Objective To investigate the potential therapeutic targets and underlying molecular mechanisms of Z-ligustilide(Z-LIG)in treating retinitis pigmentosa(RP).Methods By integrating multiple databases,such as GeneCards and TargetNet,common targets for RP and Z-LIG were identified.Protein-protein interaction(PPI)network analysis of the targets was conducted using the STRING database and analyzed in Cytoscape to identify core targets.The DAVID database was employed for the functional enrichment analysis of Gene Ontology(GO)and the pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)for the core targets.The PubChem database was accessed for molecular docking verification to validate the binding affinity between Z-LIG and the core targets.Finally,male rd10 mice were randomly divided into a control group(n=5)and a Z-LIG treatment group(n=5).The protective effect of Z-LIG on the visual function in rd10 mice was verified through visual electrophysiology and behavioral tests.Western blotting and RT-qPCR were utilized to investigate the molecular mechanism of action.Results A total of 66 shared targets between RP and Z-LIG were identified through the screening process.PPI network analysis identified 55 key targets.GO enrichment analysis yielded 623 terms,which covering 3 dimensions,including cellular component(CC),molecular function(MF),and biological process(BP),such as inflammatory response.KEGG pathway enrichment analysis further concentrated 124 terms,which were enriched in the PI3K-Akt signaling pathway.Molecular docking suggested that Z-LIG could specifically bind with high affinity to RP-related core targets(such as EGFR and STAT3)via hydrogen bonds.In animal experiments,compared to the control group,the rd10 mice from the Z-LIG group showed a greater preference for the dark environment in the light/dark transition test(P<0.05),exhibited significantly higher amplitudes of A-wave and B-wave in electroretinogram(ERG)(P<0.05),greater number of outer nuclear layers,with fewer apoptotic cells and less microglial activation(P<0.05),demonstrated obviously reduced protein levels of p-PI3K/PI3K and p-AKT/AKT in the retina(P<0.05),and had notably down-regulated mRNA levels of pro-inflammatory cytokines IL-1β and IL-6(P<0.05).Conclusion Z-LIG may exert a protective effect on the retina of rd10 mice by inhibiting the activation of the PI3K/AKT-inflammatory axis,thereby delaying retinal degeneration.

As one of the key enzymes in cell metabolism, the activity of citrate synthase 3 (CS3) regulates the substance and energy metabolism of organisms. The protein members of CS3 family were identified from the whole genome of apple, and bioinformatics analysis was performed and expression patterns were analyzed to provide a theoretical basis for studying the potential function of CS3 gene in apple. BLASTp was used to identify members of the apple CS3 family based on the GDR database, and the basic information of CS3 protein sequence, subcellular localization, domain composition, phylogenetic relationship and chromosome localization were analyzed by Pfam, SMART, MEGA5.0, clustalx.exe, ExPASy Proteomics Server, MEGAX, SOPMA, MEME, WoLF PSORT and other software. The tissue expression and inducible expression characteristics of 6 CS3 genes in apple were determined by acid content and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR). Apple CS3 gene family contains 6 members, and these CS3 proteins contain 473-608 amino acid residues, with isoelectric point distribution between 7.21 and 8.82. Subcellular localization results showed that CS3 protein was located in mitochondria and chloroplasts, respectively. Phylogenetic analysis divided them into 3 categories, and the number of genes in each subfamily was 2. Chromosome localization analysis showed that CS3 gene was distributed on different chromosomes of apple. The secondary structure of protein is mainly α-helix, followed by random curling, and the proportion of β-angle is the smallest. The 6 members were all expressed in different apple tissues. The overall expression trend from high to low was the highest relative expression content of MdCS3.4, followed by MdCS3.6, and the relative expression level of other members was in the order of MdCS3.3 > MdCS3.2 > MdCS3.1 > MdCS3.5. qRT-PCR results showed that MdCS3.1 and MdCS3.3 genes had the highest relative expression in the pulp of 'Chengji No. 1' with low acid content, and MdCS3.2 and MdCS3.3 genes in the pulp of 'Asda' with higher acid content had the highest relative expression. Therefore, in this study, the relative expression of CS3 gene in apple cultivars with different acid content in different apple varieties was detected, and its role in apple fruit acid synthesis was analyzed. The experimental results showed that the relative expression of CS3 gene in different apple varieties was different, which provided a reference for the subsequent study of the quality formation mechanism of apple.
Citric Acid ; Malus/genetics* ; Citrate (si)-Synthase ; Phylogeny ; Citrates

Lysine-specific demethylase 1 (LSD1) is the firstly discovered histone demethylase. In recent years, LSD1 has become a hot topic in the study of the development and progression of malignancies, and its expression is closely related to the poor prognosis of malignancies. At present, some studies have showed that LSD1 is strongly related to the proliferation, invasion and metastasis of triple-negative breast cancer (TNBC). However, the specific mechanism is not fully understood. This article summarizes the possible mechanism of the development and progression in LSD1 and TNBC, and reviews the latest progress of LSD1 in the clinical research application of TNBC, so as to provide a reference for drug combination therapy in TNBC patients.

Pyruvate dehydrogenase E1 component subunit beta-1 (PDHB-1) is a gene encoding the β-subunit of pyruvate dehydrogenase complex, which plays an important role in fruit acid accumulation. The aim of this study was to investigate the evolution characteristics of apple PDHB-1 family and its expression in apples with different acid contents. Bioinformatics analysis was performed using databases including NCBI, Pfam and software including ClustalX, MEGA, and TBtools. By combining titratable acid content determination and quantitative real-time PCR (qRT-PCR), the expression of this family genes in the peel and pulp of apple 'Asda' and 'Chengji No.1' with different acid content were obtained, respectively. The family members were mainly located in chloroplast, cytoplasm and mitochondria. α-helix and random coil were the main factors for the formation of secondary structure in this family. Tissue-specific expression profiles showed that the expression of most members were higher in fruit than in other tissues. qRT-PCR results showed that the expression profile of most members was consistent with the profile of titratable acid contents. In the peel, the expression levels of 14 members in 'Asda' apples with high acid content were significantly higher than that in 'Chengji No.1' apples with low acid content, where the expression difference of MdPDHB1-15 was the most significant. In the pulp, the expression levels of 17 members in 'Asda' apples were significantly higher than that in 'Chengji No.1' apples, where MdPDHB1-01 was the most highly expressed. It was predicted that PDHB-1 gene family in apple plays an important role in the regulation of fruit acidity.
Malus/metabolism* ; Fruit/genetics* ; Protein Structure, Secondary

Hydrocephalus is often treated with a cerebrospinal fluid shunt (CFS) for excessive amounts of cerebrospinal fluid in the brain. However, it is very difficult to distinguish whether the ventricular enlargement is due to hydrocephalus or other causes, such as brain atrophy after brain damage and surgery. The non-trivial evaluation of the consciousness level, along with a continuous drainage test of the lumbar cistern is thus clinically important before the decision for CFS is made. We studied 32 secondary mild hydrocephalus patients with different consciousness levels, who received T1 and diffusion tensor imaging magnetic resonance scans before and after lumbar cerebrospinal fluid drainage. We applied a novel machine-learning method to find the most discriminative features from the multi-modal neuroimages. Then, we built a regression model to regress the JFK Coma Recovery Scale-Revised (CRS-R) scores to quantify the level of consciousness. The experimental results showed that our method not only approximated the CRS-R scores but also tracked the temporal changes in individual patients. The regression model has high potential for the evaluation of consciousness in clinical practice.