We discovered a novel cancer immunostimulant, trichosanthin (TCS), that is a clinically used protein drug in China, and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide, TCS, and a cell-penetrating peptide (CPP), termed an "all-in-one" vaccine, for transcutaneous cancer immunization. The TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor models. The vaccines were prepared
4. Homeobox Gene Six3 is Required for the Differentiation of D2-Type Medium Spiny Neurons
Xiaolei SONG ; Haotian CHEN ; Zicong SHANG ; Heng DU ; Zhenmeiyu LI ; Yan WEN ; Guoping LIU ; Dashi QI ; Yan YOU ; Zhengang YANG ; Zhuangzhi ZHANG ; Zhejun XU
Neuroscience Bulletin 2021;37(7):985-998
Medium spiny neurons (MSNs) in the striatum, which can be divided into D1 and D2 MSNs, originate from the lateral ganglionic eminence (LGE). Previously, we reported that Six3 is a downstream target of Sp8/Sp9 in the transcriptional regulatory cascade of D2 MSN development and that conditionally knocking out Six3 leads to a severe loss of D2 MSNs. Here, we showed that Six3 mainly functions in D2 MSN precursor cells and gradually loses its function as D2 MSNs mature. Conditional deletion of Six3 had little effect on cell proliferation but blocked the differentiation of D2 MSN precursor cells. In addition, conditional overexpression of Six3 promoted the differentiation of precursor cells in the LGE. We measured an increase of apoptosis in the postnatal striatum of conditional Six3-knockout mice. This suggests that, in the absence of Six3, abnormally differentiated D2 MSNs are eliminated by programmed cell death. These results further identify Six3 as an important regulatory element during D2 MSN differentiation.
5. Decoding Cortical Glial Cell Development
Xiaosu LI ; Guoping LIU ; Lin YANG ; Zhenmeiyu LI ; Zhuangzhi ZHANG ; Zhejun XU ; Yuqun CAI ; Heng DU ; Zihao SU ; Ziwu WANG ; Yangyang DUAN ; Haotian CHEN ; Zicong SHANG ; Yan YOU ; Qi ZHANG ; Miao HE ; Zhengang YANG ; Bin CHEN
Neuroscience Bulletin 2021;37(4):440-460
Mouse cortical radial glial cells (RGCs) are primary neural stem cells that give rise to cortical oligodendrocytes, astrocytes, and olfactory bulb (OB) GABAergic interneurons in late embryogenesis. There are fundamental gaps in understanding how these diverse cell subtypes are generated. Here, by combining single-cell RNA-Seq with intersectional lineage analyses, we show that beginning at around E16.5, neocortical RGCs start to generate ASCL1
6.Prevalence and Molecular Characterization of Echinococcus granulosus Sensu Stricto in Northern Xinjiang, China
Baoping GUO ; Zhuangzhi ZHANG ; Xueting ZHENG ; Yongzhong GUO ; Gang GUO ; Li ZHAO ; Ren CAI ; Bingjie WANG ; Mei YANG ; Xi SHOU ; Wenbao ZHANG ; Bin JIA
The Korean Journal of Parasitology 2019;57(2):153-159
Echinococcus granulosus is an important zoonotic parasite globally causing cystic echinococcosis (CE) in humans and animals. In this study, prevalence of CE and variation of cox1 gene sequence were analyzed with isolates E. granulosus collected from different areas in northern Xinjiang, China. The survey showed that 3.5% of sheep and 4.1% of cattle were infected with CE. Fragment of cox1 was amplified from all the positive sheep and cattle samples by PCR. In addition, 26 positive samples across the 4 areas were included. The isolates were all E. granulosus sensu stricto (s.s.) containing 15 haplotypes (Hap1-15), and clustered into 2 genotypes, G1 (90.1%, 91/101) and G3 (9.9%, 10/101). Hap1 was the most common haplotype (48.5%, 49/101). Hap9 were found in humans samples, indicating that sheep and cattle reservoir human CE. It is indicate that E. granulosus may impact on control of CE in livestock and humans in the region.
Animals
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Cattle
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China
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Cross-Sectional Studies
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Echinococcosis
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Echinococcus granulosus
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Echinococcus
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Genotype
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Haplotypes
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Humans
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Livestock
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Parasites
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Polymerase Chain Reaction
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Prevalence
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Sheep
7. Efficacy and safety of domestic dasatinib as second-line treatment for chronic myeloid leukemia patients in the chronic phase
Yilin CHEN ; Long WANG ; Guolin YAN ; Zhuangzhi YANG ; Zhiping HUANG ; Youshan ZHANG ; Zhe ZHAO ; Chucheng WAN ; Ying BAO ; Hang XIANG ; Hua YIN ; Lifeng CHEN ; Yingyuan XIONG ; Li MENG ; Weiming LI
Chinese Journal of Hematology 2019;40(2):98-104
Objective:
To investigate the efficiency and safety of domestic tyrosine kinase inhibitor (TKI) dasatinib (Yinishu) as second-line treatment for patients with chronic myeloid leukemia in chronic phase (CML-CP).
Methods:
A retrospective analysis of clinical data of CML-CP patients who received domestic dasatinib as second-line treatment in the CML collaborative group hospitals of Hubei province from March 2016 to July 2018 was performed. The optimal response rate, the cumulative complete cytogenetic response (CCyR), the cumulative major molecular responses (MMR), progression free survival (PFS), event free survival (EFS) and adverse effects (AEs) of the patients were assessed at 3, 6 and 12 months of treatment.
Results:
A total of 83 CML-CP patients were enrolled in this study. The median follow-up time was 23 months. The optimal response rates at 3, 6 and 12 months in 83 CML-CP patients treated with dasatinib were 77.5% (54/71), 72.6% (61/75) and 60.7% (51/69), respectively. By the end of follow-up, the cumulative CCyR and MMR rates were 65.5% (55/80) and 57.1% (48/73), respectively. The median time to achieving CCyR and MMR was 3 months. During follow-up time, the PFS rate was 94.0% (79/83) and the EFS rate was 77.4% (65/83). The most common non-hematological AEs of dasatinib were edema (32.5%), rash itching (18.1%) and fatigue (13.3%). The common hematological AEs of dasatinib were thrombocytopenia (31.3%), leukopenia (19.3%) and anemia (6.0%).
Conclusion
Domestic dasatinib was effective and safe as the second-line treatment of CML-CP patients and it can be used as an option for CML-CP patients.
8. Physiological characteristics of Echinococcus and their association with interventions against echinococcosis
Jun LI ; Gang GUO ; Zhuangzhi ZHANG ; Wenbao ZHANG
Chinese Journal of Preventive Medicine 2018;52(2):210-214
Alveolar and cystic echinococcosis are important zoonotic diseases caused by the dog/fox tapeworms of Echinococcus granulosus and E. multilocularis, which are distributed in almost whole the world. The diseases remarkably impact on the people's health and economic development of communities. Echinococcus tapeworms need two mammalian animals to complete their lifecycle. The worms undergo different developmental stages (adult, egg/oncosphere, cyst, and protoscolex). Each stage has its own distinct physiological characteristics. We summarize the characteristics and emphasize that some features that strongly impact on design of control program. Based on the lifecycle of these worms, two stages are infectious, one is egg the only stage for primarily infecting humans and intermediate host, and another stage is protoscolex, the only stage for infecting the definite hosts of the worms. Eggs are produced by the adult worms parasitized in the intestine of definite hosts. It takes 45 days for eggs becoming mature in dogs. With this feature of the tapeworm, New Zealand and Tasmania in Australia designed control program for deworming 8 times annually with an interval between deworms at 45 days. E. multilocularis takes 28-30 days in dog/fox producing mature eggs. Given that co-existence of E. granulosus and E. multilocularis in western China, a control measure so called "prepatent deworming control measure" has been used in these endemic areas with dosing worms in dogs every month. It normally takes 12-15 months for producing protosocleces in E. granulosus cysts in sheep. If meat markets attract most lambs, that is an effective measure for controlling cystic echinococcosis given that there are no protoscoleces produced from those lambs. In addition, Echinococcus has its own unique biological characteristics, such as sexual reproduction and asexual reproduction, single-cell layer structure of cyst, bidirectional development of protoscoleces induced by bile salts, and long term of infection causing host asymptomatic reaction make the parasites a models for addressing some biological and biomedical issues. And more, hydatid cyst fluid is the antigen resource for identifying diagnostic reagents; the specific gene expressed in oncospheres has been developed as an effective vaccine used for control program. With the development and application of high-throughput omics, including genomics, transcriptomics and proteomics, we can use the physiological characteristics of Echinococcus for searching diagnostic reagents, developing preventive vaccines and identify new drug targets.
9.Identification of Medicinal Insect Vespa mandarinia from Its Adulterants Using DNA Barcode
Kaige XU ; Zhuangzhi CHEN ; Zizhong YANG ; Yunjiao GUO ; Chenggong LI ; Yu ZHAO ; Chenggui ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(2):313-318
This study aimed at exploring a fast method to accurately identify the medicinal insect Vespa mandarinia Smith from its adulterants using DNA barcode and COI sequences.The extracted DNAs from V.mandarinia and its adulterants V.soror were amplified by polymerase chain reaction (PCR) and sequenced bilaterally based on COI barcode sequence investigation.The information of the COI sequences of V.mandarinia and V.soror were gathered from GenBank.All the sequences were compared and analyzed,and their intraspecific and interspecific genetic distances were calculated using MEGA 6.06.In addition,the phylogenetic tree was established with neighbor-joining (NJ) method.As a result,the COI sequences of V.mandarinia and V.soror were successfully amplified.The minimum interspecific distance between V.mandarinia and its adulterants was 0.152 ± 0.017,being considerably larger than the maximal intraspecific distance between V.mandarinia,0.009±0.004.The constructed phylogenetic tree showed an independent branch for each species.It was concluded that the DNA barcode based on COI sequence can efficiently identify V.mandarinia and its adulterants.This study provided an innovative tool for the quality control and market regulation of Chinese materia medica,securing the safe medication of V.mandarinia.
10.Clinical anatomical study on the development of pedicle of atlantoaxial pedicle in preschool children
Chunli WU ; Zhuangzhi YOU ; Jun SHI ; Shaojie ZHANG ; Zhijun LI ; Jinghong YU ; Xing WANG
Journal of Regional Anatomy and Operative Surgery 2017;26(8):547-551
Objective To discuss the characteristics,growth and development of atlantoaxial pedicle in preschool children,and to provide the basic theoretical basis for the design,production and clinical application of pedicle screw technique in the treatment of atlantoaxial disease in preschool children.Methods Excluded patients with atlantoaxial fractures,deformities,tuberculosis and tumor,the clinical data of 60 children aged from 3 to 6 years old with cervical spondylolisthesis were collected.The original CT images were reconstructed in DICOM format and the subjects were reconstructed with Mimics software.The subjects were grouped by age to measure and analyze the atlantoaxial pedicle correlation.Results The pedicle width(PW),pedicle height(PH) and total length of pedicle bone channel (PL) increased gradually with age.The PW/PH ratio of the vertebrae(C1) is greater than 1.0,and that is, the width of the pedicle of the C1 pedicle is greater than the height.The PW/PH ratio of the vertebral (C2) is less than 1.0,which means the width of the pedicle of the C1 pedicle is less than the height.Conclusion The growth and development of spine in preschool children are fast, and the pedicle of atlantoaxial calculus in different age groups has different developmental characteristics.In this study,the diameter of the pedicle of the atlantoaxial pedicle in the 3 to 6 year old children is increasing with age.The pedicle screw with the smallest diameter of 3.5 mm can be implanted into the atlantoaxial pedicle with feasibility in theory.

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