A site-resolved two-dimensional quantum simulator with hundreds of trapped ions.

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation1. As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap2-4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap5,6. However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms7,8 using 2D ion trap quantum simulators.

Probing Complex-Energy Topology via Non-Hermitian Absorption Spectroscopy in a Trapped Ion Simulator.

Non-Hermitian systems generically have complex energies, which may host topological structures, such as links or knots. While there has been great progress in experimentally engineering non-Hermitian models in quantum simulators, it remains a significant challenge to experimentally probe complex energies in these systems, thereby making it difficult to directly diagnose complex-energy topology. Here, we experimentally realize a two-band non-Hermitian model with a single trapped ion whose complex eigenenergies exhibit the unlink, unknot, or Hopf link topological structures. Based on non-Hermitian absorption spectroscopy, we couple one system level to an auxiliary level through a laser beam and then experimentally measure the population of the ion on the auxiliary level after a long period of time. Complex eigenenergies are then extracted, illustrating the unlink, unknot, or Hopf link topological structure. Our work demonstrates that complex energies can be experimentally measured in quantum simulators via non-Hermitian absorption spectroscopy, thereby opening the door for exploring various complex-energy properties in non-Hermitian quantum systems, such as trapped ions, cold atoms, superconducting circuits, or solid-state spin systems.

Construction of CTC-ALK gene fusion detection system based on the multi-site magnetic separation in lung cancer and its clinical verification.

Detected in a variety of solid tumors, including lung cancer, the EML4-ALK fusion gene plays an important role in promoting the occurrence and development of cancer. The existing detection methods for EML4-ALK fusion gene are all targeted at surgical or post-sampling tumor tissues, which cannot achieve early detection and real-time monitoring; therefore, a minimally invasive ALK gene fusion detection system is explored and constructed. Vimentin, EpCAM, and EGFR antibodies were grafted, respectively, to prepare multi-site immunoliposome magnetic beads, so as to capture CTC in blood for RT-PCR detection, and then the feasibility of this method was verified by detecting the positive rate of the EML4-ALK fusion gene and clinical information in combination with WB and IHC. The prepared multi-site immunoliposome magnetic beads showed high specificity and stability, and the average proliferation rate and capture rate of cells were 95% and 85%, respectively. In clinical blood samples, the CTC level of the grade I (G1) patients before the operation was lower than grade 2 (G2), and that of grade II (G2) was significantly lower than grade III (G3), but the difference was not significant after the operation. The RT-PCR results of CTC and the RT-PCR, WB, and IHC results of tissues were highly consistent in the fusion gene detection, and the positive rate of ALK gene fusion in 60 lung cancer patients was 31.67% and 28.33% before and after the operation, mostly EML4-ALK (V3) gene fusion. The CTC-ALK gene fusion detection system constructed successfully could avoid the problem of difficult sampling and post-sampling complications, and truly achieve the minimally invasive biopsy, so it was of important clinical significance for the diagnosis and efficacy evaluation of lung.

Realization of a crosstalk-avoided quantum network node using dual-type qubits of the same ion species.

Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of 171Yb+ ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.

Chinese herbal medicine therapy for hyperlipidemic acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Chinese herbal medicine (CHM) has been widely used in the treatment of hyperlipidemic acute pancreatitis (HLAP), but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of CHM therapy for HLAP. MATERIALS AND METHODS: In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, PubMed, EMBASE, CBM, CNKI, VIP, and Wanfang databases from inception to October 16, 2022, for randomized controlled trials comparing the combination of CHM and Western medicine therapy vs. Western medicine therapy alone in HLAP adults. This study is registered with PROSPERO (No. CRD 42022371052). RESULTS: A total of 50 eligible studies involving 3,635 patients were assessed in this meta-analysis. Compared with Western medicine therapy, the combination of CHM increased the total effective rate by 19% in HLAP patients [relative risk (RR): 1.19, 95% CI: (1.16, 1.23)]. There were significant differences between the two groups in improving clinical symptoms, promoting serum amylase and triglyceride recovery, reducing mortality [RR: 0.28, 95% CI: (0.14, 0.56)] and complication rates [RR:0.40, 95% CI: (0.31, 0.52)], and shortening the length of hospital stay [MD: -3.96, 95% CI: (-4.76, -3.16)]. Adverse reactions were similar between groups. Findings were robust in the sensitivity analysis. CONCLUSIONS: The combined CHM treatment was more effective than Western medicine alone in HLAP patients. However, due to the methodological shortcoming of the eligible studies, caution is needed when interpreting these findings.

First Report of Pomegranate Wilt Caused by Ceratocystis fimbriata in Sichuan Province.

During May of 2009, a new devastating disease was observed on pomegranate (Punica granatum L.) that caused losses estimated at 30% as surveyed by 10 orchards in Panzhihua-Xichang Region of Sichuan Province, Southwest China. Characteristic symptoms were yellow and wilting leaves. Initial symptoms only occurred on shoots, but later, leaves of the whole tree turned yellow and wilted, causing extensive defoliation and dieback and the xylem of the trunk turned brown to black with a star burst-like pattern. Finally, heavy infection resulted in the whole tree dying, causing severe yield losses. A fungus was consistently isolated from basal stems and roots of diseased plants. Single conidia were obtained and cultured on potato dextrose agar (PDA) and incubated at 25 ± 1°C with a 12-h light/dark photoperiod. Mycelium was initially hyaline and then rapidly became dark greenish brown. Two types of endoconidia were produced in 5 days. Barrel-shaped conidia were hyaline, 1-celled, and measured 7.3 to 9.4 × 11.6 to 13.2 µm. Cylindrical conidia were hyaline, 1-celled, and measured 9.2 to 29.6 × 3.1 to 6.8 µm. Aleurioconidia were brownish, thick walled, near globose, and measured 8.7 to 18.1 × 8.2 to 10.7 µm. Perithecia were dark brown to black, globose, measured 90.8 to 149.8 µm in diameter, and had a long thin neck, 254.4 to 533.8 µm long, through which ascospores exuded. Ascospores were small, hyaline, hat shaped, measured 3.7 to 6.5 × 3.1 to 5.7 µm, and accumulated in a sticky matrix at the tip of the ascomal neck. The fungus was identified as Ceratocystis fimbriata (anamorph Chalara sp.) (1). The internal transcribed spacer (ITS) region of rDNA was amplified with universal primers ITS4/ITS5 and sequenced (GenBank Accession No. HQ529711), and comparisons with GenBank showed 99% similarity with C. fimbriata on Colocasia esculenta from Brazil (Accession No. AM712448.1). Pathogenicity tests were conducted. Two-week-old seedlings of pomegranate cv. Qingpiruanzi, germinated in plastic containers in the greenhouse, were wounded with a needle to a depth of 0.5 mm at the base of the stem below the soil level and near the root system, and then inoculated by drenching the wounds with a spore suspension (105 conidia per ml). Control plants were inoculated with sterile water. There were four replicates for each treatment. The treated plants were incubated at 25 ± 1°C with 80 to 95% relative humidity under a 12-h light/dark photoperiod in a greenhouse. All inoculated plants wilted within 25 days after inoculation and C. fimbriata was reisolated. All control plants remained healthily. To our knowledge, this is the first finding of pomegranate wilt caused by C. fimbriata in Sichuan Province. This pathogen may pose a serious threat to pomegranate production in Sichuan where it is a major fruit tree. This pathogen has been previously reported in India (3) and Yunnan Province, China (2), but is not known elsewhere. References: (1) C. J. B. Engelbrecht and T. C. Harrington. Mycologia 97:57, 2005. (2) Q. Huang et al. Plant Dis. 87:1150, 2003. (3) Y. M. Somasekhara. Plant Dis. 83:400, 1999.

TRIM56 suppresses the malignant development of hepatocellular carcinoma via targeting RBM24 and inactivating the Wnt signaling.

OBJECTIVE: The aim of this study was to explore the expression pattern of TRIM56 in Hepatocellular carcinoma (HCC) patients and its influence on the prognosis, and to illustrate the molecular mechanisms of TRIM56 in regulating HCC cell behaviors. PATIENTS AND METHODS: TRIM56 levels in HCC specimens and paracancerous specimens were detected. Then, the influences of TRIM56 on clinical data and prognosis in HCC patients were assessed. Next, the regulatory effects of TRIM56 on proliferative potential in Huh7 and Bel-7402 cells were determined, and the role of TRIM56 on the Wnt signaling was examined. Finally, biological characteristics between TRIM56 and RBM24 in HCC development were illustrated by Luciferase assay and rescue experiments. RESULTS: TRIM56 was lowly expressed in HCC tissues and cell lines. HCC patients expressing a low level of TRIM56 suffered advanced T stage and poor survival. Besides, overexpression of TRIM56 inhibited proliferative potential of Huh7 cells, while knockdown of TRIM56 in Bel-7402 yielded the opposite result. TRIM56 was able to negatively regulate key genes in the Wnt signaling. In addition, RBM24 was proven to be the downstream target of TRIM56, which was involved in TRIM56-influenced HCC development. CONCLUSIONS: Downregulated TRIM56 in HCC samples is closely linked to pathological staging and prognosis. TRIM56 alleviates the malignant development of HCC by inactivating the Wnt signaling and targeting RBM24.

Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma.

BACKGROUND: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT. METHODS: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT. RESULTS: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM. CONCLUSION: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC.

Circular RNA hsa_circ_103809 promotes cell migration and invasion of gastric cancer cells by binding to microRNA-101-3p.

OBJECTIVE: Studies have found that hsa_circ_103809, a newly discovered circRNA in recent years, can serve as an oncogene involved in the progression of hepatocellular carcinoma. However, its role in gastric cancer (GCa) remains elusive. The aim of this study was to reveal the molecular mechanism of hsa_circ_103809 affecting the process of GCa, thus providing new ideas for its treatment. PATIENTS AND METHODS: Hsa_circ_103809 expression in GCa and adjacent tissues specimens were studied by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis, and its effect on the prognosis of GCa patients was analyzed. In GCa cells lines, hsa_circ_103809 was knocked down by small interfering RNA, and GCa cell metastasis ability was detected by cell wound healing test and transwell assay. Finally, the potential target gene of hsa_circ_103809 was predicted through bioinformatics website and verified by Luciferase assay. RESULTS: Hsa_circ_103809 showed an increased expression both in GCa tissues and cell lines, predicting a poor prognosis of GCa patients. Meanwhile, the invasive and migration capacities of GCa cells were remarkably reduced after the knockdown of hsa_circ_103809. Bioinformatics website predicted that there existed binding sites of hsa_circ_103809 on microRNA-101-3p, and Luciferase assay verified that hsa_circ_103809 can adsorb microRNA-101-3p. In GCa tissues, qPCR detected a significantly reduced expression of microRNA-101-3p, which was negatively correlated with that of hsa_circ_103809. In addition, the knockdown of hsa_circ_103809 enhanced microRNA-101-3p expression in GCa cell lines. Subsequent in vitro experiments further detected that the overexpression of hsa_circ_103809 partially reversed the inhibitory effect of microRNA-101-3p overexpression on GCa cell migration ability and invasiveness. CONCLUSIONS: Hsa_circ_103809, highly expressed in GCa, may promote the migration capacity of GCa cells by adsorbing microRNA-101-3p and thus become a new therapeutic target for GCa.

Long non-coding RNA PLAC2 suppresses the survival of gastric cancer cells through down-regulating C-Myc.

OBJECTIVE: The aim of this study was to explore the effects of long non-coding ribonucleic acid (lncRNA) placenta-specific protein 2 (PLAC2) on the biological behaviors of gastric cancer (GC) cells by regulating the expression of c-Myc gene and its mechanism. PATIENTS AND METHODS: The expression of PLAC2 in GC tissues and different GC cell lines was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The effects of PLAC2 on apoptosis and cycle, migration, and invasion of GC cells were detected using flow cytometry, wound healing assay, and transwell assay, respectively. After interference in PLAC2 expression, the changes in c-Myc expression were determined through qRT-PCR and Western blotting. RESULTS: The expression level of PLAC2 was downregulated in 38 out of 45 cases of GC tissues compared with that in normal gastric tissues, and it also declined in GC cells. The results of flow cytometry showed that after overexpression of PLAC2, the cell cycle was arrested in the G1/G0 phase, and the apoptosis rate was increased. The results of wound healing assay and transwell assay revealed that both migration and invasion of GC cells were inhibited. After overexpression of PLAC2, the mRNA and protein expression levels of c-Myc declined. CONCLUSIONS: LncRNA PLAC2 affects the biological behaviors of GC cells by regulating the expression of c-Myc gene.

Inhibition of AIDS-Kaposi's sarcoma cell proliferation following retinoic acid receptor activation.

Retinoids, a group of natural and synthetic vitamin A analogues the receptors of which belong to the superfamily of steroid receptors, can exert profound effects on growth and/or differentiation of embryonic and neoplastic cells. Kaposi's sarcoma (KS), previously a rare multicentric neoplasm, has become epidemic with HIV infection, although the etiology of KS remains obscure. In the present study, the effects of two potent retinoids, all-trans-retinoic acid (RA) and 13-cis-RA, on the expression of retinoic acid receptor alpha and the growth of AIDS-related KS (AIDS-KS) cells were examined. The proliferation of AIDS-KS cells was significantly inhibited by RA and 13-cis-RA in a dose-dependent manner with 50% inhibitory concentration of 1.4 x 10(-10) M and 4.7 x 10(-9) M, respectively, which correlate with their potency. Growth inhibition was time dependent with maximal inhibition of 90% after 3 days of treatment with 10(-8) M RA. Growth inhibition by RA was further potentiated by forskolin (1 microM), an intracellular cyclic AMP-inducing agent. Moreover, RA treatment blocked the proliferative effect of oncostatin M and tumor necrosis factor alpha, two major KS autocrine growth factors. The effects of RA were accompanied by a dramatic increase in nuclear staining for retinoic acid receptor alpha and in the relative number of strongly positive retinoic acid receptor alpha nuclei. Finally, RA induced morphological changes as KS cells became more flattened, better spread, and more adhesive to the substrate. These results suggest that retinoids inhibit proliferation of AIDS-KS cells and further support their utility as therapeutic agents in AIDS-KS.

N-(4-hydroxyphenyl)retinamide increases ceramide and is cytotoxic to acute lymphoblastic leukemia cell lines, but not to non-malignant lymphocytes.

The retinoid, N-(4-hydroxyphenyl)retinamide (4-HPR), mediates p53-independent cytotoxicity and can increase reactive oxygen species and ceramide in solid tumor cell lines. We determined changes in ceramide and cytotoxicity upon treatment with 4-HPR (3-12 microM) in six human acute lymphoblastic leukemia (ALL) cell lines: T cell (MOLT-3, MOLT-4, CEM), pre-B-cell (NALM-6, SMS-SB), and null cell (NALL-1). Exposure to 4-HPR (12 microM) for 96 h caused 4.7 (MOLT-3), 3.5 (MOLT-4), 3.9 (CEM), 2.9 (NALM-6), 4.7 (SMS-SB), AND 4.5 (NALL-1) logs of cell kill. The average 4-HPR concentration that killed 99% of cells (LC(99)) for all six lines was 4.8 microM (range: 1.5-8.9 microM). Treatment with 4-HPR (9 microM) for 24 h resulted in an 8.9 +/- 1.0-fold (range: 4.9-15.7-fold) increase of ceramide. Ceramide increase was time- and dose-dependent and abrogated by inhibitors of de novo ceramide synthesis. Concurrent inhibition of ceramide glycosylation/acylation by d,l-threo-(1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol) (PPMP) further increased ceramide levels, and synergistically increased 4-HPR cytotoxicity in four of six ALL cell lines. 4-HPR was minimally cytotoxic to peripheral blood mononuclear cells and a lymphoblastoid cell line, and increased ceramide <2-fold. Thus, 4-HPR was cytotoxic and increased ceramide in ALL cell lines, but not in non-malignant lymphoid cell types.

Low molecular weight components but not dimeric HCG inhibit growth and down-regulate AP-1 transcription factor in Kaposi's sarcoma cells.

Kaposi's sarcoma, a sexually dimorphic disease inflicting high mortality in AIDS, remains at present without effective treatment. A recent report (Nature 375:64, 1995) showed that the placental glycoprotein hormone, human chorionic gonadotropin (HCG), and surprisingly its beta subunit, inhibit tumorigenicity and metastasis of Kaposi's sarcoma cells in mice xenografts. The anti-KS efficacy of a commercial HCG was subsequently demonstrated in clinical trials. Experimental data presented herein confirm that commercial HCG preparations (known to be about 25% pure) display significant inhibitory action in a dose-dependent manner. However, pure and biologically active HCG has no effect on Kaposi's sarcoma growth in culture. In fact, incubation of Kaposi's sarcoma cells with either one of four different well characterized preparations of pure HCG dimer or any of its two subunits did not alter cellular proliferation suggesting that a contaminant (or degradation product) may be the active agent. Commercial HCG preparations were subfractionated based on molecular size and each fraction was tested with respect to inhibition of KS cell growth, HCG radioreceptor binding and steroidogenic bioactivity. Results demonstrate that the anti-KS activity resides among low molecular weight components, and not in bona fide (macromolecular) HCG. Our study indicates that HCG activity and anti-KS action are separable. Interestingly, the active components in the crude HCG markedly down-regulate AP-1, a complex of transcription factors of the immediate-early response genes associated with cell growth. We conclude that, as yet unidentified molecules, present in the commercial HCG preparations, are responsible for the growth inhibitory effects presumably via the AP-1 signalling pathway.

Cloning and expression of full length mouse utrophin: the differential association of utrophin and dystrophin with AChR clusters.

We have cloned and sequenced mouse utrophin cDNA, and successfully expressed full length utrophin (400 kDa) in both muscle and non-muscle cells. The expression of recombinant utrophin is compared with that of its homologue, dystrophin (427 kDa). We demonstrate that recombinant utrophin is targeted into agrin-induced acetylcholine receptor (AChR) clusters, while recombinant dystrophin is evenly distributed along cell membranes in cultured Sol 8 muscle cells. This observation suggests that utrophin and dystrophin may interact with different cytoskeletal proteins. The C-terminal domains are found to be responsible for the association of utrophin with AChR clusters.

Use of thiocarbamides as selective substrate probes for isoforms of flavin-containing monooxygenases.

The oxidation of thiourea, phenylthiourea, 1,3-diphenylthiourea, 1,3-bis-(3,4-dichlorophenyl)-2-thiourea and 1,1-dibenzyl-3-phenyl-2-thiourea was measured in reactions catalyzed by purified pig liver flavin-containing monooxygenase (FMO-1) and by microsomal fractions isolated from pig, guinea pig, chicken, rat and rabbit tissues. The reactions, followed by measuring substrate-dependent thiocholine oxidation [Guo and Ziegler, Anal Biochem 198: 143-148, 1991], were carried out in the presence of 2 mM 1-benzylimidazole to minimize potential interference from reactions other than those catalyzed by isoforms of the flavin-containing monooxygenase (FMO). While at saturating substrate concentrations the Vmax for purified FMO-1 catalyzed oxidation of all five thiocarbamides was essentially constant, velocities for the microsomal catalyzed reactions varied not only with tissue and species but also with the van der Waals' surface area of the thiocarbamide. Rat liver, rat kidney and rabbit liver microsomes failed to catalyze detectable oxidation of thiocarbamides larger than 1,3-diphenylthiourea and lung microsomes from a female rabbit only accepted substrates smaller than 1,3-diphenylthiourea. On the other hand, liver microsomes from chickens, pigs and guinea pigs catalyzed the oxidation of larger thiocarbamides, but the rates decreased with increasing substrate size and chicken liver microsomes showed no detectable activity with the largest thiocarbamide tested. To define more precisely the parameters affecting thiocarbamide substrate specificity of microsomal preparations, activities present in detergent extracts of guinea pig liver microsomes were separated into three distinct fractions. The substrate specificities of these partially purified fractions were different and consistent with the difference observed with microsomal catalyzed reactions. This strongly suggests that thiocarbamides that differ in size may be useful probes for measuring the number of activities of FMO isoforms in crude tissue preparations.

Changes in substrate specificity of the recombinant form of phenol sulfotransferase IV (tyrosine-ester sulfotransferase).

The over-expression of mammalian enzymes in bacterial systems by means of recombinant DNA technology has provided the enzymologist with a supply of catalyst sufficiently abundant to identify suboptimal substrates. Such large quantities are particularly useful when working with the enzymes of detoxication, a family of proteins that are distinguished by their broad substrate specificity for generally lipophilic compounds, i.e., by their very low specificity for features other than the functional group [1]. We have achieved bountiful expression of a sulfotransferase active with phenols [2], an enzyme originally purified and characterized from rat liver [3], and classified as tyrosine-ester sulfotransferase, EC 2.8.2.9 [4,5], but usually referred to as rat liver phenol or aryl sulfotransferase IV. Having improved the sensitivity and versatility of some of the assays for sulfotransferases, we examined the substrate spectrum of this enzyme. As presented here, the results of this examination point to the limitations of enzyme nomenclature and to the danger of equating enzymes isolated from their normal habitat with those formed by recombinant technology in a foreign cell. Our experiments also establish a greater catalytic scope for the natural rat liver enzyme than that previously described.

Effects of silica on serum phospholipid, lipid peroxide and morphological characteristics of rat lung.

The effects of instilled silica have been studied on the serum-phospholipid (PL), lipid peroxide (LPO) and histopathology of rat lung up to 140 days from the first day of instillation. Silica induced relatively higher serum-PL throughout the experiment. The level of LPO also increased appreciably. They presented positive linear correlation. The early lesion was acute alveolitis with silica particles. These lesions became silicotic nodules on the 30th day, which then were enlarged gradually and fused by fibrosis. Alveolar macrophages (AM) were activated and surface structure was damaged. These results indicate that instilled silica can induce lipid peroxidation of cell membrane and selective accumulation of lung PL.

AIDS-related Kaposi's sarcoma: evidence for direct stimulatory effect of glucocorticoid on cell proliferation.

Glucocorticoid therapy has been linked to increased risk of development of Kaposi's sarcoma (KS), which has become epidemic among HIV-infected individuals. However, no experimental evidence is available to explain the role of glucocorticoid in KS biopathology. We investigated the direct effect of dexamethasone (Dex) on the growth of cultured KS cells derived from acquired immune deficiency syndrome (AIDS) patients (AIDS-KS). Dex significantly stimulated the proliferation of AIDS-KS cells. Moreover, simultaneous exposure to Dex and oncostatin M, a KS major cytokine, produced a dramatic synergistic effect on proliferation of AIDS-KS cell. This suggests an interaction between glucocorticoid and growth factor intracellular pathways in KS cells. The expression of glucocorticoid receptor protein and mRNA in AIDS-KS cell cultures was examined by radioimmunoassay and in situ hybridization, respectively. Compared with other well studied cell lines, AIDS-KS cells contain an unusually high level of glucocorticoid receptor protein, which is further upregulated by glucocorticoid treatment. RU-486, a glucocorticoid receptor antagonist, completely abolished the stimulatory effect of Dex and reduced the synergistic effect of Dex and oncostatin M on proliferation of AIDS-KS. These findings demonstrate that glucocorticoid stimulates directly the proliferation of AIDS-KS cells via the modulation of glucocorticoid receptor expression.

Estimation of flavin-containing monooxygenase activities in crude tissue preparations by thiourea-dependent oxidation of thiocholine.

The activity of flavin-containing monooxygenases in microsomes and whole homogenates is readily estimated by following the thiourea-dependent oxidation of thiocholine. NADPH- and oxygen-dependent flavin-containing monooxygenases catalyze the oxidation of thiourea to formamidine sulfenic acid, which oxidizes thiocholine to thiocholine disulfide. The latter reaction is quite rapid and never rate limiting even at concentrations of thiocholine below 30 microM. The loss of thiocholine in deproteinized aliquots of the reaction medium is measured colorimetrically with the thiol reagent, DTNB [5,5'-dithiobis(2-nitrobenzoate)]. In the absence of thiourea, thiocholine is not oxidized and its disulfide is not reduced at a detectable rate even in reactions containing 4-5 mg of liver or kidney homogenate protein per milliliter. In all tissues where both can be measured, rates of thiocholine oxidation and N,N-dimethylaniline N-oxygenation were virtually identical, which suggests that both activities are catalyzed by the same monooxygenase.

CLN3 defines a novel antiapoptotic pathway operative in neurodegeneration and mediated by ceramide.

Juvenile neuronal ceroid lipofuscinosis or Batten disease (JNCL) is a neurodegenerative disorder characterized by blindness, seizures, cognitive decline and early death. Brain atrophy and retinitis pigmentosa ensue because of neuronal and photoreceptor apoptosis. The CLN3 gene defective in JNCL encodes a novel 438 amino acid protein. Most affected genes harbor a deletion resulting in a truncated protein. CLN3 overexpression in NT2 cells enhances growth, reverses growth inhibition induced by serum starvation and protects from apoptosis induced by vincristine, staurosporine, and etoposide but not from death caused by ceramide. CLN3 modulates endogenous and vincristine-activated ceramide, and therefore suppresses apoptosis by impacting generation of ceramide.