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Xiaomin Zhang

Publications and source records attributed to Xiaomin Zhang.

11 recordsLinked to original sources
PubMed2025

Natural variation in the cytokinin oxidase gene ZmCKX6 influences leaf morphology and yield-related traits in maize.

Leaf width (LW) is a critical determinant of maize architecture and yield. To uncover its genetic basis, we performed a genome-wide association study (GWAS) on 348 maize inbred lines and identified ZmCKX6, encoding cytokinin oxidase/dehydrogenase, as a key gene associated with LW. Natural variation in the ZmCKX6 promoter significantly influenced its expression levels, leading to differences in LW across various haplotypes. Functional validation using CRISPR/Cas9 revealed that ZmCKX6 knockout results in pleiotropic effects, including narrower leaves, reduced plant height, and decreased grain yield components. These phenotypes were accompanied by elevated levels of active cytokinins but reduced levels of auxin, gibberellins, and salicylic acid. Transcriptome analysis revealed a significant downregulation of photosynthesis-related genes, corresponding to reduced photosynthetic rates in knockout lines. Evolutionary analysis demonstrated that the allele associated with narrower leaves were preferentially selected during maize domestication and breeding. This study highlights the role of ZmCKX6 in modulating cytokinin homeostasis and its subsequent impact on multiple agronomic traits in maize, providing insights into the complex genetic control of plant architecture and yield. The identified natural variations could be valuable for marker-assisted selection aimed at optimizing plant architecture and improving yield.

Zea mays↗
PubMed2024

The AKR1C1-CYP1B1-cAMP signaling axis controls tumorigenicity and ferroptosis susceptibility of extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma (ECC), a highly malignant type of cancer with increasing incidence, has a poor prognosis due to limited treatment options. Based on genomic analysis of ECC patient samples, here we report that aldo-keto reductase family 1 member C1 (AKR1C1) is highly expressed in human ECC tissues and closely associated with ECC progression and poor prognosis. Intriguingly, we show that inducible AKR1C1 knockdown triggers ECC cells to undergo ferroptosis. Mechanistically, AKR1C1 degrades the protein stability of the cytochrome P450 family member CYP1B1, a newly discovered mediator of ferroptosis, via ubiquitin-proteasomal degradation. Additionally, AKR1C1 decreases CYP1B1 mRNA level through the transcriptional factor aryl-hydrocarbon receptor (AHR). Furthermore, the AKR1C1-CYP1B1 axis modulates ferroptosis in ECC cells via the cAMP-PKA signaling pathway. Finally, in a xenograft mouse model of ECC, AKR1C1 depletion sensitizes cancer cells to ferroptosis and synergizes with ferroptosis inducers to suppress tumor growth. Therefore, the AKR1C1-CYP1B1-cAMP signaling axis is a promising therapeutic target for ECC treatment, especially in combination with ferroptosis inducers.

Humans↗
PubMed2006

Maintaining serum response factor activity in the older heart equal to that of the young adult is associated with better cardiac response to isoproterenol stress.

To understand the effect of transcription regulation in modulating cardiac aging, we sought to study the role of serum response factor (SRF), a key transcription factor in the heart that is normally increased with senescence and also in congestive heart failure. A Tet-Off gene expression system was used for cardiac-specific over-expression of a mutant SRF protein. In these binary transgenic mice, there is no age-related increase in SRF protein expression; in fact, there appeared to be a mild reduction of SRF protein (Mild-R SRF Tg). The older, middle-aged (15 mo) Mild-R SRF Tg mice appeared healthier and were better able to maintain their left ventricular systolic pressure (LVSP) in response to moderate â-adrenergic stimulation compared with age-matched Non-Tg mice, which demonstrated a negative ionotropic response. The Mild-R SRF Tg hearts had lower mRNA expression of BNP (p < 0.05), and the sodium calcium exchanger (p < 0.05), compared to Non-Tg. Mild-R SRF Tg had higher mRNA levels of SERCA2 (p < 0.05) and ryanodine receptor 2 (p < 0.05) compared to Non-Tg hearts. These findings suggest that preventing the age-associated increase in SRF is associated with better preserved intracellular calcium handling and functional response to stress; it might be advantageous for the older adult heart. This mouse model could be helpful in elucidating the molecular mechanisms underlying certain age-related changes in cardiac reserve capacity and response to stress.

Age Factors↗
PubMed2006

Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation.

BACKGROUND: Problems associated with the hepatic transplantation of islets may preclude the broad application of islet transplantation. Thus, we sought to develop an approach to the extrahepatic transplantation of islets using a synthetic biodegradable polymer scaffold. METHODS: Microporous polymer scaffolds that allow vascular ingrowth and nutrient diffusion from host tissues were fabricated from copolymers of lactide and glycolide. Murine islets were transplanted without or with a scaffold onto intraperitoneal fat of syngeneic diabetic recipients. Bioluminescence imaging using a cooled charge-coupled device camera, immunohistochemistry, and glycemia were used to assess islet engraftment and function posttransplant. RESULTS: By bioluminescence imaging, islets transplanted on a polymer scaffold remain localized to the transplant site and survive for an extended period of time. Islets transplanted on scaffolds retained the architecture of native islets and developed a functional islet vasculature. Transplantation of marginal masses of islets on the polymer scaffold demonstrated improved islet function compared to transplantation without a scaffold as assessed by the effectiveness of diabetes reversal, including mean time required to achieve euglycemia, weight gain, and glucose levels during an intraperitoneal glucose tolerance test. CONCLUSION: These findings indicate that a synthetic polymer scaffold can serve as a platform for islet transplantation and improves the function of extrahepatically transplanted islets compared to islets transplanted without a scaffold. The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function.

Animals↗
PubMed2006

Zipzap/p200 is a novel zinc finger protein contributing to cardiac gene regulation.

Serum response factor (SRF) plays an important role in the regulation of immediate-early genes and muscle-specific genes, while SRF cofactors may contribute significantly to assist in tissue-specific, development-stage related regulation of SRF-target genes. We recently cloned a novel SRF cofactor, termed zipzap/p200, which is a zinc finger protein yet to be characterized. We determined that zipzap/p200 is a 200-kDa protein with two classic C2H2 zinc fingers at the carboxyl terminus where the nucleotide sequence was highly conserved among human, mouse, and rat. The zipzap gene was expressed in multiple tissues and at multiple ages, including the fetal and adult heart. The zipzap protein interacted with SRF in vivo and was found in protein complexes containing SRF and other SRF cofactors, including p49/strap and Nkx2.5. Zipzap/p200 activated the promoter of cardiac genes and potentiated the effect of myocardin on ANF promoter activity. Therefore, zipzap may serve as a transcription co-activator for the regulation of cardiac gene expression. Our data support the notion that a number of SRF cofactors may participate in gene regulation and thereby contribute to the delicate control of gene expression in complex biological processes.

Adult↗
PubMed2006

In vivo bioluminescence imaging of transplanted islets and early detection of graft rejection.

BACKGROUND: Bioluminescence imaging (BLI) modalities are being developed to monitor islet transplant mass and function in vivo. The aim of this study was to use the BLI system to determine how the change in functional islet mass correlated to metabolic abnormalities during the course of alloimmune rejection in a murine transplant model. METHODS: Islets obtained from a transgenic mouse strain (FVB/NJ-luc) that constitutively expressed firefly luciferase were transplanted to various implantation sites of syngeneic wild-type FVB/NJ or allogeneic Balb/C streptozotocin-induced diabetic recipients. In vivo graft luminescent signals were repeatedly measured after transplantation using the BLI system and related to blood glucose levels and graft site histologic findings. RESULTS: The BLI signals were detected in as few as 10 islets implanted in the renal subcapsular space, intrahepatic, intraabdominal, and subcutaneous locations. There was a linear relationship between the number of islets transplanted and luminescence intensity. In isografts, stable luminescence intensity signals occurred within 2 weeks of transplantation and remained consistent on a long-term basis (18 months) after transplantation. In allografts, after normoglycemia was achieved and stable luminescence intensity occurred, graft bioluminescent intensity progressively decreased several days before permanent recurrence of hyperglycemia as a result of histologically proven rejection ensued. CONCLUSIONS: Bioluminescence imaging is a sensitive method for tracking the fate of islets after transplantation and is a useful method to detect early loss of functional islet mass caused by host immune responses even before overt metabolic dysfunction is evident. Bioluminescence imaging holds promise for use in designing and testing interventions to prolong islet graft survival.

Animals↗
PubMed2006

Acquiring 1053 nm femtosecond laser emission by optical parametric amplification based on supercontinuum white-light injection.

We report a terawatt-Ti:sapphire-laser-pumped high-energy femtosecond optical parametric amplifier (OPA) with supercontinuum white-light injection. Signal pulses with a duration less than 100 fs and energy up to 4 mJ are obtained with large-aperture LiNbO3 crystals. This megajoule-class femtosecond OPA at 1053 nm presents a feasible alternative to optical parametric chirped-pulse amplification and is ready to be applied to petawatt lasers.

Journal Article↗
PubMed2005

Comparison of cell-suspension and explant culture of rabbit limbal epithelial cells.

Currently, most investigators directly use limbal explants to culture corneal epithelial cells. However, it has not been identified that limbal stem cells do readily migrate from the limbal explants onto culture plate or amniotic membrane carrier. In this study a cell-suspension culture system for rabbit limbal stem cells was developed and compared with the direct explant method in the aspect of stem cells content in the culture system. Rabbit limbal epithelial cells were dissociated from rabbit eyes by dispase and single cell suspension was made for cell-suspension culture. DeltaNp63 expression of cultured rabbit limbal epithelial cells by cell-suspension technique and explant technique was detected. In cell-suspension culture, isolated cell-suspension was evaluated by flow cytometric analysis for vimentin expression and residual limbal tissue after dispase treatment was examined by scanning electron microscopy. In limbal epithelial cells suspension less than 5% cells were vimentin positive. Examination of residual limbal tissue confirmed that all the limbal epithelial cells had been removed. Histological examination revealed that with cell-suspension culture the cultured epithelial cells could differentiate better than with explant technique. In cells cultured with cell-suspension, there were much more cells expressing DeltaNp63 than in explant cultured cells. In cells cultured with explants, most of DeltaNp63 labelling cells mustered around the explants, and peripheral cells on the slides were DeltaNp63 negative. These results suggested that with pure limbal epithelial cells suspension including basal cells, which could directly enter into culture system, cell-suspension culture technique was significantly superior to explant culture technique in terms of stem cells content.

Animals↗
PubMed2004

Identification of a novel serum response factor cofactor in cardiac gene regulation.

The transcription factor serum response factor (SRF) plays an important role in the regulation of a variety of cardiac genes during development and during adult aging. A novel SRF cofactor, herein called p49/STRAP, for SRF-dependent transcription regulation-associated protein, was recently identified in our laboratory. This protein interacted mainly with the transcriptional activation domain of the SRF protein and was found to bind to SRF or to the complex of SRF and another cofactor, such as myocardin or Nkx2.5. The expression of p49/STRAP affected the promoter activity of SRF target genes in a non-uniform manner. For example, p49 activated MLC2v and cardiac actin promoters when it was co-transfected with SRF, but it repressed atrial natriuretic factor promoter activity, which was strongly induced by myocardin. The p49/STRAP mRNA was observed to be highly expressed in fetal, adult, and senescent human hearts, and also in hearts of young adult and old mice, suggesting that p49/STRAP may be an important SRF cofactor in the transcriptional regulation of mammalian cardiac muscle genes throughout the life span.

Actins↗
PubMed2003

Model of functional cardiac aging: young adult mice with mild overexpression of serum response factor.

Serum response factor (SRF) is an important transcription factor that may have a role in the maintenance of cardiac structure and function. The level of SRF mRNA expression increases approximately 16% in the hearts of mice during adult aging. To model the effect of mild SRF elevation in the aging heart, transgenic mice with low levels of SRF overexpression were generated. By 6 mo of age, the transgenic mice had a 19% increase of heart-to-body weight ratio compared with nontransgenic mice. In addition, they had a 12% increase in myocyte size, a 6.7% increase in collagen deposition, and altered gene expression of a number of muscle-specific and cardiac genes. Doppler echocardiography revealed that these transgenic mice had increased left ventricular wall thickness and decreased left ventricular (LV) volumes, increased LV stiffness with 20% reduction in early diastolic LV filling (peak E), and 35% decline in peak E-to-peak A (late diastolic filling) ratio. The observed changes, especially those in the E/A ratio, are similar to those seen clinically in late life as a part of human adult myocardial aging.

Aging↗