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Biomedical subjects

Lin Jiang

Publications and source records attributed to Lin Jiang.

At least 19 recordsLinked to original sources

The astragaloside-brucea javanica oil nanoemulsion inhibiting the progression of oral squamous cell carcinoma through CDK1- HOXC10-MTFR2 pathway.

OBJECTIVE: This study aimed to investigate whether Astragaloside-Brucea javanica oil nanoemulsion (AS/BJO-NEs) inhibits the malignant progression of oral squamous cell carcinoma (OSCC) and to further explore its potential regulatory mechanisms. METHODS: Immunohistochemistry (IHC) was used to evaluate the expression of related pathway proteins in human OSCC and adjacent normal tissues. Stable OSCC cell lines with knockdown or overexpression of CDK1/HOXC10 were established. The effects of AS/BJO-NEs and the underlying mechanisms were assessed in vitro through colony formation, wound healing, and Transwell invasion assays, as well as RT-qPCR, western blot, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays. An OSCC subcutaneous xenograft model in nude mice was constructed for in vivo validation using RT-qPCR, western blot, hematoxylin and eosin (H&E) staining, and IHC. RESULTS: Analysis of clinical samples revealed upregulated expression of CDK1, P-EZH2, HOXC10, MTFR2, and N-cadherin, alongside downregulated expression of H3K27me3 and E-cadherin in OSCC tissues. In vitro experiments confirmed that AS/BJO-NEs downregulated CDK1 in a concentration-dependent manner, subsequently reducing the expression of P-EZH2, HOXC10, and MTFR2, increasing H3K27me3 levels, and inhibiting cell proliferation, migration, and invasion. H3K27me3 was enriched in the HOXC10 promoter region, and HOXC10 directly bound to and activated MTFR2 transcription. In vivo experiments demonstrated that AS/BJO-NEs effectively inhibited tumor growth, regulated molecules within this pathway and epithelial-mesenchymal transition (EMT) markers, whereas CDK1 overexpression counteracted these effects CONCLUSION: This study demonstrates that AS/BJO-NEs exert anti-OSCC effects by inhibiting CDK1, downregulating HOXC10, thereby reducing MTFR2 expression, and suppressing cell proliferation, migration, invasion, and the EMT process.

Squamous Cell Carcinoma of Head and Neck↗

Lactacystin inhibits 3T3-L1 adipocyte differentiation through induction of CHOP-10 expression.

Hormonal induction triggers a cascade leading to the expression of CCAAT/enhancer-binding protein(C/EBP)alpha and peroxisome proliferator-activated receptor (PPAR) gamma, C/EBPalpha, and PPARgamma turns on series of adipocyte genes that give rise to the adipocyte phenotype. Previous findings indicate that C/EBPbeta, a transcriptional activator of the C/EBPalpha and PPARgamma genes, is rapidly expressed after induction, but lacks DNA-binding activity and therefore cannot activate transcription of the C/EBPalpha and PPARgamma genes early in the differentiation program. Acquisition of DNA-binding activity of C/EBPbeta occurs when CHOP-10, a dominant-negative form of C/EBP family members, is down-regulated and becomes hyperphosphorylated as preadipocytes traverse the G1-S checkpoint of mitotic clonal expansion. Evidences are presented in this report that lactacystin, a proteasome inhibitor, up-regulated the CHOP-10 expression, blocked the DNA-binding activity of C/EBPbeta, and subsequently inhibited MCE as well as adipocyte differentiation.

3T3-L1 Cells↗

Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium complex in water.

Hydrophobic Fréchet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III) complexes have been applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source. The catalysts were found to be finely dissolved in the liquid substrates in the aqueous mixture and exhibited high catalytic activity and enantioselectivity (52-97% ee). The catalytic loading could be decreased to 0.01 mol% and good conversion was still obtained with excellent enantioselectivity. Moreover, the catalyst could be easily precipitated from the mixture by adding hexane and reused several times without affecting the high enantioselectivity.

Catalysis↗

Prediction of mitochondrial proteins using discrete wavelet transform.

A new method was proposed for prediction of mitochondrial proteins by the discrete wavelet transform, based on the sequence-scale similarity measurement. This sequence-scale similarity, revealing more information than other conventional methods, does not rely on subcellular location information and can directly predict protein sequences with different length. In our experiments, 499 mitochondrial protein sequences, constituting a mitochondria database, were used as training dataset, and 681 non-mitochondrial protein sequences were tested. The system can predict these sequences with sensitivity, specificity, accuracy and MCC of 50.30%, 95.74%, 76.53% and 0.54, respectively. Source code of the new program is available on request from the authors.

Amino Acid Sequence↗

New algorithms and an in silico benchmark for computational enzyme design.

The creation of novel enzymes capable of catalyzing any desired chemical reaction is a grand challenge for computational protein design. Here we describe two new algorithms for enzyme design that employ hashing techniques to allow searching through large numbers of protein scaffolds for optimal catalytic site placement. We also describe an in silico benchmark, based on the recapitulation of the active sites of native enzymes, that allows rapid evaluation and testing of enzyme design methodologies. In the benchmark test, which consists of designing sites for each of 10 different chemical reactions in backbone scaffolds derived from 10 enzymes catalyzing the reactions, the new methods succeed in identifying the native site in the native scaffold and ranking it within the top five designs for six of the 10 reactions. The new methods can be directly applied to the design of new enzymes, and the benchmark provides a powerful in silico test for guiding improvements in computational enzyme design.

Algorithms↗

Local sequence information-based support vector machine to classify voltage-gated potassium channels.

In our previous work, we developed a computational tool, PreK-ClassK-ClassKv, to predict and classify potassium (K+) channels. For K+ channel prediction (PreK) and classification at family level (ClassK), this method performs well. However, it does not perform so well in classifying voltage-gated potassium (Kv) channels (ClassKv). In this paper, a new method based on the local sequence information of Kv channels is introduced to classify Kv channels. Six transmembrane domains of a Kv channel protein are used to define a protein, and the dipeptide composition technique is used to transform an amino acid sequence to a numerical sequence. A Kv channel protein is represented by a vector with 2000 elements, and a support vector machine algorithm is applied to classify Kv channels. This method shows good performance with averages of total accuracy (Acc), sensitivity (SE), specificity (SP), reliability (R) and Matthews correlation coefficient (MCC) of 98.0%, 89.9%, 100%, 0.95 and 0.94 respectively. The results indicate that the local sequence information-based method is better than the global sequence information-based method to classify Kv channels.

Algorithms↗

[Integrated model system for environmental policy analysis].

An integrated model system for environmental policy analysis is built up with a Computable General Equilibrium (CGE) model as a core model, which is linked with an environmental model, air dispersion model, and health effect model (exposure-response functions) in an explicit way, therefore the model system is capable of evaluating the effects of policies on environment, health and economy and their interactions comprehensively. This method is used to analyze the effects of Beijing presumptive (energy) taxes on air quality, health, welfare and economic growth, and the conclusion is that sole presumptive taxes may slow down the economic growth, but the presumptive taxes with green tax reform can promote Beijing sustainable development.

Environment↗

Structure-activity relationships for a new family of sulfonylurea herbicides.

Acetohydroxyacid synthase (AHAS; EC 2.2.1.6) catalyzes the first common step in branched-chain amino acid biosynthesis. The enzyme is inhibited by several chemical classes of compounds and this inhibition is the basis of action of the sulfonylurea and imidazolinone herbicides. The commercial sulfonylureas contain a pyrimidine or a triazine ring that is substituted at both meta positions, thus obeying the initial rules proposed by Levitt. Here we assess the activity of 69 monosubstituted sulfonylurea analogs and related compounds as inhibitors of pure recombinant Arabidopsis thaliana AHAS and show that disubstitution is not absolutely essential as exemplified by our novel herbicide, monosulfuron (2-nitro-N-(4'-methyl-pyrimidin-2'-yl) phenyl-sulfonylurea), which has a pyrimidine ring with a single meta substituent. A subset of these compounds was tested for herbicidal activity and it was shown that their effect in vivo correlates well with their potency in vitro as AHAS inhibitors. Three-dimensional quantitative structure-activity relationships were developed using comparative molecular field analysis and comparative molecular similarity indices analysis. For the latter, the best result was obtained when steric, electrostatic, hydrophobic and H-bond acceptor factors were taken into consideration. The resulting fields were mapped on to the published crystal structure of the yeast enzyme and it was shown that the steric and hydrophobic fields are in good agreement with sulfonylurea-AHAS interaction geometry.

Acetolactate Synthase↗

Adaptive evolution of phytoplankton cell size.

We present a simple nutrient-phytoplankton-zooplankton (NPZ) model that incorporates adaptive evolution and allometric relations to examine the patterns and consequences of adaptive changes in plankton body size. Assuming stable environmental conditions, the model makes the following predictions. First, phytoplankton should evolve toward small sizes typical of picoplankton. Second, in the absence of grazers, nutrient concentration is minimized as phytoplankton reach their fitness maximum. Third, increasing nutrient flux tends to increase phytoplankton cell size in the presence of phytoplankton-zooplankton coevolution but has no effect in the absence of zooplankton. Fourth, phytoplankton reach their fitness maximum in the absence of grazers, and the evolutionary nutrient-phytoplankton system has a stable equilibrium. In contrast, phytoplankton may approach their fitness minimum in the evolutionary NPZ system where phytoplankton and zooplankton are allowed to coevolve, which may result in oscillatory (unstable) dynamics of the evolutionary NPZ system, compared with the otherwise stable nonevolutionary NPZ system. These results suggest that evolutionary interactions between phytoplankton and zooplankton may have contributed to observed changes in phytoplankton sizes and associated biogeochemical cycles over geological time scales.

Adaptation, Physiological↗

Protein interactions limit the rate of evolution of photosynthetic genes in cyanobacteria.

Using a bioinformatic approach, we analyzed the correspondence in genetic distance matrices between all possible pairwise combinations of 82 photosynthetic genes in 10 species of cyanobacteria. Our analysis reveals significant correlations between proteins linked in a conserved gene order and between structurally identified interacting protein scaffolds that coordinate the binding of cofactors involved in photosynthetic electron transport. Analyses of amino acid substitution rates suggest that the tempo of evolution of genes encoding core metabolic processes in the photosynthetic apparatus is highly constrained by protein-protein, protein-lipid, and protein-cofactor interactions (collectively called "protein interactions"). These interactions are critical for energy transduction, primary charge separation, and electron transport and effectively act as an internal selection pressure governing the conservation of clusters of photosynthetic genes in oxygenic prokaryotic photoautotrophs. Consequently, although several proteins within the photosynthetic apparatus are biophysically and physiologically inefficient, selection has not significantly altered the genes encoding these essential proteins over billions of years of evolution. In effect, these core proteins have become "frozen metabolic accidents."

Computational Biology↗

An artificial aspartic proteinase system.

A series of aza crown ether derivatives with or without carboxyl groups in their side arms were synthesized and the former showed deacylation activities toward amino acid p-nitrophenyl ester hydrohalides. Substrate-selective phenomena were also observed. The relationship between the structures and deacylation activities of corresponding compounds suggested a nucleophilic catalytic mechanism. The results partially simulate some aspartic proteinases in the case of catalytic mechanism and are also useful for us to understand the detailed catalytic process of aspartic proteinases.

Aspartic Acid Endopeptidases↗

A "solvated rotamer" approach to modeling water-mediated hydrogen bonds at protein-protein interfaces.

Water-mediated hydrogen bonds play critical roles at protein-protein and protein-nucleic acid interfaces, and the interactions formed by discrete water molecules cannot be captured using continuum solvent models. We describe a simple model for the energetics of water-mediated hydrogen bonds, and show that, together with knowledge of the positions of buried water molecules observed in X-ray crystal structures, the model improves the prediction of free-energy changes upon mutation at protein-protein interfaces, and the recovery of native amino acid sequences in protein interface design calculations. We then describe a "solvated rotamer" approach to efficiently predict the positions of water molecules, at protein-protein interfaces and in monomeric proteins, that is compatible with widely used rotamer-based side-chain packing and protein design algorithms. Finally, we examine the extent to which the predicted water molecules can be used to improve prediction of amino acid identities and protein-protein interface stability, and discuss avenues for overcoming current limitations of the approach.

Algorithms↗

Predator diet breadth influences the relative importance of bottom-up and top-down control of prey biomass and diversity.

We investigated the effects of predator diet breadth on the relative importance of bottom-up and top-down control of prey assemblages, using microbial food webs containing bacteria, bacterivorous protists and rotifers, and two different top predators. The experiment used a factorial design that independently manipulated productivity and the presence or absence of two top predators with different diet breadths. Predators included a "specialist" predatory ciliate Euplotes aediculatus, which was restricted to feeding on small prey, and a "generalist" predatory ciliate Stentor coeruleus, which could feed on the entire range of prey sizes. Both total prey biomass and prey diversity increased with productivity in the predator-free control and specialist predator treatments, a pattern consistent with bottom-up control, but both remained unchanged by productivity in the generalist predator treatment, a pattern consistent with top-down control. Linear food chain models adequately described responses in the generalist predator treatment, whereas food web models incorporating edible and inedible prey (which can coexist in the absence of predators) adequately described responses in the specialist predator treatment. These results suggest that predator diet breadth can play an important role in modulating the relative strength of bottom-up and top-down forces in ecological communities.

Animals↗

Synthesis of dendritic catalysts and application in asymmetric transfer hydrogenation.

Frechet-type core-functionalized chiral diamine-based dendritic ligands and hybrid dendritic ligands condensed from polyether wedge and Newkome-type poly(ether-amide) supported multiple ligands were designed and synthesized. The solubility of hybrid dendrimers was found to be finely controlled by the polyether dendron. The catalytic efficiency and recovery use of dendritic ruthenium complexes were compared in the transfer hydrogenation of acetophenone. The core-functionalized dendritic catalysts demonstrated much better recyclability, which verified the stabilizing effects of the bulky polyether wedge on the catalytically active complex. Moreover, the dendritic catalysts were applied in the asymmetric transfer hydrogenation of ketones, enones, imine, and activated olefin, and moderate to excellent enantioselectivitiy was achieved comparable to that of monomeric catalysts.

Journal Article↗

Effects of development and iron status on ceruloplasmin expression in rat brain.

The increased iron content in the brain of subjects with aceruloplasminemia has implicated ceruloplasmin (CP) as a major factor in the regulation of regional brain iron content. In this study, we investigated the effects of age and iron on CP expression in rat brain. In all four regions, the iron concentrations increased with developmental age. There is a similar trend in age-induced changes in CP mRNA and protein. The CP mRNA and protein levels were both lowest at postnatal day (PND) 7. The expression increased gradually with age, reaching the highest at PND196 in the striatum and substantia nigra, and at PND21 and PND63 in the cortex and hippocampus, respectively. This suggests the existence of an age-dependent pre-transcriptional regulation and a regionally specific effect of age on CP expression in the brain. Although total iron in all four regions was significantly lower in the rats fed with a low-iron diet for 6 weeks and higher in the rats with a high-iron diet than those in the control animals, no significant between-group differences in CP mRNA and protein were found in these animals, except in the substantia nigra where a significant increase in CP protein in high-iron rats was observed, and the reverse in low-iron rats. These findings suggested that the effects of iron on CP expression in the brain may be region-specific, and that regulation of CP expression by iron in the substantia nigra was at the post-transcriptional level.

Aging↗

Fast fourier transform-based support vector machine for prediction of G-protein coupled receptor subfamilies.

Although the sequence information on G-protein coupled receptors (GPCRs) continues to grow, many GPCRs remain orphaned (i.e. ligand specificity unknown) or poorly characterized with little structural information available, so an automated and reliable method is badly needed to facilitate the identification of novel receptors. In this study, a method of fast Fourier transform-based support vector machine has been developed for predicting GPCR subfamilies according to protein's hydrophobicity. In classifying Class B, C, D and F subfamilies, the method achieved an overall Matthe's correlation coefficient and accuracy of 0.95 and 93.3%, respectively, when evaluated using the jackknife test. The method achieved an accuracy of 100% on the Class B independent dataset. The results show that this method can classify GPCR subfamilies as well as their functional classification with high accuracy. A web server implementing the prediction is available at http://chem.scu.edu.cn/blast/Pred-GPCR.

Algorithms↗

Red environmental noise and the appearance of delayed density dependence in age-structured populations.

Previous work suggests that red environmental noise can lead to the spurious appearance of delayed density dependence (DDD) in unstructured populations regulated only by direct density dependence. We analysed the effect of noise reddening on the pattern of spurious DDD in several variants of the density-dependent age-structured population model. We found patterns of spurious DDD in structured populations with either density-dependent fertility or density-dependent survival of the first age class, inconsistent with predictions from unstructured population models. Moreover, we found that nonspurious negative DDD always emerges in populations with deterministic chaotic dynamics, regardless of population structure or the type of environmental noise. The effect of noise reddening in generating spurious DDD is often negligible in the chaotic region of population deterministic dynamics. Our findings suggest that differences in species' life histories may exhibit different patterns of spurious DDD (owing to noise reddening) than predicted by unstructured models.

Age Factors↗