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Biomedical subjects

Jing Zhu

Publications and source records attributed to Jing Zhu.

At least 19 recordsLinked to original sources

Spatially defined microenvironmental niches are associated with clinical outcome and tumor ecosystem diversity in head and neck cancer.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) exhibits substantial biological heterogeneity that is not fully explained by human papillomavirus (HPV) status. The spatial organization of tumor, immune, and stromal cell populations and its relationship to clinical outcome remain incompletely understood. METHODS: We performed single-cell spatial transcriptomic and proteomic profiling of 44 primary HNSCC tumors, generating a spatial atlas of 19,471,501 cells across whole-slide tissue sections. Spatial niches and ecosystem states were identified through integrated computational analyses and evaluated for associations with tumor programs, clinicopathologic features, and patient outcomes. FINDINGS: HPV-negative tumors were enriched for fibroblast-rich, immune-poor niches associated with epithelial-mesenchymal transition and hypometabolic tumor programs, whereas HPV-positive tumors displayed more diverse immune, stromal, and vascular niche combinations and were enriched for immunogenic ecosystem states. Approximately 20% of HPV-positive tumors exhibited fibroblast-rich ecosystem architectures resembling HPV-negative disease and were associated with less favorable outcomes than other HPV-positive tumors of similar stage. In patient-derived co-culture models, extracellular matrix-associated fibroblasts were associated with epithelial-mesenchymal transition (EMT)-like tumor states, CD8+ T cell dysfunction, and chemotherapy resistance-associated phenotypes. CONCLUSIONS: Spatial ecosystem architecture is associated with clinically relevant heterogeneity beyond conventional HPV-based classification. Fibroblast-rich, immune-poor ecosystem states characterize a high-risk subset of HPV-positive tumors and may provide a framework for improved biological classification and risk stratification in HNSCC. FUNDING: This work was supported by the National Institutes of Health (R01CA291607 and R21CA267527-01) and the Feldstein Medical Foundation.

Humans↗

Loss of Methylthioadenosine Phosphorylase (MTAP) Expression: A Potentially Useful Tool for Distinguishing Sarcomatoid Urothelial Carcinoma From Inflammatory Myofibroblastic Tumor.

Inflammatory myofibroblastic tumor (IMT) and sarcomatoid urothelial carcinoma (SarUC) can have striking histologic overlap but have significantly different prognoses and clinical management paradigms. Loss of methylthioadenosine phosphorylase (MTAP) protein expression by immunohistochemistry (IHC) serves as a useful surrogate for homozygous 9p21 deletion, a recurrent genomic alteration in urothelial carcinoma (UC). We analyzed MTAP expression by IHC in 65 SarUCs and 27 urinary tract IMTs to evaluate its utility in navigating this challenging differential diagnosis. Overall, MTAP loss was significantly more frequent in SarUC (55%) compared with IMT (4%) (P < .0001). Among 46 biphasic SarUCs with independently evaluable epithelial and mesenchymal components, divergent expression patterns were frequent. The most common pattern was retention of MTAP staining in both epithelial and mesenchymal components (19/46; 41% of cases), followed by selective retention of MTAP in the epithelial component and loss in the mesenchymal component (16/46; 35% of cases). MTAP loss was observed in both the epithelial and mesenchymal components in 11 out of 46 (24%) SarUC cases. None of the 46 biphasic SarUC cases showed selective MTAP loss in the epithelial component but retention in the mesenchymal component. MTAP IHC was also particularly valuable in assessing clonal relationships in 2 challenging biphasic cases in which the differential diagnosis included a collision between a noninvasive low-grade papillary UC and an IMT versus a subtle IMT-like SarUC arising in association with an overlying noninvasive low-grade papillary UC. Next-generation sequencing on a subset of cases (n = 11) was useful for confirming 9p deletion in cases with MTAP loss by IHC, and for demonstrating molecular hallmarks of urothelial neoplasia thereby providing additional diagnostic support for morphologically challenging SarUC cases with IMT-like morphology. Therefore, MTAP IHC can be useful in evaluating spindle cell lesions of the urinary tract, as loss is significantly more common in SarUC than in IMT, and enriched in the mesenchymal component of biphasic SarUC. However, MTAP loss can be seen in both entities, and the diagnosis of IMT-like spindle cell tumors in the urinary tract requires careful integration of morphologic, immunohistochemical, and molecular data.

Humans↗

TCF25 serves as a nutrient sensor to orchestrate metabolic adaptation and cell death by enhancing lysosomal acidification under glucose starvation.

Cells adapt to nutrient limitation by activating catabolic and inhibiting anabolic pathways, yet prolonged stress may lead to cell death. How cells orchestrate metabolic adaptation and cell death to nutrient stress is poorly understood. We conduct a genome-wide CRISPR-Cas9 screen to identify regulators in glucose-starvation-induced cell death and find a group of genes in lysosomal pathway is enriched following glucose starvation. We focus on one candidate gene, Transcriptional Factor 25 (TCF25). We find TCF25 enhances lysosomal acidification by targeting V-ATPase, promoting autophagy and ATP generation under glucose starvation. However, prolonged glucose starvation constitutively activates ferritinophagy via TCF25, increasing lysosomal membrane permeability (LMP) and leading to lysosome-dependent cell death (LDCD). Knocking out TCF25 or V-ATPase components prevents cell death. Furthermore, TCF25 deficiency protects mice from hepatic ischemia-reperfusion injury. Our findings identify TCF25 as a crucial nutrient sensor that regulates lysosomal activity, offering potential therapeutic targets for metabolic and ischemic disorders.

Lysosomes↗

Synthesis, crystal structure, and optical properties of LiGd5P2O13, a layered lithium gadolinium phosphate containing one-dimensional Li chains.

A lithium gadolinium phosphate crystal, LiGd5P2O13, has been synthesized by a high temperature solution reaction and solved by single-crystal X-ray diffraction data. The structure is monoclinic, space group C2/m, with unit cell parameters a = 18.645(3), b = 5.6257(5), c = 12.014(2) A, beta = 117.55(6)degrees, V = 1117.3(3) A3, and Z = 4. LiGd5P2O13 presents a new structural type and is built up from [Gd5P2O13]- layers and one-dimensional Li chains with an unusual Li-Li distance. The optical properties were investigated in terms of the absorption and emission spectra. Additionally, the calculations of band structure, density of states, dielectric constants, and refractive indexes were performed with the density functional threory method. The obtained results tend to support the experimental data.

Journal Article↗

Metal-particle-induced, highly localized site-specific etching of Si and formation of single-crystalline Si nanowires in aqueous fluoride solution.

A straightforward metal-particle-induced, highly localized site-specific corrosion-like mechanism was proposed for the formation of aligned silicon-nanowire arrays on silicon in aqueous HF/AgNO3 solution on the basis of convincing experimental results. The etching process features weak dependence on the doping of the silicon wafers and, thus, provides an efficient method to prepare silicon nanowires with desirable doping characteristics. The novel electrochemical properties between silicon and active noble metals should be useful for preparing novel silicon nanostructures and also new optoelectronic devices.

Journal Article↗

[Effects of peroxisome proliferator-activated receptor-gamma ligand troglitazone on colon cancer cell growth].

OBJECTIVE: To investigate the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in colon cancer cell lines and the effects of PPARgamma activation by its ligand troglitazone on cell growth in SW-480 cells. METHODS: PPARgamma expression was detected in Lovo, HT-29 and SW-480 cells using western blot. The effects of PPARgamma activation by its ligand troglitazone (TGZ) and selective antagonist T0070907 on cell growth were assessed by MTT and cell count methods; apoptosis was detected by flow cytometry method. RESULTS: Western blot result revealed that PPARgamma protein was highly expressed in Lovo and HT-29 cells and there was relatively lower expression in SW-480 cells. Cell count method and MTT revealed that activation of SW-480 cells with TGZ resulted in inhibition of growth in a dose dependent manner. The effect of anti-proliferation increased with increasing doses of TGZ. Rates of growth inhibition were 3.3%, 8.3%, 25%, and 29% for different doses 5, 10, 20 and 25 micromol/L respectively. Flow cytometry method detected apoptosis in a dose-dependent manner. When the concentration of TGZ was less than 15 micromol/L , the apoptotic effect was found to be weak. The apoptotic effect was prominent when the concentration exceeded 20 micromol/L. Cell count method revealed that selective antagonist of PPARgamma stimulated cell growth of SW-480 cells in a dose dependent manner. CONCLUSION: PPARgamma is expressed in colon cancer cells. Activation of PPARgamma by its ligands in colon cells has potent anti-proliferative and pro-apoptotic effects, suggesting that PPARgamma activation by its ligands may provide therapeutic value for colorectal cancer patients.

Antineoplastic Agents↗

Effects of replacing the unreliable cDNA microarray measurements on the disease classification based on gene expression profiles and functional modules.

MOTIVATION: Microarrays datasets frequently contain a large number of missing values (MVs), which need to be estimated and replaced for subsequent data mining. The focus of the paper is to study the effects of different MV treatments for cDNA microarray data on disease classification analysis. RESULTS: By analyzing five datasets, we demonstrate that among three kinds of classifiers evaluated in this study, support vector machine (SVM) classifiers are robust to varied MV imputation methods [e.g. replacing MVs by zero, K nearest-neighbor (KNN) imputation algorithm, local least square imputation and Bayesian principal component analysis], while the classification and regression tree classifiers are sensitive in terms of classification accuracy. The KNNclassifiers built on differentially expressed genes (DEGs) are robust to the varied MV treatments, but the performances of the KNN classifiers based on all measured genes can be significantly deteriorated when imputing MVs for genes with larger missing rate (MR) (e.g. MR > 5%). Generally, while replacing MVs by zero performs relatively poor, the other imputation algorithms have little difference in affecting classification performances of the SVM or KNN classifiers. We further demonstrate the power and feasibility of our recently proposed functional expression profile (FEP) approach as means to handle microarray data with MVs. The FEPs, which are derived from the functional modules that are enriched with sets of DEGs and thus can be consistently identified under varied MV treatments, achieve precise disease classification with better biological interpretation. We conclude that the choice of MV treatments should be determined in context of the later approaches used for disease classification. The suggested exclusion criterion of ignoring the genes with larger MR (e.g. >5%), while justifiable for some classifiers such as KNN classifiers, might not be considered as a general rule for all classifiers.

Algorithms↗

Oxidation of carbon monoxide on Rh(111): a density functional theory study.

The adsorption of CO on the oxygen precovered Rh(111) and the oxidation of CO are investigated with density functional theory. The preferred adsorption site and the possible reaction channel are determined. The experimentally observed inertness of the (2 x 2)-O-CO structure is explained by the reaction barrier and the stability of the reactants.

Journal Article↗

[Expression of HIC-5/ARA55 in colonrectal cancer and its mechanisms of action].

OBJECTIVE: To investigate the relationship between HIC-5 and colonrectal cancer. METHODS: Samples were obtained from 42 patients with colonrectal cancer, and the mRNA and protein expressions of HIC-5/ARA55 were determined by RT-PCR and Western-blot respectively. FCM was used to investigate the apoptosis of Lovo in the HIC-5/ARA55 transfection cells. The expression of apoptosis related proteins Bax and Bcl-2 was determined by Western-blot, and the MTT assay was used to test cell growth speed affected by HIC-5/ARA55. RESULTS: The expression of HIC-5 significantly decreased on colonrectal cancer tissues as compared with adjacent normal tissues on mRNA level and protein level(P<0.05). The apoptosis rate increase significantly in the HIC-5/ARA55 transfected cells. HIC-5/ARA55 could restrain tumor cell grow speed. CONCLUSION: HIC-5/ARA55 is the protein that can reduce tumor cell growth rate, and induce apoptosis in colonrectal cancer cells.

Apoptosis↗

Synthesis and characterization of indole-containing chromophores for second-order nonlinear optics.

Push-pull indole-containing nonlinear optical chromophores with different acceptor and pi-conjugated moieties have been synthesized and characterized. Experimental measurements of the second-order nonlinear optical response demonstrated that the chromophores exhibit similar or superior optical nonlinearity compared with their analogues with an aniline moiety as the donor group, but the indole-based chromophores display blue-shifted absorption, even up to 30 nm.

Journal Article↗

Enantioselective determination of dencichine in rabbit plasma by high-performance liquid chromatography-electrospray mass spectrometry.

An analytical method was developed for the determination of enantiomers of dencichine in plasma. Sample extraction from plasma was achieved by a solid-phase extraction (SPE) procedure using a C(18) cartridge, with carbocisteine as the internal standard. Plasma was deproteinized using inorganic acid and derivatizated before the SPE. Chiral separation of dencichine enantiomers was achieved by pre-column derivatization using o-phthaldialdehyde (OPA) and the chiral thiol N-isobutanoyl-L-cysteine (NIBC) to form diastereoisomeric isoindole derivatives that were separable by ODS column using a gradient solvent programme. The column eluent was monitored using mass spectrometry (MS). The conditions of MS detection were optimized, and selected ion monitoring was used to selectively detect D-dencichine and its arrangement isomer. High sensitivity and selectivity were obtained using this method. The limit of detection was determined to be 10 ng/ml for D-dencichine and 8 ng/ml for L-dencichine in plasma. The linearity was demonstrated over a wide range of concentrations, from 0.5 to 50 microg/ml for both enatiomers. The intra- and inter-day precision (C.V.), studied at four concentrations, was less than 7.0%. No interferences from endogenous amino acids and isomers of dencichine were found. The method was suitable for pharmacokinetic studies of dencichine enantiomers.

Amino Acids, Diamino↗

Influence of the interaction between metal particles on optical properties of Ag-Si3N4 composite films. I. Experiment.

Ag-Si3N4 composite films with metal fractions of 20% and 33% were prepared by magnetron sputtering. The Ag particles inside the composite films were less than 5 nm in radius. The optical absorption and near-field enhancement properties of the composite films were measured. On the plots of optical absorption, the extra absorption was observed as well as the surface plasmon resonance absorption. The intensity of the extra absorption depended on the particle size and metal fraction. Moreover, the composite films with higher extra absorption had better near-field enhancement properties. These phenomena were possibly related with the interaction between Ag particles in composite films.

Journal Article↗

Influence of the interaction between metal particles on optical properties of Ag-Si3N4 composite films. II. Two-particle approximation.

The interaction between metal particles was calculated based on the discrete dipole method. The calculated results revealed that the multiple interactions in a collection of metal particles are dominated by the interaction between the neighboring particles. Thus, a two-particle approximation was deduced and applied to estimate the optical absorption and near-field enhancement property of Ag-Si3N4 composite films. The calculated results indicated that the interaction between Ag particles will induce extra absorption near the surface plasmon resonance peak and improve the near-field enhancement property of composite films. Calculated results were consistent with the experimental results.

Journal Article↗

In vitro osteogenetic activity of pearl.

In vivo and in vitro studies have shown that shell nacre and hydroxyapatite (HA) are promising bioactive materials for bone repair. In this work, the osteogenetic activity of pearl is evaluated by soaking it in simulated body fluid (SBF) and cell culture, taking shell nacre and HA as control materials at the same time. After soaking in SBF, HA particles were rapidly formed on the surface of pearl, the dissolution of CaCO3 and the binding between organic components and Ca2+ ions in pearl provide favorable conditions for the HA precipitation, and the whole process follows a dissolution-binding-precipitation mechanism. Calcium surplus, not conventional calcium deficiency, is found in HA crystal structure; it implies that type B-HA is formed on pearl surface in this study. HRTEM observation shows that HA is poorly crystallized with so many dislocations and shuttle-like amorphous areas. Cell culture reveals that pearl could stimulate osteoblast proliferation, which proceeded more quickly and smoothly than that on shell nacre and HA, and abundant extracellular matrix occupied the whole pearl surface by 5 days. It is concluded that pearl is a superior osteoinductive material with high osteogenetic activity.

Animals↗

Size effect on the crystal structure of silver nanowires.

A 4H structural silver nanowire (4H-AgNW) is discovered to coexist with a face-centered cubic (FCC) one prepared by electrochemical deposition and to have the highest concentration in the total of 4H- and FCC-AgNWs with diameters around 30 nm. Moreover, the concentration becomes smaller when the diameters deviate from 30 nm. This size effect arises from the fact that 4H-AgNW has a more favorable surface configuration but higher volume internal energy than FCC-AgNW, which is proved by our model.

Journal Article↗

[Constructions of Gcn5 shRNAs interfere the histone acetylation modification with stem cell differentiation].

OBJECTIVE: To construct the Gcn5 shRNA plasmids and to explore the Gcn5 shRNA role in histone acetylation modification with the differentiation of stem cells. METHODS: Seven shRNA fragments were recombined into pGenesil-1 vector to form 7. Gcn5 shRNA constructions. The mesenchymal stem cells (MSCs) induced for two weeks with 5-aza were transfected by the plasmids with lipofectamine2000. Polyclonal antibodies labeled with TRITC were used to identify the acetylation in MSCs with or without Gcn5 shRNA constructions. The efficiencies of transfection and RNAi were calculated based on the ratio of GFP (green fluorescence)/DAPI (blue fluorescence) and TRITC (red fluorescence)/DAPI, respectively. RESULTS: Seven Gcn5 shRNA plasmids or constructions were identified by restriction endonucleases Pst I/Sal I and DNA sequencing. Acetylation block was observed after Gcn5 shRNA plasmids transfected into cells. Fluorescent intensity of TRITC in nucleuses were decreased remarkably, or even disappeared in MSCs. The efficiencies of transfection and RNAi were 93.7% and 46.6%, respectively. CONCLUSION: The Gcn5 shRNA plasmids constructed in the present study can decrease the histone acetylation during cell differentiation. It sets the basis for further exploring the role of acetylation in the regulation of cell differentiation.

Acetylation↗

[Near infrared spectrometry (NIRS) method for the determination of borneol in sustained-release drugs].

In order to detect the release profile of borneol in sustained-release preparations, a series of NIRS calibration models were established on the basis of chemometrics and internal relationships between NIRS and analytical concentrations of samples, which contained the same substances as the preparations. Partial least square (PLS) algorithm was used to establish the model for predicting the content of borneol. The effect of spectra types, concentration range of samples, and calibration range on the models and predicting results were investigated. It was found that the best calibration models and prediction results can be obtained by using original spectra in the 5,314-7,032 cm(-1) region. The models established according to standards' concentration levels are better than those established without considering concentration levels. Using the model 2 in which calibration standards had medium or high concentration levels, rapid and accurate measurement of borneol released from sustained-release preparation was realized. The results indicated that the method and models provide valuable criteria for developing sustained-release borneol preparations.

Camphanes↗