Background: Hypochondroplasia (HCH) is a prevalent form of dwarfism linked to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, causing missense alterations. We previous report was the first to identify FGFR3(G382D) gain-of-function variants with a positive family history as a novel cause of HCH. However, the precise contribution of FGFR3 to the pathogenesis of HCH remains elusive. Methods: We generated an Fgfr3 (V376D) mutation mouse model using CRISPR/Cas9 technology and performed proteomic analyses to investigate the molecular mechanisms and potential therapeutic targets of HCH. Radiography and micro-computed tomography were employed to assess the bone-specific phenotype in Fgfr3 (V376D)mutant mice. Immunofluorescence, western blotting, and flow cytometry were used to systematically investigate the underlying mechanisms and therapeutic targets. Results: We observed that Fgfr3 (V376D) mutant mice exhibit a bone-specific phenotype, with symmetrically short limb bones, partially resembling the dwarfism phenotype of patients with HCH. We demonstrated that the mutant-activated FGFR3 promotes heat shock protein B 6 (HSPB6)-mediated cuproptosis by inhibiting chondrocyte autophagy both in vivo and in vitro. Additionally, we revealed that FGFR3 (G382D) mutation leads to enhanced ERK signaling, increased Drp1-mediated mitochondrial fission, and upregulated cuproptosis-related protein ferredoxin 1 (FDX1). Furthermore, genetic and pharmacological inhibition of the HSPB6-ERK-Drp1-FDX1 pathway partially alleviate the phenotypes of FGFR3 mutants. Conclusions: Our study provides the first evidence for the pathogenicity of a gain-of-function mutation in FGFR3 (G382D) using mouse and cell models, and it underscores the potential of targeting the HSPB6-ERK-Drp1-FDX1 axis as a novel therapeutic approach for HCH. Translational potential of this article: We first demonstrate that impaired autophagy and enhanced cuproptosis are pivotal in the pathogenesis of HCH. This study not only enlarged the therapeutic potential of targeting cuproptosis for treating FGFR3 mutation-related HCH but also provided a novel perspective on the role of the HSPB6-ERK-Drp1-FDX1 signaling pathway in the development of HCH. Consequently, this article provides valuable insights into the mechanisms and treatment strategies for FGFR3 mutation-related chondrodysplasia.
In this study, the self-developed silkworm excrement deodorant special preservative was used and the silkworm excrement was treated by field composting in order to realize safely silkworm excrement quick safety decomposing and utilization of cleaner fertilizer in paddy field and ecological nutrient of rice growth.The treated silkworm excrement organic fertilizer was applied as rice base fertilizer and tillering fertilizer for the study on rice habitat and security growth under excrement fast-rotting.The results showed that the temperature of the compost after the silkworm excremen transformation promoter was increased rapidly, and could convert stinky organics degradation or conversion into antioxidants.The heater temperature showed that the temperature of 5 d during the treating 10 d could maintain above 60 ℃.Rapid decomposition process, could effectively inhibit the growth of harmful microorganisms and kill pathogenic microorganisms silkworm excrement.After the quick-rot, we conducted a safety test, the Escherichia coli showed a descending trend.The odor eliminated after 4-5 d silkworm excrement fast rot.After application of this fertilizer to paddy fields, leaf chlorophyll content was 30.9% higher at the tillering stage, nitrate reductase activity increased by 48.9%, root activity increased by 21.3%, dry matter increased by 26.5%.Paddy yield increased 10.8%-22.9% and paddy soil permeability increased.Silkworm excrement fast-rotting to promote security growth and health utilization of rice growth is a safe, ecological, and healthy method, and the application effect is good.
根据已发表的猪链球菌9型(SS9)荷兰5218分离株的基因核苷酸序列保守区域,设计一对特异性引物,以SS9钦州分离株抽提的DNA为模板,通过PCR方法扩增cps9H基因片段,并对其进行克隆、测序和分析.结果表明,4株SS9钦州分离株的cps9H目的基因长为389bp,与已知的7个国内外SS9毒株cps9H基因片段的核苷酸及推导的氨基酸序列比较,同源性分别为96.7%~100%和91.5%~100%.
A pair of primer was designed using the nucleotide sequence of Northeast white goose IFN-α gene obtained from GenBank(Accession No.AY524422).Total RNA was extracted from cultures of goose peripheral blood lymphocytes under stimulation of GPMV,and the cDNA was amplified using reverse transcription-polymerase chain reaction(RT-PCR),which was subsequently cloned into pMD18-T vector and sequenced.The results showed that the open reading frame(ORF) of Guangxi goose interferon-α(GoIFN-α) gene consisted of 576 bp,encoding 192 amino acid residues.Among them,there were seven cysteine residues and two potential glycosyl binding site(NDT and NHT).Compared with the sequences of other goose IFN-α gene in GenBank,the homologies of nucleotide and amino acid between Guangxi goose and white Northeast goose(AY524422) was found the highest(98.3 and 96.4%,respectively).However,these two indices among Guangxi goose and chicken,cow,swine,rat,dog and human,etc.were lower.These results indicated that the IFN had species specificity,the homologies of interferon among different animal species depend on their genetic relationships.
Gene chip technology is based on the achievements of human geneome project.It is a new technology combining microeletronics,biology,physics,chemistry,and computer science.It can be widely used in analysis of gene expression,mutation detection,analysis of nucleic acid polymorphism,gene sequencing,drug screening and so on in the field of biology research.The paper reviewed the development process of gene chip,principle,procedure of bacterium detection,application in biology research,existing problems and prospect.
According to the sequences of American type strain VR2332 and natural variant strain of PRRSV in recent years,two specific primers were designed and two specific gene fragments of 225 bp and 427 bp were amplified respectively.By adjusting RT-PCR conditions,multiplex PCR method was established for detecting PRRSV type strain and NSP2 variant strain simultaneously.The blood and lung of sixteen samples isolated from diseased or dead porcine in different districts of Guangxi were detected by this method,and the results showed that 15 samples were positive,among them,one sample was American type strain(225 bp) and 14 samples were variant strains(427 bp).These results indicated that multiplex PCR method had high specificity and sensitivity,which could be applied in clinical diagnosis and would provide bases on studying pathogen of epidemiological swine high fever and control of PRRSV in Guangxi.
小鹅瘟是由鹅细小病毒 (Goose Parvovirus,GPV)引起的雏鹅和雏番鸭的一种急性或亚急性、败血性传染病.该病主要侵害3~20日龄小鹅,以渗出性肠炎、肝脏、肾脏、心脏等实质器官炎症为主要特征.该病传播快,发病率和死亡率高,是严重危害养鹅业的重要传染病.