[A Real-World Single-Center Study of Adult Hodgkin's Lymphoma].

OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

A single fluorescent probe to examine the dynamics of mitochondria-lysosome interplay and extracellular vesicle role in ferroptosis.

Ferroptosis is a non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation and glutathione (GSH) depletion. Despite recent advances, challenges remain in understanding the bidirectional interactions or interplay between organelles during ferroptosis. In this study, we aimed to understand the interplay between mitochondria (Mito) and lysosomes (Lyso) in cell homeostasis and ferroptosis. For this purpose, we designed a single fluorescent probe that marks GSH in Mito and hypochlorous acid (HOCl) in Lyso with two distinct emissions. Using this dual-targeted single fluorescent probe (9-morphorino pyronine), we detected Mito-Lyso interplay in ferroptosis. We disclosed differences in Mito-Lyso interplay depending on the induction of ferroptosis. Although erastin treatment decreased GSH, RSL3 triggered a HOCl burst, and FIN56- and FINO2-induced ferroptosis increased GSH and HOCl. Additionally, we showed that only extracellular vesicles generated during erastin-induced ferroptosis could spontaneously move and dock to neighboring cells, resulting in accelerated cell death.

AcHZP45 is a repressor of chlorophyll biosynthesis and activator of chlorophyll degradation in kiwifruit.

The degradation of chlorophyll during fruit development is essential to reveal a more 'ripe' color that signals readiness to wild dispersers of seeds and the human consumer. Here, comparative biochemical analysis of developing fruit of Actinidia deliciosa cv. Xuxiang ('XX', green-fleshed) and Actinidia chinensis cv. Jinshi No.1 ('JS', yellow-fleshed) indicated that variation in chlorophyll content is the major contributor to differences in flesh color. Four differentially expressed candidate genes were identified: the down-regulated genes AcCRD1 and AcPOR1 involved in chlorophyll biosynthesis, and the up-regulated genes AcSGR1 and AcSGR2 driving chlorophyll degradation. Prochlorophyllide and chlorophyllide, the metabolites produced by AcCRD1 and AcPOR1, progressively reduced in 'JS', but not in 'XX', indicating that chlorophyll biosynthesis was less active in yellow-fleshed fruit. AcSGR1 and AcSGR2 were verified to be involved in chlorophyll degradation, using both transient expression in tobacco and stable overexpression in kiwifruit. Furthermore, a homeobox-leucine zipper (HD-Zip II), AcHZP45, showed significantly increased expression during 'JS' fruit ripening, which led to both repressed expression of AcCRD1 and AcPOR1 and activated expression of AcSGR1 and AcSGR2. Collectively, the present study indicated that different dynamics of chlorophyll biosynthesis and degradation coordinate the changes in chlorophyll content in kiwifruit flesh, which are orchestrated by the key transcription factor AcHZP45.

Association between late gadolinium enhancement and outcome in dilated cardiomyopathy: A meta-analysis.

BACKGROUND: The prognostic value of late gadolinium enhancement (LGE) derived from cardiovascular magnetic resonance (CMR) is well studied, and several new metrics of LGE have emerged. However, some controversies remain; therefore, further discussion is needed, and more precise risk stratification should be explored. AIM: To investigate the associations between the positivity, extent, location, and pattern of LGE and multiple outcomes in dilated cardiomyopathy (DCM). METHODS: PubMed, Ovid MEDLINE, and Cochrane Library were searched for studies that investigated the prognostic value of LGE in patients with DCM. Pooled hazard ratios (HRs) and 95% confidence intervals were calculated to assess the role of LGE in the risk stratification of DCM. RESULTS: Nineteen studies involving 7330 patients with DCM were included in this meta-analysis and covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 21% and 50%. The meta-analysis revealed that the presence of LGE was associated with an increased risk of multiple adverse outcomes (all-cause mortality, HR: 2.14; arrhythmic events, HR: 5.12; and composite endpoints, HR: 2.38; all P < 0.001). Furthermore, every 1% increment in the extent of LGE was associated with an increased risk of all-cause mortality. Analysis of a subgroup revealed that the prognostic value varied based on different location and pattern of LGE. Additionally, we found that LGE was a stronger predictor of arrhythmic events in patients with greater left ventricular ejection fraction. CONCLUSION: LGE by CMR in patients with DCM exhibited a substantial value in predicting adverse outcomes, and the extent, location, and pattern of LGE could provide additional information for risk stratification.

Association of radiotherapy with thoracic vertebral fractures in esophageal squamous cell carcinoma: A retrospective cohort study.

To investigate the association between radiotherapy (RT) and thoracic vertebral fractures in esophageal squamous cell carcinoma (ESCC) and explore the risk factors of thoracic vertebral fracture in ESCC who underwent RT. This retrospective cohort study including 602 consecutive ESCC patients examined the association between RT and thoracic vertebral fractures using multivariable Cox proportional hazard models and relevant risk factors of thoracic vertebral fractures based on clinical and RT parameters in patients with ESCC. Followed for a median follow-up of 24 months, 54 patients had thoracic vertebral fractures. The multivariable analysis revealed RT as an independent risk factor after adjusting for clinical risk factors. Univariable analyses associated a 5-Gy increase in vertebral dose to single vertebrae and a 1-time increase in RT fraction with higher risk of vertebral fracture. Adding RT factors (vertebral dose and fraction) and mean vertebral hounsfield unit to the Cox models containing conventional clinical risk factors significantly improved the χ2 value for predicting vertebral fractures (all P < .001). This study revealed RT, as well as increased vertebral dose and RT fractions, as a significant, consistent, and strong vertebral fracture predictor in ESCC. Combined vertebral dose, RT fractions, and vertebral hounsfield unit provided optimal risk stratification for ESCC patients.

Application of instantaneous nebulization dispersive liquid-phase microextraction combined with HPLC for the determination of chalcone and isoflavone in traditional Chinese medicines.

A simple and rapid instantaneous nebulization dispersive liquid-phase microextraction method was developed, and combined with high-performance liquid chromatography for determination of the contents of seven analytes in traditional Chinese medicines. In this study, using the sprinkler device to achieve instantaneous synchronous dispersion and extraction, only one spray can rapidly achieve the concentration and enrichment of seven kinds of chalcone and isoflavones. The key factors affecting the extraction efficiency were optimized including the type and volume of extractant, the pH and salt concentration of the sample phase, and the number of dispersion. Under the optimal conditions, the enrichment factor of the target analytes ranged from 103.1 to 180.9, with good linearity and correlation coefficients above 0.9970. The limits of detection ranged from 0.02 to 0.15 ng/mL, with good accuracy (recoveries 91.1 to 108.9%) and precision (relative standard deviations 1.5-7.1%). This method has short extraction time (2 s), low organic solvent consumption and high enrichment effect, so it has a wide application prospects.

Evidence for exposure biomarkers in dictamnine-induced liver injury resulting from metabolic activation in vitro and in mice.

Dictamnine (DTN), a furoquinoline alkaloid isolated from Dictamni Cortex, is responsible for the liver injury caused by Dictamni Cortex and the preparations. Discovering new biomarkers with high specificity and sensitivity for diagnosis and tracing the source of DTN-induced liver injury is urgently needed. Considering that metabolic activation of DTN has been suggested as a primary trigger initiating hepatotoxicity, the present study aimed to investigate the bio-activation process of DTN in vitro and in mice and to explore whether the adducts could be developed as exposure biomarkers. When trapping with N-acetyl-cysteine (NAC) and glutathione (GSH) in mouse liver microsomes and CYP3A4 overexpressed L02 cells, two isomers of DTN-NAC adducts were detected in both systems and one DTN-GSH adduct was found in mouse liver microsomes. As expected, one DTN-NAC adduct was also found in plasma and bile of mice with liver injury after DTN exposure. Moreover, mouse liver microsomes were used to simulate the conjugation of serum albumin with metabolically activated DTN. The sole modified peptide 25 DAHKSEVAHR34 was found, and the oxidative metabolites of DTN might bind to the side chain amino of albumin at Arg34. The above findings not only provided confirmative evidence that DTN was metabolically activated to induce liver injury but also suggested that the adducts had the potential to be developed as exposure biomarkers of DTN-induced liver injury.

Bruguiera gymnorrhiza (L.) Lam. Fruit Accelerates Healing in Gastric Injury via the Regulation of the NF-κB Pathway.

Objective: The present study aimed at the anti-inflammatory and antioxidant effects of the extract of Bruguiera gymnorrhiza (L.) Lam. fruit (BGF) on the gastric injury. Materials and Methods: The chemical components in the extract of BGF were used in UPLC/Q-Orbitrap analysis. 60 SD rats were randomized into six groups: normal group (MC), ethanol-injured control group (EC), omeprazole group, and three groups with different doses (50, 100, and 200 mg/kg) of BGF. After continuous administration for seven days, the stomachs of rats were taken out to observe the pathological gastric tissue changes; inflammatory factors and oxidative stress markers in the stomach tissues were measured. Western blot (WB) analyses were conducted to explore the mechanism of BGF on gastric tissue and RAW 246.7 cells with excessive inflammation. Results: BGF enhanced gastric mucosal protection by improving the mucosal blood flow of the stomach and significantly decreased inflammatory factors and oxidative stress markers. Moreover, BGF significantly reduced the expression of p-NF-κB p65. Consistently, BGF demonstrated similar effects on LPS-induced RAW 264.7 cells as it did in vivo. Conclusion: BGF could accelerate the healing of gastric injury by exerting antioxidant and anti-inflammatory effects and maintaining mucosal integrity.

Isolation and Characterization of a Novel Lytic Halotolerant Phage from Yuncheng Saline Lake.

Halophilic phage are a type of virus that exist in salty environments within halophilic archaeal or bacterial hosts. However, relatively few reports on halophilic bacteriophages exist, and our overall understanding of halophilic bacteriophages is quite limited. We used SYBR Green I fluorescent staining to detect the abundance of viruses in Yuncheng Saline Lake, China. Using the double-layer plate method, a lytic phage that could infect halophilic bacterium Salinivibrio sp. YM-43 was isolated and named YXM43. We studied host range, optimal host, morphological characteristics, nucleic acid type, protein composition, and other biological characteristics of the virus. Results reveal a high abundance of this halophilic virus in Yuncheng Saline Lake. The newly isolated bacteriophage YXM43 has a narrow host range, with the most suitable host being Virgibacillus sp. SK39. After purification and enrichment, YXM43 is observed as a spherical particle with a diameter of approximately 30 nm, with no tail. No lipid envelope can be seen in YXM43. The capsid protein of the virus can be separated into seven proteins with molecular weights ranging from 62.0 to 13.0 kDa. YXM43 is a DNA virus with a genome approximately 23 kb. The virus is tolerant of low salinity, and its activity is highest at a temperature of 60 °C and a pH of 10. YXM43 is temperature and pH tolerant, and can adapt to environmental change, even withstanding chloroform treatment. The results indicate that bacteriophage YXM43 is a novel halophilic bacteriophage with broad tolerance to environmental change.

Metabolomics and integrated network pharmacology analysis reveal attenuates cardiac hypertrophic mechanisms of HuoXin pill.

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac hypertrophy (CH) is maladaptive and contributes to the pathogenesis of heart failure. Huoxin pill (HXP), a Chinese herbal prescription, is widely applied in the treatment of cardiovascular disease (CAD). Its mechanism, however, is unclear. AIM OF THE STUDY: This study investigated the mechanism of action for Huoxin pill in the treatment of CH, an important stage of CAD. MATERIALS AND METHODS: A total of 60 rats were injected with isoprenaline (ISO) to establish a model of CH. Echocardiography and histopathologic evaluation were performed to evaluate the disease severity, whereas ELISAs were conducted to determine the expression of oxidative stress. Network pharmacology and metabolomic analyses were conducted to identify the key compounds, core targets and pathways that mediate the effects of HXP against CH. Western blotting and immunohistochemistry were used to test apoptosis protein levels. RESULTS: HXP administration in ISO-treated rats decreased hypertrophy indices, alleviated cardiac pathological damage, and downregulated oxidative stress levels when compared to those of rats subjected to ISO treatment only. Moreover, network pharmacology results suggested that the PI3K-Akt pathway is a main mechanism by which HXP inhibits cardiac hypertrophy, and experimental verification showed that HXP inhibited cardiomyocyte apoptosis via activation of the PI3K-Akt pathway. The results of metabolomic analysis identified 21 differential metabolites between the HXPH group and ISO group, which were considered to be metabolic biomarkers of HXP in the treatment of CH. Among them, 6 differential metabolites were significantly upregulated, and 15 were significantly downregulated. CONCLUSIONS: The present study presents an integrated strategy for investigating the mechanisms of HXP in the treatment of CH and sheds new light on the application of HXP as a traditional Chinese medicine.

Simultaneous imaging of hypochlorous acid and nitric oxide in live cells based on a dual-channel fluorescent probe.

Both reactive oxygen species (ROS) and reactive nitrogen species (RNS) are inevitably produced during normal human metabolism. Various ROS and RNS together form tangled networks that play important roles in many physiological and pathological processes. Here we used 1,8-naphthalene diamine as a reactive group to develop a fluorescent probe, N-[2-(6-phenylethynyl)quinolinylmethyl]-1,8-diamino naphthalene (QBN), for HOCl and NO. QBN showed a "turn-on" fluorescent response at 464 nm to HOCl in the range of 0-75 µM with rapid responding time (10 s) and detection limit (0.11 ± 0.03 µM). Furthermore, a "turn-on" fluorescent responses at 512 nm to NO in the range of 0-40 µM with responding time (20 s) and detection limit (25.7 ± 3.4 nM) was found. The response mechanisms of QBN to HOCl and NO were discussed based on mass analysis of the different products. The dual-channel probe was then successfully applied for simultaneous imaging of both exogenous and endogenous HOCl and NO in live cells.

Polydatin prevents bleomycin-induced pulmonary fibrosis by inhibiting the TGF-ß/Smad/ERK signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible interstitial lung disease, with no effective cure. Polydatin is a resveratrol glucoside with strong antioxidant, anti-inflammatory and anti-apoptotic properties, which is used for treating health-related disorders such as cardiac disabilities, various types of carcinoma, hepatitis and hepatic fibrosis. The present study aimed to investigate the protective effect of polydatin against bleomycin-induced IPF and the possible underlying mechanism. A549 cells were treated with transforming growth factor-ß1 (TGF-ß1) and polydatin to observe phenotypic transformation and the related gene expression was detected. Sprague-Dawley rats were divided into seven groups and intratracheally infused with bleomycin to establish a pulmonary fibrosis model (the sham control group received saline). The rats were given pirfenidone (50 mg/kg), resveratrol (40 mg/kg) and polydatin (10, 40 and 160 mg/kg) for 28 days. The results demonstrated that polydatin had low toxicity to A549 cells and inhibited TGF-ß1-induced phenotypic transformation as determined by MTS assay or observed using a light microscope. It also decreased the gene expression levels of α-smooth muscle actin and collagen I and increased the gene expression levels of epithelial cell cadherin in vitro and in vivo by reverse transcription-quantitative PCR. Furthermore, polydatin ameliorated the pathological damage and fiber production in lung tissues found by hematoxylin and eosin staining and Masson trichrome staining. Polydatin administration markedly reduced the levels of hydroxyproline, tumor necrosis factor-α, interleukin (IL)-6, IL-13, myeloperoxidase and malondialdehyde and promoted total superoxide dismutase activity in lung tissues as determined using ELISA kits or biochemical reagent kits. It inhibited TGF-ß1 expression and phosphorylation of Smad 2 and 3 and ERK-1 and -2 in vivo as determined by western blot assays. These results suggest that polydatin protects against IPF via its anti-inflammatory, antioxidant and antifibrotic activities, and the mechanism may be associated with its regulatory effect on the TGF-ß pathway.

Matrix Metalloproteinases (MMPs) in Targeted Drug Delivery: Synthesis of a Potent and Highly Selective Inhibitor against Matrix Metalloproteinase- 7.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that play a key role in both physiological and pathological tissue degradation. MMPs have reportedly shown great potentials in the degradation of the Extracellular Matrix (ECM), have shown great potentials in targeting bioactive and imaging agents in cancer treatment. MMPs could provoke Epithelial to Mesenchymal Transition (EMT) of cancer cells and manipulate their signaling, adhesion, migration and invasion to promote cancer cell aggressiveness. Therefore, targeting and particularly inhibiting MMPs within the tumor microenvironment is an effective strategy for cancer treatment. Based on this idea, different MMP inhibitors (MMPIs) have been developed to manipulate the tumor microenvironment towards conditions appropriate for the actions of antitumor agents. Studies are ongoing to improve the selectivity and specificity of MMPIs. Structural optimization has facilitated the discovery of selective inhibitors of the MMPs. However, so far no selective inhibitor for MMP-7 has been proposed. AIMS: This study aims to comprehensively review the potentials and advances in applications of MMPs particularly MMP-7 in targeted cancer treatment approaches with the main focus on targeted drug delivery. Different targeting strategies for manipulating and inhibiting MMPs for the treatment of cancer are discussed. MMPs are upregulated at all stages of expression in cancers. Different MMP subtypes have shown significant targeting applicability at the genetic, protein, and activity levels in both physiological and pathophysiological conditions in a variety of cancers. The expression of MMPs significantly increases at advanced cancer stages, which can be used for controlled release in cancers in advance stages. METHODS: Moreover, this study presents the synthesis and characteristics of a new and highly selective inhibitor against MMP-7 and discusses its applications in targeted drug delivery systems for therapeutics and diagnostics modalities. RESULTS: Our findings showed that the structure of the inhibitor P3' side chains play the crucial role in developing an optimized MMP-7 inhibitor with high selectivity and significant degradation activities against ECM. CONCLUSION: Optimized NDC can serve as a highly potent and selective inhibitor against MMP-7 following screening and optimization of the P3' side chains, with a Ki of 38.6 nM and an inhibitory selectivity of 575 of MMP-7 over MMP-1.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera.

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.

Integration of transcriptomics and metabolomics profiling reveals the metabolic pathways affected in dictamnine-induced hepatotoxicity in mice.

Dictamnine (DTN), a major furoquinoline alkoloid from Dictamni Cortex, was reported to induce hepatotoxicity. However, the underlying mechanism is unclear. In the present study, integrated transcriptomic and metabolomics analysis of mouse liver was performed in combination with serum biochemical and histopathological evaluation to investigate the potential mechanism. The results suggested that 640 mg/kg DTN significantly increased serum alanine transaminase and aspartate transaminase levels and induced serious cellular degeneration, with no changes occurring with 4 mg/kg DTN. Integrated analysis suggested that the metabolism of xenobiotics by cytochrome P450, drug metabolism-other enzymes, bile secretion and glutathione metabolism were the major metabolic pathways involved in DTN-induced hepatotoxicity. Notably, 640 mg/kg DTN exposure increased hepatic GSH, GSH peroxidase, superoxide dismutase and malondialdehyde, and decreased ROS, together with altered expression of Idh2 and Nedd9. Representative genes, including Mup12, Lipc, NTCP, MRP3, MRP4, CYP2E1, CYP2D9 and UGT1A9, in altered pathways were verified through PCR and Western blot. Collectively, the combined strategy of transcriptomics and metabolomics profiling could facilitate a better understanding for the discovery of metabolic pathways and that oxidative damage, ABC transporters and lipid metabolism might be the mechanisms linked to DTN-induced hepatotoxicity in mice. SIGNIFICANCE: Dictamnine (DTN) was reported to induce hepatotoxicity. Nevertheless, the underlying mechanism is unknown. This study is the first to utilize integrated transcriptomics and metabolomics in combination with general toxicity evaluation to characterize the potential molecular mechanism in DTN-induced hepatotoxicity in mice. We found that acute exposure to higher dose of DTN induced hepatocellular liver injury with more changes in biochemical parameters, genes and metabolites. Gene expression and metabolite profiles were more sensitive than general toxicity studies for detecting earlier hepatotoxicity. Integrated analysis suggested that oxidative damage, ABC transporters and lipid metabolism were closely correlated with DTN-induced hepatotoxicity. Overall, our results provide insights into the mechanism responsible for DTN-induced hepatotoxicity.

Metabolomic-transcriptomic landscape of 8-epidiosbulbin E acetate -a major diterpenoid lactone from Dioscorea bulbifera tuber induces hepatotoxicity.

Studies have shown that 8-epidiosbulbin E acetate (EEA), a major diterpenoid lactone in the tuber of Dioscorea bulbifera, can induce hepatotoxicity in vivo. However, the underlying mechanisms remain unknown. Using the integrated transcriptomic and metabolomics method, in this study we investigated the global effect of EEA exposure on the transcriptomic and metabolomic profiles in mice. The abundance of 7131 genes and 42 metabolites in the liver, as well as 43 metabolites in the serum were altered. It should be noted that EEA mainly damaged hepatic cells through the aberrant regulation of multiple systems primarily including bile acid metabolism, and taurine and hypotaurine metabolism. In addition, an imbalance of bile acid metabolism was found to play a key pat in response to EEA-triggered hepatotoxicity. In summary, these findings contributed to understanding the underlying mechanisms of EEA hepatotoxicity.

Salisbury screen optical color filter with ultra-thin titanium nitride film.

Titanium nitride (TiN) is a metal-like refractory material that can be used as a substitution for metals in many applications. In this paper, we report the use of an ultra-thin TiN film in the Salisbury screen structure to spectral selectively absorb visible light for forming an optical color filter. The ultra-thin TiN film functions as a partial reflector as well as a protection capping layer in the structure. Spectral selective perfect absorption color filters with TiN-ZnO-Al multilayer films were fabricated and characterized.

Rapid detection of PAH gene mutations in Chinese people.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive genetic disease, caused by the phenylalanine hydroxylase (PAH) deficiency in the metabolic pathway, which prevents phenylalanine from being converted into tyrosine, leading to a large amount of phenylalanine discharged from the urine. Therefore, it is necessary to establish a simple, fast, accurate and reliable PKU molecular diagnostic method for clinical diagnosis. METHODS: We established a novel diagnostic method by combining a single-tube multiplex PCR technique with molecular hybridization technique. The method was verified by DNA sequencing technology. The established new technology successfully detected 9 common PAH gene mutations in the Chinese population. RESULTS: Double-blind analysis indicated that the diagnostic accuracy and specificity of the PKU sample were all 100%. Frequencies of single mutation R111X, R176X, Ex6-96A, R241C, R243Q, R252Q, Y356X, V399 V and R413P genotypes were 8, 0.5, 16.5, 1.5, 27, 4.5, 13, 10.5, 8.5% respectively. CONCLUSIONS: The established method of combing single-tube multiplex PCR with molecular hybridization technology can accurately and rapidly detect PAH gene mutations in Chinese and is suitable for screening of large PKU populations with clinical samples.

The Modulatory Role of CYP3A4 in Dictamnine-Induced Hepatotoxicity.

Dictamni Cortex (DC) has been reported to be associated with acute hepatitis in clinic and may lead to a selective sub-chronic hepatotoxicity in rats. Nevertheless, the potent toxic ingredient and the underlying mechanism remain unknown. Dictamnine (DTN), the main alkaloid from DC, possesses a furan ring which was suspected of being responsible for hepatotoxicity via metabolic activation primarily by CYP3A4. Herein, the present study aimed to evaluate the role of CYP3A4 in DTN-induced liver injury. The in vitro results showed that the EC50 values in primary human hepatocytes (PHH), L02, HepG2 and NIH3T3 cells were correlated with the CYP3A4 expression levels in corresponding cells. Furthermore, the toxicity was increased in CYP3A4-induced PHH by rifampicin, and CYP3A4 over-expressed (OE) HepG2 and L02 cells. Contrarily, the cytotoxicity was decreased in CYP3A4-inhibited PHH and CYP3A4 OE HepG2 and L02 cells inhibited by ketoconazole (KTZ). In addition, the hepatotoxicity of DTN in enzyme induction/inhibition mice was further investigated in the aspects of biochemistry, histopathology, and pharmacokinetics. Administration of DTN in combination with KTZ resulted in attenuated liver injury, including lower alanine transaminase and aspartate transaminase activities and greater AUC and C max of serum DTN, whereas, pretreatment with dexamethasone aggravated the injury. Collectively, our findings illustrated that DTN-induced hepatotoxicity correlated well with the expression of CYP3A4, namely inhibition of CYP3A4 alleviated the toxicity both in vitro and in vivo, and induction aggravated the toxicity effects.