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Biomedical subjects

Gang Zhang

Publications and source records attributed to Gang Zhang.

At least 19 recordsLinked to original sources

Age as a core disease modifier: Distinct clinical, molecular and prognostic landscapes of essential thrombocythaemia in adolescents and young adults.

Essential thrombocythaemia (ET) in adolescents and young adults (AYA, 15-39 years) is a distinct entity with an incompletely defined prognosis. In this multicentre retrospective study, 1728 ET patients from 29 centres across China were stratified into AYA (n = 328) and non-AYA (≥40 years, n = 1400) cohorts. We compared their clinical profiles, genomic landscapes, long-term outcomes and risk factors for progression to post-ET myelofibrosis (MF). AYA patients had fewer cardiovascular risks and lower thrombosis rates, but higher rates of extreme thrombocytosis. Molecularly, AYA patients were enriched for calreticulin (CALR) mutations, whereas Janus kinase 2 (JAK2) predominated in older patients. The burden of non-driver mutations (tet methylcytosine dioxygenase 2 [TET2], DNA methyltransferase 3A [DNMT3A], ASXL transcriptional regulator 1 [ASXL1], SH2‑B adaptor protein 3 [SH2B3]) was lower in AYA patients. Consequently, AYA patients achieved superior long-term outcomes across all key survival endpoints, including overall, myelofibrosis-free and leukaemia-free survival. Analysis of post-ET MF progression risks identified age-specific patterns: CALR mutations are enriched in younger patients and show an age-specific association with MF progression. AYA-ET constitutes a unique clinicomolecular subtype with a favourable prognosis, supporting age-stratified management. The enrichment of CALR mutations and their specific link to MF progression in young patients underscore the urgent need for targeted therapies against CALR-mutant clones.

adolescents and young adults (AYA)↗

Assembly and Characterization of the First Complete Mitochondrial Genome of Tussilago farfara L.: Insights into Biological Functions and Phylogenetic Relationships within the Asteraceae Family.

Tussilago farfara L., a member of the Asteraceae family, is an economically valuable species due to its edible and medicinal properties. To elucidate the structural characteristics, genetic mechanisms, and evolutionary pathways of the organelle genomes of T. farfara, we sequenced, assembled, and annotated its mitochondrial genome for the first time. The complete mitochondrial genome of T. farfara spans 306,024 bp and contains 33 mitochondrial protein-coding genes (PCGs), 3 rRNAs, and 22 tRNAs. Analysis of the nucleotide substitution rate and genetic diversity revealed that most mitochondrial genome genes may have undergone purifying selection, indicating a slow evolutionary rate and a relatively conserved genomic structure. We further identified 13 fragments of chloroplast-derived DNA integrated into the mitochondrial genome, evidencing intracellular gene transfer. Collinearity analysis showed that Arctium lappa shares the most extensive mitochondrial homologous sequences and the highest sequence similarity with T. farfara. Phylogenetic analysis based on the mitochondrial genome helped to clarify the evolutionary and taxonomic position of T. farfara within the Asteraceae family. The mitochondrial genome sequence of T. farfara provides a valuable genomic resource for species identification and for evolutionary studies within the Asteraceae family.

Genome, Mitochondrial↗

Generation of Cdc20 RNAi-Sensitive Cell Lines to Study Mitotic Exit.

Accurate mitotic progression ensures the fidelity of genome passage. Cdc20 is a key mitotic regulator. It promotes mitotic exit by activating the anaphase-promoting complex or cyclosome (APC/C) and monitors kinetochore-microtubule attachment through activating the spindle assembly checkpoint (SAC). Precise characterization of Cdc20 requires efficient depletion of endogenous Cdc20, which is extremely difficult to achieve by RNA interference (RNAi). This chapter describes the methodology to generate Cdc20 RNAi-sensitive cell lines with the help of CRISPR/Cas9 technology. These cell lines are highly sensitive to Cdc20 RNAi and provide a very useful tool for Cdc20 functionality investigation without the interference of endogenous Cdc20 protein. Similar strategy could be applied to other genes.

Cdc20 Proteins↗

Passive immunization with anti-ganglioside antibodies directly inhibits axon regeneration in an animal model.

Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.

Animals↗

Ordered binary arrays of Au nanoparticles derived from colloidal lithography.

By using angle-resolved colloidal lithography and O2-plasma etched bilayers of hexagonally packed spheres as templates, we succeeded in fabrication of highly ordered binary arrays of gold nanoparticles with varied shapes, for instance, with a shuttlecock-like shape composed of a small crescent-shaped nanoparticle and a big fan-shaped one. The size and shape of both small and big nanoparticles obtained were manipulated by the plasma etching period and the incidence angle of Au vapor flow. The subsequent thermal annealing led to binary arrays of round Au nanoparticles with a rather narrow distribution in terms of size and shape. Our approach should pave a simple and versatile colloidal way to form binary nanoparticle arrays, holding immense promise for technical applications such as nanoelectronics and nanophotonics.

Colloids↗

Evidence of influenza a virus RNA in siberian lake ice.

Influenza A virus infects a large proportion of the human population annually, sometimes leading to the deaths of millions. The biotic cycles of infection are well characterized in the literature, including in studies of populations of humans, poultry, swine, and migratory waterfowl. However, there are few studies of abiotic reservoirs for this virus. Here, we report the preservation of influenza A virus genes in ice and water from high-latitude lakes that are visited by large numbers of migratory birds. The lakes are along the migratory flight paths of birds flying into Asia, North America, Europe, and Africa. The data suggest that influenza A virus, deposited as the birds begin their autumn migration, can be preserved in lake ice. As birds return in the spring, the ice melts, releasing the viruses. Therefore, temporal gene flow is facilitated between the viruses shed during the previous year and the viruses newly acquired by birds during winter months spent in the south. Above the Arctic Circle, the cycles of entrapment in the ice and release by melting can be variable in length, because some ice persists for several years, decades, or longer. This type of temporal gene flow might be a feature common to viruses that can survive entrapment in environmental ice and snow.

Base Sequence↗

The NPro product of bovine viral diarrhea virus inhibits DNA binding by interferon regulatory factor 3 and targets it for proteasomal degradation.

Bovine viral diarrhea virus (BVDV) is a pestivirus that can establish a persistent infection in the developing fetus and has the ability to disable the production of type I interferon. In this report, we extend our previous observations that BVDV encodes a protein able to specifically block the activity of interferon regulatory factor 3 (IRF-3), a transcription factor essential for interferon promoter activation, by demonstrating that this is a property of the N-terminal protease fragment (NPro) of the BVDV polyprotein. Although BVDV infections cause relocalization of cellular IRF-3 from the cytoplasm to the nucleus early in infection, NPro blocks IRF-3 from binding to DNA. NPro has the additional property of targeting IRF-3 for polyubiquitination and subsequent destruction by cellular multicatalytic proteasomes. The autoprotease activity of NPro is not required for the inhibition of type I interferon induction or the targeting of IRF-3 for degradation.

Animals↗

Exit from mitosis triggers Chs2p transport from the endoplasmic reticulum to mother-daughter neck via the secretory pathway in budding yeast.

Budding yeast chitin synthase 2 (Chs2p), which lays down the primary septum, localizes to the mother-daughter neck in telophase. However, the mechanism underlying the timely neck localization of Chs2p is not known. Recently, it was found that a component of the exocyst complex, Sec3p-green fluorescent protein, arrives at the neck upon mitotic exit. It is not clear whether the neck localization of Chs2p, which is a cargo of the exocyst complex, was similarly regulated by mitotic exit. We report that Chs2p was restrained in the endoplasmic reticulum (ER) during metaphase. Furthermore, mitotic exit was sufficient to cause Chs2p neck localization specifically by triggering the Sec12p-dependent transport of Chs2p out of the ER. Chs2p was "forced" prematurely to the neck by mitotic kinase inactivation at metaphase, with chitin deposition occurring between mother and daughter cells. The dependence of Chs2p exit from the ER followed by its transport to the neck upon mitotic exit ensures that septum formation occurs only after the completion of mitotic events.

Cell Cycle Proteins↗

Comparison of different brands of IVIg in an in vitro model of immune neuropathy.

Intravenous immunoglobulin (IVIg) is used for the treatment of a number of autoimmune neurological disorders. Whether different brands of IVIg or different lots of the same brand are comparably efficacious for the treatment of neurological disorders is not clear. To examine this issue we compared the efficacy of different brands and/or lots of IVIg in a cell culture model of immune neuropathy. We report that products examined were equally effective and there was no lot-to-lot variability in our experimental model. These findings support the notion that efficacy of different IVIg products is comparable in a standardized model.

Autoimmune Diseases↗

A new method to realize cluster synchronization in connected chaotic networks.

In this article, a new method, which constructs a coupling scheme with cooperative and competitive weight-couplings, is used to stabilize arbitrarily selected cluster synchronization patterns with several clusters for connected chaotic networks. By the coupling scheme, a sufficient condition about the global stability of the selected cluster synchronization patterns is derived. That is to say, when the sufficient condition is satisfied, arbitrarily selected cluster synchronization patterns in connected chaotic networks can be achieved via an appropriate coupled scheme. The effectiveness of the method is illustrated by an example.

Algorithms↗

[Study on vibrational spectra and structure of 4-mercaptopyridine monomer and dimer using density functional theory].

The optimized molecular structure and vibrational frequencies of 4-mercaptopyridine monomer and dimer were studied by density functional theory using B3LYP method with the 6-311++G(d, p) basis set. On the basis of the calculations, the assignments of vibrational spectra were performed on monomer and dimer, and the change in structure and vibrational spectrum of dimer as well as the intermolecular force of forming dimer were investigated. It was found that the two pyridine ring planes are vertical to each other, and the dimer was formed through H-bonding, which is between the nitrogen on one ring and the hydrogen of SH moieties on another. Furthermore, the structure and vibrational spectrum of the dimer have some changes with respect to those of the monomer.

English Abstract↗

Wall "thickness" effects on Raman spectrum shift, thermal conductivity, and Young's modulus of single-walled nanotubes.

We demonstrate that at a finite temperature, an effective wall thickness of a single-walled carbon nanotube (SWNT) should be W = Ws + Wd, where Ws is the static thickness defined as the extension of the outmost electronic orbit and Wd the dynamic thickness due to thermal vibration of atoms. Both molecular simulations and a theoretical analysis show that Wd is proportional to T1/2. We find that the increase of dynamic thickness with temperature is the main mechanism of Raman spectrum shift. The introduction of the dynamic thickness changes some conclusions about Young's modulus and reduces the values of thermal conductivity.

Journal Article↗

pH-responsive capsules derived from nanocrystal templating.

In the current work we demonstrate a facile and versatile way to create hydrophilic polymeric capsules by integration of Au nanocrystal templating, surface-initiated atom-transfer radical polymerization, and selective chemical cross-linking of polymer shells. Capsules of the homopolymer of 2-(dimethylamino)ethyl methacrylate and its copolymers with 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate were constructed. They swell at low pH and shrink at high pH. On the basis of the pH sensitivity of the resulting capsules, encapsulation and release of a drug model, rhodamine 6G, were realized. Furthermore, by cleaving Au-S bonds between Au cores and polymer shells, capsules containing free Au cores were generated, paving a simple pathway to introduce more functionality to the polymeric capsules.

Journal Article↗

Kinetics and template nucleation of self-assembled hydroxyapatite nanocrystallites by chondroitin sulfate.

Biomineralization is an important process, which is often assisted by biomolecules. In this paper, the effect of chondroitin sulfate on the crystallization of hydroxyapatite was examined quantitatively based on a generic heterogeneous nucleation model. It is found that chondroitin sulfate can suppress the supersaturation-driven interfacial structure mismatch between the hydroxyapatite crystal and the substrate and promote the formation of ordered hydroxyapatite nanocrystallite assemblies. The nucleation mechanism of self-aligned hydroxyapatite nanocrystallites was examined from the viewpoints of kinetics and interfacial structure and properties, which contributes to an understanding of the fundamentals of biomineralization of self-assembled structures. The results obtained from this study will provide a basic principle to design and fabricate highly orderly organic-inorganic hybrid materials.

Biocompatible Materials↗

Fabrication of superhydrophobic surfaces from binary colloidal assembly.

In this work, superhydrophobic surfaces were derived from binary colloidal assemblies. CaCO(3)-loaded hydrogel spheres and silica or polystyrene ones were consecutively dip-coated on silicon wafers. The former assemblies were recruited as templates for the latter self-assembly. Due to the hydrophilicity difference between silicon wafers and CaCO(3)-loaded hydrogel spheres, the region selective localization of silica or polystyrene spheres leads to irregular binary structures with a hierarchical roughness. The subsequent modification with low surface energy molecules yields a superhydrophobic surface. The heating treatment may largely enhance the mechanical stability of the resulting binary structures, which allows regeneration of the surface superhydrophobicity, providing a good durability in practice.

Journal Article↗

Theoretical studies on the structure and aromaticity of Ti2P6+.

Cationic cluster Ti2P6+ has been studied within density functional theory. The structure of this cluster is predicted to be a slightly distorted tetragonal prism. The dissociation energy of this cationic cluster is higher than that of the known sandwich compound, [(P5)2Ti]2-, because of the different bonding in these two compounds. In Ti2P6+, the hybridization of P atoms of the ring is sp3. The bonding between the metal atoms and the P ring is mainly sigma-pi. While in [(P5)2Ti]2-, the P atoms take sp2 hybridization, the bonding between the metal atom and the rings is the typical pi-pi interaction. The electronic delocalization is another stabilizing factor for Ti2P6+. The nuclear independent chemical shift indicates that Ti2P6+ is a three-dimensional aromatic molecule. The predicted infrared and NMR help to identify the Ti2P6+ conformations in experiment.

Journal Article↗