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The pathogenic mechanism of syndactyly type V identified in aHoxd13Q50R knock-in mice

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Bone Research 2024年第2期12卷 349-360页

作者： Han Wang Xiumin Chen Xiaolu Meng Yixuan Cao Shirui Han Keqiang Liu Ximeng Zhao Xiuli Zhao Xue Zhang McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Complex Severe and Rare DiseasesDepartment of Medical GeneticsInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China department of Orthopedics State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifthmetacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) ofHOXD13 in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlyingpathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed togenerate a Hoxd13Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly andpartial syndactyly between digits 2-4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in *** on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limbdevelopment, we found the ectopically expressed Shh, Grem1 and Fgf8 and down-regulated Bmp2 in the embryonic limb bud atE10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibitednotable disparities in mRNA level between the Hoxd13Q50R homozygotes and the wild-type. These genes are known to be involvedin various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopicexpression of Shh and Fgf8, in conjunction with the down-regulation of Bmp2, results in a failure of patterning along both theanterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascadeultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations inhomozygous mice. These findings suggest that abnormal expression of SHH, FGF8, and BMP2 induced by HOXD13Q50R may beresponsible for the manifestation of human SDTY5.

关键词： BMP2 mechanism finding

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration

Study on the flow structure in curved open channels with suspended vegetation using multi relaxation time lattice Boltzmann method

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Journal of Hydrodynamics 2024年第2期36卷 300-315页

作者： He-fang Jing Qiao-ling Zhang Wei-hong Wang Zong-ning Zhang School of Mathematics and Information Science North Minzu UniversityYinchuan750021China School of Civil Engineering North Minzu UniversityYinchuan750021China department of basic Courses Zhengzhou University of Science and TechnologyZhengzhou450064China

Suspended vegetation in rivers,lakes,reservoirs and canals can change flow structure,which will in turn affect the sediment transport and cause the variation of water ecological *** order to study the characteristics of bend flow through suspended vegetation,three-dimensional numerical simulations are carried out by using the multi-relaxation-time lattice Boltzmann method(MRT-LBM).The drag force induced by vegetation is added in the velocity correction in the equilibrium distribution and a hybrid format combined bounce and specular reflection scheme is applied in the solid-fluid *** the validation of this model,six cases are designed to conduct the numerical simulations according to the root depth and the arrangement of *** simulated results show that the suspended vegetation can redistribute the flow structure in curved open *** the arrangement of suspended vegetation,the main flow moves to the side without vegetation,and the distribution of velocity tends to be balanced when vegetation is arranged on the entire cross section,the range of circulating current is reduced from the whole cross section to the local position without vegetation,however,the circulating current can still exist in the curve where the suspended vegetation enters less than half of the water *** addition,it can also be concluded that the suspended vegetation can affect the lateral gradient of flow velocity,and the bed shear stress in the curved channel.

关键词： Multi-relaxation-time lattice Boltzmann method(MRT-LBM) suspended vegetation curved open channel circulating current bed shearstress

The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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Neural Regeneration Research 2024年第5期19卷 1084-1091页

作者： Yijing Zhao Tong Li Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Key Laboratory of Birth Regulation and Control Technology of National Health Commission of China Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao UniversityJinanShandong ProvinceChina

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal ***,the precise mechanism underlying the role of H2S in this situation remains *** this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal *** also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ***,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these *** findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关键词： chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-cysteine lipopolysaccharide microglia miR-9-5p neuroprotection

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military Medical Research 2024年第4期11卷 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong department of Histology and Embryology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China department of Hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying ***:The expression level of GPR65 was evaluated in both human and mouse fibrotic ***,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver ***,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic ***,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 Hepatic fibrosis Hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

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BIOCELL 2024年第6期48卷 945-958页

作者： YUNBAO GUO XU LIU QI XU XIAOTONG ZHOU JIAWEI LIU YANYAN XU YAN LU HAIYAN LIU The department of Neurosurgery First Hospital of Jilin UniversityChangchun130021China The department of Anatomy College of Basic Medical SciencesJilin UniversityChangchun130021China The Third College of Clinical Medicine Jilin UniversityChangchun130021China

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve *** is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae *** also has anti-infection,antitumor,and immunomodulatory *** this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and ***,the mechanism through which honokiol regulates glioma cell apoptosis is still ***:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control ***-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative ***,MAPK signaling and ferroptosis were detected via western ***:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased *** of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were veriﬁ***:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling *** data could lead to new ideas for future research and therapy for patients with glioma.

关键词： Human glioma Honokiol RNA-seq Apoptosis Ferroptosis MAPK

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

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Current Medical Science 2024年第1期44卷 102-109页

作者： Tian-ci LIU Mo-han ZHENG Xing-yue ZENG Rui KANG Ayibaota Bahabayi Bulidierxin Tuerhanbayi Song-song LU Chen LIU department of Clinical Laboratory Peking University People's HospitalBeijing 100044China School of basic Medical Sciences Peking University Health Science CenterBeijing 100191China

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their *** Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy *** cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also *** correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further *** The TFR/TFH ratio increased significantly in NSCLC *** CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage ***-1^(+)ICOS+TFH cells showed a downward trend with increasing *** IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy ***,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar *** numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage *** Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

关键词： non-small cell lung cancer follicular helper T cells follicular regulatory T cells progression

Low-rank spectral estimation algorithm of learning Markov model

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Frontiers of Mathematics in China 2024年第3期19卷 137-155页

作者： Yongye ZHAO Shujun BI department of basic Courses Guangzhou Maritime UniversityGuangzhou 510725China department of Mathematics South China University of TechnologyGuangzhou 510640China

This paper proposes a low-rank spectral estimation algorithm of learning Markov ***,an approximate projection algorithm for the rank-constrained frequency matrix set is proposed,and thereafter its local Lipschitzian error bound ***,we propose a low-rank spectral estimation algorithm for estimating the state transition frequency matrix and the probability matrix of Markov model by applying the approximate projection algorithm to correct the maximum likelihood estimation of the frequency matrix,and prove that there is only a multiplying constant difference in estimation errors between the low-rank spectral estimation and the maximum likelihood estimation under appropriate ***,numerical comparisons with the prevailing maximum likelihood estimation,spectral estimation,and rank-constrained maxi-mum likelihood estimation show that the low-rank spectral estimation algorithm is effective.

关键词： Markov model low-rank spectral estimation error bound approximate projection

Film Flow of Nano-Micropolar Fluid with Dissipation Effect

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Computer Modeling in Engineering & Sciences 2024年第9期140卷 2487-2512页

作者： Abuzar Abid Siddiqui Mustafa Turkyilmazoglu department of basic Sciences&Humanities Faculty of Engineering&TechnologyBahauddin Zakariya UniversityMultanPakistan department of Mathematics Hacettepe UniversityAnkaraTürkiye department of Medical Research China Medical University HospitalChina Medical UniversityTaichungTaiwanChina

The physical problem of the thin film flow of a micropolar fluid over a dynamic and inclined substrate under the influence of gravitational and thermal forces in the presence of nanoparticles is *** different types of nanoparticle samples are accounted for in this current study,namely gold Au,silver Ag,molybdenum disulfide MoS_(2),aluminum oxide Al_(2)O_(3),and silicon dioxide SiO_(2).Blood,a micropolar fluid,serves as the common base *** exact closed-form solution for this problem is derived for the first time in the *** results are particularly validated against those for the Newtonian fluid and show excellent *** was found that increasing values of the spin boundary condition and micropolarity lead to a reduction in both the thermal and momentum boundary layers.A quantitative decay in the Nusselt number for a micropolar fluid,as compared to a Newtonian one for all the tested nanoparticles,is *** and silver nanoparticles(i)intensify in the flow parameter as the concentration of nanoparticles increases(ii)yield a higher thermal transfer rate,whereas molybdenum disulfide,aluminum oxide,and silicon dioxide exhibit a converse attitude for both Newtonian and micropolar *** reduction in film thickness for fluid comprising gold particles,as compared to the rest of the nanoparticles,is remarkable.

关键词： Thin film flow micropolar fluid nanoparticles molybdenum disulfide inclined substrate