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Biomedical subjects

Y A Wang

Publications and source records attributed to Y A Wang.

14 recordsLinked to original sources
PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗
PubMed2006

Vibrational assignment and structure of dibenzoylmethane. A density functional theoretical study.

Molecular structure and vibrational frequencies of 1,3-diphenyl-1,3-propanedione, known as dibenzoylmethane (DBM), have been investigated by means of density functional theory (DFT) calculations. The results were compared with those of benzoylacetone (BA) and acetylacetone (AA), the parent molecule. IR and Raman spectra of DBM and its deuterated analogue were clearly assigned. The calculated hydrogen bond energy of DBM is 16.15 kcal/mol, calculated at B3LYP/6-311++G** level of theory, which is 0.28 kcal/mol more than that of AA. This result is in agreement with the vibrational and NMR spectroscopy results. The molecular stability and the hydrogen bond strength were investigated by applying the Natural Bond Orbital analysis (NBO) and geometry calculations. The theoretical calculations indicate that the hydrogen bond in DBM is relatively stronger than that in BA and AA.

Butanones↗
PubMed2001

Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols.

The photochemical instability of CdSe nanocrystals coated by hydrophilic thiols was studied nondestructively and systematically in water. The results revealed that the photochemical instability of the nanocrystals actually included three distinguishable processes, namely the photocatalytic oxidation of the thiol ligands on the surface of nanocrystals, the photooxidation of the nanocrystals, and the precipitation of the nanocrystals. At first, the thiol ligands on the surface of a nanocrystal were gradually photocatalytically oxidized using the CdSe nanocrystal core as the photocatalyst. This photocatalytic oxidation process was observed as a zero-order reaction in terms of the concentration of the free thiols in the solution. The photogenerated holes in a nanocrystal were trapped onto the thiol ligands bound on the surface of the nanocrystal, which initiated the photooxidation of the ligands and protected the nanocrystal from any photooxidation. After nearly all of the thiol ligands on the surface of the nanocrystals were converted into disulfides, the system underwent several different pathways. If the disulfides were soluble in water, then all of the disulfides fell into the solution at the end of this initial process, and the nanocrystals precipitated out of the solution without much variation over their size and size distribution. When the disulfides were insoluble in water, they likely formed a micelle-like structure around the nanocrystal core and kept it soluble in the solution. In this case, the nanocrystals only precipitated after severe oxidation, which took a long period of time. If the system contained excess free thiol ligands, they replaced the photochemically generated disulfides and maintained the stability and solubility of the nanocrystals. The initiation stage of the photooxidation of CdSe nanocrystals themselves increased as the thickness and packing density of the ligand shell increased. This was explained by considering the ligand shell on the surface of a nanocrystal as the diffusion barrier of the oxygen species from the bulk solution into the interface between the nanocrystal and the surface ligands. Experimental results clearly indicated that the initiation stage of the photooxidation was not caused by the chemical oxidation of the system kept in air under dark conditions or the hydrolysis of the cadmium-thiol bonds on the surface of the nanocrystals, both of which were magnitudes slower than the photocatalytic oxidation of the surface ligands if they occurred at all. The results described in this contribution have already been applied for designing new types of thiol ligands which dramatically improved the photochemical stability of CdSe nanocrystals with a ligand shell that is as thin as approximately 1 nm.

Journal Article↗
PubMed2001

Prediction of electronic excited states of adsorbates on metal surfaces from first principles.

We present the first ab initio prediction of localized electronic excited states in a periodically infinite condensed phase, a heretofore intractable goal. In particular, we examined local excitations within a CO molecule adsorbed on Pd(111). The calculation allows a configuration interaction treatment of a local region, while its interaction with the extended condensed phase is described via an embedding potential obtained from periodic density functional theory. Our work lays the foundation of a microscopic understanding of photochemistry and spectroscopy on metal surfaces.

Journal Article↗
PubMed2001

The combination of SKY and specific loci detection with FISH or immunostaining.

Spectral karyotyping (SKY) represents an effective tool to detect individual chromosomes and analyze major karyotype abnormalities within an entire genome. We have tested the feasibility of combining SKY and FISH/protein detection in order to combine SKY's unique abilities with specific loci detection. Our experimental results demonstrate that various combined protocols involving SKY, FISH and immunostaining work well when proper procedures are used. This combined approach allows the tracking of key genes or targeted chromosome regions while monitoring changes throughout the whole genome. It is particularly useful when simultaneously monitoring the behavior of both protein complexes and DNA loci within the genome. The details of this methodology are described and systematically tested in this communication.

Animals↗
PubMed2000

Meiotic telomere distribution and Sertoli cell nuclear architecture are altered in Atm- and Atm-p53-deficient mice.

The ataxia telangiectasia mutant (ATM) protein is an intrinsic part of the cell cycle machinery that surveys genomic integrity and responses to genotoxic insult. Individuals with ataxia telangiectasia as well as Atm(-/-) mice are predisposed to cancer and are infertile due to spermatogenesis disruption during first meiotic prophase. Atm(-/-) spermatocytes frequently display aberrant synapsis and clustered telomeres (bouquet topology). Here, we used telomere fluorescent in situ hybridization and immunofluorescence (IF) staining of SCP3 and testes-specific histone H1 (H1t) to spermatocytes of Atm- and Atm-p53-deficient mice and investigated whether gonadal atrophy in Atm-null mice is associated with stalling of telomere motility in meiotic prophase. SCP3-H1t IF revealed that most Atm(-/-) p53(-/-) spermatocytes degenerated during late zygotene, while a few progressed to pachytene and diplotene and some even beyond metaphase II, as indicated by the presence of a few round spermatids. In Atm(-/-) p53(-/-) meiosis, the frequency of spermatocytes I with bouquet topology was elevated 72-fold. Bouquet spermatocytes with clustered telomeres were generally void of H1t signals, while mid-late pachytene and diplotene Atm(-/-) p53(-/-) spermatocytes displayed expression of H1t and showed telomeres dispersed over the nuclear periphery. Thus, it appears that meiotic telomere movements occur independently of ATM signaling. Atm inactivation more likely leads to accumulation of spermatocytes I with bouquet topology by slowing progression through initial stages of first meiotic prophase and an ensuing arrest and demise of spermatocytes I. Sertoli cells (SECs), which contribute to faithful spermatogenesis, in the Atm mutants were found to frequently display numerous heterochromatin and telomere clusters-a nuclear topology which resembles that of immature SECs. However, Atm(-/-) SECs exhibited a mature vimentin and cytokeratin 8 intermediate filament expression signature. Upon IF with ATM antibodies, we observed ATM signals throughout the nuclei of human and mouse SECs, spermatocytes I, and haploid round spermatids. ATM but not H1t was absent from elongating spermatid nuclei. Thus, ATM appears to be removed from spermatid nuclei prior to the occurrence of DNA nicks which emanate as a consequence of nucleoprotamine formation.

Animals↗
PubMed1999

Localization of putative stem cells in dental epithelium and their association with Notch and FGF signaling.

The continuously growing mouse incisor is an excellent model to analyze the mechanisms for stem cell lineage. We designed an organ culture method for the apical end of the incisor and analyzed the epithelial cell lineage by 5-bromo-2'-deoxyuridine and DiI labeling. Our results indicate that stem cells reside in the cervical loop epithelium consisting of a central core of stellate reticulum cells surrounded by a layer of basal epithelial cells, and that they give rise to transit-amplifying progeny differentiating into enamel forming ameloblasts. We identified slowly dividing cells among the Notch1-expressing stellate reticulum cells in specific locations near the basal epithelial cells expressing lunatic fringe, a secretory molecule modulating Notch signaling. It is known from tissue recombination studies that in the mouse incisor the mesenchyme regulates the continuous growth of epithelium. Expression of Fgf-3 and Fgf-10 were restricted to the mesenchyme underlying the basal epithelial cells and the transit-amplifying cells expressing their receptors Fgfr1b and Fgfr2b. When FGF-10 protein was applied with beads on the cultured cervical loop epithelium it stimulated cell proliferation as well as expression of lunatic fringe. We present a model in which FGF signaling from the mesenchyme regulates the Notch pathway in dental epithelial stem cells via stimulation of lunatic fringe expression and, thereby, has a central role in coupling the mitogenesis and fate decision of stem cells.

Ameloblasts↗
PubMed1997

Loss of p21 increases sensitivity to ionizing radiation and delays the onset of lymphoma in atm-deficient mice.

Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by growth retardation, cerebellar ataxia, oculocutaneous telangiectasias, and a high incidence of lymphomas and leukemias. In addition, AT patients are sensitive to ionizing radiation. Atm-deficient mice recapitulate most of the AT phenotype. p21(cip1/waf1 )(p21 hereafter), an inhibitor of cyclin-dependent kinases, has been implicated in cellular senescence and response to gamma-radiation-induced DNA damage. To study the role of p21 in ATM-mediated signal transduction pathways, we examined the combined effect of the genetic loss of atm and p21 on growth control, radiation sensitivity, and tumorigenesis. As might have been expected, our data provide evidence that p21 modifies the in vitro senescent response seen in AT fibroblasts. Further, it is a downstream effector of ATM-mediated growth control. In addition, however, we find that loss of p21 in the context of an atm-deficient mouse leads to a delay in thymic lymphomagenesis and an increase in acute radiation sensitivity in vivo (the latter principally because of effects on the gut epithelium). Modification of these two crucial aspects of the ATM phenotype can be related to an apparent increase in spontaneous apoptosis seen in tumor cells and in the irradiated intestinal epithelium of mice doubly null for atm and p21. Thus, loss of p21 seems to contribute to tumor suppression by a mechanism that operates via a sensitized apoptotic response. These results have implications for cancer therapy in general and AT patients in particular.

Animals↗
PubMed1990

[Tentative study of geographical epidemiology of schistosomiasis japonica in Yunnan province].

Schistosomiasis prevails in 17 counties and cities in Yunnan Province. Approximately, a population of 301,511 were affected and the snail-ridden area amounted to 219,000,000m2 in the past years. These endemic areas were not evenly distributed, but rather scattered. The endemic foci were vertically distributed at an altitude of 1,350-2,450 metres above sea level. Human cases were found mostly in areas with an elevation of greater than or equal to 1,800 metres, and became progressively fewer with the ascent. However, in areas with an-elevation of less than or equal to 1800 metres, the infection rate in the inhabitants decreased with the descent. In areas with an average temperature of 11.8-19.5 degrees C and the annual rainfall up to 574-970mm, transmission of the schistosomiasis was always present, suggesting an annual mean temperature around 15.7 degrees C and rainfall 800-900mm were favourable factors for schistosomiasis transmission. The cultivated areas with paddy soils were most suitable for the breeding of Oncomelania snails, where schistosmiasis was severely prevalent. Only a few Oncomelania snails and patients were observed in areas covered with red loam. No patient or snail was found in areas with brown loam or mountain meadow soil.

Animals↗
PubMed1990

Expression and secretion of preS containing hepatitis B surface antigen in vaccinia virus system.

The expression and secretion of preS containing hepatitis B surface antigen in vaccinia virus system was investigated. The human TK- 143 cells were infected with the recombinant vaccinia viruses vTMS-1 or vTLS-1. Cells infected with vTMS-1, which contains the preS2 + S gene, produced preS2 containing middle HBsAg proteins. Similarly, cells produced preS1 containing large HBsAg proteins upon infection with vTLS-1, which carries the preS1 + preS2 + S gene. The expression products could be secreted and form 22 nm particles. They reacted specifically with anti-preS1 and/or anti-preS2 monoclonal antibodies, and exhibited pHSA-receptor (for polymerized human serum albumin) activity. In addition, the major S components of hepatitis B surface antigen were also present in the products expressed by vTMS-1 and vTLS-1.

Cells, Cultured↗
PubMed1987

Isolated colonic tuberculosis.

Two cases of isolated colonic tuberculosis are reported, and recent literature on this field is reviewed. Isolated colonic tuberculosis is defined as a tuberculosis which exists in the colon except for ileocaecum, without focus in any other organ. The morphological changes are tuberculous granulation primarily located to the submucosa layer of the colon with smooth surfaces of both mucous and serous membrane. Its clinical features are atypical, just like those on X-ray examination, and even on frozen biopsy, it may sometimes be misdiagnosed. The treatment of choice is resecting the diseased segment of colon combined with anti-tuberculosis therapy.

Adult↗