Nanotechnology-based non-viral vectors for gene delivery in cardiovascular diseases.

Gene therapy is a technique that rectifies defective or abnormal genes by introducing exogenous genes into target cells to cure the disease. Although gene therapy has gained some accomplishment for the diagnosis and therapy of inherited or acquired cardiovascular diseases, how to efficiently and specifically deliver targeted genes to the lesion sites without being cleared by the blood system remains challenging. Based on nanotechnology development, the non-viral vectors provide a promising strategy for overcoming the difficulties in gene therapy. At present, according to the physicochemical properties, nanotechnology-based non-viral vectors include polymers, liposomes, lipid nanoparticles, and inorganic nanoparticles. Non-viral vectors have an advantage in safety, efficiency, and easy production, possessing potential clinical application value when compared with viral vectors. Therefore, we summarized recent research progress of gene therapy for cardiovascular diseases based on commonly used non-viral vectors, hopefully providing guidance and orientation for future relevant research.

Engineered Extracellular Vesicles Expressing Siglec-10 Camouflaged AIE Photosensitizer to Reprogram Macrophages to Active M1 Phenotype and Present Tumor-Associated Antigens for Photodynamic Immunotherapy.

Cancer immunotherapy has attracted considerable attention due to its advantages of persistence, targeting, and ability to kill tumor cells. However, the efficacy of tumor immunotherapy in practical applications is limited by tumor heterogeneity and complex tumor immunosuppressive microenvironments in which abundant of M2 macrophages and immune checkpoints (ICs) are present. Herein, two type-I aggregation-induced emission (AIE)-active photosensitizers with various reactive oxygen species (ROS)-generating efficiencies are designed and synthesized. Engineered extracellular vesicles (EVs) that express ICs Siglec-10 are first obtained from 4T1 tumor cells. The engineered EVs are then fused with the AIE photosensitizer-loaded lipidic nanosystem to form SEx@Fc-NPs. The ROS generated by the inner type-I AIE photosensitizer of the SEx@Fc-NPs through photodynamic therapy (PDT) can convert M2 macrophages into M1 macrophages to improve tumor immunosuppressive microenvironment. The outer EV-antigens that carry 4T1 tumor-associated antigens directly stimulate dendritic cells maturation to activate different types of tumor-specific T cells in overcoming tumor heterogeneity. In addition, blocking Siglec-10 reversed macrophage exhaustion for enhanced antitumor ability. This study presents that a combination of PDT, immune checkpoints, and EV-antigens can greatly improve the efficiency of tumor immunotherapy and is expected to serve as an emerging strategy to improve tumor immunosuppressive microenvironment and overcome immune escape.

Indoleamine 2,3-Dioxygenase 1 Deletion-Mediated Kynurenine Insufficiency Inhibits Pathological Cardiac Hypertrophy.

BACKGROUND: Aberrant amino acid metabolism is implicated in cardiac hypertrophy, while the involvement of tryptophan metabolism in pathological cardiac hypertrophy remains elusive. Herein, we aimed to investigate the effect and potential mechanism of IDO1 (indoleamine 2,3-dioxygenase) and its metabolite kynurenine (Kyn) on pathological cardiac hypertrophy. METHODS: Transverse aortic constriction was performed to induce cardiac hypertrophy in IDO1-knockout (KO) mice and AAV9-cTNT-shIDO1 mice. Liquid chromatography-mass spectrometry was used to detect the metabolites of tryptophan-Kyn pathway. Chromatin immunoprecipitation assay and dual luciferase assay were used to validate the binding of protein and DNA. RESULTS: IDO1 expression was upregulated in both human and murine hypertrophic myocardium, alongside with increased IDO1 activity and Kyn content in transverse aortic constriction-induced mice's hearts using liquid chromatography-mass spectrometry analysis. Myocardial remodeling and heart function were significantly improved in transverse aortic constriction-induced IDO1-KO mice, but were greatly exacerbated with subcutaneous Kyn administration. IDO1 inhibition or Kyn addition confirmed the alleviation or aggravation of hypertrophy in cardiomyocyte treated with isoprenaline, respectively. Mechanistically, IDO1 and metabolite Kyn contributed to pathological hypertrophy via the AhR (aryl hydrocarbon receptor)-GATA4 (GATA binding protein 4) axis. CONCLUSIONS: This study demonstrated that IDO1 deficiency and consequent Kyn insufficiency can protect against pathological cardiac hypertrophy by decreasing GATA4 expression in an AhR-dependent manner.

The occurrence, tissue distribution, and PBT potential of per- and polyfluoroalkyl substances in the freshwater organisms from the Yangtze river via nontarget analysis.

Numerous emerging per- and polyfluoroalkyl substances (PFASs) occur in the aquatic environment, posing a threat to aquatic ecosystems and human health. In this study, we conducted a nontarget analysis on 3 surface water samples and 92 tissue samples of 16 fish collected from the Yangtze River to investigate the patterns, tissue distribution, and environmental impacts of emerging PFASs. A total of 43 PFASs from 11 classes were identified, including 17 legacy PFASs and 26 emerging PFASs. Among the 43 PFASs, seven PFASs were reported in biota for the first time while five PFASs were reported in the environment for the first time. Chlorine substituted perfluoroalyl ether sulfonic acids were the major emerging PFASs detected in organisms. Our results showed that most emerging PFASs tended to accumulate in the liver whereas perfluorinated sulfonamides tended to accumulate in the blood, and all of the emerging PFASs accumulated less in the muscle. Methods for evaluating the persistence, bioaccumulation, and toxicity (PBT) of PFASs were developed by combining the in-silico methods and experimental methods. Long-chain PFASs were found to have extremely high PBT scores compared to short-chain PFASs. Additionally, most emerging PFASs exhibited comparable PBT characteristics with legacy PFASs, especially Cl-substituted PFASs.

Occurrence, partitioning and transport of perfluoroalkyl acids in gas and particles from the southeast coastal and mountainous areas of China.

Perfluoroalkyl acids (PFAA) in gas and particles were analyzed in southeast coastal and mountainous cities, including Fuzhou, Xiamen, Zhangzhou and Nanping, to study the pollution characteristics, particle size distribution, phase partitioning and atmospheric transport. PFAA ranged from 7.8 to 290 pg m-3 in gaseous phase, 27 - 1200 pg m-3 in particulate phase, and perfluorobutanoic acid (PFBA), perfluorooctanoic acid (PFOA) were main compounds. PFAA had the highest concentration in Nanping with perfluorohexanoic acid (PFHxA) dominant, which could be related to the emission of PFAS from local industrial plants. Perfluorocarboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) exhibited different particle size distribution characteristics, with PFSAs preferring to distribute on coarse particles, which could be affected by the salt, minerals and organic matter in different particle sizes. The gas - particle partitioning coefficient (KPA) had a line relationship with the fluorinated carbon chain length of PFAA, suggesting that long-chain PFAA tended to exist in particulate phase. The Winter Monsoon could transport to the study area and drive atmospheric PFAS to southern cities. HIGHLIGHTS: • Industrial plants contributed high concentrations of PFAA. • PFSAs tended to present in coarse particles. • Log KPA increased linearly with increasing carbon chain length of PFAA. • Winter Monsoon drove atmospheric PFAA to southern cities.

The Function and Therapeutic Implications of TNF Signaling in MDSCs.

Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous myeloid cells with immunosuppressive functions. MDSCs play important roles in the pathogenesis of cancer, chronic inflammatory diseases, and many autoimmune disorders. The accumulation and activation of MDSCs can be regulated by tumor necrosis factor α (TNF-α). In this review, we summarize the roles played by TNF-α in the recruitment, immunosuppressive functions, and chemotaxis of MDSCs, and discuss the potential therapeutic effects of TNF-α upon these cells in tumor growth and some inflammatory disorders.

[Rapid determination of 16 polycyclic aromatic hydrocarbons in atmospheric fine particles by molecularly imprinted column-high performance liquid chromatography].

OBJECTIVE: A high performance liquid chromatographic method based on the purification of polycyclic aromatic hydrocarbon molecularly imprinted columns was developed, this method was used for the rapid quantitative determination of 16 polycyclic aromatic hydrocarbons(PAHs) in fine particulate matter(PM_(2.5)). METHODS: The polycyclic aromatic hydrocarbons of the sample were extracted with acetonitrile ultrasonically, purified by molecular imprinting column(MIP-PAHs), and tested after being concentrated by nitrogen blowing. RESULTS: The 16 PAHs showed a good linear relationship in the range of 1-40 ng/mL, and the correlation coefficient r>0.9996; the recoveries were 77.13%-107.67% at the three standard addition levels of 5.0, 10.0 and 20.0 ng/mL, the relative standard deviation was 0.15%-4.63%(n=7); the detection limit of the method was 0.004-0.078 ng/m~3, and the quantification limit was 0.016-0.336 ng/m~3. CONCLUSION: The detection of 16 PAHs in PM_(2.5) using this method is more accurate, more sensitive and less time consuming than the result of the simple ultrasonic extraction method and the Soxhlet extraction method in Determination of PAHs in ambient air and exhaust gases in gas phase and particulate matter by high performance liquid chromatography(HJ 647-2013).

Dry-deposition of inorganic and organic nitrogen aerosols in Xiamen Bay: Fluxes, sources, and biogeochemical significance.

Increased dry deposition of nitrogen aerosols (aerosol-N) as a result of anthropogenic emissions has caused large negative impacts on marine ecosystems. We monitored the number concentrations and sizes of inorganic nitrogen aerosols (aerosol-IN: NH4+ and NO3-) and organic nitrogen aerosols (aerosol-ON: methylamine, dimethylamine, trimethylamine, ethylamine, diethylamine, and triethylamine) by single-particle aerosol mass spectrometry (SPAMS) during the warm season (WS) and cold season (CS) of 2013 and 2015 in Xiamen Bay. The mean hourly number concentration of aerosol-IN (874/h) overwhelmed that of aerosol-ON (103/h), accounting for 83.9 ± 16.1% of aerosol-N. More than 90% of aerosol-N was concentrated in the condensation mode (0.1-0.5 µm) and droplet mode (0.5-2.0 µm). Aerosol-IN was the main contributor (80.1-94.2%) to aerosol-N deposition. New production potentially supported by the ocean's external nitrogen supply provided aerosol-N input of 11.51-11.96 g C m-2 yr-1, which contributed 17.5-18.2% of total new production in the southern East China Sea. Four potential sources of aerosol-N were identified based on the results of positive matrix factorization analysis, including secondary formation (F1), biogenic source (F2), sea spray, soil dust, biomass burning (F3), and anthropogenic sources (F4). Aerosol-N concentrations in Xiamen Bay were mainly affected by the ocean air masses during the WS and inland air masses during the CS. The percentages of aerosol-N at each backward trajectory cluster showed that the inland air masses brought more aerosol-IN emitted from biomass burning, soil dust, and secondary formation sources, whereas the ocean air masses brought more aerosol-ON emitted from a marine biogenic source into Xiamen Bay. This study provides an example of determining the number concentrations and sizes of IN and ON in aerosols by SPAMS, and helps us further understand the dry deposition and sources of IN and ON in aerosols in Xiamen Bay.

Development and performance evaluation of TaqMan real-time fluorescence quantitative methylation specific PCR for detecting methylation level of PER2.

BACKGROUND: PER2 gene methylation is closely related to the occurrence and progress of some cancers, but there is no method to quantitatively detect PER2 methylation in conventional laboratories. So, we established a TaqMan real-time fluorescence quantitative methylation specific PCR (TaqMan real-time FQ-MSP) assay and use it for quantitative detection of PER2 methylation in leukemia patients. METHODS: According to the PER2 sequence searched by GenBank, a CpG sequence enrichment region of the PER2 gene promoter was selected, and the methylated and unmethylated target sequences were designed according to the law of bisulfite conversion of DNA to construct PER2 methylation positive and negative reference materials. Specific primers and probe were designed. The reference materials were continuously diluted into gradient samples by tenfold ratio to evaluate the analytical sensitivity, specificity, accuracy and reproducibility of the method, and the analytical sensitivity of TaqMan real-time FQ-MSP assay was compared with that of the conventional MSP assay. At the same time, the new-established TaqMan real-time FQ-MSP assay and the conventional MSP assay were used to detect the PER2 methylation level of 81 patients with leukemia, and the samples with inconsistent detection results of the two assays were sent to pyromethylation sequencing to evaluate the clinical detection performance. RESULTS: The minimum detection limit of TaqMan real-time FQ-MSP assay for detecting PER2 methylation level established in this study was 6 copies/uL, and the coefficient of variation(CV) of intra-assay and inter-assay was less than 3%. Compared with the conventional MSP assay, it has higher analytical sensitivity. For the samples with inconsistent detection results, the results of pyrosequencing and TaqMan real-time FQ-MSP assay are consistent. CONCLUSION: TaqMan real-time FQ-MSP assay of PER2 methylation established in this study has high detection performance and can be used for the detection of clinical samples.

[Genetic analysis of an individual with a fragile site at 16q22].

OBJECTIVE: To analyze a patient with infertility and a fragile site found at 16q22 by using cytogenetic methods. METHODS: Peripheral blood sample was taken from the patient and subjected to chromosomal karyotyping and single nucleotide polymorphism microarray (SNP-array) analysis. RESULTS: The patient was found to be a mosaicism for a fragile site at 16q22, which has a variable morphology and cannot be induced by folic acid treatment. No abnormality was found by SNP-array analysis. CONCLUSION: A rare fragile site, which can be induced without folic acid treatment, has been identified at 16q22. The strategy of assisted reproduction for such individuals is yet to be explored.

Identifying the competencies of China's paediatric residents: a modified Delphi method study.

PURPOSE: Standardised Training of Paediatric Resident (STPR) plays an essential role in training qualified paediatricians. Until now, China had no paediatric resident competency index system to effectively guide and evaluate the competence of paediatric residents. This study aimed to establish a competency index system for paediatric residents in China to provide a reference for improving the training system and quality of STPR. STUDY DESIGN AND SETTING: This study conducted two rounds of Delphi expert consultation survey among paediatric medical experts (n=16), followed by screening, revising and supplementing indicators using the boundary value method. Next, the analytic hierarchy process was used to determine the weight of indicators and finally establish a competency index system for paediatric residents. RESULTS: The results of the statistical analysis revealed a positive coefficient of 100% for both rounds of expert consultation. The expert authority coefficient values were 0.82 and 0.83, and the expert coordination coefficient test was p<0.01. After referring to experts' opinions, a competency index system for paediatric residents with 5 primary indicators, 14 secondary indicators and 73 tertiary indicators was finally formed and the weight of each indicator was calculated. The five primary indicators were professional quality (0.3187), knowledge and skills (0.2734), communication and cooperation (0.1986), lifelong learning (0.1302), and teaching ability (0.0791). CONCLUSIONS: In this study, a competency index system for paediatric residents was constructed following the characteristics and quality requirements for paediatric residents in China and is expected to significantly improve the overall level of paediatricians' medical service quality and supply.

Distribution and sources of polycyclic aromatic hydrocarbons in the water column of Kongsfjorden, Arctic.

Kongsfjorden is known for its characteristic multi-layer water mass formed by the convergence of freshwaters from nearby glaciers and rivers and saline water from the Atlantic and Arctic. The distribution of polycyclic aromatic hydrocarbons (PAHs) in the water column of Kongsfjorden was investigated and their potential sources were analyzed. The total concentrations of 16 PAHs in the surface seawater and river water were in the range of 33.4-79.8 ng/L (mean 48.5 ng/L) and 2.3-201.4 ng/L (mean 126.1 ng/L), respectively. Horizontally, PAHs were mainly concentrated around river estuaries and the glacier front in the dissolved phase. Vertically, the PAHs in the particulate phase followed surface-enrichment and depth-depletion patterns in most stations, with the maximum concentration found at 50 m depth in the central area of Kongsfjorden. The compositions of PAHs in seawater and rivers were similar, with two-ring and tricyclic PAHs comprising the majority of the dissolved and particulate phases. PAHs found in Kongsfjorden waters appeared to be derived from multiple sources such as petroleum and coal combustion. PAHs in the bay mouth of Kongsfjorden were mainly introduced by the West Spitsbergen Current and the Arctic waters, while in the inner bay, atmospheric deposition and local sources were the major contributors. The distribution of PAHs was mainly attributed to the suspended particulate distribution.

Occurrence, distribution, air-seawater exchange and atmospheric deposition of organophosphate esters (OPEs) from the Northwestern Pacific to the Arctic Ocean.

Eleven organophosphate esters (OPEs) in air and seawater were investigated from the Northwestern Pacific to the Arctic Ocean. The concentration of Σ11OPEs in air and seawater ranged from 231.56 to 1884.25 pg/m3 and from 8.47 to 143.45 ng/L, respectively. Halogenated OPEs dominated in both two media. The slight decreasing trend was observed for OPEs in gaseous air, no obvious trend for particle-bound OPEs and in seawater. The net air-seawater exchange flux ranged from -792.68 to 590.29 pg/m2/day. The dry deposition flux ranged from 16.4 to 185 ng/m2/day with high value observed at the Bering Strait (64.70 ng/m2/day). The relationship between temperature and OPEs particle-bound fractions suggests that temperature might be a driving factor of OPEs long-range atmospheric transport (LRAT). This research highlighted that OPEs are subject to LRAT from the Asian continent to the northwestern Pacific and Arctic Oceans and demonstrated the "sink" in polar regions of OPEs atmospheric transportation.

Effect of calcium chloride on the uniformity of colouring in sushi red ginger slices by modulating the properties of starch.

The colour of sushi red ginger slices without blanching is not uniform, which seriously affects their sensory quality. The effect of calcium chloride (CaCl2) pretreatment on the uniformity of colouring and the properties of ginger starch have been studied. The crystalline region of the starch in blanched ginger slices was broken, which might be beneficial for uniform colouring. The effect of CaCl2 pretreatment on starch properties depended on the concentration. The influence of CaCl2 at a concentration higher than 3.5 mol L-1 was more pronounced than that at a lower concentration. The uniformity of colouring was close to the effect of blanching treatment. Furthermore, the starch crystallization was destroyed, the granules were broken, and the polarized cross disappeared, which was consistent with that observed for the starch in blanched ginger slices. Therefore, it is possible to achieve a uniform colour in red ginger slices at room temperature through CaCl2 pretreatment.

A de novo complex chromosome rearrangement associated with multisystematic abnormalities, a case report.

BACKGROUND: Complex chromosomal rearrangements (CCRs) are constitutional structural rearrangements that involve three or more chromosomes or that have more than two breakpoints. CASE PRESENTATION: Here, we describe a four-way CCR involving chromosomes 4, 5, 6 and 8. The patient had mild multisystematic abnormalities during his development, including defects in his eyes and teeth, exomphalos and asthenozoospermia. His wife had two spontaneous abortions during the first trimester. The translocations in 4q27, 5q22, 6q22.3, and 8p11.2 were diagnosed by conventional cytogenetic analysis and confirmed by fluorescence in situ hybridization(FISH). After analysis using a SNP array, we defined three microdeletions, including 0.89 Mb on chromosome 4, 5.39 Mb on chromosome 5 and 0.43 Mb on chromosome 8. His mother had a chimera karyotype of 47, XXX[5]/45, X[4]/46, XX[91]; the other chromosomes were normal. After one cycle of in vitro fertility (IVF) treatment followed by preimplantation genetic diagnosis (PGD), they obtained two embryos, but neither was balanced. CONCLUSIONS: The patient's phenotype resulted from the CCR and microdeletion of chromosomes 4, 5 and 8. The couple decided to use artificial insemination by donor (AID) technology.

Distribution and sources of polycyclic aromatic hydrocarbons in surface sediments from the Bering Sea and western Arctic Ocean.

To analyze the distribution and sources of polycyclic aromatic hydrocarbons (PAHs) and evaluate their potential ecological risks, the concentrations of 16 PAHs were measured in 43 surface sediment samples from the Bering Sea and western Arctic Ocean. Total PAH (tPAH) concentrations ranged from 36.95 to 150.21 ng/g (dry weight). In descending order, the surface sediment tPAH concentrations were as follows: Canada Basin>northern Chukchi Sea>Chukchi Basin>southern Chukchi Sea>Aleutian Basin>Makarov Basin>Bering Sea shelf. The Bering Sea and western Arctic Ocean mainly received PAHs of pyrogenic origin due to pollution caused by the incomplete combustion of fossil fuels. The concentrations of PAHs in the sediments of the study areas did not exceed effects range low (ERL) values.

Multi-label classification for colon cancer using histopathological images.

Colon cancer classification has a significant guidance value in clinical diagnoses and medical prognoses. The classification of colon cancers with high accuracy is the premise of efficient treatment. Our task is to build a system for colon cancer detection and classification based on slide histopathological images. Some former researches focus on single label classification. Through analyzing large amount of colon cancer images, we found that one image may contain cancer regions of multiple types. Therefore, we reformulated the task as multi-label problem. Four kinds of features (Color Histogram, Gray-Level Co-occurrence Matrix, Histogram of Oriented Gradients and Euler number) were introduced to compose our discriminative feature set, extracted from our dataset that includes six single categories and four multi-label categories. In order to evaluate the performance and make comparison with our multi-label model, three commonly used multi-classification methods were designed in our experiment including one-against-all SVM (OAA), one-against-one SVM (OAO) and multi-structure SVM. Four indicators (Precision, Recall, F-measure, and Accuracy) under 3-fold cross-validation were used to validate the performance of our approach. Experiment results show that the precision, recall and F-measure of multi-label method as 73.7%, 68.2%, and 70.8% with all features, which are higher than the other three classifiers. These results demonstrate the effectiveness and efficiency of our method on colon histopathological images analysis.

Pharmaceuticals in tap water: human health risk assessment and proposed monitoring framework in China.

BACKGROUND: Pharmaceuticals are known to contaminate tap water worldwide, but the relevant human health risks have not been assessed in China. OBJECTIVES: We monitored 32 pharmaceuticals in Chinese tap water and evaluated the life-long human health risks of exposure in order to provide information for future prioritization and risk management. METHODS: We analyzed samples (n = 113) from 13 cities and compared detected concentrations with existing or newly-derived safety levels for assessing risk quotients (RQs) at different life stages, excluding the prenatal stage. RESULTS: We detected 17 pharmaceuticals in 89% of samples, with most detectable concentrations (92%) at < 50 ng/L. Caffeine (median-maximum, nanograms per liter: 24.4-564), metronidazole (1.8-19.3), salicylic acid (16.6-41.2), clofibric acid (1.2-3.3), carbamazepine (1.3-6.7), and dimetridazole (6.9-14.7) were found in ≥ 20% of samples. Cities within the Yangtze River region and Guangzhou were regarded as contamination hot spots because of elevated levels and frequent positive detections. Of the 17 pharmaceuticals detected, 13 showed very low risk levels, but 4 (i.e., dimetridazole, thiamphenicol, sulfamethazine, and clarithromycin) were found to have at least one life-stage RQ ≥ 0.01, especially for the infant and child life stages, and should be considered of high priority for management. We propose an indicator-based monitoring framework for providing information for source identification, water treatment effectiveness, and water safety management in China. CONCLUSION: Chinese tap water is an additional route of human exposure to pharmaceuticals, particularly for dimetridazole, although the risk to human health is low based on current toxicity data. Pharmaceutical detection and application of the proposed monitoring framework can be used for water source protection and risk management in China and elsewhere.

Purification and characterization of a novel antifungal protein secreted by Penicillium chrysogenum from an Arctic sediment.

A fungal strain, Penicillium chrysogenum A096, was isolated from an Arctic sediment sample. Its culture supernatant inhibited mycelial growth of some plant pathogenic fungi. After saturation of P. chrysogenum A096 culture supernatant with ammonium sulfate and ion exchange chromatography, a novel antifungal protein (Pc-Arctin) was purified and identified by matrix assisted laser desorption ionization-time of flight-time of flight-mass spectrometry (MALDI-TOF-TOF-MS). The gene encoding for Pc-Arctin consisting of 195 nucleotides was cloned from P. chrysogenum A096 to confirm the mass spectrometry result. Pc-Arctin displays antifungal activity against Paecilomyces variotii, Alternaria longipes, and Trichoderma viride at minimum inhibitory concentrations (MIC) of 24, 48, and 192 ng/disc, respectively. Pc-Arctin was most sensitive to proteinase K and then to trypsin but insensitive to papain. Pc-Arctin possesses high thermostability and cannot be antagonized by common surfactants, except for sodium dodecyl sulfate (SDS). Divalent ions, such as Mn(2+), Mg(2+), and Zn(2+), inhibited the antifungal activity of Pc-Arctin. Hemagglutination assays showed that Pc-Arctin had no hemagglutinating or hemolytic activity against red blood cells (RBC) from rabbits, rats, and guinea pigs. Therefore, Pc-Arctin from Arctic P. chrysogenum may represent a novel antifungal protein with potential for application in controlling plant pathogenic fungal infection.

Clinical, cytogenetic, and molecular analysis with 46,XX male sex reversal syndrome: case reports.

PURPOSE: To investigate the clinical characteristics of different categories of sex-reversed 46,XX individuals and their relationships with chromosomal karyotype and the SRY gene. METHODS: Chromosome karyotyping for peripheral blood culture and multi-PCR and FISH were performed. RESULTS: Endocrinological data showed that their endocrine hormone levels were similar to that observed for Klinefelter syndrome, with higher FSH and LH levels and lower T levels. Chromosome karyotyping for peripheral blood culture revealed 46, XX complement for 11 males. Molecular studies showed that there were locus deletions at SY84, SY86, SY127, SY134, SY254 and SY255 in AZF on chromosome Y in 9 cases, with the SRY gene present at the terminus of the X chromosome short arm. In one case, besides 6 locus deletions in AZF, there was also SRY gene deletion. In another case, there were locus deletions only at SY254 and SY255, with SY84, SY86, SY127 SY134 loci and SRY present. CONCLUSIONS: The majority (10/11) of 46,XX males were SRY positive, with the SRY gene translocated into the terminus of the X chromosome short arm. These patients were caused mainly by an X/Y chromosomal inter-change during paternal meiosis, leading to the differentiation of primary gonads into testes. Only a single patient (1/11) was SRY-negative, in which there might be some unknown downstream genes involved in sex determination.