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Biomedical subjects

Xi Zhang

Publications and source records attributed to Xi Zhang.

At least 19 recordsLinked to original sources

Improving recombinant protein productivity in CHO cells via multi-omics data integration.

Chinese hamster ovary (CHO) cells represent the dominant host system for the production of recombinant therapeutic proteins. In recent decades, extensive research has focused on process/media optimization and cell line engineering to improve both the productivity and quality of biopharmaceutical proteins produced in CHO cells. Nevertheless, the inherent complexity of biological pathways and the heterogeneous cellular responses to different environmental conditions have posed substantial challenges to traditional methodologies. Recent advances in omics technologies have enabled comprehensive characterization of CHO cell physiology, providing multidimensional molecular and phenotypic insights that facilitate the enhancement of recombinant protein production. This review first summarizes the methodologies and advances in CHO omics research, including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. It then examines contemporary approaches to integrate and analyze multi-omics data in CHO cells. The review further elucidates how these multi-omics datasets can be strategically applied across various developmental stages, including cell line selection, genetic engineering, expression vector design, and bioprocess optimization. Finally, we explore the transformative potential of integrating multi-omics with artificial intelligence and discuss promising future research directions in CHO cell studies. These emerging paradigms offer novel opportunities for data-driven cell engineering and bioprocess optimization in CHO-based biomanufacturing.

Bioprocessing↗

CaMYB121-CaABF2 negative feedback loop modulates CaNHX2 expression to confer salt tolerance in pepper.

Salt stress is a major abiotic factor that severely restricts pepper (Capsicum annuum) production. Although abscisic acid (ABA) is vital for salt tolerance, the transcriptional regulatory networks governing ABA-mediated salt defense remain largely unknown. Here, we uncovered a negative feedback loop between CaMYB121 and CaABF2.1/2 that modulates the expression of CaNHX2.1/2/3, thereby enhancing salt tolerance in pepper plants. RNA-seq analysis revealed that CaMYB121 displayed an expression pattern consistent with that of CaNHX2 after salt treatment. Silencing CaMYB121 markedly reduced salt tolerance and inhibited root growth. Mechanistically, CaMYB121 directly binds to the CaNHX2 promoter to activate transcription, thereby promoting salt resilience. Salt stress also robustly triggered ABA signaling genes, with CaABF2.1/2 displaying expression patterns closely mirroring those of CaMYB121. Transient silencing of CaABF2.1/2 results in phenotypes similar to those observed with CaMYB121 suppression. Notably, CaMYB121 activates CaABF2.1/2 transcription by binding to its promoters, whereas CaABF2.1/2 represses CaMYB121 expression by directly targeting its promoter, forming a self-regulating feedback loop that prevents excessive defense activation. Collectively, our findings reveal a CaMYB121-CaABF2 feedback circuit that dynamically balances growth and defense to optimize salt tolerance in pepper plants.

Salt Tolerance↗

Recipient-derived vs. donor-derived CAR-T-cell therapy in relapsed B-cell acute lymphoblastic leukemia patients after transplantation: A multi-center retrospective study.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cells have been demonstrated to be an effective treatment for relapsed B-cell acute lymphoblastic leukemia (B-ALL) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells for CAR-T therapy can be derived from the peripheral blood (recipient) of the patient or donor. Despite having identical genomes, the different maturation environments of these T cells can lead to functional differences. This study aimed to compare the clinical outcomes of CAR-T cells derived from these two sources. METHODS: This multicenter, retrospective cohort study collected clinical data from 36 patients who experienced B-ALL relapse after allo-HSCT and received CD19 CAR-T cell therapy between January 2016 and October 2023 across seven centers. The primary endpoint was complete remission (CR)/CR with an incomplete hematologic recovery (CRi) rate at 28 days post-CAR-T cell infusion. Secondary endpoints included the 2-year overall survival (OS) rate, 2-year event-free survival (EFS) rate, incidence of graft-versus-host disease (GVHD), cytokine release syndrome (CRS), and CAR-T cell-related encephalopathy syndrome (CRES). RESULTS: A retrospective analysis was performed on 36 patients: 12 in the recipient group and 24 in the donor group. The recipient and donor groups showed no statistically significant differences in CR/CRi rates (83.3% vs. 100.0%, P = 0.105), 2-year EFS rates (50.8% vs. 51.6%, P = 0.617), or 2-year OS rates (49.5% vs. 63.6%, P = 0.215). In addition, the incidences of GVHD, CRS, and CRES did not significantly differ between the two groups. Further analysis within the donor group revealed 12 matched sibling donors (MSDs) and 12 haploidentical donors (HIDs). The 2-year EFS rate was statistically significantly greater in the HID group than in the MSD group (75.0% vs. 30.7%, P = 0.043), whereas no significant differences were observed in the CR/CRi rates, 2-year OS, or the incidence of GVHD, CRS, and CRES between these subgroups. CONCLUSIONS: Both recipient-derived and donor-derived CD19 CAR-T cell therapies are effective treatment options for B-ALL relapsed post-allo-HSCT patients. HID-derived CAR-T cells offer a longer EFS and may be considered the optimal choice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2400085297.

Adolescent↗

Molecular mechanisms and breeding strategies for heat tolerance in vegetable crops under global warming.

Extreme heat driven by climate change poses a catastrophic threat to global vegetable production, undermining nutritional security because of the heightened physiological sensitivity and succulent tissues of these crops. This review synthesizes the multistage impacts of heat stress across critical developmental phases-from germination to reproduction-emphasizing morphological impairments (such as leaf wilting and floral abortion) and physiological disruptions (including photosynthetic inhibition and oxidative damage). We systematically dissect thermotolerance mechanisms in vegetables, highlighting transcriptional reprogramming by HSFs, WRKY, and NAC transcription factors; chaperone-mediated proteostasis via HSPs; epigenetic remodeling; Ca2+-ROS signaling pathways; and the role of phase separation dynamics. Importantly, we propose six strategic pathways to develop heat-resilient vegetables: harnessing natural variation through pan-genome-driven allele mining; employing biotechnological interventions such as CRISPR-mediated editing and synthetic promoters; engineering multistress tolerance by targeting conserved 'core response' pathways; exploiting epigenetic memory to achieve transgenerational resilience; optimizing source-sink dynamics with ''Climate-Responsive Carbon Optimization; and applying plant growth regulators and nanotechnology to enhance thermotolerance. Together, these strategies chart a clear roadmap for climate-smart vegetable breeding and call for interdisciplinary collaboration to translate molecular discoveries into practical breeding approaches for sustainable food systems under escalating thermal extremes.

Journal Article↗

HSDSnake: a user-friendly SnakeMake pipeline for analysis of duplicate genes in eukaryotic genomes.

SUMMARY: Gene duplication is a well-known driver of molecular evolution-it acts as a source of genetic novelty, thereby providing the raw substrate for organismal adaption. However, detecting different types of gene duplicates and comparing them in sequence datasets can be difficult. Existing tools can identify and classify gene duplicates that have arisen by various processes, but have limitations; for example, some do not have a user-friendly workflow and can include many intermediate steps requiring manual adjustments of parameters and/or are not maintained for the benefit of research community members. Here, we have developed HSDSnake, a user-friendly SnakeMake pipeline that can detect and classify gene duplications into five categories: dispersed, proximal, tandem, transposed, and whole genome. It also curates and evaluates the highly similar gene duplicates (HSDs) in each gene duplication category with reliance on both sequence similarity and conserved domains. Lastly, the detected gene duplicates can be visualized within a KEGG functional pathway framework and the substitution rates (Ka, Ks, and their Ka/Ks ratio) can be analyzed for all the duplicate gene pairs. We demonstrate HSDSnake's capabilities by analyzing two reference genomes directly downloaded from NCBI and provide detailed instructions for each step. AVAILABILITY AND IMPLEMENTATION: The HSDSnake pipeline uses SnakeMake and Conda to run and install dependencies. The distribution version is available online at GitHub: https://github.com/zx0223winner/HSDSnake and the archived version at Zenodo is https://doi.org/10.5281/zenodo.15521945.

Software↗

A general approach to porous crystalline TiO2, SrTiO3, and BaTiO3 spheres.

Monodispersed porous crystalline TiO(2), SrTiO(3), and BaTiO(3) spheres were produced through a one-step hydrothermal process from amorphous TiO(2) spheres. The resulting samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and nitrogen sorption measurements. On the basis of the characterization results, we proposed a formation process of these porous spheres according to a mechanism analogous to the Kirkendall effect. This study provides a general way to synthesize porous titania-based spheres.

Adsorption↗

Block copolymer micelles as matrixes for incorporating diselenide compounds: a model system for a water-soluble glutathione peroxidase mimic fine-tuned by ionic strength.

We report on the use of block copolymer micelles of polystyrene-b-poly(acrylic acid) (PS-b-PAA) as matrixes for incorporating dibenzyl diselenide. We found that the water-insoluble diselenide, after being incorporated into the micelles, demonstrates glutathione peroxidase (GPx) activity in water. Surprisingly, the mimicking system can be adjusted to show higher GPx activity by increasing the ionic strength of the solution simply upon addition of NaCl. Moreover, dibenzyl diselenide incorporated into the micelles is quite stable and maintains its GPx activity even after exposure to the atmosphere.

Acrylates↗

Surface gradient material: from superhydrophobicity to superhydrophilicity.

We have developed a simple method to fabricate a gradient from superhydrophobicity to superhydrophilicity. It is based on the controlled self-assembled monolayer consisting of a thiol molecule on a gold surface and the amplifying effect of the wetting property on a rough surface. Using a relatively dilute HS(CH2)11CH3 solution (0.05 mmol/L), we found that the density of molecules on the surface can be controlled by varying the immersion time. Slowly adding the dilute solution to the container holding the rough gold substrate will lead to a density gradient along the surface. After the complementary adsorption of HS(CH2)10CH2OH, the surface exhibits a gradient from superhydrophobicity to superhydrophilicity. The slope of the gradient can be conveniently tuned by varying the speed of addition. Cassie-Baxter and Wenzel equations are employed to explain this special property based on the rough structure and the molecular composition gradient that have been determined by XPS. This kind of material would provide a larger oriented driving force for many important biological and physical processes and might have potential applications in water droplet movement, oriented axonal specification of neurons, protein adhesion, and so on.

Gold↗

Investigation into pH-responsive self-assembled monolayers of acylated anthranilate-terminated alkanethiol on a gold surface.

This article describes the preparation of pH-responsive self-assembled monolayers (SAMs) of acylated anthranilate-terminated alkanethiol. These monolayers are formed by chemisorption of the alkanethiol molecules onto a gold surface, resulting in different wetting properties of the surfaces depending upon the pH. By using various characterization techniques (e.g., infrared spectroscopy, cyclic voltammetry, contact angle measurements, and surface energy analysis), we have found that the changes in the wetting properties originate from the different surface structures of the monolayers in different pH environments. From surface energy analysis, we found that the disperse components of the surface energy on such SAMs predominate after treatment with pH 1 water, whereas the polar components of the surface energy on such SAMs predominate after treatment with pH 13 water. It is greatly anticipated that this line of research will provide new insight into the mechanism behind pH-responsive properties, facilitating the design and synthesis of new surface-active molecules for the fabrication of pH-responsive functional surfaces.

Journal Article↗

Polymer micelles as building blocks for the incorporation of azobenzene: enhancing the photochromic properties in layer-by-layer films.

We described the use of block copolymer micelles as building blocks for the incorporation of water-insoluble photochromic species of azobenzene and the fabrication of multilayer films by alternating the deposition of the block copolymer micelles of poly(styrene-b-acrylic acid), incorporating azobenzene and poly(diallyl-dimethylammonium chloride). The azobenzene incorporated into the block copolymer micelles can undergo a reversible photoisomerization under the irradiation of UV and visible light sources. An interesting finding is that the photoisomerization of the azobenzene in the multilayer film is faster than it is in its normal solid film, but very similar to that in its diluted solution. Furthermore, the amount of azobenzene incorporated into the micelles can influence the photoisomerization rates in the films. Therefore, we expect that the block copolymer micelles may provide a proper microenvironment for the photoisomerization of azobenzene and the as-prepared polyelectrolyte/block copolymer micelle thin films will be useful for photoswitching materials.

Journal Article↗

Human umbilical cord blood-derived stromal cell, a new resource of feeder layer to expand human umbilical cord blood CD34+ cells in vitro.

Allogeneic transplantation with human umbilical cord blood (hUCB) in adult recipients is mainly limited by a low CD34+ cell dose. To break the limit, hUCB as a novel source of hUCB-derived stromal cells was incorporated in an attempt to expand CD34+ cells from hUCB in vitro. Cord blood CD34 cells were separated by MACS system. HUCB-derived stromal cells were cultured by the Dexter system and characterized by morphologic, immunophenotypical, and functional analysis. We studied the effects of hUCB-derived stromal cells, cytokines, and hUCB-derived stromal cells combined with cytokines on expansion of hUCB CD34 cells. The CD34+ cells were assessed for the degree of expansion and the number of colony-forming units in semisolid culture. Our research found that hUCB-derived stromal cells were mainly composed of three kinds of cell components, with CD106, CD29, CD44, CD45, CD50, CD68, CD31, Fn, Lm, and collagen IV positive, but CD34 negative immunophenotype. Functionally, it was discovered by cell cycle and growth curve analyses that the capability of colony and parietal layer formation of hUCB-derived stromal cells was poorer than that of BM stromal cells, and the doubling time of hUCB-derived stromal cells was longer than that of BM stromal cells. It was indicated by ELISA and RT-PCR that hUCB-derived stromal cells express higher level of TPO and less GM-CSF and SCF than BM stromal cell. Adherent layer of hUCB-derived stromal cells alone or combining with cytokines, increased CD34+ cell expansion. In vitro formation of CFUs by expanded CCD34 cells was significantly higher than that of unexpanded CD34+ cells (P < 0.05). When cocultured with hUCB-derived stromal cells in the presence of cytokines, cell growth was significantly enhanced: CD34 cells by 8.02 +/- 0.96-fold, CFU-GM by 217.60 +/- 6.72-fold, CFU-E by 1940.80 +/- 52.78-fold, and CFU-Mg by 142.60 +/- 4.39-fold. HUCB-derived stromal cells have significant superiority on the expansion of CFU-Mg (P < 0.05). The results indicate that human umbilical cord blood-derived stromal cells may be a suitable feeder layer for expansion of hematopoietic progenitors from hUCB in vitro.

Antigens, CD34↗

Switchable surface properties through the electrochemical or biocatalytic generation of Ag0 nanoclusters on monolayer-functionalized electrodes.

The electroswitchable and the biocatalytic/electrochemical switchable interfacial properties of a Ag(+)-biphenyldithiol (BPDT) monolayer associated with a Au surface are described. Upon the application of a potential corresponding to -0.2 V the Ag(+)-BPDT is reduced to the Ag(0)-BPDT interface, and silver nanoclusters are generated on the interface. The application of a potential that corresponds to 0.2 V reoxidizes the monolayer to the Ag(+)-BPDT monolayer. The reversible electrochemical transformation of the Ag(+)-BPDT monolayer and of the Ag(0)-BPDT surface was followed by electrochemical means and surface plasmon resonance spectroscopy (SPR). The SPR experiments enabled us to follow the kinetics of nanoclustering of Ag(0) on the surface. The hydrophobic/hydrophilic properties of the surface are controlled by the electrochemically induced transformation of the interface between the Ag(+)-BPDT and Ag(0)-BPDT states. The Ag(0)-BPDT monolayer reveals enhanced hydrophilicity. The hydrophobic/hydrophilic properties of the interface were probed by contact angle measurements and force interactions with a hydrophobically-functionalized AFM tip. The Ag(0)-BPDT interface was also biocatalytically generated using alkaline phosphatase, AlkPh, and p-aminophenyl phosphate as substrate. The biocatalytically generated p-aminophenol reduces Ag(+) ions associated with the surface to Ag(0) nanoclusters. This enables the cyclic biocatalytic/electrochemical control of the surface properties of the modified electrode.

Alkaline Phosphatase↗

Quantitative in vivo retinal thickness measurement in chinese healthy subjects with retinal thickness analyzer.

PURPOSE: To measure the retinal thickness of the posterior pole in healthy Chinese subjects using a retinal thickness analyzer and to compare the retinal thicknesses between different age, gender, and refractive error groups. METHODS: Between February 2002 and September 2004, healthy Chinese subjects (age range, 21-50 years), underwent measurements of visual acuity, refractive error, intraocular pressure, and posterior pole retinal thickness with the RTA, as well as ophthalmoscopy and slit lamp examinations. Eleven retinal thickness parameters were directly derived from the reports of the RTA measurement. The average value of each parameter was compared between the male and female groups, the emmetropia and low-myopia groups, and the three age groups (21-30, 31-40, and 41-50 years). Linear regression analysis was also applied to determine the effect of age on 11 parameters. Some participants were also enrolled in the reproducibility assessment procedure. RESULTS: The 272 eyes of 272 subjects (mean age, 34.4 years) were included. The intraclass correlation coefficients of intravisit and intervisit reproducibility were 0.95 and 0.88, respectively. The average retinal thicknesses at the foveola and fovea are 147.6 and 160.0 microm, respectively. No significant difference was found in any of the parameters between the different gender groups, emmetropia and low-myopia groups, or age groups. Regression analysis revealed no significant negative linear correlation between any of the parameter values and age. CONCLUSIONS: The retinal thickness of macular region in the Chinese is a little lower than in Westerners, but not statistically significant. The Chinese retinal thickness was not gender or refractive error related.

Adult↗

[Effect of particles on the photodegradation of PAHs in natural waters of the Yellow River].

Photodegradation of chrysene, benzo(a)pyrene and benzo(ghi)perylene in natural water of the Yellow River was studied using simulation sunlight. The effects of particulates on the photodegradation were explored. Several results arose from this study: (1) The photodegradation of PAHs can be fitted with first-order kinetics when no particulates exist in water system, and the first-order constant increase with the decrease of initial concentration of PAHs. The photodegradation rates of the three PAHs are related to their molecule absorption spectrum. (2) The presence of loess exerts two kinds of effects on the photodegradation of PAHs, which include the inner filter effects and the photosensitizing effects of humic substance in Loess. These two opposite effects lead to the difference of net effects among different contents of loess. When the loess contents are 0.1 g/L and 5.0 g/L, the presence of loess stimulates the photodegradation of chrysene, benzo(a)pyrene. When the loess content is 5.0 g/L, the presence of loess stimulates the photodegradation of benzo(ghi)perylene. In addition, the photodegradation of PAHs can be fitted with the second-order kinetics when there is loess in the water system. (3) The dissolvable humic substances in loess can accelerate the photodegradation of PAHs while the indissoluble part cannot. (4) Since the dissolvable humic substances in the suspended solids of the river have been dissolved in water, the addition of suspended solids to the water system can only cause the decrease of photodegradation rate of PAHs due to its inner filter effects, and the photodegradation rate decreases with the suspended solid content as a power exponent function.

Benzo(a)pyrene↗

Self-assembled morphologies of monotethered polyhedral oligomeric silsesquioxane nanocubes from computer simulation.

Self-assembly of functionalized nanoscale building blocks is a promising strategy for "bottom-up" materials design. Recent experiments have demonstrated that the self-assembly of polyhedral oligomeric silsesquioxane (POSS) "nanocubes" functionalized with organic tethers can be utilized to synthesize novel materials with highly ordered, complex nanostructures. We have performed molecular simulations for a simplified model of monotethered POSS nanocubes to investigate systematically how the parameters that control the assembly process and the resulting equilibrium structures, including concentration, temperature, tether lengths, and solvent conditions, can be manipulated to achieve useful structures via self-assembly. We report conventional lamellar and cylindrical structures that are typically found in block copolymer and surfactant systems, including a thermotropic order-order transition, but with interesting stabilization of the lamellar phase caused by the bulkiness and cubic geometry of the POSS nanocubes.

Journal Article↗